Short Intracortical Inhibition Research Articles

Femoral cortical excitability differs between people with knee osteoarthritis and healthy controls: a pilot study

BACKGROUND: Knee osteoarthritis (OA) is associated with changes in corticospinal and intracortical excitability which may be due to persistent pain. OBJECTIVE: To investigate the cortical excitability profile of the femoral quadriceps in people with knee OA and healthy volunteers. METHODS: Cortical excitability was assessed using transcranial magnetic stimulation (TMS) in 7 participants with knee OA and 6 age- and sex-matched healthy volunteers. The motor evoked potential (MEP), cortical silent period (CSP), short intracortical inhibition (SICI) and intracortical facilitation (ICF) of the rectus femoris (RF), vastus medialis (VM) and vastus lateralis (VL) were measured using standard single pulse and paired-pulse TMS techniques. Data analysis was performed using Mann-Whitney test considering alpha <0.05. RESULTS: Participants with knee OA demonstrated reduced MEP amplitude in the RF and VM muscles and augmented MEP amplitude in the VL muscle. SICI was reduced only in the RF and ICF was reduced in the VM and VL. CSP was reduced in all muscles. CONCLUSION: People with knee OA exhibit altered corticospinal and intracortical excitability profile in specific portions of the quadriceps muscle. This suggests a possible adaptive strategy to maintain quadriceps motor activity.

Multi-focal Stimulation of the Cortico-cerebellar Loop During the Acquisition of a Novel Hand Motor Skill in Chronic Stroke Survivors

Impairment of hand motor function is a frequent consequence after a stroke and strongly determines the ability to regain a self-determined life. An influential research strategy for improving motor deficits is the combined application of behavioral training and non-invasive brain stimulation of the motor cortex (M1). However, a convincing clinical translation of the present stimulation strategies has not been achieved yet. One alternative and innovative approach is to target the functionally relevant brain network-based architecture, e.g., the dynamic interactions within the cortico-cerebellar system during learning. Here, we tested a sequential multifocal stimulation strategy targeting the cortico-cerebellar loop. Anodal transcranial direct current stimulation (tDCS) was applied simultaneously to a hand-based motor training in N = 11 chronic stroke survivors during four training sessions on two consecutive days. The tested conditions were: sequential multifocal (M1-cerebellum (CB)-M1-CB) vs. monofocal control stimulation (M1-sham-M1-sham). Additionally, skill retention was assessed 1 and 10 days after the training phase. Paired-pulse transcranial magnetic stimulation data were recorded to characterize stimulation response determining features. The application of CB-tDCS boosted motor behavior in the early training phase in comparison to the control condition. No faciliatory effects on the late training phase or skill retention were detected. Stimulation response variability was related to the magnitude of baseline motor ability and short intracortical inhibition (SICI). The present findings suggest a learning phase-specific role of the cerebellar cortex during the acquisition of a motor skill in stroke and that personalized stimulation strategies encompassing several nodes of the underlying brain network should be considered.

Inhibitory and excitatory responses in the dorso-medial prefrontal cortex during threat processing.

To evaluate cortical excitability during instructed threat processing. Single and paired transcranial magnetic stimulation (TMS) pulses were applied to the right dorsomedial prefrontal cortex (dmPFC) during high-density electroencephalography (EEG) recording in young healthy participants (n = 17) performing an instructed threat paradigm in which one of two conditioned stimuli (CS+ but not CS-) was paired with an electric shock (unconditioned stimulus [US]). We assessed TMS-induced EEG responses with spectral power (both at electrode and source level) and information flow (effective connectivity) using Time-resolved Partial Directed Coherence (TPDC). Support vector regression (SVR) was used to predict behavioral fear ratings for CS+ based on TMS impact on excitability. During intracortical facilitation (ICF), frontal lobe theta power was enhanced for CS+ compared to single pulse TMS for the time window 0-0.5 s after TMS pulse onset (t(16) = 3.9, p < 0.05). At source level, ICF led to an increase and short intracortical inhibition (SICI) to a decrease of theta power in the bilateral dmPFC, relative to single pulse TMS during 0-0.5 s. Compared to single pulse TMS, ICF increased information flows, whereas SICI reduced the information flows in theta band between dmPFC, amygdala, and hippocampus (all at p < 0.05). The magnitude of information flows between dmPFC to amygdala and dmPFC to hippocampus during ICF (0-0.5 s), predicted individual behavioral fear ratings (CS+; coefficient above 0.75). Distinct excitatory and inhibitory mechanisms take place in the dmPFC. These findings may facilitate future research attempting to investigate inhibitory/facilitatory mechanisms alterations in psychiatric disorders and their behavioral correlates.

Exploring the links between gut microbiota and excitatory and inhibitory brain processes in alcohol use disorder: A TMS study

While the impact of the gut microbiota on brain and behavior is increasingly recognized, human studies examining this question are still scarce. The primary objective of the current study was to explore the potential relationships between the gut microbiota composition, motor cortical excitability at rest and during inhibitory control, as well as behavioral inhibition, in healthy volunteers and in patients suffering from alcohol use disorder. Motor cortical excitability was examined using a range of transcranial magnetic stimulation (TMS) measures probed at rest, including the recruitment curve, short and long intracortical inhibition, and intracortical facilitation within the primary motor cortex. Moreover, TMS was applied during a choice reaction time task to assess changes in motor excitability associated with inhibitory control. Finally, behavioral inhibition was investigated using a neuropsychological task (anti-saccade). Overall, our results highlight several interesting correlations between microbial composition and brain measures. Hence, higher bacterial diversity, as well as higher relative abundances of UGC-002 and Christensenellaceae R-7 group were correlated with stronger changes in motor excitability associated with inhibitory control. Also, higher abundance of Anaerostipes was associated with higher level of corticospinal excitability. Finally, relative abundances of Bifidobacterium and Faecalibacterium were positively related to performance in the neuropsychological task, suggesting that they might have a positive impact on behavioral inhibition. Although correlation is not causation, the present study suggests that excitatory and inhibitory brain processes might be related to gut microbiota composition.This article is part of the Special Issue on ‘Microbiome & the Brain: Mechanisms & Maladies’.

Baseline Measures of Cortical Inhibition Predict Motor Performance Changes after Exercise Interventions

<h3>Research Objectives</h3> To investigate the relationship of transcranial magnetic stimulation (TMS) measures on cortical inhibition before and after an exercise intervention in older adults. Our hypothesis is that higher levels of cortical inhibition would predict greater motor skill acquisition. We predicted that persons randomized to an aerobic spin exercise intervention would increase cortical inhibition and motor performance as compared to light strength training. <h3>Design</h3> The study design is randomized controlled trial with two groups investigating a balance and strength training intervention (both lasting 12-weeks or 36 sessions) against an Aerobic Cycling Intervention. The assessment sessions included behavioral testing, TMS taken at study baseline and after 12-weeks. <h3>Setting</h3> This project involved community dwelling older adults and was performed in a medical center. The main study sites were the Atlanta VA and Emory University. <h3>Participants</h3> We randomized 20 participants to either an exercise intervention or a balance and strength training group after obtaining informed consent. Participants were required to be over the age of 60 years and reportedly healthy at inclusion. This report is on 13 completers. <h3>Interventions</h3> Participants were randomized to either a 12-week interval aerobic spin cycling (HIIT spin) or a 12-week intervention involving light strength training both under supervised trainers thrice weekly for up to 45 minutes per session. <h3>Main Outcome Measures</h3> We acquired transcranial magnetic stimulation measures of: cortical excitability (motor threshold), Short intracortical inhibition, Long Intracortical Inhibition, Short Interhemispheric inhibition, long interhemispheric inhibition. Speed and accuracy of motor learning was the behavioral outcome. <h3>Results</h3> Baseline measures of SICI and LICI showed participants with higher levels of disinhibition showed better motor performance. We found no effect for group. Contrary to our hypothesis, individuals with greater increases in TMS inhibition showed lower motor skill performance after interventions. <h3>Conclusions</h3> We can conclude from the preliminary data that measures of cortical inhibition taken from TMS do show change associated with interventions in older adults and predict improvement in motor skill acquisition. Additional study is needed to identify the mechanisms of change in cortical inhibition. <h3>Author(s) Disclosures</h3> None.

Mechanisms of Hebbian-like plasticity in the ventral premotor - primary motor network.

The functional connection between ventral premotor cortex (PMv) and primary motor cortex (M1) is critical for the organization of goal-directed actions. Repeated activation of this connection by means of cortico-cortical paired associative stimulation (cc-PAS), a transcranial magnetic stimulation (TMS) protocol, may induce Hebbian-like plasticity. However, the physiological modifications produced by Hebbian-like plasticity in the PMv-M1 network are poorly understood. To fill this gap, we investigated the effects of cc-PAS on PMv-M1 circuits. We hypothesized that specific interactions would occur with I2 -wave interneurons as measured by the short intracortical facilitation protocol (SICF). We used different paired-pulse TMS protocols to examine the effects of PMv-M1 cc-PAS on SICF, on GABAergic circuits as measured by short (SICI) and long (LICI) intracortical inhibition protocols, and varied the current direction in M1 to target different M1 neuronal populations. Finally, we examined the effects of cc-PAS on PMv-M1 connectivity using a dual coil approach. We found that PMv-M1 cc-PAS induces both a long-term potentiation (LTP)- or long-term depression (LTD)-like after-effect in M1 neuronal activity that is strongly associated with a bidirectional-specific change in I2 -wave activity (SICF=2.5ms ISI). Moreover, cc-PAS induces a specific modulation of the LICI circuit and separately modulates PMv-M1 connectivity. We suggest that plasticity within the PMv-M1 circuit is mediated by a selective mechanism exerted by PMv on M1 by targeting I2 -wave interneurons. These results provide new mechanistic insights into how PMv modulates M1 activity that are relevant for the design of brain stimulation protocols in health and disease. KEY POINTS: The I2 -wave is specifically modulated by the induction of ventral premotor cortex - primary motor cortex (PMv-M1) plasticity. After PMv-M1 cortico-cortical paired associative stimulation (cc-PAS), corticospinal excitability correlates negatively with I2 -wave amplitude. Different cc-PAS coil orientations can lead to a long-term potentiation- or long-term depression-like after-effect in M1.

Association of Mu opioid receptor (A118G) and BDNF (G196A) polymorphisms with rehabilitation-induced cortical inhibition and analgesic response in chronic osteoarthritis pain

Background/objectiveChronic pain due to osteoarthritis (OA) is a prevalent cause of global disability. New biomarkers are needed to improve treatment allocation, and genetic polymorphisms are promising candidates. MethodWe aimed to assess the association of OPRM1 (A118G and C17T) and brain-derived neurotrophic factor (BDNF [G196A]) polymorphisms with pain-related outcomes and motor cortex excitability metrics (measured by transcranial magnetic stimulation) in 113 knee OA patients with chronic pain. We performed adjusted multivariate regression analyses to compare carriers versus non-carriers in terms of clinical and neurophysiological characteristics at baseline, and treatment response (pain reduction and increased cortical inhibitory tonus) after rehabilitation. ResultsCompared to non-carriers, participants with polymorphisms on both OPRM1 (A118G) and BDNF (G196A) genes were less likely to improve pain after rehabilitation (85 and 72% fewer odds of improvement, respectively). Likewise, both carriers of OPRM1 polymorphisms (A118G and C17T) were also less likely to improve cortical inhibition (short intracortical inhibition [SICI], and intracortical facilitation [ICF], respectively). While pain and cortical inhibition improvement did not correlate in the total sample, the presence of OPRM1 (A118G) and BDNF (G196A) polymorphisms moderated this relationship. ConclusionsThese results underscore the promising role of combining genetic and neurophysiological markers to endotype the treatment response in this population.

A single bout of aerobic exercise modulates motor learning performance and cortical excitability in humans

BackgroundEvidence indicates beneficial effects of aerobic exercise on motor learning performance, which might be caused by the impact of aerobic exercise on cortical excitability. It is thus suggested that physiological effects of aerobic exercise on cortical excitability determine the effects of aerobic exercise on motor learning. Nevertheless, respective results usually come from independent studies, and a prove of the causal relationship between neurophysiological and motor learning effects is still missing. This study aims to explore the impact of a single bout of aerobic exercise on brain physiology and motor learning, and the association between these phenomena in humans MethodThe study was conducted in a cross-over design. In twenty healthy subjects, cortical excitability and motor learning were assessed before and after a single bout of aerobic exercise or a control intervention ResultsThe results show that aerobic exercise improved motor sequence learning and enhanced cortical excitability in humans. Furthermore, a correlation between the exercise-dependent alteration of cortical excitability (short intracortical inhibition, which is determined primarily by the GABAergic system) and improvement of motor learning has been found DiscussionThe study found motor learning performance-improving effects of aerobic exercise, and these results might be explained by an exercised-caused alteration of cortical excitability, especially a reduction of GABA activity.

TH-189. Are short intracortical inhibition (SICI) and intracortical facilitation (ICF) abnormal in ALS patients? – A threshold tracking TMS study

TH-189. Are short intracortical inhibition (SICI) and intracortical facilitation (ICF) abnormal in ALS patients? – A threshold tracking TMS study

The effects of pain induced by blood flow occlusion in one leg on exercise tolerance and corticospinal excitability and inhibition of the contralateral leg in males.

Experiencing pain in one leg can alter exercise tolerance and neuromuscular fatigue (NMF) responses in the contralateral leg; however, the corticospinal modulations to nonlocal experimental pain induced by blood flow occlusion remain unknown. In three randomized visits, 13 male participants performed 25% of isometric maximal voluntary contraction (25%IMVC) to task failure with one leg preceded by (i) 6-min rest (CON), (ii) cycling at 80% of peak power output until task failure with the contralateral leg (CYCL), or (iii) CYCL followed by blood flow occlusion (OCCL) during 25%IMVC. NMF assessments (IMVC, voluntary activation [VA], and potentiated twitch [Qtw]) were performed at baseline and task failure. During the 25%IMVC, transcranial magnetic stimulations were performed to obtain motor-evoked potential (MEP), silent period (SP), and short intracortical inhibition (SICI). 25%IMVC was the shortest in OCCL (105±50s)and shorter in CYCL (154±68s)than CON (219±105s)(p<0.05). IMVC declined less after OCCL (-24±19%) and CYCL (-27±18%), then CON (-35±11%) (p<0.05). Qtw declined less in OCCL (-40±25%) compared to CYCL (-50±22%) and CON (-50±21%) (p<0.05). VA was similar amongst conditions. MEP and SP increased and SICI decreased throughout the task, while SP was longer for OCCL compared to CYC condition (p<0.05). The results suggest that pain in one leg diminishes contralateral limb exercise tolerance and NMF development and modulate corticospinal inhibition in males. Novelty: Pain in one leg diminished MVC and twitch force decline in the contralateral limb. Experimental pain induced by blood flow occlusion may modulation corticospinal inhibition of the neural circuitries innervating the contralateral exercise limb.

Strengthening the GABAergic System Through Neurofeedback Training Suppresses Implicit Motor Learning

Gamma-aminobutyric acid (GABA) activity within the primary motor cortex (M1) is essential for motor learning in cortical plasticity, and a recent study has suggested that real-time neurofeedback training (NFT) can self-regulate GABA activity. Therefore, this study aimed to investigate the effect of GABA activity strengthening via NFT on subsequent motor learning. Thirty-six healthy participants were randomly assigned to either an NFT group or control group, which received sham feedback. GABA activity was assessed for short intracortical inhibition (SICI) within the right M1 using paired-pulse transcranial magnetic stimulation. During the NFT intervention period, the participants tried to modulate the size of a circle, which was altered according to the degree of SICI in the NFT group. However, the size was altered independently of the degree of SICI in the control group. We measured the reaction time before, after (online learning), and 24 h after (offline learning) the finger-tapping task. Results showed the strengthening of GABA activity induced by the NFT intervention, and the suppression of the online but not the offline learning. These findings suggest that prior GABA activity modulation may affect online motor learning.

Transcranial magnetic stimulation as biomarker of excitability in drug development: A randomized, double-blind, placebo-controlled, cross-over study.

AimsThe purpose of this study was to investigate pharmacodynamic effects of drugs targeting cortical excitability using transcranial magnetic stimulation (TMS) combined with electromyography (EMG) and electroencephalography (EEG) in healthy subjects, to further develop TMS outcomes as biomarkers for proof‐of‐mechanism in early‐phase clinical drug development. Antiepileptic drugs presumably modulate cortical excitability. Therefore, we studied effects of levetiracetam, valproic acid and lorazepam on cortical excitability in a double‐blind, placebo‐controlled, 4‐way cross‐over study.MethodsIn 16 healthy male subjects, single‐ and paired‐pulse TMS‐EMG–EEG measurements were performed predose and 1.5, 7 and 24 hours postdose. Treatment effects on motor‐evoked potential, short and long intracortical inhibition and TMS‐evoked potential amplitudes, were analysed using a mixed model ANCOVA and cluster‐based permutation analysis.ResultsWe show that motor‐evoked potential amplitudes decreased after administration of levetiracetam (estimated difference [ED] −378.4 μV; 95%CI: −644.3, −112.5 μV; P < .01), valproic acid (ED −268.8 μV; 95%CI: −532.9, −4.6 μV; P = .047) and lorazepam (ED −330.7 μV; 95%CI: −595.6, −65.8 μV; P = .02) when compared with placebo. Long intracortical inhibition was enhanced by levetiracetam (ED −60.3%; 95%CI: −87.1%, −33.5%; P < .001) and lorazepam (ED −68.2%; 95%CI: −94.7%, −41.7%; P < .001) at a 50‐ms interstimulus interval. Levetiracetam increased TMS‐evoked potential component N45 (P = .004) in a central cluster and decreased N100 (P < .001) in a contralateral cluster.ConclusionThis study shows that levetiracetam, valproic acid and lorazepam decrease cortical excitability, which can be detected using TMS‐EMG–EEG in healthy subjects. These findings provide support for the use of TMS excitability measures as biomarkers to demonstrate pharmacodynamic effects of drugs that influence cortical excitability.

Abstract WMP37: Differential Montage Effect On Cortical Excitability In Ischemic Stroke Patients By Single Session Of High Amperage Transcranial Direct Current Stimulation

Background and Objective: We aim to assess the cortical excitability under three montages with single session of transcranial direct current stimulation (tDCS) at 4 mA on ischemic stroke patients. Methods: Adult subjects with first-ever unilateral ischemic stroke ≥6 months and inducible motor evoked potentials (MEP) underwent 3 sessions (washed out ≥2 days apart) of 30 minutes 4 mA tDCS in anodal, cathodal or bihemispheric montage (in pseudorandom order) combined with t upper extremity repetitive task training administered by an Occupational Therapist. We collected MEP responses to transcranial magnetic stimulation (TMS) single pulse, short intracortical inhibition (SICI, 3 ms) and intracortical facilitation (ICF, 15 ms) on bilateral abductor pollicis brevis (APB) muscles at baseline and four post-stimulation timepoints 12 minutes apart. We also monitored safety by recording adverse events, surveying subjects with a questionnaire on tolerability issues and collecting biometric measures (body resistance, skin temperature under the tDCS electrode). Results: Eighteen subjects completed 54 tDCS sessions in total. We observed montage ( P &lt;0.0001) and time ( P &lt;0.01) effects only on the lesioned hemisphere, with bihemispheric tDCS showing relatively higher peak-to-peak MEP. Lack of montage effect in baseline ( P &gt;0.949) suggested sufficient washout interval across the visits. No subjects experienced any adverse events. Biometric measures and tolerability were comparable across the three montages. The most common tolerability issue was transient redness under the tDCS electrodes (70% at anode, 48% at cathode). Conclusions: The bihemispheric montage increased ipsilateral cortical excitability the most in a single session of 4 mA tDCS in chronic ischemic stroke patients. Additionally, a current level of 4 mA is safe and tolerable over multiple sessions.

Are Neurophysiological Biomarkers Able to Discriminate Multiple Sclerosis Clinical Subtypes?

Secondary progressive multiple sclerosis (SPMS) subtype is retrospectively diagnosed, and biomarkers of the SPMS are not available. We aimed to identify possible neurophysiological markers exploring grey matter structures that could be used in clinical practice to better identify SPMS. Fifty-five people with MS and 31 healthy controls underwent a transcranial magnetic stimulation protocol to test intracortical interneuron excitability in the primary motor cortex and somatosensory temporal discrimination threshold (STDT) to test sensory function encoded in cortical and deep grey matter nuclei. A logistic regression model was used to identify a combined neurophysiological index associated with the SP subtype. We observed that short intracortical inhibition (SICI) and STDT were the only variables that differentiated the RR from the SP subtype. The logistic regression model provided a formula to compute the probability of a subject being assigned to an SP subtype based on age and combined SICI and STDT values. While only STDT correlated with disability level at baseline evaluation, both SICI and STDT were associated with disability at follow-up. SICI and STDT abnormalities reflect age-dependent grey matter neurodegenerative processes that likely play a role in SPMS pathophysiology and may represent easily accessible neurophysiological biomarkers for the SPMS subtype.

Electroacupuncture modulates cortical excitability in a manner dependent on the parameters used.

There is evidence that electroacupuncture (EA) acts through the modulation of brain activity, but little is known about its influence on corticospinal excitability of the primary motor cortex (M1). To investigate the influence of EA parameters on the excitability of M1 in healthy individuals. A parallel, double blind, randomized controlled trial in healthy subjects, evaluating the influence of an EA intervention on M1 excitability. Participants had a needle inserted at LI4 in the dominant hand and received electrical stimulation of different frequencies (10 or 100 Hz) and amplitude (sensory or motor threshold) for 20 min. In the control group, only a brief (30 s) electrical stimulation was applied. Single and paired pulse transcranial magnetic stimulation coupled with electromyography was applied before and immediately after the EA intervention. Resting motor threshold, motor evoked potential, short intracortical inhibition and intracortical facilitation were measured. EA increased corticospinal excitability of M1 compared to the control group only when administered with a frequency of 100 Hz at the sensory threshold (p < 0.05). There were no significant changes in the other measures. The results suggest that EA with an intensity level at the sensorial threshold and 100 Hz frequency increases the corticospinal excitability of M1. This effect may be associated with a decrease in the activity of inhibitory intracortical mechanisms. U1111-1173-1946 (Registro Brasileiro de Ensaios Clínicos; http://www.ensaiosclinicos.gov.br/).

Increased motor cortex inhibition as a marker of compensation to chronic pain in knee osteoarthritis

This study aims to investigate the associative and multivariate relationship between different sociodemographic and clinical variables with cortical excitability as indexed by transcranial magnetic stimulation (TMS) markers in subjects with chronic pain caused by knee osteoarthritis (OA). This was a cross-sectional study. Sociodemographic and clinical data were extracted from 107 knee OA subjects. To identify associated factors, we performed independent univariate and multivariate regression models per TMS markers: motor threshold (MT), motor evoked potential (MEP), short intracortical inhibition (SICI), intracortical facilitation (ICF), and cortical silent period (CSP). In our multivariate models, the two markers of intracortical inhibition, SICI and CSP, had a similar signature. SICI was associated with age (β: 0.01), WOMAC pain (β: 0.023), OA severity (as indexed by Kellgren–Lawrence Classification) (β: − 0.07), and anxiety (β: − 0.015). Similarly, CSP was associated with age (β: − 0.929), OA severity (β: 6.755), and cognition (as indexed by the Montreal Cognitive Assessment) (β: − 2.106). ICF and MT showed distinct signatures from SICI and CSP. ICF was associated with pain measured through the Visual Analogue Scale (β: − 0.094) and WOMAC (β: 0.062), and anxiety (β: − 0.039). Likewise, MT was associated with WOMAC (β: 1.029) and VAS (β: − 2.003) pain scales, anxiety (β: − 0.813), and age (β: − 0.306). These associations showed the fundamental role of intracortical inhibition as a marker of adaptation to chronic pain. Subjects with higher intracortical inhibition (likely subjects with more compensation) are younger, have greater cartilage degeneration (as seen by radiographic severity), and have less pain in WOMAC scale. While it does seem that ICF and MT may indicate a more acute marker of adaptation, such as that higher ICF and MT in the motor cortex is associated with lesser pain and anxiety.

Hyperexcitability and dysfunction of cortical excitation / inhibition mechanisms in migraine: A paired pulse TMS study

Paired-pulse TMS paradigms can be used to test connectivity within the primary motor cortex. Aim of the study was to provide additional information on short intracortical inhibition (SICI) and intracortical facilitation(ICF) using different intensities of the test stimulus (TS) in episodic and chronic migraine(CM, EM) patients.

Are there differences in cortical excitability between akinetic-rigid and tremor-dominant subtypes of Parkinson's disease?

ObjectiveTo assess by transcranial magnetic stimulation (TMS) the excitability of various cortical circuits in akinetic-rigid and tremor-dominant subtypes of Parkinson's disease (PD). MethodsThe study included 92 patients with PD according to UK Brain Bank criteria, with akinetic-rigid (n = 64) or tremor-dominant (n = 28) subtype. Cortical excitability study, including resting and active motor thresholds (rMT and aMT), input—output curve of motor evoked potentials, contralateral and ipsilateral silent periods (cSP and iSP), short and long-interval intracortical inhibition (SICI and LICI), and intracortical facilitation (ICF) were measured. The results obtained were compared to a control group of 30 age- and sex-matched healthy subjects. ResultsThe patients in the tremor group had significantly lower rMT and aMT compared to controls and akinetic-rigid patients and significantly shorter iSP duration compared to akinetic-rigid patients, while iSP latency tended to be longer in akinetic-rigid patients compared to controls. There were no significant differences between the two PD subgroups regarding other cortical excitability parameters, including paired-pulse TMS parameters. ConclusionsOnly subtle differences of cortical excitability were found between patients with akinetic-rigid vs. tremor-dominant subtype of PD. SignificanceThe clinical heterogeneity of PD patients probably has an impact on cortical excitability measures, far beyond the akinetic-rigid versus tremor-dominant profile.

Graded motor imagery modifies movement pain, cortical excitability and sensorimotor function in complex regional pain syndrome.

Patients with complex regional pain syndrome suffer from chronic neuropathic pain and also show a decrease in sensorimotor performance associated with characteristic central and peripheral neural system parameters. In the brain imaging domain, these comprise altered functional sensorimotor representation for the affected hand side. With regard to neurophysiology, a decrease in intracortical inhibition for the sensorimotor cortex contralateral to the affected hand has been repetitively verified, which might be related to increased primary somatosensory cortex functional activation for the affected limb. Rare longitudinal intervention studies in randomized controlled trials have demonstrated that a decrease in primary somatosensory cortex functional MRI activation coincided with pain relief and recovery in sensorimotor performance. By applying a randomized wait-list control crossover study design, we tested possible associations of clinical, imaging and neurophysiology parameters in 21 patients with complex regional pain syndrome in the chronic stage (>6 months). In more detail, we applied graded motor imagery over 6 weeks to relieve movement pain of the affected upper limb. First, baseline parameters were tested between the affected and the non-affected upper limb side and age-matched healthy controls. Second, longitudinal changes in clinical and testing parameters were associated with neurophysiological and imaging parameters. During baseline short intracortical inhibition, as assessed with transcranial magnetic stimulation, was decreased only for hand muscles of the affected hand side. During movement of the affected limb, primary somatosensory cortex functional MRI activation was increased. Hand representation area size for somatosensory stimulation in functional MRI was smaller on the affected side with longer disease duration. Graded motor imagery intervention but not waiting, resulted in a decrease of movement pain. An increase of somatosensory hand representation size over graded motor imagery intervention was related to movement pain relief. Over graded motor imagery intervention, pathological parameters like the increased primary somatosensory cortex activation during fist movement or decreased short intracortical inhibition were modified in the same way as movement pain and hand performance improved. No such changes were observed during the waiting period. Overall, we demonstrated characteristic changes in clinical, behaviour and neuropathology parameters applying graded motor imagery in patients with upper limb complex regional pain syndrome, which casts light on the effects of graded motor imagery intervention on biomarkers for chronic neuropathic pain.

SY1.3. Probing the pathophysiology of movement disorders with transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) is a widely-used noninvasive brain stimulation method for research in the field of neurology, psychiatry, and rehabilitation. TMS can be used to study connectivity and therefore help to shed light on brain networks. This mode of noninvasive brain stimulation is particularly useful to study brain regions relevant to movement, as stimulating the primary motor cortex results in motor-evoked potential (MEP)s, which can be useful for interpreting the effects of various brain regions on the motor cortex. Connectivity among the primary motor cortex and other movement-relevant regions can be studied by using a paired- or multiple-pulse technique. This is possible by assessing the effects of a pre- conditioning stimulus on the conditioning-test pair or a conditioning stimulus on the test pulse. TMS can also be used in conjunction with electroencephalography (EEG), magnetoencephalography (MEG) or imaging tools such as functional magnetic resonance imaging (fMRI) or positron emission tomography (PET) to further assess TMS-induced changes. Combining these techniques can enable researchers to obtain spatial or temporal information of the effects of TMS on the brain. Movement in healthy human subjects has been studied using TMS, and information obtained from these studies has been useful in understanding which brain regions are relevant in producing movement. Furthermore, there are various TMS measures of the motor cortex that reflect different aspects of cortical excitability. Some examples are short and long intracortical inhibition (SICI and LICI), intracortical facilitation (ICF), short- and long- afferent inhibition (SAI and LAI), transcallosal inhibition, premotor cortex inhibition, etc. TMS has also been used to study movement disorders such as Parkinson’s disease, dystonia, essential tremor, and Huntington’s disease. While TMS still has limited use in the clinical realm, it has provided a wealth of data in our understanding of movement disorders. In this talk, I will give an overview of TMS studies that probe the physiology of normal human movement and also discuss those focusing on movement disorders. I will also review limitations of TMS and the findings of TMS studies to date, and briefly discuss the need for future studies.