Over the last two decades, important leaps in technological development have enabled major discoveries in modern neuroscience. Undoubtedly, functional magnetic resonance imaging (fMRI) became thereby the gold standard technique to identify task-dependent local activity patterns by recording hemodynamic responses to neuronal activity using the so-called blood oxygenation level-dependent (BOLD) MRI contrast. This success story, however, was mostly restricted to studies with human subjects and larger non-human primates like macaques, until high field preclinical MRI systems were developed that gave access to rats and mice. Moreover a new method in rodents, manganese-enhanced magnetic resonance imaging (MEMRI) provided a more direct measurement of neuronal activity due to the ability of Mn2+ to enter cells through voltage-gated Ca2+ channels. Also nuclear imaging tools such as positron emission tomography (PET) and Single Photon Emission Computed Tomography (SPECT) provide functional neuroimages using injectable radioactive and biologically active tracers to map brain metabolism and brain perfusion or to monitor neurotransmitter-receptor binding even in small laboratory animals. Unfortunately, PET and SPECT have limited spatial and temporal resolution while the time grain of fMRI is insufficient to resolve fast neural activity patterns. In contrast, optical imaging, functional ultrasound (fUS) and optoacoustic techniques provide excellent spatiotemporal resolution. Intrinsic Optical Signal Imaging (IOSI) techniques record neural activity from changes in blood flow and metabolism by interpreting changes in light reflectance from the brain’s surface. Recently, whole-brain high-resolution functional ultrasound imaging (fUS) based on ultrafast Doppler and Optoacoustic imaging based on ultrasonic emission following light absorption of biological tissues offered a different way of monitoring hemodynamics by measuring real-time cerebral blood volume (CBV). Optoacoustic and fUS hereby bridge the depth limits of optical imaging tools by recording activity in the entire brain of rats and mice even during behavior.
However, most neuroimaging studies on small animals have been conducted under anesthesia. Despite the significant role that anesthesia plays in neuroimaging studies to avoid the effects of motion and physiological stress during functional imaging, it has become increasingly clear that anesthesia differentially affects brain metabolism, neuronal activity, and neurovascular coupling. This limits the translation to humans and affects reproducibility. In addition, the vast majority of studies in cognitive neurosciences require awake conditions to unravel neural mechanisms underlying different behaviors. Similarly in studies on the effect of neurological/psychiatric drugs, anesthesia might bias the outcome. Given that technical developments have made it possible to immobilize animals while investigating brain metabolism, neurovascular coupling, and brain circuitry in awake, behaving conditions, the time has come to move forward with awake small animal imaging. However, several awake functional imaging approaches are still facing several hurdles such as (i) smart restrained behavioral setups; (ii) stress associated with (head) fixation; (iii) body and head movements during behavioral tasks and (iv) characterization of hemodynamic response function in different animals to reliably model brain signals under awake and anesthetized conditions, just to mention a few.
This Research Topic calls for papers focusing on awake whole-brain functional imaging techniques such as fMRI, MEMRI, PET, SPECT, optical imaging, fUS, and Optoacoustics in small animals. The small animal models considered in the current research topic are, besides the traditional rodents (rat and mouse), also avian models (songbirds, pigeons, corvids, parrots), cats, marmosets, rabbits, and ferrets. We are seeking Review-, Opinion- and Methodological papers addressing the current challenges in awake and behaving small animal neuroimaging studies and Original Research Articles on the application of the established protocols in awake animals to address a variety of scientific questions. Topics of interest include, but are not limited to:
(1) Stress associated with immobilization and habituation protocols
(2) Behavioral training protocols
(3) Imaging protocols
(4) Resting-state networks and their dynamics under awake or anesthetized conditions
(5) Data processing of awake functional neuroimaging data to correct motion artifacts
(6) Sensory evoked responses in awake animals
(7) Task-based functional imaging protocols and data
(8) Neurovascular coupling studies using different functional neuroimaging readouts
(9) Effect of anesthesia on different neuroimaging readouts
(10) Characterizing awake hemodynamic response functions
(11) Effect of anesthesia on hemodynamic responses
(12) Monitoring wakefulness/attention networks during imaging
Over the last two decades, important leaps in technological development have enabled major discoveries in modern neuroscience. Undoubtedly, functional magnetic resonance imaging (fMRI) became thereby the gold standard technique to identify task-dependent local activity patterns by recording hemodynamic responses to neuronal activity using the so-called blood oxygenation level-dependent (BOLD) MRI contrast. This success story, however, was mostly restricted to studies with human subjects and larger non-human primates like macaques, until high field preclinical MRI systems were developed that gave access to rats and mice. Moreover a new method in rodents, manganese-enhanced magnetic resonance imaging (MEMRI) provided a more direct measurement of neuronal activity due to the ability of Mn2+ to enter cells through voltage-gated Ca2+ channels. Also nuclear imaging tools such as positron emission tomography (PET) and Single Photon Emission Computed Tomography (SPECT) provide functional neuroimages using injectable radioactive and biologically active tracers to map brain metabolism and brain perfusion or to monitor neurotransmitter-receptor binding even in small laboratory animals. Unfortunately, PET and SPECT have limited spatial and temporal resolution while the time grain of fMRI is insufficient to resolve fast neural activity patterns. In contrast, optical imaging, functional ultrasound (fUS) and optoacoustic techniques provide excellent spatiotemporal resolution. Intrinsic Optical Signal Imaging (IOSI) techniques record neural activity from changes in blood flow and metabolism by interpreting changes in light reflectance from the brain’s surface. Recently, whole-brain high-resolution functional ultrasound imaging (fUS) based on ultrafast Doppler and Optoacoustic imaging based on ultrasonic emission following light absorption of biological tissues offered a different way of monitoring hemodynamics by measuring real-time cerebral blood volume (CBV). Optoacoustic and fUS hereby bridge the depth limits of optical imaging tools by recording activity in the entire brain of rats and mice even during behavior.
However, most neuroimaging studies on small animals have been conducted under anesthesia. Despite the significant role that anesthesia plays in neuroimaging studies to avoid the effects of motion and physiological stress during functional imaging, it has become increasingly clear that anesthesia differentially affects brain metabolism, neuronal activity, and neurovascular coupling. This limits the translation to humans and affects reproducibility. In addition, the vast majority of studies in cognitive neurosciences require awake conditions to unravel neural mechanisms underlying different behaviors. Similarly in studies on the effect of neurological/psychiatric drugs, anesthesia might bias the outcome. Given that technical developments have made it possible to immobilize animals while investigating brain metabolism, neurovascular coupling, and brain circuitry in awake, behaving conditions, the time has come to move forward with awake small animal imaging. However, several awake functional imaging approaches are still facing several hurdles such as (i) smart restrained behavioral setups; (ii) stress associated with (head) fixation; (iii) body and head movements during behavioral tasks and (iv) characterization of hemodynamic response function in different animals to reliably model brain signals under awake and anesthetized conditions, just to mention a few.
This Research Topic calls for papers focusing on awake whole-brain functional imaging techniques such as fMRI, MEMRI, PET, SPECT, optical imaging, fUS, and Optoacoustics in small animals. The small animal models considered in the current research topic are, besides the traditional rodents (rat and mouse), also avian models (songbirds, pigeons, corvids, parrots), cats, marmosets, rabbits, and ferrets. We are seeking Review-, Opinion- and Methodological papers addressing the current challenges in awake and behaving small animal neuroimaging studies and Original Research Articles on the application of the established protocols in awake animals to address a variety of scientific questions. Topics of interest include, but are not limited to:
(1) Stress associated with immobilization and habituation protocols
(2) Behavioral training protocols
(3) Imaging protocols
(4) Resting-state networks and their dynamics under awake or anesthetized conditions
(5) Data processing of awake functional neuroimaging data to correct motion artifacts
(6) Sensory evoked responses in awake animals
(7) Task-based functional imaging protocols and data
(8) Neurovascular coupling studies using different functional neuroimaging readouts
(9) Effect of anesthesia on different neuroimaging readouts
(10) Characterizing awake hemodynamic response functions
(11) Effect of anesthesia on hemodynamic responses
(12) Monitoring wakefulness/attention networks during imaging
