Plasticity induction in the pre-supplementary motor area (pre-SMA) and SMA-proper differentially affects visuomotor sequence learning

BackgroundBoth pre-supplementary motor area (pre-SMA) and SMA-proper (SMA) must play important roles in visuomotor sequence learning. However, functional differences between the pre-SMA and SMA have not been well studied in humans.ObjectiveTo elucidate the functional differences between the pre-SMA and SMA in sequence learning in humans.MethodsTo induce LTP/LTD, we administered quadripulse transcranial magnetic stimulation (QPS) with an inter-stimulus interval of 5 or 50 ms (QPS-5/50) over the pre-SMA or SMA in healthy volunteers. The sham stimulation was also done as a control. We studied the effects of LTP/LTD in the pre-SMA/SMA on a new sequence learning and the performance of well-learned sequence by using sequence learning task called the “2 × 10 task”. Effects on the simple choice reaction time task were also studied for comparison.ResultsQPS-5 over the pre-SMA increased the error rate without any changes in movement speed. When administered over the SMA, QPS-5 decreased, and QPS-50 increased the rate of reaction time reduction across trials without changes in the error rate. QPS over neither the pre-SMA nor SMA affected the performances of a well-learned sequence or a simple choice reaction time task.ConclusionsOur findings that QPS over the pre-SMA correlated with sequence learning performance and that over the SMA with execution speed are consistent with the previous results in animals and humans. Our results lend further support to the utility of QPS for modulating motor learning in humans.     

Acute effects of lithium on excitability of human motor cortex

ObjectiveLithium has been widely used to treat bipolar affective disorder for over 60 years. Still, its acute effects in human cerebral cortex are poorly understood. This study aimed at investigating the acute effects of lithium on motor cortex excitability as measured by transcranial magnetic stimulation (TMS).MethodsTen healthy young adults participated in a double-blind placebo-controlled randomized crossover study with four sessions, where a single oral dose of lithium carbonate (450 mg, 900 mg, or 1350 mg) or placebo was tested. Focal TMS of the hand area of left motor cortex was used to test resting and active motor thresholds, motor evoked potential input–output curve (MEP IO-curve), slope of the MEP IO-curve and paired-pulse measures of intracortical inhibition and facilitation before, and two and four hours after drug administration.ResultsTwo hours post drug administration, 450 mg of lithium carbonate increased the slope of the MEP IO-curve while 1350 mg tended to decrease it. Lithium had no effect on motor thresholds, or intracortical inhibition or facilitation.ConclusionsThe acute effects of lithium on MEP IO-curve, a marker of corticospinal excitability, are consistent with an inverted U-shaped dose–response relationship.SignificanceFindings are important for our understanding of the therapeutic and toxic effects of lithium on the human central nervous system.     

Continuous Theta Burst Stimulation of the Supplementary Motor Area: Effect Upon Perception and Somatosensory and Motor Evoked Potentials

BackgroundThe supplementary motor area (SMA) has been implicated in many aspects of movement preparation and execution. In addition to motor roles, the SMA is responsive to somesthetic stimuli though it is unclear exactly what role the SMA plays in a somatosensory network.Objective/HypothesisIt is the purpose of this study to assess how continuous theta burst stimulation (cTBS) of the SMA affects both somatosensory (SEPs) and motor evoked potentials (MEPs) and if cTBS leads to alterations in tactile perception thresholds of the index fingertip.MethodsIn experiment 1, cTBS was delivered over scalp sites FCZ (SMA stimulation) (n = 10) and CZ (control stimulation) (n = 10) in separate groups for 40 s (600 pulses) at 90% of participants' resting motor threshold. For both groups, median nerve SEPs were elicited from the right wrist at rest via electrical stimulation (0.5 ms pulse) before and at 10 min intervals post-cTBS out to 30 min (t = pre, 10, 20, and 30 min). Subjects' perceptual thresholds were assessed at similar time intervals as the SEP data using a biothesiometer (120 Hz vibration). In experiment 2 (n = 10) the effect of cTBS to SMA upon single and paired-pulse MEP amplitudes from the right first dorsal interosseous (FDI) was assessed.ResultscTBS to scalp site FCZ (SMA stimulation) reduced the frontal N30 SEP and increased tactile perceptual thresholds 30 min post-stimulation. However, parietal SEPs and MEP amplitudes from both single and paired-pulse stimulation were unaffected at all time points post-stimulation. cTBS to stimulation site CZ (control) did not result in any physiological or behavioral changes.Conclusion(s)These data demonstrate cTBS to the SMA reduces the amplitude of the N30 coincident with an increase in vibration sensation threshold but does not affect primary somatosensory or motor cortex excitability. The SMA may play a significant role in a somatosensory tactile attention network.     

Effects of polarity of bipolar sensorimotor direct cortical stimulation on intraoperative motor evoked potentials

ObjectiveThe present study investigated the effects of the stimulus polarity and location of motor evoked potential (MEP) to establish a stimulation protocol.MethodsNineteen patients who intraoperatively underwent MEP in bipolar direct cortical stimulation were enrolled in the present study. Somatosensory evoked potentials (SEP) of the contralateral median nerve stimulation were recorded to determine stimulation sites. MEP was performed under two settings in all patients: 1. Anodal bipolar stimulation: an anode on the precentral gyrus and a cathode on the postcentral gyrus, 2. Cathodal bipolar stimulation: a cathode on the precentral gyrus and an anode on the postcentral gyrus. MEP amplitudes and the coefficient of variation (CV) at a stimulation intensity of 25 mA and the thresholds of induced MEP were compared between the two settings.ResultsAn electrical stimulation at 25 mA induced a significantly higher amplitude in cathodal bipolar stimulation than in anodal bipolar stimulation. Cathodal bipolar stimulation also showed significantly lower thresholds than anodal stimulation. CV did not significantly differ between the two groups.ConclusionsThese results indicate that cathodal bipolar stimulation is superior to anodal bipolar stimulation for intraoperative MEP monitoring.SignificanceMEP in cathodal bipolar cortical stimulation may be used in a safe and useful evaluation method of motor fiber damage that combines sensitivity and specificity.     

Quadro-pulse stimulation is more effective than paired-pulse stimulation for plasticity induction of the human motor cortex

OBJECTIVE: Repetitive paired-pulse transcranial magnetic stimulation (TMS) at I-wave periodicity has been shown to induce a motor-evoked potential (MEP) facilitation. We hypothesized that a greater enhancement of motor cortical excitability is provoked by increasing the number of pulses per train beyond those by paired-pulse stimulation (PPS). METHODS: We explored motor cortical excitability changes induced by repetitive application of trains of four monophasic magnetic pulses (quadro-pulse stimulation: QPS) at 1.5-ms intervals, repeated every 5s over the motor cortex projecting to the hand muscles. The aftereffects of QPS were evaluated with MEPs to a single-pulse TMS, motor threshold (MT), and responses to brain-stem stimulation. These effects were compared to those after PPS. To evaluate the QPS safety, we also studied the spread of excitation and after discharge using surface electromyograms (EMGs) of hand and arm muscles. RESULTS: Sizes of MEPs from the hand muscle were enhanced for longer than 75min after QPS; they reverted to the baseline at 90min. Responses to brain-stem stimulation from the hand muscle and cortical MEPs from the forearm muscle were unchanged after QPS over the hand motor area. MT was unaffected by QPS. No spreads of excitation were detected after QPS. The appearance rate of after discharges during QPS was not different from that during sham stimulation. CONCLUSIONS: Results show that QPS can safely induce long-lasting, topographically specific enhancement of motor cortical excitability. SIGNIFICANCE: QPS is more effective than PPS for inducing motor cortical plasticity.     

Postoperative navigated transcranial magnetic stimulation to predict motor recovery after surgery of tumors in motor eloquent areas

ObjectiveTo know whether motor deficits after tumor surgery are transient is reassuring for the patient and crucial for planning rehabilitation and adjuvant treatment. We analyze the value of postoperative MRI navigated transcranial magnetic stimulation (nTMS) compared to intraoperative MEP monitoring in predicting recovery of motor function.MethodsRetrospective series of nTMS mappings within 14 days after surgery for supratentorial tumors (09/2014–05/2018). All patients with motor deficits of Medical-Research-Council-Grade (MRCS) 0–4- were included.ResultsWe performed nTMS mapping on average 3.8 days after surgery and recorded nTMS MEP in 11 of 13 patients. Motor strength recovered to at least MRCS 4 within one month if postoperative nTMS elicited MEPs (positive predictive value 90.9%). If nTMS did not elicit MEPs, the patient did not recover (negative predictive value 100%). Intraoperative MEP and postoperative nTMS were equally predictive for long-term motor recovery. In cases of intraoperative MEP alteration/signal loss, but a positive postoperative nTMS mapping, 2/3 patients demonstrated a good motor recovery.ConclusionnTMS may predict long-term motor recovery of patients suffering from severe motor deficits directly after resection of tumors located in motor eloquent areas.SignificanceIn cases of intraoperative MEP alterations, postoperative nTMS may clarify the potential for motor recovery.     

Region-dependent bidirectional plasticity in M1 following quadripulse transcranial magnetic stimulation in the inferior parietal cortex

BackgroundThe ability to manipulate the excitability of the network between the inferior parietal lobule (IPL) and primary motor cortex (M1) may have clinical value.ObjectiveTo investigate the possibility of inducing long-lasting changes in M1 excitability by applying quadripulse transcranial magnetic stimulation (QPS) to the IPL, and to ascertain stimulus condition- and site-dependent differences in the effects.MethodsQPS was applied to M1, the primary somatosensory cortex (S1), the supramarginal gyrus (SMG) and angular gyrus (AG) IPL areas, with the inter-stimulus interval (ISI) in the train of pulses set to either 5 ms (QPS-5) or 50 ms (QPS-50). QPS was repeated at 0.2 Hz for 30 min, or not presented (sham condition). Excitability changes in the target site were examined by means of single-pulse transcranial magnetic stimulation (TMS).ResultsQPS-5 and QPS-50 at M1 increased and decreased M1 excitability, respectively. QPS at S1 induced no obvious change in M1 excitability. However, QPS at the SMG induced mainly suppressive effects in M1 for at least 30 min, regardless of the ISI length. Both QPS ISIs at the AG yielded significantly different MEP compared to those at the SMG. Thus, the direction of the plastic effect of QPS differed depending on the site, even under the same stimulation conditions.ConclusionsQPS at the IPL produced long-lasting changes in M1 excitability, which differed depending on the precise stimulation site within the IPL. These results raise the possibility of noninvasive induction of functional plasticity in M1 via input from the IPL.     

Prediction of postoperative motor deficits using motor evoked potential deterioration duration in intracranial aneurysm surgery

ObjectiveThe study aimed to investigate the predictive value of motor evoked potential (MEP) deterioration duration for postoperative motor deficits in patients undergoing intracranial aneurysm surgery.MethodsData from 587 patients were reviewed and 92 patients with MEP deterioration were enrolled. MEP deterioration duration was compared between patients with and without postoperative motor deficits. Receiver operating characteristic (ROC) curve analysis was performed to define the threshold value for predicting postoperative motor deficit risk. Additionally, the association between MEP deterioration duration and postoperative CT findings was explored.ResultsPatients with postoperative motor deficits had a significantly longer MEP deterioration duration (p < 0.01). An MEP deterioration duration greater than or equal to 13 min was identified as an independent predictor of immediate (p < 0.01), short-term (p < 0.01), and long-term postoperative motor deficits (p < 0.05). There was no significant association between MEP deterioration duration and new CT abnormalities.ConclusionMEP deterioration duration could be used for predicting intracranial aneurysm surgical outcome.SignificanceThe study first proposed a threshold value of MEP deterioration duration (13 min) for predicting the risk of postoperative motor deficits in patients undergoing intracranial aneurysm surgery.     

Direct comparison of efficacy of the motor cortical plasticity induction and the interindividual variability between TBS and QPS

BackgroundTheta burst stimulation (TBS) and quadripulse stimulation (QPS) are known to induce synaptic plasticity in humans. There have been no head-to-head comparisons of the efficacy and variability between TBS and QPS.ObjectiveTo compare the efficacy and interindividual variability between the original TBS and QPS protocols. We hypothesized that QPS would be more effective and less variable than TBS.MethodsForty-six healthy subjects participated in this study. Thirty subjects participated in the main comparison experiment, and the other sixteen subjects participated in the experiment to obtain natural variation in motor-evoked potentials. The facilitatory effects were compared between intermittent TBS (iTBS) and QPS5, and the inhibitory effects were compared between continuous TBS (cTBS) and QPS50. The motor-evoked potential amplitudes elicited by transcranial magnetic stimulation over the primary motor cortex were measured before the intervention and every 5 min after the intervention for 1 h. To investigate the interindividual variability, the responder/nonresponder/opposite-responder rates were also analyzed.ResultsThe facilitatory effects of QPS5 were greater than those of iTBS, and the inhibitory effects of QPS50 were much stronger than those of cTBS. The responder rate of QPS was significantly higher than that of TBS. QPS had a smaller number of opposite responders than TBS.ConclusionQPS is more effective and stable for synaptic plasticity induction than TBS.     

Behavioral and electrophysiological evidence for GABAergic modulation through transcutaneous vagus nerve stimulation

Objective

Transcutaneous vagus nerve stimulation (tVNS) has been hypothesized to modulate γ-aminobutyric (GABA) transmission in the human brain. GABA in the motor cortex is highly correlated to measures of automatic motor inhibition that can be obtained in simple response priming paradigms. To test the effects of tVNS on GABA transmission, we measured tVNS-induced alterations in behavioral and electrophysiology during automatic motor inhibition.

Increased motor cortical excitability after whole-hand electrical stimulation: A TMS study

ObjectiveTo examine the neuromodulatory effect of whole-hand mesh-glove (MG) stimulation on motor cortical pathways, we explored motor cortical excitability before and after suprathreshold whole-hand MG stimulation using transcranial magnetic stimulation (TMS).MethodsTwenty-eight healthy volunteers (14 controls) were studied at baseline, immediately post and 1 h post-MG stimulation for 30 min. Motor thresholds (MTs), motor evoked potentials (MEPs) recruitment curve, short intracortical inhibition (SICI) and intracortical facilitation (ICF) after paired magnetic stimuli were evaluated.ResultsAfter MG stimulation the MTs were significantly reduced and slope of MEP recruitment curve significantly increased; furthermore, the stimulation led to a sustained decrease of SICI and increase of ICF in the contralateral motor cortex. These effects lasted for at least 60 min and were stronger 1 h post-stimulation compared with testing immediately after stimulation. A sham group did not show any differences before and after MG stimulation.ConclusionsWe provide a first demonstration that MG whole-hand stimulation induces increases in motor cortical excitability lasting at least 1 h. Both the strength of the corticospinal projections and the inhibitory and facilitatory intracortical mechanisms are involved. Synaptic modifications such as long-term potentiation mechanisms may underlie this stimulation-induced cortical plasticity changes.SignificancePresent results prove the MG stimulation to be a promising tool in neurorehabilitation.     

EEG oscillations and magnetically evoked motor potentials reflect motor system excitability in overlapping neuronal populations

ObjectiveTo understand the relationship between neuronal excitability reflected by transcranial magnetic stimulation (TMS) evoked motor potentials (MEPs) and spontaneous oscillation amplitude and phase.MethodsWe combined spontaneous EEG measurement with motor cortex TMS and recorded MEP amplitudes from abductor digiti minimi (ADM).ResultsMidrange-beta oscillations over the stimulated left motor cortex were, on average, weaker before large- than small-amplitude MEPs. The phase of occipital midrange-beta oscillations was related to the MEP amplitudes.ConclusionsThe present results support the view that MEP and Rolandic beta oscillation amplitudes are associated with motor cortical excitability. However, oscillations seen in EEG reflect the excitability of a large population of cortical neurons, and MEP amplitude is affected also by spinal excitability and action potential desynchronization. Thus, MEP and EEG oscillation amplitudes are not strongly correlated. In addition, even during rest, motor system excitability appears to be related to activity in occipital areas at frequency ranges associated with visuomotor processing.SignificanceThe ability of spontaneous oscillations and MEPs to inform us about cortical excitability is clarified. For example, it is suggested that oscillatory activity at non-motor sites might be related to motor system excitability at rest.     

Quadri-pulse stimulation induces stimulation frequency dependent cortical hemoglobin concentration changes within the ipsilateral motor cortical network

BackgroundImaging studies investigating repetitive transcranial magnetic stimulation (rTMS) mediated hemodynamic consequences revealed inconsistent results, mainly due to differences in rTMS parameters and technical difficulties with simultaneous recordings during rTMS.Objective/HypothesisQuadri-pulse rTMS (QPS) induces bidirectional long-term plasticity of the human primary motor cortex (M1). To evaluate its on-line effects, near infrared spectroscopy (NIRS) recordings were performed during QPS. We hypothesized that on-line effects during QPS are different from long-term aftereffects.MethodsUsing a novel TMS - on-line multi-channel NIRS setup we recorded hemoglobin concentration [Hb] changes at the stimulated M1 and adjacent sensory-motor areas during QPS protocols inducing oppositely directed aftereffects (QPS-5: interstimulus interval (ISI) 5 ms, potentiation; QPS-50: ISI 50 ms, depression). In two experiments we studied NIRS changes during either single or repeated QPS bursts.ResultsThe repetitive QPS-5 bursts significantly decreased oxyhemoglobin concentration ([oxy-Hb]) in the ipsilateral M1. A single QPS-5 burst decreased [oxy-Hb] in the M1 and premotor cortex. QPS-50 induced no significant NIRS changes at any sites.ConclusionsQPS can significantly alter cortical hemodynamics depending on the stimulation frequency. While bidirectional long-term aftereffects of QPS reflect synaptic efficacy changes, unidirectional on-line effects during QPS may represent pure electrophysiological property changes within the cell membrane or synapse. Since neuronal postexcitatory inhibitory postsynaptic potentials typically peak within the first 10–20 ms, only pulses delivered at higher frequencies may lead to summation of the inhibitory effects, resulting in [oxy-Hb] decrease only after QPS-5. Our new TMS-NIRS setup may be valuable to investigate TMS induced neurovascular coupling mechanisms in humans.     

The degree of cortical plasticity correlates with cognitive performance in patients with Multiple Sclerosis

BackgroundCortical reorganization and plasticity may compensate for structural damage in Multiple Sclerosis (MS). It is important to establish sensitive methods to measure these compensatory mechanisms, as they may be of prognostic value.ObjectiveTo investigate the association between the degree of cortical plasticity and cognitive performance and to compare plasticity between MS patients and healthy controls (HCs).MethodsThe amplitudes of the motor evoked potential (MEP) pre and post quadripulse stimulation (QPS) applied over the contralateral motor cortex served as measure of the degree of cortical plasticity in 63 patients with relapsing-remitting MS (RRMS) and 55 matched HCs. The main outcomes were the correlation coefficients between the difference of MEP amplitudes post and pre QPS and the Symbol Digit Modalities Test (SDMT) and Brief Visuospatial Memory Test-Revised (BVMT-R), and the QPS^xgroup interaction in a mixed model predicting the MEP amplitude.ResultsSDMT and BVMT-R correlated significantly with QPS-induced cortical plasticity in RRMS patients. Plasticity was significantly reduced in patients with cognitive impairment compared to patients with preserved cognitive function and the degree of plasticity differentiated between both patient groups. Interestingly, the overall RRMS patient cohort did not show reduced plasticity compared to HCs.ConclusionsWe provide first evidence that QPS-induced plasticity may inform about the global synaptic plasticity in RRMS which correlates with cognitive performance as well as clinical disability. Larger longitudinal studies on patients with MS are needed to investigate the relevance and prognostic value of this measure for disease progression and recovery.     

Asymmetric bilateral effect of the supplementary motor area proper in the human motor system

ObjectiveThis study aimed to clarify the function of human supplementary motor area proper (SMA) by the single-pulse electric stimulation method and its clinical usefulness for SMA mapping.MethodsWe studied five patients with epilepsy or brain tumour who underwent invasive functional mapping with subdural electrodes. Single-pulse electric stimulation of primary motor area (MI) and SMA was carried out through pairs of subdural electrodes, and motor-evoked potentials (MEPs) were recorded from surface electromyogram on both sides and also cortico-cortical-evoked potentials (CCEPs) from electrocorticogram.ResultsSMA stimulation elicited: (1) MEPs and following silent periods (SPs) in the contralateral upper and lower extremities, (2) SPs with or without minimal MEPs in the ipsilateral upper extremity and (3) CCEPs in the somatotopically corresponding region of the ipsilateral MI. Compared with MI stimulation, SMA stimulation required higher stimulus intensities (mean 14.2 mA (SMA) vs. 8.5 mA (MI)) to elicit MEPs and showed significantly longer onset latencies in upper extremity (range: 4–10 ms).ConclusionsThe results demonstrated an asymmetric bilateral effect of human SMA upon the corticospinal pathway.SignificanceSingle-pulse electric cortical stimulation would be clinically useful for distinguishing SMA from MI. The asymmetric bilateral effect of SMA might be conveyed through the direct descending pathway.     

Repeated motor cortex theta-burst stimulation produces persistent strengthening of corticospinal motor output and durable spinal cord structural changes in the rat

BackgroundThe strength of connections between motor cortex (MCX) and muscle can be augmented with a variety of stimulation protocols. Augmenting MCX-to-muscle connection strength by neuromodulation may be a way to enhance the intact motor system's capacity for acquiring motor skills and promote function after injury to strengthen spared connections. But this enhancement must be maintained for functional improvements.ObjectiveWe determined if brief MCX muscle evoked potential (MEP) enhancement produced by single-block intermittent theta burst stimulation (iTBS) can be converted into a longer and structurally durable form of response enhancement with repeated daily and longer-term application.MethodsElectrical iTBS was delivered through an implanted MCX epidural electrode and MEPs were recorded using implanted EMG electrodes in awake naïve rats. MCX activity was modulated further using chemogenetic (DREADDs) excitation and inhibition. Corticospinal tract (CST) axons were traced and immunochemistry used to measure CST synapses.ResultsA single MCX iTBS block (600 pulses) produced MEP LTP lasting ～30–45 min. Concatenating five iTBS blocks within a 30-min session produced MEP LTP lasting 24–48 h, which could be strengthened or weakened by bidirectional MCX activity modulation. Effect duration was not changed. Finally, daily induction of this persistent MEP LTP with daily iTBS for 10-days produced MEP enhancement outlasting the stimulation period by at least 10 days, and accompanied by CST axonal outgrowth and structural changes at the CST-spinal interneuron synapse.ConclusionOur findings inform the mechanisms of iTBS and provide a framework for designing neuromodulatory strategies to promote durable enhancement of cortical motor actions.     

Anodal transcranial direct current stimulation (tDCS) over supplementary motor area (SMA) but not pre-SMA promotes short-term visuomotor learning

BackgroundNon-invasive brain stimulation such as transcranial direct current stimulation (tDCS) has been shown to modulate cortical excitability and thereby influencing motor behaviour and learning.HypothesisWhile there is increasing knowledge about the importance of the primary motor cortex (M1) in short- and long-term motor skill learning, little is known about the role of secondary motor areas such as the supplementary and pre-supplementary motor area (SMA/pre-SMA) especially in short-term motor performance. Since SMA but not pre-SMA is directly connected to M1, we hypothesize that anodal tDCS over SMA but not pre-SMA will facilitate visuomotor learning.MethodsWe applied anodal tDCS (tDCS_anodal) over left SMA, pre-SMA or M1 (n = 12 in each group) while subjects performed a visuomotor pinch force task (VPFT) with their right hand and compared VPFT performance relative to sham (tDCS_sham).ResultsFor the first time, we could show that apart from tDCS_anodal over left M1 also SMA but not pre-SMA stimulation promotes short-term improvements in visuomotor learning relative to tDCS_sham.ConclusionsOur findings provide novel evidence about the role of SMA in short-term visuomotor performance. This knowledge might be beneficial in developing hypothesis-driven clinical studies in neurorehabilitation.     

Initial motor impairment influences activation pattern of motor recovery

Abstract

Objectives: We investigated the functional magnetic resonance imaging (fMRI) activation pattern of a motor task in patients with acute subcortical lesions to examine the relationship between activation pattern and recovery of motor impairment.

Methods: Five patients (one with subcortical infarction and four with thalamic hemorrhage) were examined using fMRI 1 month after the insult. Impairment was assessed by the Medical Research Council motor strength classification (MRC). One patient with severe motor deficits was also studied at 4 months when her motor deficits improved up to MRC grade 4.

Results: Three patients with relatively mild deficits (MRC grade 3 or 4) at their onsets, improved fully up to grade 5 within 1 month. FMRI performed at 1 month showed activation in the contralateral primary motor cortex and supplementary motor area (SMA), but no significant activation was seen on the ipsilateral unaffected side. Two patients with severe motor impairment (MRC grade 1) improved up to 3 and 4 of MRC at 1 month or later. They showed activation of the ipsilateral premotor area as well as contralateral primary motor cortex and SMA. One of them, whose severe motor deficit improved at 4 month, also showed activation of the ipsilateral postcentral gyrus and the activated area expanded longitudinally corresponding with her functional recovery.

Discussion: Our study demonstrates that the fMRI pattern varies according to functional recovery, suggesting the importance of the ipsilateral premotor area and postcentral gyrus especially for those patients with severe motor impairment initially.     

Associative plasticity in intracortical inhibitory circuits in human motor cortex

ObjectivePaired associative stimulation (PAS) is a transcranial magnetic stimulation technique inducing Hebbian-like synaptic plasticity in the human motor cortex (M1). PAS is produced by repetitive pairing of a peripheral nerve shock and a transcranial magnetic stimulus (TMS). Its effect is assessed by a change in size of a motor evoked response (MEP). MEP size results from excitatory and inhibitory influences exerted on cortical pyramidal cells, but no robust effects on inhibitory networks have been demonstrated so far.MethodIn 38 healthy volunteers, we assessed whether a PAS intervention influences three intracortical inhibitory circuits: short (SICI) and long (LICI) intracortical inhibitions reflecting activity of GABA_A and GABA_B interneurons, respectively, and long afferent inhibition (LAI) reflecting activity of somatosensory inputs.ResultsAfter PAS, MEP sizes, LICI and LAI levels were significantly changed while changes of SICI were inconsistent. The changes in LICI and LAI lasted 45 min after PAS. Their direction depended on the delay between the arrival time of the afferent volley at the cortex and the TMS-induced cortical activation during the PAS.ConclusionsPAS influences inhibitory circuits in M1.SignificancePAS paradigms can demonstrate Hebbian-like plasticity at selected inhibitory networks as well as excitatory networks.     

Deficits in corticospinal control of stretch reflex thresholds in stroke: Implications for motor impairment

ObjectivesThe corticospinal system (CS) regulates muscle activation through shifts in muscle-level tonic stretch-reflex thresholds (TSRT). This ability is impaired in stroke and contributes to sensorimotor impairments such as spasticity. We determined the role of CS in elbow flexor activity regulation in healthy and post-stroke subjects. We also determined whether CS modulation deficits were related to sensorimotor impairment intensity in post-stroke individuals.MethodsSeventeen healthy (59.8 ± 12.2 yr) and 27 stroke subjects (58.7 ± 10.1 yr) had transcranial magnetic stimulation (TMS) applied over the primary motor cortex (M1) flexor representation to elicit motor-evoked potentials (MEPs) in elbow flexors in different angular positions. In a subset of post-stroke subjects (n = 12), flexor TSRTs were measured in passive and active conditions, and TSRT modulation was determined.ResultsPosition-related MEP amplitude modulation was similar in healthy and mild stroke subjects, while subjects with more severe stroke exhibited less consistent modulation. MEP modulation in stroke was related to clinical upper limb motor impairment, spasticity, and the ability to modulate TSRTs between passive and active elbow movements.ConclusionsCS output was closely related to TSRT modulation. Impairments in TSRT regulation may underlie motor deficits in moderate-to-severe post-stroke individuals.SignificanceTranslation of these neurophysiological findings to clinical applications may enhance post-stroke motor recovery.