Increase In Motor Evoked Potentials Amplitude Research Articles

Plasticity-Induced Effects of Theta Burst Transcranial Ultrasound Stimulation in Parkinson's Disease.

Low-intensity transcranial ultrasound stimulation (TUS) is a noninvasive brain stimulation (NIBS) technique with high spatial specificity. Previous studies showed that TUS delivered in a theta burst pattern (tbTUS) increased motor cortex (MI) excitability up to 30 minutes due to long-term potentiation (LTP)-like plasticity. Studies using other forms of NIBS suggested that cortical plasticity may be impaired in patients with Parkinson's disease (PD). The aim was to investigate the neurophysiological effects of tbTUS in PD patients off and on dopaminergic medications compared to healthy controls. We studied 20 moderately affected PD patients in on and off dopaminergic medication states (7 with and 13 without dyskinesia) and 17 age-matched healthy controls in a case-controlled study. tbTUS was applied for 80 seconds to the MI. Motor-evoked potentials (MEP), short-interval intracortical inhibition (SICI), and short-interval intracortical facilitation (SICF) were recorded at baseline, and at 5 minutes (T5), T30, and T60 after tbTUS. Motor Unified Parkinson's Disease Rating Scale (mUPDRS) was measured at baseline and T60. tbTUS significantly increased MEP amplitude at T30 compared to baseline in controls and in PD patients on but not in PD patients off medications. SICI was reduced in PD off medications compared to controls. tbTUS did not change in SICI or SICF. The bradykinesia subscore of mUPDRS was reduced at T60 compared to baseline in PD on but not in the off medication state. The presence of dyskinesia did not affect tbTUS-induced plasticity. tbTUS-induced LTP plasticity is impaired in PD patients off medications and is restored by dopaminergic medications. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Facilitation of motor evoked potentials after tetanic peripheral nerve stimulation

ObjectiveTetanic stimulation of a peripheral nerve prior to transcranial electrical stimulation (TES) may enhance motor evoked potential (MEP) amplitudes. The purpose of this study was to investigate the post-tetanic MEP (p-MEP) technique in improving MEP amplitudes. MethodsConventional TES MEPs (c-MEP) and p-MEPs with left upper limb stimulation (p-MEPUL) or left lower limb stimulation (p-MEPLL) were performed in 26 patients. Bilateral hand and foot MEP amplitudes obtained with each protocol were compared. Subgroup comparisons were performed for myelopathy and peripheral neuropathy patients. Within-subject amplitude differences between c-MEP and each p-MEP technique were compared using a Wilcoxon test. ResultsThe mean age of the patients was 52.7 years (range, 12–79 years). Overall, p-MEPUL resulted in MEP improvement in 25 of 26 (96%) patients, and p-MEPLL improved MEPs in 19 of 26 (73%) patients. The increase in MEP amplitudes were statistically significant in all muscle groups except left foot. Similar improvements were seen in the myelopathy group; in the neuropathy group, p-MEPUL produced similar results, but p-MEPLL did not. ConclusionsThe p-MEP technique can improve MEP amplitudes, including in patients with myelopathy. In patients with peripheral neuropathy, the results were mixed. SignificanceTetanic stimulation can enhance intraoperative MEP amplitudes.

Effect of optimized transcranial direct current stimulation on motor cortex activation in patients with sub-acute or chronic stroke: a study protocol for a single-blinded cross-over randomized control trial.

Transcranial direct current stimulation (tDCS) has shown positive but inconsistent results in stroke rehabilitation. This could be attributed to inter-individual variations in brain characteristics and stroke lesions, which limit the use of a single tDCS protocol for all post-stroke patients. Optimizing the electrode location in tDCS for each individual using magnetic resonance imaging (MRI) to generate three-dimensional computer models and calculate the electric field (E-field) induced by tDCS at a specific target point in the primary motor cortex may help reduce these inconsistencies. In stroke rehabilitation, locating the optimal position that generates a high E-field in a target area can influence motor recovery. Therefore, this study was designed to determine the effect of personalized tDCS electrode positions on hand-knob activation in post-stroke patients. This is a crossover study with a sample size of 50 participants, who will be randomly assigned to one of six groups and will receive one session of either optimized-active, conventional-active, or sham tDCS, with 24 h between sessions. The tDCS parameters will be 1 mA (5 × 5 cm electrodes) for 20 min. The motor-evoked potential (MEP) will be recorded before and after each session over the target area (motor cortex hand-knob) and the MEP hotspot. The MEP amplitude at the target location will be the primary outcome. We hypothesize that the optimized-active tDCS session would show a greater increase in MEP amplitude over the target area in patients with subacute and chronic stroke than conventional and sham tDCS sessions.Clinical trial registration: https://cris.nih.go.kr, identifier KCT0007536.

The Impact of the Perception of Primary Facial Emotions on Corticospinal Excitability.

The link between emotional experience and motor body responses has long been acknowledged. A well-established approach to exploring the effect of the perception of emotional stimuli on the motor system is measuring variations in the excitability of the corticospinal tract (CSE) through motor-evoked potentials (MEP) elicited via transcranial magnetic stimulation (TMS). Previous evidence has indicated a selective increase in MEP amplitude while participants view emotional stimuli, such as emotional facial expressions, compared to neutral cues. However, it is still not clear whether this effect depends on the specific emotional meaning conveyed by the stimulus. In the present study, we explored whether viewing faces expressing the primary emotions compared to faces with a neutral expression affects individuals' CSE, measured using TMS-elicited MEPs. Specifically, we elicited MEPs from the left motor cortex (M1) while participants passively viewed the same faces expressing either anger, fear, disgust, happiness, sadness, surprise, and no emotion (in different blocks). We found that the observation of fearful, angry, disgusted, and happy facial expressions was associated with a significant increase in the MEPs' amplitude compared to neutral facial expressions, with a comparable enhancement in the CSE occurring across these emotions. In turn, viewing sad and surprised faces did not modulate the CSE. Overall, our findings suggest that only facial expressions that signal (real or potential) danger or a rewarding stimulus, but not emotional facial expressions per se, are capable of activating action-related mechanisms.

Moderate intensity aerobic exercise may enhance neuroplasticity of the contralesional hemisphere after stroke: a randomised controlled study

Upregulation of neuroplasticity might help maximize stroke recovery. One intervention that appears worthy of investigation is aerobic exercise. This study aimed to determine whether a single bout of moderate intensity aerobic exercise can enhance neuroplasticity in people with stroke. Participants were randomly assigned (1:1) to a 20-min moderate intensity exercise intervention or remained sedentary (control). Transcranial magnetic stimulation measured corticospinal excitability of the contralesional hemisphere by recording motor evoked potentials (MEPs). Intermittent Theta Burst Stimulation (iTBS) was used to repetitively activate synapses in the contralesional primary motor cortex, initiating the early stages of neuroplasticity and increasing excitability. It was surmised that if exercise increased neuroplasticity, there would be a greater facilitation of MEPs following iTBS. Thirty-three people with stroke participated in this study (aged 63.87 ± 10.30 years, 20 male, 6.13 ± 4.33 years since stroke). There was an interaction between Time*Group on MEP amplitudes (P = 0.009). Participants allocated to aerobic exercise had a stronger increase in MEP amplitude following iTBS. A non-significant trend indicated time since stroke might moderate this interaction (P = 0.055). Exploratory analysis suggested participants who were 2–7.5 years post stroke had a strong MEP facilitation following iTBS (P < 0.001). There was no effect of age, sex, resting motor threshold, self-reported physical activity levels, lesion volume or weighted lesion load (all P > 0.208). Moderate intensity cycling may enhance neuroplasticity in people with stroke. This therapy adjuvant could provide opportunities to maximize stroke recovery.

Clinical and Physiological Effects of Single Day Accelerated Theta Burst Transcranial Focused Ultrasound in Parkinson’s Disease (P4-11.008)

<h3>Objective:</h3> To evaluate the tolerability and efficacy of an accelerated schedule of theta burst focused ultrasound stimulation (tbTUS) delivered to the primary motor cortex in Parkinson’s disease (PD) patients assessed by transcranial magnetic stimulation (TMS) and United Parkinson’s Disease Rating Scale (UPDRS)-Part III. <h3>Background:</h3> Low intensity transcranial focused ultrasound stimulation (TUS) is an emerging technology for non-invasive brain stimulation (NIBS) that can penetrate deeper in the brain with more focal stimulation compared to currently used forms of NIBS. TUS delivered in a theta burst pattern (tbTUS) for 80s induces sustained increases in motor cortex excitability lasting at least 30 minutes and is a promising NIBS protocol for treatment of neurological disorders. Accelerated stimulation schedules with several treatments per day can shorten treatment duration and improve accessibility. <h3>Design/Methods:</h3> Three sets of tbTUS were delivered in consecutive order to the right and left primary motor cortices at 30-minute intervals. 10 PD patients attended one visit each for real and sham treatments in random order. Before and after interventions, TMS measures of motor-evoked potentials (MEP), short-interval intracortical inhibition (SICI), short-interval intracortical excitation (SICF), and UPDRS-Part III scores were collected. Patients and UPDRS raters were blinded to the stimulation condition. <h3>Results:</h3> Real but not sham tbTUS treatment led to increased MEP amplitude and SICF. While both conditions led to similar changes in UPDRS-III scores, rigidity subscores were reduced only with real treatment. There were no adverse effects. <h3>Conclusions:</h3> The study is ongoing, and more patients are being recruited. Preliminary findings show that accelerated tbTUS is a safe and tolerable treatment schedule for PD patients. Improvements in rigidity suggests that tbTUS could be further studied as a non-invasive treatment for PD. Future research may investigate the optimal time between sonications with a longer treatment duration and a larger number of patients. <b>Disclosure:</b> Yi Rong Ding has nothing to disclose. Dr. Samuel has nothing to disclose. Dr. Grippe has nothing to disclose. Dr. SARICA has nothing to disclose. Dr. Lozano has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbott. Dr. Lozano has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Insightec. Dr. Lozano has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Boston Scientific. Dr. Lozano has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medtronic. Dr. Lozano has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Functional Neuromodulation. Dr. Chen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Chen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merz. Dr. Chen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Paladin Labs. Dr. Chen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ipsen. Dr. Chen has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Canadian Journal of Neurological Sciences. Dr. Chen has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Movement Disorders. The institution of Dr. Chen has received research support from Canadian Institutes of Health Research. The institution of Dr. Chen has received research support from NIH. The institution of Dr. Chen has received research support from Natural Science and Engineering Research Council of Canada. Dr. Chen has received research support from Parkinson Foundation. The institution of Dr. Chen has received research support from National Organization for Rare Disease. The institution of Dr. Chen has received research support from Merz.

Paired corticomotoneuronal stimulation of the preactivated ankle dorsiflexor: an open-label study of magnetic and electrical painless protocols.

Paired corticomotoneuronal stimulation (or electrical PCMS: ePCMS) is the repetitive pairing of an electrical stimulus to a nerve with a transcranial magnetic stimulation of the primary motor cortex (TMS-of-M1) to noninvasively influence spinal plasticity. We compared ePCMS with the new painless PCMS protocol pairing a magnetic stimulus to the nerve with TMS-of-M1 (mPCMS) in the preactivated tibial anterior muscle (TA). Sixteen healthy adults participated in two sessions (mPCMS, ePCMS), each with 180 pairs of [low-intensity TMS-of-M1 + nerve stimulation] at 0.2Hz. TA motor-evoked potentials (MEP) to single-pulse TMS at pre-PCMS, immediately and 30min after PCMS, were cluster-analyzed to discriminate responders and non-responders. Paired-pulse TMS-of-M1 and F-waves were also tested and BDNF polymorphism influence was explored. Both PCMS protocols significantly increased MEP amplitudes (n = 9 responders each), but the time-course differed with mPCMS inducing larger MEP increase over time. The number of BDNF-methionine carriers tended to be larger than Val66Val in mPCMS and the reverse in ePCMS, thus warranting further investigations. The MEP changes of the preactivated TA likely occurred at the pre-motoneuronal level and larger mPCMS after-effects over time may be related to the afferents recruited. mPCMS seems relevant to be testedin future studies as a painlessnoninvasiveapproach to induce sustained pre-motoneuronal plasticity in spinal cord injury.

Normal parameters for diagnostic transcranial magnetic stimulation using a parabolic coil with biphasic pulse stimulation

BackgroundTMS is being used to aid in the diagnosis of central nervous system (CNS) illnesses. It is useful in planning rehabilitation programs and setting appropriate goals for patients. We used a parabolic coil with biphasic pulse stimulation to find normal values for diagnostic TMS parameters.Objectives1. To determine the normal motor threshold (MT), motor evoked potentials (MEP), central motor conduction time (CMCT), intracortical facilitation (ICF), short-interval intracortical inhibition (SICI), and silent period (SP) values. 2. To measure the MEP latencies of abductor pollicis brevis (APB) and extensor digitorum brevis (EDB) at various ages, heights, and arm and leg lengths.Study designDescriptive Study.SettingDepartment of Rehabilitation Medicine, Chiang Mai University, Thailand.SubjectsForty-eight healthy participants volunteered for the study.MethodsAll participants received a single diagnostic TMS using a parabolic coil with biphasic pulse stimulation on the left primary motor cortex (M1). All parameters: MT, MEP, CMCT, ICF, SICI, and SP were recorded through surface EMGs at the right APB and EDB. Outcome parameters were reported by the mean and standard deviation (SD) or median and interquartile range (IQR), according to data distribution. MEP latencies of APB and EDB were also measured at various ages, heights, and arm and leg lengths.ResultsAPB-MEP latencies at 120% and 140% MT were 21.77 ± 1.47 and 21.17 ± 1.44 ms. APB-CMCT at 120% and 140% MT were 7.81 ± 1.32 and 7.19 ± 1.21 ms. APB-MEP amplitudes at 120% and 140% MT were 1.04 (0.80–1.68) and 2.24 (1.47–3.52) mV. EDB-MEP latencies at 120% and 140% MT were 37.14 ± 2.85 and 36.46 ± 2.53 ms. EDB-CMCT at 120% and 140% MT were 14.33 ± 2.50 and 13.63 ± 2.57 ms. EDB-MEP amplitudes at 120% and 140% MT were 0.60 (0.38–0.98) and 0.95 (0.69–1.55) mV. ICF amplitudes of APB and EDB were 2.26 (1.61–3.49) and 1.26 (0.88–1.98) mV. SICI amplitudes of APB and EDB were 0.21 (0.13–0.51) and 0.18 (0.09–0.29) mV. MEP latencies of APB at 120% and 140% MT were different between heights < 160 cm and ≥ 160 cm (p < 0.001 and p < 0.001) and different between arm lengths < 65 and ≥ 65 cm (p = 0.022 and p = 0.002).ConclusionWe established diagnostic TMS measurements using a parabolic coil with a biphasic pulse configuration. EDB has a higher MT than APB. The 140/120 MEP ratio of APB and EDB is two-fold. The optimal MEP recording for APB is 120%, whereas EDB is 140% of MT. CMCT by the F-wave is more convenient and tolerable for patients. ICF provides a twofold increase in MEP amplitude. SICI provides a ¼-fold of MEP amplitude. SP from APB and EDB are 121.58 ± 21.50 and 181.01 ± 40.99 ms, respectively. Height and MEP latencies have a modest relationship, whereas height and arm length share a strong positive correlation.

Multi-modal investigation of transcranial ultrasound-induced neuroplasticity of the human motor cortex

IntroductionThere is currently a gap in accessibility to neuromodulation tools that can approximate the efficacy and spatial resolution of invasive methods. Low intensity transcranial focused ultrasound stimulation (TUS) is an emerging technology for non-invasive brain stimulation (NIBS) that can penetrate cortical and deep brain structures with more focal stimulation compared to existing NIBS modalities. Theta burst TUS (tbTUS, TUS delivered in a theta burst pattern) is a novel repetitive TUS protocol that can induce durable changes in motor cortex excitability, thereby holding promise as a novel neuromodulation tool with durable effects. ObjectiveThe aim of the present study was to elucidate the neurophysiologic effects of tbTUS motor cortical excitability, as well on local and global neural oscillations and network connectivity. MethodsAn 80-s train of active or sham tbTUS was delivered to the left motor cortex in 15 healthy subjects. Motor cortical excitability was investigated through transcranial magnetic stimulation (TMS)-elicited motor-evoked potentials (MEPs), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF) using paired-pulse TMS. Magnetoencephalography (MEG) recordings during resting state and an index finger abduction-adduction task were used to assess oscillatory brain responses and network connectivity. The correlations between the changes in neural oscillations and motor cortical excitability were also evaluated. ResultstbTUS to the motor cortex results in a sustained increase in MEP amplitude and decreased SICI, but no change in ICF. MEG spectral power analysis revealed TUS-mediated desynchronization in alpha and beta spectral power. Significant changes in alpha power were detected within the supplementary motor cortex (Right > Left) and changes in beta power within bilateral supplementary motor cortices, right basal ganglia and parietal regions. Coherence analysis revealed increased local connectivity in motor areas. MEP and SICI changes correlated with both local and inter-regional coherence. ConclusionThe findings from this study provide novel insights into the neurophysiologic basis of TUS-mediated neuroplasticity and point to the involvement of regions within the motor network in mediating this sustained response. Future studies may further characterize the durability of TUS-mediated neuroplasticity and its clinical applications as a neuromodulation strategy for neurological and psychiatric disorders.

Motor cortex plasticity is greater in endurance-trained cyclists following acute exercise.

Previous research using transcranial magnetic stimulation (TMS) has shown that plasticity within primary motor cortex (M1) is greater in people who undertake regular exercise, and a single session of aerobic exercise can increase M1 plasticity in untrained participants. This study aimed to examine the effect of an acute bout of exercise on M1 plasticity in endurance-trained (cyclists) and untrained individuals. Fourteen endurance-trained cyclists (mean ± SD; 23 ± 3.8 yr) and 14 untrained individuals (22 ± 1.8 yr) performed two experimental sessions. One session included an acute bout of high-intensity interval training (HIIT) exercise involving stationary cycling, whereas another session involved no-exercise (control). Following exercise (or control), I-wave periodicity repetitive TMS (iTMS) was used (1.5-ms interval, 180 pairs) to induce plasticity within M1. Motor evoked potentials (MEPs) induced by single and paired-pulse TMS over M1 were recorded from a hand muscle at baseline, after HIIT (or control) exercise and after iTMS. Corticospinal and intracortical excitability was not influenced by HIIT exercise in either group (all P > 0.05). There was an increase in MEP amplitude after iTMS, and this was greater after HIIT exercise (compared with control) for all subjects (P < 0.001). However, the magnitude of this response was larger in endurance cyclists compared with the untrained group (P = 0.049). These findings indicate that M1 plasticity induced by iTMS was greater in endurance-trained cyclists following HIIT. Prior history of exercise training is, therefore, an important consideration for understanding factors that contribute to exercise-induced plasticity.NEW & NOTEWORTHY We use a novel form of repetitive transcranial magnetic stimulation to show that motor cortex plasticity is increased after acute exercise and that this effect is bolstered in endurance-trained cyclists. These findings indicate that participation in regular endurance exercise (involving lower limb muscles) has widespread effects on cortical plasticity (assessed in unexercised upper limb muscles) following acute lower-limb cycling exercise. It also highlights that exercise history is an important factor in exercise-induced cortical plasticity.

High-Frequency Cerebellar rTMS Improves the Swallowing Function of Patients with Dysphagia after Brainstem Stroke.

Objective To explore the efficacy of high-frequency repetitive transcranial magnetic stimulation (rTMS) of the swallowing motor area of the cerebellum in patients with dysphagia after brainstem stroke. Methods A total of 36 patients with dysphagia after brainstem stroke were recruited and divided into 3 groups. Before stimulation, single-pulse transcranial magnetic stimulation (TMS) was used to determine the swallowing dominant cerebellar hemisphere and the representation of the mylohyoid muscle. The three groups of patients received bilateral cerebellar sham stimulation, dominant cerebellar rTMS + contralateral sham stimulation, or bilateral cerebellar rTMS. The stimulus plan for each side was 10 Hz, 80% resting movement threshold (rMT), 250 pulses, 1 s per stimulus, and 9 s intervals. Sham rTMS was performed with the coil held at 90° to the scalp. The changes in the motor evoked potential (MEP) amplitude and the clinical swallowing function scales of the patients after stimulation were compared among the three groups. Results 34 patients were finally included for statistical analysis. The scores of penetration aspiration scale (PAS) and functional dysphagia scale (FDS) of the patients after 2 weeks of rTMS in the unilateral stimulation group and bilateral stimulation group were better than that in the sham stimulation group, and there was no significant difference between the two groups. The increase in the MEP amplitude of the cerebral hemisphere in the bilateral stimulation group was higher than that in the other two groups, and the increase in the MEP amplitude in the unilateral stimulation group was higher than that in sham stimulation group. There was no correlation between the improvement in patients' clinical swallowing function (PAS scores and FDS scores) and the increase in MEP amplitude in either the unilateral stimulation group or the bilateral stimulation group. Conclusion High-frequency rTMS in the cerebellum can improve swallowing function in PSD patients and increase the excitability of the representation of swallowing in the bilateral cerebral hemispheres. Compared with unilateral cerebellar rTMS, bilateral stimulation increased the excitability of the cerebral swallowing cortex more significantly, but there was no significant difference in clinical swallowing function.

Quantitative Assessment of Cortical Excitability in Alzheimer’s Dementia and Its Association with Clinical Symptoms: A Systematic Review and Meta-Analyses

Background: Alzheimer’s disease (AD) is characterized by cognitive and neuropsychiatric symptoms (NPS) due to underlying neurodegenerative pathology. Some studies using electroencephalography (EEG) have shown increased epileptiform and epileptic activity in AD. Objective: This review and meta-analyses aims to synthesize the existing evidence for quantitative abnormalities of cortical excitability in AD and their relationship with clinical symptoms. Methods: We systematically searched and reviewed publications that quantitatively assessed cortical excitability, using transcranial magnetic stimulation (TMS) resting motor threshold (rMT), active motor threshold (aMT), motor evoked potential (MEP) or directly from the cortex using TMS-EEG via TMS-evoked potential (TEP). We meta-analyzed studies that assessed rMT and aMT using random effects model. Results: We identified 895 publications out of which 37 were included in the qualitative review and 30 studies using rMT or aMT were included in the meta-analyses. The AD group had reduced rMT (Hedges’ g = –0.99, 95% CI [–1.29, –0.68], p &lt; 0.00001) and aMT (Hedges’ g = –0.87, 95% CI [–1.50, –0.24], p &lt; 0.00001) as compared with control groups, indicative of higher cortical excitability. Qualitative review found some evidence of increased MEP amplitude, whereas findings related to TEP were inconsistent. There was some evidence supporting an inverse association between cortical excitability and global cognition. No publications reported on the relationship between cortical excitability and NPS. Conclusion: There is strong evidence of increased motor cortex excitability in AD and some evidence of an inverse association between excitability and cognition. Future studies should assess cortical excitability from non-motor areas using TMS-EEG and examine its relationship with cognition and NPS.

Location-specific cutaneous electrical stimulation of the footsole modulates corticospinal excitability to the plantarflexors and dorsiflexors during standing.

Non‐noxious electrical stimulation to distinct locations of the foot sole evokes location‐specific cutaneous reflex responses in lower limb muscles. These reflexes occur at latencies that may enable them to be mediated via a transcortical pathway. Corticospinal excitability to the plantarflexors and dorsiflexors was measured in 16 participants using motor evoked potentials (MEPs). Spinal excitability was measured in eight of the original participants using cervicomedullary motor evoked potentials (CMEPs). Measurements were collected with and without preceding cutaneous stimulus to either the heel (HEEL) or metatarsal (MET) locations of the foot sole, and evoked potentials were elicited to coincide with the arrival of the cutaneous volley at either the motor cortex or spinal cord. Plantarflexor MEPs and CMEPs were facilitated with cutaneous stimulation to the HEEL for MEPs (soleus p = 0.04, medial gastrocnemius (MG) p = 0.017) and CMEPs (soleus p = 0.047 and MG p = 0.015), but they were unchanged following MET stimulation for MEPs or CMEPs. Dorsiflexor MEPs were unchanged with cutaneous stimulation at either location, but dorsiflexor CMEPs increased with cutaneous stimulation (p = 0.05). In general, the increase in CMEP amplitudes was larger than the increase in MEP amplitudes, indicating that an increase in spinal excitability likely explains most of the increase in corticospinal excitability. The larger change observed in the CMEP also indicates that excitability from supraspinal sources likely decreased, which could be due to a net change in the excitability of intracortical circuits. This study provides evidence that cutaneous reflexes from foot sole skin are likely influenced by a transcortical pathway.

Brain–computer interface-based action observation combined with peripheral electrical stimulation enhances corticospinal excitability in healthy subjects and stroke patients

Objective. Action observation (AO) combined with brain–computer interface (BCI) technology enhances cortical activation. Peripheral electrical stimulation (PES) increases corticospinal excitability, thereby activating brain plasticity. To maximize motor recovery, we assessed the effects of BCI-AO combined with PES on corticospinal plasticity. Approach. Seventeen patients with chronic hemiplegic stroke and 17 healthy subjects were recruited. The participants watched a video of repetitive grasping actions with four different tasks for 15 min: (A) AO alone; (B) AO + PES; (C) BCI-AO + continuous PES; and (D) BCI-AO + triggered PES. PES was applied at the ulnar nerve of the wrist. The tasks were performed in a random order at least three days apart. We assessed the latency and amplitude of motor evoked potentials (MEPs). We examined changes in MEP parameters pre-and post-exercise across the four tasks in the first dorsal interosseous muscle of the dominant hand (healthy subjects) and affected hand (stroke patients). Main results. The decrease in MEP latency and increase in MEP amplitude after the four tasks were significant in both groups. The increase in MEP amplitude was sustained for 20 min after tasks B, C, and D in both groups. The increase in MEP amplitude was significant between tasks A vs. B, B vs. C, and C vs. D. The estimated mean difference in MEP amplitude post-exercise was the highest for A and D in both groups. Significance. The results indicate that BCI-AO combined with PES is superior to AO alone or AO + PES for facilitating corticospinal plasticity in both healthy subjects and patients with stroke. Furthermore, this study supports the idea that synchronized activation of cortical and peripheral networks can enhance neuroplasticity after stroke. We suggest that the BCI-AO paradigm and PES could provide a novel neurorehabilitation strategy for patients with stroke.

Quantitative assessment of cortical excitability in Alzheimer’s dementia and its association with clinical symptoms: A systematic review and meta‐analyses

AbstractBackgroundAlzheimer’s Disease (AD) is characterized by cognitive and neuropsychiatric symptoms (NPS). Studies using electroencephalography (EEG) have shown increased epileptiform and epileptic activity in AD. Transcranial magnetic stimulation (TMS) studies have also shown abnormal cortical excitability in AD, however findings have been inconsistent. Further, relationship between cortical excitability and clinical symptoms of AD is not clear. This review and meta‐analyses aims to synthesize the existing evidence for abnormal cortical excitability in AD and its relationship with clinical symptoms.MethodWe systematically searched and reviewed publications that quantitatively assessed cortical excitability, using TMS resting motor threshold (rMT), active motor threshold (aMT), motor evoked potential (MEP) or directly from the cortex using TMS‐EEG via TMS‐evoked potential (TEP). Effect sizes and 95% confidence intervals (CI) of rMT and aMT were calculated using Hedges’ g and meta‐analyzed using a random effects model. Heterogeneity among studies was assessed by Cochran’s Q and I2 statistic.ResultWe identified 895 publications out of which 68 were reviewed in full‐text and 37 were included in the final review. Thirty studies using rMT and seven using aMT were included in the meta‐analyses. The AD group had reduced rMT (Hedges’ g = ‐0.99, 95% CI [‐1.29, ‐0.68], p &lt; 0.00001) and aMT (Hedges’ g = ‐0.87, 95% CI [‐1.50, ‐0.24], p &lt; 0.00001) as compared with control groups, indicative of higher cortical excitability. Evidence of considerable heterogeneity was found across the studies (Q (29) = 85.68, p &lt; 0.00001, I2 =81%). Qualitative review of the literature showed some evidence of increased MEP amplitude (n = 2 studies), however findings related to TEP were inconsistent. Further, there was some evidence (n = 4 studies) supporting an inverse association between cortical excitability and global cognition. No publications reported on the relationship between cortical excitability and neuropsychiatric symptoms (NPS).ConclusionThere is strong evidence of increased motor cortex excitability in AD and some evidence of an inverse association between excitability and cognition. Future studies should assess cortical excitability from non‐motor areas and examine its relationship with cognition and NPS.

Cerebellar Intermittent Theta-Burst Stimulation Reduces Upper Limb Spasticity After Subacute Stroke: A Randomized Controlled Trial.

Objective: This study aims to explore the efficacy of cerebellar intermittent theta-burst stimulation (iTBS) on upper limb spasticity in subacute stroke patients.Methods: A total of 32 patients with upper limb spasticity were enrolled and randomly assigned to treatment with cerebellar iTBS or sham stimulation before conventional physical therapy daily for 2 weeks. The primary outcomes included the modified Ashworth scale (MAS), the modified Tardieu scale (MTS), and the shear wave velocity (SWV). The secondary outcomes were the H-maximum wave/M-maximum wave amplitude ratio (Hmax/Mmax ratio), motor-evoked potential (MEP) latency and amplitude, central motor conduction time (CMCT), and the Barthel Index (BI). All outcomes were evaluated at baseline and after 10 sessions of intervention.Results: After the intervention, both groups showed significant improvements in the MAS, MTS, SWV, and BI. In addition, patients treated with cerebellar iTBS had a significant increase in MEP amplitude, and patients treated with sham stimulation had a significant decrease in Hmax/Mmax ratio. Compared with the sham stimulation group, the MAS, MTS, and SWV decreased more in the cerebellar iTBS group.Conclusion: Cerebellar iTBS is a promising adjuvant tool to reinforce the therapeutic effect of conventional physical therapy in upper limb spasticity management after subacute stroke (Chinese Clinical Trial Registry: ChiCTR1900026516).

P 36. rTMS-induced offline-modulation of premotor-motor interaction after motor sequence learning does not affect consolidation

Introduction. The acquisition of novel motor skills depends on active training and further offline processing of the motor engram (i.e., consolidation). Previous studies suggest an essential role of post-training corticospinal excitability (CSE) for the induction of offline motor memory consolidation. Furthermore, it was shown that the interaction of the primary motor cortex (M1) and the premotor cortex (PMC) after training affects the consolidation process. In this study, we modulated the post-training interaction of M1 and PMC by applying inhibitory repetitive transcranial magnetic stimulation (rTMS) and investigated the effects on CSE and consolidation. Methods. 48 healthy, right-handed subjects (age 22.13 ± 3.2 a) were assigned to 3 groups. All participants practiced an explicit motor sequence learning task with their right hand. Immediately after training, participants received 1 Hz rTMS to either left M1, left PMC, or sham stimulation. Motor evoked potentials (MEP) were recorded before training and after rTMS. Task performance was retested eight hours after the end of stimulation to assess offline performance changes. Task performance was assessed using a performance index (PI) that integrated speed and accuracy of sequence execution. Consolidation was quantified as the difference of task performance at the end of the training session compared to the beginning of the retest (mean PI of 4 blocks each). Results. In terms of changes of MEP amplitudes, rmANOVA revealed an interaction of factors group*time ( p = 0.001). When applied to M1, rTMS induced a decrease of CSE compared to the pre-training assessments ( p = 0.007), whereas stimulation of the PMC led to an increase of MEP amplitudes ( p = 0.009). No relevant change of corticospinal excitability was seen after sham stimulation ( p = 0.862). Training performance did not differ between groups (group*block, p = 0.781) and all groups demonstrated significant offline-improvements at delayed retesting. However, there were no significant differences of consolidation between groups ( p = 0.456). Furthermore, correlation analysis revealed no significant association of CSE modulation and offline performance changes ( r = 0.101, p = 0.493). Discussion. The increase of CSE induced by post-training PMC demonstrated here differs from results of previous studies that applied inhibitory PMC stimulation at rest or before a training intervention, which resulted in decreased CSE. We, therefore, interpret our findings as further evidence of a state-dependent function of the PMC. Despite significant modulation of CSE by post-training rTMS of M1 and PMC, there was no behavioral effect on consolidation. This challenges the relevance of immediate post-training CSE changes as a key mechanism in terms of the induction of consolidation. Although proximal intracortical physiological mechanisms are still not excluded, they are not detected by changes in post-training corticospinal excitability.

Effect of reversal of residual neuromuscular blockade on the amplitude of motor evoked potentials: a randomized controlled crossover study comparing sugammadex and placebo.

To compare the amplitude changes in motor evoked potentials (MEP) with reversal of residual neuromuscular blockade using sugammadex or placebo in patients with cervical myelopathy. In this prospective randomized double-blind, placebo-controlled crossover trial, 38 patients with cervical myelopathy undergoing posterior cervical decompression and fusion were randomized to either sugammadex (2mg/kg) or placebo. The primary outcome measure was the increase in amplitude of the MEP in the first dorsal interossei (FDI) muscle at 3 min. Mann-Whitney U test was used to analyze the primary outcome measure. There was a significant increase in the amplitude of MEP at 3 min with sugammadex when compared to placebo group. The median (IQR) increase in MEP amplitude (μV) at 3 min from the left FDI in sugammadex and placebo group was 652.9 (142:1650) and 20.6 (-183.5:297.5) (p <0.001), respectively. Corresponding values from right FDI were 2153.4 (1400:4536.8) and 55(-65.2:480.8) (p=<0.001). Our study showed that there was a 200% increase in the MEP amplitude in the first dorsal interosseous muscle at 3 min following reversal of residual neuromuscular blockade with sugammadex. By ensuring that maximal MEP amplitude is recorded at baseline, early commencement of neuromonitoring can be achieved. The study was registered at http://clinicaltrials.gov , ID NCT03087513, Feb 5th 2018.

Feasibility of cerebello-cortical stimulation for intraoperative neurophysiological monitoring of cerebellar mutism

BackgroundCerebellar mutism can occur in a third of children undergoing cerebellar resections. Recent evidence proposes it may arise from uni- or bilateral damage of cerebellar efferents to the cortex along the cerebello-dento-thalamo-cortical pathway. At present, no neurophysiological procedure is available to monitor this pathway intraoperatively. Here, we specifically aimed at filling this gap.MethodsWe assessed 10 patients undergoing posterior fossa surgery using a conditioning-test stimulus paradigm. Electrical conditioning stimuli (cStim) were delivered to the exposed cerebellar cortex at interstimulus intervals (ISIs) of 8–24 ms prior to transcranial electric stimulation of the motor cortex, which served as test stimulus (tStim). The variation of motor-evoked potentials (MEP) to cStim + tStim compared with tStim alone was taken as a measure of cerebello-cortical connectivity.ResultscStim alone did not produce any MEP. cStim preceding tStim produced a significant inhibition at 8 ms (p < 0.0001) compared with other ISIs when applied to the lobules IV-V-VI in the anterior cerebellum and the lobule VIIB in the posterior cerebellum. Mixed effects of decrease and increase in MEP amplitude were observed in these areas for longer ISIs.ConclusionsThe inhibition exerted by cStim at 8 ms on the motor cortex excitability is likely to be the product of activity along the cerebello-dento-thalamo-cortical pathway. We show that monitoring efferent cerebellar pathways to the motor cortex is feasible in intraoperative settings. This study has promising implications for pediatric posterior fossa surgery with the aim to preserve the cerebello-cortical pathways and thus prevent cerebellar mutism.

Association of Cortical Hyperexcitability and Cognitive Impairment in Patients With Amyotrophic Lateral Sclerosis

To determine whether cortical hyperexcitability was more prominent in cognitively impaired patients with amyotrophic lateral sclerosis (ALS). Threshold tracking transcranial magnetic stimulation (TMS) was used to assess cortical excitability and cognitive function was determined by the Edinburgh Cognitive and Behavioural ALS Screen (ECAS). Cognitive impairment was defined by ECAS < 105. Patients with ALS, defined by the Awaji criteria, were prospectively recruited. Patients unable to undergo TMS, or in whom TMS indices were compromised by coexistent medical conditions, were excluded. Cortical hyperexcitability was defined by reduced short interval intracortical inhibition (SICI) and increased short interval intracortical facilitation (SICF), index of excitability (IE), and motor evoked potential (MEP) amplitude. Student t test determined differences between groups and multivariable regression modeling was used to assess association among cognitive, clinical, and TMS measures. TMS results were compared with those of 42 controls. Cognitive impairment was evident in 36% of the 40 patients with ALS (23 male, mean age 62.1 years). Cortical hyperexcitability was more prominent in cognitively impaired patients as indicated by an increase in SICF (ECAS≥105 -15.3 ± 1.7%, ECAS<105 -20.6 ± 1.2%; p < 0.01), IE (ECAS ≥105 80.9 ± 7.8, ECAS <105 95.0 ± 4.5; p < 0.01), and MEP amplitude (ECAS≥105 28.7 ± 3.3%, ECAS<105 43.1 ± 5.9%; p < 0.05). SICF was independently associated with the ECAS score (β = 2.410; p < 0.05). Reduced SICI was evident in ALS, being more prominent in patients with reduced executive score (ECASexecutive score>33 6.2 ± 1.3%, ECASexecutive score<33 1.5 ± 2.1%; p < 0.01). Cortical hyperexcitability was more prominent in cognitively impaired patients with ALS than in controls. Given that ECAS is a valid predictor of TDP-43 pathology, the increase in cortical hyperexcitability may be associated with TDP-43 accumulation.