Paired Transcranial Magnetic Stimulation Research Articles

Long-interval afferent inhibition measurement using two different methods: Normative values, repeatability and reliability

BackgroundThe mechanism of Short-Latency Afferent Inhibition (SAI) is relatively well understood. In contrast, Long-Latency Afferent Inhibition (LAI) has not been as extensively studied as SAI, and its underlying mechanism remains unclear. Objective/HypothesisThis study had two primary objectives: first, to determine the optimal ISIs for LAI measured by amplitude changes (A-LAI) using high-resolution ISI ranges; and second, to compare measurements of LAI by threshold-tracking (T-LAI). MethodsTwenty-eight healthy volunteers (12 males aged 24- 45 years) participated in the study. Paired peripheral electrical and transcranial magnetic stimulation (TMS) stimuli (TS1mv) were applied at varying (ISIs)- 100, 200, 250, 300, 350, 400, 450, 500, 550, 600, 700, 800, 900, 1000 ms. ResultsBoth A-LAI and T-LAI showed that LAI decreased progressively from a peak at 200 or 250 ms to 1000 ms. Using the A-LAI method, pronounced inhibition was observed at three specific ISIs: 100 ms, 250 ms and 450 ms. When A-LAI values were converted to equivalent threshold changes, they did not differ significantly from T-LAI. Reliability at distinguishing individuals, as indicated by intraclass correlation coefficient (ICC) was greater for A-LAI, with a peak value of 0.82 at 250 ms. Conclusion(s)The study demonstrates that ISIs of 100 ms and 250 ms can be reliably used in amplitude measurement LAI. The study demonstrates that both LAI measurements record a similar decline of inhibition with increasing ISI.

Paired DBS and TMS Reveals Dentato-Cortical Facilitation Underlying Upper Extremity Movement in Chronic Stroke Survivors

Background Cerebellum shares robust di-synaptic dentato-thalamo-cortical (DTC) connections with the contralateral motor cortex. Preclinical studies have shown that DTC are excitatory in nature. Structural integrity of DTC is associated with better upper extremity (UE) motor function in people with stroke, indicating DTC are important for cerebellar influences on movement. However, there is a lack of understanding of physiologic influence of DTC in humans, largely due to difficulty in accessing the dentate nucleus. Objective Characterize DTC physiology using dentate nucleus deep brain stimulation (DBS) combined with transcranial magnetic stimulation (TMS) in stroke. Methods Nine chronic stroke survivors with moderate-to-severe UE impairment (Fugl-Meyer 13-38) underwent a paired DBS–TMS experiment before receiving experimental dentate nucleus DBS in our first-in-human phase I trial (Baker et al., 2023, Nature Medicine). Conditioning DBS pulses were given to dentate nucleus 1 to 10 ms prior to supra-threshold TMS pulses given to ipsilesional motor cortex. Effects were assessed on motor evoked potentials (MEPs). Size of DBS-conditioned MEPs was expressed relative to TMS MEPs, where values >1 indicate facilitation. Results Dentate nucleus DBS led to facilitation of MEPs at short-latency intervals (3.5 and 5 ms, P = .049 and .021, respectively), a phenomenon we have termed dentato-cortical facilitation (DCF). Higher DCF was observed among patients with more severe UE impairment. Diffusion tensor imaging revealed microstructure of thalamo-cortical portion of DTC was related to higher corticomotor excitability. Conclusions Our in vivo investigation reveals for the first time in humans the intrinsic excitatory properties of DTC, which can serve as a novel therapeutic target for post-stroke motor recovery.

GABAA Receptor Availability in Relation to Cortical Excitability in Depressed and Healthy: A Positron Emission Tomography and Transcranial Magnetic Stimulation Study

Introduction: Gamma-aminobutyric acid (GABA) deficiency is suggested in depressive disorders, along with alterations in cortical excitability. However, whether these excitability changes are related to GABA_A receptor availability is largely unknown. Our aim was to assess the correlation between these measures in depressed patients and healthy controls. Methods: Twenty-eight patients with a major depressive episode, measured before and after participating in a clinical trial with repetitive transcranial magnetic stimulation (TMS), and 15 controls underwent [¹¹C]flumazenil positron emission tomography to assess GABA_A receptor availability and paired pulse TMS (ppTMS) to evaluate cortical excitability. Both whole-brain voxel-wise GABA_A receptor availability and mean values from left hand motor cortex and left paracentral lobule were correlated to the ppTMS outcomes: short-interval intracortical inhibition reflecting GABA_A receptor activity, long-interval intracortical inhibition representing GABA_B receptor activity, intracortical facilitation reflecting glutamate N-methyl-D-aspartate-receptor activity, as well as the resting motor threshold (rMT), considered a global measure of corticospinal excitability. Results: No significant differences in baseline GABA_A receptor availability or cortical excitability were found between patients and controls. Additionally, no correlations were observed between baseline measurements of GABA_A receptor availability and TMS outcomes. Changes in GABA_A receptor availability in the hand motor cortex, between pre- and post-assessments, were inversely related to pre-post changes in hand rMT. Conclusion: We found that a change in GABA_A receptor availability was inversely related to a change in rMT, suggesting a link between GABA deficiency and increased rMT previously observed in depressive episodes. The results highlight the complex mechanisms governing cortical excitability measures and offer new insight into their properties during the depressive state.

Remote ischaemic conditioning combined with bimanual task training to enhance bimanual skill learning and corticospinal excitability in children with unilateral cerebral palsy: a study protocol of a single centre, phase II randomised controlled trial

IntroductionChildren with unilateral cerebral palsy (UCP) have difficulty in bimanual coordination that restricts the child’s independence in daily activities. Although several efficacious interventions to improve bimanual coordination exist, these interventions...

The efficacy of non-invasive brain stimulation in the treatment of children and adolescents with Anorexia Nervosa: study protocol of a randomized, double blind, placebo-controlled trial

BackgroundCurrent psychological and pharmacological treatments for Anorexia Nervosa (AN) provide only moderate effective support, and there is an urgent need for research to improve therapies, especially in developing age. Non-invasive brain stimulation has suggested to have the potential to reducing AN symptomatology, via targeting brain alterations, such as hyperactivity of right prefrontal cortex (PFC). We suppose that transcranial direct current stimulation (tDCS) to the PFC may be effective in children and adolescents with AN.MethodsWe will conduct a randomized, double blind, add-on, placebo-controlled trial to investigate the efficacy of tDCS treatment on clinical improvement. We will also investigate brain mechanisms and biomarkers changes acting in AN after tDCS treatment. Eighty children or adolescent with AN (age range 10–18 years) will undergo treatment-as-usual including psychiatric, nutritional and psychological support, plus tDCS treatment (active or sham) to PFC (F3 anode/F4 cathode), for six weeks, delivered three times a week. Psychological, neurophysiological and physiological measures will be collected at baseline and at the end of treatment. Participants will be followed-up one, three, six months and one year after the end of treatment. Psychological measures will include parent- and self-report questionnaires on AN symptomatology and other psychopathological symptoms. Neurophysiological measures will include transcranial magnetic stimulation (TMS) with electroencephalography and paired pulse TMS and repetitive TMS to investigate changes in PFC connectivity, reactivity and plasticity after treatment. Physiological measures will include changes in the functioning of the endogenous stress response system, body mass index (BMI) and nutritional state.DiscussionWe expect that tDCS treatment to improve clinical outcome by reducing the symptoms of AN assessed as changes in Eating Disorder Risk composite score of the Eating Disorder Inventory-3. We also expect that at baseline there will be differences between the right and left hemisphere in some electrophysiological measures and that such differences will be reduced after tDCS treatment. Finally, we expect a reduction of endogenous stress response and an improvement in BMI and nutritional status after tDCS treatment. This project would provide scientific foundation for new treatment perspectives in AN in developmental age, as well as insight into brain mechanisms acting in AN and its recovery.Trial registration The study was registered at ClinicalTrials.gov (ID: NCT05674266) and ethical approval for the study was granted by the local research ethics committee (process number 763_OPBG_2014).

Probing the link between cortical inhibitory and excitatory processes and muscle fascicle dynamics

During movements, neural signals are translated into muscle fibre shortening, lengthening or they remain isometric. This study investigated cortical excitatory and inhibitory processes in relation to muscle fascicle dynamics during fixed-end rapid contractions. Fourteen adults performed submaximal and maximal ankle dorsiflexions. Single and paired pulse transcranial magnetic stimulation over the cortical representation projecting to the tibialis anterior (TA) was applied during rest, the activation and deactivation phase of contractions to test for short- (SICI) and long-interval intracortical inhibition (LICI) and intracortical facilitation (ICF). Ultrasound images were taken to measure muscle fascicle dynamics of the superficial (TASF) and deep (TADP) TA compartments. The results show significantly greater maximal shortening velocities (p = 0.003, d = 0.26, CI [4.89, 18.52]) and greater maximal fascicle shortening (p = 0.003, d = 0.86, CI [0.29, 3.13]) in TASF than TADP during submaximal dorsiflexions. Significantly lower SICI levels during activation compared to deactivation (p = 0.019, d = 1.12, CI [19.82, 1.76]) and at rest (p < 0.0001) were observed. ICF was significantly greater during activation (p = 0.03) than during rest while LICI did not modulate significantly. Maximal TASF but not TADP shortening velocity correlated with SICI levels at activation (p = 0.06) and with the rate of torque development (p = 0.02). The results suggest that SICI might be related to muscle fascicle behavior and that intracortical inhibition and excitation are phase-dependently modulated.

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.

Paired pulse transcranial magnetic stimulation in the assessment of biceps voluntary activation in individuals with tetraplegia.

After spinal cord injury (SCI), motoneuron death occurs at and around the level of injury which induces changes in function and organization throughout the nervous system, including cortical changes. Muscle affected by SCI may consist of both innervated (accessible to voluntary drive) and denervated (inaccessible to voluntary drive) muscle fibers. Voluntary activation measured with transcranial magnetic stimulation (VATMS) can quantify voluntary cortical/subcortical drive to muscle but is limited by technical challenges including suboptimal stimulation of target muscle relative to its antagonist. The motor evoked potential (MEP) in the biceps compared to the triceps (i.e., MEP ratio) may be a key parameter in the measurement of biceps VATMS after SCI. We used paired pulse TMS, which can inhibit or facilitate MEPs, to determine whether the MEP ratio affects VATMS in individuals with tetraplegia. Ten individuals with tetraplegia following cervical SCI and ten non-impaired individuals completed single pulse and paired pulse VATMS protocols. Paired pulse stimulation was delivered at 1.5, 10, and 30 ms inter-stimulus intervals (ISI). In both the SCI and non-impaired groups, the main effect of the stimulation pulse (paired pulse compared to single pulse) on VATMS was not significant in the linear mixed-effects models. In both groups for the stimulation parameters we tested, the MEP ratio was not modulated across all effort levels and did not affect VATMS. Linearity of the voluntary moment and superimposed twitch moment relation was lower in SCI participants compared to non-impaired. Poor linearity in the SCI group limits interpretation of VATMS. Future work is needed to address methodological issues that limit clinical application of VATMS.

Transcranial direct current stimulation in stroke – Motor excitability and motor function

ObjectiveTo characterize motor excitability changes and changes of motor performance induced by a single anodal and cathodal transcranial direct current stimulation (tDCS) session in stroke patients. MethodsTwenty subacute stroke patients participated. Motor performance was tested with the Box and Block Test [BBT]. Motor cortex excitability (short interval intracortical inhibition [SICI], intracortical facilitation [ICF], long interval intracortical inhibition [LICI]) was examined by paired pulse transcranial magnetic stimulation before and after a single tDCS session (20 minutes, 1,0 mA). On two different occasions, patients received anodal and cathodal tDCS over the affected hemisphere. TMS recordings were taken from both hands consecutively. ResultsAnodal tDCS significantly reduced SICI without changing ICF or LICI. Cathodal tDCS did not change motor excitability. Both types of tDCS did not alter motor performance. Even prior to anodal tDCS, SICI in the affected hemisphere was lower than in the unaffected hemisphere and was correlated with BBT changes after anodal tDCS. ConclusionsAnodal, but not cathodal tDCS specifically modulated intracortical inhibitory circuits, leading to a disinhibition. SignificanceThe results amplify our knowledge on excitability modulations of tDCS in stroke patients.

Different Modalities of Transcranial Magnetic Stimulation to Manage Schizophrenia.

Objective: To analyze all current literature related to different transcranial magnetic stimulation (TMS) modalities in the management of schizophrenia symptoms and compare the main controversies in the outcome measures. Data Sources: A comprehensive search in Ovid MEDLINE, APA PsycINFO, and PubMed was conducted (1996 to present) to identify all articles using the search terms schizophrenia and single pulse TMS, schizophrenia and paired pulse TMS, schizophrenia and repetitive TMS, schizophrenia and deep TMS, and schizophrenia and TBS. Data Selection: Search results were limited to the English language and human subjects. Unrelated articles were excluded after the initial review. Nineteen studies fulfilled the eligibility criteria. These studies included 531 schizophrenia patients and 283 healthy controls. Results: While some adverse effects of TMS are reported, the process is generally considered safe. However, discrepancies exist regarding the length of the cortical silent period. The cortical silent period is thought to be mediated by γ-aminobutyric acid (GABA) receptors and is considered a useful probe to assess motor cortical inhibition. It is generally believed that patients with schizophrenia present changes in the cortical silent period due to GABA abnormalities. A few physiologic studies utilized TMS to study motor cortical excitability in schizophrenia and reported longer, and some shorter, cortical silent periods compared with healthy controls. Also, some studies reported a shorter cortical silent period for unmedicated versus medicated patients, while others reported no differences. Conclusion: TMS treatment is commonly reported to improve auditory hallucination in schizophrenia. Advantage of use of deep TMS over repetitive TMS, however, is controversial.

Human perceptual and metacognitive decision-making rely on distinct brain networks.

Perceptual decisions depend on the ability to exploit available sensory information in order to select the most adaptive option from a set of alternatives. Such decisions depend on the perceptual sensitivity of the organism, which is generally accompanied by a corresponding level of certainty about the choice made. Here, by use of corticocortical paired associative transcranial magnetic stimulation protocol (ccPAS) aimed at inducing plastic changes, we shaped perceptual sensitivity and metacognitive ability in a motion discrimination task depending on the targeted network, demonstrating their functional dissociation. Neurostimulation aimed at boosting V5/MT+-to-V1/V2 back-projections enhanced motion sensitivity without impacting metacognition, whereas boosting IPS/LIP-to-V1/V2 back-projections increased metacognitive efficiency without impacting motion sensitivity. This double-dissociation provides causal evidence of distinct networks for perceptual sensitivity and metacognitive ability in humans.

Exploring the connections between basal ganglia and cortex revealed by transcranial magnetic stimulation, evoked potential and deep brain stimulation in dystonia.

We review the findings for motor cortical excitability, plasticity and evoked potentials in dystonia. Plasticity can be induced and assessed in cortical areas by non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) and the invasive technique of deep brain stimulation (DBS), which allows access to deep brain structures. Single-pulse TMS measures have been widely studied in dystonia and consistently showed reduced silent period duration. Paired pulse TMS measures showed reduced short and long interval intracortical inhibition, interhemispheric inhibition, long-latency afferent inhibition and increased intracortical facilitation in dystonia. Repetitive transcranial magnetic stimulation (rTMS) of the premotor cortex improved handwriting with prolongation of the silent period in focal hand dystonia patients. Continuous theta-burst stimulation (cTBS) of the cerebellum or cTBS of the dorsal premotor cortex improved dystonia in some studies. Plasticity induction protocols in dystonia demonstrated excessive motor cortical plasticity with the reduction in cortico-motor topographic specificity. Bilateral DBS of the globus pallidus internus (GPi) improves dystonia, associated pain and functional disability. Local field potentials recordings in dystonia patients suggested that there is increased power in the low-frequency band (4-12Hz) in the GPi. Cortical evoked potentials at peak latencies of 10 and 25ms can be recorded with GPi stimulation in dystonia. Plasticity induction protocols based on the principles of spike timing dependent plasticity that involved repeated pairing of GPi-DBS and motor cortical TMS at latencies of cortical evoked potentials induced motor cortical plasticity. These studies expanded our knowledge of the pathophysiology of dystonia and how cortical excitability and plasticity are altered with different treatments such as DBS.

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/).

SY2.2. Evaluation of myoclonus

Myoclonus is a shock-like jerky movement observed in the extremities or the trunk without consciousness loss. This involuntary movement is generated by abnormal neuronal discharges in the central nerve system caused by many kinds of etiologies. Based on the physiological generator mechanism, myoclonus is classified mainly into the three groups; cortical myoclonus, subcortical myoclonus and spinal myoclonus. Cortical myoclonus includes spontaneous cortical myoclonus and cortical reflex myoclonus. In cortical myoclonus, an EEG spike precedes a muscle jerk. Backward EEG averaging time-locked to the onset of myoclonus (jerk-locked back averaging: JLA) often detects cortical spike preceding the myoclonus, which is unable to be shown by EEG-EMG polygraph recordings. The duration of EMG jerks is usually shorter than 50-100ms. Somatosensory evoked potentials are often enlarged (giant SEP) in cortical reflex myoclonus. Enhanced long loop reflex is also often seen in the polygraph in the cortical reflex myoclonus (so called “C” reflex). The disinhibition of the sensory cortex can be revealed by SEP recovery curve studied by paired pulse stimulation. The hyperexcitability of the motor cortex is shown by the paired pulse transcranial magnetic stimulation (TMS) technique. The short interval intra-cortical inhibition (SICI) was abnormally reduced. These physiological features indicate the cortical hyper- excitability. Subcortical myoclonus is supposed to be generated at the basal ganglia or brainstem. The duration of muscle jerk is longer than 50-100ms. In some subcortical myoclonus (reticular myoclonus), the latency of long loop reflexes is shorter than those of enhanced C-reflexes. JLA reveals no cortical spikes, and no giant SEPs are seen. Spinal myoclonus includes “segmental spinal myoclonus” which is generated by activation of certain spinal segments, and “propriospinal myoclonus” which originates from a certain spinal segment and spreads upward/downward slowly though the propriospinal tract. Simultaneous EMG recordings of many muscles are useful to estimate the spinal conduction between different spinal cord levels. Electrophysiological studies are useful to evaluate myoclonus and to suggest the generator mechanisms for myoclonus. Here, I will introduce some neurophysiological methods for analyses of myoclonus.

Relationship between GABA levels and task-dependent cortical excitability in children with attention-deficit/hyperactivity disorder

ObjectiveCompared to typically developing (TD) peers, children with attention deficit hyperactivity disorder (ADHD) manifest reduced short interval cortical inhibition (SICI) in the dominant motor cortex measured with transcranial magnetic stimulation (TMS). This multimodal study investigates the inhibitory neurophysiology and neurochemistry by evaluating the relationship between SICI and γ-amino butyric acid (GABA+) levels, measured with magnetic resonance spectroscopy (MRS). MethodsAcross two sites, 37 children with ADHD and 45 TD children, ages 8–12 years, participated. Single and paired pulse TMS to left motor cortex quantified SICI during REST and at times of action selection (GO) and inhibition (STOP) during a modified Slater-Hammel stop signal reaction task. MRS quantified GABA+ levels in the left sensorimotor cortex. Relationships between SICI and GABA+, as well as stopping efficiency and clinical symptoms, were analyzed with correlations and repeated-measure, mixed-models. ResultsIn both groups, higher GABA+ levels correlated with less SICI. In TD children only, higher GABA+ levels correlated with larger TMS motor evoked potentials (MEPs) at REST. In GO and STOP trials, higher GABA+ was associated with smaller MEP amplitudes, for both groups. Overall, GABA+ levels did not differ between groups or correlate with ADHD clinical symptoms. ConclusionsIn children with higher motor cortex GABA+, motor cortex is less responsive to inhibitory TMS (SICI). Comparing the relationships between MRS-GABA+ levels and responses to TMS at REST vs. GO/STOP trials suggests differences in inhibitory neurophysiology and neurotransmitters in children with ADHD. These differences are more prominent at rest than during response inhibition task engagement. SignificanceEvaluating relationships between GABA+ and SICI may provide a biomarker useful for understanding behavioral diagnoses.

Chronic Neurophysiological Effects of Repeated Head Trauma in Retired Australian Male Sport Athletes.

Aim: This study investigated the somatosensory and corticomotor physiology of retired contact sport athletes with a history of repeated concussion/subconcussion head trauma.Methods: Retired male athletes with a history of playing contact sports and repeated head trauma (n = 122) were divided into two groups: those who expressed concerns regarding their mental and cognitive health (“symptomatic”: n = 83), and those who did not express any ongoing concerns (“asymptomatic”: n = 39). Both groups were compared to age-matched male controls (n = 50) with no history of concussions or participation in contact sports, an absence of self-reported cognitive, or mood impairments. Transcranial magnetic stimulation (TMS) and vibrotactile stimulation were used to assess corticomotor and somatosensory pathways respectively. TMS and vibrotactile stimulation were correlated to self-reported responses using the Fatigue and Related Symptom Survey. Linear regression was used to associate concussion history with TMS, somatosensory variables.Results: Significant differences were found in symptom survey scores between all groups (p < 0.001). TMS showed significant differences between the “symptomatic” and control groups for intracortical inhibition and paired pulse TMS measures. Somatosensory measures showed significant differences for reaction time (p < 0.01) and reaction time variability (p < 0.01) between the “symptomatic” group to the “asymptomatic” and control groups. For other somatosensory measures, the “symptomatic” measures showed differences to the “control” group. Correlations showed significant associations between severity of symptom reporting with TMS and somatosensory measure, and regression revealed the number of concussions reported was shown to have significant relationships to increased intracortical inhibition and poorer somatosensory performance.Conclusion: This study shows that retired contact sport athletes expressing chronic symptoms showed significant pathophysiology compared to those with no ongoing concerns and non-concussed controls. Further, there is a linear dose-response relationship between number of reported concussions and abnormal neurophysiology. Neurophysiological assessments such as TMS and somatosensory measures represent useful and objective biomarkers to assess cortical impairments and progression of neuropsychological impairment in individuals with a history of repeated head trauma.

Convergent Associative Motor Cortical Plasticity Induced by Conditional Somatosensory and Motor Reaction Afferents.

Objective: Associative motor cortical plasticity can be non-invasively induced by paired median nerve electric stimulation and transcranial magnetic stimulation (TMS) of the primary motor cortex (M1). This study investigates whether a simultaneous motor reaction of the other hand advances the associative plasticity in M1.Methods: Twenty-four right-handed subjects received conventional paired associative stimulation (PAS) and PAS with simultaneous motor reaction (PASmr) with at least a 1-week interval. The PASmr protocol additionally included left abductor pollicis brevis muscle movement responding to a digital sound. The motor reaction time was individually measured. The M1 excitability was examined by the motor evoked potential (MEP), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF) before and after the PAS protocols.Results: The conventional PAS protocol significantly facilitated MEP and suppressed SICI. A negative correlation between the reaction time and the MEP change, and a positive correlation between the reaction time and the ICF change were found in the PASmr protocol. By subgrouping analysis, we further found significant facilitation of MEP and a reduction of ICF in the subjects with fast reaction times but not in those with slow reaction times.Conclusion: Synchronized motor reaction ipsilateral to the stimulated M1 induces associative M1 motor plasticity through the spike-timing dependent principle. MEP and ICF change could represent this kind of plasticity. The current findings provide a novel insight into designing rehabilitation programs concerning motor function.

Multimodal assessment of motor pathways and intracortical connections in functional hemispherectomy.

For selected children with medically intractable epilepsy, hemispherectomy can be an excellent treatment option and its efficacy in achieving seizure freedom or reduction in seizure frequency has been shown in several studies, but patients' selection could not be straightforward and often it is taken on subjective basis. We described a multimodal approach to assess patient eligible for hemispherectomy and possibly predicting post-surgical outcomes. We describe pre- and post-surgical clinical features along with neuroradiological results by magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI), MR-tractography (MRT), and neurophysiological study by single and paired pulses transcranial magnetic stimulation (TMS) in a child with cerebral palsy with epileptic encephalopathy, eligible for epilepsy surgery. Presurgical TMS evaluation showed a lateralization of motor function on the left motor cortex for both arms, and results were confirmed by MRI studies. Interestingly, after surgery, both epilepsy and motor performances improved and TMS showed enhancement of intracortical inhibition and facilitation activity. Functional hemispherectomy is an effective treatment for drug-resistant epilepsy, and multimodal presurgical assessment may be a useful approach to guide surgeons in selecting patients. Moreover, pre- and post-surgical evaluation of these patients may enhance our understanding of brain plasticity phenomena.

Spatiotemporal Dynamics of Single and Paired Pulse TMS-EEG Responses

For physiological brain function a particular balance between excitation and inhibition is essential. Paired pulse transcranial magnetic stimulation (TMS) can estimate cortical excitability and the relative contribution of inhibitory and excitatory networks. Combining TMS with electroencephalography (EEG) enables additional assessment of the spatiotemporal dynamics of neuronal responses in the stimulated brain. This study aims to evaluate the spatiotemporal dynamics and stability of single and paired pulse TMS-EEG responses, and assess long intracortical inhibition (LICI) at the cortical level. Twenty-five healthy subjects were studied twice, approximately one week apart. Manual coil positioning was applied in sixteen subjects and robot-guided positioning in nine. Both motor cortices were stimulated with 50 single pulses and 50 paired pulses at each of the five interstimulus intervals (ISIs): 100, 150, 200, 250 and 300 ms. To assess stability and LICI, the intraclass correlation coefficient and cluster-based permutation analysis were used. We found great resemblance in the topographical distribution of the characteristic TMS-EEG components for single and paired pulse TMS. Stimulation of the dominant and non-dominant hemisphere resulted in a mirrored spatiotemporal dynamics. No significant effect on the TMS-EEG responses was found for either stimulated hemisphere, time or coil positioning method, indicating the stability of both single and paired pulse TMS-EEG responses. For all ISIs, LICI was characterized by significant suppression of the late N100 and P180 components in the central areas, without affecting the early P30, N45 and P60 components. These observations in healthy subjects can serve as reference values for future neuropsychiatric and pharmacological studies.

P10 Efficacy of repetitive dual-site paired associative transcranial magnetic stimulation in the treatment of generalized anxiety disorder

P10 Efficacy of repetitive dual-site paired associative transcranial magnetic stimulation in the treatment of generalized anxiety disorder