Cortical Silent Period Research Articles

Preoperative nTMS analysis: a sensitive tool to detect imminent motor deficits in brain tumor patients.

One of the challenges in surgery of tumors in motor eloquent areas is the individual risk assessment for postoperative motor disorder. Previously a regression model was developed that permits estimation of the risk prior to surgery based on topographical and neurophysiological data derived from investigation with nTMS (navigated Transcranial Magnetic Stimulation). This study aims to analyze the impact of including additional neurophysiological TMS parameters into the established risk stratification model for motor outcome after brain tumor surgery. Biometric and clinical data of 170 patients with glioma in motor eloquent areas were collected prospectively. In addition, the following nTMS parameters were collected bihemispherically prior to surgery: resting motor threshold (RMT), recruitment curve (RC), cortical silent period (CSP) and a nTMS based fibertracking to measure the tumor tract distance (TTD). Motor function was quantified by Medical Research Council Scale (MRCS) preoperatively, seven days and three months postoperatively. Association between nTMS parameters and postoperative motor outcome was investigated in bivariate and multivariable analyses. The bivariate analysis confirmed the association of RMT ratio with the postoperative motor outcome after seven days with higher rates of worsening in patients with RMT ratio > 1.1 compared to patients with RMT ratio ≤ 1.1 (31.6% vs. 15.1%, p = 0.009). Similarly, an association between a pathological CSP ratio and a higher risk of new postoperative motor deficits after seven days was observed (35.3% vs. 16.7% worsening, p = 0.025). A pathological RC Ratio was associated postoperative deterioration of motor function after three months (42.9% vs. 16.2% worsening, p = 0.004). In multiple regression analysis, none of these associations were statistically robust. The current results suggest that the RC ratio, CSP ratio and RMT ratio individually are sensitive markers associated with the motor outcome 7days and 3months after tumor resection in a presumed motor eloquent location. They can therefore supply valuable information during preoperative risk-benefit-balancing. However, underlying neurophysiological mechanisms might be too similar to make the parameters meaningful in a combined model.

Examining motor evidence for the pause-then-cancel model of action-stopping: Insights from motor system physiology.

Stopping initiated actions is fundamental to adaptive behavior. Longstanding, single-process accounts of action-stopping have been challenged by recent, two-process, 'pause-then-cancel' models. These models propose that action-stopping involves two inhibitory processes: 1) a fast Pause process, which broadly suppresses the motor system as the result of detecting any salient event, and 2) a slower Cancel process, which involves motor suppression specific to the cancelled action. A purported signature of the Pause process is global suppression, or the reduced corticospinal excitability (CSE) of task-unrelated effectors early on in action-stopping. However, unlike the Pause process, few (if any) motor system signatures of a Cancel process have been identified. Here, we used single- and paired-pulse TMS methods to comprehensively measure the local physiological excitation and inhibition of both responding and task-unrelated motor effector systems during action-stopping. Specifically, we measured CSE, short-interval intracortical inhibition (SICI), and the duration of the cortical silent period (CSP). Consistent with key predictions from the pause-then-cancel model, CSE measurements at the responding effector indicated that additional suppression was necessary to counteract Go-related increases in CSE during action-stopping, particularly at later timepoints. Increases in SICI on Stop-signal trials did not differ across task-related and task-unrelated effectors, or across timepoints. This suggests SICI as a potential source of global suppression. Increases in CSP duration on Stop-signal trials were more prominent at later timepoints and were related to individual differences in CSE. Our study provides further evidence from motor system physiology that multiple inhibitory processes influence action-stopping.

The effects of exercise, heat-induced hypo-hydration and rehydration on blood-brain-barrier permeability, corticospinal and peripheral excitability.

The effects of low-intensity exercise, heat-induced hypo-hydration and rehydration on maximal strength and the underlying neurophysiological mechanisms are not well understood. To assess this, 12 participants took part in a randomised crossover study, in a prolonged (3h) submaximal (60W) cycling protocol under 3 conditions: (i) in 45°C (achieving ~ 5% body mass reduction), with post-exercise rehydration in 2h (RHY2), (ii) with rehydration across 24h (RHY24), and (iii) a euhydrated trial in 25°C (CON). Dependent variables included maximal voluntary contractions (MVC), maximum motor unit potential (MMAX), motor evoked potential (MEPRAW) amplitude and cortical silent period (cSP) duration. Blood-brain-barrier integrity was also assessed by serum Ubiquitin Carboxyl-terminal Hydrolase (UCH-L1) concentrations. All measures were obtained immediately pre, post, post 2h and 24h. During both dehydration trials, MVC (RHY2: p < 0.001, RHY24: p = 0.001) and MEPRAW (RHY2: p = 0.025, RHY24: p = 0.045) decreased from pre- to post-exercise. MEPRAW returned to baseline during RHY2 and CON, but not RHY24 (p = 0.020). MEP/MMAX ratio decreased across time for all trials (p = 0.009) and returned to baseline, except RHY24 (p < 0.026). Increased cSP (p = 0.011) was observed during CON post-exercise, but not during RHY2 and RHY24. Serum UCH-L1 increased across time for all conditions (p < 0.001) but was not significantly different between conditions. Our findings demonstrate an increase in corticospinal inhibition after exercise with fluid ingestion, but a decrease in corticospinal excitability after heat-induced hypo-hydration. In addition, low-intensity exercise increases peripheral markers of blood-brain-barrier permeability.Kindly check and confirm inserted city name correctly identified in affiliation 7This is correct.

Clinical and neurophysiological effects of bilateral repetitive transcranial magnetic stimulation and EEG-guided neurofeedback in Parkinson’s disease: a randomized, four-arm controlled trial

BackgroundRepetitive Transcranial Magnetic Stimulation (rTMS) and EEG-guided neurofeedback techniques can reduce motor symptoms in Parkinson’s disease (PD). However, the effects of their combination are unknown. Our objective was to determine the immediate and short-term effects on motor and non-motor symptoms, and neurophysiological measures, of rTMS and EEG-guided neurofeedback, alone or combined, compared to no intervention, in people with PD.MethodsA randomized, single-blinded controlled trial with 4 arms was conducted. Group A received eight bilateral, high-frequency (10 Hz) rTMS sessions over the Primary Motor Cortices; Group B received eight 30-minute EEG-guided neurofeedback sessions focused on reducing average bilateral alpha and beta bands; Group C received a combination of A and B; Group D did not receive any therapy. The primary outcome measure was the UPDRS-III at post-intervention and two weeks later. Secondary outcomes were functional mobility, limits of stability, depression, health-related quality-of-life and cortical silent periods. Treatment effects were obtained by longitudinal analysis of covariance mixed-effects models.ResultsForty people with PD participated (27 males, age = 63 ± 8.26 years, baseline UPDRS-III = 15.63 ± 6.99 points, H&Y = 1–3). Group C showed the largest effect on motor symptoms, health-related quality-of-life and cortical silent periods, followed by Group A and Group B. Negligible differences between Groups A-C and Group D for functional mobility or limits of stability were found.ConclusionsThe combination of rTMS and EEG-guided neurofeedback diminished overall motor symptoms and increased quality-of-life, but this was not reflected by changes in functional mobility, postural stability or depression levels.Trial registrationNCT04017481.

Lowered ratio of corticospinal excitation to inhibition predicts greater disability, poorer motor and cognitive function in multiple sclerosis

ObjectiveInvestigate excitatory-inhibitory (E/I) (im)balance using transcranial magnetic stimulation (TMS) in individuals with Multiple Sclerosis (MS) and determine its validity as a neurophysiological biomarker of disability. MethodsParticipants with MS (n = 83) underwent TMS, cognitive, and motor function assessments. TMS-induced motor evoked potential amplitudes (excitability) and cortical silent periods (inhibition) were assessed bilaterally through recruitment curves. The E/I ratio was calculated as the ratio of excitation to inhibition. ResultsParticipants with greater disability (Expanded Disability Status Scale, EDSS≥3) exhibited lower excitability and increased inhibition compared to those with lower disability (EDSS<3). This resulted in lower E/I ratios in the higher disability group. Individuals with higher disability presented with asymmetrical E/I ratios between brain hemispheres, a pattern not present in the group with lower disability. In regression analyses controlling for demographics, lowered TMS-probed E/I ratio predicted variance in disability (R2 = 0.37, p < 0.001), upper extremity function (R2 = 0.35, p < 0.001), walking speed (R2 = 0.22, p = 0.005), and cognitive performance (R2 = 0.25, p = 0.007). Receiver Operating Characteristic curve analysis confirmed ‘excellent’ discriminative ability of the E/I ratio in distinguishing high and low disability. Finally, excitation superiorly correlated with the E/I ratio than overall inhibition in both hemispheres (p ≤ 0.01). ConclusionThe E/I ratio is a potential neurophysiological biomarker of disability level in MS, especially when assessed in the hemisphere corresponding to the weaker body side. Interventions aimed at increasing cortical excitation or reducing inhibition may restore E/I balance potentially stalling progression or improving function in MS.

Exploring stimulus-response characteristics of late cortical silent period in major depressive disorder

Exploring stimulus-response characteristics of late cortical silent period in major depressive disorder

Water and brain function: effects of hydration status on neurostimulation with transcranial magnetic stimulation.

Neurostimulation/neurorecording are tools to study, diagnose, and treat neurological/psychiatric conditions. Both techniques depend on volume conduction between scalp and excitable brain tissue. Here, we examine how neurostimulation with transcranial magnetic stimulation (TMS) is affected by hydration status, a physiological variable that can influence the volume of fluid spaces/cells, excitability, and cellular/global brain functioning. Normal healthy adult participants (32, 9 males) had common motor TMS measures taken in a repeated-measures design from dehydrated (12-h overnight fast/thirst) and rehydrated (identical dehydration protocol followed by rehydration with 1 L water in 1 h) testing days. The target region was left primary motor cortex hand area. Response at the target muscle was recorded with electromyography. Urinalysis confirmed hydration status. Motor hotspot shifted in half of participants. Motor threshold decreased in rehydration, indicating increased excitability. Even after redosing/relocalizing TMS to the new threshold/hotspot, rehydration still showed evidence of increased excitability: recruitment curve measures generally shifted upward and the glutamate-dependent paired-pulse protocol, short intracortical facilitation (SICF), was increased. Short intracortical inhibition (SICI), long intracortical inhibition (LICI), long intracortical facilitation (LICF), and cortical silent period (CSP) were relatively unaffected. The hydration perturbations were mild/subclinical based on the magnitude/speed and urinalysis. Motor TMS measures showed evidence of expected physiological changes of osmotic challenges. Rehydration showed signs of macroscopic and microscopic volume changes including decreased scalp-cortex distance (brain closer to stimulator) and astrocyte swelling-induced glutamate release. Hydration may be a source of variability affecting any techniques dependent on brain volumes/volume conduction. These concepts are important for researchers/clinicians using such techniques or dealing with the wide variety of disease processes involving water balance.NEW & NOTEWORTHY Hydration status can affect brain volumes and excitability, which should affect techniques dependent on electrical volume conduction, including neurostimulation/recording. We test the previously unknown effects of hydration on neurostimulation with TMS and briefly review relevant physiology of hydration. Rehydration showed lower motor threshold, shifted motor hotspot, and generally larger responses even after compensating for threshold/hotspot changes. This is important for clinical and research applications of neurostimulation/neurorecording and the many clinical disorders related to water balance.

Excitation/inhibition imbalance in schizophrenia: a meta-analysis of inhibitory and excitatory TMS-EMG paradigms

Cortical excitation-inhibition (E/I) imbalance is a potential model for the pathophysiology of schizophrenia. Previous research using transcranial magnetic stimulation (TMS) and electromyography (EMG) has suggested inhibitory deficits in schizophrenia. In this meta-analysis we assessed the reliability and clinical potential of TMS-EMG paradigms in schizophrenia following the methodological recommendations of the PRISMA guideline and the Cochrane Handbook. The search was conducted in three databases in November 2022. Included articles reported Short-Interval Intracortical Inhibition (SICI), Intracortical Facilitation (ICF), Long-Interval Intracortical Inhibition (LICI) and Cortical Silent Period (CSP) in patients with schizophrenia and healthy controls. Meta-analyses were conducted using a random-effects model. Subgroup analysis and meta-regressions were used to assess heterogeneity. Results of 36 studies revealed a robust inhibitory deficit in schizophrenia with a significant decrease in SICI (Cohen’s d: 0.62). A trend-level association was found between SICI and antipsychotic medication. Our findings support the E/I imbalance hypothesis in schizophrenia and suggest that SICI may be a potential pathophysiological characteristic of the disorder.

Different descending pathways mediate early and late portions of lower limb responses to transcranial magnetic stimulation.

Although recent studies in nonhuman primates have provided evidence that transcranial magnetic stimulation (TMS) activates cells within the reticular formation, it remains unclear whether descending brain stem projections contribute to the generation of TMS-induced motor evoked potentials (MEPs) in skeletal muscles. We compared MEPs in muscles with extensive direct corticomotoneuronal input (first dorsal interosseous) versus a prominent role in postural control (gastrocnemius) to determine whether the amplitudes of early and late MEPs were differentially modulated by cortical suppression. Suprathreshold TMS was applied with and without a preceding suprathreshold TMS pulse at two interstimulus intervals (50 and 80 ms). H reflexes in target muscles were also tested with and without TMS conditioning. Early and late gastrocnemius MEPs were differentially modulated by cortical inhibition, the amplitude of the early MEP being significantly reduced by cortical suppression and the late MEP facilitated. The amplitude of H reflexes in the gastrocnemius was reduced within the cortical silent period. Early MEPs in the first dorsal interosseous were also reduced during the silent period, but late MEPs were unaffected. Independent modulation of early and late MEPs in the gastrocnemius muscle supports the idea that the MEP is generated by multiple descending pathways. Suppression of the early MEP is consistent with transmission along the fast-conducting corticospinal tract, whereas facilitation of the late MEP suggests transmission along a corticofugal, potentially cortico-reticulospinal, pathway. Accordingly, differences in late MEP modulation between the first dorsal interosseous and gastrocnemius reflect an increased role of corticofugal pathways in the control of postural muscles.NEW & NOTEWORTHY Early and late portions of the response to transcranial magnetic stimulation (TMS) in a lower limb postural muscle are modulated independently by cortical suppression, late motor evoked potentials (MEPs) being facilitated during cortical inhibition. These results suggest a cortico-brain stem transmission pathway for late portions of the TMS-induced MEP.

Can the cross-education of strength attenuate the impact of detraining after a period of strength training? A quasi-randomized trial

PurposeUnilateral strength training may attenuate the decline in muscle strength and size in homologous, contralateral muscles. This study aimed to determine whether the cross-education of strength could specifically attenuate the effects of detraining immediately after a short (prehabilitation-type) period of strength training.MethodsTwenty-six strength-trained participants were assigned to either four weeks of unilateral strength training of the stronger arm (UNI) or detraining (Detrain). Motor evoked potential (MEP) and cortical silent period (cSP) responses, muscle cross-sectional area (CSAFlexor; peripheral quantitative computed tomography) and maximal strength, rate of force development (RFD) and muscle activation (EMG) were examined in both elbow flexors before and after the intervention period.ResultsIn UNI, one-repetition maximum (1-RM) strength improved in both the trained (∆ = 2.0 ± 0.9 kg) and non-trained (∆ = 0.8 ± 0.9 kg) arms despite cessation of training of the weaker arm, whereas 1-RM strength was unchanged in Detrain. Maximal voluntary isometric contraction, isokinetic peak torque, and RFD did not change in either group. No neural changes were detected in UNI, but cSP increased in Detrain (∆ = 0.010 ± 0.015 s). CSAFlexor increased in the trained arm (∆ = 51 ± 43 mm2) but decreased in the non-trained arm (∆ = -53 ± 50 mm2) in UNI. CSAFlexor decreased in both arms in Detrain and at a similar rate to the non-trained arm in UNI.ConclusionUNI attenuated the effects of detraining in the weaker arm as shown by the improvement in 1-RM strength. However, the cross-education of strength did not attenuate the decline in muscle size in the contralateral arm.

Zolpidem improves task-specific dystonia: A randomized clinical trial integrating exploratory transcranial magnetic stimulation and [18F] FDG-PET imaging

BackgroundTask-specific dystonia (TSFD) is a disabling movement disorder. Effective treatment options are currently limited. Zolpidem was reported to improve primary focal and generalized dystonia in a proportion of patients. The mechanisms underlying its therapeutic effects have not yet been investigated. MethodsWe conducted a randomized, double-blind, placebo-controlled, crossover trial of single-dose zolpidem in 24 patients with TSFD. Patients were clinically assessed using Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), Writers' Cramp Rating Scale (WCRS), and Visual Analogue Scale (VAS), before and after receiving placebo and zolpidem. Transcranial magnetic stimulation was conducted on placebo and zolpidem to compare corticospinal excitability – active and resting motor thresholds (AMT and RMT), resting and active input/output curves and intracortical excitability - cortical silent period (CSP), short-interval intracortical inhibition curve (SICI), long-interval intracortical inhibition (LICI) and intracortical facilitation (ICF). Eight patients underwent brain FDG-PET imaging on zolpidem and placebo. ResultsZolpidem treatment improved TSFD. Zolpidem compared to placebo flattened rest and active input/output curves, reduced ICF and was associated with hypometabolism in the right cerebellum and hypermetabolism in the left inferior parietal lobule and left cingulum. Correlations were found between changes in dystonia severity on WCRS and changes in active input/output curve and in brain metabolism, respectively. Patients with lower RMT, and higher rest and active input/output curves exhibited better response to zolpidem compared to placebo. ConclusionsZolpidem improved TSFD by reducing corticomotor output and influencing crucial nodes in higher-order sensory and motor networks.

Excitatory/inhibitory motor balance reflects individual differences during joint action coordination.

Joint action (JA) is a continuous process of motor co-regulation based on the integration of contextual (top-down) and kinematic (bottom-up) cues from partners. The fine equilibrium between excitation and inhibition in sensorimotor circuits is, thus, central to such a dynamic process of action selection and execution. In a bimanual task adapted to become a unimanual JA task, the participant held a bottle (JA), while a confederate had to reach and unscrew either that bottle or another stabilized by a mechanical clamp (No_JA). Prior knowledge was manipulated in each trial such that the participant knew (K) or not (No_K) the target bottle in advance. Online transcranial magnetic stimulation (TMS) was administered at action-relevant landmarks to explore corticospinal excitability (CSE) and inhibition (cortical silent period [cSP]). CSE was modulated early on before the action started if prior information was available. In contrast, cSP modulation emerged later during the reaching action, regardless of prior information. These two indexes could thus reflect the concurrent elaboration of contextual priors (top-down) and the online sampling of partner's kinematic cues (bottom-up). Furthermore, participants selected either one of two possible behavioural strategies, preferring early or late force exertion on the bottle. One translates into a reduced risk of motor coordination failure and the other into reduced metabolic expenditure. Each strategy was characterised by a specific excitatory/inhibitory profile. In conclusion, the study of excitatory/inhibitory balance paves the way for the neurophysiological determination of individual differences in the combination of top-down and bottom-up processing during JA coordination.

Reduction in short interval intracortical inhibition from the early stage reflects the pathophysiology in amyotrophic lateral sclerosis: A meta-analysis study.

Cortical hyperexcitability has been identified as a diagnostic and pathogenic biomarker of amyotrophic lateral sclerosis (ALS). Cortical excitability is assessed by transcranial magnetic stimulation (TMS), a non-invasive neurophysiological technique. The TMS biomarkers exhibiting highest sensitivity for cortical hyperexcitability in ALS remain to be elucidated. A meta-analysis was performed to determine the TMS biomarkers exhibiting the highest sensitivity for cortical hyperexcitability in ALS. A systematic literature review was conducted of all relevant studies published in the English language by searching PubMed, MEDLINE, Embase and Scopus electronic databases from 1 January 2006 to 28 February 2023. Inclusion criteria included studies reporting the utility of threshold tracking TMS (serial ascending method) in ALS and controls. In total, more than 2500 participants, incorporating 1530 ALS patients and 1102 controls (healthy, 907; neuromuscular, 195) were assessed with threshold tracking TMS across 25 studies. Significant reduction of mean short interval intracortical inhibition (interstimulus interval 1-7 ms) exhibited the highest standardized mean difference with moderate heterogeneity (-0.994, 95% confidence interval -1.12 to -0.873, p < 0.001; Q = 38.61, p < 0.05; I2 = 40%). The reduction of cortical silent period duration along with an increase in motor evoked potential amplitude and intracortical facilitation also exhibited significant, albeit smaller, standardized mean differences. This large meta-analysis study disclosed that mean short interval intracortical inhibition reduction exhibited the highest sensitivity for cortical hyperexcitability in ALS. Combined findings from this meta-analysis suggest that research strategies aimed at understanding the cause of inhibitory interneuronal circuit dysfunction could enhance understanding of ALS pathogenesis.

The role of dorsal premotor cortex in joint action inhibition

Behavioral interpersonal coordination requires smooth negotiation of actions in time and space (joint action—JA). Inhibitory control may play a role in fine-tuning appropriate coordinative responses. To date, little research has been conducted on motor inhibition during JA and on the modulatory influence that premotor areas might exert on inhibitory control. Here, we used an interactive task in which subjects were required to reach and open a bottle using one hand. The bottle was held and stabilized by a co-actor (JA) or by a mechanical holder (vice clamp, no-JA). We recorded two TMS-based indices of inhibition (short-interval intracortical inhibition—sICI; cortical silent period—cSP) during the reaching phase of the task. These reflect fast intracortical (GABAa-mediated) and slow corticospinal (GABAb-mediated) inhibition. Offline continuous theta burst stimulation (cTBS) was used to interfere with dorsal premotor cortex (PMd), ventral premotor cortex (PMv), and control site (vertex) before the execution of the task. Our results confirm a dissociation between fast and slow inhibition during JA coordination and provide evidence that premotor areas drive only slow inhibitory mechanisms, which in turn may reflect behavioral co-adaptation between trials. Exploratory analyses further suggest that PMd, more than PMv, is the key source of modulatory drive sculpting movements, according to the socio-interactive context.

Differential modulation of corticomotor excitability in older compared to young adults following a single bout of strength -exercise

Evidence shows corticomotor plasticity diminishes with age. Nevertheless, whether strength-training, a proven intervention that induces corticomotor plasticity in younger adults, also takes effect in older adults, remains untested. This study examined the effect of a single-session of strength-exercise on corticomotor plasticity in older and younger adults. Thirteen older adults (72.3 ± 6.5 years) and eleven younger adults (29.9 ± 6.9 years), novice to strength-exercise, participated. Strength-exercise involved four sets of 6–8 repetitions of a dumbbell biceps curl at 70–75% of their one-repetition maximum (1-RM). Muscle strength, cortical, corticomotor and spinal excitability, before and up to 60-minutes after the strength-exercise session were assessed. We observed significant changes over time (p < 0.05) and an interaction between time and age group (p < 0.05) indicating a decrease in corticomotor excitability (18% p < 0.05) for older adults at 30- and 60-minutes post strength-exercise and an increase (26% and 40%, all p < 0.05) in younger adults at the same time points. Voluntary activation (VA) declined in older adults immediately post and 60-minutes post strength-exercise (36% and 25%, all p < 0.05). Exercise had no effect on the cortical silent period (cSP) in older adults however, in young adults cSP durations were shorter at both 30- and 60- minute time points (17% 30-minute post and 9% 60-minute post, p < 0.05). There were no differences in short-interval cortical inhibition (SICI) or intracortical facilitation (ICF) between groups. Although the corticomotor responses to strength-exercise were different within groups, overall, the neural responses seem to be independent of age.

Shock waves modulate corticospinal excitability: A proof of concept for further rehabilitation purposes?

Focal extracorporeal shock wave therapy (fESWT) is a physical therapy vastly studied and used for various musculoskeletal disorders. However, the effect of fESWT on central nervous system is still to be determined. To elucidate spinal and supra-spinal mechanisms of fESWT in healthy subjects, in order to widen the spectrum of its clinical applications. In this quasi-experimental, unblinded, proof-of-concept clinical study, 10 voluntary healthy subjects underwent fESWT and were assessed immediately before (T0), immediately after (T1) and seven days after (T2) the intervention. As neurophysiological outcomes, motor evoked potentials (resting motor threshold, maximal motor evoked potential and maximal compound muscle action potential ratio, cortical silent period, total conduction motor time, direct and indirect central motor conduction time), F-waves (minimal and mean latency, persistence and temporal dispersion) and H-reflex (threshold, amplitude, maximal H reflex and maximal compound muscle action potential ratio, latency) were considered. Resting motor threshold and F-waves temporal dispersion significantly decreased, respectively, from T1 and T2 and from T0 and T2 (for both, p < 0.05). H-reflex threshold increase between T0 and T1. Analysis disclosed a strong negative correlation between Δ3 cortical silent period (i.e., T2 -T1 recordings) and Δ1 Hr threshold (i.e., T1 -T0 recordings) (r = -0.66, p < 0.05), and a positive strong relationship between Δ3 cortical silent period and Δ3 Hr threshold (r = 0.63, p < 0.05). fESWT modulates corticospinal tract excitability in healthy volunteers, possibly inducing an early inhibition followed by a later facilitation after one week.

Motor Pathways Reorganization following Surgical Decompression for Degenerative Cervical Myelopathy: A Combined Navigated Transcranial Magnetic Stimulation and Clinical Outcome Study.

(1) Background: Degenerative cervical myelopathy is one of the main causes of disability in the elderly. The treatment of choice in patients with clear symptomatology and radiological correlation is surgical decompression. The application of navigated transcranial magnetic stimulation (nTMS) techniques has the potential to provide additional insights into the cortical and corticospinal behavior of the myelopathic cord and to better characterize the possible extent of clinical recovery. The objective of our study was to use nTMS to evaluate the effect of surgical decompression on neurophysiological properties at the cortical and corticospinal level and to better characterize the extent of possible clinical recovery. (2) Methods: We conducted a longitudinal study in which we assessed and compared nTMS neurophysiological indexes and clinical parameters (modified Japanese Orthopedic Association score and nine-hole pegboard test) before surgery, at 6 months, and at 12 months' follow-up in a population of 15 patients. (3) Results: We found a significant reduction in resting motor threshold (RMT; average 7%), cortical silent period (CSP; average 15%), and motor area (average 25%) at both 6 months and 12 months. A statistically significant linear correlation emerged between recruitment curve (RC) values obtained at follow-up appointments and at baseline (r = 0.95 at 6 months, r = 0.98 at 12 months). A concomitant improvement in the mJOA score and in the nine-hole pegboard task was observed after surgery. (4) Conclusions: Our results suggest that surgical decompression of the myelopathic spinal cord improves the neurophysiological balance at the cortical and corticospinal level, resulting in clinically significant recovery. Such findings contribute to the existing evidence characterizing the brain and the spinal cord as a dynamic system capable of functional and reversible plasticity and provide useful clinical insights to be used for patient counseling.

Effect of Propranolol on Motor Cortex Excitability in Essential Tremor: An Exploratory Study.

Essential tremor, the world's most prevalent movement disorder, lacks a clear understanding of its pathophysiology. Propranolol, a non-specific beta-blocker capable of crossing the blood-brain barrier, is a primary choice for essential tremor treatment. While its tremor-reducing effects are generally attributed to peripheral actions, various uses hint at central adrenergic effects. Nevertheless, propranolol's precise impact on the central nervous system in essential tremor subjects remains unexplored. In this study, we employed transcranial magnetic stimulation to assess the influence of propranolol on the excitability of the primary motor cortex (M1) in patients with essential tremor, compared to an age- and sex-matched control group. Cortical excitability parameters were measured following placebo and propranolol administration, encompassing resting and active motor thresholds, motor evoked potential characteristics, cortical silent period, and the input/output curve. Distinct effects were observed across the two cortical hemispheres. Essential tremor patients displayed inhibition of the left M1 cortex and heightened excitability in the right M1 cortex four hours after propranolol administration, but not following placebo. These findings suggest potential differential noradrenergic excitatory and inhibitory modulation. However, comprehensive understanding necessitates further investigations, including left-handed participants and more diverse essential tremor subpopulations. This study underscores the need for continued exploration to unravel propranolol's complex effects on motor cortex excitability in essential tremor.

The distinct and potentially conflicting effects of tDCS and tRNS on brain connectivity, cortical inhibition, and visuospatial memory.

Noninvasive brain stimulation (NIBS) techniques, including transcranial direct current stimulation (tDCS) and transcranial random noise stimulation (tRNS), are emerging as promising tools for enhancing cognitive functions by modulating brain activity and enhancing cognitive functions. Despite their potential, the specific and combined effects of tDCS and tRNS on brain functions, especially regarding functional connectivity, cortical inhibition, and memory performance, are not well-understood. This study aims to explore the distinct and combined impacts of tDCS and tRNS on these neural and cognitive parameters. Using a within-subject design, ten participants underwent four stimulation conditions: sham, tDCS, tRNS, and combined tDCS + tRNS. We assessed the impact on resting-state functional connectivity, cortical inhibition via Cortical Silent Period (CSP), and visuospatial memory performance using the Corsi Block-tapping Test (CBT). Our results indicate that while tDCS appears to induce brain lateralization, tRNS has more generalized and dispersive effects. Interestingly, the combined application of tDCS and tRNS did not amplify these effects but rather suggested a non-synergistic interaction, possibly due to divergent mechanistic pathways, as observed across fMRI, CSP, and CBT measures. These findings illuminate the complex interplay between tDCS and tRNS, highlighting their non-additive effects when used concurrently and underscoring the necessity for further research to optimize their application for cognitive enhancement.

Effects of Clozapine on Cortical Inhibition

Abstract Background Preclinical and clinical investigations have revealed deficits in cortical inhibition in individuals with schizophrenia. Transcranial magnetic stimulation, a commonly used noninvasive measurement technique, is used for assessing these deficits. Limited research has been conducted on the effects of antipsychotic medications on cortical inhibition. This study aimed to evaluate the effects of clozapine on cortical inhibition with transcranial magnetic stimulation longitudinally and compare it with unaffected controls. Methods Ten patients who started clozapine were assessed at baseline, with 8 reassessed after 4 months. Eight age- and sex-matched unaffected controls were included. Psychopathology, neurocognitive performance, formal thought disorder, and disability were assessed, and the cortical excitability parameters (resting motor threshold, cortical silent period, short-interval intracortical inhibition, intracortical facilitation, and short-latency afferent inhibition [SAI]) were measured at baseline and four months after clozapine treatment. Results Resting motor threshold, ICF, and SAI were significantly different between patients and controls at baseline, whereas resting motor threshold, SAI, and ICF became similar to controls after clozapine with only ICF having a trend for significance. Clozapine prolonged cortical silent period significantly in the patients. Conclusions This is the first study to investigate the effect of clozapine on SAI, a potential cholinergic biomarker, and the first follow-up study to investigate the relationship between the effects of clozapine on cortical inhibition and cognition. Clozapine seems to cause an increase in cortical inhibition through GABAergic and possibly cholinergic mechanisms. However, additional follow-up studies with larger sample sizes are required to reach more robust conclusions.