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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. [ABSTRACT FROM AUTHOR]

Maladaptive cortical plasticity has been described in individuals with heroin and methamphetamine addiction and may mediate other substance abuse disorders. It is unknown whether cannabis dependence in humans alters the capacity for induction of cortical plasticity. The aim of this study was to non-invasively investigate cortical plasticity with transcranial magnetic stimulation in young adults who meet DSM-5 criteria for cannabis use disorder (CUD). Thirty men (ages 20- 30) who used cannabis daily over the previous 6 months (15 diagnosed of CUD) and 15 demographically matched non-users were enrolled in this study. All participants underwent two sessions of theta burst stimulation (TBS) in which either continuous TBS (cTBS; 600 pulses, 80% active motor threshold) or intermittent TBS (iTBS; 2-s train of cTBS repeated every 10 s for a total of 190 s, 600 pulses) was applied over the primary motor cortex. The effects of these protocols were assessed by analysing the contralateral motor evoked potentials (MEPs). The relationships between cortical plasticity and problematic cannabis use, degree of dependence, and nicotine addiction were also investigated. Significant MEP inhibition after cTBS was observed in both cannabis users without CUD and non-users, while this inhibition was not seen in cannabis users with CUD. Strikingly, less motor cortical plasticity was observed in subjects with severe problematic cannabis use. No significant differences between users and non-users were found in the iTBS-induced cortical plasticity measures. Our study provides the first evidence of maladaptive cortical plasticity associated with cannabis use disorder and problematic cannabis use in humans. [ABSTRACT FROM AUTHOR]

Introduction:This review will first discuss evidence of motor and sensory abnormalities as yielded by neurophysiological techniques in patients with PD. It will then go on to describe the effects of L-dopa replacement on motor and sensory abnormalities in PD as assessed by neurophysiological studies. Areas covered:We analyzed papers in English using Pubmed with the following keywords: L-dopa, dopamine, bradykinesia, basal ganglia, kinematic analysis, TMS, motor cortex plasticity, motor cortex excitability, somatosensory discrimination threshold, pain Expert commentary:L-dopa improves the amplitude and speed of upper limb voluntary movements, but it does not restore abnormalities in the sequence effect or voluntary facial movements. L-dopa only partially normalizes changes in motor cortex excitability and plasticity and has also contrasting effects on the sensory system and on sensory-motor integration. The neurophysiological studies reviewed here show that PD is more than a hypo-dopaminergic disease, and non-dopaminergic mechanisms should also be considered. [ABSTRACT FROM PUBLISHER]

Background: Pairing peripheral electrical stimulation (ES) and transcranial magnetic stimulation (TMS) increases corticospinal excitability when applied with a specific temporal pattern. When the two stimulation techniques are applied separately, motor imagery (MI)-related oscillatory modulation amplifies both ES-related cortical effects--sensorimotor event-related desynchronization (ERD), and TMS-induced peripheral responses--motor-evoked potentials (MEP). However, the influence of brain self-regulation on the associative pairing of these stimulation techniques is still unclear. Objective: The aim of this pilot study was to investigate the effects of MI-related ERD during associative ES and TMS on subsequent corticospinal excitability. Method: The paired application of functional electrical stimulation (FES) of the extensor digitorum communis (EDC) muscle and subsequent single-pulse TMS (110% resting motor threshold (RMT)) of the contralateral primary motor cortex (M1) was controlled by beta-band (16-22 Hz) ERD during MI of finger extension and applied within a brainmachine interface environment in six healthy subjects. Neural correlates were probed by acquiring the stimulus-response curve (SRC) of both MEP peak-to-peak amplitude and area under the curve (AUC) before and after the intervention. Result: The application of approximately 150 pairs of associative FES and TMS resulted in a significant increase of MEP amplitudes and AUC, indicating that the induced increase of corticospinal excitability was mediated by the recruitment of additional neuronal pools. MEP increases were brain state-dependent and correlated with beta-band ERD, but not with the background EDC muscle activity; this finding was independent of the FES intensity applied. Conclusion: These results could be relevant for developing closed-loop therapeutic approaches such as the application of brain state-dependent, paired associative stimulation (PAS) in the context of neurorehabilitation. [ABSTRACT FROM AUTHOR]

We used transcranial magnetic stimulation (TMS) to investigate whether an acute bout of resistance exercise with blood flow restriction (BFR) stimulated changes in corticomotor excitability (motor evoked potential, MEP) and short-interval intracortical inhibition (SICI), and compared the responses to two traditional resistance exercise methods. Ten males completed four unilateral elbow flexion exercise trials in a balanced, randomized crossover design: (1) heavy-load (HL: 80% one-repetition maximum [1-RM]); (2) light-load (LL; 20% 1-RM) and two other light-load trials with BFR applied; (3) continuously at 80% resting systolic blood pressure (BFR-C); or (4) intermittently at 130% resting systolic blood pressure (BFR-I). MEP amplitude and SICI were measured using TMS at baseline, and at four time-points over a 60 min post-exercise period. MEP amplitude increased rapidly (within 5 min post-exercise) for BFR-C and remained elevated for 60 min post-exercise compared with all other trials. MEP amplitudes increased for up to 20 and 40 min for LL and BFR-I, respectively. These findings provide evidence that BFR resistance exercise can modulate corticomotor excitability, possibly due to altered sensory feedback via group III and IV afferents. This response may be an acute indication of neuromuscular adaptations that underpin changes in muscle strength following a BFR resistance training programme. [ABSTRACT FROM AUTHOR]

Background Motor cortex excitability was found to be changed after repetitive transcranial magnetic stimulation (rTMS) of the temporal cortex highlighting the occurrence of cross-modal plasticity in non-invasive brain stimulation. Here, we investigated the effects of temporal low-frequency rTMS on motor cortex plasticity in a large sample of tinnitus patients. In 116 patients with chronic tinnitus different parameters of cortical excitability were assessed before and after ten rTMS treatment sessions. Patients received one of three different protocols all including 1 Hz rTMS over the left temporal cortex. Treatment response was defined as improvement by at least five points in the tinnitus questionnaire (TQ). Variables of interest were resting motor threshold (RMT), short-interval intra-cortical inhibition (SICI), intracortical facilitation (ICF), and cortical silent period (CSP). Results After rTMS treatment RMT was decreased by about 1% of stimulator output nearsignificantly in the whole group of patients. SICI was associated with significant changes with respect to treatment response. The group of treatment responders showed a decrease of SICI over the course of treatment, the group of non-responders the reverse pattern. Conclusions Minor RMT changes during rTMS treatment do not necessarily suggest the need for systematic re-examination of the RMT for safety and efficacy issues. Treatment response to rTMS was shown to be related to changes in SICI that might reflect modulation of GABAergic mechanisms directly or indirectly related to rTMS treatment effects. [ABSTRACT FROM AUTHOR]

Normal motor behavior involves the creation of appropriate activity patterns across motor networks, enabling firing synchrony, synaptic integration, and normal functioning of these networks. Strong topography-specific connections among the basal ganglia, cerebellum, and their projections to overlapping areas in the motor cortices suggest that these networks could influence each other's plastic responses and functions. The defective striatal signaling in Parkinson's disease (PD) could therefore lead to abnormal oscillatory activity and aberrant plasticity at multiple levels within the interlinked motor networks. Normal striatal dopaminergic signaling and cerebellar sensory processing functions influence the scaling and topographic specificity of M1 plasticity. Both these functions are abnormal in PD and appear to contribute to the abnormal M1 plasticity. Defective motor map plasticity and topographic specificity within M1 could lead to incorrect muscle synergies, which could manifest as abnormal or undesired movements, and as abnormal motor learning in PD. We propose that the loss of M1 plasticity in PD reflects a loss of co-ordination among the basal ganglia, cerebellar, and cortical inputs which translates to an abnormal plasticity of motor maps within M1 and eventually to some of the motor signs of PD. The initial benefits of dopamine replacement therapy on M1 plasticity and motor signs are lost during the progressive course of disease. Levodopa-induced dyskinesias in patients with advanced PD is linked to a loss of M1 sensorimotor plasticity and the attenuation of dyskinesias by cerebellar inhibitory stimulation is associated with restoration of M1 plasticity. Complimentary interventions should target reestablishing physiological communication between the striatal and cerebellar circuits, and within striato-cerebellar loop. This may facilitate correct motor synergies and reduce abnormal movements in PD. [ABSTRACT FROM AUTHOR]

Background: Transcranial direct current stimulation (tDCS) is a non-invasive technique that modulates the excitability of neurons within the primary motor cortex (M1). Research shows that anodal-tDCS applied over the non-dominant M1 (i.e. unilateral stimulation) improves motor function of the non-dominant hand. Similarly, previous studies also show that applying cathodal tDCS over the dominant M1 improves motor function of the non-dominant hand, presumably by reducing interhemispheric inhibition. In the present study, one condition involved anodal-tDCS over the non-dominant M1 (unilateral stimulation) whilst a second condition involved applying cathodal-tDCS over the dominant M1 and anodal-tDCS over non-dominant M1 (bilateral stimulation) to determine if unilateral or bilateral stimulation differentially modulates motor function of the non-dominant hand. Using a randomized, cross-over design, 11 right-handed participants underwent three stimulation conditions: 1) unilateral stimulation, that involved anodal-tDCS applied over the non-dominant M1, 2) bilateral stimulation, whereby anodal-tDCS was applied over the non-dominant M1, and cathodal-tDCS over the dominant M1, and 3) sham stimulation. Transcranial magnetic stimulation (TMS) was performed before, immediately after, 30 and 60 minutes after stimulation to elucidate the neural mechanisms underlying any potential after-effects on motor performance. Motor function was evaluated by the Purdue pegboard test. Results: There were significant improvements in motor function following unilateral and bilateral stimulation when compared to sham stimulation at all-time points (all P < 0.05); however there was no difference across time points between unilateral and bilateral stimulation. There was also a similar significant increase in corticomotor excitability with both unilateral and bilateral stimulation immediately post, 30 minutes and 60 minutes compared to sham stimulation (all P < 0.05). Unilateral and bilateral stimulation reduced short-interval intracortical inhibition (SICI) immediately post and at 30 minutes (all P < 0.05), but returned to baseline in both conditions at 60 minutes. There was no difference between unilateral and bilateral stimulation for SICI (P > 0.05). Furthermore, changes in corticomotor plasticity were not related to changes in motor performance. Conclusion: These results indicate that tDCS induced behavioural changes in the non-dominant hand as a consequence of mechanisms associated with use-dependant cortical plasticity that is independent of the electrode arrangement. [ABSTRACT FROM AUTHOR]

Animal studies using polarising currents have shown that induction of synaptic long-term potentiation (LTP) and long-term depression (LTD) by bursts of patterned stimulation is affected by the membrane potential of the postsynaptic neurone. The aim of the present experiments was to test whether it is possible to observe similar phenomena in humans with the aim of improving present protocols of inducing synaptic plasticity for therapeutic purposes. We tested whether the LTP/LTD-like after effects of transcranial theta-burst stimulation (TBS) of human motor cortex, an analogue of patterned electrical stimulation in animals, were affected by simultaneous transcranial direct-current stimulation (tDCS), a non-invasive method of polarising cortical neurones in humans. Nine healthy volunteers were investigated in a single-blind, balanced cross-over study; continuous TBS (cTBS) was used to introduce LTD-like after effects, whereas intermittent TBS (iTBS) produced LTP-like effects. Each pattern was coupled with concurrent application of tDCS (<200 s, anodal, cathodal, sham). Cathodal tDCS increased the response to iTBS and abolished the effects of cTBS. Anodal tDCS changed the effects of cTBS towards facilitation, but had no impact on iTBS. Cortical motor thresholds and intracortical inhibitory/facilitatory networks were not altered by any of the stimulation protocols. We conclude that the after effects of TBS can be modulated by concurrent tDCS. We hypothesise that tDCS changes the membrane potential of the apical dendrites of cortical pyramidal neurones and that this changes the response to patterned synaptic input evoked by TBS. The data show that it may be possible to enhance LTP-like plasticity after TBS in the human cortex. [ABSTRACT FROM AUTHOR]

The motor cortex and spinal cord possess the remarkable ability to alter structure and function in response to differential motor training. Here we review the evidence that the corticospinal system is not only plastic but that the nature and locus of this plasticity is dictated by the specifics of the motor experience. Skill training induces synaptogenesis, synaptic potentiation, and reorganization of movement representations within motor cortex. Endurance training induces angiogenesis in motor cortex, but it does not alter motor map organization or synapse number. Strength training alters spinal motoneuron excitability and induces synaptogenesis within spinal cord, but it does not alter motor map organization. All three training experiences induce changes in spinal reflexes that are dependent on the specific behavioral demands of the task. These results demonstrate that the acquisition of skilled movement induces a reorganization of neural circuitry within motor cortex that supports the production and refinement of skilled movement sequences. We present data that suggest increases in strength may be mediated by an increased capacity for activation and/or recruitment of spinal motoneurons while the increased metabolic demands associated with endurance training induce cortical angiogenesis. Together these results show the robust pattern of anatomic and physiological plasticity that occurs within the corticospinal system in response to differential motor experience. The consequences of such distributed, experience-specific plasticity for the encoding of motor experience by the motor system are discussed. [ABSTRACT FROM AUTHOR]

It is generally accepted that functional properties of the motor cortex in adult humans can be altered through behavioral or pharmacological manipulations, as well as in some pathological conditions. The ability and capacity of adult human cortex to undergo any adaptive or reorganizational changes is referred to as plasticity. Much of the evidence concerning motor cortical plasticity have been derived from studies using the non-invasive technique of transcranial magnetic stimulation (TMS). TMS has proven to be a suitable tool to explore representational plasticity and to interact with neuronal activity in settings of induction protocols either alone or coupled with altered sensory inputs. Furthermore, plastic changes induced by motor learning protocols have attracted particular interest because of their relevance in functional recovery. Recent studies support the view that learning in human motor cortex occurs through long-term potentiation (LTP)-like mechanisms. Purposeful modulation of motor cortical plastic changes by manipulative TMS protocols may offer useful rehabilitative strategies in patients with chronic motor deficits. [ABSTRACT FROM AUTHOR]

The present study investigates the time course and pattern of movement representation recovery in the motor cortex during the recovery after a peripheral paralysis. To this end a transitory flaccid paralysis of the vibrissae muscle was induced in adult rats that underwent two unilateral injections of 8 U of botulinum toxin (BTX) into a vibrissal pad, at a duration of 12 days from one another. The compound muscle action potential (MAP) of the vibrissae muscle began to reappear 4 weeks after the first BTX injection. Intracortical microstimulation (ICMS) was used to map rat motor cortices 4, 5, 6, 7 and 8 weeks after the first BTX injection. Findings demonstrated that: (i) contralateral vibrissae movement reappears in the medial part of its normal cortical territory when the MAP is almost 10% of the control value; in the remaining part, ICMS elicits eye, ipsilateral vibrissae, neck and forelimb movements; (ii) the contralateral vibrissae movement reappears in sites where ipsilateral vibrissae and/or neck movement are co-represented; (iii) as MAP recovers, the vibrissae representation expands until it recovers the 90.8% of its territory after 7 weeks, when the MAP was almost 43.4% of the control value; (iv) from 4 to 7 weeks, the ICMS-evoked contralateral vibrissae movement shows a significantly higher electrical threshold vs. the control group; (v) recovery of the baseline excitability uniformly involves the vibrissae representation 1 week later, after its cortical territory has recovered 93.1% of the control value and the MAP has returned to 78.8% of the baseline value. [ABSTRACT FROM AUTHOR]

Background: Spasticity arises from hyperexcitability of the neural stretch reflex arc secondary to injury of the corticospinal tract. In response to injury, the density of glutamatergic inputs from afferent 1A fibers to motor neurons increases dramatically and adaptive changes occur in the morphology of microglia cells in the spinal cord. Summary: Involvement of the endocannabinoid system in pathophysiological mechanisms responsible for spasticity has been demonstrated in animal models of MS. Stimulation of cannabinoid (CB)1 receptors reduces the hyperglutamatergic drive from sensory afferents to spinal cord motor neurons and blocks the synaptic effects of activated microglia and pro-inflammatory mediators (e.g. TNF-α) on glutamatergic transmission. Enhancing corticospinal tract excitability through intermittent theta burst stimulation inhibits the stretch reflex and spasticity by promoting long-term potentiation, a form of synaptic plasticity that requires stimulation of CB1 receptors. Evidence indicates that the antispasticity effects of THC:CBD oromucosal spray (Sativex®) are associated with enhanced cortical long-term potentiation. Key Messages: Glutamatergic and GABAergic pathways are involved in the regulation of muscle tone. CB1 receptors, which are associated with movement, postural control, and pain and sensory perception, influence glutamatergic pathways. THC:CBD oromucosal spray was shown to reverse motor cortex plasticity from long-term depression through long-term potentiation of synaptic transmission, thereby restoring, at least in part, effective corticospinal inputs to spinal circuits. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Using paired pulse transcranial magnetic stimulation (TMS) paradigms, we studied cortical excitability in a patient with spinal cord lesion. During posterior tibial nerve stimulation, the contextual flexion of hand fingers contralateral to the stimulated lower limb had suggested a change in motor cortex excitability. Results showed a decrease in the activity of motor cortex inhibitory circuits. This could suggest that in spinal cord injury, just as in stroke and peripheral deafferentation, a disinhibition of latent synapses within the motor cortex and the rewriting of a new motor map can occur. [ABSTRACT FROM AUTHOR]