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Primary motor cortex (M1) network stability depends on activity of inhibitory interneurons, for which susceptibility to stress was previously demonstrated in limbic regions. Hyperexcitability in M1 following changes in the excitatory/inhibitory balance is a key pathological hallmark of amyotrophic lateral sclerosis (ALS). Using electrophysiological approaches, we assessed the impact of acute restraint stress on inhibitory interneurons excitability and global synaptic plasticity in M1 of the SOD1 G93A ALS mouse model at a late pre-symptomatic stage (10-12.5 weeks). Based on their firing type (continuous, discontinuous, with accommodation or not) and electrophysiological characteristics (resting potential, rheobase, firing frequency), interneurons from M1 slices were separated into four clusters, labelled from 1 to 4. Among them, only interneurons from the first cluster, presenting continuous firing with few accommodations, tended to show increased excitability in wild-type (WT) and decreased excitability in SOD1 G93A animals following stress. In vivo analyses of evoked field potentials showed that stress suppressed the theta burst-induced plasticity of an excitatory component (N1) recorded in the superficial layers of M1 in WT, with no impact on an inhibitory complex (N2-P1) from the deeper layers. In SOD1 G93A mice, stress did not affect N1 but suppressed the N2-P1 plasticity. These data suggest that stress can alter M1 network functioning in a different manner in WT and SOD1 G93A mice, possibly through changes of inhibitory interneurons excitability and synaptic plasticity. This suggests that stress-induced activity changes in M1 may therefore influence ALS outcomes. KEY POINTS: Disruption of the excitatory/inhibitory balance in the primary motor cortex (M1) has been linked to cortical hyperexcitability development, a key pathological hallmark of amyotrophic lateral sclerosis (ALS). Psychological stress was reported to influence excitatory/inhibitory balance in limbic regions, but very little is known about its influence on the M1 functioning under physiological or pathological conditions. Our study revealed that acute stress influences the excitatory/inhibitory balance within the M1, through changes in interneurons excitability along with network plasticity. Such changes were different in pathological (SOD1 G93A ALS mouse model) vs. physiological (wild-type) conditions. The results of our study help us to better understand how stress modulates the M1 and highlight the need to further characterize stress-induced motor cortex changes because it may be of importance when evaluating ALS outcomes., (© 2024 The Author(s). The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

The ability of non-invasive brain stimulation to induce neuroplasticity and cause long-lasting functional changes is of considerable interest for the reversal of chronic pain and disability. Stimulation of the primary motor cortex (M1) has provided some of the most encouraging after-effects for therapeutic purposes, but little is known about its underlying mechanisms. In this study we combined transcranial Direct Current Stimulation (tDCS) and fMRI to measure changes in task-specific activity and interregional functional connectivity between M1 and the whole brain. Using a randomized counterbalanced sham-controlled design, we applied anodal and cathodal tDCS stimulation over the left M1. In agreement with previous studies, we demonstrate that tDCS applied to the target region induces task-specific facilitation of local brain activity after anodal tDCS, with the stimulation effects having a negative relationship to the resting motor threshold. Beyond the local effects, tDCS also induced changes in multiple downstream regions distinct from the motor system that may be important for therapeutic efficacy, including the operculo-insular and cingulate cortex. These results offer opportunities to improve outcomes of tDCS for the individual patient based on the degree of presumed neuroplasticity. Further research is still warranted to address the optimal stimulation targets and parameters for those with disease-specific symptoms of chronic pain.

ObjectiveThis systematic review aims to analyze existing literature of the effects of transcranial direct current stimulation (tDCS) on motor skills learning of healthy adults and discuss the underlying neurophysiological mechanism that influences motor skills learning.MethodsThis systematic review has followed the recommendations of the Preferred Reporting Items for Systematic reviews and Meta-Analyses. The PubMed, EBSCO, and Web of Science databases were systematically searched for relevant studies that were published from database inception to May 2022. Studies were included based on the Participants, Intervention, Comparison, Outcomes, and Setting inclusion strategy. The risk of bias was evaluated by using the Review manager 5.4 tool. The quality of each study was assessed with the Physiotherapy Evidence Database (PEDro) scale.ResultsThe electronic search produced 142 studies. Only 11 studies were included after filtering. These studies performed well in terms of distribution, blinding availability and selective reporting. They reported that tDCS significantly improved motor skills learning. The main outcomes measure were the improvement of the motor sequence tasks and specific motor skills. Nine studies showed that tDCS interventions reduced reaction time to complete motor sequence tasks in healthy adults and two studies showed that tDCS interventions improved golf putting task performance.ConclusionThe included studies showed that tDCS can help healthy adults to improve the motor skills learning by activating different brain regions, such as the primary motor cortex, left dorsolateral prefrontal cortex and right cerebellum. However, the number of included studies was limited, and the sample sizes were small. Therefore, more studies are urgently needed to validate the results of current studies and further explore the underlying neurophysiological mechanisms of tDCS in the future.

Stroke is a leading cause of morbidity and mortality among elderly populations worldwide. During the early phase of stroke, restoring blood circulation is of utmost importance to protect neurons from further injury. Once the initial condition is stabilized, various rehabilitation techniques can be applied to help stroke survivors gradually regain their affected functions. Among these techniques, transcranial magnetic stimulation (TMS) has emerged as a novel method to assess and modulate cortical excitability non-invasively and aid stroke survivors in the rehabilitation process. Different cortical regions have been targeted using TMS based on the underlying pathology and distorted function. Despite the lack of a standard operational procedure, repetitive TMS (rTMS) of the primary motor cortex (M1) is considered a promising intervention for post-stroke motor rehabilitation. However, apart from the motor response, mounting evidence suggests that M1 stimulation can be employed to treat other symptoms such as dysphagia, speech impairments, central post-stroke pain, depression, and cognitive dysfunction. In this mini-review, we summarize the therapeutic uses of rTMS stimulation over M1 in stroke survivors and discuss the potential mechanistic rationale behind it.

Efficient interhemispheric integration of neural activity between left and right primary motor cortex (M1) is critical for inter-limb motor control. We employed optogenetic stimulation to establish a framework for probing transcallosal M1–M1 interactions in rats. We performed optogenetic stimulation of excitatory neurons in right M1 of male Sprague-Dawley rats. We recorded the transcallosal evoked potential in contralateral left M1 via chronically implanted electrodes. Recordings were performed under anesthesia combination of dexmedetomidine and a low concentration of isoflurane. We systematically varied the stimulation intensity and duration to characterize the relationship between stimulation parameters in right M1 and the characteristics of the evoked intracortical potentials in left M1. Optogenetic stimulation of right M1 consistently evoked a transcallosal response in left M1 with a consistent negative peak (N1) that sometimes was preceded by a smaller positive peak (P1). Higher stimulation intensity or longer stimulation duration gradually increased N1 amplitude and reduced N1 variability across trials. A combination of stimulation intensities of 5–10 mW with stimulus durations of 1–10 ms were generally sufficient to elicit a robust transcallosal response in most animal, with our optic fiber setup. Optogenetically stimulated excitatory neurons in M1 can reliably evoke a transcallosal response in anesthetized rats. Characterizing the relationship between “stimulation dose” and “response magnitude” (i.e., the gain function) of transcallosal M1-to-M1 excitatory connections can be used to optimize the variables of optogenetic stimulation and ensure stimulation efficacy.

A recent study has reported that prefrontal cortex (PFC) activity during incremental exercise may be related to exercise termination on exhaustion. However, few studies have focused on motor-related areas during incremental exercise. This study investigated changes in the oxygenation of the PFC and motor-related areas using near-infrared spectroscopy during incremental exercise. Moreover, we analyzed the effect of exercise termination on changes in cortical oxygenation based on exercise intensity and respiratory metabolism. Sixteen healthy young male patients participated in this study. After a 4-min rest and 4-min warm-up period, incremental exercise was started at an incremental load corresponding to 20 W/min. Oxyhemoglobin (O2Hb), deoxyhemoglobin (HHb), and total hemoglobin (THb) in the bilateral PFC, supplementary motor area, and primary motor cortex were measured. We evaluated changes in oxygenation in each cortex before and after the anaerobic threshold (AT) and respiratory compensation point to identify changes due to respiratory metabolism. O2Hb and THb increased from moderate intensity or after AT to maximal exercise, and HHb increased slowly compared to O2Hb and THb; these changes in hemoglobin levels were consistent in all cortical areas we measured. However, the increase in each hemoglobin level in the bilateral PFC during incremental exercise was faster than that in motor-related areas. Moreover, changes in cortical oxygenation in the right PFC were faster than those in the left PFC. These results suggest changes based on differences in neural activity due to the cortical area. [ABSTRACT FROM AUTHOR]

Recovery of motor function following stroke requires interventions to enhance ipsilesional cortical activity. To improve finger motor function following stroke, we developed a movement task with visuomotor feedback and measured changes in motor cortex activity by electroencephalography. Stroke patients performed two types of movement task on separate days using the paretic fingers: a visuomotor tracking task requiring the patient to match a target muscle force pattern with ongoing feedback and a simple finger flexion/extension task without feedback. Movement-related cortical potentials (MRCPs) were recorded before and after the two motor interventions. The amplitudes of MRCPs measured from the ipsilesional hemisphere were significantly enhanced after the visuomotor tracking task but were unchanged by the simple manual movement task. Increased MRCP amplitude preceding movement onset revealed that the control of manual movement using visual feedback acted on the preparatory stage from motor planning to execution. A visuomotor tracking task can enhance motor cortex activity following a brief motor intervention, suggesting efficient induction of use-dependent cortical plasticity in stroke. [ABSTRACT FROM AUTHOR]

Intraoperative neuromonitoring of motor functions experienced a dramatical revolution in the last years thanks to significant advances in anesthesiology procedures and both preoperative and intraoperative mapping techniques. Asleep, awake, and combined intraoperative mapping techniques were responsible for an improvement in the functional outcomes in neurosurgery, providing reliable and reproducible mapping of both projection and association fibers involved in motor control. We report inter-M1 cortico-cortical evoked potential (CCEP) recording during asleep resection of a bilateral parasagittal meningioma with intraoperative neuromonitoring and motor mapping. CCEPs were recorded between both M1 cortices with bipolar stimulations of both supplementary motor areas (10.5–11.5 μV). Here, we provide evidence of intraoperative mapping of commissural fibres involved in motor control in a patient with asleep technique as well as a review of the potential tracts involved in the connectivity underlying the motor function. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) is a treatment procedure for some neuropsychiatric disorders, and it has been used for brain mapping, as well as diagnosis and treatment of neuromuscular dysfunctions. There is a disconnect between TMS modeling and clinical data: several groups have reported the simulated induced electric field and measured resting motor threshold (RMT) with inconsistent results in the relationship between RMT and brain scalp distance. This necessitates the use of simulation parameters that further account for individual differences in neuroanatomy. We recruited ten healthy subjects and obtained empirical RMT, magnetic resonance imaging (MRI), and diffusion tensor imaging (DTI). We developed anatomically accurate brain models from MRI and simulated TMS to determine the percent depolarized volume of gray matter (DVG) from TMS-induced electric fields. Corticospinal fiber tracts were extracted from the primary motor cortex from DTI to obtain fiber tract surface areas (FTSAs) for each participant. Linear mixed-effects models were used to evaluate the effect of DVG and FTSA on RMT. We report that DVG correlates with RMT when accounting for corticospinal FTSA. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) can depolarize cortical neurons through the intact skin and skull. The characteristics of the induced electric field (E-field) have a major impact on specific outcomes of TMS. Using multi-scale computational modeling, we explored whether the stimulation parameters derived from the primary motor cortex (M1) induce comparable macroscopic E-field strengths and subcellular/cellular responses in the dorsolateral prefrontal cortex (DLPFC). To this aim, we calculated the TMS-induced E-field in 16 anatomically realistic head models and simulated the changes in membrane voltage and intracellular calcium levels of morphologically and biophysically realistic human pyramidal cells in the M1 and DLPFC. We found that the conventional intensity selection methods (i.e., motor threshold and fixed intensities) produce variable macroscopic E-fields. Consequently, it was challenging to produce comparable subcellular/cellular responses across cortical regions with distinct folding characteristics. Prospectively, personalized stimulation intensity selection could standardize the E-fields and the subcellular/cellular responses to repetitive TMS across cortical regions and individuals. The suggested computational approach points to the shortcomings of the conventional intensity selection methods used in clinical settings. We propose that multi-scale modeling has the potential to overcome some of these limitations and broaden our understanding of the neuronal mechanisms for TMS. [ABSTRACT FROM AUTHOR]

• Tactile perception of middle fingertip suppresses motor cortical excitability. • Motor execution process interrupts this suppression. • Tactile perception of right middle fingertip likely induces surround inhibition. The present study examined whether tactile perception of the fingertip modulates excitability of the motor cortex supplying the intrinsic hand muscle and whether this modulation is specific to the fingertip stimulated and the muscle and hand tested. Tactile stimulation was given to one of the five fingertips in the left or right hand, and transcranial magnetic stimulation eliciting motor evoked potential in the first dorsal interosseous muscle (FDI) or abductor digiti minimi was given 200 ms after the onset of tactile stimulation. The corticospinal excitability of the FDI at rest was suppressed by the tactile stimulation of the right middle fingertip, but such suppression was absent for the other fingers stimulated and for the other muscle or hand tested. The persistence and amplitude of the F-wave was not significantly influenced by tactile stimulation of the fingertip in the right hand. These findings indicate that tactile perception of the right middle fingertip suppresses excitability of the motor cortex supplying the right FDI at rest. The suppression of corticospinal excitability was absent during tonic contraction of the right FDI, indicating that the motor execution process interrupts the tactile perception-induced suppression of motor cortical excitability supplying the right FDI. These findings are in line with a view that the tactile perception of the right middle finger induces surround inhibition of the motor cortex supplying the prime mover of the finger neighboring the stimulated finger. [ABSTRACT FROM AUTHOR]

Objectives: Anodal transcranial direct current stimulation (tDCS) of primary motor cortex (M1) and cathodal of the primary sensory cortex (S1) have previously shown to modulate the sensory thresholds when administered with the reference electrode located over the contralateral supraorbital area (SO). Combining the two stimulation paradigms into one with simultaneous stimulation of the two brain areas (M1 + S1 - tDCS) may result in a synergistic effect inducing a prominent neuromodulation, noticeable in the pain thresholds. The aim of this study is to assess the efficacy of the novel M1 + S1 - tDCS montage compared to sham-stimulation in modulating the pain thresholds in healthy adults. Methods: Thirty-nine (20 males) subjects were randomly assigned to either receiving 20 min. active M1 + S1 - tDCS or sham tDCS in a double-blinded single session study. Thermal and mechanical pain thresholds were assessed before and after the intervention. Results: There were no significant differences in the pain thresholds within either group, or between the M1 + S1 - tDCS group and the Sham-tDCS group (p>0.05), indicating that the intervention was ineffective in inducing a neuromodulation of the somatosensory system. Conclusions: Experimental investigations of novel tDCS electrode montages, that are scientifically based on existing studies or computational modelling, are essential to establish better tDCS protocols. Here simultaneous transcranial direct current stimulation of the primary motor cortex and primary sensory cortex showed no effect on the pain thresholds of the neck musculature in healthy subjects. This tDCS montage may have been ineffective due to how the electrical field reaches the targeted neurons, or may have been limited by the design of a single tDCS administration. The study adds to the existing literature of the studies investigating effects of new tDCS montages with the aim of establishing novel non-invasive brain stimulation interventions for chronic neck pain rehabilitation. North Denmark Region Committee on Health Research Ethics (VN-20180085) ClinicalTrials.gov (NCT04658485). [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD), a neurodevelopmental condition affecting approximately 1 in 44 children in North America, is thought to be a connectivity disorder. Valproic acid (VPA) is a multi-target drug widely used to treat epilepsy. It is also a toxic teratogen as well as a histone deacetylase inhibitor, and fetal exposure to VPA increases the risk of ASD. While the VPA model has been well-characterized for behavioral and neuronal deficits including hyperconnectivity, microglia, the principal immune cells of CNS that regulate dendrite and synapse formation during early brain development, have not been well-characterized and may provide potential hints regarding the etiology of this disorder. Therefore, in this study, we determined the effect of prenatal exposure to VPA on microglial numbers during early postnatal brain development. We found that prenatal exposure to VPA causes a significant reduction in the number of microglia in the primary motor cortex (PMC) during early postnatal brain development, particularly at postnatal day 6 (P6) and postnatal day 10 (P10) in male mice. The early microglial reduction in the VPA model coincides with active cortical synaptogenesis and is significant because it may potentially play a role in mediating impaired connectivity in ASD. [ABSTRACT FROM AUTHOR]

The integration of somatosensory signals across fingers is essential for dexterous object manipulation. Previous experiments suggest that this integration occurs in neural populations in the primary somatosensory cortex (S1). However, the integration process has not been fully characterized, as previous studies have mainly used 2-finger stimulation paradigms. Here, we addressed this gap by stimulating all 31 single- and multifinger combinations. We measured population-wide activity patterns evoked during finger stimulation in human S1 and primary motor cortex (M1) using 7T fMRI in female and male participants. Using multivariate fMRI analyses, we found clear evidence of unique nonlinear interactions between fingers. In Brodmann area (BA) 3b, interactions predominantly occurred between pairs of neighboring fingers. In BA 2, however, we found equally strong interactions between spatially distant fingers, as well as interactions between finger triplets and quadruplets. We additionally observed strong interactions in the hand area of M1. In both M1 and S1, these nonlinear interactions did not reflect a general suppression of overall activity, suggesting instead that the interactions we observed reflect rich, nonlinear integration of sensory inputs from the fingers. We suggest that this nonlinear finger integration allows for a highly flexible mapping from finger sensory inputs to motor responses that facilitates dexterous object manipulation. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a multilayered progressive brain disease characterized by motor dysfunction and a variety of other symptoms. Although acupuncture has been used to ameliorate various symptoms of neurodegenerative disorders, including PD, the underlying mechanisms are unclear. Here, we investigated the mechanism of acupuncture by revealing the effects of acupuncture treatment on brain neural responses and its functional connectivity in an animal model of PD. We observed that destruction of neuronal network between many brain regions in PD mice were reversed by acupuncture. Using machine learning analysis, we found that the key region associated with the improvement of abnormal behaviors might be related to the neural activity of M1, suggesting that the changes of c-Fos in M1 could predict the improvement of motor function induced by acupuncture treatment. In addition, acupuncture treatment was shown to significantly normalize the brain neural activity not only in M1 but also in other brain regions related to motor behavior (striatum, substantia nigra pars compacta, and globus pallidus) and non-motor symptoms (hippocampus, lateral hypothalamus, and solitary tract) of PD. Taken together, our results demonstrate that acupuncture treatment might improve the PD symptoms by normalizing the brain functional connectivity in PD mice model and provide new insights that enhance our current understanding of acupuncture mechanisms for non-motor symptoms. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) has emerged as a novel technique to stimulate the human brain through the scalp. Over the years, identifying the optimal brain region and stimulation parameters has been a subject of debate in the literature on therapeutic uses of repetitive TMS (rTMS). Nevertheless, the primary motor cortex (M1) has been a conventional target for rTMS to treat motor symptoms, such as hemiplegia and spasticity, as it controls the voluntary movement of the body. However, with an expanding knowledge base of the M1 cortical and subcortical connections, M1-rTMS has shown a therapeutic efficacy that goes beyond the conventional motor rehabilitation to involve pain, headache, fatigue, dysphagia, speech and voice impairments, sleep disorders, cognitive dysfunction, disorders of consciousness, anxiety, depression, and bladder dysfunction. In this review, we summarize the latest evidence on using M1-rTMS to treat non-motor symptoms of diverse etiologies and discuss the potential mechanistic rationale behind the management of each of these symptoms. [ABSTRACT FROM AUTHOR]

Background and purpose: Fatigue and cognitive difficulties are reported as the most frequently persistent symptoms in patients after mild SARS‐CoV‐2 infection. An extensive neurophysiological and neuropsychological assessment of such patients was performed focusing on motor cortex physiology and executive cognitive functions. Methods: Sixty‐seven patients complaining of fatigue and/or cognitive difficulties after resolution of mild SARS‐CoV‐2 infection were enrolled together with 22 healthy controls (HCs). Persistent clinical symptoms were investigated by means of a 16‐item questionnaire. Fatigue, exertion, cognitive difficulties, mood and 'well‐being' were evaluated through self‐administered tools. Utilizing transcranial magnetic stimulation of the primary motor cortex (M1) resting motor threshold, motor evoked potential amplitude, cortical silent period duration, short‐interval intracortical inhibition, intracortical facilitation, long‐interval intracortical inhibition and short‐latency afferent inhibition were evaluated. Global cognition and executive functions were assessed with screening tests. Attention was measured with computerized tasks. Results: Post COVID‐19 patients reported a mean of 4.9 persistent symptoms, high levels of fatigue, exertion, cognitive difficulties, low levels of well‐being and reduced mental well‐being. Compared to HCs, patients presented higher resting motor thresholds, lower motor evoked potential amplitudes and longer cortical silent periods, concurring with reduced M1 excitability. Long‐interval intracortical inhibition and short‐latency afferent inhibition were also impaired, indicating altered GABAB‐ergic and cholinergic neurotransmission. Short‐interval intracortical inhibition and intracortical facilitation were not affected. Patients also showed poorer global cognition and executive functions compared to HCs and a clear impairment in sustained and executive attention. Conclusions: Patients with fatigue and cognitive difficulties following mild COVID‐19 present altered excitability and neurotransmission within M1 and deficits in executive functions and attention. [ABSTRACT FROM AUTHOR]

Objective: To investigate the brain mechanism of non-correspondence between diseases severity and compression degree of the spinal cord in cervical spondylotic myelopathy (CSM) patients and to test the utility of brain imaging biomarkers for predicting prognosis of CSM. Methods: We calculated voxel-wise zALFF from 54 CSM patients and 50 healthy controls using resting-state fMRI data. In analysis 1, we identified the brain regions exhibited significant differences of zALFF between CSM patients and healthy controls. In analyses 2 through 3, we investigated the zALFF differences between light-symptom CSM patients and severe-symptom CSM patients while carefully matching the degree of compression between these two groups. In analysis 4, we tested the utility of zALFF within the primary motor cortex (M1) for predicting the prognosis of CSM. Results: We found that (1) compared with the healthy controls, CSM patients exhibited higher ALFF within left M1, bilateral superior frontal gyrus, and lower zALFF within right precuneus and calcarine, suggesting altered brain neural activity in CSM patients; (2) after matching the compression degree, the CSM patients with more severe clinical symptoms exhibited higher zALFF within M1, indicating cortical function contributes to disease's severity of CSM; (3) taking the M1 zALFF as features in the prognosis prediction model improves the prediction accuracy, indicating that the M1 zALFF provide additional value for predicting the prognosis of CSM patients following decompression surgery. Conclusion: The functional state of M1 contributes to the disease's severity of CSM and can provide complementary information for predicting the prognosis of CSM following decompression surgery. Key Points: • Cervical spondylotic myelopathy (CSM) patients exhibited increased zALFF within the primary motor cortex (M1), bilateral superior frontal gyrus, and decreased zALFF within the right precuneus and calcarine. • After matching the compression degree, the CSM patients with more severe clinical symptoms exhibited higher zALFF within M1, indicating cortical function contributes to disease severity of CSM. • zALFF within M1 provided additional value for predicting the prognosis of CSM patients. [ABSTRACT FROM AUTHOR]

Motor impairments and sensory processing abnormalities are prevalent in autism spectrum disorder (ASD), closely related to the core functions of the primary motor cortex (M1) and the primary somatosensory cortex (S1). Currently, there is limited knowledge about potential therapeutic targets in the subregions of M1 and S1 in ASD patients. This study aims to map clinically significant functional subregions of M1 and S1. Resting-state functional magnetic resonance imaging data (NTD = 266) from Autism Brain Imaging Data Exchange (ABIDE) were used for subregion modeling. We proposed a distance-weighted sparse representation algorithm to construct brain functional networks. Functional subregions of M1 and S1 were identified through consensus clustering at the group level. Differences in the characteristics of functional subregions were analyzed, along with their correlation with clinical scores. We observed symmetrical and continuous subregion organization from dorsal to ventral aspects in M1 and S1, with M1 subregions conforming to the functional pattern of the motor homunculus. Significant intergroup differences and clinical correlations were found in the dorsal and ventral aspects of M1 (p < 0.05/3, Bonferroni correction) and the ventromedial BA3 of S1 (p < 0.05/5). These functional characteristics were positively correlated with autism severity. All subregions showed significant results in the ROI-to-ROI intergroup differential analysis (p < 0.05/80). The generalizability of the segmentation model requires further evaluation. This study highlights the significance of M1 and S1 in ASD treatment and may provide new insights into brain parcellation and the identification of therapeutic targets for ASD. • Distance-weighted sparse learning aids in constructing robust brain functional networks. • The primary motor cortex is a targeted brain region for potential autism spectrum disorder patients. • The primary somatosensory cortex is a targeted brain region for potential autism spectrum disorder patients. [ABSTRACT FROM AUTHOR]

OBJECTIVE Contemporary theories of the pathophysiology of movement disorders emphasize abnormal oscillatory activity in basal ganglia-thalamocortical loops, but these have been studied in humans mainly using depth recordings. Recording from the surface of the cortex using electrocorticography (ECoG) provides a much higher amplitude signal than depth recordings, is less susceptible to deep brain stimulation (DBS) artifacts, and yields a surrogate measure of population spiking via "broadband gamma" (50-200 Hz) activity. Therefore, a technical approach to movement disorders surgery was developed that employs intraoperative ECoG as a research tool. METHODS One hundred eighty-eight patients undergoing DBS for the treatment of movement disorders were studied under an institutional review board-approved protocol. Through the standard bur hole exposure that is clinically indicated for DBS lead insertion, a strip electrode (6 or 28 contacts) was inserted to cover the primary motor or prefrontal cortical areas. Localization was confirmed by the reversal of the somatosensory evoked potential and intraoperative CT or 2D fluoroscopy. The ECoG potentials were recorded at rest and during a variety of tasks and analyzed offline in the frequency domain, focusing on activity between 3 and 200 Hz. Strips were removed prior to closure. Postoperative MRI was inspected for edema, signal change, or hematoma that could be related to the placement of the ECoG strip. RESULTS One hundred ninety-eight (99%) strips were successfully placed. Two ECoG placements were aborted due to resistance during the attempted passage of the electrode. Perioperative surgical complications occurred in 8 patients, including 5 hardware infections, 1 delayed chronic subdural hematoma requiring evacuation, 1 intraparenchymal hematoma, and 1 venous infarction distant from the site of the recording. None of these appeared to be directly related to the use of ECoG. CONCLUSIONS Intraoperative ECoG has long been used in neurosurgery for functional mapping and localization of seizure foci. As applied during DBS surgery, it has become an important research tool for understanding the brain networks in movement disorders and the mechanisms of therapeutic stimulation. In experienced hands, the technique appears to add minimal risk to surgery.

Transcranial magnetic stimulation (TMS) can depolarize cortical neurons through the intact skin and skull. The characteristics of the induced electric field (E-field) have a major impact on specific outcomes of TMS. Using multi-scale computational modeling, we explored whether the stimulation parameters derived from the primary motor cortex (M1) induce comparable macroscopic E-field strengths and subcellular/cellular responses in the dorsolateral prefrontal cortex (DLPFC). To this aim, we calculated the TMS-induced E-field in 16 anatomically realistic head models and simulated the changes in membrane voltage and intracellular calcium levels of morphologically and biophysically realistic human pyramidal cells in the M1 and DLPFC. We found that the conventional intensity selection methods (i.e., motor threshold and fixed intensities) produce variable macroscopic E-fields. Consequently, it was challenging to produce comparable subcellular/cellular responses across cortical regions with distinct folding characteristics. Prospectively, personalized stimulation intensity selection could standardize the E-fields and the subcellular/cellular responses to repetitive TMS across cortical regions and individuals. The suggested computational approach points to the shortcomings of the conventional intensity selection methods used in clinical settings. We propose that multi-scale modeling has the potential to overcome some of these limitations and broaden our understanding of the neuronal mechanisms for TMS.

Parkinson’s disease (PD) is a multilayered progressive brain disease characterized by motor dysfunction and a variety of other symptoms. Although acupuncture has been used to ameliorate various symptoms of neurodegenerative disorders, including PD, the underlying mechanisms are unclear. Here, we investigated the mechanism of acupuncture by revealing the effects of acupuncture treatment on brain neural responses and its functional connectivity in an animal model of PD. We observed that destruction of neuronal network between many brain regions in PD mice were reversed by acupuncture. Using machine learning analysis, we found that the key region associated with the improvement of abnormal behaviors might be related to the neural activity of M1, suggesting that the changes of c-Fos in M1 could predict the improvement of motor function induced by acupuncture treatment. In addition, acupuncture treatment was shown to significantly normalize the brain neural activity not only in M1 but also in other brain regions related to motor behavior (striatum, substantia nigra pars compacta, and globus pallidus) and non-motor symptoms (hippocampus, lateral hypothalamus, and solitary tract) of PD. Taken together, our results demonstrate that acupuncture treatment might improve the PD symptoms by normalizing the brain functional connectivity in PD mice model and provide new insights that enhance our current understanding of acupuncture mechanisms for non-motor symptoms.

The primary motor cortex (M1) is crucial for movement execution, especially dexterous ones, but also for cognitive functions like motor learning. The acquisition of motor skills to execute dexterous movements requires dopamine-dependent and -independent plasticity mechanisms within M1. In addition to the basal ganglia, M1 is disturbed in Parkinson’s disease (PD). However, little is known about how the lack of dopamine (DA), characteristic of PD, directly or indirectly impacts M1 circuitry. Here we review data from studies of PD patients and the substantial research in non-human primate and rodent models of DA depletion. These models enable us to understand the importance of DA in M1 physiology at the behavioral, network, cellular, and synaptic levels. We first summarize M1 functions and neuronal populations in mammals. We then look at the origin of M1 DA and the cellular location of its receptors and explore the impact of DA loss on M1 physiology, motor, and executive functions. Finally, we discuss how PD treatments impact M1 functions.

The potential of transcranial direct current stimulation (tDCS) as a non-invasive brain stimulation technique for treating pain has been studied. However, its effectiveness in patients with central post-stroke pain (CPSP) and the impact of lesion location remain unclear. This study investigated tDCS’s pain reduction effects in patients with CPSP. Twenty-two patients with CPSP were randomized into the tDCS or sham groups. The tDCS group received stimulation of the primary motor cortex (M1) for 20 min, five times weekly, for two weeks, and underwent evaluations at baseline, immediately after the intervention, and one week after the intervention. The tDCS group had no significant improvement compared to the sham group in pain, depression, and quality of life. Nevertheless, significant changes were identified within the tDCS group, and the pain trends appeared to be influenced by the lesion location. These findings provide important insights into the use of tDCS in patients with CPSP, which could inform further research and development of pain treatment options.

Introduction: Non-invasive brain stimulation can modulate both neural processing and behavioral performance. Its effects may be influenced by the stimulated area and hemisphere. In this study (EC no. 09083), repetitive transcranial magnetic stimulation (rTMS) was applied to the primary motor cortex (M1) or dorsal premotor cortex (dPMC) of either the right or left hemisphere, while evaluating cortical neurophysiology and hand function. Methods: Fifteen healthy subjects participated in this placebo-controlled crossover study. Four sessions of real 1 Hz rTMS (110% of rMT, 900 pulses) over (i) left M1, (ii) right M1, (iii) left dPMC, (iv) right dPMC, and one session of (v) placebo 1 Hz rTMS (0% of rMT, 900 pulses) over the left M1 were applied in randomized order. Motor function of both hands (Jebsen–Taylor Hand Function Test (JTHFT)) and neural processing within both hemispheres (motor evoked potentials (MEPs), cortical silent period (CSP), and ipsilateral silent period (ISP)) were evaluated prior and after each intervention session. Results: A lengthening of CSP and ISP durations within the right hemisphere was induced by 1 Hz rTMS over both areas and hemispheres. No such intervention-induced neurophysiological changes were detected within the left hemisphere. Regarding JTHFT and MEP, no intervention-induced changes ensued. Changes of hand function correlated with neurophysiological changes within both hemispheres, more often for the left than the right hand. Conclusions: Effects of 1 Hz rTMS can be better captured by neurophysiological than behavioral measures. Hemispheric differences need to be considered for this intervention.

Heart rate variability (HRV) is a useful tool for evaluating cardiovascular autonomic nervous system (ANS) functions. This systematic review and meta-analysis examined the potential effects of transcranial direct current stimulation (tDCS) protocols on HRV parameters. This study acquired 97 comparisons from 24 qualified studies for data synthesis. Using standardized mean difference (SMD), individual and overall effect sizes were estimated to show differences in HRV variables between active tDCS and sham stimulation conditions. More positive effect size values indicated that active tDCS caused greater increases in HRV than sham stimulation. Furthermore, moderator variable analyses were performed to determine whether changes in HRV variables differed depending on (a) task types (physical stress versus psychological stress versus resting condition), (b) targeted brain regions, (c) stimulation polarity, (d) characteristics of participants, and (e) specific HRV variables. Finally, we used meta-regression analyses to determine whether different tDCS parameters (i.e., the number of tDCS sessions, stimulation duration, and density) were associated with changes in HRV patterns. The random-effects model meta-analysis showed that tDCS protocols significantly improved HRV variables (SMD = 0.400; P < 0.001). Moreover, for increasing HRV during the physical stress task (SMD = 1.352; P = 0.001), anodal stimulation on the M1 was effective, while combined polarity stimulation on the PFC improved HRV during the psychological stress task (SMD = 0.550; P < 0.001) and resting condition (SMD = 0.192; P = 0.012). Additional moderator variables and meta-regression analyses failed to show that tDCS protocols had positive effects in certain conditions, such as different stimulus polarity, characteristics of participants, specific HRV variables, and tDCS parameters. These findings tentatively suggest that using tDCS protocols to stimulate optimal targeted brain areas may be effective in improving HRV patterns potentially related to cardiovascular ANS functions. • Primary motor cortical stimulation improved HRV during physical stress tasks. • Prefrontal cortical stimulation improved HRV in psychological stress and at rest. • The tDCS improved HRV in patients with hypertension during physical stress tasks. [ABSTRACT FROM AUTHOR]

Introduction: Balance impairment significantly impact the daily activities of individuals with chronic stroke, often stemming from issues like spasticity, muscle weakness, and other neurological symptoms. tDCS has shown promise in enhancing both balance and walking abilities among chronic stroke patients. Aim: To evaluate the efficacy of anodal tDCS in enhancing balance performance among chronic stroke patients, comparing its effectiveness between stimulation of the cerebellum and the primary motor cortex region. Materials and Methods: The study aimed to evaluate the efficacy of anodal tDCS in enhancing balance performance among chronic stroke patients, comparing its effectiveness between stimulation of the cerebellum and the primary motor cortex region. Results: Both groups showed significant improvement in all outcome measures (TUG, BESS, MRMI, DGI) (p<0.05). Betweengroup analysis revealed significant changes in TUG, BESS, and DGI (p=0.0016, 0.019, 0.003 respectively). However, there was no significant change between groups in MRMI (p=0.528). Conclusion: Anodal cerebellar tDCS is more effective to improve balance and gait than Cerebral tDCS. [ABSTRACT FROM AUTHOR]

Resting tremor is the most common presenting motor symptom in Parkinson's disease (PD). The supplementary motor area (SMA) is a main target of the basal-ganglia-thalamo-cortical circuit and has direct, facilitatory connections with the primary motor cortex (M1), which is important for the execution of voluntary movement. Dopamine potentially modulates SMA and M1 activity, and both regions have been implicated in resting tremor. This study investigated SMA-M1 connectivity in individuals with PD ON and OFF dopamine medication, and whether SMA-M1 connectivity is implicated in resting tremor. Dual-site transcranial magnetic stimulation was used to measure SMA-M1 connectivity in PD participants ON and OFF levodopa. Resting tremor was measured using electromyography and accelerometry. Stimulating SMA inhibited M1 excitability OFF levodopa, and facilitated M1 excitability ON levodopa. ON medication, SMA-M1 facilitation was significantly associated with smaller tremor than SMA-M1 inhibition. The current findings contribute to our understanding of the neural networks involved in PD which are altered by levodopa medication and provide a neurophysiological basis for the development of interventions to treat resting tremor. • SMA inhibits M1 activity in people with Parkinson's when OFF levodopa. • SMA facilitates M1 activity in people with Parkinson's when ON levodopa. • ON levodopa, SMA-M1 facilitation was significantly associated with less tremor. [ABSTRACT FROM AUTHOR]

A spinal cord injury (SCI) damages the axonal projections of neurons residing in the neocortex. This axotomy changes cortical excitability and results in dysfunctional activity and output of infragranular cortical layers. Thus, addressing cortical pathophysiology after SCI will be instrumental in promoting recovery. However, the cellular and molecular mechanisms of cortical dysfunction after SCI are poorly resolved. In this study, we determined that the principal neurons of the primary motor cortex layer V (M1LV), those suffering from axotomy upon SCI, become hyperexcitable following injury. Therefore, we questioned the role of hyperpolarization cyclic nucleotide gated channels (HCN channels) in this context. Patch clamp experiments on axotomized M1LV neurons and acute pharmacological manipulation of HCN channels allowed us to resolve a dysfunctional mechanism controlling intrinsic neuronal excitability one week after SCI. Some axotomized M1LV neurons became excessively depolarized. In those cells, the HCN channels were less active and less relevant to control neuronal excitability because the membrane potential exceeded the window of HCN channel activation. Care should be taken when manipulating HCN channels pharmacologically after SCI. Even though the dysfunction of HCN channels partakes in the pathophysiology of axotomized M1LV neurons, their dysfunctional contribution varies remarkably between neurons and combines with other pathophysiological mechanisms.

The purpose of this study was to quantify the effect of repetitive transcranial magnetic stimulation (rTMS), which is recommended for the improvement of some pain-related symptoms and for antidepressant treatment, on the primary motor cortex (M1) in patients with fibromyalgia (FM). We searched for studies comparing rTMS and sham rTMS in the M1 of FM patients. Pain intensity, quality of life, health status, and depression were compared with or without rTMS for at least 10 sessions. We searched four databases. Quality assessment and quantitative analysis were performed using RevMan 5.4. After screening, five randomized controlled trials of 170 patients with FM were included in the analysis. As a result of the meta-analysis of rTMS on the M1 of individuals with FM, high-frequency rTMS resulted in a significant improvement on quality of life (MD = −2.50; 95% CI: −3.99 to −1.01) compared with sham rTMS. On the other hand, low-frequency rTMS resulted in a significant improvement on health status (MD = 15.02; 95% CI: 5.59 to 24.45). The application of rTMS to the M1 is proposed as an adjunctive measure in the treatment of individuals with FM. Because rTMS has various effects depending on each application site, it is necessary to classify sites or set frequencies as variables. [ABSTRACT FROM AUTHOR]

Background and purpose: Sensory symptoms, especially neuropathic pain, are common in polyneuropathy. Conventional diagnostic tools can evaluate structural or functional impairment of nerves but cannot reveal mechanisms of neuropathic pain. Changes in the brain after polyneuropathy may play roles in the genesis of neuropathic pain. Methods: This cross‐sectional study investigated changes of cortical excitability within left primary motor cortex (M1) by measuring resting motor thresholds, short‐interval intracortical inhibition (SICI), intracortical facilitation (ICF), and afferent inhibition between polyneuropathy patients and controls, and investigated the correlates of these parameters with neuropathic pain and M1 structural and functional connectivity assessed by diffusion tractography imaging and functional magnetic resonance imaging. Results: Thirty‐three painful and 15 nonpainful neuropathic patients and 21 controls were enrolled. There were no differences in intraepidermal nerve fiber density, nerve conduction studies, thermal thresholds, or autonomic functional tests between patients with and without neuropathic pain. Compared to controls, neuropathic patients exhibited similar resting motor thresholds or afferent inhibition, but attenuated SICI and augmented ICF, especially in painful patients. Changes of intracortical excitability in neuropathic patients were correlated with intensities of neuropathic pain, and different presentations of SICI and ICF were noted between patients with and without thermal paresthesia. Additionally, short‐latency afferent inhibition at an interstimulus interval of 20 ms was associated with structural connectivity of left M1 with brain areas associated with pain perception. Conclusions: Maladaptive cortical excitability with altered structural connectivity in left M1 developed after peripheral nerve degeneration and was associated with neuropathic pain and sensory symptoms in polyneuropathy. [ABSTRACT FROM AUTHOR]

• GABAergic system within M1 is important for motor learning. • Neurofeedback training intervention strengthens the inhibitory system. • Strengthening GABA activity suppresses only online, not offline motor learning. Gamma-aminobutyric acid (GABA) activity within the primary motor cortex (M1) is essential for motor learning in cortical plasticity, and a recent study has suggested that real-time neurofeedback training (NFT) can self-regulate GABA activity. Therefore, this study aimed to investigate the effect of GABA activity strengthening via NFT on subsequent motor learning. Thirty-six healthy participants were randomly assigned to either an NFT group or control group, which received sham feedback. GABA activity was assessed for short intracortical inhibition (SICI) within the right M1 using paired-pulse transcranial magnetic stimulation. During the NFT intervention period, the participants tried to modulate the size of a circle, which was altered according to the degree of SICI in the NFT group. However, the size was altered independently of the degree of SICI in the control group. We measured the reaction time before, after (online learning), and 24 h after (offline learning) the finger-tapping task. Results showed the strengthening of GABA activity induced by the NFT intervention, and the suppression of the online but not the offline learning. These findings suggest that prior GABA activity modulation may affect online motor learning. [ABSTRACT FROM AUTHOR]

The human brain has the capacity to drastically alter its somatotopic representations in response to congenital or acquired limb deficiencies and dysfunctions. The main purpose of the present study was to elucidate such extreme adaptability in the brain of an active top wheelchair racing Paralympian (participant P1) who has congenital paraplegia (dysfunction of bilateral lower limbs). Participant P1 has undergone long-term wheelchair racing training using bilateral upper limbs and has won a total of 19 medals in six consecutive summer Paralympic games as of 2021. We examined the functional and structural changes in the foot section of the primary motor cortex (M1) in participant P1 as compared to able-bodied control participants. We also examined the functional and structural changes in three other individuals (participants P2, P3, and P4) with acquired paraplegia, who also had long-term non-use period of the lower limbs and had undergone long-term training for wheelchair sports (but not top athletes at the level of participant P1). We measured brain activity in all the participants using functional magnetic resonance imaging (MRI) when bimanual wrist extension-flexion movement was performed, and the structural MRI images were collected. Compared to 37 control participants, participant P1 showed significantly greater activity in the M1 foot section during the bimanual task, and significant local GM expansion in this section. Significantly greater activity in the M1 foot section was also observed in participant P4, but not in P2 and P3, and the significant local GM expansion was observed in participant P2, but not in P3 and P4. Thus, functional or structural change was observed in an acquired paraplegic participant, but was not observed in all the paraplegic participants. The functional and structural changes typically observed in participant P1 may represent extreme adaptability of the human brain. We discuss the results in terms of a new idea of hyper-adaptation. [ABSTRACT FROM AUTHOR]

Removal of the monosynaptic corticospinal pathway (CSP) terminating within the forelimb segments severely impairs manual dexterity. Functional recovery from the monosynaptic CSP lesion can be achieved through the remaining multisynaptic CSP toward the forelimb segments. In the present study, we applied retrograde transsynaptic labeling with rabies virus to a monkey model of spinal cord injury. By injecting the virus into the spinal forelimb segments immediately after the monosynaptic CSP lesion, we showed that the contralateral primary motor cortex (M1), especially its caudal and bank region (so-called "new" M1), was the principal origin of the CSP linking the motor cortex to the spinal forelimb segments disynaptically (disynaptic CSP). This forms a striking contrast to the architecture of the monosynaptic CSP that involves extensively other motor-related areas, together with M1. Next, the rabies injections were made at the recovery period of 3 months after the monosynaptic CSP lesion. The second-order labeled neurons were located in the ipsilateral as well as in the contralateral "new" M1. This indicates that the disynaptic CSP input from the ipsilateral "new" M1 is recruited during the motor recovery from the monosynaptic CSP lesion. Our results suggest that the disynaptic CSP is reorganized to connect the ipsilateral "new" M1 to the forelimb motoneurons for functional compensation after the monosynaptic CSP lesion. [ABSTRACT FROM AUTHOR]

Beta band (12–30 Hz) hypersynchrony within the basal ganglia-thalamocortical network has been suggested as a hallmark of Parkinson's disease (PD) pathophysiology. Abnormal beta band oscillations are found in the pedunculopontine nucleus (PPN) and primary motor cortex (M1) and are correlated with dopamine depletion. Dopamine acts locomotion and motor performance mainly through dopamine receptors (D1 and D2). However, the precise mechanism by which dopamine receptors regulate beta band electrophysiological activities between the PPN and M1 is still unknown. Here, we recorded the neuronal activity of the PPN and M1 simultaneously by the administration of the drug (SCH23390 and raclopride), selectively blocking the dopamine D1 receptor and D2 receptor. We discovered that the increased coherent activity of the beta band (12–30 Hz) between M1 and PPN in the lesioned group could be reduced and restored by injecting raclopride in the resting and wheel running states. Our studies revealed the unique role of D2 dopamine receptor signaling in regulating β band oscillatory activity in M1 and PPN and their relationship after the loss of dopamine, which contributes to elucidating the underlying mechanism of the pathophysiology of PD. • Increased β frequency band was shown in M1 and PPN in the PD condition. • The increased β frequency band activities could be rescued by the raclopride. • SCH23390 could not correct the increased β band activities. [ABSTRACT FROM AUTHOR]

Implicit motor learning and memory involve complex cortical and subcortical networks. The induction of plasticity in these network components via non-invasive brain stimulation, including transcranial direct current stimulation (tDCS), has shown to improve motor learning. However, studies showing these effects are mostly restricted to stimulation of the primary motor cortex (M1) during the early stage of learning. Because of this, we aimed to explore the efficacy of anodal tDCS applied over the posterior parietal cortex (PPC), which is involved in memory processes, on serial reaction time task (SRTT) performance. Specifically, to evaluate the involvement of both motor learning network components, we compared the effects of tDCS applied over regions corresponding to M1 and PPC during the early and late stages of learning. The results revealed a selective improvement of reaction time (RT) during anodal stimulation over the PPC in the late stage of learning. These findings support the assumption that the PPC is relevant during specific phases of learning, at least for SRTT performance. The results also indicate that not only the target area (i.e., PPC), but also timing is crucial for achieving the effects of stimulation on motor learning. [ABSTRACT FROM AUTHOR]

Objective: Pain sensation at the site of stimulation is a side effect of transcranial magnetic stimulation (TMS). The purpose of this study was to investigate how or whether the coil orientation affected TMS-induced pain on Broca’s area (BA) or primary motor cortex (M1). Methods: In Experiment 1, we measured pain thresholds during single-pulse TMS delivered over BA or left M1 at seven coil orientation angles (−90° to 90°, in 30° increments) relative to the posterior-anterior (PA) orientation. In Experiment 2, we evaluated subjective pain intensity when delivering TMS at an intensity of 110% of the resting motor threshold, which is commonly used in conventional TMS studies. Results: In Experiment 1, we found a significant relationship between coil orientation and pain thresholds during BA stimulation but not M1 stimulation. During BA stimulation, pain thresholds were significantly lower when the coil orientation was 30° upward (−30° condition) relative to the PA orientation compared with 60° downward (60° condition). In Experiment 2, pain sensations were significantly stronger in the −30° condition compared with those in the 60° condition. We also confirmed that the averaged location of pain on the head in both conditions were more than 25 mm from the left lateral orbital rim. Conclusions: The coil orientation of TMS over BA affects pain sensations. This might be attributable to the activation of nociceptors and nociceptive fibers in the muscle tissues above BA, rather than the orbicularis oculi muscle. Significance: Although the influence of coil orientation on the TMS efficacy is unclear, this study suggests that manipulating the orientation of the TMS coil may be helpful in reducing pain when applying TMS to BA.

The human brain has the capacity to drastically alter its somatotopic representations in response to congenital or acquired limb deficiencies and dysfunctions. The main purpose of the present study was to elucidate such extreme adaptability in the brain of an active top wheelchair racing Paralympian (participant P1) who has congenital paraplegia (dysfunction of bilateral lower limbs). Participant P1 has undergone long-term wheelchair racing training using bilateral upper limbs and has won a total of 19 medals in six consecutive summer Paralympic games as of 2021. We examined the functional and structural changes in the foot section of the primary motor cortex (M1) in participant P1 as compared to able-bodied control participants. We also examined the functional and structural changes in three other individuals (participants P2, P3, and P4) with acquired paraplegia, who also had long-term non-use period of the lower limbs and had undergone long-term training for wheelchair sports (but not top athletes at the level of participant P1). We measured brain activity in all the participants using functional magnetic resonance imaging (MRI) when bimanual wrist extension-flexion movement was performed, and the structural MRI images were collected. Compared to 37 control participants, participant P1 showed significantly greater activity in the M1 foot section during the bimanual task, and significant local GM expansion in this section. Significantly greater activity in the M1 foot section was also observed in participant P4, but not in P2 and P3, and the significant local GM expansion was observed in participant P2, but not in P3 and P4. Thus, functional or structural change was observed in an acquired paraplegic participant, but was not observed in all the paraplegic participants. The functional and structural changes typically observed in participant P1 may represent extreme adaptability of the human brain. We discuss the results in terms of a new idea of hyper-adaptation.

Removal of the monosynaptic corticospinal pathway (CSP) terminating within the forelimb segments severely impairs manual dexterity. Functional recovery from the monosynaptic CSP lesion can be achieved through the remaining multisynaptic CSP toward the forelimb segments. In the present study, we applied retrograde transsynaptic labeling with rabies virus to a monkey model of spinal cord injury. By injecting the virus into the spinal forelimb segments immediately after the monosynaptic CSP lesion, we showed that the contralateral primary motor cortex (M1), especially its caudal and bank region (so-called “new” M1), was the principal origin of the CSP linking the motor cortex to the spinal forelimb segments disynaptically (disynaptic CSP). This forms a striking contrast to the architecture of the monosynaptic CSP that involves extensively other motor-related areas, together with M1. Next, the rabies injections were made at the recovery period of 3 months after the monosynaptic CSP lesion. The second-order labeled neurons were located in the ipsilateral as well as in the contralateral “new” M1. This indicates that the disynaptic CSP input from the ipsilateral “new” M1 is recruited during the motor recovery from the monosynaptic CSP lesion. Our results suggest that the disynaptic CSP is reorganized to connect the ipsilateral “new” M1 to the forelimb motoneurons for functional compensation after the monosynaptic CSP lesion.

Key Points: • Conventional and advanced MR techniques may aid in the diagnosis of motor neuron disease.• Iron-sensitive MR imaging of the primary motor cortex may reveal changes to help differentiate hereditary spastic paraplegia (HSP) from UMM predominant amyotrophic lateral sclerosis (UMN-ALS) and primary lateral sclerosis (PLS).• Additional research in this area is necessary. [ABSTRACT FROM AUTHOR]

Rodents generate rhythmic whisking movements to explore their environment. Whisking trajectories, for one, appear as a fixed pattern of whisk cycles at 5–10 Hz driven by a brain stem central pattern generator. In contrast, whisking behavior is thought to be versatile and adaptable to behavioral goals. To begin to systematically investigate such behavioral adaptation, we established a whisking task, in which mice altered the trajectories of whisking in a goal-oriented fashion to gain rewards. Mice were trained to set the whisker to a defined starting position and generate a protraction movement across a virtual target (no touch-related tactile feedback). By ramping up target distance based on reward history, we observed that mice are able to generate highly specific whisking patterns suited to keep reward probability constant. On a sensorimotor level, the behavioral adaptation was realized by adjusting whisker kinematics: more distant locations were targeted using higher velocities (i.e., pointing to longer force generation), rather than by generating higher acceleration (i.e., pointing to stronger forces). We tested the suitability of the paradigm of tracking subtle alteration in whisking motor commands using small lesions in the rhythmic whisking subfield (RW) of the whisking-related primary motor cortex. Small contralateral RW lesions generated the deterioration of whisking kinematics with a latency of 12 days post-lesion, a change that was readily discriminated from changes in the behavioral adaptation by the paradigm. [ABSTRACT FROM AUTHOR]

Learning or performing new behaviors requires significant neuronal signaling and is metabolically demanding. The metabolic cost of performing a behavior is mitigated by exposure and practice which result in diminished signaling and metabolic requirements. We examined the impact of novel and habituated wheel running, as well as effortful behaviors on the modulation of extracellular glucose and lactate using biosensors inserted in the primary motor cortex of mice. We found that motor behaviors produce increases in extracellular lactate and decreases in extracellular glucose in the primary motor cortex. These effects were modulated by experience, novelty and intensity of the behavior. The increase in extracellular lactate appears to be strongly associated with novelty of a behavior as well as the difficulty of performing a behavior. Our observations are consistent with the view that a main function of aerobic glycolysis is not to fuel the current neuronal activity but to sustain new bio-infrastructure as learning changes neural networks, chiefly through the shuttling of glucose derived carbons into the pentose phosphate pathway for the biosynthesis of nucleotides. [ABSTRACT FROM AUTHOR]

Background: Upper limb dystonia is a frequent complication of Wilson's disease (WD). It can lead to poor quality of life and disability. Currently, no effective treatment for it exists. Therefore, we carried out a clinical trial to determine whether high frequency repetitive transcranial magnetic stimulation (rTMS) on the primary motor cortex alleviates upper limb dystonia in WD patients. Methods: This study was a single-center, double-blind, randomized clinical study, included 60 WD patients with upper limb dystonia from a research base of WD in Hefei, China. Participants were randomly divided into a treatment group (TG) and a control group (CG). The TG received rTMS at 10 Hz, while the CG received sham stimulation for 7 consecutive days. Participants were assessed at baseline, after the seventh treatment session, and at 2 and 4 weeks after the seventh treatment session. The primary outcomes included patients' objective muscle tension and stiffness as measured with the MyotonPRO device. The secondary results were scores on clinical scales assessing muscle spasm and motor symptoms, which included the Modified Ashworth Scale (MAS), Unified Wilson's Disease Rating Scale (UWDRS), Burke Fahn Marsden Scale (BFM), and the Activities of Daily Living (ADL) scale. Results: The analysis revealed that after 10 Hz rTMS, muscle tension (P < 0.01) and stiffness (P < 0.01) as measured by the MyotonPRO device decreased significantly in the TG compared to the CG. Moreover, clinically relevant scale scores, including the MAS (P < 0.01), UWDRS (P < 0.01), BFM (P < 0.01), and ADL (P < 0.01) were also significantly reduced. Conclusion: High-frequency rTMS over the primary motor cortex may be an effective complementary and alternative therapy to alleviating upper limb dystonia in WD patients. Clinical Trial Registration: http://www.chictr.org.cn/, identifier: ChiCTR2100046258. [ABSTRACT FROM AUTHOR]

Participation in physical activity benefits brain health and function. Cognitive function generally demonstrates a noticeable effect of physical activity, but much less is known about areas responsible for controlling movement, such as primary motor cortex (M1). While more physical activity may support M1 plasticity in older adults, the neural mechanisms underlying this beneficial effect remain poorly understood. Aging is inevitably accompanied by diminished motor performance, and the extent of plasticity may also be less in older adults compared with young. Motor complications with aging may, perhaps unsurprisingly, contribute to reduced physical activity in older adults. While the development of non-invasive brain stimulation techniques have identified that human M1 is a crucial site for learning motor skills and recovery of motor function after injury, a considerable lack of knowledge remains about how physical activity impacts M1 with healthy aging. Reducing impaired neural activity in older adults may have important implications after neurological insult, such as stroke, which is more common with advancing age. Therefore, a better understanding about the effects of physical activity on M1 processes and motor learning in older adults may promote healthy aging, but also allow us to facilitate recovery of motor function after neurological injury. This article will initially provide a brief overview of the neurophysiology of M1 in the context of learning motor skills, with a focus on healthy aging in humans. This information will then be proceeded by a more detailed assessment that focuses on whether physical activity benefits motor function and human M1 processes. [ABSTRACT FROM AUTHOR]