Resting Motor Threshold Research Articles

Brain state-dependent repetitive transcranial magnetic stimulation for motor stroke rehabilitation: a proof of concept randomized controlled trial.

In healthy subjects, repetitive transcranial magnetic stimulation (rTMS) targeting the primary motor cortex (M1) demonstrated plasticity effects contingent on electroencephalography (EEG)-derived excitability states, defined by the phase of the ongoing sensorimotor μ-oscillation. The therapeutic potential of brain state-dependent rTMS in the rehabilitation of upper limb motor impairment post-stroke remains unexplored. Proof-of-concept trial to assess the efficacy of rTMS, synchronized to the sensorimotor μ-oscillation, in improving motor impairment and reducing upper-limb spasticity in stroke patients. We conducted a parallel group, randomized double-blind controlled trial in 30 chronic stroke patients (clinical trial registration number: NCT05005780). The experimental intervention group received EEG-triggered rTMS of the ipsilesional M1 [1,200 pulses; 0.33 Hz; 100% of the resting motor threshold (RMT)], while the control group received low-frequency rTMS of the contralesional motor cortex (1,200 pulses; 1 Hz, 115% RMT), i.e., an established treatment protocol. Both groups received 12 rTMS sessions (20 min, 3× per week, 4 weeks) followed by 50 min of physiotherapy. The primary outcome measure was the change in upper-extremity Fugl-Meyer assessment (FMA-UE) scores between baseline, immediately post-treatment and 3 months' follow-up. Both groups showed significant improvement in the primary outcome measure (FMA-UE) and the secondary outcome measures. This included the reduction in spasticity, measured objectively using the hand-held dynamometer, and enhanced motor function as measured by the Wolf Motor Function Test (WMFT). There were no significant differences between the groups in any of the outcome measures. The application of brain state-dependent rTMS for rehabilitation in chronic stroke patients is feasible. This pilot study demonstrated that the brain oscillation-synchronized rTMS protocol produced beneficial effects on motor impairment, motor function and spasticity that were comparable to those observed with an established therapeutic rTMS protocol. ClinicalTrials.gov, identifier [NCT05005780].

The Influence of Body Position on the Resting Motor Threshold of Posterior Root-Muscle Reflexes Evoked via Transcutaneous Spinal Cord Stimulation.

Background: Thoracolumbar transcutaneous spinal cord stimulation (tSCS) non-invasively evokes posterior root-muscle reflexes (PRMR) with the aim of neuromodulating sensorimotor function following spinal cord injury. Research is still in its infancy regarding the effect of body position on the nature of these spinally evoked responses. Therefore, the aim of this study was to investigate the influence of body position on the nature of PRMR responses during tSCS. Methods: A total of 11 (6M, 5F) participants completed a full PRMR recruitment curve from 10 ma up to 120 ma (10 ma increments) at the T11/12 intervertebral space using a singular 3.2 cm diameter cathode. At each intensity, three paired pulses (50 ms inter-pulse interval), followed by three singular pulses with a six-second delay were applied in each body position (supine, supine 90-90, sitting and standing) in a randomised order. The PRMR responses in lower limb muscles were recorded using wireless electromyographic sensors placed on the Soleus, Tibialis Anterior, Rectus Femoris and Bicep Femoris long head. A two-way (body position × muscle) repeated measures analysis of variance was used to investigate the effect of body position on PRMR-evoked responses. Results: There was a significant main effect of body position on PRMR resting motor threshold (RMT) (p < 0.001), first response peak-to-peak amplitude (p = 0.003) and percentage post-activation depression (%PAD) (p = 0.012). Sitting had significantly higher RMT and significantly lower first response peak-to-peak amplitudes compared to all other positions, but significant differences in %PAD were only detectible between supine and standing. Conclusions: Body position influences the nature of PRMR-evoked responses during tSCS.

Immediate Effects of Preconditioning Intermittent Theta Burst Stimulation on Lower Extremity Motor Cortex Excitability in Healthy Participants.

Previous studies have found that inhibitory priming with continuous theta burst stimulation (cTBS) can enhance the effect of subsequent excitatory conditioning stimuli with intermittent theta burst stimulation (iTBS) in the upper limbs. However, whether this combined stimulation approach elicits a comparable compensatory response in the lower extremities remains unclear. This study aimed to investigate how cTBS preconditioning modulated the effect of iTBS on motor cortex excitability related to the lower limb in healthy individuals. Using a randomised cross-over design, a total of 25 healthy participants (19 females, mean age = 24.80 yr) were recruited to undergo three different TBS protocols (cTBS + iTBS, sham cTBS + iTBS, sham cTBS + sham iTBS) in a random order. Each TBS intervention was administered with one-week intervals. cTBS and iTBS were administered at an intensity of 80% active motor threshold (AMT) delivering a total of 600 pulses. Before intervention (T0), immediately following intervention (T1), and 20 min after intervention (T2), the corticomotor excitability was measured for the tibialis anterior muscle of participants' non-dominant leg using a Magneuro100 stimulator and matched double-cone coil. The average amplitude of the motor-evoked potential (MEP) induced by applying 20 consecutive monopulse stimuli at an intensity of 130% resting motor threshold (RMT) was collected and analysed. Compare with T0 time, the MEP amplitude (raw and normalised) at T1 and T2 showed a statistically significant increase following the cTBS + iTBS protocol (p < 0.01), but no significant differences were observed in amplitude changes following other protocols (sham cTBS + iTBS and sham cTBS + sham iTBS) (p > 0.05). Furthermore, no statistically significant difference was found among the three protocols at any given time point (p > 0.05). Preconditioning the lower extremity motor cortex with cTBS prior to iTBS intervention can promptly enhance its excitability in healthy participants. This effect persists for a minimum duration of 20 min. No: ChiCTR2300069315. Registered 13 March, 2023, https://www.chictr.org.cn.

Trans-spinal magnetic stimulation combined with kinesiotherapy as a new method for enhancing functional recovery in patients with spinal cord injury due to neuromyelitis optica: a case report

BackgroundExperimental studies have shown that repetitive trans-spinal magnetic stimulation (TsMS) decreases demyelination and enables recovery after spinal cord injury (SCI). However, the usefulness of TsMS in humans with SCI remains unclear. Therefore, the main objective of this study is to evaluate the effects of TsMS combined with kinesiotherapy on SCI symptoms. We describe a protocol treatment with TsMS and kinesiotherapy in a patient with SCI due to neuromyelitis optica (NMO)-associated transverse myelitis.Case presentationA 23-year-old white male with NMO spectrum disorders started symptoms in 2014 and included lumbar pain evolving into a mild loss of strength and sensitivity in both lower limbs. Five months later, the symptoms improved spontaneously, and there were no sensorimotor deficits. Two years later, in 2016, the symptoms recurred with a total loss of strength and sensitivity in both lower limbs. Initially, physiotherapy was provided in 15 sessions with goals of motor-sensory recovery and improving balance and functional mobility. Subsequently, TsMS (10 Hz, 600 pulses, 20-seconds inter-trains interval, at 90% of resting motor threshold of the paravertebral muscle) was applied at the 10th thoracic vertebral spinous process before physiotherapy in 12 sessions. Outcomes were assessed at three time points: prior to physiotherapy alone (T-1), before the first session of TsMS combined with kinesiotherapy (T0), and after 12 sessions of TsMS combined with kinesiotherapy (T1). The patient showed a 25% improvement in walking independence, a 125% improvement in balance, and an 18.8% improvement in functional mobility. The Patient Global Impression of Change Scale assessed the patient’s global impression of change as ‘much improved’.ConclusionTsMS combined with kinesiotherapy may safely and effectively improve balance, walking independence, and functional mobility of patients with SCI due to NMO-associated transverse myelitis.

Effects of DLPFC tDCS Followed by Treadmill Training on Dual-Task Gait and Cortical Excitability in Parkinson’s Disease: A Randomized Controlled Trial

Background Gait disturbances are exacerbated in people with Parkinson’s disease (PD) during dual-task walking (DTW). Transcranial direct current stimulation (tDCS) has been shown to exert beneficial effects on gait performance and cortical excitability in PD; however, its combined effects with treadmill training (TT) remain undetermined. Objective To investigate the effects of tDCS followed by TT on DTW performance and cortical excitability in individuals with PD. Methods Thirty-four PD participants were randomized to dorsal lateral prefrontal cortex (DLPFC) tDCS and TT group (DLPFC tDCS + TT group) or sham tDCS and TT group (sham tDCS + TT group) for 50 minutes per session (20 minutes tDCS followed by 30 minutes TT), 12 sessions within 5 weeks (2-3 sessions each week). Outcome measures included cognitive dual-task walking (CDTW), motor dual-task walking (MDTW), usual walking performance, cortical excitability, functional mobility, cognitive function, and quality of life. Results The DLPFC tDCS + TT group exerted significantly greater improvement in CDTW velocity (P = .046), cadence (P = .043), and stride time (P = .041) compared to sham tDCS + TT group. In addition, DLPFC tDCS + TT group demonstrated a significant increase in resting motor threshold of stimulated hemisphere compared with sham tDCS + TT group (P = .026). However, no significant differences between groups were found in MDTW performance and other outcomes. Conclusion Twelve-session DLPFC tDCS followed by TT significantly improved CDTW performance and decreased cortical excitability more than TT alone in individuals with PD. Applying DLPFC tDCS prior to TT could be suggested for gait rehabilitation in individuals with PD. Clinical trial registration number: Australian New Zealand Clinical Trials Registry ACTRN12622000101785

‘Remote inhibition’ of motor cortex in Epileptic encephalopathy with spike-wave activation in sleep (EE-SWAS): A TMS based cortical excitability study

ObjectivesThe study compared real-time motor cortex excitability using transcranial magnetic stimulation (TMS)-derived parameters between children with epileptic encephalopathy with spike-wave activation in sleep (EE-SWAS) and age-matched neurotypical controls. The EE-SWAS group received steroids as standard of care and were longitudinally followed for three months. Materials & MethodsChildren aged 5–12 years with immunotherapy-naive EE-SWAS (spike-wave-index≥50 %) and neurotypical controls were enrolled. Cognitive and behavioral assessments were performed using valid psychometric tools. Real-time motor cortex excitability was assessed by measuring resting motor threshold (RMT), short intra-cortical inhibition (SICI) and long intra-cortical inhibition (LICI) in both groups. In EE-SWAS group, a follow up evaluation with TMS at 4- and 12-week intervals, EEG, and neurobehavioral assessments at 12-weeks were performed to assess the effect of steroids on cortical excitability and to determine electroclinical outcome. ResultsForty-eight children with suspected EE-SWAS and 26 neurotypical controls were screened; 20 were enrolled in each group. Children with EE-SWAS (mean age: 8.05 ± 1.76 years) had cognitive and behavioral problems (20/20), and ongoing seizures (12/20). At baseline, the dominant motor cortex was significantly inhibited in the EE-SWAS group compared to neurotypical children{RMT(%)[86.3 ± 6.96 vs 58.05 ± 4.71(p < 0.0001)]; LICI(%)[55.05 ± 4.39 vs 73.9 ± 3.75(p < 0.0001)]; SICI(%)[39.2 ± 4.36 vs 55.45 ± 4.78(p < 0.0001)]}. Reversal of motor cortex inhibition was sequentially observed in EE-SWAS group at 4- and 12-week follow-ups{(RMT[4, 12 weeks]: 71.45 ± 9.83, 63.45 ± 8.48); (LICI[4, 12 weeks]: 66.00 ± 6.26, 74.50 ± 5.36); (SICI[4, 12 weeks]: 49.35 ± 6.24, 56.05 ± 5.57)}[repeated-measures ANOVA: p < 0.0001]. ConclusionMotor cortex is remotely inhibited in EE-SWAS, which may contribute to neurobehavioral impairment. Steroids can disinhibit/reverse the epilepsy-induced motor cortex inhibition leading to improvement in neurobehavior.

Dose-Dependent Target Engagement of a Clinical iTBS Protocol: An Interleaved TMS-fMRI Study in Healthy Subjects

BackgroundIntermittent theta burst stimulation (iTBS) of the dorsolateral prefrontal cortex (DLPFC) is widely applied as a therapeutic intervention in mental health; however, the understanding of its mechanisms is still incomplete. Prior magnetic resonance imaging studies have mainly used offline iTBS or short sequences in concurrent transcranial magnetic stimulation functional magnetic resonance imaging (fMRI). This study investigated a full 600-stimuli iTBS protocol using interleaved transcranial magnetic stimulation fMRI in comparison with 2 control conditions in healthy subjects. MethodsIn a crossover design, 18 participants underwent 3 sessions of interleaved iTBS-fMRI: 1) the left DLPFC at 40% resting motor threshold (rMT) intensity, 2) the left DLPFC at 80% rMT intensity, and 3) the left primary motor cortex (M1) at 80% rMT intensity. We compared immediate blood oxygen level–dependent (BOLD) responses during interleaved iTBS-fMRI across these conditions including correlations between individual fMRI BOLD activation and iTBS-induced electric field strength at the target sites. ResultsWhole-brain analysis showed increased activation in several regions following iTBS. Specifically, the left DLPFC, as well as the bilateral M1, anterior cingulate cortex, and insula, showed increased activation during 80% rMT left DLPFC stimulation. Increased BOLD activity in the left DLPFC was observed with neither 40% rMT left DLPFC stimulation nor left M1 80% rMT iTBS, whereas activation in other regions was found to overlap between conditions. Of note, BOLD activation and electric field intensities were only correlated for M1 stimulation and not for the DLPFC conditions. ConclusionsThe study showed dosage- and target-specific BOLD activation during interleaved transcranial magnetic stimulation fMRI with 600-stimuli iTBS in healthy individuals. Future studies may use our approach for demonstrating target engagement.

Effects of the intermittent theta burst stimulation on gait, balance and lower limbs motor function in stroke: study protocol for a double-blind randomised controlled trial with multimodal neuroimaging assessments

IntroductionApproximately, 50% of stroke survivors experience impaired walking ability 6 months after conventional rehabilitation and standard care. However, compared with upper limb motor function, research on lower limbs rehabilitation through...

Effects of a Single Session of Repetitive Transcranial Stimulation in Parkinson Disease

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique proposed for recovery of gait and balance in patients with Parkinson&amp;apos;s disease (PD). Our aim was to evaluate the effects of rTMS in PD patients by clinical evaluation and computerized gait analysis. Ten patients were recruited. Each patient was assessed before and after a single session of rTMS by: Berg Scale, Unified Parkinson Disease Rating Scale (UPDRS), 6 Minute Walking Test (6MWT), 10MWT, Time Up and Go (TUG) and spatial-temporal gait analysis by Pablo Gait Assessment sensor. We availed of STM 9000, stimulating with 2000 pulses of 20 Hz rTMS, delivered in 5-second trains with 25 seconds between trains, on the hand area of the motor cortex at 90% resting motor threshold (RMT) on each hemisphere, with 5 minutes pause between hemispheres. Eighty percent of the patient reported subjective benefits, corroborated by objective examination of the results. A significant improvement on the Berg scale was observed. Moreover, a tendence to a significant decrease of stiffness at the lower limbs was evident at UPDRS. Gait analysis showed not significant improvements of evaluated parameters. Although it is premature to draw conclusions, because of the small number of patients, underwent to a single session of rTMS, we confirm the possible beneficial effects and the safety of rTMS. Further studies are needed to validate our findings by clinical evaluation and gait analysis at short, medium, and long term. These may be different in relation to the age, duration and stage of the disease, prevalence of tremor or akinesia and rigidity.

Posterior insula repetitive transcranial magnetic stimulation for chronic pain in patients with Parkinson disease – pain type matters: A double-blinded randomized sham-controlled trial

ObjectivesAltered somatosensory processing in the posterior insula may play a role in chronic pain development and contribute to Parkinson disease (PD)-related pain. Posterior-superior insula (PSI) repetitive transcranial magnetic stimulation (rTMS) has been demonstrated to have analgesic effects among patients with some chronic pain conditions. This study aimed at assessing the efficacy of PSI-rTMS for treating PD-related pain. MethodsThis was a double-blinded, randomized, sham-controlled, parallel-arm trial (NCT03504748). People with PD (PwP)-related chronic pain underwent five daily PSI-rTMS sessions for a week, followed by once weekly maintenance stimulations for seven weeks. rTMS was delivered at 10 Hz and 80% of the resting motor threshold. The primary outcome was a ≥ 30% pain intensity reduction at 8 weeks compared to baseline. Functionality, mood, cognitive, motor status, and somatosensory thresholds were also assessed. ResultsTwenty-five patients were enrolled. Mean age was 55.2 ± 9.5 years-old, and 56% were female. Nociceptive pain accounted for 60%, and neuropathic and nociplastic for 20% each. No significant difference was found for 30% pain reduction response rates between active (42.7%) and sham groups (14.6%, p = 0.26). Secondary clinical outcomes and sensory thresholds also did not differ significantly. In a post hoc analysis, PwP with nociceptive pain sub-type experienced more pain relief after active (85.7%) compared to sham PSI-rTMS (25%, p = 0.032). ConclusionOur preliminary results suggest that different types of PD-related pain may respond differently to treatment, and therefore people with PD may benefit from having PD-related pain well characterized in research trials and in clinical practice.

Tumor-Specific Alterations in Motor Cortex Excitability and Tractography of the Corticospinal Tract-A Navigated Transcranial Magnetic Stimulation Study.

Non-invasive brain mapping using navigated transcranial magnetic stimulation (nTMS) is a valuable tool prior to resection of malignant brain tumors. With nTMS motor mapping, it is additionally possible to analyze the function of the motor system and to evaluate tumor-induced neuroplasticity. Distinct changes in motor cortex excitability induced by certain malignant brain tumors are a focal point of research. A retrospective single-center study was conducted involving patients with malignant brain tumors. Clinical data, resting motor threshold (rMT), and nTMS-based tractography were evaluated. The interhemispheric rMT-ratio (rMTTumor/rMTControl) was calculated for each extremity and considered pathological if it was >110% or <90%. Distances between the corticospinal tract and the tumor (lesion-to-tract-distance - LTD) were measured. 49 patients were evaluated. 16 patients (32.7%) had a preoperative motor deficit. The cohort comprised 22 glioblastomas (44.9%), 5 gliomas of Classification of Tumors of the Central Nervous System (CNS WHO) grade 3 (10.2%), 6 gliomas of CNS WHO grade 2 (12.2%) and 16 cerebral metastases (32.7%). 26 (53.1%) had a pathological rMT-ratio for the upper extremity and 35 (71.4%) for the lower extremity. All patients with tumor-induced motor deficits had pathological interhemispheric rMT-ratios, and presence of tumor-induced motor deficits was associated with infiltration of the tumor to the nTMS-positive cortex (p = 0.04) and shorter LTDs (all p < 0.021). Pathological interhemispheric rMT-ratio for the upper extremity was associated with cerebral metastases, but not with gliomas (p = 0.002). Our study underlines the diagnostic potential of nTMS motor mapping to go beyond surgical risk stratification. Pathological alterations in motor cortex excitability can be measured with nTMS mapping. Pathological cortical excitability was more frequent in cerebral metastases than in gliomas.

Distinguishable neural circuit mechanisms associated with the clinical efficacy of rTMS in aMCI patients.

Repetitive transcranial magnetic stimulation is used in early-stage Alzheimer's disease to slow progression, but heterogeneity in response results in different treatment outcomes. The mechanisms underlying this heterogeneity are unclear. This study used resting-state neuroimaging to investigate the variability in episodic memory improvement from angular gyrus repetitive transcranial magnetic stimulation and tracked the neural circuits involved. Thirty-four amnestic mild cognitive impairment patients underwent angular gyrus repetitive transcranial magnetic stimulation (4weeks, 20Hz, 100% resting motor threshold) and were divided into high-response and low-response groups based on minimal clinically important differences in auditory verbal learning test scores. Baseline and pre/post-treatment neural circuit activities were compared. Results indicated that the orbital middle frontal gyrus in the orbitofrontal cortex network and the precuneus in the default mode network had higher local activity in the low-response group. After treatment, changes in local and remote connectivity within brain regions of the orbitofrontal cortex, default mode network, visual network, and sensorimotor network showed opposite trends and were related to treatment effects. This suggests that the activity states of brain regions within the orbitofrontal cortex and default mode network could serve as imaging markers for early cognitive compensation in amnestic mild cognitive impairment patients and predict the aftereffects of repetitive transcranial magnetic stimulation response.

Reduced Auditory Perception and Brain Response with Quiet TMS Coil.

Electromagnetic forces in transcranial magnetic stimulation (TMS) coils generate a loud clicking sound that produces confounding auditory activation and is potentially hazardous to hearing. To reduce this noise while maintaining stimulation efficiency similar to conventional TMS coils, we previously developed a quiet TMS double containment coil (qTMS-DCC). To compare the stimulation strength, perceived loudness, and EEG response between qTMS-DCC and a commercial TMS coil. Nine healthy volunteers participated in a within-subject study design. The resting motor thresholds (RMTs) for qTMS-DCC and MagVenture Cool-B65 were measured. Psychoacoustic titration matched the Cool-B65 loudness to qTMS-DCC pulsed at 80, 100, and 120% RMT. Event-related potentials (ERPs) were recorded for both coils. The psychoacoustic titration and ERPs were acquired with the coils both on and 6 cm off the scalp, the latter isolating the effects of airborne auditory stimulation from body sound and electromagnetic stimulation. The ERP comparisons focused on a centro-frontal region that encompassed peak responses in the global signal. RMT did not differ significantly between the coils, with or without the EEG cap on the head. qTMS-DCC was perceived to be substantially quieter than Cool-B65. For example, qTMS-DCC at 100% coil-specific RMT sounded like Cool-B65 at 34% RMT. The general ERP waveform and topography were similar between the two coils, as were early-latency components, indicating comparable electromagnetic brain stimulation in the on-scalp condition. qTMS-DCC had a significantly smaller P180 component in both on-scalp and off-scalp conditions, supporting reduced auditory activation. The stimulation efficiency of qTMS-DCC matched Cool-B65, while having substantially lower perceived loudness and auditory-evoked potentials. qTMS coil is subjectively and objectively quieter than conventional Cool-B65 coilqTMS coil at 100% motor threshold was as loud as Cool-B65 at 34% motor thresholdAttenuated coil noise reduced auditory N100 and P180 evoked response componentsqTMS coil enables reduction of auditory activation without masking.

The Impact of Obesity as a Peripheral Disruptor of Brain Inhibitory Mechanisms in Fibromyalgia: A Cross-Sectional Study.

Background/Objective: Obesity, characterized by chronic inflammation, may serve as a surrogate marker for more dysfunctional peripheral inflammation, potentially exacerbating FM symptomatology. Given this premise, this study aimed to investigate the effects of obesity as an effect modifier on neural and clinical variables, specifically those indexing pain-compensatory mechanisms in FM symptoms. Methods: A cross-sectional study was conducted with 108 participants who underwent a standardized TMS protocol assessment to measure resting motor threshold (MT), intracortical facilitation (ICF), and intracortical inhibition (ICI). Clinical data were collected using Beck's Depression Index (BDI), PROMIS, the Brief Pain Inventory (BPI), and conditioned pain modulation (CPM). Linear regression models were used to explore the relationship between these variables while examining Body Mass Index (BMI) as a potential effect modifier. If it was found to be a modifier, we stratified the sample into two groups with a BMI cutoff of 30 and performed another regression model within the subgroups. Results: BMI was identified as an effect modifier in the relationships between ICI and BDI, PROMIS fatigue, and CPM and in MT versus CPM. After stratification, non-obese fibromyalgia subjects demonstrated significant correlations between clinical symptoms and CPM and ICI activity. However, these correlations were absent in the obese group, suggesting obesity disrupts pain mechanisms and their compensatory effects. Higher MT values were associated with weaker endogenous pain control, particularly evident in the obese group. Conclusions: Obesity appears to be a significant effect modifier and delineates two patient groups across multiple clinical and neural assessments of fibromyalgia. Additionally, it suggests a role for obesity in exacerbating fibromyalgia symptoms and disrupting physiological pain-inhibitory mechanisms.

Search for approaches to transcranial neuromodulation in patients with post-stroke hemiparesis in real clinical practice

BACKGROUND: To increase the efficiency of motor recovery after a stroke in routine clinical practice, the search for selective biomarkers that determine the choice of the optimal strategy for noninvasive neuromodulation of the brain remains relevant. The study of interhemispheric interaction patterns can hypothetically help in determining the correct conceptual model of neuromodulation. AIM: To determine variants of interhemispheric interaction based on a correlation analysis of motor cortex excitability in patients with poststroke hemiparesis stratified by the degree of motor deficit. MATERIALS AND METHODS: This retrospective observational study involved 185 people (men, 56.2%; women, 43.8%) aged 19–88 years with verified poststroke hemiparesis and 40 healthy volunteers (men, 55.0%; women, 45.0%) aged 20–85 years. The patients underwent diagnostic transcranial magnetic stimulation in the projection of the cortical representation of m. abductor pollicis brevis and m. tibialis anterior of both brain hemispheres. The excitability level of the motor cortex and its interhemispheric asymmetry were recorded, and correlation analysis in subgroups stratified by the degree of paresis was performed. RESULTS: No interhemispheric correlation of resting motor thresholds (rMT) was found in patients with a level of muscle strength for the “hand” segment of 0–2 points (р 0.05). In the remaining subgroups, positive interhemispheric correlations of the rMT were noted (p 0.02). A positive correlation of the rMT of the damaged brain hemisphere and interhemispheric asymmetry of the motor cortex excitability for all degrees of paresis was observed when evaluating the cortical representation of the upper limb muscles. A negative correlation between the rMT of the unaffected brain hemisphere and interhemispheric asymmetry was detected for all degrees of motor deficit of the “foot” segment (p 0.02). CONCLUSION: The study did not confirm the concept of interhemispheric competition of the studied functional activity of the brain. Three authentic variants of interhemispheric interaction were identified: unidirectional hemispheric interaction with predominant reactivity of the affected hemisphere, unidirectional hemispheric interaction with predominant reactivity of the unaffected hemisphere, and functional interhemispheric dissociation. The results indicate the need to rethink some approaches to transcranial neuromodulation strategies in the analyzed cohort.

Distinct patterns of electrophysiologic-neuroimaging correlations between Parkinson's disease and multiple system atrophy

Due to a high degree of symptom overlap in the early stages, with movement disorders predominating, Parkinson's disease (PD) and multiple system atrophy (MSA) may exhibit a similar decline in motor areas, yet they differ in their spread throughout the brain, ultimately resulting in two distinct diseases. Drawing upon neuroimaging analyses and altered motor cortex excitability, potential diffusion mechanisms were delved into, and comparisons of correlations across distinct disease groups were conducted in a bid to uncover significant pathological disparities. We recruited thirty-five PD, thirty-seven MSA, and twenty-eight matched controls to conduct clinical assessments, electromyographic recording, and magnetic resonance imaging scanning during the "on medication" state. Patients with neurodegeneration displayed a widespread decrease in electrophysiology in bilateral M1. Brain function in early PD was still in the self-compensatory phase and there was no significant change. MSA patients demonstrated an increase in intra-hemispheric function coupled with a decrease in diffusivity, indicating a reduction in the spread of neural signals. The level of resting motor threshold in healthy aged showed broad correlations with both clinical manifestations and brain circuits related to left M1, which was absent in disease states. Besides, ICF exhibited distinct correlations with functional connections between right M1 and left middle temporal gyrus in all groups. The present study identified subtle differences in the functioning of PD and MSA related to bilateral M1. By combining clinical information, cortical excitability, and neuroimaging intuitively, we attempt to bring light on the potential mechanisms that may underlie the development of neurodegenerative disease.

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

the aim of this study was to investigate the neurophysiological effect of anti-CGRP monoclonal antibodies on central and peripheral levels in migraine patients. 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. 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. 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.

Test-retest reliability of intrahemispheric dorsal premotor and primary motor cortex dual-site TMS connectivity measures

ObjectiveInvestigating the optimal interstimulus interval (ISI) and the 24-hour test–retest reliability for intrahemispheric dorsal premotor cortex (PMd) – primary motor cortex (M1) connectivity using dual-site transcranial magnetic stimulation (dsTMS). MethodsIn 21 right-handed adults, left intrahemispheric PMd–M1 connectivity has been investigated with a stacked-coil dsTMS setup (conditioning stimulus: 75% of resting motor threshold; test stimulus: eliciting MEPs of 1–1.5 mV) at ISIs of 3, 5–8, and 10 ms. Additionally, M1–M1 short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) were investigated to assess comparability to standard paired-pulse setups. ResultsConditioning PMd led to significant inhibition of M1 output at ISIs of 3 and 5 ms, whereas 10 ms resulted in facilitation (all, p < 0.001), with a fair test–retest reliability for 3 (ICC: 0.47) and 6 ms (ICC: 0.44) ISIs. Replication of SICI (p < 0.001) and ICF (p = 0.017) was successful, with excellent test–retest reliability for SICI (ICC: 0.81). ConclusionThis dsTMS setup can probe the inhibitory and facilitatory PMd–M1 connections, as well as reliably replicate SICI and ICF paradigms. SignificanceThe stacked-coil dsTMS setup for investigating intrahemispheric PMd–M1 connectivity offers promising possibilities to better understand motor control.

Abnormalities of cortical stimulation strength-duration time constant in amyotrophic lateral sclerosis

ObjectivesStrength-duration time constant (SDTC) may now be determined for cortical motor neurones, with activity mediated by transient Na+ conductances. The present study determined whether cortical SDTC is abnormal and linked to the pathogenesis of amyotrophic lateral sclerosis. MethodsCortical SDTC and rheobase were estimated from 17 ALS patients using a controllable pulse parameter transcranial magnetic stimulation (cTMS) device. Resting motor thresholds (RMTs) were determined at pulse widths (PW) of 30, 45, 60, 90 and 120 µs and M−ratio of 0.1, using a figure-of-eight coil applied to the primary motor cortex. ResultsSDTC was significantly reduced in ALS patients (150.58 ± 9.98 µs; controls 205.94 ± 13.7 µs, P < 0.01). The reduced SDTC correlated with a rate of disease progression (Rho = -0.440, P < 0.05), ALS functional rating score (ALSFRS-R) score (Rho = 0.446, P < 0.05), and disease duration (R = 0.428, P < 0.05). The degree of change in SDTC was greater in patients with cognitive abnormalities as manifested by an abnormal total Edinburgh Cognitive ALS Screen score (140.5 ± 28.7 µs, P < 0.001) and ALS-specific subscore (141.7 ± 33.2 µs, P = 0.003). ConclusionsCortical SDTC reduction was associated with a more aggressive ALS phenotype, or with more prominent cognitive impairment. SignificanceAn increase in transient Na+ conductances may account for the reduction in SDTC, linked to the pathogenesis of ALS.

Ultra-early navigated transcranial magnetic stimulation for perioperative stroke: anatomo-functional report.

Navigated repetitive transmagnetic stimulation is a non-invasive and safe brain activity modulation technique. When combined with the classical rehabilitation process in stroke patients it has the potential to enhance the overall neurologic recovery. We present a case of a peri-operative stroke, treated with ultra-early low frequency navigated repetitive transmagnetic stimulation over the contralesional hemisphere. The patient received low frequency navigated repetitive transmagnetic stimulation within 12hours of stroke onset for seven consecutive days and a significant improvement in his right sided weakness was noticed and he was discharge with normal power. This was accompanied by an increase in the number of positive responses evoked by navigated repetitive transmagnetic stimulation and a decrease of the resting motor thresholds at a cortical level. Subcortically, a decrease in the radial, axial, and mean diffusivity were recorded in the ipsilateral corticospinal tract and an increase in fractional anisotropy, axial diffusivity, and mean diffusivity was observed in the interhemispheric fibers of the corpus callosum responsible for the interhemispheric connectivity between motor areas. Our case demonstrates clearly that ultra-early low frequency navigated repetitive transmagnetic stimulation applied to the contralateral motor cortex can lead to significant clinical motor improvement in patients with subcortical stroke.