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Transcranial magnetic stimulation coupled with electroencephalography (TMS-EEG) is a novel technique to investigate cortical physiology in health and disease. The cerebellum has recently gained attention as a possible new hotspot in the field of TMS-EEG, with several reports published recently. However, EEG responses obtained by cerebellar stimulation vary considerably across the literature, possibly due to different experimental methods. Compared to conventional TMS-EEG, which involves stimulation of the cortex, cerebellar TMS-EEG presents some technical difficulties, including strong muscle twitches in the neck area and a loud TMS click when double-cone coils are used, resulting in contamination of responses by electromyographic activity and sensory potentials. Understanding technical difficulties and limitations is essential for the development of cerebellar TMS-EEG research. In this review, we summarize findings of cerebellar TMS-EEG studies, highlighting limitations in experimental design and potential issues that can result in discrepancies between experimental outcomes. Lastly, we propose a possible direction for academic and clinical research with cerebellar TMS-EEG. [ABSTRACT FROM AUTHOR]

Botulinum toxin (BT) therapy may be blocked by antibodies (BT-AB) resulting in BT-AB induced therapy failure (ABF). BT-AB may be detected by the mouse lethality assay (MLA), the mouse diaphragm assay (MDA) and the sternocleidomastoid test (SCMT). For the first time, we wanted to compare all three BT-AB tests and correlate them to subjective complaint of complete or partial secondary therapy failure in 37 patients with cervical dystonia (25 females, 12 males, age 51.2 ± 11.4 years, disease duration 12.4 ± 6.3 years). Complaint of therapy failure was not correlated with any of the BT-AB tests. MDA and MLA are closely correlated, indicating that the MDA might replace the MLA as the current gold standard for BT-AB measurement. The SCMT is closely correlated with MDA and MLA confirming that BT-AB titres and BT's paretic effect are in a functional balance: low BT-AB titres are reducing BT's paretic effect only marginally, whereas high BT-AB titres may completely block it. When therapy failure is classified as secondary and permanent, BT-AB evaluation is recommended and any BT-AB test may be applied. For MDA > 10 mU/ml, MLA > 3 and SCMT < 25%, ABF is highly likely. MDA < 0.6 mU/ml are therapeutically irrelevant. They are neither correlated with pathologic MLA nor with pathologic SCMT. They should not be the basis for treatment decisions, such as switching dystonia therapy to deep brain stimulation. All other results are intermediate results. Their interactions with therapy efficacy is unpredictable. In these cases, BT-AB tests should be repeated or one or two additional test methods should be applied. [ABSTRACT FROM AUTHOR]

• The paper corrects discrepancies in the difference equations of the previously suggested model of theta-burst stimulation. • The corrected stages are consistently calibrated to experimental data to serve for quantitative analysis. • This work improves the model accuracy in various conditions and secures the model that underlies a rich body of research. Calcium dependency is presently an essential assumption in modelling the neuromodulatory effects of transcranial magnetic stimulation. Y.Z. Huang et al. developed the first neuromodulation model to explain the bidirectional effects of theta-burst stimulation (TBS) based on the postsynaptic intracellular calcium concentration elevation. However, we discover that the published computer code is not consistent with the model formulation, neither do the parameters and derived plots consequently match the formulations. Here we intend to fix the computer code and re-calibrate the model. We corrected the affected difference equations and re-calibrated the revised model with experimental data using non-convex optimisation based on a L 2 penalty. The revised model outperforms the initial model in characterising the relative motor-evoked potential levels of TBS-induced after-effects in various conditions. We corrected the inconsistencies in the previous model and computer code and provided a complete calibration to support the research that is based on it. This work improves the accuracy and secures the scope of the model, which is necessary to retain a rich body of research resulting from the model. Furthermore, this model provides both a quantitative model for several parameters of TBS and a basic model foundation for future refinement. [ABSTRACT FROM AUTHOR]

Dopamine is crucially involved in decision-making and overstimulation within dopaminergic pathways can lead to impulsive behaviour, including a desire to take risks and reduced deliberation before acting. These behavioural changes are side effects of treatment with dopaminergic drugs in Parkinson disease, but their likelihood of occurrence is difficult to predict and may be influenced by the individual's baseline endogenous dopamine state, and indeed correlate with sensation-seeking personality traits. We here collected data on a standard gambling task in healthy volunteers given either placebo, 2.5 mg of the dopamine antagonist haloperidol or 100/25 mg of the dopamine precursor levodopa in a within-subject design. We found an increase in risky choices on levodopa. Choices were, however, made faster on haloperidol with no effect of levodopa on deliberation time. Shortened deliberation times on haloperidol occurred in low sensation-seekers only, suggesting a correlation between sensation-seeking personality trait and baseline dopamine levels. We hypothesise that levodopa increases risk-taking behaviour via overstimulation at both D1 and D2 receptor level, while a single low dose of haloperidol, as previously reported (Frank and O'Reilly 2006), may block D2 receptors pre- and post-synaptically and may paradoxically lead to higher striatal dopamine acting on remaining striatal D1 receptors, causing speedier decision without influencing risk tolerance. These effects could also fit with a recently proposed computational model of the basal ganglia (Moeller and Bogacz 2019; Moeller et al. 2021). Furthermore, our data suggest that the actual dopaminergic drug effect may be dependent on the individual's baseline dopamine state, which may influence our therapeutic decision as clinicians in the future. [ABSTRACT FROM AUTHOR]

Patients with movement disorders experience fluctuations unrelated to disease progression or treatment. Extrinsic factors that contribute to the variable expression of movement disorders are environment related. They influence the expression of movement disorders through sensory–motor interactions and include somatosensory, visual, and auditory stimuli. Examples of somatosensory effects are stimulus sensitivity of myoclonus on touch and sensory amelioration in dystonia but also some less‐appreciated effects on parkinsonian tremor and gait. Changes in visual input may affect practically all types of movement disorders, either by loss of its compensatory role or by disease‐related alterations in the pathways subserving visuomotor integration. The interaction between auditory input and motor function is reflected in simple protective reflexes and in complex behaviors such as singing or dancing. Various expressions range from the effect of music on parkinsonian bradykinesia to tics. Changes in body position affect muscle tone and may result in marked fluctuations of rigidity or may affect dystonic manifestations. Factors intrinsic to the patient are related to their voluntary activity and cognitive, motivational, and emotional states. Depending on the situation or disease, they may improve or worsen movement disorders. We discuss various factors that can influence the phenotypic variability of movement disorders, highlighting the potential mechanisms underlying these manifestations. We also describe how motor fluctuations can be provoked during the clinical assessment to help reach the diagnosis and appreciated to understand complaints that seem discrepant with objective findings. We summarize advice and interventions based on the variability of movement disorders that may improve patients' functioning in everyday life. © 2020 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

[Display omitted] • Short- (SAI) and long-latency (LAI) afferent inhibition result from cortical integration of sensory inputs and motor output. • This work shows that SAI and LAI depend on type of sensory receptors, muscle function and cortical motor area. • This finding has pathophysiological implications in motor disorders involving specific muscular districts, such as focal dystonia. To compressively investigate sensorimotor integration in the cranial-cervical muscles in healthy adults. Short- (SAI) and long-latency afferent (LAI) inhibition were probed in the anterior digastric (AD), the depressor anguli oris (DAO) and upper trapezius (UT) muscles. A transcranial magnetic stimulation pulse over primary motor cortex was preceded by peripheral stimulation delivered to the trigeminal, facial and accessory nerves using interstimulus intervals of 15–25 ms and 100–200 ms for SAI and LAI respectively. In the AD, both SAI and LAI were detected following trigeminal nerve stimulation , but not following facial nerve stimulation. In the DAO, SAI was observed only following trigeminal nerve stimulation, while LAI depended only on facial nerve stimulation, only at an intensity suprathreshold for the compound motor action potential (cMAP). In the UT we could only detect LAI following accessory nerve stimulation at an intensity suprathreshold for a cMAP. The results suggest that integration of sensory inputs with motor output is profoundly influenced by the type of sensory afferent involved and by the functional role played by the target muscle. Data indicate the importance of taking into account the sensory receptors involved as well as the function of the target muscle when studying sensorimotor integration, both in physiological and neurological conditions. [ABSTRACT FROM AUTHOR]

• Evidence supporting the electrophysiological criteria of cortical myoclonus is not very solid. • Although they can be useful if properly used, the electrophysiological criteria of cortical myoclonus should be reviewed. • Combining more than one test, together with clinical features, may increase the diagnostic accuracy of cortical myoclonus. Cortical myoclonus is thought to result from abnormal electrical discharges arising in the sensorimotor cortex. Given the ease of recording of cortical discharges, electrophysiological features of cortical myoclonus have been better characterized than those of subcortical forms, and electrophysiological criteria for cortical myoclonus have been proposed. These include the presence of giant somatosensory evoked potentials, enhanced long-latency reflexes, electroencephalographic discharges time-locked to individual myoclonic jerks and significant cortico-muscular connectivity. Other features that are assumed to support the cortical origin of myoclonus are short-duration electromyographic bursts, the presence of both positive and negative myoclonus and cranial-caudal progression of the jerks. While these criteria are widely used in clinical practice and research settings, their application can be difficult in practice and, as a result, they are fulfilled only by a minority of patients. In this review we reappraise the evidence that led to the definition of the electrophysiological criteria of cortical myoclonus, highlighting possible methodological incongruencies and misconceptions. We believe that, at present, the diagnostic accuracy of cortical myoclonus can be increased only by combining observations from multiple tests, according to their pathophysiological rationale; nevertheless, larger studies are needed to standardise the methods, to resolve methodological issues, to establish the diagnostic criteria sensitivity and specificity and to develop further methods that might be useful to clarify the pathophysiology of myoclonus. [ABSTRACT FROM AUTHOR]

• Ca spike is initiated by synaptic input and backpropagation of action potentials at the dendrite. • The Calcium spike initiates a burst of somatic action potentials causing repetitive firing of CSTN. • The bursting of CSTNs may determine the intervals of successive I-waves in the motor cortical TMS. A single pulse of TMS or direct electric stimulation over M1 causes repetitive synchronized firing of corticospinal tract (CST) neurons. Two mechanisms for the repetitive firing have been proposed: a cascade of synaptic inputs to the pyramidal neurons and a single reverberating circuit of interneurons. Here, we propose another possibility in which bursting of CST neurons is produced by dendritic Ca2+-spikes. Backpropagation of the initial action potential (I1-wave) from the soma interacts with synaptic input in the dendrites to initiate a dendritic calcium spike. These Ca2+-spikes produce a burst of somatic action potentials that starts about 1.5 ms after the initial discharge of the neuron, which may produce the later I-waves. [ABSTRACT FROM AUTHOR]

Objective To assess the impact of electrode arrangement on the efficacy of tDCS in stroke survivors and determine whether changes in transcallosal inhibition (TCI) underlie improvements. Methods 24 stroke survivors (3–124 months post-stroke) with upper limb impairment participated. They received blinded tDCS during a motor sequence learning task, requiring the paretic arm to direct a cursor to illuminating targets on a monitor. Four tDCS conditions were studied (crossover); anodal to ipsilesional M1, cathodal to contralesional M1, bihemispheric, sham. The Jebsen Taylor hand function test (JTT) was assessed pre- and post-stimulation and TCI assessed as the ipsilateral silent period (iSP) duration using transcranial magnetic stimulation. Results The time to react to target illumination reduced with learning of the movement sequence, irrespective of tDCS condition ( p > 0.1). JTT performance improved after unilateral tDCS (anodal or cathodal) compared with sham ( p < 0.05), but not after bihemispheric ( p > 0.1). There was no effect of tDCS on change in iSP duration ( p > 0.1). Conclusions Unilateral tDCS is effective for improving JTT performance, but not motor sequence learning. Significance This has implications for the design of future clinical trials. [ABSTRACT FROM AUTHOR]

Recently, it has been proposed that similar to goal-directed and habitual action mediated by the fronto-striatal circuits, the fronto-striato-subthalamic-pallidal-thalamo-cortical network may also mediate goal-directed and habitual (automatic) inhibition in both the motor and non-motor domains. Within this framework, some of the clinical manifestations of Parkinson's disease, dystonia, Tourette syndrome and obsessive-compulsive disorder can be considered to represent an imbalance between goal-directed and habitual action and inhibition. It is possible that surgical interventions targeting the basal ganglia nuclei, such as deep brain stimulation of the subthalamic nucleus or the internal segment of the globus pallidus, improve these disorders by restoring a functional balance between facilitation and inhibition in the fronto-striatal networks. These proposals require investigation in future studies. This article is part of the themed issue 'Movement suppression: brain mechanisms for stopping and stillness'. [ABSTRACT FROM AUTHOR]

Activation of neurons not only changes their membrane potential and firing rate but as a secondary action reduces membrane resistance. This loss of resistance, or increase of conductance, may be of central importance in non-invasive magnetic or electric stimulation of the human brain since electrical fields cause larger changes in transmembrane voltage in resting neurons with low membrane conductances than in active neurons with high conductance. This may explain why both the immediate effects and after-effects of brain stimulation are smaller or even reversed during voluntary activity compared with rest. Membrane conductance is also increased during shunting inhibition, which accompanies the classic GABAA IPSP. This short-circuits nearby EPSPs and is suggested here to contribute to the magnitude and time course of short-interval intracortical inhibition and intracortical facilitation. [ABSTRACT FROM AUTHOR]

We recently showed that subcortical circuits contribute to control the gain of motor cortical inputs to spinal motoneurons during precision grip of a small object. Here, we examine whether the involvement of the motor cortex could be revealed by grasping with different hand postures. Using noninvasive cortical, cervicomedullary, and peripheral nerve stimulation we examined in humans motorevoked potentials (MEPs) and the activity in intracortical circuits (suppression of voluntary electromyography) and spinal motoneurons (F-waves) in intrinsic hand muscles when graspinga6mm cylinder with the index finger and thumb while the hand was held in the neutral position or during full pronation and supination. We demonstrate that the size of cortically evoked MEPs in the first dorsal interosseous, but not in the abductor pollicis brevis and abductor digit minimi muscles, was reduced to a similar extent during grasping with the hand pronated or supinated compared with the neutralposition. Notably, the suppression of MEPs was present from the MEP onset, suggesting that indirect corticospinal pathways were less likely to be involved than direct connections. There was less intracortical inhibition targeting the first dorsal interosseous during hand pronation and supination compared with neutral and this negatively correlated with changes in MEP size. In contrast, cervicomedullary MEPs and F-waves remained unchanged across conditions, as did MEPs evoked during unopposed weak flexion of the index finger. Our findings reveal a distinct influence of the posture of the hand on the activity of cortical pathways controlling different hand muscles during grasping. [ABSTRACT FROM AUTHOR]

A number of methods have been developed recently that stimulate the human brain non-invasively through the intact scalp. The most common are transcranial magnetic stimulation (TMS), transcranial electric stimulation (TES) and transcranial direct current stimulation (TDCS). They are widely used to probe function and connectivity of brain areas as well as therapeutically in a variety of conditions such as depression or stroke. They are much less focal than conventional invasive methods which use small electrodes placed on or in the brain and are often thought to activate all classes of neurones in the stimulated area. However, this is not true. A large body of evidence from experiments on the motor cortex shows that non-invasive methods of brain stimulation can be surprisingly selective and that adjusting the intensity and direction of stimulation can activate different classes of inhibitory and excitatory inputs to the corticospinal output cells. Here we review data that have elucidated the action of TMS and TES, concentrating mainly on the most direct evidence available from spinal epidural recordings of the descending corticospinal volleys. The results show that it is potentially possible to test and condition specific neural circuits in motor cortex that could be affected differentially by disease, or be used in different forms of natural behaviour. However, there is substantial interindividual variability in the specificity of these protocols. Perhaps in the future it will be possible, with the advances currently being made to model the electrical fields induced in individual brains, to develop forms of stimulation that can reliably target more specific populations of neurones, and open up the internal circuitry of the motor cortex for study in behaving humans. [ABSTRACT FROM AUTHOR]

Highlights: [•] We evaluated if inhibitory modulation of stroke hemisphere can enhance recovery. [•] We found no deleterious effects of inhibitory stimulation on recovery. [•] All patients showed some improvement from a retraining protocol for the upper limb. [•] Inhibition of stroke hemisphere is safe and has the potential to enhance recovery. [ABSTRACT FROM AUTHOR]

Sensory and motor systems interact closely during movement performance. Furthermore, proprioceptive feedback from ongoing movements provides an important input for successful learning of a new motor skill. Here, we show in humans that attention to proprioceptive input during a purely sensory task can influence subsequent learning of a novel motor task. We applied low-amplitude vibration to the abductor pollicis brevis (APB) muscle of eight healthy volunteers for 15 min while they discriminated either a small change in vibration frequency or the presence of a simultaneous weak cutaneous stimulus. Before and after the sensory attention tasks, we evaluated the following in separate experiments: (1) sensorimotor interaction in the motor cortex by testing the efficacy of proprioceptive input to reduce GABAAergic intracortical inhibition using paired-pulse transcranial magnetic stimulation, and (2) how well the same subjects learned a ballistic thumb abduction task using the APB muscle. Performance of the vibration discrimination task increased the interaction of proprioceptive input with motor cortex excitability in the APB muscle, whereas performance in the cutaneous discrimination task had the opposite effect. There was a significant correlation between the integration of proprioceptive input in the motor cortex and the motor learning gain: increasing the integration of proprioceptive input from the APB increased the rate of motor learning and reduced performance variability, while decreasing proprioceptive integration had opposite effects. These findings suggest that the sensory attention tasks transiently change how proprioceptive input is integrated into the motor cortex and that these sensory changes drive subsequent learning behavior in the human motor cortex. [ABSTRACT FROM AUTHOR]

Abstract: Transcranial magnetic stimulation is increasingly used as a tool to explore cortical motor function in healthy subjects and in patients with neurological disease or injury. This review describes a “twin coil” TMS approach that allows investigation of time related changes in functional connectivity between primary motor cortex and other areas in preparation for a forthcoming movement. Investigations into premotor–motor interactions show that these are specific to the type of task that is performed as well as the muscles used to control the movement, allowing us to monitor information flow within motor networks with millisecond time resolution. [Copyright &y& Elsevier]

The past 25 years have seen a resurgence of interest in the basal ganglia. In the 1980s, a series of studies yielded the now classic descriptions of basal ganglia connectivity and information flow that now dominates textbook descriptions. This was followed by the appearance of reward-based learning theories of corticostriatal function in which dopamine played a critical role in modulating corticostriatal connectivity. These advances have contributed enormously to our understanding of the basic principles of some of the circuits within these structures, and have dominated novel approaches to treatment of basal ganglia diseases. Yet even so, many of the common symptoms of Parkinson's disease or dystonia are incompletely understood, suggesting that these "dark basements of the brain" still harbor hidden secrets. [ABSTRACT FROM AUTHOR]

Levodopa-induced dyskinesia is a major complication of long-term dopamine replacement therapy for Parkinson’s disease that becomes increasingly problematic in advanced Parkinson’s disease. Although the cause of levodopa-induced dyskinesias is still unclear, recent work in animal models of the corticostriatal system has suggested that levodopa-induced dyskinesias might result from abnormal control of synaptic plasticity. In the present study, we aimed to explore control of plasticity in patients with Parkinson’s disease with and without levodopa-induced dyskinesias by taking advantage of a newly developed protocol that tests depotentiation of pre-existing long-term potentiation-like synaptic facilitation. Long-term potentiation-like plasticity and its reversibility were studied in the motor cortex of 10 healthy subjects, 10 patients with Parkinson’s disease and levodopa-induced dyskinesias, who took half of the regular dose of levodopa and 10 patients with Parkinson’s disease without levodopa-induced dyskinesias, who took either half or the full dose of levodopa. Patients with Parkinson’s disease without levodopa-induced dyskinesias had normal long-term potentiation- and depotentiation-like effects when they took their full dose of levodopa, but there was no long-term potentiation-like effect when they were on half dose of levodopa. In contrast, patients with levodopa-induced dyskinesias could be successfully potentiated when they were on half their usual dose of levodopa; however, they were unresponsive to the depotentiation protocol. The results suggest that depotentiation is abnormal in the motor cortex of patients with Parkinson’s disease with levodopa-induced dyskinesias and that their long-term potentiation-like plasticity is more readily affected by administration of levodopa than their clinical symptoms. [ABSTRACT FROM AUTHOR]

Repetitive transcranial magnetic stimulation paradigms such as continuous theta burst stimulation (cTBS) induce long-term potentiation- and long-term depression-like plasticity in the human motor cortex. However, responses to cTBS are highly variable and may depend on the activity of the cortex at the time of stimulation. We investigated whether power in different electroencephalogram (EEG) frequency bands predicted the response to subsequent cTBS, and conversely whether cTBS had after-effects on the EEG. cTBS may utilize similar mechanisms of plasticity to motor learning; thus, we conducted a parallel set of experiments to test whether ongoing electroencephalography could predict performance of a visuomotor training task, and whether training itself had effects on the EEG. Motor evoked potentials (MEPs) provided an index of cortical excitability pre- and post-intervention. The EEG was recorded over the motor cortex pre- and post-intervention, and power spectra were computed. cTBS reduced MEP amplitudes; however, baseline power in the delta, theta, alpha or beta frequencies did not predict responses to cTBS or learning of the visuomotor training task. cTBS had no effect on delta, theta, alpha or beta power. In contrast, there was an increase in alpha power following visuomotor training that was positively correlated with changes in MEP amplitude post-training. The results suggest that the EEG is not a useful state-marker for predicting responses to plasticity-inducing paradigms. The correlation between alpha power and changes in corticospinal excitability following visuomotor training requires further investigation, but may be related to disengagement of the somatosensory system important for motor memory consolidation. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Theta burst stimulation, a form of repetitive transcranial magnetic stimulation, can induce lasting changes in corticospinal excitability that are thought to involve long-term potentiation/depression (LTD/LTD)-like effects on cortical synapses. The pattern of delivery of TBS is crucial in determining the direction of change in synaptic efficiency. Previously we explained this by postulating (1) that a single burst of stimulation induces a mixture of excitatory and inhibitory effects and (2) those effects may cascade to produce long-lasting effects. Here we formalise those ideas into a simple mathematical model. Methods: The model is based on a simplified description of the glutamatergic synapse in which post-synaptic Ca2+ entry initiates processes leading to different amount of potentiation and depression of synaptic transmission. The final effect on the synapse results from summation of the two effects. Results: The model using these assumptions can fit reported data. Metaplastic effects of voluntary contraction on the response to TBS can be incorporated by changing time constants in the model. Conclusions: The pattern-dependent after-effects and interactions with voluntary contraction can be successfully modelled by using reasonable assumptions about known cellular mechanisms of plasticity. Significance: The model could provide insight into development of new plasticity induction protocols using TMS. [Copyright &y& Elsevier]

A number of experiments in animals have shown that successful induction of plasticity can be abolished if an individually ineffective intervention is given shortly afterwards. Such effects are termed depotentiation/de-depression. These effects contrast with metaplasticity/homeostatic plasticity in which pretreatment of the system with one protocol modulates the response to a second plasticity-inducing protocol. Homeostatic plasticity maintains the balance of plasticity in the nervous system at a stable level whereas depotentiation/de-depression abolishes synaptic plasticity that has just occurred in order to prevent ongoing learning. In the present study, we developed novel protocols to explore the reversal of LTP- and LTD-like effects in healthy conscious humans based on the recently developed theta burst form of repetitive transcranial magnetic stimulation (TBS). The potentiation effect induced by intermittent TBS (iTBS) was completely erased by a short form of continuous TBS (cTBS150) given 1 min after iTBS, whereas the depressive effect of continuous TBS (cTBS) was successfully abolished by a short form of iTBS (iTBS150). The reversal was specific to the nature of the second protocol and was time dependent since it was less effective when the intervention was given 10 min after induction of plasticity. All these features are compatible with those of depotentiation and de-depression demonstrated in animal studies. The development of the present protocols would be helpful to study the physiology of the reversal of plasticity and learning and to probe the abnormal depotentiation/de-depression shown in animal models of neurological diseases (e.g. Parkinson's disease with dyskinesia, dystonia and Huntingon's disease). [ABSTRACT FROM AUTHOR]

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive method of stimulating the brain that changes excitability at the site of stimulation as well as at distant anatomically connected sites. Since the effects can outlast the period of stimulation for minutes or hours and are thought to be depend, at least in part, on changes in the efficiency of synaptic connections in the cortex, the method has generated much interest as a potential therapeutic intervention in a wide range of neurological and psychiatric conditions. A symposium on brain stimulation and brain recovery was held in Greifswald (Germany) in 2010 to exchange of state-of-the-art knowledge about rTMS effects from animal experiments to clinical trials in conditions such as stroke, Parkinson disease, and depression. There was enormous interest in the effects of rTMS and signs of therapeutic success in mainly small clinical trials. However, it was also clear that some of our models of the effects of rTMS, such as upregulation or downregulation of specific brain areas may need further development if they are to account for all the observations that have been made so far. The results of the symposium are made available by lab reviews of members of the symposium's faculty. This editorial provides an overview. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Low-frequency (⩽1Hz) rTMS (LF-rTMS) can reduce excitability in the underlying cortex and/or promote inhibition. In patients with Parkinson’s disease (PD) several TMS elicited features of motor corticospinal physiology suggest presence of impaired inhibitory mechanisms. These include shortened silent period (SP) and slightly steeper input–output (I–O) curve of motor evoked potential (MEP) size than in normal controls. However, studies of LF-rTMS effects on inhibitory mechanisms in PD are scarce. In this companion paper to the clinical paper describing effects of four consecutive days of LF-rTMS on dyskinesia in PD (), we evaluate the delayed (24h) effects of the LF-rTMS treatment on physiological measures of excitability of the motor cortex in the same patients. There are very few studies of physiological follow up of daily rTMS treatments. Methods: Nine patients with PD in Hoehn and Yahr stages 2 or 3 and prominent medication-induced dyskinesia were studied. This was a placebo-controlled, crossover study, with two treatment arms, “real” rTMS and “sham” rTMS (placebo). In each of the treatment arms, rTMS (1800 pulses; 1Hz rate; intensity of the real stimuli just-below the active motor threshold) was delivered over the motor cortex for four consecutive days. Motor cortex excitability was evaluated at the beginning of the study and the next day following each of the four-day rTMS series (real and sham) with patients first in the practically defined “off” state, following 12h withdrawal of medication, and subsequently in a typical “on” state following usual morning medication dose. Results: The SP was significantly longer following real rTMS in comparison to both baseline and sham rTMS. The effect was independent from the effects of dopaminergic treatment. There was no difference in MEP size, rest and active motor threshold. The I–O curve, recorded from the relaxed muscle, showed a trend towards diminished slope in comparison to baseline, but the difference was not significant. There was no consistent correlation between prolongation of SP and concomitant reduction in dyskinesia following real rTMS. Conclusions: Low-frequency rTMS delivered over several consecutive days changes the excitability of motor cortex by increasing the excitability of inhibitory circuits. The effects persist for at least a day after rTMS. Significance: The results confirm the existence of a residual after-effect of consecutive daily applications of rTMS that might be relevant to the clinical effect that was observed in this group of patients and could be further exploited for potential therapeutic uses. [Copyright &y& Elsevier]

To clarify the rationale for using rTMS of dorsal premotor cortex (PMd) to treat dystonia, we examined how the motor system reacts to an inhibitory form of rTMS applied to the PMd in healthy subjects and in a group of patients with focal hand dystonia and DYT1 gene carriers. Continuous theta burst transcranial magnetic stimulation (cTBS) with 300 and 600 pulses (cTBS300 and cTBS600) was applied to PMd, and its after-effects were quantified by measuring the amplitude of MEPs evoked by single pulse transcranial magnetic stimulation (TMS) over the primary motor cortex (M1), short interval intracortical inhibition/facilitation (SICI/ICF) within M1, the third phase of spinal reciprocal inhibition (RI), and writing tests. In addition, in DYT1 gene carriers, the effects of cTBS300 over M1 and PMd on MEPs were studied in separate experiments. In healthy subjects, cTBS300 and cTBS600 over PMd suppressed MEPs for 30 min or more and cTBS600 decreased SICI and RI. In contrast, neither form of cTBS over PMd had any significant effect on MEPs, while cTBS600 increased effectiveness of SICI and RI and improved writing in patients with writer's cramp. NMDYT1 had a normal response to cTBS300 over left PMd. We suggest that the reduced PMd to M1 interaction in dystonic patients is likely to be due to reduced excitability of PMd-M1 connections. The possible therapeutic effects of premotor rTMS may therefore involve indirect effects of PMd on SICI and RI, which this study has shown can be normalised by cTBS. © 2010 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Abstract: Repetitive transcranial magnetic stimulation (rTMS) can modulate cortical excitability and activation and consequently may affect clinical symptoms in neurological conditions characterized by altered motor cortex functions. There are conflicting reports whether low-frequency rTMS has any clinical effects in Parkinson''s disease (PD). Ten patients with PD had rTMS (1800 stimuli at just below active motor threshold intensity) at 1Hz rate delivered over the motor cortex for four consecutive days on two separate occasions. On one of these real rTMS was used and on the other sham rTMS (placebo) was used. Evaluations with UPDRS Part 3 (Motor Scale) were done in practically defined off-phase at the baseline and one day after the end of each of the treatment series. Neither total Motor Scale scores nor subscores for axial symptoms, rigidity, bradykinesia, and tremor showed any significant difference. The results do not confirm presence of residual beneficial clinical after-effects of consecutive daily applications of low-frequency rTMS on motor symptoms in PD, at least when 1800 stimuli at subthreshold intensity are applied for four days. [Copyright &y& Elsevier]

Summary: The cortical visuomotor grasping circuit, comprising the anterior intraparietal area (AIP), ventral premotor (PMv), and primary motor cortex (M1) allows transformation of an object''s physical properties into a suitable motor command for grasp . However, little is known about how AIP contributes to the processing of grasp-related information conveyed through the cortical grasping circuit. We addressed this by studying the consequences of AIP “virtual lesions” on physiological interactions between PMv and M1 at rest or during preparation to grasp objects with either a precision grip or a whole-hand grasp. We used a conditioning-test transcranial magnetic stimulation (TMS) paradigm to test how PMv-M1 interactions were modified by disrupting AIP function with theta-burst TMS (cTBS) . At rest, AIP virtual lesions did not modify PMv-M1 interactions. In contrast, the usual muscle-specific PMv-M1 interactions that appeared during grasp preparation were significantly reduced following AIP cTBS without directly modifying corticospinal excitability. Behaviorally, disruption of AIP was also associated with a relative loss of the grasp-specific pattern of digit muscle activity. These findings suggest that grasp-related and muscle-specific PMv-M1 interactions are driven by information about object properties provided by AIP. [Copyright &y& Elsevier]

Abstract: Transcranial magnetic stimulation (TMS) can be used in two different ways to investigate the contribution of cortical areas involved in grasp/reach movements in humans. It can produce “virtual lesions” that interfere with activity in particular cortical areas at specific times during a task, or it can be used in a twin coil design to test the excitability of cortical projections to M1 at different times during a task. The former method has described how cortical structures such as the ventral premotor cortex (PMv), dorsal premotor cortex (PMd) and the anterior intraparietal sulcus (aIPS) are important for specific aspects of reaching, grasping and lifting objects. In the latter method, a conditioning stimulus (CS) is first used to activate putative pathways to the motor cortex from, for example, posterior parietal cortex (PPC) or PMd, while a second, test stimulus (TS), delivered over the primary motor cortex a few ms later probes any changes in excitability that are produced by the input. Thus changes in the effectiveness of the conditioning pulse give an indication of how the excitability of the connection changes over time and during a specific task. Here we review studies describing the time course of operation of parallel intracortical circuits and cortico-cortical connections between the PMd, PMv, PPC and M1, thus demonstrating that functional interplay between these areas and the primary motor cortices is not fixed, but can change in a highly task-, condition- and time-dependent manner. [Copyright &y& Elsevier]

Abstract: Objective: To understand the effect of continuous theta burst stimulation (cTBS) given to the premotor area, we studied the circuits within the primary motor cortex and spinal cord after cTBS over the dorsal premotor area (PMd). Methods: Three sets of parameters, including corticospinal excitability, short interval intracortical inhibition (SICI) and intracortical facilitation (ICF) and forearm reciprocal inhibition (RI) were tested. Results: Paralleling the effects of cTBS applied directly to the primary motor cortex, cTBS over the left PMd suppressed corticospinal excitability as measured by the change in the size of MEPs evoked by single pulse TMS over primary motor cortex. Premotor cTBS appeared to have a longer lasting, but no more powerful effect on corticospinal excitability than motor cTBS, however, unlike motor cTBS it had no effect on SICI or ICF. Finally, although premotor cTBS had no effect on spinal H-reflexes, it did reduce the third phase of RI between forearm extensor and flexor muscles. Conclusions: Premotor cTBS is a quick and useful way of modulating excitability in cortical and possibly subcortical motor circuits. Significance: Premotor cTBS can be used as an alternative to regular rTMS to evaluate cortical function, motor behaviours and the response to disease therapy. [Copyright &y& Elsevier]

In a placebo-controlled, single-blinded, crossover study, we assessed the effect of 'real' repetitive transcranial magnetic stimulation (rTMS) versus 'sham' rTMS (placebo) on peak dose dyskinesias in patients with Parkinson's disease (PD). Ten patients with PD and prominent dyskinesias had rTMS (1,800 pulses; 1 Hz rate) delivered over the motor cortex for 4 consecutive days twice, once real stimuli and once sham stimulation were used; evaluations were done at the baseline and 1 day after the end of each of the treatment series. Direct comparison between sham and real rTMS effects showed no significant difference in clinician-assessed dyskinesia severity. However, comparison with the baseline showed small but significant reduction in dyskinesia severity following real rTMS but not placebo. The major effect was on dystonia subscore. Similarly, in patient diaries, although both treatments caused reduction in subjective dyskinesia scores during the days of intervention, the effect was sustained for 3 days after the intervention for the real rTMS only. Following rTMS, no side effects and no adverse effects on motor function and PD symptoms were noted. The results suggest the existence of residual beneficial clinical aftereffects of consecutive daily applications of low-frequency rTMS on dyskinesias in PD. The effects may be further exploited for potential therapeutic uses. © 2008 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Deep brain stimulation (DBS) of globus pallidus internus (GPi) has emerged as an effective treatment for primary generalized dystonia. However, the physiological mechanisms of improvement are not fully understood. Cortical activity in response to pallidal stimulation was recorded in 6 patients with primary generalized dystonia >6 months after bilateral GPi DBS. Scalp electroencephalogram was recorded using 60 surface electrodes during 10 Hz bipolar pallidal DBS at each electrode contact pair. Anatomical position of the electrode contacts in relation to the GPi, medial medullary lamina and globus pallidus externus (GPe) was determined from the postoperative stereotactic MRI. In all six patients an evoked potential (EP) was observed with average onset latency of 10.9 ms ± 0.77, peak latency 26.6 ms ± 1.6, distributed mainly over the ipsilateral hemisphere, maximal centrally. The mean amplitude of this potential was larger with stimulation in posteroventral GPi than in GPe (3.36 μV vs. 0.50 μV, P < 0.0001). The EP was absent in one patient-side, ipsilateral to a previous thalamotomy. Low frequency GPi stimulation produces an EP distributed centrally over the ipsilateral hemisphere. The latency and distribution of the EP are consistent with stimulation of pallidothalamic neurons projecting to the sensorimotor cortex. Because the EP is larger and more consistently present with stimulation of posteroventral GPi than GPe, it may provide a physiological tool to identify contacts within the optimal surgical target. © 2007 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Abstract: Objective: To study the modulation of somatosensory evoked potentials (SEP) using transcranial magnetic intermittent theta burst stimulation (iTBS) over human primary motor (M1) and sensory (S1) cortices. Methods: Eleven healthy subjects participated in the study. Median nerve SEP were elicited by electrical stimulation at the right wrist before and after 600-pulse iTBS over M1 or S1 of the left hemispheres at the intensity of 80% active motor threshold. Results: iTBS over S1 facilitated the N20o–N20p, N20p–P25 and P25–N33 amplitudes significantly and the maximal effect appeared 15min after the stimulation. The facilitating effect was observed when the initial phase of the current in the brain was directed antero-medially, whereas the facilitation did not appear when the inverted coil direction was applied. On the other hand, no changes were observed after iTBS over M1. The latencies of the measured onsets and peaks were not affected through the experiments. Conclusions: iTBS over S1 has the facilitating effect on the central somatosensory pathway, and the position and direction of the coil are the determinant factors of the effects. Significance: iTBS can be useful technique to induce synaptic plasticity in human central somatosensory pathway. [Copyright &y& Elsevier]

Abstract: Objective: To determine the effect of globus pallidus internus (GPi) deep brain stimulation (DBS) on motor cortex plasticity in patients with primary generalised dystonia. Methods: We studied 10 patients with primary generalised dystonia (5 DYT1+, 5 idiopathic, 5 female, mean age 42) following GPi DBS and 10 healthy subjects. Motor cortex plasticity was assessed using transcranial magnetic stimulation (TMS) paired associative stimulation (PAS) of motor cortex and median nerve, a method which has been shown in healthy subjects to produce LTP-like effects. Thresholds and TMS intensity to produce a resting motor evoked potential (MEP) of 1 mV were determined. Resting MEP amplitude and stimulus response curves were recorded before and after PAS. Patients were recorded ON and OFF DBS in separate sessions. Results: The mean TMS intensity to produce a resting MEP of 1 mV was 54% of maximum stimulator output when OFF and 52% ON DBS. Fifteen minutes after PAS the resting MEP amplitude increased in patients OFF DBS and in control subjects whereas it decreased in patients ON DBS. Similarly, after PAS, the mean amplitude of the stimulus response curve increased OFF DBS, but this effect was abolished with DBS ON. Furthermore, patients who had the largest clinical response to chronic DBS also had the largest difference in the effect of PAS with DBS ON vs. OFF. Conclusions: After PAS, patients with primary generalised dystonia showed a similar pattern of increased motor cortex excitability as healthy subjects when GPi DBS was OFF but not with GPi DBS ON. These results suggest that GPi DBS may reduce LTP-like motor cortex plasticity, which could contribute to its mechanism of action in dystonia. [Copyright &y& Elsevier]

Repetitive transcranial magnetic stimulation (rTMS) has in recent years been used to explore therapeutic opportunities in a bewildering variety of conditions. Although there is good evidence that this technique can modify cortical activity, the rationale for its use in many of the conditions investigated so far is not clear. Here we discuss the effects of rTMS in healthy subjects and how it has been used in a number of neurological conditions. We argue that a better understanding of both the effects of rTMS and the pathological processes underlying the conditions for which it is used will reveal whether rTMS really does offer therapeutic potential and, if so, for which conditions. [ABSTRACT FROM AUTHOR]

Background: Repeated sessions of repetitive transcranial magnetic stimulation (rTMS) over motor cortex have been reported to produce significant improvement of motor performance in patients with Parkinson's disease (PD). In addition, it is known that a single session of rTMS over motor cortex transiently increases DA in striatum. Here, we test whether repeated sessions of rTMS increase serum dopamine in PD patients and whether this correlates with changes in clinical rating scales. Material and Methods: Twenty untreated PD patients with moderate to severe symptoms (Hoehn & Yahr stage III-V 1967) were assessed on the Unified Parkinson's Disease Rating Scale (UPDRS), and with an enzyme immunoassay for quantitative determination of plasma dopamine before and after six daily sessions of 25 Hz rTMS with 3,000 stimuli over the right and left hand and leg motor cortex. Results: There was significant improvement in UPDRS compared with the baseline. Serum dopamine level also was significantly elevated ever the same interval. There was a significant correlation between UPDRS and serum dopamine level before and after treatment. Conclusion: Improved motor performance in PD after repeated sessions of rTMS may be related to an elevation of serum dopamine concentration. © 2007 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Abstract: Objective: To investigate the effect of high frequency rTMS (25Hz at 90–100% of resting motor threshold) on the excitability of the motor cortex of healthy human subjects. Methods: Resting and active motor threshold, MEP recruitment curve (I/O curve), short interval intracortical inhibition (SICI) and facilitation (ICF), and the duration of the silent period (SP) were tested in the right first dorsal interosseous muscle (FDI) before and twice after the end of 1500 pulses in 16 normal young adult male volunteers. Results: Twenty-five Hertz rTMS decreased motor thresholds, reduced the duration of the silent period and had a tendency to increase the slope of the I/O curve. Most of these effects lasted for the duration of the two post-testing sessions (at least 30min) and had returned to normal by 2h. There were no significant effects on SICI/ICF. Conclusion: Twenty-five Hertz rTMS can produce a long lasting increase in cortical excitability in healthy subjects. Significance: This method may prove useful for the study of normal human physiology and for therapeutic manipulation of brain plasticity. [Copyright &y& Elsevier]

Previous studies in patients with Parkinson's disease have reported that a single session of repetitive transcranial magnetic stimulation (rTMS) can improve some or all of the motor symptoms for 30 to 60 minutes. A recent study suggested that repeated sessions of rTMS lead to effects that can last for at least 1 month. Here we report data that both confirm and extend this work. Fifty-five unmedicated PD patients were classified into four groups: two groups (early and late PD) received 25 Hz rTMS bilaterally on the motor arm and leg areas; other groups acted as control for frequency (10 Hz) and for site of stimulation (occipital stimulation). All patients received six consecutive daily sessions (3,000 pulses for each session). The first two groups then received a further three booster sessions (3 consecutive days of rTMS) after 1, 2, and 3 months, while the third group had only one additional session after the first month. Unified Parkinson's Disease Rating Scale (UPDRS), walking time, key-tapping speed, and self-assessment scale were measured for each patient before and after each rTMS session and before and after the monthly sessions. Compared to occipital stimulation, 25 Hz rTMS over motor areas improved all measures in both early and late groups; the group that received 10 Hz rTMS improved more than the occipital group but less than the 25 Hz groups. The effect built up gradually during the sessions and was maintained for 1 month after, with a slight reduction in efficacy. Interestingly, the effect was restored and maintained for the next month by the booster sessions. We conclude that 25 Hz rTMS can lead to cumulative and long-lasting effects on motor performance. © 2006 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Human swallowing involves the integration of sensorimotor information with complexities such as taste; however, the interaction between the taste of food and its effects on swallowing control remains unknown. We assessed the effects of pleasant (sweet) and aversive (bitter) tastes on human cortical swallowing motor pathway excitability. Healthy adult male volunteers underwent a transcranial magnetic stimulation (TMS) mapping study (n = 9, mean age: 34 yr) to assess corticobulbar excitability before and up to 60 mm after 10-min liquid infusions either 1) as swallowing tasks or 2) delivered directly into the stomach. Infusions were composed of sterile water (neutral), 10% glucose (sweet), and 0.5 mM quinine hydrochloride (bitter). The order of delivery was randomized, and each infusion was given on separate days. Pharyngeal motor-evoked potentials (PMEPs) were recorded from an intraluminal catheter as a measure of corticobulbar excitability and compared using repeated-measures and one-way ANOVA. After the swallowing task (water, glucose, or quinine), repeated-measures ANOVA revealed a significant time interaction across tastants (P ≤= 0.01). One-way ANOVA for each taste showed changes in PMEP amplitudes for both quinine (P ≤= 0.001) and glucose (P ≤ 0.009) solutions but not for water (P = 0.1). Subsequent t-tests showed that glucose and quinine reduced PMEPs by 47% (SD 34) and 37% (SD 54), respectively, at 30 mm (P ≤= 0.03). No changes were. observed after the infusion of any solution directly into the stomach (P = 0.51). In conclusion, cortical swallowing pathways are similarly modulated by both sweet and bitter tasting stimuli. Changes likely reflect a close interaction between taste and swallowing activity mediated in the central nervous system. [ABSTRACT FROM AUTHOR]

Several experimental protocols induce lasting changes in the excitability of motor cortex. Some involve direct cortical stimulation, others activate the somatosensory system and some combine motor and sensory stimulation. The effects usually are measured as changes in amplitude of the motor-evoked-potential (MEP) or short-interval intracortical inhibition (SICI) elicited by a single or paired pulses of transcranial magnetic stimulation (TMS). Recent work has also tested sensorimotor organization within the motor cortex by recording MEPs and SICI during short periods of vibration applied to single intrinsic hand muscles. Here sensorimotor organization is focal: MEPs increase and SICI decreases in the vibrated muscle, whilst the opposite occurs in neighbouring muscles. In six volunteers we compared the after effects of three protocols that lead to lasting changes in cortical excitability: (i) paired associative stimulation (PAS) between a TMS pulse and an electrical stimulus to the median nerve; (ii) motor practice of rapid thumb abduction; and (iii) sensory input produced by semicontinuous muscle vibration, on MEPs and SICI at rest and on the sensorimotor organization. PAS increased MEP amplitudes, whereas vibration changed sensorimotor organization. Motor practice had a dual effect and increased MEPs as well as affecting sensorimotor organization. The implication is that different protocols target different sets of cortical circuits. We speculate that protocols that involve repeated activation of motor cortical output lead to lasting changes in efficacy of synaptic connections in output circuits, whereas protocols that emphasize sensory inputs affect the strength of sensory inputs to motor circuits. [ABSTRACT FROM AUTHOR]

Sensory input can remodel representations in the sensory cortex, and this effect is heavily influenced by attention to the stimulus. Here we ask whether pure sensory input can also influence the spatial distribution of sensory effects on motor cortical hand area (sensorimotor organization) and whether this is modulated by attention. Sensorimotor organization was tested by applying short (1.5 s) periods of low amplitude vibration to single intrinsic hand muscles and measuring motor cortex excitability with transcranial magnetic stimulation (TMS). In healthy subjects, sensorimotor organization in the hand is focal, with input from one hand muscle increasing motor-evoked potentials (MEPs), decreasing short and increasing long-interval intracortical inhibition (SICI and LICI) in the vibrated muscle (‘homotopic’ effects) and having opposite effects on neighbouring muscles (‘heterotopic’ effects). Here we show that a 15 min intervention of vibration applied simultaneously to two hand muscles can lead to long-term (>30 min) changes in the spatial pattern of sensorimotor interaction. The amount and direction of the effects depended on the subject's attention during the intervention: if subjects attended to both muscles when they were receiving simultaneous vibration, subsequent short-term vibration applied to one of them produced‘homotopic’ effects onbothmuscles.‘Heterotopic’ effects on a muscle not vibrated during the intervention were unaffected. If subjects did not attend to simultaneous vibration, subsequent short-term vibration of the muscles involved in the intervention no longer had any effect on them although the‘heterotopic’ effects on a muscle not involved in the intervention were unchanged. We conclude that a 15 min period of pure sensory input can remodel the way that subsequent sensory inputs interact with motor output, that the effects are specific for the motor output to muscles involved in the intervention and that they are modulated by the subject's attention. [ABSTRACT FROM AUTHOR]

Objective: To test whether the after effects of 5 Hz focal rTMS over the primary motor cortex are modulated by the state of muscle contraction when the rTMS is applied.Methods: Ten healthy volunteers gave informed consent to the studies. Fifty stimuli at active motor threshold intensity were applied at 5 Hz to the forearm motor area during 10% MVC isometric wrist flexion, 10% MVC wrist extension and at rest. Short interval intracortical inhibition (SICI: interstimulus intervals of 2–5 ms) and intracortical facilitation (interstimulus intervals of 7 and 10 ms) were recorded at rest before and after rTMS from flexor carpi radialis (FCR) and extensor carpi radialis (ECR) muscles with surface electrodes.Results: rTMS during wrist flexion decreased SICI in the FCR whereas SICI was increased if rTMS was given during wrist extension. The opposite was true in ECR: SICI was increased if rTMS was applied during wrist flexion, whereas it was reduced if rTMS was given during wrist extension. rTMS applied at rest produced a small overall decrease of SICI in FCR and ECR but this was not individually significant in the FCR. The 10 s wrist flexion without any rTMS did not have any effect on SICI.Conclusions: The after effects of motor cortex rTMS can be selectively modulated by the pattern of muscle contraction. [Copyright &y& Elsevier]

Objective: To explore the effect of applying a short burst of high-frequency repetitive transcranial magnetic stimulation (rTMS) to the human motor cortex as a preparatory investigation before attempting theta burst stimulation in humans.Methods: Five or15 pulses of 50 Hz rTMS were given at 50–80% active motor threshold (AMT). The time course of changes in motor-evoked potential (MEP) size and short interval intracortical inhibition (SICI) were evaluated from 20 to 300 ms after the end of each burst in the relaxed first dorsal interosseous muscle of 15 healthy volunteers.Results: No subjects noted any adverse effects. MEPs were enhanced and SICIs were reduced at 20 ms after a burst of either 5 or 15 pulses at 70 or 80% AMT, but not at 50% AMT. Subsequent experiments used a 5 pulse burst at 80% AMT. The threshold for producing SICI increased from 60 to 80% AMT when tested 10 or 20 ms after the end of the burst. MEPs were enhanced for 100 ms, whereas SICI was reduced for 200–300 ms.Conclusions: A short burst of low-intensity 50 Hz rTMS over the hand motor area transiently increases MEP amplitude with a longer lasting decrease in SICI.Significance: This means that it may be possible in future experiments to apply theta burst conditioning safely to the human cortex. [Copyright &y& Elsevier]

For many years pathophysiological studies on patients with movement disorders were viewed as inferior to those in animal models because, given the complexity of dealing with the complete interconnected CNS, it was difficult to assign any particular physiological abnormality exclusively to the site of a known lesion. More recently this has come to be seen as an advantage. All the articles reviewed below focus on how healthy parts of the CNS react to damage at a distance, with the result that we are now beginning to have much more insight into how these reactions both compensate and exacerbate the primary deficit. [Copyright &y& Elsevier]

When saccading to a silent clock, observers sometimes think that the second hand has paused momentarily. This effect has been termed chronostasis and occurs because observers overestimate the time that they have seen the object of an eye movement . They seem to extrapolate its appearance back to just prior to the onset of the saccade rather than the time that it is actually fixated on the retina. Here, we describe a similar effect following an arm movement: subjects overestimate the time that their hand has been in contact with a newly touched object. The illusion''s magnitude suggests backward extrapolation of tactile perception to a moment during the preceding reach. The illusion does not occur if the arm movement triggers a change in a continuously visible visual target: the time of onset of the change is estimated correctly. We hypothesize that chronostasis-like effects occur when movement produces uncertainty about the onset of a sensory event. Under these circumstances, the time at which neurons with receptive fields that shift in the temporal vicinity of a movement change their mappings may be used as a time marker for the onset of perceptual properties that are only established later. [Copyright &y& Elsevier]

Presents a study that developed a pain-induced model of altered esophageal corticobulbar excitability to understand the relationship between cortical plasticity and visceral pain. Examination of electromyographic responses; Analysis of the esophageal corticobulbar projection; Assessment of the thenar corticospinal projection.

This scientific commentary refers to ‘A network centred on the inferior frontal cortex is critically involved in levodopa-induced dyskinesias’ by Cerasa et al. (doi: 10.1093/brain/awu329). [ABSTRACT FROM AUTHOR]

The cerebellum receives and integrates a large amount of sensory information that is important for motor coordination and learning. The aim of the present work was to investigate whether peripheral nerve and cerebellum paired associative stimulation (cPAS) could induce plasticity in both the cerebellum and the cortex. In a cross-over design, we delivered right median nerve electrical stimulation 25 or 10 ms before applying transcranial magnetic stimulation over the cerebellum. We assessed changes in motor evoked potentials (MEP), somatosensory evoked potentials (SEP), short-afferent inhibition (SAI), and cerebellum-brain inhibition (CBI) immediately, and 30 min after cPAS. Our results showed a significant reduction in CBI 30 minutes after cPAS, with no discernible changes in MEP, SEP, and SAI. Notably, cPAS10 did not produce any modulatory effects on these parameters. In summary, cPAS25 demonstrated the capacity to induce plasticity effects in the cerebellar cortex, leading to a reduction in CBI. This novel intervention may be used to modulate plasticity mechanisms and motor learning in healthy individuals and patients with neurological conditions. [ABSTRACT FROM AUTHOR]

Provides information on the organization and reorganization of human swallowing motor cortex during recovery after stroke. Cortical organization of swallowing based on direct stimulation and lesional data; Cortical representation of human swallowing musculatures using transcranial magnetic stimulation; Mechanisms of dysphagia after unilateral cerebral stroke.

Removal of sensory input can induce changes in cortical motor representation that reverse when sensation is restored. Here we ask whether manipulation of sensory input can induce long-term reorganization in human motor cortex that outlasts the initial conditioning. We report that for at least 30 minutes after pharyngeal stimulation, motor cortex excitability and area of representation for the pharynx increased, while esophagus representation decreased, without parallel changes in the excitability of brainstem-mediated reflexes. Therefore increased sensory input can drive long-term cross-system changes in motor areas of the cerebral cortex, which suggests that sensory stimulation might rehabilitate dysphagia, a frequent consequence of cerebral injury. [ABSTRACT FROM AUTHOR]