Plasticity In Primary Motor Cortex Research Articles

The effects of intermittent theta burst stimulation over dorsal premotor cortex on primary motor cortex plasticity in young and older adults.

Previous transcranial magnetic stimulation (TMS) research suggests that the dorsal premotor cortex (PMd) influences neuroplasticity within the primary motor cortex (M1) through indirect (I) wave interneuronal circuits. However, it is unclear how the influence of PMd on the plasticity of M1 I-waves changes with advancing age. This study therefore investigated the neuroplastic effects of intermittent theta burst stimulation (iTBS) to M1 early and late I-wave circuits when preceded by iTBS (PMd iTBS-M1 iTBS) or sham stimulation (PMd sham-M1 iTBS) to PMd in 15 young and 16 older adults. M1 excitability was assessed with motor evoked potentials (MEP) recorded from the right first dorsal interosseous using posterior-anterior (PA) and anterior-posterior (AP) current TMS at standard stimulation intensities (PA1mV, AP1mV) and reduced stimulation intensities (PA0.5mV, early I-waves; AP0.5mV, late I-waves). PMd iTBS-M1 iTBS lowered the expected facilitation of PA0.5mV (to M1 iTBS) in young and older adults (P = 0.009), whereas the intervention had no effect on AP0.5mV facilitation in either group (P = 0.305). The modulation of PA0.5mV following PMd iTBS-M1 iTBS may reflect a specific influence of PMd on different I-wave circuits that are involved in M1 plasticity within young and older adults.

Global research hotspots and trends in constraint-induced movement therapy in rehabilitation over the past 30 years: a bibliometric and visualization study.

Stroke is a cerebrovascular disease with high prevalence and mortality, and upper limb hemiparesis is a major factor limiting functional recovery in stroke patients. Improvement of motor function in stroke patients through various forms of constraint-induced movement therapy (CITM) has been recognized as safe and effective in recent years. This research field lacks a comprehensive systematic and clear vein combing analysis, analyzing the literature research of CIMT in the field of rehabilitation in the past three decades, summarizing the research hotspots and cutting-edge trends in this field, in an effort to offer ideas and references for subsequent researchers. Relevant literature on CIMT in rehabilitation was collected from 1996 to 2024 within the Web of Science database's core dataset by using CiteSpace6.1, VOSviewer1.6.18, R-bibliometrix4.6.1, Pajek5.16, Scimago Graphica 1.0.26 software for visualization and analysis. There were 970 papers in all United States was ranked first with 401 papers. Alabama Univ was ranked first for institutions with 53 papers. Neurorehabilitation and Neural Repair was ranked first for journals with 78 papers, and Taub E was ranked first for author publications with 64 papers. Research keywords were CIMT, stroke rehabilitation, upper extremity function, lower extremity gait balance, randomized controlled trials, physical therapy techniques (transcranial magnetic stimulation and sensory amplitude electrical stimulation), primary motor cortex plasticity, lateral dominance (spatial behaviors), cerebral vascular accidents, activities of daily living, hand function, disability, functional restoration, bimanual training, aphasia, acquired invalidity, type A Botulinum toxin and joystick riding toys. The current state of research shows that CIMT still has a vast potential for development in the field of rehabilitation research. The research hotspots are the clinical efficacy of CIMT combined with other therapies (botulinum toxin type A, transcranial direct current stimulation, virtual reality, mirror therapy, robotic-assisted) to enhance the functionality of upper limb hemiparesis in stroke patients, the mechanism of CIMT to improve the plasticity of the motor cortex through electrophysiological and imaging methods, and improvement of lower limb gait balance function in stroke patients and aphasia applications, the optimal intervention time and dose, and exploration of CIMT in new settings such as robot-assisted, telemedicine, and home rehabilitation.

Ageing attenuates exercise-enhanced motor cortical plasticity.

Cardiorespiratory exercise is known to modulate motor cortical plasticity in young adults, but the influence of ageing on this relationship is unknown. Here, we compared the effects of a single session of cardiorespiratory exercise on motor cortical plasticity in young and older adults. We acquired measures of cortical excitatory and inhibitory activity of the primary motor cortex using transcranial magnetic stimulation (TMS) from 20 young (mean±SD = 25.30 ± 4.00 years, 14 females) and 20 older (mean±SD = 64.10 ± 6.50 years, 11 females) healthy adults. Single- and paired-pulse TMS measurements were collected before and after a 20min bout of high-intensity interval cycling exercise or an equivalent period of rest, and again after intermittent theta burst stimulation (iTBS). In both young (P = 0.027, Cohen's d = 0.87) and older adults (P = 0.006, Cohen's d = 0.85), there was an increase in glutamatergic excitation and a reduction in GABAergic inhibition from pre- to postexercise. However, in contrast to younger adults, older adults showed an attenuated plasticity response to iTBS following exercise (P = 0.011, Cohen's d = 0.85). These results demonstrate an age-dependent decline in cortical plasticity and indicate that a preceding bout of high-intensity interval exercise might be less effective for enhancing primary motor cortex plasticity in older adults. Our findings align with the hypothesis that the capacity for cortical plasticity is altered in older age. KEY POINTS: Exercise enhances motor cortical plasticity in young adults, but how ageing influences this effect is unknown. Here, we compared primary motor cortical plasticity responses in young and older adults before and after a bout of high-intensity interval exercise and again after a plasticity-inducing protocol, intermittent theta burst stimulation. In both young and older adults, exercise led to an increase in glutamatergic excitation and a reduction in GABAergic inhibition. Our key result was that older adults showed an attenuated plasticity response to theta burst stimulation following exercise, relative to younger adults. Our findings demonstrate an age-dependent decline in exercise-enhanced cortical plasticity and indicate that a preceding bout of high-intensity interval exercise might be less effective for enhancing primary motor cortex plasticity in older adults.

Effect of current direction and muscle activation on motor cortex neuroplasticity induced by repetitive paired-pulse transcranial magnetic stimulation.

Repetitive paired-pulse transcranial magnetic stimulation (TMS) at indirect (I)-wave periodicity (iTMS) can increase plasticity in primary motor cortex (M1). Both TMS coil orientation and muscle activation can influence I-wave activity, but it remains unclear how these factors influence M1 plasticity with iTMS. We therefore investigated the influence of TMS coil orientation and muscle activation on the response to iTMS. Thirty-two young adults (24.2 ± 4.8years) participated in three experiments. Each experiment included two sessions using a modified iTMS intervention with either a posterior-anterior orientation (PA) or anterior-posterior (AP) coil orientation over M1. Stimulation was applied in resting (Experiments 1 and 3) or active muscle (Experiments 2 and 3). Effects of iTMS on M1 excitability were assessed by recording motor evoked potentials (MEPs) and short-interval intracortical facilitation (SICF) with PA and AP orientations in both resting (all experiments) and active (Experiment 2) muscle. For the resting intervention, MEPs were greater after AP iTMS (Experiment 1, P = .046), whereas SICF was comparable between interventions (all P > .10). For the active intervention, responses did not vary between PA and AP iTMS (Experiment 2, all P > .14), and muscle activation reduced the effect of AP iTMS during the intervention (Experiment 3, P = .002). Coil orientation influenced the MEP response after iTMS, and muscle activation reduced the response during iTMS. While this suggests that AP iTMS may be beneficial in producing a neuroplastic modulation of I-wave circuits in resting muscle, further exploration of factors such as dosing is required.

Combined neuromuscular electrical stimulation and transcutaneous spinal direct current stimulation increases motor cortical plasticity in healthy humans.

Neuromuscular electrical stimulation (NMES) induces neural plasticity of the central nervous system (CNS) and improves motor function in patients with CNS lesions. However, the extended stimulus duration of NMES reduces its clinical applicability. Transcutaneous spinal direct current stimulation (tsDCS), which increases afferent input, may enhance the effects and reduce the stimulus duration of NMES. This study investigated the excitability of the motor cortex, somatosensory cortex, and spinal motor neurons after the combined stimulation of NMES and tsDCS. Among the 55 participants in this study, 24 were allocated to experiment 1, 15 to experiment 2, and 16 to experiment 3. They received intervention for 20 min on different days: (1) NMES combined with tsDCS (NMES + tsDCS), (2) NMES combined with sham tsDCS (NMES + sham tsDCS), and (3) sham NMES combined with tsDCS (sham NMES + tsDCS). NMES was delivered to the right common peroneal nerve at 25 Hz with the intensity at 120% of the motor threshold. For tsDCS, the cathodal electrode was positioned on the thoracic 10th-12th vertebral levels, and the anodal electrode was located on the right shoulder. The stimulus intensity was 2.5 mA. In experiment 1, motor evoked potentials (MEPs) and short-latency intracortical inhibition (SICI) were measured by transcranial magnetic stimulation up to 60 min after stimulation. The spinal motor neurons' excitability was assessed by recording the posterior root muscle reflex (PRMR) induced via transcutaneous spinal cord stimulation in experiment 2, and the primary somatosensory cortex excitability was evaluated by recording the somatosensory evoked potentials (SEPs) in experiment 3 up to 15 min after stimulation. Compared to before the stimulation, NMES + tsDCS significantly increased MEP for 60 min or more, and significantly decreased SICI immediately after. Conversely contrast, the PRMR significantly decreased immediately after, and SEPs were unchanged. These results suggest that simultaneous afferent inputs from different stimulus positions critically induce primary motor cortex plasticity. The combined stimulation of NMES with tsDCS may facilitate the development of a new neurorehabilitation technique.

Assessing the interaction between L-dopa and γ-transcranial alternating current stimulation effects on primary motor cortex plasticity in Parkinson's disease.

L-dopa variably influences transcranial magnetic stimulation (TMS) parameters of motor cortex (M1) excitability and plasticity in Parkinson's disease (PD). In patients OFF dopaminergic medication, impaired M1 plasticity and defective GABA-A-ergic inhibition can be restored by boosting gamma (γ) oscillations via transcranial alternating current stimulation (tACS) during intermittent theta-burst stimulation (iTBS). However, it is unknown whether L-dopa modifies the beneficial effects of iTBS-γ-tACS on M1 in PD. In this study, a PD patients group underwent combined iTBS-γ-tACS and iTBS-sham-tACS, each performed both OFF and ON dopaminergic therapy (four sessions in total). Motor evoked potentials (MEPs) elicited by single TMS pulses and short-interval intracortical inhibition (SICI) were assessed before and after iTBS-tACS. We also evaluated possible SICI changes during γ-tACS delivered alone in OFF and ON conditions. The amplitude of MEP elicited by single TMS pulses and the degree of SICI inhibition significantly increased after iTBS-γ-tACS. The amount of change produced by iTBS-γ-tACS was similar in patients OFF and ON therapy. Finally, γ-tACS (delivered alone) modulated SICI during stimulation and this effect did not depend on the dopaminergic condition of patients. In conclusion, boosting cortical γ oscillatory activity via tACS during iTBS improved M1 plasticity and enhanced GABA-A-ergic transmission in PD patients to the same extent regardless of dopaminergic state. These results suggest a lack of interaction between L-dopa and γ-tACS effects at the M1 level. The possible neural substrate underlying iTBS-γ tACS effects, that is, γ-resonant GABA-A-ergic interneurons activity, may explain our findings.

Short-term arm immobilization modulates excitability of inhibitory circuits within, and between, primary motor cortices.

Previous research has suggested that short‐term immobilization of the arm may be a low‐cost, non‐invasive strategy to enhance the capacity for long‐term potentiation (LTP)‐like plasticity in primary motor cortex (M1). Short‐term immobilization reduces corticospinal excitability (CSE) in the contralateral M1, and interhemispheric inhibition (IHI) from ipsi‐ onto contralateral M1 is increased. However, it is unclear whether reduced CSE and increased IHI are associated with changes in intracortical inhibition, which has been shown to be important for regulating neuroplasticity in M1. The current study used transcranial magnetic stimulation to evaluate the effects of short‐term (6 h) arm immobilization on CSE, IHI, and intracortical inhibition measured bilaterally in 43 neurotypical young adults (23 immobilized). We replicated previous findings demonstrating that immobilization decreased CSE in, and increased IHI onto, the immobilized hemisphere, but a significant change in intracortical inhibition was not observed at the group level. Across individuals, decreased CSE was associated with a decreased short‐interval intracortical inhibition, an index of GABAA‐ergic inhibition, within the immobilized hemisphere only in the immobilization group. Previous research has demonstrated that decreases in GABAA‐ergic inhibition are necessary for the induction of LTP‐like plasticity in M1; therefore, decreased intracortical inhibition after short‐term arm immobilization may provide a novel mechanism to enhance the capacity for LTP‐like plasticity within M1 and may be a potential target for strategies to augment plasticity capacity to enhance motor learning in health and disease.

Functional MRI evidence for primary motor cortex plasticity contributes to the disease's severity and prognosis of cervical spondylotic myelopathy patients.

To investigate the brain mechanism of non-correspondence between diseases severity and compression degree of the spinal cord in cervical spondylotic myelopathy (CSM) patients and to test the utility of brain imaging biomarkers for predicting prognosis of CSM. We calculated voxel-wise zALFF from 54 CSM patients and 50 healthy controls using resting-state fMRI data. In analysis 1, we identified the brain regions exhibited significant differences of zALFF between CSM patients and healthy controls. In analyses 2 through 3, we investigated the zALFF differences between light-symptom CSM patients and severe-symptom CSM patients while carefully matching the degree of compression between these two groups. In analysis 4, we tested the utility of zALFF within the primary motor cortex (M1) for predicting the prognosis of CSM. We found that (1) compared with the healthy controls, CSM patients exhibited higher ALFF within left M1, bilateral superior frontal gyrus, and lower zALFF within right precuneus and calcarine, suggesting altered brain neural activity in CSM patients; (2) after matching the compression degree, the CSM patients with more severe clinical symptoms exhibited higher zALFF within M1, indicating cortical function contributes to disease's severity of CSM; (3) taking the M1 zALFF as features in the prognosis prediction model improves the prediction accuracy, indicating that the M1 zALFF provide additional value for predicting the prognosis of CSM patients following decompression surgery. The functional state of M1 contributes to the disease's severity of CSM and can provide complementary information for predicting the prognosis of CSM following decompression surgery. • Cervical spondylotic myelopathy (CSM) patients exhibited increased zALFF within the primary motor cortex (M1), bilateral superior frontal gyrus, and decreased zALFF within the right precuneus and calcarine. • After matching the compression degree, the CSM patients with more severe clinical symptoms exhibited higher zALFF within M1, indicating cortical function contributes to disease severity of CSM. • zALFF within M1 provided additional value for predicting the prognosis of CSM patients.

High-frequency repetitive transcranial magnetic stimulation enhances layer II/III morphological dendritic plasticity in mouse primary motor cortex

High-frequency repeated transcranial magnetic stimulation (HF-rTMS) is a safe non-invasive neuromodulatory technique and there is a body of evidence shows that it can modulate plasticity in different brain areas. One of the most interesting application of HF-rTMS is the modulation of plasticity in primary motor cortex (M1) to promote recovery after brain injuries. However, the underlying mechanism by which HF-rTMS modulates motor cortex plasticity remain to be investigated.In this study, we investigated the effects of HF-rTMS treatment on morphological plasticity of pyramidal neurons in layer II/III (L2/3) of the primary motor cortex in mice. Our results show that the treatment did not increase anxiety in mice in the open field test and the elevated plus-maze test. Treated mice displayed increased total spine density in apical and basal dendrites, with a predominance of thin spines. The treatment also increased dendritic complexity, as assessed by Sholl analysis at both apical and basal dendrites.Collectively, the results show that HF-rTMS induced remarkable changes in dendritic complexity in primary motor cortex L2/3 connections which may strengthen corticocortical connections increasing integration of information across cortical areas. The data support the use of HF-rTMS as a circuit-targeting neuromodulation strategy.

The effect of gamma oscillations in boosting primary motor cortex plasticity is greater in young than older adults

ObjectiveIn healthy subjects, the long-term potentiation (LTP)-like plasticity of the primary motor cortex (M1) induced by intermittent theta-burst stimulation (iTBS) can be boosted by modulating gamma (γ) oscillations through transcranial alternating current stimulation (tACS). γ-tACS also reduces short-interval intracortical inhibition (SICI). We tested whether the effects of γ-tACS differ between young (YA) and older adults (OA). MethodsTwenty YA (27.2 ± 2.7 years) and twenty OA (65.3 ± 9.5 years) underwent iTBS-γ tACS and iTBS-sham tACS in randomized sessions. In a separate session, we delivered γ-tACS alone and recorded SICI during stimulation. ResultsiTBS-sham tACS produced comparable motor evoked potential (MEP) facilitation between groups. While iTBS-γ tACS boosted MEP facilitation in both the YA and OA groups, the magnitude of its effect was significantly lower in OA. Similarly, γ-tACS-induced modulation of GABA-A-ergic neurotransmission, as tested by SICI, was reduced in OA. The effect of iTBS-γ tACS negatively correlated with the age of OA subjects. ConclusionsMechanisms underlying the effects of γ oscillations on LTP-like plasticity become less efficient in older adults. This could reflect age-related changes in neural elements of M1 resonant to γ oscillations, including GABA-A-ergic interneurons. SignificanceThe beneficial effect of γ-tACS on iTBS-induced plasticity is reduced in older adults.

Motor dysfunction in mild cognitive impairment as tested by kinematic analysis and transcranial magnetic stimulation

ObjectivePrevious studies have demonstrated voluntary movement alterations as well as motor cortex excitability and plasticity changes in patients with mild cognitive impairment (MCI). To investigate the pathophysiology of movement abnormalities in MCI, we tested possible relationships between movement abnormalities and primary motor cortex alterations in patients. MethodsFourteen amnestic MCI (aMCI) patients and 16 healthy controls were studied. Cognitive assessment was performed using clinical scales. Finger tapping was recorded by a motion analysis system. Transcranial magnetic stimulation was used to test the input/output curve of motor evoked potentials, intracortical inhibition, and short-latency afferent inhibition. Primary motor cortex plasticity was probed by theta burst stimulation. We investigated correlations between movement abnormalities, clinical scores, and cortical neurophysiological parameters. ResultsMCI patients showed less rhythmic movement but no other movement abnormalities. Cortical excitability measures were normal in patients, whereas plasticity was reduced. Movement rhythm abnormalities correlated with frontal dysfunction scores. ConclusionOur study in MCI patients demonstrated abnormal voluntary movement and plasticity changes, with no correlation between the two. Altered rhythm correlated with frontal dysfunction. SignificanceOur results contribute to the understanding of pathophysiological mechanisms of motor impairment in MCI.

Plasticity of the Primary Motor Cortex in Patients with Primary Brain Tumors.

There are two neuron-level mechanisms proposed to underlie neural plasticity: recruiting neurons nearby to support the lost function (ipsilesional plasticity) and uncovering latent pathways that can assume the function that was lost (contralesional plasticity). While both patterns have been demonstrated in patient groups following injury, the specific mechanisms underlying each mode of plasticity are poorly understood. In a retrospective case series of 13 patients, we utilize a novel paradigm that analyzes serial fMRI scans in patients harboring intrinsic brain tumors that vary in location and growth kinetics to better understand the mechanisms underlying these two modes of plasticity in the human primary motor cortex. Twelve patients in our series had some degree of primary motor cortex plasticity, an area previously thought to have limited plasticity. Patients harboring smaller lesions with slower growth kinetics and increasing distance from the primary motor region demonstrated recruitment of ipsilateral motor regions. Conversely, larger, faster-growing lesions in close proximity to the primary motor region were associated with activation of the contralesional primary motor cortex, along with increased activation of the supplementary motor area. These data increase our understanding of the adaptive abilities of the brain and may lead to improved treatment strategies for those suffering from motor loss secondary to brain injuries.

Enhancing Gamma Oscillations Restores Primary Motor Cortex Plasticity in Parkinson's Disease.

In humans, γ oscillations in cortical motor areas reflect asynchronous synaptic activity and contribute to plasticity processes. In Parkinson's disease (PD), γ oscillatory activity in the basal ganglia-thalamo-cortical network is altered and the LTP-like plasticity elicited by intermittent theta burst stimulation (iTBS) is reduced in the primary motor cortex (M1). In this study, we tested whether transcranial alternating current stimulation (tACS) delivered at γ frequency promotes iTBS-induced LTP-like plasticity in M1 in PD patients. Sixteen patients (OFF condition) and 16 healthy subjects (HSs) underwent iTBS during γ-tACS (iTBS-γ tACS) and during sham-tACS (iTBS-sham tACS) in two sessions. Motor-evoked potentials (MEPs) evoked by single-pulse transcranial magnetic stimulation and short-interval intracortical inhibition (SICI) were recorded before and after the costimulation. A subgroup of patients also underwent iTBS during β tACS. iTBS-sham tACS facilitated single-pulse MEPs in HSs, but not in patients. iTBS-γ tACS induced a larger MEP facilitation than iTBS-sham tACS in both groups, with similar values in patients and HSs. In patients, SICI improved after iTBS-γ tACS. The effect produced by iTBS-γ tACS on single-pulse MEPs correlated with disease duration, while changes in SICI correlated with Unified Parkinson's Disease Rating Scale Part III scores. The effect of iTBS-β tACS on both single-pulse MEPs and SICI was similar to that obtained in the iTBS-sham tACS session. Our data suggest that γ oscillations have a role in the pathophysiology of the abnormal LTP-like plasticity in PD. Entraining M1 neurons at the γ rhythm through tACS may be an effective method to restore impaired plasticity.SIGNIFICANCE STATEMENT In Parkinson's disease, the LTP-like plasticity of the primary motor cortex is impaired, and γ oscillations are altered in the basal ganglia-thalamo-cortical network. Using a combined transcranial magnetic stimulation-transcranial alternating current stimulation approach (iTBS-γ tACS costimulation), we demonstrate that driving γ oscillations restores the LTP-like plasticity in patients with Parkinson's disease. The effects correlate with clinical characteristics of patients, being more evident in less affected patients and weaker in patients with longer disease duration. These findings suggest that cortical γ oscillations play a beneficial role in modulating the LTP-like plasticity of M1 in Parkinson's disease. The iTBS-γ tACS approach may be potentially useful in rehabilitative settings in patients.

P108 Combining action observation with kinesthetic illusion of movement shapes primary motor cortex plasticity

P108 Combining action observation with kinesthetic illusion of movement shapes primary motor cortex plasticity

LTD-like plasticity of the human primary motor cortex can be reversed by γ-tACS

BackgroundCortical oscillatory activities play a role in regulating several brain functions in humans. However, whether motor resonant oscillations (i.e. β and γ) modulate long-term depression (LTD)-like plasticity of the primary motor cortex (M1) is still unclear. ObjectiveTo address this issue, we combined transcranial alternating current stimulation (tACS), a technique able to entrain cortical oscillations, with continuous theta burst stimulation (cTBS), a transcranial magnetic stimulation (TMS) protocol commonly used to induce LTD-like plasticity in M1. MethodsMotor evoked potentials (MEPs) elicited by single-pulse TMS, short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) were evaluated before and 5, 15 and 30 min after cTBS alone or cTBS delivered during β-tACS (cTBS-β) or γ-tACS (cTBS-γ). Moreover, we tested the effects of β-tACS (alone) on short-latency afferent inhibition (SAI) and γ-tACS on SICI in order to verify whether tACS-related interneuronal modulation contributes to the effects of tACS-cTBS co-stimulation. ResultscTBS-γ turned the expected after-effects of cTBS from inhibition to facilitation. By contrast, responses to cTBS-β were similar to those induced by cTBS alone. β- and γ-tACS did not change MEPs evoked by single-pulse TMS. β-tACS reduced SAI and γ-tACS reduced SICI. However, the degree of γ-tACS-induced modulation of SICI did not correlate with the effects of cTBS-γ. Conclusionγ-tACS reverses cTBS-induced plasticity of the human M1. γ-oscillations may therefore regulate LTD-like plasticity mechanisms.

Corticobasal syndrome: neuroimaging and neurophysiological advances.

Corticobasal degeneration (CBD) is a neurodegenerative condition characterized by 4R tau protein deposition in several brain regions that clinically manifests itself as a heterogeneous atypical parkinsonism typically expressed in adulthood. The prototypical clinical phenotype of CBD is corticobasal syndrome (CBS). Important insights into the pathophysiological mechanisms underlying motor and higher cortical symptoms in CBS have been gained by using advanced neuroimaging and neurophysiological techniques. Structural and functional neuroimaging studies often show asymmetric cortical and subcortical abnormalities, mainly involving perirolandic and parietal regions and basal ganglia structures. Neurophysiological investigations including electroencephalography and somatosensory evoked potentials provide useful information on the origin of myoclonus and on cortical sensory loss. Transcranial magnetic stimulation demonstrates heterogeneous and asymmetric changes in the excitability and plasticity of primary motor cortex and abnormal hemispheric connectivity. Neuroimaging and neurophysiological abnormalities in multiple brain areas reflect asymmetric neurodegeneration, leading to asymmetric motor and higher cortical symptoms in CBS.

Primary motor cortex plasticity is enhanced by transcranial direct current stimulation in mice: underlying molecular mechanisms and impact on motor performance

There is a consistent body of evidence showing that transcranial direct current stimulation (tDCS) over the motor cortex facilitates motor learning and promotes motor recovery after stroke.

Parkinsonism is associated with altered primary motor cortex plasticity in frontotemporal dementia-primary progressive aphasia variant.

In frontotemporal dementia (FTD), the behavioral variant (bv-FTD) and nonfluent variant of primary progressive aphasia (nfv-PPA) reflect a prominent neurodegenerative involvement of the frontal lobe networks, which may include the premotor and motor areas and thus cause heterogeneous clinical symptoms including parkinsonism. With the technique of transcranial magnetic stimulation, we investigated long-term potentiation- and long-term depression-like plasticity in the primary motor cortex of bv-FTD and nfv-PPA patients, with and without parkinsonism, by using the theta-burst stimulation (TBS) protocol. We applied the intermittent TBS and continuous TBS in 20 FTD patients and 18 age-matched healthy subjects. Results were also compared with those achieved in a cohort of age-matched patients with Parkinson's disease. The responses to TBS were abnormal in FTD patients with parkinsonism. By contrast, the TBS induced normal responses in patients with both nfv-PPA and bv-FTD without parkinsonism. Finally, responses to TBS were comparable in patients with FTD with parkinsonism and patients with Parkinson's disease. We provide evidence of abnormal primary motor cortex long-term potentiation-/long-term depression-like plasticity in patients with FTD and parkinsonism suggesting neurodegenerative processes in the corticobasal ganglia-thalamo-cortical motor networks in these patients.

Reversal of long term potentiation-like plasticity in primary motor cortex in patients with progressive supranuclear palsy.

Abnormal primary motor cortex plasticity might be involved in the pathophysiology of progressive supranuclear palsy. In the present study we aimed to investigate possible abnormalities of depotentiation, a mechanism involved in plasticity regulation, in this condition. Primary motor cortex excitability, investigated with single and paired-pulse transcranial magnetic stimulation, as well as long-term potentiation-like plasticity and its reversibility, were studied using theta burst stimulation in 15 patients with progressive supranuclear palsy and 11 healthy controls. Participants underwent two sessions using (1) the intermittent theta-burst stimulation (potentiation protocol) and (2) intermittent theta-burst stimulation combined with a depotentiation protocol (a short continuous theta-burst stimulation). Patients with PSP had higher corticospinal excitability and lower intracortical inhibition than healthy controls. Intermittent theta-burst stimulation elicited an abnormally increased long term potentiation-like effect in patients in comparison to healthy subjects. However, the depotentiation protocol was able to reverse the effects intermittent theta-burst stimulation on motor cortex excitability both in patients and in healthy controls. Altered primary motor cortex plasticity in patients with PSP does not reflect an abnormality of depotentiation. This study provides information for a deeper understanding of the possible pathophysiological mechanisms underlying the altered M1 plasticity in PSP.

P026 Impaired cerebellum to motor cortex associative plasticity in spinocerebellar ataxia

Introduction The previous evidence has showed that bidirectional spike-timing dependent plasticity (STDP)-like plasticity in primary motor cortex (M1) can be mediated by associative stimulation of the cerebello-dentato-thalamo-cortical (CDTC) pathway and M1 in young healthy adults. The pattern of such plasticity has never been studied in patients with cerebellar degeneration. Objectives To compare the corticocortical paired associative stimulation (PAS)-induced STDP-like plasticity between healthy subjects and patients with hereditary spinocerebellar ataxia (SCA). Patients & methods Seven gene-confirmed patients with SCA (5 with type 3, 2 with type 2) and nine healthy subjects were studied. One hundred and twenty pairs of transcranial magnetic stimulation (TMS) of the left M1 preceded by right lateral cerebellum (CB) TMS at an interstimulus interval of 2 ms (CB→M1 PAS 2 ms ) or 6 ms (CB→M1 PAS 6 ms ) were applied. M1 excitability was assessed by motor-evoked potential (MEP) amplitude, short-interval intracortical inhibition (SICI), intracortical facilitation (ICF) and cerebellar inhibition (CBI) in the first dorsal interosseous muscle of the right hand before and after CB →M1 PAS. Results In the healthy subjects, a significant MEP potentiation was found after the CB →M1 PAS 2 ms protocol. In contrast, CB →M1 PAS 6 ms resulted in suppression of the MEP amplitude. This phenomenon was not observed in the patients with SCA. SICI, ICF and CBI did not show any significant change in both groups. Conclusion The current findings suggest that CB →M1 PAS-induced bidirectional STDP-like plasticity in M1 is significantly impaired in patients with SCA. The interpretation would be functional perturbation within the CDTC circuit in the patients with SCA.