Secondary Motor Areas Research Articles

A comparative study of simulated electric fields of transcranial magnetic stimulation targeting different cortical motor regions.

This computational simulation study investigates the strength of transcranial magnetic stimulation (TMS)-induced electric fields (EF) in primary motor cortex (M1) and secondary motor areas. Our results reveal high interindividual variability in the strength of TMS-induced EF responses in secondary motor areas, relative to the stimulation threshold in M1. Notably, the activation of the supplementary motor area requires high-intensity stimulation, which could be attributed to the greater scalp-to-cortex distance observed over this area. These findings emphasize the importance of individualized planning using computational simulation for optimizing neuromodulation strategies targeting the cortical motor system.

Neuromodulation modifies α-synuclein spreading dynamics in vivo and the pattern is predicted by changes in whole-brain function

BackgroundMany neurodegenerative disease treatments, such as deep brain stimulation for Parkinson's Disease, can alleviate symptoms by primarily compensating for circuit dysfunctions. However, the stimulation's effect on the underlying disease progression remains relatively unknown. Here, we report that neuromodulation can not only modulate circuit function but also modulate the in vivo spreading dynamics of α-synuclein pathology, the primary pathological hallmark observed in Parkinson's Disease. MethodsIn a mouse model, pre-formed fibrils were injected into the striatum to induce widespread α-synuclein pathology. Two days after fibril injection, mice were treated for two weeks with daily optogenetic stimulation of the Secondary Motor Area, Layer V. Whole brains were then extracted, immunolabeled, cleared, and imaged with light-sheet fluorescent microscopy. ResultsRepeated optogenetic stimulation led to a decrease in pathology at the site of stimulation and at various cortical and subcortical regions, while the contralateral cortex saw a consistent increase. Aligning the pathology changes with optogenetic-fMRI measured brain activity, we found that the changes in pathology and brain function had similar spatial locations but opposite polarity. ConclusionThese results demonstrate the ability to modulate and predict whole brain pathology changes using neuromodulation, opening a new horizon for investigating optimized neuromodulation therapies.

Mouse frontal cortex nonlinearly encodes stimuli, choices, and outcomes

Frontal area MOs (secondary motor area) is a key brain structure in rodents for making decisions based on sensory evidence and on reward value. Its neurons can encode sensory stimuli, upcoming choices, expected rewards, ongoing actions, and recent outcomes. However, the information encoded, and the nature of the resulting code, may depend on the task being performed. We recorded MOs population activity using two-photon calcium imaging, in a task requiring mice to integrate sensory evidence with reward value. Mice turned a wheel to report the location of a visual stimulus following a delay period, to receive a reward whose size varied over trial blocks. MOs neurons encoded multiple task variables, but not all of those seen in other tasks. In the delay period, MOs neurons strongly encoded the stimulus side but did not significantly encode the reward-size block. A correlation of MOs activity with upcoming choice could be explained by a common effect of stimuli on those two correlates. After the wheel turn and the feedback, the MOs population encoded choice side and choice outcome jointly and nonlinearly according to an exclusive-or (XOR) operation. This nonlinear operation would allow a downstream linear decoder to infer the correct choice side (i.e., the side that would have been rewarded) even on zero contrast trials, when there had been no visible stimulus. These results indicate that MOs neurons flexibly encode some but not all variables that determine behavior, depending on task. Moreover, they reveal that MOs activity can reflect a nonlinear combination of these behavioral variables, allowing simple linear inference of task events that would not have been directly observable.

A wireless, solar-powered, optoelectronic system for spatial restriction-free long-term optogenetic neuromodulations.

Numerous wireless optogenetic systems have been reported for practical tether-free optogenetics in freely moving animals. However, most devices rely on battery-powered or coil-powered systems requiring periodic battery replacement or bulky, high-cost charging equipment with delicate antenna design. This leads to spatiotemporal constraints, such as limited experimental duration due to battery life or animals' restricted movement within specific areas to maintain wireless power transmission. In this study, we present a wireless, solar-powered, flexible optoelectronic device for neuromodulation of the complete freely behaving subject. This device provides chronic operation without battery replacement or other external settings including impedance matching technique and radio frequency generators. Our device uses high-efficiency, thin InGaP/GaAs tandem flexible photovoltaics to harvest energy from various light sources, which powers Bluetooth system to facilitate long-term, on-demand use. Observation of sustained locomotion behaviors for a month in mice via secondary motor cortex area stimulation demonstrates the notable capabilities of our device, highlighting its potential for space-free neuromodulating applications.

Cortical changes during the learning of sequences of simultaneous finger presses

Abstract The cortical alterations underpinning the acquisition of motor skills remain debated. In this longitudinal study in younger adults, we acquired performance and neuroimaging (7 T MRI) measures weekly over the course of 6 weeks to investigate neural changes associated with learning sequences of simultaneous finger presses executed with the non-dominant hand. Both the intervention group (n = 33), which practiced the finger sequences at home, and the control group (n = 30, no home practice) showed general performance improvements, but performance improved more and became more consistent for sequences that were intensively trained by the intervention group, relative to those that were not. Brain activity for trained sequences decreased compared with untrained sequences in the bilateral parietal and premotor cortices. No training-related changes in the primary sensorimotor areas were detected. The similarity of activation patterns between trained and untrained sequences decreased in secondary, but not primary, sensorimotor areas, while the similarity of the activation patterns between different trained sequences did not show reliable changes. Neither the variability of activation patterns across trials, nor the estimates of brain structure displayed practice-related changes that reached statistical significance. Overall, the main correlate of learning configural sequences was a reduction in brain activity in secondary motor areas.

Excitatory-inhibitory mismatch shapes node recruitment in an epileptic network.

Focal epilepsy is thought to be a network disease, in which epileptiform activity can spread noncontiguously through the brain via highly interconnected nodes, or hubs, within existing networks. Animal models confirming this hypothesis are scarce, and our understanding of how distant nodes are recruited is also lacking. Whether interictal spikes (IISs) also create and reverberate through a network is not well understood. We injected bicuculline into the S1 barrel cortex and employed multisite local field potential and Thy-1 and parvalbumin (PV) cell mesoscopic calcium imaging during IISs to monitor excitatory and inhibitory cells in two monosynaptically connected nodes and one disynaptically connected node: ipsilateral secondary motor area (iM2), contralateral S1 (cS1), and contralateral secondary motor area (cM2). Node participation was analyzed with spike-triggered coactivity maps. Experiments were repeated with 4-aminopyridine as an epileptic agent. We found that each IIS reverberated throughout the network, differentially recruiting both excitatory and inhibitory cells in all connected nodes. The strongest response was found in iM2. Paradoxically, node cM2, which was connected disynaptically to the focus, was recruited more intensely than node cS1, which was connected monosynaptically. The explanation for this effect could be found in node-specific excitatory/inhibitory (E/I) balance, as cS1 demonstrated greater PV inhibitory cell activation compared with cM2, where Thy-1 excitatory cells were more heavily recruited. Our data show that IISs spread noncontiguously by exploiting fiber pathways that connect nodes in a distributed network and that E/I balance plays a critical role in node recruitment. This multinodal IIS network model can be used to investigate cell-specific dynamics in the spatial propagation of epileptiform activity.

Structure, place, and clinical efficacy of the interactive brain therapy (stimulation) technology in cerebrovascular diseases

Highlights.Interactive brain stimulation is the next step in neurofeedback technology, it implies the possibility of volitional regulation of the hemodynamic response of specific brain region in order to transform entire brain network and obtain the desired clinical and behavioral dynamics in patients (subjects). One of the indications for using the technology is post-stroke movements disorders when the volitional influence is focused on the motor area of the brain.Background.Neurofeedback and closely related concepts of neural interface system and “interactive brain” are considered as the foundation for developing algorithms for controlling neuroplasticity. Interactive brain therapy (stimulation) is a recently developed type of neurofeedback therapy, which implies dependence of feedback on a hemodynamic response signal recorded by functional magnetic resonance imaging (fMRI). The technology focuses on the region of interest with good accuracy and enables teaching the subject to control the activity of both individual cerebral structures and the functional connectivity between them, causing behavioral metamorphoses.Aim.To demonstrate the study design involving interactive stimulation of secondary motor areas of the brain using a bimodal fMRI-electroencephalography platform, and to describe the dynamics of the motor networks during treatment in patients with hemiparesis in the early period of recovery from stroke.Methods.The study involved 11 patients who were trained to regulate the activity of the secondary motor area and premotor cortex of the affected hemisphere, receiving feedback on the fMRI signal and the activity of the mu- (8–13 Hz) and beta2 (18–26 Hz) EEG ranges of the areas of interest. The block-designed training consisted of 6 sessions (imagination of movement – rest) with an interval of 2–3 days. During treatment the dynamics of the hemodynamic response of the areas of interest was analyzed. In test sessions (before treatment, immediately after the end, and six months later) functional connections within the motor network were reconstructed and hand function was assessed (grip strength, Fugle-Meyer Assessment, Box and Blocks test).Results.Upon completion of treatment, an increase in grip strength and dexterity was achieved; there was an increase in the fMRI signal of the premotor cortex of the ipsilateral hemisphere, and a strengthening of the interhemispheric functional connectivity of the secondary motor areas.Conclusion.fMRI and the interactive brain therapy technology built on its basis, on the one hand, provide the technological foundation for the “interactive brain” and the transformation of spontaneous neuroplasticity into a controlled one, and on the other hand, serve as an important tool for monitoring the process of restructuring of cerebral networks after a stroke, providing the ability to record the emergence (or disappearance) of connectivity between brain regions, and to measure its strength in dynamics, that is, to give a numerical description of neuroplasticity.

Early motor skill acquisition in healthy older adults: brain correlates of the learning process.

Motor skill learning is a crucial process at all ages. However, healthy aging is often accompanied by a reduction in motor learning capabilities. This study characterized the brain dynamics of healthy older adults during motor skill acquisition and identified brain regions associated with changes in different components of performance. Forty-three subjects participated in a functional magnetic resonance imaging study during which they learned a sequential grip force modulation task. We evaluated the continuous changes in brain activation during practice as well as the continuous performance-related changes in brain activation. Practice of the motor skill was accompanied by increased activation in secondary motor and associative areas. In contrast, visual and frontal areas were less recruited as task execution progressed. Subjects showed significant improvements on the motor skill. While faster execution relied on parietal areas and was inversely associated with frontal activation, accuracy was related to activation in primary and secondary motor areas. Better performance was achieved by the contribution of parietal regions responsible for efficient visuomotor processing and cortical motor regions involved in the correct action selection. The results add to the understanding of online motor learning in healthy older adults, showing complementary roles of specific networks for implementing changes in precision and speed.

Regional and cell-type-specific afferent and efferent projections of the mouse claustrum.

The claustrum (CLA) is a conspicuous subcortical structure interconnected with cortical and subcortical regions. Its regional anatomy and cell-type-specific connections in the mouse remain not fully determined. Using multimodal reference datasets, we confirmed the delineation of the mouse CLA as a single group of neurons embedded in the agranular insular cortex. We quantitatively investigated brain-wide inputs and outputs of CLA using bulk anterograde and retrograde viral tracing data and single neuron tracing data. We found that the prefrontal module has more cell types projecting to the CLA than other cortical modules, with layer 5 IT neurons predominating. We found nine morphological types of CLA principal neurons that topographically innervate functionally linked cortical targets, preferentially the midline cortical areas, secondary motor area, and entorhinal area. Together, this study provides a detailed wiring diagram of the cell-type-specific connections of the mouse CLA, laying a foundation for studying its functions at the cellular level.

Learning-related contraction of gray matter in rodent sensorimotor cortex is associated with adaptive myelination.

From observations in rodents, it has been suggested that the cellular basis of learning-dependent changes, detected using structural MRI, may be increased dendritic spine density, alterations in astrocyte volume, and adaptations within intracortical myelin. Myelin plasticity is crucial for neurological function, and active myelination is required for learning and memory. However, the dynamics of myelin plasticity and how it relates to morphometric-based measurements of structural plasticity remains unknown. We used a motor skill learning paradigm in male mice to evaluate experience-dependent brain plasticity by voxel-based morphometry (VBM) in longitudinal MRI, combined with a cross-sectional immunohistochemical investigation. Whole-brain VBM revealed nonlinear decreases in gray matter volume (GMV) juxtaposed to nonlinear increases in white matter volume (WMV) within GM that were best modeled by an asymptotic time course. Using an atlas-based cortical mask, we found nonlinear changes with learning in primary and secondary motor areas and in somatosensory cortex. Analysis of cross-sectional myelin immunoreactivity in forelimb somatosensory cortex confirmed an increase in myelin immunoreactivity followed by a return towards baseline levels. Further investigations using quantitative confocal microscopy confirmed these changes specifically to the length density of myelinated axons. The absence of significant histological changes in cortical thickness suggests that nonlinear morphometric changes are likely due to changes in intracortical myelin for which morphometric WMV in somatosensory cortex significantly correlated with myelin immunoreactivity. Together, these observations indicate a nonlinear increase of intracortical myelin during learning and support the hypothesis that myelin is a component of structural changes observed by VBM during learning.

Targeting neuroplasticity to improve motor recovery after stroke: an artificial neural network model.

After a neurological injury, people develop abnormal patterns of neural activity that limit motor recovery. Traditional rehabilitation, which concentrates on practicing impaired skills, is seldom fully effective. New targeted neuroplasticity protocols interact with the central nervous system to induce beneficial plasticity in key sites and thereby enable wider beneficial plasticity. They can complement traditional therapy and enhance recovery. However, their development and validation is difficult because many different targeted neuroplasticity protocols are conceivable, and evaluating even one of them is lengthy, laborious, and expensive. Computational models can address this problem by triaging numerous candidate protocols rapidly and effectively. Animal and human empirical testing can then concentrate on the most promising ones. Here, we simulate a neural network of corticospinal neurons that control motoneurons eliciting unilateral finger extension. We use this network to (i) study the mechanisms and patterns of cortical reorganization after a stroke; and (ii) identify and parameterize a targeted neuroplasticity protocol that improves recovery of extension torque. After a simulated stroke, standard training produced abnormal bilateral cortical activation and suboptimal torque recovery. To enhance recovery, we interdigitated standard training with trials in which the network was given feedback only from a targeted population of sub-optimized neurons. Targeting neurons in secondary motor areas on ∼20% of the total trials restored lateralized cortical activation and improved recovery of extension torque. The results illuminate mechanisms underlying suboptimal cortical activity post-stroke; they enable the identification and parameterization of the most promising targeted neuroplasticity protocols. By providing initial guidance, computational models could facilitate and accelerate the realization of new therapies that improve motor recovery.

Modification of Brain Functional Connectivity in Adolescent Thoracic Idiopathic Scoliosis by Lower Extremities Position

The involvement of the brain motor system in idiopathic scoliosis remains unclear. In this paper, we question whether the functional connectivity (FC) of the central motor circuitry is abnormal in adolescent idiopathic scoliosis (AIS) and whether it can be modified by flexion of the lower extremities. Functional magnetic resonance imaging (fMRI) in 18 patients with a right thoracic idiopathic curve greater than 30° (mean angle 49.4°, mean age 15.3 years, 4 males) and 22 healthy controls (mean age 18.2 years, 4 males) was explored using a 3T MR scanner. We measured their resting-state fMRI: (a) with extended lower extremities; (b) with semiflexion of the left lower extremity and extended right lower extremity, with hip abduction. Decreased FC between the secondary motor area (SMA) and postcentral cortex, pallidum and cuneus, postcentral gyrus and cerebellum, putamen and temporal lateral neocortex was observed in AIS. This pathological connectivity was reversed by lower extremity semiflexion. The FC between cortical and subcortical motor structures is significantly decreased in AIS. The decreased FC of the SMA, basal ganglia, cuneus (a hub structure), and cerebellum indicates the functional impairment of structures involved in regulating muscular tone. FC impairment in patients with AIS appears to be a reaction to the pathological condition. This pathological pattern flexibly reacts to changes in the positioning of the lower extremities, showing that the functional impairment of brain motor circuitry in AIS is reversible. We suggest that the reactivity of cerebral activity leading to brain activity normalization could be used for a rehabilitation program for patients with AIS.

Secondary motor areas for response inhibition: an epicortical recording and stimulation study.

The areas that directly inhibit motor responses in the human brain remain not fully clarified, although the pre-supplementary motor area and lateral premotor areas have been implicated. The objective of the present study was to delineate the critical areas for response inhibition and the associated functional organization of the executive action control system in the frontal lobe. The subjects were eight intractable focal epilepsy patients with chronic subdural or depth electrode implantation for presurgical evaluation covering the frontal lobe (five for left hemisphere, three for right). We recorded event-related potentials to a Go/No-Go task. We then applied a brief 50 Hz electrical stimulation to investigate the effect of the intervention on the task. Brief stimulation was given to the cortical areas generating discrete event-related potentials specific for the No-Go trials (1–3 stimulation sites/patient, a total of 12 stimulation sites). We compared the locations of event-related potentials with the results of electrical cortical stimulation for clinical mapping. We also compared the behavioural changes induced by another brief stimulation with electrical cortical stimulation mapping. As the results, anatomically, No-Go-specific event-related potentials with relatively high amplitude, named ‘large No-Go event-related potentials’, were observed predominantly in the secondary motor areas, made up of the supplementary motor area proper, the pre-supplementary motor area, and the lateral premotor areas. Functionally, large No-Go event-related potentials in the frontal lobe were located at or around the negative motor areas or language-related areas. Brief stimulation prolonged Go reaction time at most stimulation sites (66.7%) [P < 0.0001, effect size (d) = 0.30, Wilcoxon rank sum test], and increased No-Go error at some stimulation sites (25.0%: left posterior middle frontal gyrus and left pre-supplementary motor area). The stimulation sites we adopted for brief stimulation were most frequently labelled ‘negative motor area’ (63.6%), followed by ‘language-related area’ (18.2%) by the electrical cortical stimulation mapping. The stimulation sites where the brief stimulation increased No-Go errors tended to be labelled ‘language-related area’ more frequently than ‘negative motor area’ [P = 0.0833, Fisher’s exact test (two-sided)] and were located more anteriorly than were those without a No-Go error increase. By integrating the methods of different modality, namely, event-related potentials combined with brief stimulation and clinical electrical cortical stimulation mapping, we conducted a novel neuroscientific approach, providing direct evidence that secondary motor areas, especially the pre-supplementary motor area and posterior middle frontal gyrus, play an important role in response inhibition.

Role of Diffusion Tensor Tractography in Diagnosis of Limb-Kinetic Apraxia in Stroke Patients: A Mini-Narrative Review.

Limb-kinetic apraxia (LKA) is an execution disorder of movements caused by an injury to the secondary motor area (the supplementary motor area and premotor cortex) with preservation of an intact corticospinal tract (CST). A precise diagnosis of LKA is often limited because it is made based on the clinical observation of movement characteristics with confirmation of the CST state, and no specific clinical assessment tools for LKA have been developed. Diffusion tensor tractography (DTT) enables a three-dimensional estimation of the neural tracts related to LKA, such as the CST and corticofugal tract from the secondary motor area. This article reviewed 5 DTT-based studies on LKA-related neural tracts in stroke patients. These studies suggest that DTT could be a useful diagnostic tool for LKA along with previous diagnostic tools, such as brain magnetic resonance imaging and transcranial magnetic stimulation. In particular, DTT for the affected corticofugal tract can provide useful evidence for diagnosing LKA when clinicians cannot observe the movement characteristics because of severe weakness after a severe injury to the affected CST. Furthermore, a reviewed study suggested that LKA might be related to the unaffected neural tracts for motor function when the affected neural tracts were severely injured. This review summarizes the role of DTT in the diagnosis of LKA in stroke patients.

Musicianship-Related Structural and Functional Cortical Features Are Preserved in Elderly Musicians.

BackgroundProfessional musicians are a model population for exploring basic auditory function, sensorimotor and multisensory integration, and training-induced neuroplasticity. The brain of musicians exhibits distinct structural and functional cortical features; however, little is known about how these features evolve during aging. This multiparametric study aimed to examine the functional and structural neural correlates of lifelong musical practice in elderly professional musicians.MethodsSixteen young musicians, 16 elderly musicians (age >70), and 15 elderly non-musicians participated in the study. We assessed gray matter metrics at the whole-brain and region of interest (ROI) levels using high-resolution magnetic resonance imaging (MRI) with the Freesurfer automatic segmentation and reconstruction pipeline. We used BrainVoyager semiautomated segmentation to explore individual auditory cortex morphotypes. Furthermore, we evaluated functional blood oxygenation level-dependent (BOLD) activations in auditory and non-auditory regions by functional MRI (fMRI) with an attentive tone-listening task. Finally, we performed discriminant function analyses based on structural and functional ROIs.ResultsA general reduction of gray matter metrics distinguished the elderly from the young subjects at the whole-brain level, corresponding to widespread natural brain atrophy. Age- and musicianship-dependent structural correlations revealed group-specific differences in several clusters including superior, middle, and inferior frontal as well as perirolandic areas. In addition, the elderly musicians exhibited increased gyrification of auditory cortex like the young musicians. During fMRI, the elderly non-musicians activated predominantly auditory regions, whereas the elderly musicians co-activated a much broader network of auditory association areas, primary and secondary motor areas, and prefrontal and parietal regions like, albeit weaker, the young musicians. Also, group-specific age- and musicianship-dependent functional correlations were observed in the frontal and parietal regions. Moreover, discriminant function analysis could separate groups with high accuracy based on a set of specific structural and functional, mainly temporal and occipital, ROIs.ConclusionIn conclusion, despite naturally occurring senescence, the elderly musicians maintained musicianship-specific structural and functional cortical features. The identified structural and functional brain regions, discriminating elderly musicians from non-musicians, might be of relevance for the aging musicians’ brain. To what extent lifelong musical activity may have a neuroprotective impact needs to be addressed further in larger longitudinal studies.

A secondary motor area contributing to interlimb coordination during visually guided locomotion inthecat.

We investigated the contribution of cytoarchitectonic cortical area 4δc, in the caudal bank of the cruciate sulcus of the cat, to the control of visually guided locomotion. To do so, we recorded the activity of 114 neurons in 4δc while cats walked on a treadmill and stepped over an obstacle that advanced toward them. A total of 84/114 (74%) cells were task-related and 68/84 (81%) of these cells showed significant modulation of their discharge frequency when the contralateral limbs were the first to step over the obstacle. These latter cells included a substantial proportion (27/68 40%) that discharged between the passage of the contralateral forelimb and the contralateral hindlimb over the obstacle, suggesting a contribution of this area to interlimb coordination. We further compared the discharge in area 4δc with the activity patterns of cells in the rostral division of the same cytoarchitectonic area (4δr), which has been suggested to be a separate functional region. Despite some differences in the patterns of activity in the 2 subdivisions, we suggest that activity in each is compatible with a contribution to interlimb coordination and that they should be considered as a single functional area that contributes to both forelimb-forelimb and forelimb-hindlimb coordination.

Mild Bradykinesia Due to an Injury of Corticofugal-Tract from Secondary Motor Area in a Patient with Traumatic Brain Injury

Mild Bradykinesia Due to an Injury of Corticofugal-Tract from Secondary Motor Area in a Patient with Traumatic Brain Injury

Upper and Lower Limb Motor Function Correlates with Ipsilesional Corticospinal Tract and Red Nucleus Structural Integrity in Chronic Stroke: A Cross-Sectional, ROI-Based MRI Study.

Background Structural integrity of the ipsilesional corticospinal tract (CST) is important for upper limb motor recovery after stroke. However, additional neuromechanisms associated with motor function poststroke are less well understood, especially regarding the lower limb. Objective To investigate the neural basis of upper/lower limb motor deficits poststroke by correlating measures of motor function with diffusion tensor imaging-derived indices of white matter integrity (fractional anisotropy (FA), mean diffusivity (MD)) in primary and secondary motor tracts/structures. Methods Forty-three individuals with chronic stroke (time poststroke, 64.4 ± 58.8 months) underwent a comprehensive motor assessment and MRI scanning. Correlation and multiple regression analyses were performed to examine relationships between FA/MD in a priori motor tracts/structures and motor function. Results FA in the ipsilesional CST and red nucleus (RN) was positively correlated with motor function of both the affected upper and lower limb (r = 0.36‐0.55, p ≤ 0.01), while only ipsilesional RN FA was associated with gait speed (r = 0.50). Ipsilesional CST FA explained 37.3% of the variance in grip strength (p < 0.001) and 31.5% of the variance in Arm Motricity Index (p = 0.004). Measures of MD were not predictors of motor performance. Conclusions Microstructural integrity of the ipsilesional CST is associated with both upper and lower limb motor function poststroke, but appears less important for gait speed. Integrity of the ipsilesional RN was also associated with motor performance, suggesting increased contributions from secondary motor areas may play a role in supporting chronic motor function and could become a target for interventions.

Revealing the Cortical Glutamatergic Neural Activity During Burst Suppression by Simultaneous wide Field Calcium Imaging and Electroencephalography in Mice

Burst suppression (BS) is an electroencephalogram (EEG) pattern in which signals alternates between high-amplitude slow waves (burst waves) and nearly flat low-amplitude waves (suppression waves). In this study, we used wide-field (8.32 mm × 8.32 mm) fluorescent calcium imaging to record the activity of glutamatergic neurons in the parietal and occipital cortex, in conjunction with EEG recordings under BS induced by different anesthetics (sevoflurane, isoflurane, and propofol), to investigate the spatiotemporal pattern of neural activity under BS. The calcium signal of all observed cortices was decreased during the phase of EEG suppression. However, during the phase of EEG burst, the calcium signal in areas of the medial cortex, such as the secondary motor and retrosplenial area, was excited, whereas the signal in areas of the lateral cortex, such as the hindlimb cortex, forelimb cortex, barrel field, and primary visual area, was still suppressed or only weakly excited. Correlation analysis showed a strong correlation between the EEG signal and the calcium signal in the medial cortex under BS (except for propofol induced signals). As the burst-suppression ratio (BSR) increased, the regions with strong correlation coefficients became smaller, but strong correlation coefficients were still noted in the medial cortex. Taken together, our results reveal the landscape of cortical activity underlying BS.

Interference of commissural connections through the genu of the corpus callosum specifically impairs sensorimotor gating

White matter abnormalities in schizophrenic patients are characterized as regional tract-specific. Myelin loss at the genu of the corpus callosum (GCC) is one of the most consistent findings in schizophrenic patients across the different populations. We characterized the axons that pass through the GCC by stereotactically injecting an anterograde axonal tracing viral vector into the forceps minor of the corpus callosum in one hemisphere, and identified the homotopic brain structures that have commissural connections in the two hemispheres of the prefrontal cortex, including the anterior cingulate area, the prelimbic area, the secondary motor area, and the dorsal part of the agranular insular area, along with commissural connections with the primary motor area, caudoputamen, and claustrum. To investigate whether dysmyelination in these commissural connections is critical for the development of schizophrenia symptoms, we generated a mouse model with focal demyelination at the GCC by stereotactically injecting demyelinating agent lysolecithin into this site, and tested these mice in a battery of behavioral tasks that are used to model the schizophrenia-like symptom domains. We found that demyelination at the GCC influenced neither the social interest or mood state, nor the locomotive activity or motor coordination. Nevertheless, it specifically reduced the prepulse inhibition of acoustic startle that is a well-known measure of sensorimotor gating. This study advances our understanding of the pathophysiological contributions of the GCC-specific white matter lesion to the related disease, and demonstrates an indispensable role of interhemispheric communication between the frontal cortices for the top-down regulation of the sensorimotor gating.