The role of torso stiffness and prediction in the biomechanics of anxiety: a narrative review

Abstract

Although anxiety is a common psychological condition, its symptoms are related to a cardiopulmonary strain which can cause palpitation, dyspnea, dizziness, and syncope. Severe anxiety can be disabling and lead to cardiac events such as those seen in Takotsubo cardiomyopathy. Since torso stiffness is a stress response to unpredictable situations or unexpected outcomes, studying the biomechanics behind it may provide a better understanding of the pathophysiology of anxiety on circulation, especially on venous impedance. Any degree of torso stiffness related to anxiety would limit venous return, which in turn drops cardiac output because the heart can pump only what it receives. Various methods and habits used to relieve stress seem to reduce torso stiffness. Humans are large obligatory bipedal upright primates and thus need to use the torso carefully for smooth upright activities with an accurate prediction. The upright nature of human activity itself seems to contribute to anxiety due to the needed torso stiffness using the very unstable spine. Proper planning of actions with an accurate prediction of outcomes of self and non-self would be critical to achieving motor control and ventilation in bipedal activities. Many conditions linked to prediction errors are likely to cause various degrees of torso stiffness due to incomplete learning and unsatisfactory execution of actions, which will ultimately contribute to anxiety. Modifying environmental factors to improve predictability seems to be an important step in treating anxiety. The benefit of playful aerobic activity and proper breathing on anxiety may be from the modulation of torso stiffness and enhancement of central circulation resulting in prevention of the negative effect on the cardiopulmonary system.

1 Introduction

Anxiety can be a normal presence in stressful situations. Still, excessive anxiety can lead to a panic attack, which can cause the sensation of suffocation and doom, as well as common symptoms of palpitation, rapid breathing, sweating, and dizziness. Some people may pass out, risking injuries. Anxiety is also linked to an increased risk of cardiovascular disorders (1), premature mortality (2), sudden cardiac arrest (3), self-harm (4, 5), and suicidality that is not explained by depression (6, 7). While the pathophysiology of anxiety and panic disorder is not well understood, many professionals advise doing other things to take one's mind off of the stressor: knitting, coloring books, deep breathing, regular exercise, hiking, and partaking in hobbies.

Hyperventilation is common in panic attacks and characterized by a shift from a diaphragmatic to a thoracic breathing pattern, which imposes a biomechanical stress on the neck and shoulder region due to the ancillary recruitment of the sternocleidomastoid, scalene, and trapezius muscles in support of thoracic breathing (8). In hyperventilation theory, hyperventilation causes a drop in arterial CO₂ and a change in the blood pH (i.e., respiratory alkalosis), disrupting blood acid-base equilibrium. This disruption can further induce adverse effects, including muscle tension and muscle spasms from an amplified response to catecholamines. Even though hyperventilation theory is appealing and provides some clues to many symptoms of anxiety and panic disorders, this theory has lost popularity due to a lack of experimental evidence (9).

Instead, aerobic exercise, which would cause hyperventilation, appears beneficial in mitigating anxiety (10). Even acute aerobic exercise mitigates negative symptoms of obsessive-compulsive disorder (OCD), a severe form of anxiety disorder characterized by unwanted thoughts and repetitive irrational behaviors (11). While the beneficial effect of physical activity on anxiety seems to be far superior to medications and cognitive behavioral therapy (12), there is no single major mechanism to explain the positive effects of exercise, thus limiting the development of optimal strategies in the application of exercise for the treatment of anxiety (10, 13).

Anxiety with an increased adrenergic tone has a lowered heart rate variability (HRV) (14) which is a valuable tool to evaluate the function of the autonomic nervous system. HRV is lower in cardiovascular disorders (15), metabolic disorders (16), and other mental conditions known to cause anxiety (17, 18). How aerobic exercise (19, 20) and quiet breathing (21) improve HRV may be understood through a biomechanical approach to the effects of anxiety on circulation and ventilation.

In this review of the biomechanics of anxiety, we will discuss the complexity of bipedalism which is the evolutionary hallmark of humans for energy-efficient endurance running and walking (22). Using the upper body and arms via successful bipedalism, humans developed sophisticated skills to use various tools including weapons. However, due to inherent instability, upper body activity requires torso stabilization and accurate prediction for balance in complex bipedal locomotion. Torso stiffness (23) is common in anxiety and seems to present as various symptoms of the circulatory system. A biomechanical approach to the roles of the respiratory muscles and abdominal wall muscles in torso stabilization (24–28) and circulation (29–33) may help understand the pathophysiology of anxiety in many disorders including autism.

2 Expanded spinal canal and trunk control in bipedal humans

In a study on the evolution of human speech (34), the authors suggested that the evolution of breathing control through increased thoracic innervation to abdominal muscles and thoracic muscles (including intercostal and subcostal muscles) was essential for developing human language. They reported that Neanderthals and early modern humans had expanded thoracic canals. They also suggested that earlier hominids did not possess the enhanced breathing control necessary for modern language until at least 1.6 Mya, the time of Homo ergaster (or early Homo erectus). Increased thoracic innervation to thoracic muscles and abdominal muscles is also necessary for many functions of humans: upright bipedal locomotion, flexion, breathing, and expulsion (e.g., coughing and defecation).

Compared to Eocene primates, the evolutionary expansion of the spinal canal in modern-day primates is to support sophisticated locomotor control of both the forelimb and the hindlimb (35). Spinal cord expansion in early hominins occurred well before the expansion of the brain and was necessary for complex balance control of obligate bipedal movement (36). In addition, the control of breathing for speech needs delicate control of the thoracoabdominal muscles to prevent the fading of sound volume from the uncontrolled elastic recoil of the lungs. Humans can produce a more than 7-fold increase in the duration of exhalation compared to the 2–3 times increase seen in the majority of nonhuman primate species (34).

3 Functional anatomy of torso stabilization

3.1 Abdominal wall muscles

Among the multiple anterior abdominal muscles, the rectus abdominis (RA) is a paired muscle located in the midline of the anterior wall. This muscle is covered by a rectus sheath which consists of the aponeuroses of the lateral abdominal muscles. The transverse tendinous intersections of the muscle give the appearance of a “six pack”. It runs vertically between the anterior lower rib cage and the pubic bone. It functions as an antagonist to the erector spinae muscles to flex the lumbar spine during sit-ups. It is also important for respiration during forced expiration. The sides of the abdominal wall are supported by the external oblique muscle (EO), the internal oblique muscle (IO), and the transversus abdominis muscle (TrA) (37).

The external oblique muscle (EO) is the most superficial of the three flat muscles of the lateral anterior abdomen. It is attached to the external surfaces and inferior borders of the fifth to twelfth ribs. The serratus anterior muscle is in proximity to the EO on the ribs. The aponeurosis of the external oblique muscle forms the inguinal ligament (37).

The internal oblique muscle (IO) is located just under EO and over TrA. It runs perpendicular to EO. Beginning in the lumbodorsal fascia of the lower back, IO reaches the anterior 2/3 of the iliac crest and the lateral half of the inguinal ligament. The muscle fibers run up to the inferior borders of the 10th through 12th ribs and the linea alba (abdominal midline seam). During expiration, it can contract to compress the abdominal cavity to push the internal organs up into the diaphragm while the diaphragm is returning back into the chest cavity with the elastic recoil of the lung structure (37).

The transverse abdominal muscle (TrA) is the innermost of the flat muscles of the abdomen just under IO. It has many attachment sites: the lumbodorsal fascia, the lateral third of the inguinal ligament, the anterior three-fourths of the inner lip of the iliac crest, the inner surfaces of the cartilages of the lower six ribs, and the diaphragm. It inserts into the linea alba; its upper three-fourths lie behind the rectus muscle and blend with the posterior lamella of the aponeurosis of the internal oblique; its lower fourth is in front of the rectus abdominis. The contraction of TrA can help to compress the ribs and viscera to provide spinal stability (37).

3.2 diaphragm and pelvic floor muscles in torso stabilization

In a study on diaphragm contraction (24), the authors found that the electromyogram (EMG) activity of the diaphragm and the transverse abdominal muscle (TrA) showed about 20 milli-seconds earlier to the onset of the EMG activity of the deltoid muscle during rapid flexion of the shoulder to a visual stimulus. The authors also visualized the eccentric contraction of the diaphragm after initial shortening (at the time of low intra-abdominal pressure) when TrA was co-contracting to increase the intra-abdominal pressure. The contraction was independent of the phase of respiration. However, during rapid movement of the thumb and wrist, a posture not nearly as challenging as the shoulder, was not associated with this anticipatory EMG in the diaphragm. The simultaneous contraction of the diaphragm and TrA was thought to be pre-programmed and not from reflex since the EMG activities preceded that of the deltoid muscle. It was also considered to contribute postural stability of the human trunk during sudden voluntary movement of the limbs.

In another study (25), the authors found that, during limb movement (flexion and extension of a shoulder joint), the diaphragm and TrA were tonically active with added phasic modulation at the frequencies of both respiration and limb movement. They also measured intra-abdominal pressure (measured through intragastric pressure: Pga), which increased during limb movement in proportion to the reactive forces from the movement. The rapid repetitive limb movement during breathing increased mean Pga by 26 cmH₂O. During the repetitive limb movement, the diaphragm and the trunk muscles (TrA, EO, RA, and the erector spinae muscles/ES) were contracting tonically. The diaphragm and TrA showed varying patterns in EMG activity with respiration but the other trunk muscles (EO, RA, and ES) did not have the variation in EMG amplitude between respiratory phases. They concluded that the coactivation of the diaphragm and abdominal muscles caused a sustained increase in intra-abdominal pressure (Pga). They suggested that the increase of the Pga and the tonic activity of the diaphragm contributed to the mechanical stabilization of the trunk during the movement of limbs.

In a study (26) on the co-activation patterns of abdominal muscles in response to the contractions of pelvic floor muscles (PFM), the authors reported that the contraction of abdominal muscles was a normal response to PFM activity. In another study on the postural and respiratory functions of PFM (27), the EMG activity of PFM was increased in advance of deltoid muscle activity as a component of the pre-programmed anticipatory postural activity (as seen in the diaphragm and TrA). The EMG activity of PFM was primarily modulated in association with arm movement with little respiratory modulation. PFM with the diaphragm and other abdominal muscles seem to take an important role in generating and sustaining intra-abdominal pressure (IAP) to stabilize the spine for posture control. In a study using biomechanical models of the spine and its musculature, the researchers found that spinal compression force was lower, with an increase in IAP through the contraction of antagonistic muscles of the abdominal wall (28).

3.3 Other muscles in torso stabilization

Through the unique anatomical location and complex vertebral attachment (37), the psoas muscles (PS) can provide postural stability for the trunk (38) and spread the force across the lumbar area (39). However, there was no active EMG activity of PS during quiet sitting (38). The lack of PS activity during quiet sitting can have implications for the structural stability of the spine in the modern-day lifestyle with excessive sitting.

The erector spinae muscles (ES), which are important extensor muscles of the back, can be silent when the spine column is flexed beyond a certain angle, known as the flexion-relaxation phenomenon. Interestingly, the EMG activity of PS disappeared when ES were silent in a flexion position (40). At this point, force distribution for spinal stability via ES and PS would be very difficult. In a study on abdominal wall muscle activities during quiet breathing (reflecting non-stress conditions), the abdominal muscles had no muscle activity (41). Some apprehended participants had irregular activities (which ceased altogether later) of one or two abdominal muscles unrelated to the phases of respiration. The intragastric pressure (Pga) at the end of a quiet expiration was 1–15 cmH₂O above atmospheric pressure (42) with the overall variation being no more than 3–5 cmH₂O and there was no muscular activity of abdominal muscles during the quiet breathing. During maximal voluntary breathing, the Pga rose abruptly to over 50 cmH₂O at the beginning of each expiration. This type of rise in the Pga during expiration never occurred in the absence of voluntarily controlled breathing even if the subjects became cyanosed and distressed in the involuntary respiration of asphyxia. In a study on maximal inspiratory and expiratory efforts (43), the Pga could rise to a range of 57–183 mmHg (77–250 cmH₂O).

In a study on lumbopelvic stability and co-contraction of the lumbopelvic muscles (44), the authors found that, during the unpredictable trial of stability challenge, TrA remained active when the EMG activity of all lumbopelvic muscles was decreased. The EMG activity of TrA did not differ between the predictable and unpredictable trials. However, there was a tendency for TrA EMG activity to be greater when there was less predictability of the perturbation. During the lumbopelvic flexion and extension trials, TrA contraction (which does not have a directional torque when activated unlike other abdominal wall muscles) appeared to be more important for stabilization during the physical disturbances. TrA contraction, which stabilizes the torso and spine by raising IAP (45), can be important for posture control during responses to unpredictable situations or outcomes.

In another study on sudden perturbations on the trunk (46), TrA was always the first abdominal muscle (other muscles are EO/IO/RA) to be activated. The contraction of the abdominal muscles and diaphragm with an increase of IAP appears to cause increased stiffening of the intervertebral joints within the lumbar spine. Additionally, the authors noted that there was a rapid backward head movement during unexpected ventral loading. This extension movement of the head/torso seems to be a common reflexive motion that we make when we miss a step or encounter a surprise.

4 Guyton's venous return curve and intra-abdominal pressure

Bipedalism is the hallmark of human locomotive success and our ancestors were able to chase their prey through successful bipedalism and endurance running and walking (22), were able to use the arms, and developed language via delicate breathing control with complex thoracic innervation to the abdominal muscles and thoracic muscles (34). However, they still had to manage to stabilize the torso/pelvis during bipedal running on uneven natural surfaces due to the inherently unstable posture during running, as the ligamentous spine without muscular contribution is very unstable (47, 48). For the upright posture and applied stiffness to the trunk for various upper body activities, a degree of trunk stiffness is expected (25). This stiffness will affect venous return negatively, considering the very low central venous pressure (3–8 mmHg), right atrial pressure (2–6 mmHg), and left atrial pressure (6–12 mmHg). If prolonged venous impedance continues during static upright upper body activities without proper rest, extrinsic impedance will decrease the cardiac preload and performance.

Considering Guyton's venous return curve (49) with a basic principle that the heart can pump out only what it receives from the large reservoir of circulatory volume (50), the proper venous return seems critical for proper cardiac function and tissue perfusion. In the equation of the venous return curve in steady conditions, he showed that the right atrial pressure and cardiac output are inversely related (14% drop in cardiac output by every 1 mmHg increment in pressure). While the implication of his findings is very important in caring for patients, many agreements (51) and disagreements (52) surround the equation from the lack of agreement on the hypothetical mean circulatory filling pressure (MCFP, the average integrated pressure throughout the circulatory system) which needs to be higher than the right atrial filling pressure.

Considering the very high intra-abdominal pressure (IAP) of a range of 57–183 mmHg (77–250 cmH₂O) during maximal respiratory efforts, although very low IAP is achievable with a little variation during quiet breathing (42, 43), it is evident that there will be a negative impact on circulation by venous impedance (53) if a degree of torso stiffness during strenuous or stressful upright bipedal activities is prolonged. Increased adrenergic tone not only causes excessive shortening of cardiac sarcomeres (contraction band/necrosis) (54) but also worsens torso stiffness in response to decreased preload if not reversed fast enough. This contraction band necrosis of cardiac muscles is found in stressed animals (55) and humans (56). To become successful hunter-gatherers, human ancestors with endurance running must have achieved proper motor skills for safe and proper venous return. To summarize, excessive torso stiffness, if not handled safely, can deteriorate venous return and be destructive to myocardial structural integrity causing myocardial rigors.

A pressure higher than 10 mmHg in the peritoneum is defined as “Intra-Abdominal Hypertension” which needs to be avoided (57). The negative effect can be observed even at 8 mmHg in animal models (58). The increase in muscular stiffness and IAP will contribute to an increase in intrathoracic pressure and a decrease in cardiac output. In a study on the relationship between abdominal pressure, pulmonary compliance, and cardiac preload in a porcine model (59), the authors found that increased IAP was transferred to the thoracic compartment and resulted in decreased respiratory system compliance (due to decreased chest wall compliance) and stroke index (SI: ml/kg). They noted a 22% decrease in SI at 30 mmHg of IAP. Filling pressures like CVP (central venous pressure) and PAOP (pulmonary arterial occlusion pressure) also increased significantly in response to increasing IAP which indicates the increased resistance to filling cardiac chambers and subsequent drop of cardiac stroke volume.

While proper weight-bearing activity (60) and quiet breathing (61) are the most important mechanisms for venous return in humans, prolonged static sitting causes decreased venous return and cardiac output with a compensatory increase in adrenergic tone. The lack of contribution from the PS during quiet sitting (38) and the inherent instability of lumbar spines (48) will require activation of TrA and other abdominal wall muscles (62) with related increases in IAP accordingly. Various degrees of stress response (63) and stiffening of the abdominal wall muscles (25) are expected depending on the level of risk involved in the given tasks. Seemingly harmless quiet sitting with a hydrostatic pressure of 28–32 mmHg in the pelvis (64) can reach a harmful level of IAP in the pelvis during a prolonged sitting to cause various negative impacts (57, 58, 65) which would get worse during demanding near-point work on computer screens (66). When venous return gets limited during sitting by the inactive skeletal muscles and restricted respiratory muscles, additional hydrostatic intraabdominal pressure can harm internal organs, and even worse if related risk is high.

5 Expiratory flow limitation and dynamic hyperinflation: biomechanics of dyspnea

Dyspnea is a common symptom of anxiety (67) and people with panic attacks report that they are very frightened by the feeling, sometimes referencing feelings of doom and a feeling that they are going to die from the sensation of choking. The mechanisms and pathways of the sensation of dyspnea are not completely understood (68). Juxtacapillary (J) receptors (or pulmonary C-fiber receptors) are non-myelinated slow-acting sensory vagus nerve fibers located within the alveolar walls in juxtaposition to the pulmonary capillaries of the lung. They are believed to be “nociceptors” responding to tissue damage and edema. They are stimulated during pulmonary congestion produced by occluding the aorta or left atrioventricular junction, which causes an increase in left atrial pressure with a consequent rise in pulmonary arterial pressure.

In feline experiments (69), there was a delayed response time (5–10 s) after the start of the occlusion of the aorta or atrioventricular junction. The interval between the start of the rise in systolic right ventricular pressure and the onset of stimulation in different fibers varied considerably. In some fibers, it was as little as 2 s; in others, about 15 s or more. Two nerve endings were not excited even 30 s after occlusion occurred. This considerable lag was the same after an injection of alloxan (a stimulant used in similar experiments by others). The author believed that the main physiological stimulus to the receptors was an increase in interstitial fluid in the alveolar wall.

It appears that the activation of pulmonary C-fiber receptors in animals produces inhibition of spinal motoneurons, reflex bradycardia, apnea, and hypotension via the vagus nerve. The injection of lobeline (a drug that activates pulmonary C-fiber receptors) can cause small animals (like cats) to collapse from reflex spinal motor neuron inhibition. When lobeline is injected into human subjects, they report noxious sensations of smoke or fumes in their airways. The sensation evokes an element of fear. It contributes to the sense of dyspnea. Even though human subjects do not collapse after the injection, they develop bradycardia (a decrease of 10–15 beats/min) with the accompanying hypotension (a decrease of ∼40 mmHg). In human subjects, the inhibition at a spinal level by lobeline was thought to be overridden by increased descending excitation, either from arousal or voluntary cerebral command (70).

However, in the study on the mechanisms of stimulation of pulmonary C-fiber receptors (69), the author noted that the application of local pressure on the lungs of cats was a very effective way to localize the nerve endings. The peak frequency in response to pressure stimulation was greater than that following phenyl diguanide injection. He wrote:

“Effects of local pressure.Application of local pressure on the lungs was an effective method of stimulating the endings so that it became possible to localize the endings in the individual lobes… Some endings could be stimulated by stroking the surface of the lungs; others needed strong pressure in order to stimulate them… [It] was found that mechanical stimuli set off a relatively prolonged discharge of impulses which continued for several sec after the mechanical stimulus had been withdrawn.”

From the observation above, we can infer that the most important function of pulmonary C-fiber receptors may be intrathoracic pressure monitoring during trunk control. This is essential for human bipedal locomotion and speech, especially with very low central venous pressure (3–8 mmHg), right atrial pressure (2–6 mmHg), and pulmonary capillary pressure (4–12 mmHg). Because human ancestors spent a significant amount of time as arboreal animals before becoming an obligatory bipedal species (71), they must have developed the necessary skills of trunk control which eventually became an essential part of bipedal locomotion and energy efficiency. Unlike quadrupedal animals, our human ancestors had to overcome the dilemma of controlling the needed stiffness of the trunk while avoiding excessive pressure on internal organs and vascular structures. Having a well-developed sensory system to monitor internal pressure can be accomplished via pulmonary C-fiber receptors. The varying degrees of response rate can be interpreted as the results of different degrees of applied pressure during activities of torso stiffness.

In a study (72) on the central integration of signals from pulmonary vagal C-fiber receptors along with those arising from cardiac, peripheral chemoreceptor, and baroreceptor afferents to neurons within the nucleus of the solitary tract, the author found that, after stimulation of pulmonary C-fiber receptors with phenylbiguanide, none of these neurons were activated by increasing right atrial pressure. After phenylbiguanide injection, only 13% of the cells responded to the stimulation of baroreceptors and only 6% to cardiac mechanoreceptor stimulation. The author indicated that there was a high proportion of afferent convergence from pulmonary C-fibers, cardiac receptors, and peripheral chemoreceptors in the nucleus of the solitary tract. The role of pulmonary C-fiber receptors was considered to be inhibitory and a part of the defense mechanism, even though the exact role was still unknown.

The term expiratory flow limitation (EFL) is a physiological concept to indicate that maximal expiratory flow is achieved during tidal breathing (73). When we reach EFL during expiratory breathing, further effort to increase the expiratory volume cannot increase the expiratory flow rate due to intrathoracic airflow obstruction. The presence of EFL during tidal breathing promotes dynamic pulmonary hyperinflation (DH) and intrinsic positive end-expiratory pressure (PEEPi). This will cause an increase in respiratory work and an adverse change in hemodynamics commonly seen in patients with advanced chronic obstructive pulmonary disease (COPD). When EFL and DH develop, one can overcome EFL by increasing alveolar pressure and elastic recoil by increasing air through increasing inspiratory work. However, in excess, this may lead to people feeling like they “cannot breathe”. In patients with COPD with EFL, the DH will cause a further increase in inspiratory work due to air-trapping. In a study on the effect of bronchodilators on patients with COPD (74), the authors found that patients with COPD with EFL may experience less breathlessness after a bronchodilator during light exercise than those without EFL. This beneficial effect of bronchodilation occurs even in the absence of a significant improvement in forced expiratory volume at 1 s (FEV1). Grossly obese people appear to have EFL and PEEPi through small airway closure and air trapping (75). In the study subjects, EFL was more common when they were in a supine position, and tidal breathing was affected by EFL and PEEPi. A consequence of EFL will be an increase in end-expiratory lung volume, resulting in an increase in functional residual capacity (FRC) at the end of expiration. The PEEPi can impose an additional elastic load on the inspiratory muscles and thus increase the work of breathing.

The great deal of breathlessness an inexperienced swimmer undergoes is likely from an increased intrathoracic pressure and trapped air causing an increase in inspiratory work to generate the needed venous return, in addition to the activation of pulmonary C-fiber receptors. Talking in unstable postures necessitating torso stiffness with an increase in intra-abdominal pressure may bring a subsequent development of air-trapping and PEEPi. If this airway trapping and development of EFL and DH continues over an extended period of time, he/she may develop a functional impairment of inspiratory muscle and adverse effects on hemodynamics, resulting in shortness of breath (76).

6 Biomechanics of laughter and crying

Laughter, often said to be the best medicine, decreases tension (77) and anxiety and is not unique to humans. Laughter is instinctive and contagious, is a form of social play and vocalization, and is unusual in solitary settings. If loud laughter can be induced by tickling and a young infant laughs during a simple game of “peekaboo”, the primary role of laughter must be physiological rather than psychological. When rats were tickled to induce laughter, the laughing rats were more optimistic in making decisions when uncertainty was involved (78). Laughter among shelter dogs helped the shelter dogs to reduce stress and increase prosocial behavior, which could potentially lead to reducing residency time (79).

Developing delicate systems to avoid excessive and prolonged pressure on thoracoabdominal organs while maintaining necessary stiffness for postural maintenance would be a prerequisite to becoming successful obligatory bipedal primates. Young infants have to learn to control their trunks to sit and stand before they start walking and running with a much higher degree of trunk control (80). However, avoiding excessive pressure while learning trunk control will be a crucial step as we already discussed the harmful effect of sustained increased IAP. Although normal IAP of a child is reported as 7 ± 3 mmHg (81), a healthy newborn may even have a lower value. When sitting infants react to motions with a degree of trunk control, they may utilize a rapid decompression of air (laughter) that can lower the pressure inside the torso to protect internal organs and maintain bonding with parents since they are defenseless at this stage of life.

Laughter with its repetitive expiratory contractions (average frequency of 4.6 ± 1.1 Hz) causes a final drop in functional residual capacity (FRC) by 1.55 ± 0.40 L (82). As the diaphragm counteracts contracting abdominal muscles, this counteraction appears to protect intra-thoracic structures from the contracting abdominal muscles. Closure of the glottis at the beginning of each expiratory contraction slows down expiratory effort and increases intra-alveolar pressure. The contracting abdominal muscles increase both intra-gastric pressure (Pga) and intra-esophageal pressure (Pes), but the increase in Pga is much higher than Pes by an average of 27 ± 7 cmH₂O during the entire fit of laughter. Contrary to trapping of air and dynamic hyperinflation during a stress response, a fit of laughter with the drop of FRC and the abdominal compression (with the pressure gradient between Pga and Pes) and following large negative inspiratory force will increase venous return and, in turn, cardiac output. In a study on the impact of laughter through humor on air trapping in severe COPD (83), the authors noted that laughter and smiling through humor intervention could induce a decrease in total lung capacity (TLC) by up to 1.55 L via reduction of RV (residual volume). FRC did not change. This indicated that there was a reduction in air trapping. Additionally, true laughter evoking more H-reflex suppression than simulated laughter (77) can be helpful in social interaction as the person is less guarded, more relaxed, and often falls off the chair.

When an individual encounters a stressful event or news and is unable to make a “fight-or-flight” reaction, crying seems to help avoid air-trapping and excessive intrathoracic pressure by contraction of abdominal muscles with narrowing of the laryngeal airway for enhanced sighing-like expiration. Subsequent inhalation after the contraction of abdominal muscles will induce an increased venous return to maintain circulatory volume. This contraction of the abdominal wall muscle during crying seems important for ventilation in a newborn with weak elastic recoil strength of the lung, In a study on expiratory muscle activity in preterm babies (84), the authors observed that the well-preterm babies used external oblique muscles during the expiratory cry but not during the intake of breath between cries. The grunting preterm babies were using external oblique muscles during grunting by forcing gas through the partially closed larynx which may help force gas into unexpanded regions of the lung. These expiratory abdominal muscle activities can help distribute force through the compliant lung areas to increase pressure inside the torso. The proper increase of pressure during crying, unlike laughing, can help maintain a degree of torso stiffness while avoiding dangerous air-trapping and hyperinflation and may be needed for posture control, unlike laughter. When a toddler falls after leaning on an unsecured object and starts to cry immediately, the toddler may get helped by extending his/her arms out by maintaining the hypertonicity of the torso (85). During temper tantrums in neurally underdeveloped toddlers who are unable to control ventilation upon stress, excessive outbursts of anger and crying may be compensatory strategies to handle ventilation and perfusion and would be worse if there are underlying deficits in inhibitory control, leading to future psychopathology (86). Although many illnesses cause pathological crying and laughing (87), crying and laughing are also interchangeable in many situations (i.e., award ceremonies). People accepting the award are likely to show their excitement and happiness through laughter first, but soon they will need to stiffen up in front of the audience while holding the trophy. The avoidance of excessive internal pressure can be achieved by laughing, crying, or both for a proper response to the given situation.

7 Predictive processing of perception

The reason that we cannot tickle ourselves seems to be the fact that the sensory consequence of self-generated movement is accurately predicted and suppressed. The amount of attenuation is proportional to the accuracy of the sensory prediction in self-generated movement with a narrow window (<100 ms) (88). Mechanisms to suppress or attenuate unnecessary information before it reaches the brain seem to be important to keep our attention on needed targets; otherwise, any such distractions would be dangerous for the survival of animals in the wild. Without proper prediction and suppression in vision, we will not be able to see at all during fast saccades due to the carried-over visual information formed on the retina (89). Indeed, we cannot see our own eyes moving in the mirror. Additionally, sensory inputs of unexpected events can be sensed acutely with a proper amount of attention, as toe cramps at night (which don't have an efferent copy from not being planned in the brain) are sensed as quite annoying.

Predictive processing is a well-accepted theory of perception and seems to be the main mechanism to enable us to engage in complex and fast social interaction (90, 91). Additionally, spontaneous activities (SA) of sensory areas of the brain in the absence of sensory stimuli appear to contribute to the perception and filtering of relevant inputs to integrate diverse sensory and non-sensory information to modulate behaviors and facilitate learning (92) with maturity (93). The complex neural sensory computation may be critical for the survival of animals, as any delay in perception and reaction by a fraction of a second can be deadly. Especially for large animals, including humans, on-site programming of action after computation of sensory input would not be compatible with survival in nature during hunting/escaping because there is a significant sensory-motor delay due to slow nerve conduction by distance and slow force generation of large muscle mass (94). For large animals, it can also be quite challenging to properly balance during fast locomotion if reactive jerks become frequent and cause perturbation of posture. For the mechanical property of large-bodied animals, predictive processing of incoming sensory signals of self and non-self origin would be a proper strategy for smooth and fast movement (95, 96).

Among many conditions, autism and psychosis are known to cause errors in prediction (97, 98) and anxiety-related symptoms in individuals (99, 100). Due to the presence of prediction error, people with deficits in higher level supraspinal computation would have a degree of torso stiffness from activation of TrA (44, 45) during various tasks, and might avoid those tasks in the future due to experience related to the negative impact on circulation and ventilation.

The theta waves in electroencephalography reflect the resting and default modes of brain activity (101) and appear during predictable motor activity (102). Easily predictable activities can be restful for the brain, like knowing the exact time of arrival of the last bus at a bus stop without a need for constant watch-out. Mind wandering (daydreaming) can also be restful for the brain from the fact that such activities do not require preparation for the pre-programmed motor activity of abdominopelvic muscles (24, 26) and arrangement of real-life predictions and monitoring of outcomes, thus allowing for more theta activity of the brain (103). Relaxation during watching clouds or far scenery would be from the fact that there is no need for immediate motor planning and monitoring. Maladaptive daydreaming is known to be linked to various psychopathological symptoms (104) and may reflect the underlying struggle to ease the tension of the torso for circulation and ventilation. Various habits (including nail-biting and lip-biting) would be easy real-life motor tasks, as motor actions on oneself are very predictable. Simple motor activity in a state of stable balance (like knitting while sitting) may induce relaxation of the diaphragm since it no longer needs to take on a postural role in humans (24) and promote theta waves from increased predictability of ongoing action. Many rituals can be helpful to ease one's tension due to their predictability (if practiced and familiarized) and used more during stressful times (105). In the same sense, Western classical music of highly regular and predictable rhythms may give us relaxation (106), and the predictability of the next note in the music being listened to increases as it is played repeatedly. The reverberating resonance in low-pitch meditation music may do the same, as the following sound becomes predictable due to the lasting resonance.

8 Vision and inhibition of return

Visual information is important for learning, prediction, and guidance of body actions in everyday activity (107, 108) with temporal guidance in space (109, 110). While the status of external ocular muscles appears to influence vestibulo-ocular reflex (111, 112), which is known to be important for balance, significantly, gaze direction seems to guide cervical muscles (113) and override vestibular signals for postural motor responses (114). Oculomotor deficit, which is common in many psychiatric illnesses including anxiety disorder (115) and autism (116, 117), may affect learning and executing motor activities negatively in everyday life.

While viewing behavior is quite biased toward given tasks (118), the clear foveal vision is only 1–2 degrees of the visual field with rapidly fading retinal images, and the need for redevelopment of perfectly-fused binocular retinal images with frequent saccades seems quite challenging when there is constant often irregular movements of self and others. Proper allocation of visual attention (119) with an accurate prediction of the future location of moving targets (120) can be important for complex social activity and is critical for animals to search for food and avoid predators.

Inhibition of return (IOR) is a well-known concept in vision research and states that response time to previously attended areas is slower. This inhibitory mechanism allows a person to allocate visual attention to unattended areas (121). Having a degree of deficit in IOR can have a negative impact on fast learning in complex social activities. Due to errors in prediction (97) with deficits in IOR, people with autism may have significant torso tightness (44, 45) from lowered predictability and perceptions of unexpectedness (46) in challenging environments, and may feel worse during actions including gait and language which would get influenced by less efficient gaze patterns for the guidance of motor activities (107–110) and postural balance (112, 113, 122). Deficits in IOR in obsessive-compulsive disorders (123) and attention deficit hyperactivity disorders (124) can be presented as anxiety during social activity if the allocation of visual attention is impaired in a complex and rapidly changing world.

9 Common conditions related to anxiety

9.1 Vasovagal syncope: neurally mediated syncope

There are many reasons for syncopal attacks, but a neurally mediated type is the most common and quite prevalent in the general population. Although the exact pathophysiological mechanisms of neurally mediated syncope (NMS) are not well known, the Valsalva maneuver can induce lightheadedness by blowing hard against the closed vocal cords to generate positive intrathoracic pressure. During the resisted expiration procedure to bear down the force meter at 20 cmH₂O for 7 s, both end-diastolic and end-systolic volumes of the left ventricle fell precipitously during the strain phase of the procedure with a concomitant decline in cardiac output (53). These findings suggested that the change in cardiac performance was due to the altering of ventricular filling and changing afterload. However, mildly-resisted inspiration, unlike resisted expiration, improves cardiovascular performance and tissue perfusion through a decrease in intrathoracic pressure and an increase in venous return (125–127).

During the tilt-table test (used to diagnose NMS), a patient in a supine position with a foot plate is secured by straps and belts. After the patient is fully upright, the table is then gradually tilted backward at a 60–80 degree angle. Sometimes, vasodilator agents are infused intravenously to increase the sensitivity and specificity of the test. A positive (abnormal) test result is characterized by a loss of consciousness that follows various hemodynamic patterns including hypotension with or without bradycardia. Even though the test is considered a safe procedure and an asystolic pause itself is considered a positive response, extremely prolonged asystole has been reported (128, 129).

While skeletal muscles pump venous return (60) via the eccentric contraction of large posterior posture muscles during the weight-bearing stance phase of gait (130), a restrained person in a tilted backward position after the initial upright standing will not be able to recruit large eccentric posterior postural muscles. This tilted posture mimics the non-weight-bearing swing phase of the legs to limit venous return. Further, straps and belts applied to the front torso will limit outward inspiratory movement which is important in restoring circulatory volume in hypovolemia (126) and hypotension (125). If a susceptible person is on the table for a prolonged period and activates torso muscles (including the diaphragm, TrA, and pelvic floor muscles) for the needed stiffness of the spinal column (24, 25, 27, 28, 131), this will result in a further deterioration of venous return.

In a Mueller maneuver (opposite of the Valsalva maneuver), the increase in abdominal pressure using rib cage muscles can briefly increase the venous return from the abdomen (132). This mechanism can be seen during “sighing breathing”. However, a prolonged increase in IAP will cause a drop in venous return which, in turn, will decrease the volume of the left ventricle. The static contraction of the diaphragm during continued thoracic breathing for postural control will inhibit the elastic recoil of the lungs upon exhalation and cause air-trapping with dynamic hyperinflation. At higher lung volumes, the expiratory effort will cause a much higher intrathoracic pressure due to air-trapping and dynamic hyperinflation (132). Because of the higher lung volumes, the greater expulsive effort needed for expiration may induce the Valsalva effect (like blowing a balloon). When thoracic breathing (inspiration and expiration) at higher lung volumes causes a decrease in venous return and an increase in intrathoracic pressure, there will be a compressive effect on pulmonary capillaries (4–12 mmHg), right atrium (2–6 mmHg), and left atrium (<13 mmHg) with a subsequent decrease in left ventricular volume (dimension) and cardiac stroke volume (133). Infusion of vasodilating agents (including many antihypertensive drugs) will cause a decrease in preload and afterload to contribute to the pathogenesis of vasovagal syncope.

A necessary increase in adrenergic tone, when preload is low, can induce poor relaxation of muscles and further limit cardiac filling. If excessive adrenergic flow into the cardiovascular system by the activation of afferent baroreceptors is not counterbalanced, the excessive cardiac contraction with decreased venous return (underfilling) could cause an over-shortening of the sarcomere of left ventricular muscles at the end of systole (the beginning of diastole). This overshortening of sarcomere with decreased diastolic volume could allow “contraction band” formation (hypercontracted sarcomeres) which can be seen in “Takotsubo” cardiomyopathy (134, 135) and in the cardiac death of stranded animals (55, 136).

If there is an activation of pulmonary C-fiber receptors as a result of increased intrathoracic pressure (which causes bradycardia, hypotension, and a decrease in muscle tone), then the loss of consciousness (syncope) can be seen as a defense mechanism rather than an abnormal neuro-humoral reaction (like a circuit breaker in a system overload) as spontaneous breathing is beneficial over positive-pressure ventilation during hypotension (126) if maintained during syncope.

The vasovagal reaction seems to happen even after heart transplantation (137) because of the existing defensive role of pulmonary C-fiber receptors rather than paradoxical stimulation of left ventricular baroreceptors from neurohumoral dysfunction (or the reaction should not happen after denervated transplanted heart). In this study (137), patients after heart transplantation underwent head-up tilt (up to 60 degrees) testing while resting on a saddle support (bicycle saddle fixed on a steel tube which prevents proper weight-bearing for venous return and posture). During the tilt with saddle support, the patients could induce the activation of torso muscles to increase IAP and induce air-trapping with dynamic hyperinflation.

Selective Serotonin Reuptake Inhibitors (SSRIs) appear to prevent vasovagal syncope in patients with refractory NMS (138). Although negative conversion of the tilt test seems to support the efficacy of the drug on the neural mechanism, people treated with SSRIs still continue to have a positive response to lower body negative pressure (inducing decreased venous return by venous pooling) during the tilt test (139). These findings appear to indicate the possible role of SSRIs on NMS through the change of motor (behavioral) patterns during stressful situations rather than through the modification of the sympathetic tone or its withdrawal as serotonin is known to modulate the central pattern generators (CPGs) in animals (140–142).

9.2 Takotsubo cardiomyopathy (stress cardiomyopathy: broken heart syndrome)

Although many people assume that the heart pumps blood out by shortening the length of the sarcomere (concentric contraction) with widening muscle fibers based on sliding theory, if this were the case, then the concentrically contracting cardiac muscles yield 11.6% work with the rest lost as heat energy (143). While moderate heat stress is already detrimental to cardiac conduction (144), if the heart beats >100,000 times a day with that much heat, survival is impossible. For this reason, there must be other mechanisms to prevent excessive energy use leading to fatigue and rigor. Unloaded shortening-induced deactivation by the structural change of the physical state of the regulatory protein complex of the actin and myosin units, not due to the depletion of chemical energy, seems important for energy saving in skeletal muscle physiology (145). In cardiac muscles, the recoil moment of stretched elastic titins upon unloading seems to contribute to the mechanical deactivation of calcium-dependent acto-myosin bindings to spare ATPs (146). Obliquely running elastic regions of cardiac titins can provide a longitudinal and radial force that compresses the lattice upon lengthening (147). After the initial shortening of fibers upon the start of systole, through the unique spatial arrangement (148) and radial branching pattern of cardiac muscle fibers, there is a lengthening event during cardiac contraction with geometric alteration in fiber and sheet structures to induce circumferential shortening and regional wall thickening rather than an increase in fiber size (149, 150). However, when preload is low with an adrenergic surge during stressful situations, a degree of concentric contraction forming contraction band may occur (54). This may explain the sensation of internal “heat” in many people with recurrent syncope just before they pass out.

Takotsubo cardiomyopathy was once thought to be rare but now seems to have been an under-recognized condition with increasing numbers of case reports in various countries (151). In a tertiary hospital, it may account for approximately 2% of hospital admissions for acute coronary syndrome (152). Even though a complete recovery is expected in the majority of cases, it can be fatal. It is an acute illness with a sudden onset of chest pain and shortness of breath, usually triggered by an emotionally or physically stressful situation. It appears to happen more often in women over 50 years old. When they present to an emergency room for chest pain and dyspnea, the initial findings are suggestive of acute coronary syndrome with changes in EKG (electrocardiogram) and blood biochemical testing including elevation of cardiac enzymes. However, objective findings usually fail to show any significant coronary atherosclerotic stenosis, coronary vasospasm, or myocarditis (134). Instead, the patients with this condition show a distinctive pattern of apical akinesis of the left ventricle in angiographic images which is similar to the shape of a fishing pot used for trapping octopus in Japan.

If a sudden severe (emotionally or physically) stressful situation causes a severe adrenergic response, the required postural stiffness will increase intraabdominal and intrathoracic pressure. Suppose this reactive stiffness is not compensated by physical movement (fight-or-flight) and proper ventilation. In this case, there will be a significant drop in intraventricular volume (53) from decreased venous return and extrinsic compression on the cardiac chambers and vena cava veins (153). If pulmonary C-fiber receptors are not activated immediately or are overridden by supraspinal (cerebral) command (70), excessive and continuous contractions of the left ventricle under the adrenergic influence with decreased preloads will cause over-shortening of muscular fiber length to form “contraction bands” from hypercontraction of sarcomeres (134, 135). This hypercontraction of cardiac muscle fibers may be the cause of the chest pain (cramps) and happens more at the apex sparing the peri-valvular area due to its valvular attachment.

If unopposed to the excessive adrenergic surge with hypercontractility, the unsecured freely moving apical cardiomyocytes can develop rigor and contraction bands unlike the secured basal cardiomyocytes. The unique inhibitory mechanism of apical cardiodepression for cardiac protection at the time of adrenergic surge seems necessary (154) to avoid myocardial toxicity and contraction band formation and may give the unique shape in the ventriculogram by the time an angiogram is done. The extremely high level of catecholamines (much higher than in normal stress response) can be the result of cardiac pump failure (135); however, the perfusion pressure to the vital organs may be maintained by catecholamines increasing the contractillity of basal cardiomyocytes (154).

9.3 Postural orthostatic tachycardia syndrome

Postural orthostatic tachycardia syndrome (POTS) is considered an autonomic dysfunction that causes postural lightheadedness, fatigue, sweating, tremor, anxiety, palpitation, and near syncope (155). People with this condition have an increased heart rate > 120/min (or increase by 30 from resting heart rate) after standing for 10 min. The condition is more common in women (5:1 female to male ratio) in the age range of 12–50.

If a person develops patterns of excessive activation of torso muscles with an increase in intra-abdominal and intra-thoracic pressure, if the patterns are sustained with an increase in adrenergic tone but limit splanchnic reserve of blood volume (156), and if the patterns are maintained into daily life activities with a suppression of pulmonary C-fiber activation by supraspinal (cerebral) override (70), the patterns causing decreased venous return and insufficient intrathoracic blood volume (153) will not be sustainable. With a limited splanchnic reserve and an impeded venous return, an increase of sympathetic stimulation of the heart alone will result in only small increases in cardiac output (156). If activation of baroreceptors with hyperadrenergic vasoconstriction is prolonged (153), irreversible myocardial injury with ATP depletion can occur (54).

However, the sympathetic outflow and vascular resistance of the skin are not regulated by baroreceptor activity (157) but rather by central motor command (158). The activation of cutaneous sympathetic tone promoting sweating and flushing may help to prevent hyperthermia during hyper-adrenergic situations. While sitting down alleviates POTS by preventing excessive torso stiffness and bringing the venous pool closer to the torso, enhanced inspirational drive via common respiratory symptoms (159) when preload is low (160, 161) can expand central blood volume to ameliorate orthostatic hypotension (125, 162). POTS seems reactive to the circulatory compromise by an extended adrenergic response during improper upright activity rather than an autonomic dysfunction.

9.4 Abdominal pain and irritable bowel syndrome

These are common symptoms related to anxiety and often become severe enough to make an emergency room visit. Contrary to the severe pain causing “doubling-over” posture and tenderness requiring intravenous pain medications, laboratory and imaging tests often fail to reveal any significant pathologic findings to explain the severe pain (163). Other people with discomfort in the pelvic or suprapubic (bladder) area with urinary frequency or urgency and sometimes painful urination are often treated for urinary tract infections (164). It is also common for many people to have bacteria in their urine without any symptoms. Occasionally, a normal urine test is obtained when the clinical presentation is identical to prior urinary track infection events. Referral to urology is often made and patients undergo a series of tests with a diagnosis of interstitial cystitis. Sometimes, surgical implantation of a sacral nerve root stimulator is attempted with varying results (165).

A motor unit consisting of a motor neuron and all the muscle fibers it innervates can have a varying number of muscle fibers per motor unit (from a few to several hundred) and generates force determined by the number of muscle fibers in the unit. During muscular activation, because all muscles consist of many individual motor units mixed amongst fibers of other units, activation of one motor neuron can result in a weak but distributed muscle contraction. There will then be subsequent activation of more muscle fibers when additional forces are needed, known as motor unit recruitment (166). Because the motor unit recruitment reflects how many motor neurons are activated in a particular muscle, it can be used as a measure of the muscle contractile force. The larger the recruitment, the stronger the contractile force will be. The contractile force can also be increased by the motor unit firing rate. The motor unit firing rate of each individual motor unit can increase with increasing muscular effort until a maximum rate is reached.

In slow and low-amplitude muscle contractions, a minimal firing rate modulation of the early recruited (low threshold) motor units appeared to be due to an inhibitory mechanism by the newly recruited motor units (167). The motor units recruited later showed depression of active firing rates when additional motor units were recruited for higher force development. In linearly changing voluntary contractions (168), recruitment is the major mechanism at low levels of force, but increased firing rate becomes the more important mechanism at intermediate force levels. A brief voluntary contraction superimposed on sustained contraction can induce a short suppression of low-threshold motor unit activities. This recruitment, de-recruitment, and re-recruitment appear to represent a mechanism to reduce fatigue of motor units during sustained contractions (169). However, during static contractions and slow (and low degree) dynamic contractions of low force (10% of maximal voluntary contraction force: common in occupational activities), some early-recruited motor units had continuous activities without rotating bursting and depression seen in brief voluntary contraction (170). This indicates that there are many motor units prone to fatigue and metabolic injury during prolonged repetitive work with insufficient pauses for a full recovery.

During the contraction of muscles causing tissue constriction, it is surprising that resting intramuscular pressure is below 5–10 cmH₂O and intramuscular pressure can rise rarely above 20 cmH₂O during voluntary contraction (171). However, maintaining proper blood flow into the feed arteries, intramuscular arteriolar networks, and capillaries with proper coordination of the vasoconstriction and vasodilation will be important to avoid tissue ischemia resulting in injuries. In a study on vasomotor tone in resistance vessels of hamster pouch retractor muscles, the authors found that there was a progressive constriction of arterioles and feed arteries with muscle lengthening (within a physiologic range) which decreased blood flow >50% (172). The reciprocal relationship between muscle length and the diameter of arterioles and feed arteries was sustained across muscle lengths. These length-induced vasomotor responses were triggered by norepinephrine release from perivascular sympathetic nerves within the retractor muscle, independent of the central nervous system (CNS). They concluded that intramuscular and extraparenchymal resistance vessels actively respond to mechanical forces within the muscle, independent of muscle fiber activation or the release of vasoactive metabolites. While the passive extension of the retractor muscle activates periarteriolar sympathetic nerves, muscle contraction (with acetylcholine release by the motor nerve terminals within the muscle) evokes (ascending) arteriolar dilation in a reciprocal manner, which is then conducted back into feed arteries (173). With feed arteries located next to skeletal muscles giving rise to intramuscular arteriolar networks, the mechanotransduction sequence via the change of length of skeletal muscle is integrated by the neural regulation of feed artery (and arteriolar) resistance and the supply of oxygen to muscle fibers (174). The changes in the cardiovascular system (which is mediated by hormones, reflexes, and CNS drive) also appear to be graded according to the degree of muscular activity and the volume of muscle involved (175). Venules, like arterioles, dilate actively in response to muscle contraction (176). This dilatation will help reduce the rise in capillary hydrostatic pressure to limit the outward filtration of fluid.

Because local mechanisms via length change are the most important mechanism for muscle perfusion (172–174, 176), prolonged static sitting with the silent psoas muscles (38) will recruit the abdominal wall muscles for the stabilization of spine (27) and resulting ischemic injury to the involved motor units would be inevitable. Biopsy specimens of work-related chronic myalgia showed pathologic “ragged red” fibers which are usually found in ischemic injury to the mitochondria (177), with decreased levels of ATP and ADP indicating reduced muscle oxygenation (178). Tissue doppler of the area of pain showed an impaired local capillary blood flow in the tender part (179). If a similar ischemic change is to happen in abdominopelvic muscles over a prolonged period of time, painful afferents from motor units of local ischemic injury [especially the transverse abdominis (TrA) muscles with diffuse attachment and no directional vector unlike other limb muscles with joint motion] may not be suppressed to give an impression of intraperitoneal pain. The severe pain perception can be a mismatch of expectations by the lack of cerebral efferent of the cramping action (like toe-cramps while sleeping) and related stress response to the unexpected afferents would incur further tightening of the postural muscles involved in vicious cycles. It is known that the cramp threshold gets lower in subsequent cramping contractions (180) to make the situation much worse.

During prolonged stress posturing while sitting under demanding tasks, additional ischemic injury to highly aerobic intraperitoneal organs is expected due to sustained elevation of IAP. Abdominal bloating, dyspepsia, and diarrhea are common symptoms related to irritable bowel syndrome. If the diaphragm, TrA, and PFM are to contract for stress response to raise IAP for posture control, the compensatory relaxation of internal oblique muscle and upper rectus muscle will be necessary (181) which can be seen in CT scan images of patients with functional abdominal distension as the descent of diaphragm without change of intra-abdominal volume (182). Then, bloating with diarrhea can indicate a degree of ischemic strain to internal organs during stress posturing and also serve as a compensatory mechanism to decompress the peritoneal cavity from the strain. Compared to the thoracic inspiration which is common in stress response, the cyclic diaphragmatic inspiration with a higher pressure gradient by its descent into the intraabdominal cavity (30, 183) can be an efficient way to drain venous blood and lymphatic fluid and then allow the passage of the incoming perfusion to the internal organs. The static abdominopelvic muscle strain with prolonged thoracic breathing causing ischemic injuries has to be considered in various organic inflammatory disorders, as stress is known to be the most important trigger in ulcerative colitis and Crohn's disease (184).

Central pattern generators (CPGs), producing rhythmic outputs in the absence of rhythmic input, seem to be the source of rhythmic and stereotypical behaviors, like walking, scratching, chewing, and breathing. Through the contributions from CPGs, we humans can make rapid adaptations to environmental changes and store new patterns very quickly (185, 186). Likewise, the ability to recruit different patterns quickly upon unexpected outcomes seems critical to avoid falls (187) and injuries (188). Patterned startle responses, such as in a common scenario when one might make a misstep going up or down a flight of stairs, appear to be context-specific (189) and site-specific (190). Besides central sensitization of pain hypersensitivity (191), if patterned stress posturing recruits motor units with ischemic injuries upon recurrent exposures to similar stressful situations, the motor afferents from ischemic motor units will be sensed as “unexpected” to cause more painful contractions.

A similar etiology may apply to chronic pain related to fibromyalgia which is also associated with an increased risk of irritable bowel syndrome. People with a history of chronic pain of ischemic/myalgic origin will have a significantly lower cramp threshold, which can be even lower after painful cramping contraction of the affected motor units (180). During a painful contraction (sensed as an “unexpected” afferent), the “unexpected” pain sensation will not be suppressed unlike how we suppress our expected senses during everyday activities (88, 192). Although many consider the pain in fibromyalgia to be neuropathic in origin, the proper maintenance of the nerve endings embedded in the muscles will also depend on local perfusion to the muscles, mainly by length changes. The structural change of the brain is common in patients with chronic pain syndrome (but not specific) and is thought to be secondary to frequent pain stimuli. It may also be reversible when the pain is well controlled (193). The preservation of the corresponding brain cortex of chronic pain indicates that pain generation is a bottom-up process rather than a top-down process (194, 195). Due to its nature as a bottom-up process, chronic pain can be perceived as severe from lacking cerebral efferent copies.

10 Discussion

To understand the pathophysiology of anxiety, the importance of venous return in circulation needs to be considered because the heart can pump only what it receives. While weight-bearing activity is the most important mechanism for venous return (60), proper breathing (61) through careful control of the torso is needed during upright bipedal activities. Successful bipedal locomotion with an inherently unstable spine (47, 48) and significant sensory-motor delay for force generation (94) must depend on accurate prediction and acquisition of many patterns (pre-programming) while simultaneously avoiding unnecessary torso stiffness. This must have been a prerequisite in human evolution. Through CPGs and preprogramming, we can perform fast motor activities without cognitive delay even before the active top-down supraspinal command (196). Indeed, we feel clumsy and slow to learn new skills using new tools in new environments.

It is interesting that, in addition to their failed adaptation to cold climates (197), the extinction of the Neanderthals might also be attributable to preeclampsia (198, 199). During pregnancy, torso control will be even more challenging due to the rapid growth of the large fetus and significant proprioceptive challenge from the loosening process of joints and muscles. If not controlled carefully, excessive pressure in the torso can impede venous return and circulating intravascular volume. Rapid fetal growth and exponential growth of the cerebellum in the large fetal heads in late pregnancy need a secure blood supply through the invasive placenta to the mother's womb. The disturbance of its growth in premature infants can cause subsequent neurocognitive and behavioral deficits (200) including autism (201). The vascular hallmarks of preeclampsia are placental arteriolar narrowing and fibrinoid necrosis which are likely reflecting the mother's struggle to preserve her circulatory reserve for her own survival although the invasive human placenta on the uterus is supposed to secure the necessary blood supply for the developing fetal brain.

Although the large pelvic opening of modern humans with pelvic dimorphism allows the passage of the fetal head, the large fetal head is still problematic and requires rotation of the fetal head during descent in the birth canal, unlike other primates (198). The large size of the Neanderthal's fetal head might have been problematic, similar to modern humans. Unlike modern-day humans, the Neanderthals had bigger pubic bones and wider pelvises without sexual dimorphism (202) with shorter lower limbs (203). This might have allowed them to be adept at activities of the upper body in their environments near glacial perimeters (204, 205) and wooded sloped terrains (206). They might have engaged in many anaerobic activities using the upper body, unlike our ancestors from the African savanna. Both the Neanderthals and modern humans were able to use sophisticated weapons technology and well-coordinated group hunting skills with the knowledge of the anticipatory behaviors of prey animals (207). However, it appears that modern humans were able to exploit much larger areas, establish broader social networks, and use local and non-local materials compared to their Neanderthal counterparts (207). This locomotive advantage with broader social networks can be supported by the energy-efficient modern human locomotion (22), unlike the Neanderthals of high daily energy demand (208) with wider pelvises and stocky bodies. Hyperadrenergic stress responses (209) with limited aerobic muscle activities in cold, wooded, and sloped environments (204–206) might have been deleterious to the societal bonding of the groups and the fetal development in pregnant females, as we know that stress can impair the prefrontal cortex structurally and functionally (210) and fetal development (211, 212). Further, the paternal experience of stress seems to have a lasting effect on future generations through transgenerational epigenetic inheritance (213).

Women of childbearing age with wider pelvis orifices and an open-plan arrangement of pelvic floor muscles (compared to their male counterparts) would require an increased tone of abdominopelvic muscles to support intraperitoneal organs during upright activities. Increased adrenergic tone related to an increased torso tone would cause a degree of venous impedance in women of childbearing age. Progesterone is known to have an inhibitory effect on muscle contraction (214, 215) and peak saccadic velocity is diminished during the luteal phase (216). The acute withdrawal of progesterone in the premenstrual period may have effects on proprioception and gaze control resulting in errors in motor planning and sensory monitoring (217). This would be much worse in susceptible individuals with underlying oculomotor dysfunctions and prediction errors (218) because gaze has an important role in guiding everyday activities (108) and postural stability (114), reflects decisional preference (219), and can be manipulated to bias one's decisions (220). Various circulatory symptoms may occur if prediction and monitoring functions are altered because gaze, sensory discrimination, and action execution are coupled to cardiac cycles (221–223). Individuals with convergence insufficiency which is a common oculomotor dysfunction affecting 5% of the population with limited reflective convergence capacity at near-point viewing (224) would need to over-fixate eyes on near-point screen tasks to cause strain and fatigue on delicate ocular muscles, likely from the overuse of the superior rectus muscles which are recruited for needed convergence and connected to the adrenergic system. Prolonged strain and ischemic injury may cause errors in saccades accuracy for visual learning and guidance which may contribute to many psychological symptoms (225) from unfavorable patterns of viewing of a complex world.

The level of proinflammatory cytokine IL-6 increases during stress responses including social and psychological stresses (226, 227). Increased IL-6 level is found in many psychiatric conditions (227–230). The skeletal muscles become a major source of IL-6 (231), and its production can increase by muscle damage (232), excessive and fatiguing exercise (233), low pre-exercise glycogen content from prolonged exercise with limited rest (234), and insufficient nutritional intake (235). Endurance training resulting in improved performance (236) and glucose ingestion (237) attenuate IL-6 release from contracting skeletal muscles. However, forced exercise does the opposite (238). During aerobic exercise, the hepatosplanchnic viscera appears to remove IL-6 from circulation to limit the negative effect (239). Elevated IL-6 level is also found in chronic myalgia (240) which is known to have local hypoperfusion and ischemic changes (177–179) as in other chronic illnesses. Particularly, local ischemia seems an important trigger of IL-6 production (241, 242).

While IL-6 promotes the production of other cytokines related to atopy and asthma (243) and causes myocardial failure and skeletal muscle atrophy dose-dependently (244), it also crosses the brain-blood-barrier and placenta. In animal models, a maternal injection of IL-6 mediated the socio-behavioral deficit (such as autistic behavior) in offspring, but co-administration of anti-IL-6 antibodies prevented the deficit (245). Although the cause of autism is not well known, elevated levels of maternal IL-6 linked to prenatal maternal stress may contribute to the risk of autism in humans (246, 247). The increased adrenergic tone from stress during pregnancy affecting circulating volume may cause ischemic strain and elevated levels of IL-6, which in turn may contribute to an increased risk of preeclampsia and autism (201). Likewise, prolonged static sitting with poor venous return during demanding tasks may affect systemic perfusion in the same way in pregnant women. Autism is frequently related to hypoplasia of the cerebellum, which is critical to coordinate ongoing motor actions with a precise prediction of the immediate future events of the self and surrounding environment (248). Being able to precisely put one's attention to the necessary location in response to cues and quick error correction upon mistakes is critical for the development of social skills. A delay or deficit of these skills will prevent the development of social skills from fragmented information in fast-changing environments (248) causing social anxiety and avoidance of social interactions.

Aerobic activities improving tissue perfusion through increased cardiac output (cardiac index) and decreased peripheral vascular resistance are beneficial to many conditions associated with anxiety and panic disorders (10, 249–252). Aerobically working muscles seem to work in tandem with the diaphragm to be the major pump for circulation over the heart when we consider the following: First, the stimuli to the cardiovascular responses to exercise come more from the muscles themselves than others (hormones, reflexes, and CNS drive) (175). Second, proper coupling of vasodilation and vasoconstriction within near the active muscles through cardiovascular adaptation (change in blood pressure and heart rate) are graded according to the degree of muscular activity and the volume of muscle involved (175). Third, muscle perfusion depends on local mechanisms mainly through muscle length change (172–174). Lastly, venules (like arterioles) dilate actively in response to muscle contraction to reduce the rise in capillary hydrostatic pressure to limit the outward filtration of fluid (176).

A typical municipality in the U.S. spends about 25–40 percent of its total energy bill on drinking water and wastewater systems to provide safe drinking water, and 90%–99% of energy consumption at a water system either using groundwater or surface water is primarily due to pumping (253). A water tower generating sufficient pressure to deliver water relies on proper pumping with pressure monitoring, and prolonged pumping failure in a municipal water system would make the town uninhabitable.

The “lactate shuttle” is now a well-accepted concept that explains the significant roles of lactate as a major energy source, a major gluconeogenic precursor, and a signaling molecule with autocrine, paracrine, and endocrine-like effects (254, 255). A large amount of lactate in the circulation is produced by the skeletal muscles during aerobic activities (254–257) and is an important and preferred fuel for the human brain (258–260) and heart (261). Lactate also reduces inflammation and organ injury (262, 263), and has free radical scavenging and antioxidant effects (264). Since humans have relatively large aerobic muscle mass compared to other primates (265), proper perfusion to those muscles would be necessary by frequent activity (266). However, modern-day lifestyles with excessive sitting seem to do the opposite (267, 268), resulting in a lack of the main fuel and antioxidants for the brain, the heart, and other organs in addition to spinal instability (38, 39) and activation of the abdominal wall muscles (44, 45). Further, if predictive processing is the main mechanism to perceive the world, proper brain computing is necessary for accurate perception of the world, and the accurate perception is essential for the prediction of higher probability and lower error rates; the benefit of sufficient aerobic activity to maintain and improve brain function can go far beyond cardiovascular benefits (10, 249, 269–278).

Further, our locomotive behavior on the pavement with a head-up posture (nice-and-tall) seems unsafe in natural environments with many obstacles if we walk barefoot. Proper visual attention (107–110, 279) is needed for balancing (113, 114) over many ground obstacles via accurate perception and prediction (like hammering a nail). The head-down flexion posture for visual guidance will activate posterior spinal muscles before the flexion-relaxation phenomenon (40, 280) to help the unstable spine (47, 48) by tensile eccentric contraction (281) to improve stability and balance (282, 283), analogous to cable grips or the counterweight systems of elevators and ski lifts. This can help free up the front abdominal muscles (40) for easier ventilation. Although alternating leg movement in human gait seems like passive motion, the swing phase is achieved by complex motor control to perfect dynamic synchronization and to utilize elastic restoring torques (284) which must integrate accurate prediction of passive tension. One reason for the benefits of barefoot walking over shod walking (285–288) on uneven natural ground can be from leaning forward to locate visual targets in time. Subsequent measured lifting and controlled landing of the swing leg mass occur for proper weight loading and dynamic synchronization. This differs from flat, paved surfaces with limited visual guidance where the psoas muscles get immediately inactivated after the initial swing phase (38) instead of stabilizing the spine (39). Enhanced balance via barefoot walking (285–287) may positively affect the activation of postural muscles (289, 290) to lessen anxiety-related symptoms (291, 292) as anxiety is linked to a deficit in balance (293, 294) and poor balance suppresses cardiac function and activates sympathetic tone significantly (295, 296).

Improper weight bearing on pavement can affect the venous return and circulating volume negatively and may contribute to anxiety in our society that is plagued by prolonged sitting and excessive near-point activities. On the other hand, playful aerobic activities in natural environments would make it hard to use existing motor patterns habitually built on pavements and might promote sensory integration for better motor outcomes (297) to improve anxiety (298–301). A similar principle may apply to the benefit of animal-assisted therapy (302, 303). If exposure to the natural environment and playful aerobic activity cannot be applied enough, obsessive thinking as a maladaptive daydreaming and compulsive behavior as a predictable activity may help ease tension and torso stiffness for the moment.

Severe emotional experience during a panic attack can pose a serious risk of cardiovascular events in susceptible individuals (coronary heart disease, Takotsubo cardiomyopathy, or sudden cardiac arrest) (3, 304–306) in young and old (307, 308) with uncontrolled anxiety disorder. Self-harming behaviors often associated with OCD (4, 5, 309), if not suicidal, can be seen as desperate efforts to restore circulation through a highly attentive, precise, and predictable action on oneself at the moment with subsequent physical withdrawal from the painful outcome. This may be more common in people with underlying prediction and coordination errors (310, 311). If our brain is optimized for the perception of the immediate future through predictive processing and spontaneous activity (90–92), frequent panic events caused by ongoing anxiety might influence the brain to predict and prepare for one's death which could be interpreted as suicidal ideation and attempts (6, 7, 312, 313) which are not explained by depression (6, 7). Suicidal ideation and an attempt would be more common in people with underlying prediction errors (314, 315). It is possible that suicidal ideation and even planning may function as maladaptive daydreaming to ease ventilation and perfusion if panic symptoms are not well controlled. Low dose opioid and vagal nerve stimulation are known to bring a prolonged expiration and an increased tidal volume (316, 317). Increased venous return from the splanchnic and non-splanchnic vascular beds (31) and improved cardiovascular function (29) are expected by enhanced respiratory pump (125, 126) with lowered intrathoracic pressure and may contribute to lowered suicidality (318–320). Considering the hypofunctioning prefrontal cortex during hyperadrenergic crisis (210), more prompt approaches may be necessary in the treatment of severe panic disorders over the step-wise approach to prevent irreversible outcomes from poor cognitive judgements.

11 Conclusion

The brain cannot function well if the heart pauses, and the heart cannot function well if venous return pauses. A proper amount of aerobic activity (60) coupled with quiet breathing (61, 321) is important for venous return and circulation to organs including the brain and the heart. The physical manifestations of feeling anxious are related to circulatory compromise and muscular stiffness which will also impede circulation by affecting skeletal muscle pump and respiratory muscle pump negatively. The reason that various methods including physical activity (12) and quiet breathing (321, 322) ease anxiety-related symptoms seems to be by enhancement of central circulation.

However, the contribution of abdominal muscles as an auxiliary heart (32, 33) can be significantly constrained if proper control of torso muscles is limited by various causes, intrinsically, extrinsically, or both. Considering the unique roles of the human diaphragm in posture control and ventilation, accurate prediction of sensory-motor outcomes and proper allocation of attention seem essential for the complex obligate bipedal activity. The predictive role of the brain in perception will be critical to overcome the significant sensory-motor delay. Through the complex learning process and pattern development, we humans can perform various motor activities (from walking to complex social and sports activities) efficiently with proper allocation of attention. Any delay in reaction or improper allocation of attention can be detrimental. As many conditions with prediction error present as spectrum disorders, various graded therapeutic activities can be considered to treat anxiety.

Playful aerobic activity for the skeletal muscle pump and proper ventilation for the respiratory muscle pump with a biomechanical approach and behavioral modification need to be considered as the first line of treatment and prevention of anxiety rather than adjunctive therapy (12). Our society has reduced playful aerobic activity dramatically with an increasing emphasis on academic competition and accomplishment, which inherently involves excessive static near-point activity and screen time. Playful aerobic exercise can also provide an important fuel and antioxidant to the brain via the “lactate shuttle” mechanism. Although our society promotes competition (which incurs stiff emotions unlike caring and giving) and exceptionality, exceptionality is often linked to deficits in social skills with a possibility of resultant overcompensation in the areas where functional individuals can make better predictions; some of these individuals might be labeled as “Gifted” (323–325). Promotion of yielding over competition seems needed to limit many harms from excessive anxiety as we feel comfortable when the outcome is predictable with less competition, like yielding over competing for a lane change while driving. Rapid increases in anxiety among young adults (326) and exponential rise in the recorded cases of autism (327) which is characterized by prediction error and anxiety may indicate that our society is failing from excessive environmental change and self-inflicted stress: the society of the only remaining homo species who might instead be remembered as fossils next to chairs, pavements, and electronics.

References

• 1.

  BatelaanNMSeldenrijkABotMvan BalkomAJPenninxBW. Anxiety and new onset of cardiovascular disease: critical review and meta-analysis. Br J Psychiatry. (2016) 208(3):223–31. 10.1192/bjp.bp.114.156554

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 2.

  TullyPJBakerRAKnightJL. Anxiety and depression as risk factors for mortality after coronary artery bypass surgery. J Psychosom Res. (2008) 64(3):285–90. 10.1016/j.jpsychores.2007.09.007

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 3.

  BatelaanNMSeldenrijkAvan den HeuvelOAvan BalkomAJLMKaiserARenemanLet alAnxiety, mental stress, and sudden cardiac arrest: epidemiology, possible mechanisms and future research. Front Psychiatry. (2022) 12:813518. 10.3389/fpsyt.2021.813518

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 4.

  McKayDAndoverM. Should nonsuicidal self-injury be a putative obsessive-compulsive-related condition? A critical appraisal. Behav Modif. (2012) 36(1):3–17. 10.1177/0145445511417707

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 5.

  YaoZPangLXieJShiSOuyangM. The relationship between social anxiety and self-injury of junior high school students: mediation by intolerance of uncertainty and moderation by self-esteem. Front Public Health. (2023) 11:1046729. 10.3389/fpubh.2023.1046729

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 6.

  WeissmanMMKlermanGLMarkowitzJSOuelletteR. Suicidal ideation and suicide attempts in panic disorder and attacks. N Engl J Med. (1989) 321(18):1209–14. 10.1056/NEJM198911023211801

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 7.

  ZhangYWangJXiongXJianQZhangLXiangMet alSuicidality in patients with primary diagnosis of panic disorder: a single-rate meta-analysis and systematic review. J Affect Disord. (2022) 300:27–33. 10.1016/j.jad.2021.12.075

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 8.

  SchleiferLMLeyRSpaldingTW. A hyperventilation theory of job stress and musculoskeletal disorders. Am J Ind Med. (2002) 41:420–32. 10.1002/ajim.10061

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 9.

  GarssenBRuiterCDDyckRVHornsveldH. Will hyperventilation syndrome survive?A Rrejoinder to Ley ClinPsycholRev. (1993) 13(7):683–90. 10.1016/0272-7358(93)90033-I

  • CrossRef
  • Google Scholar

• 10.

  KandolaAVancampfortDHerringMRebarAHallgrenMFirthJet alMoving to beat anxiety: epidemiology and therapeutic issues with physical activity for anxiety. Curr Psychiatry Rep. (2018) 20(8):63. 10.1007/s11920-018-0923-x

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 11.

  AbrantesAMFarrisSGBrownRAGreenbergBDStrongDRMcLaughlinNCet alAcute effects of aerobic exercise on negative affect and obsessions and compulsions in individuals with obsessive-compulsive disorder. J Affect Disord. (2019) 245:991–7. 10.1016/j.jad.2018.11.074

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 12.

  SinghBOldsTCurtisRDumuidDVirgaraRWatsonAet alEffectiveness of physical activity interventions for improving depression, anxiety and distress: an overview of systematic reviews. Br J Sports Med. (2023) 57(18):1203–9. 10.1136/bjsports-2022-106195

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 13.

  AndersonEShivakumarG. Effects of exercise and physical activity on anxiety. Front Psychiatry. (2013) 4:27. 10.3389/fpsyt.2013.00027

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 14.

  TomasiJZaiCCZaiGHerbertDRichterMAMohiuddinAGet alInvestigating the association of anxiety disorders with heart rate variability measured using a wearable device. J Affect Disord. (2024) 351:569–78. 10.1016/j.jad.2024.01.137

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 15.

  KubotaYChenLYWhitselEAFolsomAR. Heart rate variability and lifetime risk of cardiovascular disease: the atherosclerosis risk in communities study. Ann Epidemiol. (2017) 27(10):619–625.e2. 10.1016/j.annepidem.2017.08.024

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 16.

  StuckeyMITulppoMPKiviniemiAMPetrellaRJ. Heart rate variability and the metabolic syndrome: a systematic review of the literature. Diabetes Metab Res Rev. (2014) 30(8):784–93. 10.1002/dmrr.2555

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 17.

  BenjaminBRValstadMElvsåshagenTJönssonEGMobergetTWintertonAet alHeart rate variability is associated with disease severity in psychosis spectrum disorders. Prog Neuropsychopharmacol Biol Psychiatry. (2021) 111:110108. 10.1016/j.pnpbp.2020.110108

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 18.

  ThapaRPokorskiIAmbarchiZThomasEDemayoMBoultonKet alHeart rate variability in children with autism spectrum disorder and associations with medication and symptom severity. Autism Res. (2021) 14(1):75–85. 10.1002/aur.2437

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 19.

  SloanRPShapiroPADeMeersmanREBagiellaEBrondoloENMcKinleyPSet alThe effect of aerobic training and cardiac autonomic regulation in young adults. Am J Public Health. (2009) 99(5):921–8. 10.2105/AJPH.2007.133165

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 20.

  SuRPengPZhangWHuangJFanJZhangDet alDose-effect of exercise intervention on heart rate variability of acclimatized young male lowlanders at 3,680 m. Front Physiol. (2024) 15:1331693. 10.3389/fphys.2024.1331693

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 21.

  NatarajanA. Heart rate variability during mindful breathing meditation. Front Physiol. (2023) 13:1017350. 10.3389/fphys.2022.1017350

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 22.

  BrambleDMLiebermanDE. Endurance running and the evolution of Homo. Nature. (2004) 432(7015):345–52. 10.1038/nature03052

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 23.

  KarayannisNVSmeetsRJvan den HoornWHodgesPW. Fear of movement is related to trunk stiffness in low back pain. PLoS One. (2013) 8(6):e67779. 10.1371/journal.pone.0067779

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 24.

  HodgesPWButlerJEMcKenzieDKGandeviaSC. Contraction of the human diaphragm during rapid postural adjustments. J Physiol (Lond). (1997) 505(Pt 2):539–48. 10.1111/j.1469-7793.1997.539bb.x

  • CrossRef
  • Google Scholar

• 25.

  HodgesPWGandeviaSC. Changes in intra-abdominal pressure during postural and respiratory activation of the human diaphragm. J Appl Physiol. (2000) 89(3):967–76. 10.1152/jappl.2000.89.3.967

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 26.

  SapsfordRRHodgesPWRichardsonCACooperDHMarkwellSJJullGAet alCo-activation of the abdominal and pelvic floor muscles during voluntary exercises. Neurourol Urodyn. (2001) 20(1):31–42.10.1002/1520-6777(2001)20:1%3C31::aid-nau5%3E3.0.co;2-P

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 27.

  HodgesPWSapsfordRRPengelLHM. Postural and respiratory functions of the pelvic floor muscles. Neurourol Urodyn. (2007) 26(3):362–71. 10.1002/nau.20232

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 28.

  StokesIAFGardner-MorseMGHenrySM. Intra-abdominal pressure and abdominal wall muscular function: spinal unloading mechanism. Clin Biomech (Bristol, Avon) (2010) 25(9):859–66. 10.1016/j.clinbiomech.2010.06.018

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 29.

  ConvertinoVA. Mechanisms of inspiration that modulate cardiovascular control: the other side of breathing. J Appl Physiol (1985). (2019) 127(5):1187–96. 10.1152/japplphysiol.00050.2019

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 30.

  MillerJDPegelowDFJacqueAJDempseyJA. Skeletal muscle pump versus respiratory muscle pump: modulation of venous return from the locomotor limb in humans. J Physiol (Lond). (2005) 563:925–43. 10.1113/jphysiol.2004.076422

  • CrossRef
  • Google Scholar

• 31.

  AlivertiAFullinIBovioDLo MauroAHeymanJPedottiAMacklemP. The abdominal circulatory pump in healthy humans. Eur Respir J. (2007) 30: (Suppl. 51): 2644.

  • Google Scholar

• 32.

  AlivertiABovioDFullinIDellacàRLLo MauroAPedottiAet alThe abdominal circulatory pump. PLoS One. (2009) 4(5):e5550. 10.1371/journal.pone.0005550

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 33.

  UvaBAlivertiABovioDKayserB. The “abdominal circulatory pump": an auxiliary heart during exercise?Front Physiol. (2016) 7(6):411. 10.3389/fphys.2015.00411

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 34.

  MacLarnonAMHewittGP. The evolution of human speech: the role of enhanced breathing control. Am J Phys Anthropol. (1999) 109(3):341–63. 10.1002/(SICI)1096-8644(199907)109:3%3C341::AID-AJPA5%3E3.0.CO;2-2

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 35.

  MacLarnonA. The evolution of the spinal cord in primates: evidence from the foramen magnum and the vertebral canal. J Hum Evol. (1996) 30(2):121–38. 10.1006/jhev.1996.0009

  • CrossRef
  • Google Scholar

• 36.

  MeyerMRHaeuslerM. Spinal cord evolution in early homo. J Hum Evol. (2015) 88:43–53. 10.1016/j.jhevol.2015.09.001

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 37.

  StandringS. Gray’s Aanatomy. 40th edChurchill Livingstone: Elsevier (2008). p. 1055–81.

  • Google Scholar

• 38.

  KeagyRDBrumlikJBerganJJ. Direct electromyography of the psoas major muscle in man. J Bone Joint Surg. (1966) 48(7):1377–82. 10.2106/00004623-196648070-00011

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 39.

  HuHMeijerOGvan DieënJHHodgesPWBruijnSMStrijersRLet alIs the psoas a hip flexor in the active straight leg raise?Eur Spine J. (2011) 20(5):759–65. 10.1007/s00586-010-1508-5

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 40.

  FloydWFSilverPHS. The function of the erectores spinae muscles in certain movements and postures in man. J Physiol (Lond). (1955) 129(1):184–203. 10.1113/jphysiol.1955.sp005347

  • CrossRef
  • Google Scholar

• 41.

  CampbellEJM. An electromyographic study of the role of the abdominal muscles in breathing. J Physiol. (1952) 117:222–33. 10.1113/jphysiol.1952.sp004742

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 42.

  CampbellEJMGreenJH. The variations in intra-abdominal pressure and the activity of the abdominal muscles during breathing; a study in man. J Physiol (Lond). (1953) 122(2):282–90. 10.1113/jphysiol.1953.sp004999

  • CrossRef
  • Google Scholar

• 43.

  MillsJN. The nature of the limitation of maximal inspiratory and expiratory efforts. J Physiol (Lond). (1950) 111:376–81. 10.1113/jphysiol.1950.sp004487

  • CrossRef
  • Google Scholar

• 44.

  McCookDTVicenzinoBHodgesPW. Activity of deep abdominal muscles increases during submaximal flexion and extension efforts but antagonist co-contraction remains unchanged. J Electromyogr Kinesiol. (2009) 19(5):754–62. 10.1016/j.jelekin.2007.11.002

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 45.

  HodgesPW. Transversus abdominis: a different view of the elephant. Br J Sports Med. (2008) 42(12):941–4. 10.1136/bjsm.2008.051037

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 46.

  CresswellAGOddssonLThorstenssonA. The influence of sudden perturbations on trunk muscle activity and intra-abdominal pressure while standing. Exp Brain Res. (1994) 98(2):336–41. 10.1007/BF00228421

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 47.

  LucasDBBreslerB. Stability of the ligamentous spine. Biomechanics Laboratory. Univ. San Francisco, California (1960).

  • Google Scholar

• 48.

  CriscoJJPanjabiMMYamamotoIOxlandTR. The Euler stability of the lumbar spine. Part II: experiment. Clin Biomech. (1992) 7(1):27–32. 10.1016/0268-0033(92)90004-N

  • CrossRef
  • Google Scholar

• 49.

  GuytonAC. Determination of cardiac output by equating venous return curves with cardiac response curves. Physiol Rev. (1955) 35(1):123–9. 10.1152/physrev.1955.35.1.123

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 50.

  MadgerS. Volume and its relationship to cardiac output and venous return. Crit Care. (2016) 20(271):1–11. 10.1186/s13054-016-1438-7

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 51.

  HendersonWRGriesdaleDEWalleyKRSheelAW. Clinical review: guyton–the role of mean circulatory filling pressure and right atrial pressure in controlling cardiac output. Crit Care. (2010) 14(6):243. 10.1186/cc9247

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 52.

  BeardDAFeiglEO. Understanding guyton’s venous return curves. Am J Physiol Heart Circ Physiol. (2011) 301(3):H629–33. 10.1152/ajpheart.00228.2011

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 53.

  BudaAJPinskyMRIngelsNBJrDaughtersGT2ndStinsonEBAldermanEL. Effect of intrathoracic pressure on left ventricular performance. N Engl J Med. (1979) 301:453–9. 10.1056/NEJM197908303010901

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 54.

  ToddGLBaroldiGPieperGMClaytonFCEliotRS. Experimental catecholamine-induced myocardial necrosis. II. Temporal development of isoproterenol-induced contraction band lesions correlated with ECG, hemodynamic and biochemical changes. J Mol Cell Cardiol. (1985) 17(7):647–56. 10.1016/S0022-2828(85)80064-X

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 55.

  TurnbullBSCowanDF. Myocardial contraction band necrosis in stranded cetaceans. J Comp Pathol. (1998) 118(4):317–27. 10.1016/S0021-9975(07)80007-7

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 56.

  AkashiYJGoldsteinDSBarbaroGUeyamaT. Takotsubo cardiomyopathy: a new form of acute, reversible heart failure. Circulation. (2008) 118:2754–62. 10.1161/CIRCULATIONAHA.108.767012

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 57.

  CheathamMLMalbrainMLKirkpatrickASugrueMParrMDe WaeleJet alResults from the international conference of experts on intra-abdominal hypertension and abdominal compartment syndrome. II. Recommendations. Intensive Care Med. (2007) 33:951–62. 10.1007/s00134-007-0592-4

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 58.

  LengYZhangKFanJYiMGeQChenLet alEffect of acute, slightly increased intra-abdominal pressure on intestinal permeability and oxidative stress in a rat model[published correction appears in PLoS One. 2014;9(12):e115133]. PLoS One. (2014) 9(10):e109350. 10.1371/journal.pone.0109350

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 59.

  WautersJClausPBrosensNMcLaughlinMHermansGMalbrainMet alRelationship between abdominal pressure, pulmonary compliance, and cardiac preload in a porcine model. Crit Care Res Pract. (2012) 2012:763181. 10.1155/2012/763181

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 60.

  BroderickBJCorleyGJQuondamatteoFBreenPPSerradorJÓlaighinG. Venous emptying from the foot: influences of weight bearing, toe curls, electrical stimulation, passive compression, and posture. J Appl Physiol. (2010) 109(4):1045–52. 10.1152/japplphysiol.00231.2010

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 61.

  SalahHMGoldbergLRMolingerJFelkerGMApplefeldWRassafTet alDiaphragmatic function in cardiovascular disease: jACC review topic of the week. J Am Coll Cardiol. (2022) 80(17):1647–59. 10.1016/j.jacc.2022.08.760

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 62.

  UrquhartDMHodgesPW. Differential activity of regions of transversus abdominis during trunk rotation. Eur Spine J. (2005) 14(4):393–400. 10.1007/s00586-004-0799-9

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 63.

  ZabackMAdkinALCarpenterMG. Adaptation of emotional state and standing balance parameters following repeated exposure to height-induced postural threat. Sci Rep. (2019) 9(1):12449. 10.1038/s41598-019-48722-z

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 64.

  WilsonWH. Effect of breathing on the intra-abdominal pressure. J Physiol. (1933) 79(4):481–6. 10.1113/jphysiol.1933.sp003061

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 65.

  KaussenTSrinivasanPKAfifyMHerwegCTolbaRConzeJet alInfluence of two different levels of intra-abdominal hypertension on bacterial translocation in a porcine model. Ann Intensive Care. (2012) 2(Suppl. 1):S17. 10.1186/2110-5820-2-S1-S17

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 66.

  ZetterbergCForsmanMO’RichterH. Effects of visually demanding near work on trapezius muscle activity. J Electromyogr Kinesiol. (2013) 23(5):1190–8. 10.1016/j.jelekin.2013.06.003

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 67.

  NeumanAGunnbjörnsdottirMTunsäterANyströmLFranklinKANorrmanEet alDyspnea in relation to symptoms of anxiety and depression: a prospective population study. Respir Med. (2006) 100(10):1843–9. 10.1016/j.rmed.2006.01.016

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 68.

  BurkiNKLeeLY. Mechanisms of dyspnea. Chest. (2010) 138(5):1196–201. 10.1378/chest.10-0534

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 69.

  PaintalAS. Mechanism of stimulation of type J pulmonary receptors. J Physiol (Lond). (1969) 203(3):511–32. 10.1113/jphysiol.1969.sp008877

  • CrossRef
  • Google Scholar

• 70.

  GandeviaSCButlerJETaylorJLCrawfordMR. Absence of viscerosomatic inhibition with injections of lobeline designed to activate human pulmonary C fibres. J Physiol (Lond). (1998) 511:289–300. 10.1111/j.1469-7793.1998.289bi.x

  • CrossRef
  • Google Scholar

• 71.

  TakemotoH. Acquisition of terrestrial life by human ancestors influenced by forest microclimate. Sci Rep. (2017) 7(1):5741. 10.1038/s41598-017-05942-5

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 72.

  PatonJF. Pattern of cardiorespiratory afferent convergence to solitary tract neurons driven by pulmonary vagal C-fiber stimulation in the mouse. J Neurophysiol. (1998) 79(5):2365–73. 10.1152/jn.1998.79.5.2365

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 73.

  TantucciC. Expiratory flow limitation definition, mechanisms, methods, and significance. Pulm Med. (2013) 2013:749860. 10.1155/2013/749860

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 74.

  BoniECordaLFranchiniDChiroliPDamianiGPPiniLet alVolume effect and exertional dyspnoea after bronchodilator in patients with COPD with and without expiratory flow limitation at rest. Thorax. (2002) 57(6):528–32. 10.1136/thorax.57.6.528

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 75.

  PankowWPodszusTGutheilTPenzelTPeterJVon WichertP. Expiratory flow limitation and intrinsic positive end-expiratory pressure in obesity. J Appl Physiol. (1998) 85(4):1236–43. 10.1152/jappl.1998.85.4.1236

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 76.

  PengBMillerMSlootskyMPatelRBaydurA. Expiratory flow limitation and its relation to dyspnea and lung hyperinflation in patients with chronic obstructive pulmonary disease: analysis using the forced expiratory flow-volume curve and critique. Open J Respir Dis. (2021) 11:91–104. 10.4236/ojrd.2021.113009

  • CrossRef
  • Google Scholar

• 77.

  OvereemSTaalWOcal GeziciELammersGJVan DijkJG. Is motor inhibition during laughter due to emotional or respiratory influences?Psychophysiology. (2004) 41(2):254–8. 10.1111/j.1469-8986.2003.00145.x

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 78.

  RygulaRPlutaHPopikP. Laughing rats are optimistic. PLoS One. (2012) 7(12):e51959. 10.1371/journal.pone.0051959

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 79.

  SimonetPVersteegDStorieD. Dog-laughter: recorded playback reduces stress related behavior in shelter dogs. Proceedings of the 7th International Conference on Environmental Enrichment (2005).

  • Google Scholar

• 80.

  RachwaniJSantamariaVSaavedraSLWoollacottMH. The development of trunk control and its relation to reaching in infancy: a longitudinal study. Front Hum Neurosci. (2015) 9:94. 10.3389/fnhum.2015.00094.Erratum in: Front Hum Neurosci. (2015) 9:406. doi: 10.3389/fnhum.2015.00406.

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 81.

  EjikeJCBahjriKMathurM. What is the normal intra-abdominal pressure in critically ill children and how should we measure it?Crit Care Med. (2008) 36(7):2157–62. 10.1097/CCM.0b013e31817b8c88

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 82.

  FilippelliMPelligrinoRIandelliIMisuriGRodarteJRDurantiRet alRespiratory dynamics during laughter. J Appl Physiol. (2001) 90(4):1441–6. 10.1152/jappl.2001.90.4.1441

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 83.

  BrutscheMHGrossmanPMüllerREWiegandJPello, BatyFet alImpact of laughter on air trapping in severe chronic obstructive lung disease. Int J Chron Obstruct Pulmon Dis. (2008) 3(1):185–92. 10.2147/COPD.S2204

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 84.

  SouthMMorleyCJHughesG. Expiratory muscle activity in preterm babies. Arch Dis Child. (1987) 62(8):825–9. 10.1136/adc.62.8.825

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 85.

  KimJS. Excessive crying: behavioral and emotional regulation disorder in infancy. Korean J Pediatr. (2011) 54(6):229–33. 10.3345/kjp.2011.54.6.229

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 86.

  HoyniakCPDonohueMRQuiñones-CamachoLEVogelACPerinoMTHennefieldLet alDevelopmental pathways from preschool temper tantrums to later psychopathology. Dev Psychopathol. (2022) 20:1–13. 10.1017/S0954579422000359

  • CrossRef
  • Google Scholar

• 87.

  OlneyNTGoodkindMSLomen-HoerthCWhalenPKWilliamsonCAHolleyDEet alBehaviour, physiology and experience of pathological laughing and crying in amyotrophic lateral sclerosis. Brain. (2011) 134(Pt 12):3458–69. 10.1093/brain/awr297

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 88.

  BlakemoreSJWolpertDFrithC. Why can't you tickle yourself?Neuroreport. (2000) 11(11):R16. 10.1097/00001756-200008030-00002

  • CrossRef
  • Google Scholar

• 89.

  Orban de XivryJJLefèvreP. Saccades and pursuit: two outcomes of a single sensorimotor process. J Physiol. (2007) 584:11–23. 10.1113/jphysiol.2007.139881

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 90.

  SethAK. A predictive processing theory of sensorimotor contingencies: explaining the puzzle of perceptual presence and its absence in synesthesia. Cogn Neurosci. (2014) 5(2):97–118. 10.1080/17588928.2013.877880

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 91.

  ThorntonMAWeaverdyckMETamirDI. The social brain automatically predicts Others’ future mental states. J Neurosci. (2019) 39(1):140–8. 10.1523/JNEUROSCI.1431-18.2018

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 92.

  BettiVDella PennaSde PasqualeFCorbettaM. Spontaneous Beta band rhythms in the predictive coding of natural stimuli. Neuroscientist. (2021) 27(2):184–201. 10.1177/1073858420928988

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 93.

  AvitanLStringerC. Not so spontaneous: multi-dimensional representations of behaviors and context in sensory areas. Neuron. (2022) 110(19):3064–75. 10.1016/j.neuron.2022.06.019

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 94.

  MoreHLDonelanJM. Scaling of sensorimotor delays in terrestrial mammals. Proc Biol Sci. (2018) 285(1885):20180613. 10.1098/rspb.2018.0613

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 95.

  LaengBNabilSKitaokaA. The eye pupil adjusts to illusorily expanding holes. Front Hum Neurosci. (2022) 16:877249. 10.3389/fnhum.2022.877249

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 96.

  FriedrichEVCZillekensICBielALO'LearyDSeegenschmiedtEVSingerJet alSeeing a Bayesian ghost: sensorimotor activation leads to an illusory social perception. iScience. (2022) 25(4):104068. 10.1016/j.isci.2022.104068

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 97.

  SinhaPKjelgaardMMGandhiTKTsouridesKCardinauxALPantazisDet alAutism as a disorder of prediction. Proc Natl Acad Sci USA. (2014) 111(42):15220–5. 10.1073/pnas.1416797111

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 98.

  LevyDLSerenoABGoodingDCO'DriscollGA. Eye tracking dysfunction in schizophrenia: characterization and pathophysiology. Curr Top Behav Neurosci. (2010) 4:311–47. 10.1007/7854_2010_60

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 99.

  NadeauJSulkowskiMLUngDWoodJJLewinABMurphyTKet alTreatment of comorbid anxiety and autism spectrum disorders. Neuropsychiatry (London). (2011) 1(6):567–78. 10.2217/npy.11.62

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 100.

  HuppertJDSmithTE. Anxiety and schizophrenia: the interaction of subtypes of anxiety and psychotic symptoms. CNS Spectr. (2005) 10(9):721–31. 10.1017/S1092852900019714

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 101.

  RaichleMESnyderAZ. A default mode of brain function: a brief history of an evolving idea. Neuroimage. (2007) 37(4):1083–90. 10.1016/j.neuroimage.2007.02.041

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 102.

  LeeSMPeltschAKilmadeMBrienDCCoeBCJohnsrudeISet alNeural correlates of predictive saccades. J Cogn Neurosci. (2016) 28(8):1210–27. 10.1162/jocn_a_00968

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 103.

  MasonMFNortonMIVan HornJDWegnerDMGraftonSTMacraeCN. Wandering minds: the default network and stimulus-independent thought. Science. (2007) 315(5810):393–5. 10.1126/science.1131295

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 104.

  ChiricoIVolpatoELandiGBassiGMancinelliEGagliardiniGet alMaladaptive daydreaming and its relationship with psychopathological symptoms, emotion regulation, and problematic social networking sites use: a network analysis approach. Int J Ment Health Addiction. (2024) 22:1484–500. 10.1007/s11469-022-00938-3

  • CrossRef
  • Google Scholar

• 105.

  LangMKrátkýJXygalatasD. The role of ritual behaviour in anxiety reduction: an investigation of Marathi religious practices in Mauritius. Philos Trans R Soc Lond B Biol Sci. (2020) 375(1805):20190431. 10.1098/rstb.2019.0431

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 106.

  LevitinDJChordiaPMenonV. Musical rhythm spectra from Bach to joplin obey a 1/f power law. Proc Natl Acad Sci U S A. (2012) 109(10):3716–20. 10.1073/pnas.1113828109

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 107.

  AbramsRAMeyerDEKornblumS. Eye-hand coordination: oculomotor control in rapid aimed limb movements. J Exp Psychol Hum Percept Perform. (1990) 16(2):248–67. 10.1037/0096-1523.16.2.248

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 108.

  LandMF. Eye movements and the control of action in everyday life. Prog Retinal Eye Res. (2006) 25(3):296–324. 10.1016/j.preteyeres.2006.01.002

  • CrossRef
  • Google Scholar

• 109.

  HollandsMAPatlaAEVickersJN. “Look where you're going!”: gaze behavior associated with maintaining and changing the direction of locomotion. Exp Brain Res. (2002) 143(2):221–30. 10.1007/s00221-001-0983-7

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 110.

  PatlaAEVickersJN. How far ahead do we look when required to step on specific locations in the travel path during locomotion?Exp Brain Res. (2003) 148:133–8. 10.1007/s00221-002-1246-y

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 111.

  KnoxPCDonaldsonIML. Afferent signals from the extraocular muscles of the pigeon modify the electromyogram of these muscles during the vestibulo-ocular reflex. Proc R Soc London Ser B. (1991) 246:243–50. 10.1098/rspb.1991.0151

  • CrossRef
  • Google Scholar

• 112.

  DonaldsonIMLKnoxPC. Afferent signals from the extraocular muscles affect the gain of the horizontal vestibulo-ocular reflex in the alert pigeon. Vision Res. (2000) 40:1001–11. 10.1016/S0042-6989(99)00246-1

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 113.

  CatharinaSMBexanderRMHodgesPW. Effect of gaze direction on neck muscle activity during cervical rotation. Exp Brain Res. (2005) 167:422–32. 10.1007/s00221-005-0048-4

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 114.

  IvanenkoYPGrassoRLacquanitiF. Effect of gaze on postural responses to neck proprioceptive and vestibular stimulation in humans. J Physiol. (1999) 519:301–14. 10.1111/j.1469-7793.1999.0301o.x

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 115.

  BittencourtJVelasquesBTeixeiraSBasileLFSallesJINardiAEet alSaccadic eye movement applications for psychiatric disorders. Neuropsychiatr Dis Treat. (2013) 9:1393–409. 10.2147/NDT.S45931

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 116.

  TakaraeYMinshewNJLunaBSweeneyJA. Oculomotor abnormalities parallel cerebellar histopathology in autism. J Neurol Neurosurg Psychiatry. (2004) 75(9):1359–61. 10.1136/jnnp.2003.022491

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 117.

  ZallaTSeassauMCazalisFGrasDLeboyerM. Saccadic eye movements in adults with high-functioning autism spectrum disorder. Autism. (2018) 22(2):195–204. 10.1177/1362361316667057

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 118.

  YarbusAL. Eye Movements and Vision. New York, NY: Plenum Press (1967).

  • Google Scholar

• 119.

  Moreno-BoteRKnillDCPougetA. Bayesian Sampling in visual perception. Proc Natl Acad Sci U S A. (2011) 108(30):12491–6. 10.1073/pnas.1101430108

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 120.

  ItohTDTakeyaRTanakaM. Spatial and temporal adaptation of predictive saccades based on motion inference. Sci Rep. (2020) 10(1):5280. 10.1038/s41598-020-62211-8

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 121.

  KleinRM. Inhibition of return. Trends Cogn Sci. (2000) 4(4):138–47. 10.1016/S1364-6613(00)01452-2

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 122.

  PettorossiVESchieppatiM. Neck proprioception shapes body orientation and perception of motion. Front Hum Neurosci. (2014) 8:895. 10.3389/fnhum.2014.00895

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 123.

  MoritzSvon MühlenenA. Inhibition of return in patients with obsessive-compulsive disorder. J Anxiety Disord. (2005) 19(1):117–26. 10.1016/j.janxdis.2003.11.003

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 124.

  LiCSChangHLLinSC. Inhibition of return in children with attention deficit hyperactivity disorder. Exp Brain Res. (2003) 149(1):125–30. 10.1007/s00221-002-1362-8

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 125.

  ConvertinoVARyanKLRickardsCAGlorskySLIdrisAHYannopoulosDet alOptimizing the respiratory pump: harnessing inspiratory resistance to treat systemic hypotension. Respir Care. (2011) 56(6):846–57. 10.4187/respcare.01018

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 126.

  SkytiotiMSøvikSElstadM. Respiratory pump maintains cardiac stroke volume during hypovolemia in young, healthy volunteers. J Appl Physiol (1985). (2018) 124(5):1319–25. 10.1152/japplphysiol.01009.2017

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 127.

  ShaferKMGarciaJABabbTGFixlerDEAyersCRLevineBD. The importance of the muscle and ventilatory blood pumps during exercise in patients without a subpulmonary ventricle (fontan operation). J Am Coll Cardiol. (2012) 60(20):2115–21. 10.1016/j.jacc.2012.08.970

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 128.

  WinkerRFrühwirthMSaulPRüdigerHWPezawasTSchmidingerHet alProlonged asystole provoked by head-up tilt testing. Clin Res Cardiol. (2006) 95(1):42–7. 10.1007/s00392-006-0310-1

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 129.

  IslamogluYCakiciMAliciHDavutogluV. Malign asystole during head-up tilt test: a case report and overview. Eur J Cardiovasc Med. (2011) 1(3):22–3. 10.5083/ejcm.20424884.22

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 130.

  CappelliniGIvanenkoYPPoppeleRELacquanitiF. Motor patterns in human walking and running. J Neurophysiol. (2006) 95(6):3426–37. 10.1152/jn.00081.2006

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 131.

  Gardner-MorseMGStokesIAF. The effects of abdominal muscle co-activation on lumbar spine stability. Spine. (1989) 23(1):86–92. 10.1097/00007632-199801010-00019

  • CrossRef
  • Google Scholar

• 132.

  AgostoniERahnH. Abdominal and thoracic pressures at different lung volumes. J Appl Physiol. (1960) 15(6):1087–92. 10.1152/jappl.1960.15.6.1087

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 133.

  MizumakiKFujikiATaniMShimonoMHayashiHInoueH. Left ventricular dimensions and autonomic balance during head-up tilt differ between patients with isoproterenol-dependent and isoproterenol-independent neurally mediated syncope. J Am Coll Cardiol. (1995) 26(1):164–73. 10.1016/0735-1097(95)00120-O

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 134.

  AkashiYJNakazawaKSakakibaraMMiyakeFKoikeHSasakaK. The clinical features of takotsubo cardiomyopathy. QJM. (2003) 96(8):563–73. 10.1093/qjmed/hcg096

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 135.

  WittsteinISThiemannDRLimaJABaughmanKLSchulmanSPGerstenblithGet alNeurohumoral features of myocardial stunning due to sudden emotional stress. N Engl J Med. (2005) 352(6):539–48. 10.1056/NEJMoa043046

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 136.

  CâmaraNSierraEFernándezAArbeloMAndradaMMonterosAELet alIncreased plasma cardiac troponin I in live-stranded cetaceans: correlation with pathological findings of acute cardiac injury. Sci Rep. (2020) 10:1555. 10.1038/s41598-020-58497-3

  • CrossRef
  • Google Scholar

• 137.

  FitzpatrickAPBannerNChengAYacoubMSuttonR. Vasovagal reactions may occur after orthotopic heart transplantation. J Am Coll Cardiol. (1993) 21(5):1132–7. 10.1016/0735-1097(93)90235-S

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 138.

  Di GirolamoEDi IorioCSabatiniPLeonzioLBarboneCBarsottiA. Effects of paroxetine hydrochloride, a selective serotonin reuptake inhibitor, on refractory vasovagal syncope: a randomized, double-blind, placebo-controlled study. J Am Coll Cardiol. (1999) 33(5):1227–30. 10.1016/S0735-1097(98)00694-9

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 139.

  TakataTSWasmundSLSmithMLLiJMJoglarJABanksKet alSerotonin reuptake inhibitor (paxil) does not prevent the vasovagal reaction associated with carotid sinus massage and/or lower body negative pressure in healthy volunteers. Circulation. (2002) 106(12):1500–4. 10.1161/01.CIR.0000029748.94931.96

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 140.

  Harris-WarrickRMCohenAH. Serotonin modulates the central pattern generator for locomotion in the isolated lamprey spinal cord. J Exp Biol. (1985) 116:27–46. 10.1242/jeb.116.1.27

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 141.

  OkusawaSKohsakaHNoseA. Serotonin and downstream leucokinin neurons modulate larval turning behavior in Drosophila. J Neurosci. (2014) 34(7):2544–58. 10.1523/JNEUROSCI.3500-13.2014

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 142.

  FlaiveACabelguenJMRyczkoD. The serotonin reuptake blocker citalopram destabilizes fictive locomotor activity in salamander axial circuits through 5-HT1A receptors. J Neurophysiol. (2020) 123(6):2326–42. 10.1152/jn.00179.2020

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 143.

  GibbsCLMommaertsWFRicchiutiNV. Energetics of cardiac contractions. J Physiol. (1967) 191(1):25–46. 10.1113/jphysiol.1967.sp008235

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 144.

  LaingJGTadrosPNGreenKSaffitzJEBeyerEC. Proteolysis of connexin43-containing gap junctions in normal and heat-stressed cardiac myocytes. Cardiovasc Res. (1998) 38(3):711–8. 10.1016/S0008-6363(98)00060-1

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 145.

  EdmanKA. Mechanical deactivation induced by active shortening in isolated muscle fibres of the frog. J Physiol (Lond). (1975) 246(1):255–75. 10.1113/jphysiol.1975.sp010889

  • CrossRef
  • Google Scholar

• 146.

  HelmesMLimCCLiaoRBhartiACuiLSawyerDB. Titin determines the frank-starling relation in early diastole. J Gen Physiol. (2003) 121(2):97–110. 10.1085/jgp.20028652

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 147.

  GranzierHLabeitS. Cardiac titin: an adjustable multi-functional spring. J Physiol. (2002) 541(Pt 2):335–42. 10.1113/jphysiol.2001.014381

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 148.

  Sánchez-QuintanaDClimentVGarcia-MartinezVRojoMHurléJM. Spatial arrangement of the heart muscle fascicles and intramyocardial connective tissue in the spanish fighting bull (Bos Taurus). J Anat. (1994) 184(Pt 2):273–83.

  • Google Scholar

• 149.

  Nielles-VallespinSKhaliqueZFerreiraPFde SilvaRScottADKilnerPet alAssessment of myocardial microstructural dynamics by in vivo diffusion tensor cardiac magnetic resonance. J Am Coll Cardiol. (2017) 69(6):661–76. 10.1016/j.jacc.2016.11.051

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 150.

  ChenJLiuWZhangHLacyLYangXSongSKet alRegional ventricular wall thickening reflects changes in cardiac fiber and sheet structure during contraction: quantification with diffusion tensor MRI. Am J Physiol Heart Circ Physiol. (2005) 289(5):H1898–907. 10.1152/ajpheart.00041.2005

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 151.

  SharkeySWLesserJRMaronBJ. Takotsubo (stress) cardiomyopathy. Circulation. (2011) 124:e460–2. 10.1161/CIRCULATIONAHA.111.052662

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 152.

  AzzarelliSGalassiARAmicoFGiacoppoMArgentinoVTomaselloSDet alClinical features of transient left ventricular apical ballooning. Am J Cardiol. (2006) 98(9):1273–6. 10.1016/j.amjcard.2006.05.065

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 153.

  StewartJMMedowMABassettBMontgomeryLD. Effects of thoracic blood volume on valsalva maneuver. Am J Physiol Heart Circ Physiol. (2004) 287(2):H798–804. 10.1152/ajpheart.01174.2003

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 154.

  PaurHWrightPTSikkelMBTranterMHMansfieldCO'GaraPet alHigh levels of circulating epinephrine trigger apical cardiodepression in a β2-adrenergic receptor/gi-dependent manner: a new model of takotsubo cardiomyopathy. Circulation. (2012) 126(6):697–706. 10.1161/CIRCULATIONAHA.112.111591

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 155.

  FedorowskiASuttonR. Autonomic dysfunction and postural orthostatic tachycardia syndrome in post-acute COVID-19 syndrome. Nat Rev Cardiol. (2023) 20(5):281–2. 10.1038/s41569-023-00842-w

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 156.

  YoungDB. Control of Cardiac Output. San Rafael (CA): Morgan & Claypool Life Sciences; 2010. Chapter 6, Analysis of Cardiac Output Control in Response to Challenges. Available online at:https://www.ncbi.nlm.nih.gov/books/NBK54474/(accessed August 28, 2024).

  • Google Scholar

• 157.

  VissingSFScherrerUVictorRG. Increase of sympathetic discharge to skeletal muscle but not to skin during mild lower body negative pressure in humans. J Physiol (Lond). (1994) 481(Pt 1):233–41. 10.1113/jphysiol.1994.sp020434

  • CrossRef
  • Google Scholar

• 158.

  VissingSFHjortsøEM. Central motor command activates sympathetic outflow to the cutaneous circulation in humans. J Physiol (Lond). (1996) 492(Pt 3):931–9. 10.1113/jphysiol.1996.sp021359

  • CrossRef
  • Google Scholar

• 159.

  StewartJMPianosiPT. Postural orthostatic tachycardia syndrome: a respiratory disorder?Curr Res Physiol. (2021) 4:1–6. 10.1016/j.crphys.2021.01.002

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 160.

  ToobaRMayugaKAWilsonRTonelliAR. Dyspnea in chronic low ventricular preload states. Ann Am Thorac Soc. (2021) 18(4):573–81. 10.1513/AnnalsATS.202005-581CME

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 161.

  OldhamWMLewisGDOpotowskyARWaxmanABSystromDM. Unexplained exertional dyspnea caused by low ventricular filling pressures: results from clinical invasive cardiopulmonary exercise testing. Pulm Circ. (2016) 6(1):55–62. 10.1086/685054

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 162.

  MelbyDPLuFSakaguchiSZookMBendittDG. Increased impedance to inspiration ameliorates hemodynamic changes associated with movement to upright posture in orthostatic hypotension: a randomized blinded pilot study. Heart Rhythm. (2007) 4(2):128–35. 10.1016/j.hrthm.2006.10.011

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 163.

  ClouseREMayerEAAzizQDrossmanDADumitrascuDLMönnikesHet alFunctional abdominal pain syndrome. Gastroenterology. (2006) 130(5):1492–7. 10.1053/j.gastro.2005.11.062

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 164.

  SantGR. Etiology, pathogenesis, and diagnosis of interstitial cystitis. Rev Urol. (2002) 4 Suppl 1(Suppl 1):S9–S15.

  • Pubmed Abstract
  • Google Scholar

• 165.

  WangJChenYChenJZhangGWuP. Sacral neuromodulation for refractory bladder pain syndrome/interstitial cystitis: a global systematic review and meta-analysis. Sci Rep. (2017) 7:11031. 10.1038/s41598-017-11062-x

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 166.

  EnokaRMDuchateauJ. Rate coding and the control of muscle force. Cold Spring Harb Perspect Med. (2017) 7(10):a029702. 10.1101/cshperspect.a029702

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 167.

  WestgaardRHDe LucaCJ. Motor control of low-threshold motor units in the human trapezius muscle. J Neurophysiol. (2001) 85:1777–81. 10.1152/jn.2001.85.4.1777

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 168.

  Milner-BrownHSSteinRBYemmR. Changes in firing rate of human motor units during linearly changing voluntary contractions. J Physiol (Lond). (1973) 230(2):371–90. 10.1113/jphysiol.1973.sp010193

  • CrossRef
  • Google Scholar

• 169.

  WestadCWestgaardRHDe LucaCJ. Motor unit recruitment and derecruitment induced by brief increase in contraction amplitude of the human trapezius muscle. J Physiol (Lond). (2003) 552(2):645–56. 10.1113/jphysiol.2003.044990

  • CrossRef
  • Google Scholar

• 170.

  SøgaardK. Motor unit recruitment pattern during low-level static and dynamic contractions. Muscle Nerve. (1995) 18(3):292–300. 10.1002/mus.880180305

  • CrossRef
  • Google Scholar

• 171.

  WellsHSYoumansJBMillerDGJr. Tissue pressure (intracutaneous, subcutaneous, and intramuscular) as related to venous pressure, capillary filtration, and other factors. J Clin Invest. (1938) 17(4):489–99. 10.1172/JCI100976

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 172.

  WelshDGSegalSS. Muscle length directs sympathetic nerve activity and vasomotor tone in resistance vessels of hamster retractor. Circ Res. (1996) 79:551–9. 10.1161/01.RES.79.3.551

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 173.

  WelshDGSegalSS. Coactivation of resistance vessels and muscle fibers with acetylcholine release from motor nerves. Am J Physiol Heart Circ Physiol. (1997) 273(1):H156–63. 10.1152/ajpheart.1997.273.1.H156

  • CrossRef
  • Google Scholar

• 174.

  SegalSS. Integration of blood flow control to skeletal muscle: key role of feed arteries. Acta Physiol Scand. (2000) 168(4):511–8. 10.1046/j.1365-201x.2000.00703.x

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 175.

  LindARMcNicolGW. Muscular factors which determine the cardiovascular responses to sustained and rhythmic exercise. Canad Med Ass J. (1967) 96:706–15.

  • Pubmed Abstract
  • Google Scholar

• 176.

  MarshallJMTandonHC. Direct observations of muscle arterioles and venules following contraction of skeletal muscle fibres in the rat. J Physiol (Lond). (1984) 350:447–59. 10.1113/jphysiol.1984.sp015211

  • CrossRef
  • Google Scholar

• 177.

  LarssonSEBengtssonABodegårdLHenrikssonKGLarssonJ. Muscle changes in work-related chronic myalgia. Acta Orthop Scand. (1988) 59(5):552–6. 10.3109/17453678809148783

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 178.

  BengtssonA. The muscle in fibromyalgia. Rheumatology (Oxford). (2002) 41(7):721–4. 10.1093/rheumatology/41.7.721

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 179.

  LarssonSEBodegårdLHenrikssonKGObergPA. Chronic trapezius myalgia. Morphology and blood flow studied in 17 patients. Acta Orthop Scand. (1990) 61(5):394–8. 10.3109/17453679008993548

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 180.

  KevinCMillerMSKnightKL. Electrical stimulation cramp threshold frequency correlates well with the occurrence of skeletal muscle cramps. Muscle Nerve. (2009) 39(3):364368.

  • Google Scholar

• 181.

  BurriEBarbaEHuamanJWCisternasDAccarinoASoldevillaAet alMechanisms of postprandial abdominal bloating and distension in functional dyspepsia. Gut. (2014) 63(3):395–400. 10.1136/gutjnl-2013-304574

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 182.

  AccarinoAPerezFAzpirozFQuirogaSMalageladaJR. Abdominal distention results from caudo-ventral redistribution of contents. Gastroenterology. (2009) 136(5):1544–51. 10.1053/j.gastro.2009.01.067

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 183.

  KimuraBJDalugduganRGilcreaseGW3rdPhanJNShowalterBKWolfsonT. The effect of breathing manner on inferior vena caval diameter. Eur J Echocardiogr. (2011) 12(2):120–3. 10.1093/ejechocard/jeq157

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 184.

  SunYLiLXieRWangBJiangKCaoH. Stress triggers flare of inflammatory bowel disease in children and adults. Front Pediatr. (2019) 7:432. 10.3389/fped.2019.00432

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 185.

  ReismanDSBlockHJBastianAJ. Interlimb coordination during locomotion: what can be adapted and stored?J Neurophysiol. (2005) 94(4):2403–15. 10.1152/jn.00089.2005

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 186.

  ChoiJTBastianAJ. Adaptation reveals independent control networks for human walking. Nat Neurosci. (2007) 10:1055–62. 10.1038/nn1930

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 187.

  PijnappelsMKingmaIWezenbergDReurinkGvan DieënJH. Armed against falls: the contribution of arm movements to balance recovery after tripping. Exp Brain Res. (2010) 201(4):689–99. 10.1007/s00221-009-2088-7

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 188.

  HsiaoETRobinovitchSN. Common protective movements govern unexpected falls from standing height. J Biomech. (1998) 31(1):1–9. 10.1016/S0021-9290(97)00114-0

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 189.

  DissegnaATurattoMChiandettiC. Context-Specific habituation: a review. Animals (Basel). (2021) 11(6):1767. 10.3390/ani11061767

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 190.

  Massé-AlarieHSalomoniSEHodgesPW. The nociceptive withdrawal reflex of the trunk is organized with unique muscle receptive fields and motor strategies. Eur J Neurosci. (2019) 50(2):1932–47. 10.1111/ejn.14369

  • CrossRef
  • Google Scholar

• 191.

  LatremoliereAWoolfCJ. Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain. (2009) 10(9):895–926. 10.1016/j.jpain.2009.06.012

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 192.

  FuehrerEVoudourisDLezkanADrewingKFiehlerK. Tactile suppression stems from specific sensorimotor predictions. Proc Natl Acad Sci U S A. (2022) 119(20):e2118445119. 10.1073/pnas.2118445119

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 193.

  MayA. Chronic pain may change the structure of the brain. Pain. (2008) 137(1):7–15. 10.1016/j.pain.2008.02.034

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 194.

  ManciniFWangAPSchiraMMIsherwoodZJMcAuleyJHIannettiGDet alFine-grained mapping of cortical somatotopies in chronic complex regional pain syndrome. J Neurosci. (2019) 39(46):9185–96. 10.1523/JNEUROSCI.2005-18.2019

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 195.

  SchoneHRMaimon MorROKollamkulamMGerrandCWoollardAKangNVet alStable cortical body maps before and after arm amputation. bioRxiv. [Preprint] (2023). 2023.12.13.571314. 10.1101/2023.12.13.571314

  • CrossRef
  • Google Scholar

• 196.

  Van LeQIsbellLAMatsumotoJNguyenMHoriEMaiorRSet alPulvinar neurons reveal neurobiological evidence of past selection for rapid detection of snakes. Proc Natl Acad Sci U S A. (2013) 110(47):19000–5. 10.1073/pnas.1312648110

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 197.

  KislevMBarkaiR. Neanderthal and woolly mammoth molecular resemblance: genetic similarities may underlie cold adaptation suite. Hum Biol. (2019) 90(2):115–28. 10.13110/humanbiology.90.2.03

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 198.

  RosenbergKRTrevathanWR. An anthropological perspective on the evolutionary context of preeclampsia in humans. J Reprod Immunol. (2007) 76(1-2):91–7. 10.1016/j.jri.2007.03.011

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 199.

  ChalineJ. Increased cranial capacity in hominid evolution and preeclampsia. J Reprod Immunol. (2003) 59(2):137–52. 10.1016/S0165-0378(03)00043-3

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 200.

  VolpeJJ. Cerebellum of the premature infant: rapidly developing, vulnerable, clinically important. J Child Neurol. (2009) 24:1085–104. 10.1177/0883073809338067

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 201.

  WalkerCKKrakowiakPBakerAHansenRLOzonoffSHertz-PicciottoI. Preeclampsia, placental insufficiency, and autism spectrum disorder or developmental delay. JAMA Pediatr. (2015) 169(2):154–62. 10.1001/jamapediatrics.2014.2645

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 202.

  RosenbergKRBraceDLFrayerDWGeiseMCGreenDLTagueRGet alThe functional significance of neandertal pubic length [and comments and reply]. Curr Anthropol. (1988) 29(4):595–617. 10.1086/203678

  • CrossRef
  • Google Scholar

• 203.

  HoraMSladekV. Influence of lower limb configuration on walking cost in late pleistocene humans. J Hum Evol. (2014) 67:19–32. 10.1016/j.jhevol.2013.09.011

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 204.

  SkrzypekGWiniewskiAGriersonP. How cold was it for neanderthals moving to central Europe during warm phases of the last glaciation?Quat Sci Rev. (2011) 30:481–7. 10.1016/j.quascirev.2010.12.018

  • CrossRef
  • Google Scholar

• 205.

  OcobockCLacySNiclouA. Between a rock and a cold place: neanderthal biocultural cold adaptations. Evol Anthropol. (2021) 30(4):262–79. 10.1002/evan.21894

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 206.

  HigginsRRuffC. The effects of distal limb segment shortening on locomotor efficiency in sloped terrain: implications for neandertal locomotor behavior. Am J Phys Anthropol. (2011) 146:336–45. 10.1002/ajpa.21575

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 207.

  AdlerDSBar-OzGBelfer-CohenABar-YosefO. Ahead of the game: middle and upper palaeolithic hunting behaviors in the southern Caucasus. Curr Anthropol. (2006) 47(1):89–118. http://digitalcommons.uconn.edu/anthro_articles/110.1086/432455

  • CrossRef
  • Google Scholar

• 208.

  SteegmannTAJrCernyFJHollidayTW. Neandertal cold adaptation: physiological and energetic factors. Am J Hum Biol. (2002) 14(5):566–83. 10.1002/ajhb.10070

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 209.

  LimmerLSSantonMMcGrathKHarvatiKEl ZaatariS. Differences in childhood stress between neanderthals and early modern humans as reflected by dental enamel growth disruptions. Sci Rep. (2024) 14(1):11293. 10.1038/s41598-024-61321-x

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 210.

  ArnstenAFT. Stress signalling pathways that impair prefrontal cortex structure and function. Nat Rev Neurosci. (2009) 10(6):410–22. 10.1038/nrn2648

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 211.

  YuYZhangSWangGHongXMallowEBWalkerSOet alThe combined association of psychosocial stress and chronic hypertension with preeclampsia. Am J Obstet Gynecol. (2013) 209(438):e1–12. 10.1016/2Fj.ajog.2013.07.003

  • CrossRef
  • Google Scholar

• 212.

  LászlóKDLiuXQSvenssonTWikströmAKLiJOlsenJet alPsychosocial stress related to the loss of a close relative the year before or during pregnancy and risk of preeclampsia. Hypertension. (2013) 62:183–9. 10.1161/HYPERTENSIONAHA.111.00550

  • CrossRef
  • Google Scholar

• 213.

  DiasBGResslerKJ. Parental olfactory experience influences behavior and neural structure in subsequent generations. Nat Neurosci. (2014) 17(1):89–96. 10.1038/nn.3594

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 214.

  GillRCBowesKLKingmaYJ. Effect of progesterone on canine colonic smooth muscle. Gastroenterology. (1985) 88(6):1941–7. 10.1016/0016-5085(85)90023-X

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 215.

  XiaoZLCaoWBiancaniPBeharJ. Nongenomic effects of progesterone on the contraction of muscle cells from the Guinea pig colon. Am J Physiol Gastrointest Liver Physiol. (2006) 290(5):G1008–15. 10.1152/ajpgi.00382.2005

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 216.

  GiddeyTThomasNHudaibARThomasEHXLeJGrayPet alPeak saccadic eye velocity across menstrual phases in naturally cycling women; A pilot study. Compr Psychoneuroendocrinol. (2020) 4:100009. 10.1016/j.cpnec.2020.100009

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 217.

  LacknerJRShenkerB. Proprioceptive influences on auditory and visual spatial localization. J Neurosci. (1985) 5(3):579–83. 10.1523/JNEUROSCI.05-03-00579.1985

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 218.

  ObaydiHPuriBK. Prevalence of premenstrual syndrome in autism: a prospective observer-rated study. J Int Med Res. (2008) 36(2):268–72. 10.1177/147323000803600208

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 219.

  ShimojoSSimionCShimojoEScheierC. Gaze bias both reflects and influences preference. Nat Neurosci. (2003) 6(12):1317–22. 10.1038/nn1150

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 220.

  PärnametsPJohanssonPHallLBalkeniusCSpiveyMJRichardsonDC. Biasing moral decisions by exploiting the dynamics of eye gaze. Proc Natl Acad Sci U S A. (2015) 112(13):4170–5. 10.1073/pnas.1415250112

  • CrossRef
  • Google Scholar

• 221.

  OhlSWohltatCKlieglRPollatosOEngbertR. Microsaccades are coupled to heartbeat. J Neurosci. (2016) 36(4):1237–41. 10.1523/JNEUROSCI.2211-15.2016

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 222.

  Galvez-PolAVirdeePVillacampaJKilnerJ. Active tactile discrimination is coupled with and modulated by the cardiac cycle. Elife. (2022) 11:e78126. 10.7554/eLife.78126

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 223.

  PalserERGlassJFotopoulouAKilnerJM. Relationship between cardiac cycle and the timing of actions during action execution and observation. Cognition. (2021) 217:104907. 10.1016/j.cognition.2021.104907

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 224.

  ErkelensIMBobierWR. Reflexive fusional vergence and its plasticity are impaired in convergence insufficiency. Invest Ophthalmol Vis Sci. (2020) 61(10):21. 10.1167/iovs.61.10.21

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 225.

  BorstingEMitchellGLArnoldLE. Behavioral and emotional problems associated with convergence insufficiency in children: an open trial. J Atten Disord. (2016) 20(10):836–44. 10.1177/1087054713511528

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 226.

  AmerSAAMFouadAMEl-SamahyMHashemAASaatiAASarhanAAet alMental stress, anxiety and depressive symptoms and interleuken-6 level among healthcare workers during the COVID-19 pandemic. J Prim Care Community Health. (2021) 12:21501327211027432. 10.1177/21501327211027432

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 227.

  O'DonovanAHughesBMSlavichGMLynchLCroninMTO'FarrellyCet alClinical anxiety, cortisol and interleukin-6: evidence for specificity in emotion-biology relationships. Brain Behav Immun. (2010) 24(7):1074–7. 10.1016/j.bbi.2010.03.003

  • CrossRef
  • Google Scholar

• 228.

  RealeMCostantiniEGreigNH. Cytokine imbalance in schizophrenia. From research to clinic: potential implications for treatment. Front Psychiatry. (2021) 12:536257. 10.3389/fpsyt.2021.536257

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 229.

  HodesGEMénardCRussoSJ. Integrating interleukin-6 into depression diagnosis and treatment. Neurobiol Stress. (2016) 4:15–22. 10.1016/j.ynstr.2016.03.003

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 230.

  ZouZZhouBHuangYWangJMinWLiT. Differences in cytokines between patients with generalised anxiety disorder and panic disorder. J Psychosom Res. (2020) 133:109975. 10.1016/j.jpsychores.2020.109975

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 231.

  PedersenBKFebbraioMA. Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat Rev Endocrinol. (2012) 8:457–65. 10.1038/nrendo.2012.49

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 232.

  BruunsgaardHGalboHHalkjaer-KristensenJJohansenTLMacLeanDAPedersenBK. Exercise-induced increase in serum interleukin-6 in humans is related to muscle damage. J Physiol. (1997) 49(Pt 3):833–41. 10.1113/jphysiol.1997.sp021972

  • CrossRef
  • Google Scholar

• 233.

  SteensbergAvan HallGOsadaTSacchettiMSaltinBKlarlund PedersenB. Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6. J Physiol. (2000) 29(Pt 1):237–42. 10.1111/j.1469-7793.2000.00237.x

  • CrossRef
  • Google Scholar

• 234.

  SteensbergAFebbraioMAOsadaTSchjerlingPvan HallGSaltinBet alInterleukin-6 production in contracting human skeletal muscle is influenced by pre-exercise muscle glycogen content. J Physiol. (2001) 537(Pt 2):633–9. 10.1111/j.1469-7793.2001.00633.x

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 235.

  HennigarSRMcClungJPPasiakosSM. Nutritional interventions and the IL-6 response to exercise. FASEB J. (2017) 31(9):3719–28. 10.1096/fj.201700080R

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 236.

  FischerCPPlomgaardPHansenAKPilegaardHSaltinBPedersenBK. Endurance training reduces the contraction-induced interleukin-6 mRNA expression in human skeletal muscle. Am J Physiol Endocrinol Metab. (2004) 287(6):E1189–94. 10.1152/ajpendo.00206.2004

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 237.

  FebbraioMASteensbergAKellerCStarkieRLNielsenHBKrustrupPet alGlucose ingestion attenuates interleukin-6 release from contracting skeletal muscle in humans. J Physiol. (2003) 549(Pt 2):607–12. 10.1113/jphysiol.2003.042374

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 238.

  CookMDMartinSAWilliamsCWhitlockKWalligMAPenceBDet alForced treadmill exercise training exacerbates inflammation and causes mortality while voluntary wheel training is protective in a mouse model of colitis. Brain Behav Immun. (2013) 33:46–56. 10.1016/j.bbi.2013.05.005

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 239.

  FebbraioMAOttPNielsenHBSteensbergAKellerCKrustrupPet alHepatosplanchnic clearance of interleukin-6 in humans during exercise. Am J Physiol Endocrinol Metab. (2003) 285(2):E397–402. 10.1152/ajpendo.00134.2003

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 240.

  HernandezMEBecerrilEPerezMLeffPAntonBEstradaSet alProinflammatory cytokine levels in fibromyalgia patients are independent of body mass index. BMC Res Notes. (2010) 3(1):156. 10.1186/1756-0500-3-156

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 241.

  YanSFTrittoIPinskyDLiaoHHuangJFullerGet alInduction of interleukin 6 (IL-6) by hypoxia in vascular cells. Central role of the binding site for nuclear factor-IL-6. J Biol Chem. (1995) 270(19):11463–71. 10.1074/jbc.270.19.11463

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 242.

  IkonomidisIAthanassopoulosGLekakisJVenetsanouKMarinouMStamatelopoulosKet alMyocardial ischemia induces interleukin-6 and tissue factor production in patients with coronary artery disease: a dobutamine stress echocardiography study. Circulation. (2005) 112(21):3272–9. 10.1161/CIRCULATIONAHA.104.532259

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 243.

  HeijinkIHVellengaEBorgerPPostmaDSde MonchyJGKauffmanHF. Interleukin-6 promotes the production of interleukin-4 and interleukin-5 by interleukin-2-dependent and -independent mechanisms in freshly isolated human T cells. Immunology. (2002) 107:316–24. 10.1046/j.1365-2567.2002.01501.x

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 244.

  JanssenSPGayan-RamirezGVan den BerghAHerijgersPMaesKVerbekenEet alInterleukin-6 causes myocardial failure and skeletal muscle atrophy in rats. Circulation. (2005) 111:996–1005. 10.1161/01.CIR.0000156469.96135.0D

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 245.

  SmithSELiJGarbettKMirnicsKPattersonPH. Maternal immune activation alters fetal brain development through interleukin-6. J Neurosci. (2007) 27(40):10695–702. 10.1523/JNEUROSCI.2178-07.2007

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 246.

  KinneyDKMillerAMCrowleyDJHuangEGerberEet alAutism prevalence following prenatal exposure to hurricanes and tropical storms in Louisiana. J Autism Dev Disord. (2008) 38:481–8. 10.1007/s10803-007-0414-0

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 247.

  KinneyDKMunirKMCrowleyDJMillerAM. Prenatal stress and risk for autism. Neurosci Biobehav Rev. (2008) 32(8):1519–32. 10.1016/j.neubiorev.2008.06.004

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 248.

  CourchesneETownsendJAkshoomoffNASaitohOYeung-CourchesneRLincolnAJet alImpairment in shifting attention in autistic and cerebellar patients. Behav Neurosci. (1994) 108(5):848–65. 10.1037//0735-7044.108.5.848

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 249.

  PontifexMBParksACDelli PaoliAGSchroderHSMoserJS. The effect of acute exercise for reducing cognitive alterations associated with individuals high in anxiety. Int J Psychophysiol. (2021) 167:47–56. 10.1016/j.ijpsycho.2021.06.008

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 250.

  JohannessonESimrenMStridHBajorASadikR. Physical activity improves symptoms in irritable bowel syndrome: a randomized controlled trial. Am J Gastroenterol. (2011) 106(5):915–22. 10.1038/ajg.2010.480

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 251.

  EngelsMCrossRKLongMD. Exercise in patients with inflammatory bowel diseases: current perspectives. Clin Exp Gastroenterol. (2017) 11:1–11. 10.2147/CEG.S120816

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 252.

  SonWKYoonWKimSByeonJHLeeJSKimDet alCan moderate-intensity aerobic exercise ameliorate atopic dermatitis?Exp Dermatol. (2020) 29(8):699–702. 10.1111/exd.14138

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 253.

  EPA. Strategies for Saving Energy at Public Water Systems. (2015). Available online at:https://www.epa.gov/sites/production/files/2015-04/documents/epa816f13004.pdf(accessed August 28, 2024).

  • Google Scholar

• 254.

  BrooksGA. The lactate shuttle during exercise and recovery. Med Sci Sports Exerc. (1986) 18(3):360–8. 10.1249/00005768-198606000-00019

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 255.

  BrooksGA. The science and translation of lactate shuttle theory. Cell Metab. (2018) 27(4):757–85. 10.1016/j.cmet.2018.03.008

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 256.

  BrooksGA. Lactate shuttles in nature. Biochem Soc Trans. (2002) 30(2):258–64. 10.1042/bst0300258

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 257.

  StanleyWCGertzEWWisneskiJAMorrisDLNeeseRABrooksA. Systemic lactate kinetics during graded exercise in man. Am J Physiol. (1985) 249(6 Pt 1):E595–602. 10.1152/ajpendo.1985.249.6.E595

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 258.

  SmithDPernetAHallettWABinghamEMarsdenPKAmielSA. Lactate: a preferred fuel for human brain metabolism in vivo. J Cereb Blood Flow Metab. (2003) 23(6):658–64. 10.1097/01.WCB.0000063991.19746.11

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 259.

  SchurrA. Lactate: the ultimate cerebral oxidative energy substrate?J Cereb Blood Flow Metab. (2006) 26(1):142–52. 10.1038/sj.jcbfm.9600174

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 260.

  van HallGStrømstadMRasmussenPJansOZaarMGamCet alBlood lactate is an important energy source for the human brain. J Cereb Blood Flow Metab. (2009) 29(6):1121–9. 10.1038/jcbfm.2009.35

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 261.

  GertzEWWisneskiJAStanleyWCNeeseRA. Myocardial substrate utilization during exercise in humans. Dual carbon-labeled carbohydrate isotope experiments. J Clin Invest. (1998) 82(6):2017–25. 10.1172/JCI113822

  • CrossRef
  • Google Scholar

• 262.

  HoqueRFarooqAGhaniAGorelickFMehalWZ. Lactate reduces liver and pancreatic injury in toll-like receptor- and inflammasome-mediated inflammation via GPR81-mediated suppression of innate immunity. Gastroenterology. (2014) 146(7):1763–74. 10.1053/j.gastro.2014.03.014

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 263.

  ErreaACayetDMarchettiPTangCKluzaJOffermannsSet alLactate inhibits the pro-inflammatory response and metabolic reprogramming in murine macrophages in a GPR81-independent manner. PLoS One. (2016) 11(11):e0163694. 10.1371/journal.pone.0163694

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 264.

  GroussardCMorelIChevanneMMonnierMCillardJDelamarcheA. Free radical scavenging and antioxidant effects of lactate ion: an in vitro study. J Appl Physiol. (2000) 89(1):169–75. 10.1152/jappl.2000.89.1.169

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 265.

  O'NeillMCUmbergerBRHolowkaNBLarsonSGReiserPJ. Chimpanzee super strength and human skeletal muscle evolution. Proc Natl Acad Sci U S A. (2017) 114(28):7343–8. 10.1073/pnas.1619071114

  • CrossRef
  • Google Scholar

• 266.

  LiebermanDE. Exercised: The Science of Physical Activity, Rest and Health. Penguin (June 3, 2021), ISBN-10:0141986360).

  • Google Scholar

• 267.

  GaoWSannaMChenYTsaiMWenC. Occupational sitting time, leisure physical activity, and all-cause and cardiovascular disease mortality. JAMA Netw Open. (2024) 7(1):e2350680. 10.1001/jamanetworkopen.2023.50680

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 268.

  StamatakisEGaleJBaumanAEkelundUHamerMDingD. Sitting time, physical activity, and risk of mortality in adults. J Am Coll Cardiol. (2019) 73(16):2062–72. 10.1016/j.jacc.2019.02.031

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 269.

  EricksonKIVossMWPrakashRSBasakCSzaboAChaddockLet alExercise training increases size of hippocampus and improves memory. Proc Natl Acad Sci U S A. (2011) 108(7):3017–22. 10.1073/pnas.1015950108

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 270.

  NgQXHoCYXChanHWYongBZJYeoWS. Managing childhood and adolescent attention-deficit/hyperactivity disorder (ADHD) with exercise: a systematic review. Complement Ther Med. (2017) 34:123–8. 10.1016/j.ctim.2017.08.018

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 271.

  AbrantesAMStrongDRCohnACameronAYGreenbergBDManceboMCet alAcute changes in obsessions and compulsions following moderate-intensity aerobic exercise among patients with obsessive-compulsive disorder. J Anxiety Disord. (2009) 23(7):923–7. 10.1016/j.janxdis.2009.06.008

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 272.

  Sá FilhoASCheniauxEde PaulaCCMurillo-RodriguezETeixeiraDMonteiroDet alExercise is medicine: a new perspective for health promotion in bipolar disorder. Expert Rev Neurother. (2020) 20(11):1099–107. 10.1080/14737175.2020.1807329

  • CrossRef
  • Google Scholar

• 273.

  ShimadaTItoSMakabeAYamanushiATakenakaAKobayashiM. Aerobic exercise and cognitive functioning in schizophrenia: a pilot randomized controlled trial. Psychiatry Res. (2019) 282:112638. 10.1016/j.psychres.2019.112638

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 274.

  DimeoFBauerMVarahramIProestGHalterU. Benefits from aerobic exercise in patients with major depression: a pilot study. Br J Sports Med. (2001) 35(2):114–7. 10.1136/bjsm.35.2.114

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 275.

  FetznerMGAsmundsonGJ. Aerobic exercise reduces symptoms of posttraumatic stress disorder: a randomized controlled trial. Cogn Behav Ther. (2015) 44(4):301–13. 10.1080/16506073.2014.916745

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 276.

  PearceEJollyKJonesLLMatthewmanGZanganehMDaleyA. Exercise for premenstrual syndrome: a systematic review and meta-analysis of randomised controlled trials. BJGP Open. (2020) 4(3):bjgpopen20X101032. 10.3399/bjgpopen20X101032

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 277.

  LevinONetzYZivG. Behavioral and neurophysiological aspects of inhibition-the effects of acute cardiovascular exercise. J Clin Med. (2021) 10(2):282. 10.3390/jcm10020282

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 278.

  BrownRAAbrantesAMReadJPMarcusBHJakicicJStrongDRet alA pilot study of aerobic exercise as an adjunctive treatment for drug dependence. Ment Health Phys Act. (2010) 3(1):27–34. 10.1016/j.mhpa.2010.03.001

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 279.

  KasperRWElliottJCGiesbrechtB. Multiple measures of visual attention predict novice motor skill performance when attention is focused externally. Hum Mov Sci. (2012) 31(5):1161–74. 10.1016/j.humov.2011.11.005

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 280.

  McGorryRWLinJH. Flexion relaxation and its relation to pain and function over the duration of a back pain episode. PLoS One. (2012) 7(6):e39207. 10.1371/journal.pone.0039207

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 281.

  HesselALLindstedtSLNishikawaKC. Physiological mechanisms of eccentric contraction and its applications: a role for the giant titin protein. Front Physiol. (2017) 8:70. 10.3389/fphys.2017.00070

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 282.

  LepleyLKLepleyASOnateJAGroomsDR. Eccentric exercise to enhance neuromuscular control. Sports Health. (2017) 9(4):333–40. 10.1177/1941738117710913

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 283.

  BaxterBABarossAWRyanDJWrightBHKayAD. The acute and repeated bout effects of multi-joint eccentric exercise on physical function and balance in older adults. Eur J Appl Physiol. (2023) 123(10):2131–43. 10.1007/s00421-023-05226-z

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 284.

  WhittleseySNvan EmmerikREHamillJ. The swing phase of human walking is not a passive movement. Motor Control. (2000) 4(3):273–92. 10.1123/mcj.4.3.273

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 285.

  CudejkoTGardinerJAkpanAD'AoûtK. Minimal footwear improves stability and physical function in middle-aged and older people compared to conventional shoes. Clin Biomech (Bristol, Avon). (2020) 71:139–45. 10.1016/j.clinbiomech.2019.11.005

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 286.

  CudejkoTGardinerJAkpanAD'AoûtK. Minimal shoes improve stability and mobility in persons with a history of falls. Sci Rep. (2020) 10(1):21755. 10.1038/s41598-020-78862-6

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 287.

  GabrielAFuchsKHallerBSulowska-DaszykIHorstmannTKonradA. A four-week minimalist shoe walking intervention influences foot posture and balance in young adults-a randomized controlled trial. PLoS One. (2024) 19(6):e0304640. 10.1371/journal.pone.0304640

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 288.

  CurtisRWillemsCPaolettiPD'AoûtK. Daily activity in minimal footwear increases foot strength. Sci Rep. (2021) 11(1):18648. 10.1038/s41598-021-98070-0

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 289.

  LimSBCleworthTWHorslenBCBlouinJSInglisJTCarpenterMG. Postural threat influences vestibular-evoked muscular responses. J Neurophysiol. (2017) 117(2):604–11. 10.1152/jn.00712.2016

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 290.

  NaranjoENAllumJHInglisJTCarpenterMG. Increased gain of vestibulospinal potentials evoked in neck and leg muscles when standing under height-induced postural threat. Neuroscience. (2015) 293:45–54. 10.1016/j.neuroscience.2015.02.026

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 291.

  BartOBar-HaimYWeizmanELevinMSadehAMintzM. Balance treatment ameliorates anxiety and increases self-esteem in children with comorbid anxiety and balance disorder. Res Dev Disabil. (2009) 30(3):486–95. 10.1016/j.ridd.2008.07.008

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 292.

  SheferSGordonCAvrahamKBMintzM. Balance deficit enhances anxiety and balance training decreases anxiety in vestibular mutant mice. Behav Brain Res. (2015) 276:76–83. 10.1016/j.bbr.2014.06.046

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 293.

  FeldmanRSchreiberSPickCGBeenE. Gait, balance, mobility and muscle strength in people with anxiety compared to healthy individuals. Hum Mov Sci. (2019) 67:102513. 10.1016/j.humov.2019.102513

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 294.

  KoganELidorRBartOBar-HaimYMintzM. Comorbidity between balance and anxiety disorders: verification in a normal population. J Psychol. (2008) 142(6):601–13. 10.3200/JRLP.142.6.601-614

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 295.

  WangHGaoXShiYWuDLiCWangW. Effects of trunk posture on cardiovascular and autonomic nervous systems: a pilot study. Front Physiol. (2022) 13:1009806. 10.3389/fphys.2022.1009806

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 296.

  Espinoza-ValdésYCórdova-ArellanoREspinoza-EspinozaMMéndez-AlfaroDBustamante-AguirreJPMaureira-ParejaHAet alAssociation between cardiac autonomic control and postural control in patients with Parkinson’s disease. Int J Environ Res Public Health. (2020) 18(1):249. 10.3390/ijerph18010249

  • CrossRef
  • Google Scholar

• 297.

  SelingerJCHicksJLJacksonRWWall-SchefflerCMChangDDelpSL. Running in the wild: energetics explain ecological running speeds. Curr Biol. (2022) 32(10):2309–2315.e3. 10.1016/j.cub.2022.03.076

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 298.

  FerneeCRGabrielsenLEAndersenAJMeselT. Emerging stories of self: long-term outcomes of wilderness therapy in Norway. J Adventure Educ Outdoor Learn. (2020) 21(1):67–81. 10.1080/14729679.2020.1730205

  • CrossRef
  • Google Scholar

• 299.

  LittmanAJBratmanGNLehavotKEngelCCFortneyJCPetersonAet alNature versus urban hiking for veterans with post-traumatic stress disorder: a pilot randomised trial conducted in the pacific northwest USA. BMJ Open. (2021) 11(9):e051885. 10.1136/bmjopen-2021-051885

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 300.

  GabrielsenLEHarperNJFerneeCR. What are constructive anxiety levels in wilderness therapy? An exploratory pilot study. Complement Ther Clin Pract. (2019) 37:51–7. 10.1016/j.ctcp.2019.08.007

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 301.

  KoteraYRichardsonMSheffieldD. Effects of shinrin-yoku (forest bathing) and nature therapy on mental health: a systematic review and meta-analysis. Int J Ment Health Addiction. (2022) 20:337–61. 10.1007/s11469-020-00363-4

  • CrossRef
  • Google Scholar

• 302.

  BarkerSBDawsonKS. The effects of animal-assisted therapy on anxiety ratings of hospitalized psychiatric patients. Psychiatr Serv. (1998) 49(6):797–801. 10.1176/ps.49.6.797

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 303.

  RossettiJKingC. Use of animal-assisted therapy with psychiatric patients. J Psychosoc Nurs Ment Health Serv. (2010) 48(11):44–8. 10.3928/02793695-20100831-05

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 304.

  GohACWongSZaroffJGShafaeeNLundstromRJ. Comparing anxiety and depression in patients with takotsubo stress cardiomyopathy to those with acute coronary syndrome. J Cardiopulm Rehabil Prev. (2016) 36(2):106–11. 10.1097/HCR.0000000000000152

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 305.

  GarciaJSheaM. Association between takotsubo cardiomyopathy, arrhythmias and anxiety or depression. A retrospective study. J Am Coll Cardiol. (2021) 77(18_Supplement_1):790. 10.1016/S0735-1097(21)02149-5

  • CrossRef
  • Google Scholar

• 306.

  AlbertCMChaeCURexrodeKMMansonJEKawachiI. Phobic anxiety and risk of coronary heart disease and sudden cardiac death among women. Circulation. (2005) 111(4):480–7. 10.1161/01.CIR.0000153813.64165.5D

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 307.

  WaltersKRaitGPetersenIWilliamsRNazarethI. Panic disorder and risk of new onset coronary heart disease, acute myocardial infarction, and cardiac mortality: cohort study using the general practice research database. Eur Heart J. (2008) 29(24):2981–8. 10.1093/eurheartj/ehn477

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 308.

  SmollerJWPollackMHWassertheil-SmollerSJacksonRDObermanAWongNDet alPanic attacks and risk of incident cardiovascular events among postmenopausal women in the women’s health initiative observational study. Arch Gen Psychiatry. (2007) 64(10):1153–60. 10.1001/archpsyc.64.10.1153

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 309.

  PalombiniERichardsonJMcAllisterEVealeDThomsonAB. When self-harm is about preventing harm: emergency management of obsessive-compulsive disorder and associated self-harm. BJPsych Bull. (2021) 45(2):109–14. 10.1192/bjb.2020.70

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 310.

  BlanchardAChihuriSDiGuiseppiCGLiG. Risk of self-harm in children and adults with autism spectrum disorder: a systematic review and meta-analysis. JAMA Netw Open. (2021) 4(10):e2130272. 10.1001/jamanetworkopen.2021.30272

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 311.

  SampsonKNUpthegroveRAbu-AkelAHaqueSWoodSJReniersR. Co-occurrence of autistic and psychotic traits: implications for depression, self-harm and suicidality. Psychol Med. (2021) 51(8):1364–72. 10.1017/S0033291720000124

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 312.

  CoxBJDirenfeldDMSwinsonRPNortonGR. Suicidal ideation and suicide attempts in panic disorder and social phobia. Am J Psychiatry. (1994) 151(6):882–7. 10.1176/ajp.151.6.882

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 313.

  HuangMYenCLungF. Moderators and mediators among panic, agoraphobia symptoms, and suicidal ideation in patients with panic disorder. Compr Psychiatry. (2010) 51(3):243–9. 10.1016/j.comppsych.2009.07.005

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 314.

  Dell'OssoLCarpitaBMutiDMorelliVSalarpiGSalerniAet alMood symptoms and suicidality across the autism spectrum. Compr Psychiatry. (2019) 91:34–8. 10.1016/j.comppsych.2019.03.004

  • CrossRef
  • Google Scholar

• 315.

  HedleyDUljarevićMCaiRYBurySMStokesMAEvansDW. Domains of the autism phenotype, cognitive control, and rumination as transdiagnostic predictors of DSM-5 suicide risk. PloS One. (2021) 16(1):e0245562. 10.1371/journal.pone.0245562

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 316.

  FergusonLMDrummondGB. Acute effects of fentanyl on breathing pattern in anaesthetized subjects. Br J Anaesth. (2006) 96(3):384–90. 10.1093/bja/ael011

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 317.

  GaziAHSundararajSHarrisonABGurelNZWittbrodtMTShahAJet alTranscutaneous cervical Vagus nerve stimulation lengthens exhalation in the context of traumatic stress. IEEE EMBS Int Conf Biomed Health Inform. (2021):1–4. 10.1109/BHI50953.2021.9508534

  • CrossRef
  • Google Scholar

• 318.

  StriebelJMKalapatapuRK. The anti-suicidal potential of buprenorphine: a case report. Int J Psychiatry Med. (2014) 42(2):169–74. 10.2190/PM.47.2.g

  • CrossRef
  • Google Scholar

• 319.

  YovellYBarGMashiahMBaruchYBriskmanIAsherovJet alUltra-low-dose buprenorphine as a time-limited treatment for severe suicidal ideation: a randomized controlled trial. Am J Psychiatry. (2016) 173(5):491–8. 10.1176/appi.ajp.2015.15040535

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 320.

  AaronsonSTSearsPRuvunaFBunkerMConwayCRDoughertyDDet alA 5-year observational study of patients with treatment-resistant depression treated with Vagus nerve stimulation or treatment as usual: comparison of response, remission, and suicidality. Am J Psychiatry. (2017) 174(7):640–8. 10.1176/appi.ajp.2017.16010034

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 321.

  BalbanMYNeriEKogonMMWeedLNourianiBJoBet alBrief structured respiration practices enhance mood and reduce physiological arousal. Cell Reports Medicine. (2023) 4:100895. 10.1016/j.xcrm.2022.100895

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 322.

  LeyroTMVersellaMVYangMJBrinkmanHRHoytDLLehrerP. Respiratory therapy for the treatment of anxiety: meta-analytic review and regression. Clin Psychol Rev. (2021) 84:101980. 10.1016/j.cpr.2021.101980

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 323.

  CainMKKaboskiJRGilgerJW. Profiles and academic trajectories of cognitively gifted children with autism spectrum disorder. Autism. (2019) 23(7):1663–74. 10.1177/1362361318804019

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 324.

  JamesI. Singular scientists. J R Soc Med. (2003) 96(1):36–9. 10.1177/014107680309600112

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 325.

  DohnAGarza-VillarrealEAHeatonPVuustP. Do musicians with perfect pitch have more autism traits than musicians without perfect pitch? An empirical study. PLoS One. (2012) 7(5):e37961. 10.1371/journal.pone.0037961

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 326.

  GoodwinRDWeinbergerAHKimJHWuMGaleaS. Trends in anxiety among adults in the United States, 2008–2018: rapid increases among young adults. J Psychiatr Res. (2020) 130:441–6. 10.1016/j.jpsychires.2020.08.014

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 327.

  RussellGStapleySNewlove-DelgadoTSalmonAWhiteRWarrenFet alTime trends in autism diagnosis over 20 years: a UK population-based cohort study. J Child Psychol Psychiatry. (2022) 63(6):674–82. 10.1111/jcpp.13505

  • Pubmed Abstract
  • CrossRef
  • Google Scholar