Applications of functional near-infrared spectroscopy in non-drug therapy of traditional Chinese medicine: a review

Non-drug therapies of traditional Chinese medicine (TCM), including acupuncture, massage, tai chi chuan, and Baduanjin, have emerged as widespread interventions for the treatment of various diseases in clinical practice. In recent years, preliminary studies on the mechanisms of non-drug therapies of TCM have been mostly based on functional near-infrared spectroscopy (fNIRS) technology. FNIRS is an innovative, non-invasive tool to monitor hemodynamic changes in the cerebral cortex. Our review included clinical research conducted over the last 10 years, establishing fNIRS as a reliable and stable neuroimaging technique. This review explores new applications of this technology in the field of neuroscience. First, we summarize the working principles of fNIRS. We then present preventive research on the use of fNIRS in healthy individuals and therapeutic research on patients undergoing non-drug therapies of TCM. Finally, we emphasize the potential for encouraging future advancements in fNIRS studies to establish a theoretical framework for research in related fields.


Introduction
Non-drug therapies of TCM, such as acupuncture, massage, tai chi chuan, and Baduanjin, are based on the theory of meridians and viscera in TCM.The advantages of TCM through body adjustments, heart adjustments, and breathing regulation, include regulating motor function, balance, coordination ability, and overall disease resistance and rehabilitation ability of patients at multiple levels and angles (Guo et al., 2023).TCM characteristics also include fewer adverse reactions and high clinical acceptance, which are widely used in the prevention and treatment of diseases (Li et al., 2018).Therefore, an increasing number of studies have focused on non-drug therapies of TCM.Although the scientific mechanisms of non-drug therapies of TCM remain unclear, recent studies have demonstrated that acupuncture, massage, tai chi chuan, and Baduanjin cause interactions within Fu et al. 10.3389/fnins.2023.1329738GRAPHICAL ABSTRACT the nervous system, especially regarding neuronal response regulation in the human brain (Chen Y. F. et al., 2022;Wang et al., 2022;Xu L. P.et al., 2022;Yao et al., 2022;Chen L. et al., 2023).However, the human brain is the least accessible organ; therefore, in vivo studies of the human brain rely predominantly on neuroimaging.Traditional brain imaging techniques include functional magnetic resonance imaging (fMRI) (Zhu et al., 2015) and electroencephalography (EEG) (Yu et al., 2019).fMRI uses magnetic fields to measure responses that depend on the blood oxygen level, a proxy for brain activity, in cortical and subcortical brain regions.Its ability to image subcortical regions and high spatial resolution has made fMRI the neuroimaging method of choice for investigating brain function in pediatric populations.fMRI is the gold standard for in vivo imaging of the human brain (Gossé et al., 2022).However, fMRI has a poor temporal resolution, high sensitivity to motion artifacts, and is relatively expensive.EEG and fMRI are complementary neuroimaging techniques.fMRI measures changes in blood flow, whereas EEG measures changes in electrical charges in the brain (Keren et al., 2018).Although EEG has fewer limitations than fMRI, its spatial positioning is poor.These limitations make the widespread application of fMRI and EEG in the study of the underlying brain mechanisms of non-drug therapies of TCM unappealing.
Functional near-infrared spectroscopy (fNIRS) uses nearinfrared light to monitor brain activity (Pinti et al., 2020).Compared to traditional functional brain imaging technologies, fNIRS is less susceptible to noise and requires less restriction of head or body activity than MRI and computed tomography (Wilcox and Biondi, 2015).Although both fNIRS and fMRI measure alterations in blood flow in the brain, fNIRS has contributed significantly to the field of neuroscience by studying real-life scenarios, high-workload environments, and face-to-face interactions that cannot be evaluated using fMRI (Hirsch et al., 2021).fNIRS is highly versatile, can be used simultaneously with electrophysiological signal monitoring equipment, has better spatial resolution than EEG, and can potentially be used in natural environments (Llana et al., 2022).fNIRS is also insensitive to the movement of study participants; therefore, motion interference in its signals is much smaller than that in electrical signals, making it more suitable for application in natural environments (Quaresima and Ferrari, 2016).In addition, fNIRS is relatively inexpensive and can be used on a large scale.
Due to frequent repeated measurements, fNIRS can be easily employed in longitudinal studies, which are becoming increasingly important for investigating the development and treatment of limb movements, mood, cognitive function, and consciousness disorders (Jang et al., 2020;Zhang et al., 2021;Khan et al., 2022;Liu et al., 2022).
Using fNIRS for assessing cerebral blood flow (CBF) changes during neuronal activation gradually increased in the mid-80s (Csipo et al., 2019).fNIRS possesses potential for widespread application in the study of non-drug therapies of TCM owing to its safety, affordability, portability, and high temporal resolution.Although several fNIRS studies on TCM applications have been conducted, to the best of our knowledge, no review article has explored most TCM applications using fNIRS.Therefore, we present a review of TCM applications of fNIRS and highlight the future perspectives of this modality and its clinical applications (Graphical Abstract).

Basic principle of fNIRS
Upon receiving stimulation from the internal body or external environment, neural activity in certain brain regions is enhanced, leading to increased oxygen consumption and changes in the concentrations of oxygenated hemoglobin (oxy-Hb, HbO 2 ) and deoxyhemoglobin (deoxy-Hb, dHb) in the blood vessels.This triggers a range of brain regulatory activities including local vasodilation and increased CBF (Claassen et al., 2021).This process is known as neurovascular coupling (Liao et al., 2013;Herold et al., 2018).Changes in HbO 2 and dHb concentrations in the blood form the basis for fNIRS testing.
Brain tissue is relatively transparent to NIRS; fNIRS is performed using near-infrared light with a wavelength of 700-900 nm in the medical field.HbO 2 and dHb, the main chromophores in the near-infrared spectrum of blood, can absorb near-infrared light and cause light intensity attenuation; however, their absorption coefficients differ (Jöbsis, 1977;Almajidy et al., 2020).During fNIRS detection, the light source emitter emits photons and projects them onto the scalp of the participant, which then passes through the skull into the upper cortical region.Some of the photons are absorbed by HbO 2 and dHb, while the unabsorbed photons are scattered, reflected, and return to the scalp surface along an elliptical path to be received by the detector of the fNIRS device (Rupawala et al., 2018;Paulmurugan et al., 2021).According to the modified Bier-Lambert law, the number of chromophore groups can be estimated by the attenuation of photons, that is, the alterations in HbO 2 and dHb concentrations can be specifically calculated, particularly the increase in HbO 2 concentration, which is an indirect reflection of the neural activity (Soekadar et al., 2021).fNIRS signals are more sensitive to microvessels with diameters of < 1 mm (Ferrari and Quaresima, 2012).Photon absorption increases with an increase in the vascular diameter, thus resulting in a decrease or even disappearance of light signals received by the scalp surface and eventually decreasing in the sensitivity of fNIRS detection (Ferrari and Quaresima, 2012).The fNIRS data contain noise from various sources, mainly physiological processes (respiration and heartbeat), head movement, and device factors, which may mask or confuse task-related cortical functional signals.
Therefore, it is necessary to preprocess the collected fNIRS data and conduct a statistical analysis.Relevant studies have reviewed these methods (Tak and Ye, 2014;Kamran et al., 2016;Chen W. L. et al., 2020;Dans et al., 2021).
Functional near-infrared spectroscopy reveals the brain effects of non-drug therapies of TCM, which have been applied for the treatment of cognitive disorders, depression, anxiety, limb movement disorders, pain, attention deficit/hyperactivity disorder, and myopia in children.Clinical research using fNIRS requires a specific data acquisition scheme, which has two main design paradigms, namely task-based and resting-state-based.In taskbased research, participants perform certain tasks or receive stimuli during the fNIRS data collection.The type of task or stimulus presentation has a block or event-related design.Most resting-state designs include longitudinal studies on treatment of a specific condition, with fNIRS data collected before and after the intervention.Acupuncture, massage, tai chi chuan, and Baduanjin are non-drug therapies of TCM, which have obvious TCM characteristics; thus, appropriate treatment methods should be adapted for designing the data-acquisition scheme for fNIRS detection.For example, acupuncture and massage operations performed by doctors have a short duration, the task method can be designed to observe brain activation areas and a resting state to observe the functional connectivity (FC) between the regions of interest.However, the tai chi chuan and Baduanjin exercises have a longer single-exercise duration, rendering the resting-state design more suitable.

Review methods
Studies were identified by a comprehensive search of the following databases: PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), Wan Fang database and Chinese Scientific Journal Database (VIP).The search was conducted between January 1, 2014, and September 30, 2023.The search terms in the English and Chinese literature were (acupuncture OR tuina OR massage OR moxibustion OR guasha OR cupping OR Tai Chi OR Baduanjin OR wuqinxi OR yijinjing OR TCM Five Element Music Therapy) and (fNIRS OR Functional Near-Infrared Spectroscopy).

Results
After searching for keywords, 46 articles about non-drug therapies of TCM and fNIRS were selected, of which 40 were conducted in China and 6 in foreign countries.There were 12 studies on traditional sports, 32 on acupuncture and 2 on massage (Tables 1, 2).et al., 2014;Liu et al., 2021).Moreover, many studies have used fNIRS to explore the effects of tai chi chuan training on brain function.Three studies investigated the impact of tai chi chuan on brain inhibition and control (Yang, 2019;Yang et al., 2020;Xie, 2022).The cognitive control task (flanker task) was conducted concurrently to measure and compare HbO 2 concentrations in elderly individuals who practiced tai chi chuan regularly and those who engaged in normal daily activities.Results revealed that tai chi chuan training enhances brain inhibition and control in older adults while increasing HbO 2 concentrations in the prefrontal lobe (Yang, 2019;Yang et al., 2020;Xie, 2022).In addition, three studies have explored the impact of tai chi chuan on brain functional connectivity.These studies demonstrated significantly higher wavelet phase coherence values, indicating the strength of functional connectivity between the prefrontal cortex (PFC), motor cortex (MC), and occipital cortex (OC) of tai chi chuan athletes compared to beginners at frequencies I, II, III, IV, and V (Xie et al., 2019;Chen W. et al., 2022;Wang et al., 2022).From a coupling direction perspective, beginners in tai chi chuan demonstrated the main coupling direction in the left brain with the right PFC, right MC (RMC), right OC, and left OC coupled toward the left MC (LMC) (Xie et al., 2019).In contrast, tai chi chuan athletes demonstrated a coupling direction from the PFC, LMC, and OC toward the RMC during rest, which varied significantly from the left-brain drive pattern observed in tai chi chuan beginners.These findings suggest changes in interactions among brain regions following long-term tai chi chuan training (Xie et al., 2019;Chen W. et al., 2022).A significant increase in functional connectivity between the left PFC and the right sensory-motor area and between the left and right sensory-motor areas was observed in longterm tai chi chuan practitioners upon transitioning from a resting state to a moving state (Wang et al., 2022).Two studies have investigated the effect of tai chi chuan on lower limb motor function.HbO 2 concentrations were measured during the singleleg standing movements of tai chi chuan.The auxiliary motor area exhibited higher activation during the right leg kicking movement in tai chi chuan than during conventional single-leg support movement.Additionally, cerebral cortex activation is negatively correlated with postural shaking (Chen et al., 2021).Another study measured hemoglobin concentrations during negotiating obstacle with cognitive task.Tai chi chuan practice improved cognitive function in the elderly through bilateral activation of the PFC and prioritized gait performance when negotiating obstacles under dual-task conditions (Chen Y. et al., 2022).In conclusion, the study of the brain mechanism of tai chi chuan using fNIRS mainly focused on the influence of tai chi chuan on inhibitory control ability, functional connectivity of brain areas, and limb motor function.Tai chi positively impacted these functions.Tai chi exercises can activate the prefrontal lobe and increase the strength of the functional connections between the prefrontal lobe and other brain areas.

Baduanjin
Baduanjin, a traditional Chinese healthcare movement that focuses on the "unity of form and spirit, " integrating control, breathing movements, and physical activities, plays an active role in disease prevention and rehabilitation.Jiang et al. (2019) used fNIRS to collect brain blood-oxygen signals from elderly individuals who had been exercising for a long time and those who had not practiced Baduanjin while also evaluating their cognitive function through language fluency tasks.They found that compared with elderly individuals who had not practiced Baduanjin, those who had been exercising for a long time performed better in language fluency tasks and had greater HbO 2 concentrations in the PFC, thereby suggesting the positive impact of Baduanjin on the cognitive performance of the elderly (Jiang et al., 2019).Yao et al. (2022) found that, in addition to the Baduanjin exercise, Baduanjin imagination can also shorten the reaction time of the inhibition control task and improve the cognitive performance of the elderly (Yao et al., 2022).Moreover, Baduanjin imagination has the following advantages: (i) it is not limited by the venue, (ii) it is safe and convenient to perform, and (iii) it can be used as an alternative training method to enhance cognitive ability in the elderly.A study using the Stroop task demonstrated improved inhibitory control ability in college students after 12 weeks of Baduanjin intervention, and a correlation between the improvement in student inhibitory control ability upon Baduanjin intervention and the left dorsolateral prefrontal lobe was also identified (Li, 2020).The language fluency task and Stroop task used in the above studies were designed to assess cognitive abilities.The research results showed that both Baduanjin training and imagination can improve cognitive abilities and activate the prefrontal lobe, an important brain area for executive function, and plays a crucial role in ensuring attention allocation and enhancing cognitive control.Therefore, it is speculated that the improvement in cognition by Baduanjin may be related to the activation of the frontal lobe.

Acupuncture
Many studies have evaluated the cortical responses of acupuncture in healthy participants using fNIRS.The block method was the mainly used study design; the evaluated parameter included deqi induced by acupuncture and acupuncture reinforcing and draining methods.Research on deqi induced by acupuncture mainly aims to observe the brain response during deqi to find possible evidence for the clinical treatment of diseases.Si et al. ( 2021) explored the effects of acupuncture deqi at the Hegu (LI4) point during fNIRS scanning.The results demonstrated that the bilateral prefrontal and motor cortices were significantly inhibited during acupuncture and the HbO 2 concentration decreased.During twirling needling, the FC of the bilateral PFC increased significantly.Graph-theory analysis revealed that twirling needling improved the global efficiency of the network and reduced the length of the shortest path.Thus, acupuncture at the Hegu acupoint can regulate functional coordination between the PFC and MC.Fernandez Rojas et al. ( 2019) also demonstrated reduced hemodynamic response of the cerebral cortex and significant cortical activity inhibition during acupuncture at the Hegu point, which could indicate the underlying mechanism of the analgesic effect of acupuncture at the Hegu point.Song et al. (2023) demonstrated that acupuncture mainly activates the bilateral prefrontal lobes and enhances the functional connectivity between the frontal, parietal, and temporal lobes through a study of the Shousanli (LI10) acupoint, thereby indicating that the brain regions related to thinking and cognition play a role in the process of needling the Zusanli (ST36) acupoint to obtain deqi.Yuan et al. (2021)  temple of healthy participants while collecting the fNIRS data.The results demonstrated that PFC excitability decreased after magnetic stimulation of the Shenmen (HT7) acupoint compared with that in the resting state; moreover, the HbO 2 concentration decreased significantly.We believe that the decrease in the blood oxygen levels confirm the sedative effect of the Shenmen acupoint.The above fNIRS research shows that acupoints have specific cortical reactions when they get deqi, and acupuncture at different acupoints has different effects on cerebral cortex hemodynamics, and acupuncture can achieve therapeutic effects through the cortical network.Hemodynamic changes and functional connections in the cerebral cortex can be used as biomarkers to quantify the regulatory effects of acupuncture.
Studies on acupuncture reinforcement and reduction have mainly focused on the differences in the brain effects attributed to various needling techniques at the same acupoint.Cao et al. (2023) recruited healthy participants to study the brain responses of three different methods of reinforcement and reduction, namely liftingthrusting reinforcing manipulation, lifting-thrusting reducing manipulation, and reinforcing-reducing manipulation with liftingthrusting at the Quchi (LI11) acupoint.The results revealed that different manipulations had different effects on inducing brain activation and altering the functional connectivity between the brain regions.Qu et al. (2023) recruited healthy participants to receive the "Shaoshanhuo reinforcing" and "Toutianliang reducing" acupuncture manipulations at the left Quchi point at different times (Qu et al., 2023).The results revealed that the Shaoshanhuo reinforcing method activated the bilateral primary MC and the left primary somatosensory cortex.During the Toutianliang reducing method, the bilateral PFC and primary MC were activated, and the FC between the left PFC and primary MC increased; however, the differences between the two reinforcement methods were not significant.In addition, Chen L. et al. (2023) found that even during reinforcing-reducing manipulation with the lifting-thrusting method at the Quchi point, the frontal lobe cortex of the participant and the acupuncturist revealed increased inter-brain neural synchronization, which was related to the participant's acupuncture sensation.Different reinforcing and reducing methods at the same acupoint can have opposite effects, and the difference of cortical response displayed by fNIRS may be the central mechanism leading to different clinical effects.

Application of fNIRS in non-drug treatment of patients 4.2.1 Cognitive dysfunction and disturbances of consciousness
Cognition is a complex process in which the brain receives and processes various types of information, such as memory, language, visual-spatial awareness, execution, calculation, understanding, and judgment.The underlying basis of cognition depends on the proper functioning of brain regions closely linked to the neural network in each brain region.Therefore, fNIRS reveals the therapeutic mechanism of TCM in treating patients with cognitive impairment by detecting changes in the HbO 2 concentration in the cerebral cortex of patients with cognitive impairment (Eun-Sun et al., 2018;Ghafoor et al., 2019;Chen J. et al., 2020;Jeong et al., 2021;Khan et al., 2022).Six fNIRS studies were conducted in patients with cognitive impairment, specifically mild cognitive impairment (MCI) and post-stroke cognitive impairment.These studies identified effective brain regions and networks for non-drug therapies of TCM by comparing oxygenation levels and connectivity patterns between patients with cognitive impairment and healthy controls (HC) (Eun-Sun et al., 2018;Ghafoor et al., 2019;Sun, 2019;Khan et al., 2022).fNIRS can detect alterations in HbO 2 concentrations in the frontal cortex of patients with cognitive impairment during both rest and task conditions (Ghafoor et al., 2019;Khan et al., 2022).FC analysis is frequently conducted during the resting state to examine the coordinated effects of various brain regions.Working memory tasks are often employed in the task state to examine the features of brain activation in the working memory paradigm.Specifically, researchers at Pusan National University sought to ascertain the potential of acupuncture to enhance the mental wellbeing of patients with MCI based on brain activation (Khan et al., 2022).Eleven HC and 11 MCI patients were recruited for this study.Patients received acupuncture treatment for 12 weeks, and fNIRS data were collected before and after the treatment.Prefrontal neuronal activation was measured during a working memory task.Findings demonstrated a significant decrease in PFC activation in patients with MCI compared with HC.However, acupuncture was proven to enhance the activation area and connectivity of the PFC, thereby bringing the activation area and connection map of patients with MCI closer to those of HC.
Currently, acupuncture has demonstrated a definite clinical effect in patients with consciousness disturbance; however, the mechanism underlying its effect on awakening remains unclear.Moreover, fNIRS allows for real-time monitoring of cerebral cortex activity during acupuncture, offering a theoretical foundation for the clinical use of acupuncture in patients with consciousness disturbances.Two fNIRS studies have been conducted on using acupuncture to treat consciousness disturbances (Liu et al., 2022;Xin et al., 2022).Both studies observed the effects of acupuncture on the frontal cortex activity, which plays a vital role in arousal and cognitive function.The left PFC is related to emotion, learning, and other advanced cognitive functions, while the RPFC is closely related to arousal and attention (Müri et al., 1996;Sturm and Willmes, 2001;Heekeren et al., 2006;Shin et al., 2016).The fNIRS collected data on HbO 2 concentration during an acupuncture-specific acupoint task comprising four modules: rest, needle injection, rotation, and needle exit.The disparities between these two studies can be attributed to their respective study designs.Xin et al. ( 2022) conducted a self-controlled study that compared the differences in cortical activation between single acupuncture sessions and resting states.Their results demonstrated that acupuncture could activate CBF in the frontal cortex of patients with a disturbance of consciousness (Xin et al., 2022).Moreover, acupuncture enhances the strength of the cerebral cortical connections.Liu et al. (2022) conducted a randomized controlled trial to compare the functional connections in the PFC between acupuncture and sham acupuncture groups.They found that a single acupuncture session significantly enhanced restingstate functional connectivity in the dorsolateral PFC (dPFC) (Liu et al., 2022).
In conclusion, studies on the therapeutic mechanisms of acupuncture for the treatment of cognitive dysfunction and disturbances of consciousness often focus on the prefrontal region as the brain region of interest (ROI).fNIRS revealed that after acupuncture, the oxygenated hemoglobin concentration in the prefrontal lobe of the patients increased, and the functional connections in the prefrontal brain region were enhanced, thus improving the cognitive function and consciousness of the patients.The potential use of the fNIRS device to detect the effect of acupuncture in patients with cognitive dysfunction and disturbances in consciousness is significant.

Motor dysfunction
Limb dysfunction is a common sequela of stroke, and nondrug therapies of TCM, such as acupuncture, moxibustion, and traditional exercises, are often used to treat limb dysfunction after stroke.fNIRS, with its advantages of easy operation and unrestricted space, is suitable for patients with motor dysfunction.Chen et al. recruited patients with ischemic stroke and healthy participants, and the cerebral cortex effect of the one-finger Zen manipulation at the Hegu point using fNIRS was observed.Results showed that the hemodynamics of the contralateral M1 were obviously enhanced during massage at the Hegu of the affected arm in stroke patients, but there was no similar pattern in the hemodynamics of the ipsilateral M1.There was a significant difference between the lateralization indices of the affected and healthy sides in stroke patients, indicating that the combination of Tuina and fNIRS could reflect the functional state of the sensorymotor nerve circuit (Chen Y. F. et al., 2023).It should be noted that the team conducted a randomized controlled study.The study plans to recruit 90 patients with ischemic stroke and divide them into two groups randomly.The experimental group will be given Tuina and rTMS interventions based on conventional rehabilitation, while the control group received only rTMS in addition to conventional rehabilitation.Improvements in motor function and cortical hemodynamic changes after 4 weeks of treatment will be observed (Chen Y. F. et al., 2022).Tang et al. (2022) employed fNIRS to collect and analyze changes in the functional intensity and lateralization index of patients with lower limb motor dysfunction following stroke before and after the 4-week acupuncture and rehabilitation therapy.During the data collection period, participants were required to complete four alternating tasks of 30-s walking and 30-s standing rest on a treadmill.Their results revealed that acupuncture and rehabilitation therapy can significantly improve the asymmetric activation of the lower limb motor function and sensory MC (SMC) in patients with stroke.Lower limb motor function recovery may be related to enhanced premotor cortex activation on the affected side (Tang et al., 2022).A resting-state study found that upper limb dysfunction in patients with stroke significantly improved after 2 weeks of ear acupuncture combined with routine rehabilitation treatment, and the fNIRS results demonstrated a significant increase in HbO 2 concentrations in the primary motor area (M1) of the brain following therapeutic intervention, suggesting that activation of the M1 area of the brain may serve as a key node for ear acupuncture treatment of upper limb dysfunction (Zhang et al., 2023).Another study used fNIRS to explore the mechanism of action of tai chi chuan imagination exercises.The study revealed that the tai chi chuan imagination exercise group displayed a higher HbO 2 concentration in the SMC than the simple imagination exercise and conventional treatment groups.This indicates that tai chi chuan imagination exercise can effectively activate the corresponding cerebral MC, thereby offering novel insights into optimizing stroke treatments (Luo et al., 2022).The above research found that the improvement in limb dysfunction was related to the activation of the primary sensorimotor cortex, auxiliary motor area, premotor cortex, and other brain areas, which provides a scientific basis for the neural mechanism of acupuncture and moxibustion, tai chi chuan, and other therapies to improve limb dysfunction after stroke.
Parkinson's disease (PD) is a common neurodegenerative disorder with motor symptoms such as tremor, stiffness, bradykinesia, and postural instability, impairing patient mobility and resulting in limited independence (Balestrino and Schapira, 2020).Some studies have demonstrated that acupuncture can increase the stride length and swing times of patients with PD and reduce the rhythm that cannot be improved by levodopa treatment; moreover, acupuncture improves balance control by activating the auxiliary motor area and PFC as demonstrated by fNIRS, thereby improving gait disorders in patients with PD.Therefore, acupuncture is considered to be an effective adjuvant treatment for the PD (Jang et al., 2020).

Mental and behavioral disorders
The PFC, which is involved in cognitive processing and emotional regulation (Dunlop et al., 2017), elucidates cognitive and emotional symptoms associated with depression and anxiety.Acupuncture is a safe and effective treatment option for depression and anxiety.Several researchers have hypothesized that the therapeutic effects of acupuncture on depression can be partially attributed to the modulation of the PFC.To gain a better understanding of the antidepressant effects of acupuncture, four studies used fNIRS to examine the prefrontal lobe activation and functional connectivity in patients with depression who received acupuncture.Commonly used task paradigms include emotional picture processing (Chen, 2015), working memory (Miao, 2016), and speech-fluency tasks (Zhang et al., 2021).Zhang et al. (2021) obtained fNIRS data from patients with severe depression who underwent speech fluency and Baihui acupoint tasks to assess PFC activation during acupuncture at the Baihui acupoint.These findings suggest that a single acupuncture session may increase frontopolar cortex activation in patients with severe depression.A correlation was noted between the left dorsolateral PFC activation during executive functioning through acupuncture and the severity of depressive symptoms in patients diagnosed with severe depression (Zhang et al., 2021).Furthermore, studies have analyzed the functional connectivity of the dorsolateral prefrontal lobe by collecting resting-state data before and after acupuncture in patients with depression (Wong et al., 2021).One study demonstrated a significant temporal correlation in functional connectivity between channel pairs in the dPFC during the resting state.Patients diagnosed with anxiety disorders exhibit inadequate prefrontal lobe activation during emotion regulation.Another fNIRS study investigated the immediate effect of acupuncture on the left dPFC function in patients with generalized anxiety disorders (Xiang, 2017).Acupuncture activates the left dPFC in individuals with generalized anxiety disorders, as evidenced by an increase in HbO 2 and a decrease in dHb concentrations.However, this finding was not observed in healthy individuals.Thus, emotion regulation by acupuncture in generalized anxiety disorders may be associated with the activation of the left dPFC.The above research shows that the central mechanism of acupuncture in improving depression and anxiety symptoms may be related to increased HbO 2 levels in the dorsolateral prefrontal lobe and that fNIRS has great potential in the application of disease severity and evaluation of curative effects.

Insomnia
Insomnia is a prevalent neurological disorder that can adversely affect patients' emotions, cognition, and mental states (Perez and Salas, 2020).To validate the efficacy of non-drug therapies of TCM for insomnia, several researchers have employed fNIRS to monitor brain function in patients with insomnia and have thus generated objective evidence for the application of non-drug therapies of TCM to further promote their clinical application.Xu Y. K. et al. (2022) used fNIRS to detect the effect of acupuncture treatment on changes in cerebral HbO 2 concentration during emotional face recognition by patients with primary insomnia.They found that acupuncture improved the function of the frontal, orbitofrontal cortex, and parietalrelated brain regions by regulating the HbO 2 concentration in the cerebral cortex, thereby enhancing the individual's control of involuntary activation of irrelevant stimuli and adjusting the state of hyperarousal to improve insomnia (Xu Y. K. et al., 2022).Moreover, acupuncture demonstrated different effects on the HbO 2 concentrations in the frontal lobe of patients with insomnia of varying ages under the emotional face conditions of "yin" and "yang" attributes.This verified the rise and fall of "yin" and "yang" as the reason for the varied effects of acupuncture treatment on insomniac patients of different ages (Wang et al., 2022).These two studies show that acupuncture can regulate the concentration of HbO 2 in the frontal lobe of patients with insomnia to reduce hypersensitivity and further explore the neural mechanism of acupuncture in the treatment of insomnia.However, because brain development and degeneration at different ages affect the concentration of HbO 2 in the brain, the effect of acupuncture on HbO 2 in specific brain regions needs to be further studied.

Pain disorders
Pain is a subjective condition involving sensory, emotional, cognitive, and other factors; thus, relying only on a patient's subjective report for pain assessment and efficacy judgment is unreliable.Pain activates corresponding areas of the cerebral cortex, and it is important to objectively assess pain by detecting cortical activation using fNIRS.Electronic wrist and ankle acupuncture bracelets (E-WAAs) combine the advantages of wrist and ankle acupuncture with percutaneous electrical nerve stimulation and have demonstrated good acute and chronic pain management.Some scholars have studied the analgesic mechanism of E-WAA through fNIRS and found that frontopolar area (FPA) and dPFC are significantly involved in pain processes and regulation; moreover, decreased blood oxygen concentration in the FPA and dPFC brain regions was related to the analgesic regulation of E-WAA (Shi et al., 2022;Du et al., 2023a,b).Thus, quantitative analysis of blood oxygen concentration may be considered a potential method for more accurately identifying the analgesic effects of E-WAA and its mechanisms.

Pediatric diseases
Functional near-infrared spectroscopy is commonly used to investigate the pathogenesis of the cerebral visual cortex and the therapeutic mechanisms of acupuncture in pediatric diseases, such as childhood myopia, amblyopia, and attentiondeficit hyperactivity disorder.Typically, HbO 2 signals are detected in the V1 and V2 visual cortices of children with myopia and amblyopia, and activation levels are assessed using a visual task paradigm.In some studies, the HbO 2 β concentration in the V2 region of children with myopia was notably lower than in healthy children (Yang, 2023), while the V1 and V2 regions of children with amblyopia exhibited noticeably lower HbO 2 β levels as compared to those of healthy children (Wu, 2022).In children, amblyopia is closely associated with functional changes in the primary and secondary visual cortices.In addition, HbO 2 content in the ipsilateral visual cortex was lower than that in the contralateral visual cortex.This asymmetry in bilateral visual cortex involvement explains alterations in brain function in children with anisometropic amblyopia.Acupuncture, a widely used method to treat children with near-amblyopia, involves acupuncture with less pain (Chai, 2020), transcutaneous acupoint electrical stimulation, and traditional acupuncture (Wu, 2022;Yang, 2023).fNIRS was used to measure HbO 2 levels before, during, and after the intervention.Statistical analysis revealed differences in the acupuncture regulation mechanisms.These findings demonstrate that acupuncture can enhance blood oxygen activity in the visual cortex and increase HbO 2 content in areas V1 and V2 (Chai, 2020;Wu, 2022).Researchers have used fNIRS to examine brain responses in children with attention-deficit/hyperactivity disorders treated with percutaneous acupoint electrical stimulation (Zhuo et al., 2022).The HbO 2 concentration was measured using a go/nogo task before and after treatment.The HbO 2 concentration in the prefrontal lobe was higher after percutaneous acupoint electrical stimulation than that in the sham stimulation group, indicating a sensitive response area to percutaneous acupoint electrical stimulation.What deserves our attention is the accessibility of fNIRS and its ability to provide valuable results during physical exercise, making it more suitable for evaluating brain function in infants and young children.

Other diseases
In addition, fNIRS has been preliminarily applied to diseases such as spinal cord injury and tinnitus.Spinal cord injury is the most serious complication of spinal-related diseases, often resulting in lower limb dysfunction and wheelchair dependency.Wheelchair tai chi chuan, an emerging practice suitable for patients with spinal cord injury, has demonstrated improved motor function and neurological recovery (Qi et al., 2018).Zu et al. (2023) performed an fNIRS analysis in patients with spinal cord injury and healthy individuals while performing wheelchair tai chi chuan.Their results demonstrated that the bilateral prefrontal lobes, primary motor areas, and premotor area of the brain of patients with spinal cord injury were more greatly activated than those of the healthy participants during the wheelchair tai chi chuan exercise, indicating that patients with spinal cord injury needed more mental activities to complete the activities of the upper limb muscles.Thus, wheelchair tai chi chuan may compensate for the reduction in cortical-muscular coupling Frontiers in Neuroscience 16 frontiersin.orgthrough muscle activation (Zu et al., 2023).Tinnitus, which is the auditory phantom perception of a ringing, hissing, or buzzing sound in the absence of an objective physical sound source, is associated with lesions of the central nervous system (Baguley et al., 2013;Dalrymple et al., 2021).Yu et al. (2023) treated patients with bilateral tinnitus using performed fNIRS measurements before and after treatment using the block paradigm of the auditory stimulus design.The results revealed that the patients' scores on the hearing impairment-related scale were reduced after acupuncture treatment; moreover, the HbO 2 concentration in the temporal auditory cortex was increased and the change in HbO 2 concentration was significantly correlated with the score of hearing impairment-related scales.This indicates that acupuncture can activate the auditory cortex to play a therapeutic role (Yu et al., 2023).

Discussion
This article is so far the first review on the application of fNIRS in non-drug therapies of TCM.In this review included 46 articles describing the effects of acupuncture, massage, Taijiquan, and Baduanjin on the brain.Although we searched for research in many countries worldwide, most research has been carried out in China, and a few studies have been conducted in South Korea and Australia.A total of 11 randomized controlled studies were included, and the subjects of the remaining studies were generally compared between patients and healthy subjects.This design was related to the purpose of the fNIRS study.One is to explore the difference of cerebral hemodynamics between a disease and healthy people, and to clarify the effect of the disease on brain function.Another is to provide a reference for the treatment of patients, that is, healthy human brain function as the baseline state, and take this as the goal of affected brain function recovery.
The fNIRS analysis revealed specific cortical responses in areas commonly associated with these therapies, such as the dPFC, sensorimotor area, and supplementary motor area.Nondrug therapies of TCM can alter blood oxygen concentration levels in specific regions of the cerebral cortex, thus resulting in "activation."Several TCM interventions can result in different degrees of "activation."For instance, practicing tai chi chuan and Baduanjin can increase the HbO 2 concentration in the prefrontal lobe, thereby enhancing cognitive, executive, and control functions.Contrastingly, certain acupuncture methods can lead to increased or decreased HbO 2 concentrations, eliciting excitatory or inhibitory effects.Furthermore, non-drug therapies of TCM can improve functional connections in certain brain regions and regulate the coordination of different regions, resulting in the integration of the cortical brain network.This intervention can enhance recovery from sports injuries, cognitive impairment, and negative emotional states and ameliorate pain responses.Modification of brain activity or functional connectivity intensity between regions provides compelling evidence for elucidating the central mechanism of non-drug therapies of TCM.Research on fNIRS related to healthy people mainly includes two aspects.The first is to explore the cortical central effect of tai chi chuan and Baduanjin in enhancing control and improving cognitive function for a long time, mainly the activation of the dorsolateral prefrontal lobe, and enhancing the functional connection with motor area and occipital lobe.The second is to observe the hemodynamic changes of acupuncture at specific points.fNIRS research shows that specific hemodynamic changes only occur when acupuncture gets deqi, and acupuncture at points can produce a negative activation effect and reduce cortical excitability, which may be the neural basis for relieving pain, insomnia, and other diseases.There are dissimilar reports on hemodynamic changes caused by different manipulations of acupuncture at the same point, which need further study.The patient-related fNIRS research mainly focuses on the improvement of symptoms or functions of cognitive dysfunction, motor dysfunction, mental and behavioral disorders, insomnia, pain, pediatric diseases and other diseases by non-drug therapies of TCM, and the mechanism of action of the cerebral cortex.The above research shows that non-drug therapies of TCM can increase blood oxygen concentration levels in the prefrontal lobe, regulate functional connection between the prefrontal lobe and the motor area and occipital lobe, improve cognitive function in patients with cognitive impairment, and relieve negative symptoms of depression and anxiety disorders.The decrease of oxygen concentration in frontal pole and dorsolateral prefrontal lobe may be one of the mechanisms to improve insomnia.Non-drug therapies of TCM can activate primary motor area and auxiliary motor area, which is helpful to improve limb motor function and balance ability of patients with hemiplegia and Parkinson's disease.
In future studies, investigating the interplay between various factors, including treatment, treatment frequency, and stimulation intensity, with brain region activation and brain network changes is necessary to enhance our understanding of the underlying mechanisms of non-drug therapies of TCM.To obtain more precise test results, the experimental protocol, number of probes, placement positions, fNIRS data acquisition, and processing methods should be standardized.Furthermore, broadening the scope of disease spectra for clinical applications of fNIRS and investigating the mechanism of action of other non-drug therapies of TCM, such as Wuqinxi, Yijinjing, and Guasha, are recommended.This will offer a more scientific, comprehensive, and standardized basis for the clinical application of non-drug therapies of TCM in the future.In summary, fNIRS, a rapidly developing brain imaging technique, has greatly contributed to elucidating the mechanism of action of non-drug therapies of TCM.This technology is anticipated to become even more instrumental in clinical diagnosis, treatment, and evaluation in the future.

Limitation
Currently, fNIRS is largely employed in studies on non-drug therapies of TCM to investigate the underlying mechanisms of action in healthy participants and the therapeutic effects in patients.fNIRS is used as a prediction method to dynamically monitor changes in hemoglobin content in the brain in real-time using a specific paradigm to determine whether it could be a potential target for healthcare or treatment.However, this review has certain limitations.First, the age range of the participants included in the study was large, with no unified standard, and brain function was not constant, especially as it changed with age (Damoiseaux, 2017).Thus, the impact of changes in the physiological state on the results of this study is unknown.Second, the sample size in most studies was approximately 10-30 patients; thus, increasing the sample size would have provided more reliable results.Third, during the resting-state measurement, the participants' thoughts could have caused disturbances, resulting in changes in brain signals.Therefore, the objectivity of the collected data should be ensured.Finally, because of the small number of RCTs included, there is a potential risk of bias.Therefore, strict RCT should be included in future studies to elaborate on the clinical application of fNIRS in non-drug therapies of TCM.

Conclusion
In this review, we introduce the principle of fNIRS and its application in non-drug therapies of TCM.Although fNIRS cannot be directly used for diagnosis, it can reflect the inhibitory control ability, cognitive ability, etc., of subjects through relevant task paradigms, and brain function changes caused by nondrug therapies of TCM through blood oxygen levels to reveal objective neural mechanisms.However, there are few randomized controlled studies in the existing literature, and there is a potential risk of bias.