The effect of resection of gliomas of the primary motor and sensory cortex on functional recovery and seizure outcome: A 10-year retrospective study.

Background: Gliomas, the most common primary brain tumors, pose surgical challenges in eloquent cortex regions due to potential deficits affecting patients' quality of life (QOL) and increased mortality risk. This study investigates motor and sensory recovery postresection of Rolandic cortex gliomas in 40 patients, alongside seizure outcomes and the efficacy of intraoperative techniques such as awake craniotomy. Methods: This was a 10-year monocentric retrospective study based on the experience of a neurosurgeon in the resection of Rolandic gliomas and its impact on 40 patients' QOL in a period from 2011 to 2020. The primary outcomes were tumor recurrence and the efficacy of the surgery defined as survival status, seizure status, and sensory and motor neurological deficits. Data collection included demographic, tumor, and surgical outcome variables. The extent of resection (EOR) was classified as gross total resection (GTR) (EOR ≥95%) or subtotal resection (EOR <95%). Statistical analysis involved descriptive statistics and inferential tests for outcome comparisons. Results: Patients were aged an average of 42.3 ± 14 years and distributed between 72.5% of males and 27.5% of females. The most common presentation was seizures (65%). The tumor was located in the frontal lobe at 65%, the motor at 75%, and the top tumor pathology was oligodendroglioma (42.5%). The recurrence rate in the study was 20% (8 of 40), and the 1-year survival rate was 92.5%. After the resection, significant improvement was shown in Karnofsky's performance status (P = 0.007), in normal daily activities (P = 0.001), in fine motor skills (P = 0.020), and work hobbies (P = 0.046). No statistically significant improvement was shown in seizures and deficit rates. Recurrence was not associated with the demographic characteristics, clinical presentation, tumor-related characteristics (location, area, side, and mutation), tumor resection, and adjuvant treatment (P > 0.05). Conclusion: GTR of Rolandic gliomas can be achieved with the use of meticulous stimulation mapping, and complete functional recovery is attainable despite common belief.

Volume electron microscopy analysis of synapses in primary regions of the human cerebral cortex.

Functional and structural studies investigating macroscopic connectivity in the human cerebral cortex suggest that high-order associative regions exhibit greater connectivity compared to primary ones. However, the synaptic organization of these brain regions remains unexplored. In the present work, we conducted volume electron microscopy to investigate the synaptic organization of the human brain obtained at autopsy. Specifically, we examined layer III of Brodmann areas 17, 3b, and 4, as representative areas of primary visual, somatosensorial, and motor cortex. Additionally, we conducted comparative analyses with our previous datasets of layer III from temporopolar and anterior cingulate associative cortical regions (Brodmann areas 24, 38, and 21). 9,690 synaptic junctions were 3D reconstructed, showing that certain synaptic characteristics are specific to particular regions. The number of synapses per volume, the proportion of the postsynaptic targets, and the synaptic size may distinguish one region from another, regardless of whether they are associative or primary cortex. By contrast, other synaptic characteristics were common to all analyzed regions, such as the proportion of excitatory and inhibitory synapses, their shapes, their spatial distribution, and a higher proportion of synapses located on dendritic spines. The present results provide further insights into the synaptic organization of the human cerebral cortex.

Investigating the Effects of Repetitive Paired-Pulse Transcranial Magnetic Stimulation on Visuomotor Training Using TMS-EEG.

I-wave periodicity repetitive paired-pulse transcranial magnetic stimulation (iTMS) can modify acquisition of a novel motor skill, but the associated neurophysiological effects remain unclear. The current study therefore used combined TMS-electroencephalography (TMS-EEG) to investigate the neurophysiological effects of iTMS on subsequent visuomotor training (VT). Sixteen young adults (26.1 ± 5.1 years) participated in three sessions including real iTMS and VT (iTMS + VT), control iTMS and VT (iTMSControl + VT), or iTMS alone. Motor-evoked potentials (MEPs) and TMS-evoked potentials (TEPs) were measured before and after iTMS, and again after VT, to assess neuroplastic changes. Irrespective of the intervention, MEP amplitude was not changed after iTMS or VT. Motor skill was improved compared with baseline, but no differences were found between stimulus conditions. In contrast, the P30 peak was altered by VT when preceded by control iTMS (P < 0.05), but this effect was not apparent when VT was preceded by iTMS or following iTMS alone (all P > 0.15). In contrast to expectations, iTMS was unable to modulate MEP amplitude or influence motor learning. Despite this, changes in P30 amplitude suggested that motor learning was associated with altered cortical reactivity. Furthermore, this effect was abolished by priming with iTMS, suggesting an influence of priming that failed to impact learning.

Motor cortex activation mediates associations between striatal dopamine depletion and manual dexterity in Parkinson's disease.

INTRODUCTION: Parkinson's disease (PD) presents with a progressive decline in manual dexterity, attributed to dysfunction in the basal ganglia-thalamus-cortex loop, influenced by dopaminergic deficits in the striatum. Recent research suggests that the motor cortex may play a pivotal role in mediating the relationship between striatal dopamine depletion and motor function in PD. Understanding this connection is crucial for comprehending the origins of manual dexterity impairments in PD. Therefore, our study aimed to explore how motor cortex activation mediates the association between striatal dopamine depletion and manual dexterity in PD. MATERIALS AND METHODS: We enrolled 26 mildly affected PD patients in their off-medication phase to undergo [18F]FDOPA PET/CT scans for evaluating striatal dopaminergic function. EEG recordings were conducted during bimanual anti-phase finger tapping tasks to evaluate motor cortex activity, specifically focusing on Event-Related Desynchronization in the beta band. Manual dexterity was assessed using the Purdue Pegboard Test. Regression-based mediation analysis was conducted to examine whether motor cortex activation mediates the association between striatal dopamine depletion and manual dexterity in PD. RESULTS: Mediation analysis revealed a significant direct effect of putamen dopamine depletion on manual dexterity for the affected hand and assembly tasks (performed with two hands), with motor cortex activity mediating this association. In contrast, while caudate nucleus dopamine depletion showed a significant direct effect on manual dexterity, motor cortex mediation on this association was not observed. CONCLUSION: Our study confirms the association between striatum dopamine depletion and impaired manual dexterity in PD, with motor cortex activity mediating this relationship.

Immersive virtual reality in orthopedic hand therapy.

Emerging advances in immersive virtual reality incorporating optical hand-tracking present promising potential for application in orthopedic hand therapy. The system is designed to analyze hand movements, enabling users to "use" their hands virtually in any fabricated setting. This article, supplemented with videos, examines practical applications of immersive virtual reality in routine hand therapy and provides a scientific presentation of the interaction of immersive virtual reality with our physiological and neurological systems. Indications for immersive virtual reality use, critical evaluations and recommendations are comprehensively discussed. Immersive virtual reality has the potential to evolve into a standard treatment modality in orthopedic hand therapy.

Functional states of prelimbic and related circuits during the acquisition of a GO/noGO task in rats.

GO/noGO tasks enable assessing decision-making processes and the ability to suppress a specific action according to the context. Here, rats had to discriminate between 2 visual stimuli (GO or noGO) shown on an iPad screen. The execution (for GO) or nonexecution (for noGO) of the selected action (to touch or not the visual display) were reinforced with food. The main goal was to record and to analyze local field potentials collected from cortical and subcortical structures when the visual stimuli were shown on the touch screen and during the subsequent activities. Rats were implanted with recording electrodes in the prelimbic cortex, primary motor cortex, nucleus accumbens septi, basolateral amygdala, dorsolateral and dorsomedial striatum, hippocampal CA1, and mediodorsal thalamic nucleus. Spectral analyses of the collected data demonstrate that the prelimbic cortex was selectively involved in the cognitive and motivational processing of the learning task but not in the execution of reward-directed behaviors. In addition, the other recorded structures presented specific tendencies to be involved in these 2 types of brain activity in response to the presentation of GO or noGO stimuli. Spectral analyses, spectrograms, and coherence between the recorded brain areas indicate their specific involvement in GO vs. noGO tasks.

Cortico-basal ganglia plasticity in motor learning.

One key function of the brain is to control our body's movements, allowing us to interact with the world around us. Yet, many motor behaviors are not innate but require learning through repeated practice. Among the brain's motor regions, the cortico-basal ganglia circuit is particularly crucial for acquiring and executing motor skills, and neuronal activity in these regions is directly linked to movement parameters. Cell-type-specific adaptations of activity patterns and synaptic connectivity support the learning of new motor skills. Functionally, neuronal activity sequences become structured and associated with learned movements. On the synaptic level, specific connections become potentiated during learning through mechanisms such as long-term synaptic plasticity and dendritic spine dynamics, which are thought to mediate functional circuit plasticity. These synaptic and circuit adaptations within the cortico-basal ganglia circuitry are thus critical for motor skill acquisition, and disruptions in this plasticity can contribute to movement disorders.

Cholinergic modulation of interhemispheric inhibition in the mouse motor cortex.

Interhemispheric inhibition of the homotopic motor cortex is believed to be effective for accurate unilateral motor function. However, the cellular mechanisms underlying interhemispheric inhibition during unilateral motor behavior remain unclear. Furthermore, the impact of the neuromodulator acetylcholine on interhemispheric inhibition and the associated cellular mechanisms are not well understood. To address this knowledge gap, we conducted recordings of neuronal activity from the bilateral motor cortex of mice during the paw-reaching task. Subsequently, we analyzed interhemispheric spike correlation at the cell-pair level, classifying putative cell types to explore the underlying cellular circuitry mechanisms of interhemispheric inhibition. We found a cell-type pair-specific enhancement of the interhemispheric spike correlation when the mice were engaged in the reaching task. We also found that the interhemispheric spike correlation was modulated by pharmacological acetylcholine manipulation. The local field responses to contralateral excitation differed along the cortical depths, and muscarinic receptor antagonism enhanced the inhibitory component of the field response in deep layers. The muscarinic subtype M2 receptor is predominantly expressed in deep cortical neurons, including GABAergic interneurons. These results suggest that GABAergic interneurons expressing muscarinic receptors in deep layers mediate the neuromodulation of interhemispheric inhibition in the homotopic motor cortex.

Primary Motor Area Activity in Phantom Limb Imagery of Traumatic Unilateral Lower Limb Amputees With Phantom Limb Pain.

Introduction: Estimates of the worldwide increase in amputees raises the awareness to solve long-standing problems. Understanding the functional brain modifications after a lower limb amputation (LLA) is one of the first steps towards proposing new rehabilitation approaches. Functional modifications in the central nervous system due the amputation could be involved in prosthesis use failures and Phantom Limb Pain (PLP), increasing costs and overwhelming the health services. Objective: This study analyses orphan primary motor area (M1-Orphan) hemodynamic and metabolic behaviour, which previously controlled the limb that was amputated, in comparison with the M1-Preserved, responsible for the intact limb (IL) during phantom limb imagery moving during Mirror Therapy (MT), compared to Isolated Intact Limb Movement Task (I-ILMT). Methodology: A case-control study with unilateral traumatic LLA with moderate PLP who measured [oxy-Hb] and [deoxy-Hb] in the M1 area by Functional Near InfraredSpectroscopy (fNIRS) during the real (I-ILMT) and MT task. Results: Sixty-five patients, with 67.69% of men, young (40.32 ± 12.91), 65.63% amputated due motorcycle accidents, 4.71 ± 7.38 years ago, predominantly above the knee (57.14%). The M1 activation in the orphan cortex did not differ from the activation in the intact cortex during MT (P > .05). Conclusion: The perception of the Phantom limb moving or intact limb moving is metabolically equivalent in M1, even in the absence of a limb. In other words, the amputation does not alter the brain metabolism in control of phantom movement.

Motor cortical inactivation impairs corrective submovements in mice performing a hold-still center-out reach task.

Holding still and aiming reaches to spatial targets may depend on distinct neural circuits. Using automated homecage training and a sensitive joystick, we trained freely-moving mice to contact a joystick, hold their forelimb still, and then reach to rewarded target locations. Mice learned the task by initiating forelimb sequences with clearly resolved submillimeter-scale micromovements followed by millimeter-scale reaches to learned spatial targets. Hundreds of thousands of trajectories were decomposed into millions of kinematic submovements, while photoinhibition was used to test roles of motor cortical areas. Inactivation of both caudal and rostral forelimb areas preserved the ability to produce aimed reaches, but reduced reach speed. Inactivation specifically of contralateral caudal forelimb area (CFA) additionally impaired the ability to aim corrective submovements to remembered locations following target undershoots. Our findings show that motor cortical inactivations reduce the gain of forelimb movements but that inactivation specifically of contralateral CFA impairs corrective movements important for reaching a target location.

Age-related decline in GABAergic intracortical inhibition can be counteracted by long-term learning of balance skills.

Ageing induces a decline in GABAergic intracortical inhibition, which seems to be associated not only with decremental changes in well-being, sleep quality, cognition and pain management but also with impaired motor control. So far, little is known regarding whether targeted interventions can prevent the decline of intracortical inhibition in the primary motor cortex in the elderly. Therefore, the present study investigated whether age-related cortical dis-inhibition could be reversed after 6 months of balance learning and whether improvements in postural control correlated with the extent of reversed dis-inhibition. The results demonstrated that intracortical inhibition can be upregulated in elderly subjects after long-term balance learning and revealed a correlation between changes in balance performance and intracortical inhibition. This is the first study to show physical activity-related upregulation of GABAergic inhibition in a population with chronic dis-inhibition and may therefore be seminal for many pathologies in which the equilibrium between inhibitory and excitatory neurotransmitters is disturbed. KEY POINTS: Ageing induces a decline in GABAergic intracortical inhibition. So far, little is known regarding whether targeted interventions can prevent the decline of intracortical inhibition in the primary motor cortex in the elderly. After 6 months of balance learning, intracortical inhibition can be upregulated in elderly subjects. The results of this study also revealed a correlation between changes in balance performance and intracortical inhibition. This is the first study to show physical activity-related upregulation of GABAergic inhibition in a population with chronic dis-inhibition.

Investigating brain structure and tDCS response in obsessive-compulsive disorder.

Obsessive-Compulsive Disorder (OCD) is characterized by intrusive thoughts and repetitive behaviors, with associated brain abnormalities in various regions. This study explores the correlation between neural biomarkers and the response to transcranial Direct Current Stimulation (tDCS) in OCD patients. Using structural MRI data from two tDCS trials involving 55 OCD patients and 28 controls, cortical thickness, and gray matter morphometry was analyzed. Findings revealed thicker precentral and paracentral areas in OCD patients, compared to control (p < 0.001). Correlations between cortical thickness and treatment response indicated a significant association between a thinner precentral area and reduced Yale-Brown Obsessive Compulsive Scale (YBOCS) scores (p = 0.02). While results highlight the complexity of treatment response predictors, this study sheds light on potential neural markers for tDCS response in OCD patients. Further investigations with larger datasets are warranted to better understand the underpinnings of these biomarkers and their implications for personalized treatment approaches.

The effects of combining sensorimotor training with transcranial direct current stimulation on the anticipatory and compensatory postural adjustments in patients with chronic low back pain.

PURPOSE: To investigate the effects of concurrent sensorimotor training (SMT) and transcranial direct current stimulation (tDCS) on the anticipatory and compensatory postural adjustments (APAs and CPAs) in patients with chronic low back pain (CLBP). METHOD: The interventions included (1) SMT plus tDCS and (2) SMT plus sham tDCS. Outcome measures were the normalized integrals of electromyography activity (NIEMG) during the phases of anticipatory and compensatory, and muscle onset latency. The investigated muscles were ipsilateral and contralateral multifidus (MF), transversus abdominus/internal oblique (TrA/IO), and gluteus medius (GM). RESULTS: Between-group comparisons demonstrated that ipsilateral TrA/IO NIEMG during CPA1 (p = 0.010) and ipsilateral GM NIEMG during CPA1 (p = 0.002) and CPA2 (p = 0.025) were significantly lower in the SMT combined with tDCS than in the control group. Furthermore, this group had greater NIEMG for contralateral GM during APA1 than the control group (p = 0.032). Moreover, the onset latency of contralateral TrA/IO was significantly earlier after SMT combined with tDCS (p = 0.011). CONCLUSIONS: Both groups that received SMT showed positive effects, but anodal tDCS had an added value over sham stimulation for improving postural control strategies in patients with CLBP. Indeed, SMT combined with tDCS leads to stronger APA and less demand for CPA. RCT REGISTRATION NUMBER: IRCT20220228054149N1. REGISTRATION DATE: 2022-04-04.

Evidence suggests that reduced excitability in the sensory and motor cortex is linked to chronic and recurring lower back pain.Increasing the excitability of these two areas using anodal transcranial direct current stimulation (tDCS), in conjunction with sensorimotor training (SMT), may improve anticipatory and compensatory postural control strategies.This study showed that the combination of SMT with tDCS targeting the sensory and motor cortex notably enhances motor preparation and refines postural control strategies in patients with chronic unilateral lumbar radiculopathy.Rehabilitation professionals are encouraged to integrate SMT with tDCS into treatment protocols to enhance the ability of individuals with back pain to handle postural disturbances in daily life, thereby potentially alleviating the persistence of their symptoms.Incorporating brain stimulation enhances the effectiveness of SMT for patients with chronic unilateral lumbar radiculopathy.

Simulating tDCS electrode placement to stimulate both M1 and SMA enhances motor performance and modulates cortical excitability depending on current flow direction.

Introduction: The conventional method of placing transcranial direct current stimulation (tDCS) electrodes is just above the target brain area. However, this strategy for electrode placement often fails to improve motor function and modulate cortical excitability. We investigated the effects of optimized electrode placement to induce maximum electrical fields in the leg regions of both M1 and SMA, estimated by electric field simulations in the T1and T2-weighted MRI-based anatomical models, on motor performance and cortical excitability in healthy individuals. Methods: A total of 36 healthy volunteers participated in this randomized, triple-blind, sham-controlled experiment. They were stratified by sex and were randomly assigned to one of three groups according to the stimulation paradigm, including tDCS with (1) anodal and cathodal electrodes positioned over FCz and POz, respectively, (A-P tDCS), (2) anodal and cathodal electrodes positioned over POz and FCz, respectively, (P-A tDCS), and (3) sham tDCS. The sit-to-stand training following tDCS (2 mA, 10 min) was conducted every 3 or 4 days over 3 weeks (5 sessions total). Results: Compared to sham tDCS, A-P tDCS led to significant increases in the number of sit-to-stands after 3 weeks training, whereas P-A tDCS significantly increased knee flexor peak torques after 3 weeks training, and decreased short-interval intracortical inhibition (SICI) immediately after the first session of training and maintained it post-training. Discussion: These results suggest that optimized electrode placement of the maximal EF estimated by electric field simulation enhances motor performance and modulates cortical excitability depending on the direction of current flow.

Effects of Tempo-Controlled Resistance Training on Corticospinal Tract Plasticity in Healthy Controls: A Systematic Review.

After musculoskeletal injuries, there is often a loss of corticospinal control. Current tendon rehabilitation may not adequately address the corticospinal control of the muscle which may contribute to the recalcitrance of symptom recurrence. This review provides a summary of the current literature regarding the effectiveness of tempo-controlled resistance training (TCRT) in (1) promoting corticospinal plasticity, (2) improving physical performance, and (3) improving strength outcomes in healthy adults. A comprehensive literature search was conducted using electronic databases (PubMed, CINAHL, Embase, and Google Scholar) to identify relevant studies published between 2010 and 2023. Randomized control (RCT) studies that included recreationally trained and untrained healthy adults between 18 and 60 years of age and that compared a TCRT intervention to a control condition were included. Twelve of the 1255 studies identified in the initial search were included in the final analysis. Throughout all included studies, TCRT was shown to elicit greater neural adaptations compared to traditional resistance training methods (i.e., self-paced strength training). These results indicate that TCRT holds promise as an effective method for modulating corticospinal plasticity in healthy adults and may enhance neuromuscular adaptations, including improvements in CSE, decreased SICI, enhanced motor unit synchronization, and voluntary muscle activation.

Exploring the Consistent Roles of Motor Areas Across Voluntary Movement and Locomotion.

Multiple cortical motor areas are critically involved in the voluntary control of discrete movement (e.g., reaching) and gait. Here, we outline experimental findings in nonhuman primates with clinical reports and research in humans that explain characteristic movement control mechanisms in the primary, supplementary, and presupplementary motor areas, as well as in the dorsal premotor area. We then focus on single-neuron activity recorded while monkeys performed motor sequences consisting of multiple discrete movements, and we consider how area-specific control mechanisms may contribute to the performance of complex movements. Following this, we explore the motor areas in cats that we have considered as analogs of those in primates based on similarities in their cortical surface topology, anatomic connections, microstimulation effects, and activity patterns. Emphasizing that discrete movement and gait modification entail similar control mechanisms, we argue that single-neuron activity in each area of the cat during gait modification is compatible with the function ascribed to the activity in the corresponding area in primates, recorded during the performance of discrete movements. The findings that demonstrate the premotor areas' contribution to locomotion, currently unique to the cat model, should offer highly valuable insights into the control mechanisms of locomotion in primates, including humans.

Sex differences in motor learning flexibility are accompanied by sex differences in mushroom spine pruning of the mouse primary motor cortex during adolescence.

Background: Although males excel at motor tasks requiring strength, females exhibit greater motor learning flexibility. Cognitive flexibility is associated with low baseline mushroom spine densities achieved by pruning which can be triggered by α4ßδ GABAA receptors (GABARs); defective synaptic pruning impairs this process. Methods: We investigated sex differences in adolescent pruning of mushroom spine pruning of layer 5 pyramidal cells of primary motor cortex (L5M1), a site essential for motor learning, using microscopic evaluation of Golgi stained sections. We assessed α4GABAR expression using immunohistochemical and electrophysiological techniques (whole cell patch clamp responses to 100 nM gaboxadol, selective for α4ßδ GABARs). We then compared performance of groups with different post-pubertal mushroom spine densities on motor learning (constant speed) and learning flexibility (accelerating speed following constant speed) rotarod tasks. Results: Mushroom spines in proximal L5M1 of female mice decreased >60% from PND35 (puberty onset) to PND56 (Pubertal: 2.23 ± 0.21 spines/10 µm; post-pubertal: 0.81 ± 0.14 spines/10 µm, P < 0.001); male mushroom spine density was unchanged. This was due to greater α4ßδ GABAR expression in the female (P < 0.0001) because α4 -/- mice did not exhibit mushroom spine pruning. Although motor learning was similar for all groups, only female wild-type mice (low mushroom spine density) learned the accelerating rotarod task after the constant speed task (P = 0.006), a measure of motor learning flexibility. Conclusions: These results suggest that optimal motor learning flexibility of female mice is associated with low baseline levels of post-pubertal mushroom spine density in L5M1 compared to male and female α4 -/- mice.

Goal-directed action preparation in humans entails a mixture of corticospinal neural computations.

The seemingly effortless ability of humans to transition from thinking about actions to initiating them relies on sculpting corticospinal output from primary motor cortex. This study tested whether canonical additive and multiplicative neural computations, well-described in sensory systems, generalize to the corticospinal pathway during human action preparation. We used non-invasive brain stimulation to measure corticospinal input-output across varying action preparation contexts during instructed-delay finger response tasks. Goal-directed action preparation was marked by increased multiplicative gain of corticospinal projections to task-relevant muscles and additive suppression of corticospinal projections to non-selected and task-irrelevant muscles. Individuals who modulated corticospinal gain to a greater extent were faster to initiate prepared responses. Our findings provide physiological evidence of combined additive suppression and gain modulation in the human motor system. We propose these computations support action preparation by enhancing the contrast between selected motor representations and surrounding background activity to facilitate response selection and execution.

Effects of Anti-CGRP Monoclonal Antibodies on Neurophysiological and Clinical Outcomes: A Combined Transcranial Magnetic Stimulation and Algometer Study.

BACKGROUND: the aim of this study was to investigate the neurophysiological effect of anti-CGRP monoclonal antibodies on central and peripheral levels in migraine patients. METHODS: An observational cohort study in patients with migraine was performed. All subjects underwent Single-Pulse and Paired-Pulse Transcranial Magnetic Stimulation, as well as a Pressure Pain Threshold assessment. The same protocol was repeated three and four months after the first injection of anti-CGRP monoclonal antibodies. RESULTS: A total of 11 patients with a diagnosis of migraine and 11 healthy controls were enrolled. The main findings of this study are the significant effects of anti-CGRP mAb treatment on the TMS parameters of intracortical inhibition and the rise in the resting motor threshold in our group of patients affected by resistant migraine. The clinical effect of therapy on migraine is associated with the increase in short-interval intracortical inhibition (SICI), resting motor threshold (RMT), and Pressure Pain Threshold (PPT). In all patients, all clinical headache parameters improved significantly 3 months after the first injection of mAbs and the improvement was maintained at the 1-month follow-up. At baseline, migraineurs and HCs had significant differences in all TMS parameters and in PPT, while at follow-up assessment, no differences were observed on RMT, SICI, and PPT between the two groups. After anti-CGRP monoclonal antibody injection, a significant increase in the intracortical inhibition, in the motor threshold, and in the Pressure Pain Threshold in critical head areas was observed in patients with migraine, which was related to significant clinical benefits. CONCLUSIONS: Anti-CGRP monoclonal antibodies improved clinical and neurophysiological outcomes, reflecting a normalization of cortical excitability and peripheral and central sensitization. By directly acting on the thalamus or hypothalamus and indirectly on the trigeminocervical complex, treatment with anti-CGRP monoclonal antibodies may modulate central sensorimotor excitability and peripheral sensitization pain.

Electroacupuncture alleviates motor dysfunction by regulating neuromuscular junction disruption and neuronal degeneration in SOD1G93A mice.

Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease characterized by the progressive destruction of the neuromuscular junction (NMJ) and the degeneration of motor neurons, eventually leading to atrophy and paralysis of voluntary muscles responsible for motion and breathing. NMJs, synaptic connections between motor neurons and skeletal muscle fibers, are extremely fragile in ALS. To determine the effects of early electroacupuncture (EA) intervention on nerve reinnervation and regeneration following injury, a model of sciatic nerve injury (SNI) was first established using SOD1G93A mice, and early electroacupuncture (EA) intervention was conducted at Baihui (DU20), and bilateral Zusanli (ST36). The results revealed that EA increased the Sciatic nerve Functional Index, the structural integrity of the gastrocnemius muscles, and the cross-sectional area of muscle fibers, as well as up-regulated the expression of acetylcholinesterase and facilitated the co-location of α7 nicotinic acetate choline receptors and α-actinin. Overall, these results suggested that EA can promote the repair and regeneration of injured nerves and delay NMJ degeneration in SOD1G93A-SNI mice. Moreover, analysis of the cerebral cortex demonstrated that EA alleviated cortical motor neuron damage in SOD1G93A mice, potentially attributed to the inhibition of the cyclic GMP-AMP synthase-stimulator of interferon genes pathway and the release of interferon-ß suppressing the activation of natural killer cells and the secretion of interferon-γ, thereby further inhibiting microglial activation and the expression of inflammatory factors. In summary, EA delayed the degeneration of NMJ and mitigated the loss of cortical motor neurons, thus delaying disease onset, accompanied by alleviation of muscle atrophy and improvements in motor function in SOD1G93A mice.