Primary Motor Cortex Research Articles

Multimodal response-predictor analysis for three non-invasive brain stimulation protocols.

Non-invasive brain stimulation (NIBS) methods such as paired associative stimulation (PAS), transcranial direct current stimulation (tDCS), and transcranial alternating current stimulation (tACS) are used to modulate cortical excitability and reduce symptoms in a variety of psychiatric disorders. Recent studies have shown significant inter-individual variability in the physiological response to these techniques when they are applied over the hand representation of primary motor cortex (M1hand). The goal of the present study was to identify neurophysiological, neuroanatomical, and neurochemical baseline characteristics that may predict response to commonly used NIBS protocols using data from a previously published study (Therrien-Blanchet et al., 2023). To this end, PAS, anodal tDCS, and 20-Hz tACS were administered to healthy participants in a repeated measures design. Pre/Post differences in transcranial magnetic stimulation-induced input-output curves were used to quantify changes in corticospinal excitability. Primary predictors were late I-wave latency, cortical thickness (CT) of M1hand, and fractional anisotropy of the corticospinal tract (CSThand) originating from M1hand. Secondary exploratory analysis was performed with CT in areas outside motor cortex, diffusion MRI (dMRI) metrics of the CSThand, magnetic resonance spectroscopy measurements of GABA, glutamate, and n-acetyl aspartate of M1hand CST, baseline corticospinal excitability, and cranial circumference. Multiple regression analysis showed that none of the primary variables predicted intervention outcome for any of the NIBS protocols. Exploratory analysis revealed no significant correlation between predictor variables and PAS outcome. tDCS and tACS were significantly correlated with some baseline measures. These data suggest that modulation of cortical excitability following several NIBS protocols may not be easily predicted by baseline characteristics, underscoring the need for a better understanding of their mechanism of action. Significant exploratory associations need to be confirmed in larger samples and confirmatory designs.

Clinical and functional outcome for gliomas located in the primary and supplementary motor area. Surgical series and systematic Literature review

IntroductionThis retrospective study and review aim to investigate diffuse adult gliomas in the motor cortex (primary motor area, M1, and secondary motor area, M2, which includes the supplementary motor area and premotor cortex). It explores the relationships between the histologic and molecular profiles of the lesions, their location, and the type of resection performed, and correlates them with patients’ outcomes post-surgery. Material and MethodsAn Institutional retrospective review was conducted on a consecutive series of 200 selected patients with histologically confirmed Glioblastomas (GBM) treated surgically between September 2018 and February 2022. These patients were categorized into three subgroups: Group A (lesions contacting CST and/or M1), Group B (lesions related to SMA and pre-SMA), and Group C (lesions outside and distal to the Motor Pathways). The study examined the relationships between the histologic and molecular profiles of the gliomas, their locations, and the types of resections performed, correlating these data with patients’ postoperative prognoses. ResultsThe findings indicate that the three subgroups did not exhibit significant deterioration in clinical and functional status. Lesions in M1/CST and SMA locations were not inherently associated with poorer outcomes. Notably, lesions involving SMA had a higher preoperative volume compared to those in other areas (Group A: 24.5 ± 24.3 cm3; Group B: 30.1 ± 22.7 cm3; Group C: 19.91 ± 15.8 cm3; p = 0.025). ConclusionsThese results align with existing literature, suggesting that although transient motor worsening is expected post-surgery, gliomas in motor areas do not significantly impact survival or functional status. Additionally, the molecular patterns of these tumors do not differ from those of lesions in other brain regions.

Are there cortical somatotopic motor maps outside of the human precentral gyrus?

Human body movements are supported by a somatotopic map - primary motor cortex (M1) - that is found along the precentral gyrus. Recent evidence has suggested two further motor maps that span the lateral occipitotemporal cortex (LOTC) and the precuneus. Confirmation of these maps is important, as they influence our understanding of the organisation of motor behaviour, for example by revealing how visual- and motor-related activity interact. However, evidence for these recently proposed maps is limited. We analysed an open fMRI dataset of 62 participants who moved performed twelve different body part movements. We analysed the magnitude of responses evoked by movements with novel quantitative indices that test for map-like organisation. We found strong evidence for bilateral somatotopic maps in precentral and postcentral gyri. In LOTC, we found much weaker responses to movement, and little evidence of somatotopy. In the precuneus, we found only limited evidence for somatotopy. We also adopted a background connectivity approach to examine correlations between M1, LOTC and the precuneus in the residual time-series data. This revealed a ventral-posterior / dorsal-anterior distinction in the connectivity between precuneus and M1, favouring the head and arms, respectively. Posterior right hemisphere LOTC showed some evidence of preferential connectivity to arm-selective regions of M1. Overall, our results do not support the existence of a somatotopic motor map in LOTC but provide some support for a coarse map in the precuneus, especially as revealed in connectivity patterns. These findings help clarify the organisation of human motor representations beyond the precentral gyrus.

The relationship between auditory verbal hallucination and gray matter volume and cortical thicknessin first-episode childhood-onset schizophrenia

Objective: To analyze the relationship of gray matter volume and cortical thickness of auditory verbal hallucination in first-episode childhood-onset schizophrenia(COS). Methods: Sixty cases of first-episode childhood-onset schizophrenia who were treated in the inpatient department of the Second Affiliated Hospital of Xinxiang Medical University from October 2020 to February 2024 were collected(case group).Thirty-two healthy students from a primary and secondary school in Xinxiang city were the control group. According to the score of "auditory hallucination" on the positive symptoms scale (SAPS), the patients were divided into the non-auditory hallucination group(nAVH) (n=16, score 0-1) and the auditory hallucination group (AVH)(n=38, score 2-5). The severity of psychiatric symptoms of patients was evaluated using Positive And Negative Syndrome Scale (PANSS). Resting-state MRI data was scanned for all subjects. REST software and FreeSurfer software was used for covariance analysis of gray matter volume and cortical thickness.Age and gender as covariates. Results: Finally, 54 case groups were included, including 16 cases in the non-auditory hallucination group, there were 8 males and 8 females, with an age of (12.9±1.7) years; in the auditory hallucination group, there were 16 males and 22 females, with an age of (13.1±1.5) years.There were Control group of 27 cases, 12 males, 15 females, with an age of (12.2±1.5) years. In the covariance analysis of gray matter volume showed that the brain regions with differences were mainly located in the left parahippocampal gyrus, cingulate gyrus, superior temporal gyrus, inferior frontal gyrus, superior temporal gyrus, occipital lobe, precentral gyrus, inferior parietal gyrus; Right superior frontal gyrus, lingual gyrus, fusiform gyrus, transverse temporal gyrus, inferior temporal gyrus, superior temporal gyrus(P<0.05, FDR correction).Post hoc tests found that compared with the control group, the cerebral areas with decreased gray matter volume in the AVH group were mainly located in the left superior temporal gyrus, hippocampus, cingulate gyrus, middle temporal gyrus, insula, inferior frontal gyrus;right superior temporal gyrus, superior frontal gyrus, supramargal gyrus and transverse temporal gyrus(P<0.05, FDR correction). In the covariance analysis of Cortical Thickness showed that the brain regions with differences were mainly located in the left inferior parietal gyrus, middle temporal gyrus, anterior central gyrus, supramarginal gyrus, transverse temporal gyrus, Lateral orbitofrontal cortex, insular lobe, anterior cingutate, precuneus, right superior temporal gyrus, cuneiform gyrus, middle frontal gyrus(P<0.05, FDR correction).Post hoc tests found that compared with the control group, the cerebral areas with decreased cortical thickness in the the left postcentral gyrus, transverse temporal gyrus, lateral orbitofrontal cortex, superior frontal gyrus, superior temporal gyrus, insular lobe; right cuneiform gyrus, superior temporal gyrus, supramarginal gyrus, middle temporal gyrus.The increased cortical thickness was found in the right anterior cingulate(P<0.05,FDR corrected). the nAVH group showed decreased cortical thickness areas mainly located in the left inferior temporal gyrus, inferior parietal gyrus, lateral orbitofrontal cortex, superior frontal gyrus, postcentral gyrus; right cuneiform gyrus, middle temporal gyrus, precentral gyrus. The rest showed no obvious abnormality, and the differences were statistically significant (P<0.05, FDR corrected). Conclusions: The decreased gray matter volume and cortical thickness is found in multiple brain regions in with or without auditory verbal hallucination in first-episode childhood-onset schizophrenia. Consequently, abnormal gray matter structure may be associated with the pathogenesis of childhood schizophrenia.The abnormal structure of the left and right superior temporal grrus, right supramarginal gyrus, right anterior cingulate cortex may be related to the mechanism of auditory hallucination.

Multiple insular-prefrontal pathways underlie perception to execution during response inhibition in humans

Inhibiting prepotent responses in the face of external stop signals requires complex information processing, from perceptual to control processing. However, the cerebral circuits underlying these processes remain elusive. In this study, we used neuroimaging and brain stimulation to investigate the interplay between human brain regions during response inhibition at the whole-brain level. Magnetic resonance imaging suggested a sequential four-step processing pathway: initiating from the primary visual cortex (V1), progressing to the dorsal anterior insula (daINS), then involving two essential regions in the inferior frontal cortex (IFC), namely the ventral posterior IFC (vpIFC) and anterior IFC (aIFC), and reaching the basal ganglia (BG)/primary motor cortex (M1). A combination of ultrasound stimulation and time-resolved magnetic stimulation elucidated the causal influence of daINS on vpIFC and the unidirectional dependence of aIFC on vpIFC. These results unveil asymmetric pathways in the insular-prefrontal cortex and outline the macroscopic cerebral circuits for response inhibition: V1→daINS→vpIFC/aIFC→BG/M1.

Chronic silencing of subsets of cortical layer 5 pyramidal neurons has a long-term influence on the laminar distribution of parvalbumin interneurons and the perineuronal nets.

Neural networks are established throughout cortical development, which require the right ratios of glutamatergic and GABAergic neurons. Developmental disturbances in pyramidal neuron number and function can impede the development of GABAergic neurons, which can have long-lasting consequences on inhibitory networks. However, the role of deep-layer pyramidal neurons in instructing the development and distribution of GABAergic neurons is still unclear. To unravel the role of deep-layer pyramidal neuron activity in orchestrating the spatial and laminar distribution of parvalbumin neurons, we selectively manipulated subsets of layer 5 projection neurons. By deleting Snap25 selectively from Rbp4-Cre + pyramidal neurons, we abolished regulated vesicle release from subsets of cortical layer 5 projection neurons. Our findings revealed that chronically silencing subsets of layer 5 projection neurons did not change the number and distribution of parvalbumin neurons in the developing brain. However, it did have a long-term impact on the laminar distribution of parvalbumin neurons and their perineuronal nets in the adult primary motor and somatosensory cortices. The laminar positioning of parvalbumin neurons was altered in layer 4 of the primary somatosensory cortex in the adult Snap25 cKO mice. We discovered that the absence of layer 5 activity only had a transient effect on the soma morphology of striatal PV neurons during the third week of postnatal development. We also showed that the relationship between parvalbumin neurons and the perineuronal nets varied across different cortical layers and regions; therefore, their relationship is far more complex than previously described. The current study will help us better understand the bidirectional interaction between deep-layer pyramidal cells and GABAergic neurons, as well as the long-term impact of interrupting pyramidal neuron activity on inhibitory network formation.

A preliminary study of fMRI and the relationship with depression and anxiety in Meniere's patients

PurposeTo examine alterations in Blood Oxygen Level-Dependent (BOLD) resting-state functional magnetic resonance imaging (rs-fMRI) signals, utilizing regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuation (fALFF) metrics, within activated brain regions. Additionally, this study aims to explore the relationship between these neural changes and clinical characteristics, as well as emotional states, in patients diagnosed with unilateral Meniere's disease (MD). MethodThe study included 24 patients diagnosed with left Meniere's disease (L-MD), 25 patients diagnosed with right Meniere's disease (R-MD), and 23 healthy control subjects. Resting-state blood‑oxygen-level-dependent functional magnetic resonance imaging (rest-BOLD-fMRI) data were preprocessed. A two-sample t-test was employed to compare the regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuation (fALFF) between the patient groups and the control group. Brain regions exhibiting significant differences were further analyzed for correlations with disease duration, vertigo severity, vertigo duration, hearing loss grade, and levels of anxiety and depression. ResultsIn patients with L-MD, fALFF values were significantly decreased in the right cerebellar hemisphere, middle occipital gyrus, among other regions. In patients with right-sided Ménière's disease (R-MD), fractional amplitude of low-frequency fluctuation (fALFF) values were elevated in the right middle inferior temporal gyrus and fusiform gyrus. Regional homogeneity (ReHo) values exhibited both increases and decreases in the temporal gyrus, parahippocampal gyrus, occipital gyrus, superior marginal gyrus, anterior central gyrus, and fusiform gyrus. In studies examining relational aspects, the parahippocampal gyrus, inferior temporal gyrus, middle occipital gyrus, superior middle occipital gyrus, superior marginal gyrus, and occipital gyrus demonstrated positive or negative correlations with clinical characteristics and emotional states. ConclusionsPatients with unilateral Meniere's disease (MD) exhibited both increased and decreased activation in various brain regions when compared to control subjects. A correlation was identified between these neural activation patterns and clinical characteristics, as well as emotional state, which holds significant implications for clinical treatment, prognosis, and rehabilitation strategies for MD patients.

Simple actions modulate context-dependent visual size perception at late processing stages

A simple button press towards a prime stimulus enhances subsequent visual search for objects that match the prime. The present study investigated whether this action effect is a general phenomenon across different task domains, and the underlying neural mechanisms. The action effect was measured in an unspeeded size-matching task, with the presentation of the central target and the surrounding inducers of the Ebbinghaus illusion together to one eye or separately to each eye, and when repetitive TMS was applied over right primary motor cortex (M1). The results showed that a prior key-press significantly reduced the illusion effect compared to passive viewing. Notably, the action effect persisted with dichoptic presentation of the Ebbinghaus configuration, but disappeared with the right M1 disruption. These results suggest that action guides visual perception to influence human behavior, which mainly affects the late visual processing stage and probably relies on feedback projections from the motor cortex.

Supraspinal Plasticity of Axonal Projections From the Motor Cortex After Spinal Cord Injury in Macaques.

During recovery following spinal cord injury in the macaque, the sensorimotor cortex on the same side as the injury (ipsilesional, unaffected) becomes activated and plays a role in guiding movements of the affected hand. Effective regulation of these movements by the ipsilesional sensorimotor cortex would depend not only on its ability to send motor commands directly to target muscles but also on coordinated functioning with higher-level motor planning systems such as the cortico-basal ganglia and cortico-cerebellar loops. In this study, using anterograde viral tracers, we analyzed the axonal trajectories of corticofugal fibers from the contralesional (affected) primary motor cortex (M1) at the brainstem level in two macaque monkeys with sub-hemisection spinal cord injury at the mid-cervical level. They showed considerable recovery of grasping movements after injury. We found an increase in axonal projections from the contralesional M1 to the contralateral putamen, ipsilateral lateral reticular nucleus, and contralateral pontine nucleus compared to projections from the ipsilesional (unaffected) M1. We propose that these increased projections from the contralesional M1 to the striatum and precerebellar nuclei on the nondominant side may function to recruit the ipsilesional M1 through the cortico-basal ganglia and cortico-cerebellar loops to control hand movements on the affected side during recovery.

Acupuncture at Weizhong (BL40) attenuates acetic acid-induced overactive bladder in rats by regulating brain neural activity through the modulation of mast cells and tibial nerves

ObjectiveThe present study evaluated the effects of deep acupuncture at Weizhong acupoint (BL40) on bladder function and brain activity in a rat model of overactive bladder (OAB), and investigated the possible mechanisms around the acupuncture area that initiate the effects of acupuncture. MethodsAdult female Sprague–Dawley rats were randomly divided into six groups, comprising a control group, model group, group treated with deep acupuncture at BL40, group treated with shallow acupuncture at BL40, group treated with acupuncture at non-acupoint next to BL40, and group treated with acupuncture at Xuanzhong (GB39). Urodynamic evaluation was used to observe the urination, and functional magnetic resonance imaging was used to observe the brain activation. The mechanism of acupuncture at BL40 in regulating bladder function was explored by toluidine blue staining and enzyme-linked immunosorbent assay, and the mechanism was verified by stabilizing mast cells (MCs) or blocking tibial nerve. ResultsDeep acupuncture at BL40 significantly increased the intercontraction interval in OAB rats and enhanced the mean amplitude of low frequency fluctuation of primary motor cortex (M1), periaquaductal gray matter (PAG), and pontine micturition center (PMC). It also increased the zero-lag functional connectivity between M1 and PAG and between PAG and PMC. Shallow acupuncture at BL40 and acupuncture at non-acupoint or GB39 had no effect on these indexes. Further studies suggested that deep acupuncture at BL40 increased the number and degranulation rate of MCs as well as the contents of 5-hydroxytryptamine, substance P, and histamine in the tissues around BL40. Blocking the tibial nerve by lidocaine injection or inhibiting MC degranulation by sodium cromoglycate injection obstructed the effects of acupuncture on restoring urinary function and modulating brain activation in OAB rats. ConclusionDeep acupuncture at BL40 may be more effective for inhibiting OAB by promoting degranulation of MCs around the acupoint and stimulating tibial nerve, thereby regulating the activation of the brain area that controls the lower urinary tract.

Bihemispheric Transcranial Direct Current Stimulation over Primary Motor Cortex Potentiates Improvement of Neurological but not Upper Limb Motor Functions in Ischemic Stroke Patients Treated with Routine Physical Therapy: A Randomized, Double-Blind, Sham-Controlled Trial.

We investigated the therapeutic effect of transcranial direct current stimulation (tDCS) combined with routine physiotherapy on the neurological and upper limb motor function in ischemic stroke patients with hemiplegia. In a Randomized double-blind controlled trial study, 52 eligible stroke patients were assigned to real tDCS receiving bihemispheric electrical current with 1.5 mA for 30 minutes over the primary motor cortex, and sham tDCS with a current intensity of 0.5 mA for 30 seconds. Both groups received routine physiotherapy, 5 sessions per week for two weeks. The National Institute of Health Stroke Scale (NIHSS) and the Medical Research Council Scale for Muscle Strength were used to assess the neurological and upper limb motor functions, respectively. Both therapeutic approaches begot a significant improvement in upper limb motor function and neurological impairment at the last session of therapy and follow-up study. However, the treatment-induced neurological amelioration at the last session of therapy in real tDCS was significantly more than sham, especially in those identified as female and under 60 years old. A gender and age-specific protocol of real tDCS combined with routine physiotherapy might be beneficial to improve neurological impairment but not upper limb motor dysfunction after stroke.

Systemic exposure to COVID-19 virus-like particles modulates firing patterns of cortical neurons in the living mouse brain.

Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) causes a systemic infection that affects the central nervous system. We used virus-like particles (VLPs) to explore how exposure to the SARS-CoV-2 proteins affects brain activity patterns in wild-type (WT) mice and in mice that express the wild-type human tau protein (htau mice). VLP exposure elicited dose-dependent changes in corticosterone and distinct chemokine levels. Longitudinal two-photon microscopy recordings of primary somatosensory and motor cortex neurons that express the jGCaMP7s calcium sensor tracked modifications of neuronal activity patterns following exposure to VLPs. There was a substantial short-term increase in stimulus-evoked activity metrics in both WT and htau VLP-injected mice, while htau mice showed also increased spontaneous activity metrics and increase activity in the vehicle-injected group. Over the following weeks, activity metrics in WT mice subsided, but remained above baseline levels. For htau mice, activity metrics either remain elevated or decreased to lower levels than baseline. Overall, our data suggest that exposure to the SARS-CoV-2 VLPs leads to strong short-term disruption of cortical activity patterns in mice with long-term residual effects. The htau mice, which have a more vulnerable genetic background, exhibited more severe pathobiology that may lead to more adverse outcomes.

A first-in-human application of OPM-MEG for localizing motor activity area: Compared to functional MRI

BackgroundAccurately localizing brain motor areas is vital for protecting motor function during neurosurgical procedures. Magnetoencephalography (MEG) based on optically pumped magnetometer (OPM) improves the availability of MEG in clinical applications. The aim of this study is to evaluate the availability, accuracy and precision of “OPM-MEG” for localizing motor areas in brain tumor patients and healthy individuals. MethodsParticipants were enrolled and subjected to primary motor area localization by both 3T-fMRI and 128-channel OPM-MEG examinations. The localization accuracy (ability of mapping on the anatomical location) and precision (activation signal centralization) were compared between the two methods, and accuracy was further validated by intraoperative direct cortical electrical stimulation (DCS) on the localized area with assistance of neuro-navigation system. ResultA total of 12 participants (7 brain tumor patients and 5 healthy individuals) were enrolled and all had successful localization for motor areas by both methods. The average time of OPM-MEG examination for each limb function was approximately 9 min. The localizations by both methods mainly covered the anatomical location of primary motor cortex and were partially overlapped. The motor activation signal identified by OPM-MEG was more centralized than fMRI did. The centroid of motor area localized by the OPM-MEG deviated from it by fMRI, with a mean distance of 19.7 mm and 27.48 mm for hand or foot localization, respectively. Furthermore, the OPM-MEG centroid for hand movement successfully triggered corresponding hand response by DCS. ConclusionsIn this first-in-human study exploring the potential of OPM-MEG in functional localization of motor areas, we revealed its availability and reliability in mapping motor areas, demonstrating it as a promising tool in assisting neurosurgical practice and neuroscience research.

Decoupling of motor cortex to movement in Parkinson's dyskinesia rescued by sub-anaesthetic ketamine.

Gamma band and single-unit neural activity in primary motor cortex (M1) are involved in the control of movement. This activity is disrupted in Parkinson's disease (PD) and levodopa-induced dyskinesia (LID), a debilitating consequence of dopamine replacement therapy for PD. Physiological features of LID include pathological narrowband gamma oscillations, finely tuned gamma (FTG), and altered M1 firing activity. Since most studies characterize LID through visual scoring, little is known about the relationships between ongoing dyskinetic movements, gamma, and neuronal activity at fast (sub-second) and slow (seconds) timescales. Here, we investigate how motor cortex activity changes with movement at multiple timescales in animal models of PD and LID. Furthermore, sub-anesthetic ketamine has emerged as a possible therapy for LID. How ketamine may reduce LID is not fully understood. Consequently, we investigate how ketamine affects the relationship between motor cortex activity and movement. To investigate these questions, local-field and single-unit activity from >3000 motor cortex neurons was acquired using a standard model of PD/LID (n = 10 male rats). Data in LID and sham animals was acquired following levodopa (L-DOPA; 12 mg/kg, i.p.) and ketamine (20 mg/kg, i.p.) administration. Movement was assessed using traditional abnormal involuntary movements (AIMs) scores and head-mounted inertial sensors sampled at 200 Hz. While correlations between movement, gamma, and single-unit activity were high in all animals during control conditions, correlations decreased considerably in animal models of LID following L-DOPA administration. This suggests that M1 can become functionally decoupled from ongoing movements in LID. Interestingly, this effect was observed in both the dopamine depleted and non-depleted hemispheres. Ketamine disrupted FTG, decreased LID, and moderately increased single-unit correlations to movement during LID. Ketamine, however, did not enhance the correlation between gamma-band activity and movement. Finally, ketamine exerted a selective effect on neuronal interactions and ensemble activity in LID animals. Specifically, analysis of cell-pair firing-rate correlations showed that ketamine induced a distinct neural ensemble state in LID by reorganizing the pattern of cell-pair interactions. These findings provide insight into the role that motor cortex neurons and gamma-band activity play during healthy movement and LID. Results suggest that primary motor cortex does not directly trigger specific dyskinetic movements during LID but, instead, dysregulated motor cortex activity may permit aberrant movements to spontaneously emerge in downstream circuits. These data further support the anti-dyskinetic properties of ketamine and suggest that ketamine acts to reduce LID by disrupting pathological interactions between motor cortex neurons during dyskinesia.

Preconfigured cortico-thalamic neural dynamics constrain movement-associated thalamic activity

Neural preconfigured activity patterns (nPAPs), conceptualized as organized activity parcellated into groups of neurons, have been proposed as building blocks for cognitive and sensory processing. However, their existence and function in motor networks have been scarcely studied. Here, we explore the possibility that nPAPs are present in the motor thalamus (VL/VM) and their potential contribution to motor-related activity. To this end, we developed a preparation where VL/VM multiunitary activity could be robustly recorded in mouse behavior evoked by primary motor cortex (M1) optogenetic stimulation and forelimb movements. VL/VM-evoked activity was organized as rigid stereotypical activity patterns at the single and population levels. These activity patterns were unable to dynamically adapt to different temporal architectures of M1 stimulation. Moreover, they were experience-independent, present in virtually all animals, and pairs of neurons with high correlations during M1-stimulation also presented higher correlations during spontaneous activity, confirming their preconfigured nature. Finally, subpopulations expressing specific M1-evoked patterns also displayed specific movement-related patterns. Our data demonstrate that the behaviorally related identity of specific neural subpopulations is tightly linked to nPAPs.

Aging modulates the impact of cognitive interference subtypes on dynamic connectivity across a distributed motor network

Research has shown age-related declines in cognitive control in the context of interference, but these studies have focused on frontoparietal networks and less is known about impacts on motor response-related dynamics in the face of distractors. Thus, we examined whether healthy aging affected connectivity between attention networks and motor circuitry using a multisource interference task and magnetoencephalography in 72 healthy-aging participants (28–63 years-old). Our results indicated stronger beta connectivity with increasing age between bilateral primary motor (M1) and occipital cortices, as well as stronger gamma fronto-motor connectivity during flanker-type interference. Regarding Simon-type interference, stronger beta interactions were observed between left M1 and right temporal and right M1 and left parietal with increasing age. Finally, the superadditivity effect (flanker + Simon presented simultaneously) indicated weaker beta connectivity between right M1 and left premotor with increasing age. These findings suggest exhaustion of age-related compensatory adaptations in the fronto-parieto-motor network with greater interference.

Primed low frequency repetitive transcranial magnetic stimulation rebalances cortical excitatory-inhibitory circuitry and improves functional outcomes in infantile cerebral palsy patients: A randomized controlled trial

BackgroundMultiple prenatal and postnatal etiologies in cerebral palsy (CP) patients cause neural tissue damage and alterations in cortical neuronal activity and plasticity, leading to motor and cognitive deficits early in life. Repetitive transcranial magnetic stimulation (rTMS) to the lesioned or contralesional hemisphere has been shown to alleviate these functional deficits. However, the underlying mechanisms of the beneficial effects of rTMS via realigning intracortical and interhemispheric circuitry and excitability remain unclear. The present study explored the ability of primed low-frequency rTMS to modulate intracortical excitatory-inhibitory circuitry, interhemispheric and corticospinal integrity, and plasticity in infantile hemiplegic CP. MethodsThe current study was a randomized, placebo-controlled trial with infantile hemiplegic CP patients. The active group received 6 Hz primed low-frequency 1Hz rTMS delivered to the contralesional primary motor cortex for 4 weeks, in 10 sessions. The placebo group received sham stimulation. Both groups also underwent 10 sessions of modified-constraint induced movement therapy (mCIMT). Pre- and post-intervention assessments were conducted using the Quality of Upper Extremity Skills Test to evaluate sensory and motor function, and the Modified Ashworth Scale (MAS) to assess spasticity. Additionally, cortical excitability and plasticity were measured using single- and paired-pulse TMS. ResultsWe found a significant increase in Quality of Upper Extremity Skills Test scores, CP Quality of Life Child (CP QOL-Child) scores, and grip strength, and a decrease in MAS scores in the active rTMS group compared with the sham group. Single- and paired-pulse paradigms revealed a significant decrease in resting and active motor threshold, a reduction in the cortical silent period, and short- and long-interval intracortical inhibition in the intervention group compared with the sham group. ConclusionPrimed low-frequency rTMS in the contralesional hemisphere combined with mCIMT shows potential for modulating motor neuronal excitability, rebalancing intracortical excitatory-inhibitory circuitry, and enhancing functional outcomes in children with infantile hemiparetic CP.

TMS-evoked potentials provide novel neurophysiological features of Tourette syndrome

IntroductionGilles de la Tourette syndrome (TS) is a neuropsychiatric disorder associated with abnormal activation of the cortico-striatal-thalamo-cortical circuits and dopaminergic system. We sought to examine changes in neurotransmission relating to cortical excitation/inhibition of TS by measuring TMS-evoked potentials (TEPs) of selected networks. MethodsThirty-three adult TS patients and 18 healthy controls underwent evaluation of symptom severity using the YGTSS (tics), PUTS (premonitory urge), Y-BOCS (OCD), CAARS (ADHD), BDI (depression), and BAI (anxiety). TMS-EEG was performed to measure TEPs obtained from the primary motor cortex (M1), dorsolateral prefrontal cortex (DLPFC), and primary visual cortex (V1). ResultsTEP analysis revealed a delayed P180 latency in M1 for TS patients compared to controls (p = 0.006). Lower early amplitude of TEP in response to stimulation of DLPFC (50–70 ms), and delayed DLPFC P180 latency were associated with higher tic severity (p = 0.001 and p = 0.003, respectively). M1 early amplitude (50–70 ms) also effectively differentiated TS with mild-moderate from severe tics (p = 0.003). Significant correlation was found between TEP V1 early amplitude (15–45 ms) and severity of TS anxiety. ConclusionDistinct TEP patterns registered in response to DLPFC, M1, and V1 stimulation may shed light on the underlying pathophysiology of TS and are associated with tic severity and comorbidities.

Theta Burst Stimulation Modulates Exercise Performance by Influencing Central Fatigue and Corticospinal Excitability.

Theta-burst stimulation (TBS) over the primary motor cortex modulates activity of the underlying neural tissue, but little is known about its consequence on neuromuscular fatigue (NMF) and its neural correlates. This study aimed to compare the effects of facilitatory versus inhibitory TBS on the NMF and excitability/inhibition of the corticospinal pathway in an unfatigued/fatigued muscle. The effects of three TBS protocols (facilitatory/intermittent: iTBS; inhibitory/continuous: cTBS, and sham: sTBS) were tested on exercise performance, neuromuscular function, corticospinal excitability and inhibition in twenty young healthy participants. Transcranial magnetic and peripheral electrical stimulations were used at baseline, following TBS (unfatigued state), and after a fatiguing sustained contraction (fatigued state) at 35% of the maximal voluntary isometric contraction (MVIC) of the elbow flexors. Time-to-task failure was shorter for cTBS (142±51 s) and longer for iTBS (214±68 s) compared with sTBS (173±65 s) (P < .05). In an unfatigued state, cTBS reduced MVIC and voluntary activation (VA), increased motor-evoked potential (MEP), and silent period (SP) (P < 0.05), while iTBS did not cause any change. In a fatigued state, MVIC and VA decreased in all TBS sessions (P < 0.05). However, the reduction in VA was larger after cTBS (Δ-18±18%) compared with iTBS (Δ-3±5%), and sTBS (Δ-9±9%) (P < 0.001). Furthermore, the increase in MEP and SP were greater for cTBS (P < .05), compared to iTBS and sTBS (P < .05). Facilitatory TBS augments exercise performance that is independent of central parameters and corticospinal mechanisms whilst inhibitory TBS attenuates exercise performance through an exacerbation in the development of central fatigue and possibly intracortical inhibition.

Functional anatomy of the subthalamic nucleus and the pathophysiology of cardinal features of Parkinson's disease unraveled by focused ultrasound ablation.

The subthalamic nucleus (STN) modulates basal ganglia output and plays a fundamental role in the pathophysiology of Parkinson's disease (PD). Blockade/ablation of the STN improves motor signs in PD. We assessed the topography of focused ultrasound subthalamotomy (n = 39) by voxel-based lesion-symptom mapping to identify statistically validated brain voxels with the optimal effect against each cardinal feature and their respective cortical connectivity patterns by diffusion-weighted tractography. Bradykinesia and rigidity amelioration were associated with ablation of the rostral motor STN subregion connected to the supplementary motor and premotor cortices, whereas antitremor effect was explained by lesioning the posterolateral STN projection to the primary motor cortex. These findings were corroborated prospectively in another PD cohort (n = 12). This work concurs with recent deep brain stimulation findings that suggest different corticosubthalamic circuits underlying each PD cardinal feature. Our results provide sound evidence in humans of segregated anatomy of subthalamic-cortical connections and their distinct role in PD pathophysiology and normal motor control.