The field of neurostimulation of the cerebellum either with transcranial magnetic stimulation (TMS; single pulse or repetitive (rTMS)) or transcranial direct current stimulation (tDCS; anodal or cathodal) is gaining popularity in the scientific community, in particular because these stimulation techniques are non-invasive and provide novel information on cerebellar functions. There is a consensus amongst the panel of experts that both TMS and tDCS can effectively influence cerebellar functions, not only in the motor domain, with effects on visually guided tracking tasks, motor surround inhibition, motor adaptation and learning, but also for the cognitive and affective operations handled by the cerebro-cerebellar circuits. Verbal working memory, semantic associations and predictive language processing are amongst these operations. Both TMS and tDCS modulate the connectivity between the cerebellum and the primary motor cortex, tuning cerebellar excitability. Cerebellar TMS is an effective and valuable method to evaluate the cerebello-thalamo-cortical loop functions and for the study of the pathophysiology of ataxia. In most circumstances, DCS induces a polarity-dependent site-specific modulation of cerebellar activity. Paired associative stimulation of the cerebello-dentato-thalamo-M1 pathway can induce bidirectional long-term spike-timing-dependent plasticity-like changes of corticospinal excitability. However, the panel of experts considers that several important issues still remain unresolved and require further research. In particular, the role of TMS in promoting cerebellar plasticity is not established. Moreover, the exact positioning of electrode stimulation and the duration of the after effects of tDCS remain unclear. Future studies are required to better define how DCS over particular regions of the cerebellum affects individual cerebellar symptoms, given the topographical organization of cerebellar symptoms. The long-term neural consequences of non-invasive cerebellar modulation are also unclear. Although there is an agreement that the clinical applications in cerebellar disorders are likely numerous, it is emphasized that rigorous large-scale clinical trials are missing. Further studies should be encouraged to better clarify the role of using non-invasive neurostimulation techniques over the cerebellum in motor, cognitive and psychiatric rehabilitation strategies.

Objective: Compensatory reorganization of the nigrostriatal system is thought to delay the onset of symptoms in early Parkinson disease (PD). Here we sought evidence that compensation may be a part of a more widespread functional reorganization in sensorimotor networks, including primary motor cortex. Methods:Several neurophysiologic measures known to be abnormal in the motor cortex (M1) of patients with advanced PD were tested on the more and less affected side of 16 newly diagnosed and drug-naive patients with PD and compared with 16 age-matched healthy participants. LTP-like effects were probed using a paired associative stimulation protocol. We also measured short interval intracortical inhibition, intracortical facilitation, cortical silent period, and input/output curves. Results:The less affected side in patients with PD had preserved intracortical inhibition and a larger response to the plasticity protocol compared to healthy participants. On the more affected side, there was no response to the plasticity protocol and inhibition was reduced. There was no difference in input/output curves between sides or between patients with PD and healthy participants. Conclusions:Increased motor cortical plasticity on the less affected side is consistent with a functional reorganization of sensorimotor cortex and may represent a compensatory change that contributes to delaying onset of clinical symptoms. Alternatively, it may reflect a maladaptive plasticity that provokes symptom onset. Plasticity deteriorates as the symptoms progress, as seen on the more affected side. The rate of change in paired associative stimulation response over time could be developed into a surrogate marker of disease progression in PD. Neurology ® 2012;78:1441-1448 GLOSSARY ADM ϭ abductor digiti minimi; AMT ϭ active motor threshold; APB ϭ abductor pollicis brevis; CS ϭ conditioning stimulus; CSP ϭ cortical silent period; DaT ϭ dopamine transporter; I/O ϭ input/output; ICF ϭ intracortical facilitation; ISI ϭ interstimulus interval; LTP ϭ long-term potentiation; MEP ϭ motor evoked potential; PAS ϭ paired associative stimulation; PD ϭ Parkinson disease; RMT ϭ resting motor threshold; SICI ϭ short-latency intracortical inhibition; TMS ϭ transcranial magnetic stimulation; UPDRS ϭ Unified Parkinson's Disease Rating Scale.Motor signs in Parkinson disease (PD) appear when striatal dopamine is depleted beyond a critical threshold of ϳ60%-80%.1 Neuropathologic and neuroimaging evidence suggests that presynaptic and synaptic changes in the nigrostriatal system compensate for dopamine deficiency.1-6 Indeed, given the extent of preclinical dopaminergic denervation, 7 it is conceivable that compensatory changes extend also beyond the nigrostriatal portion of the motor circuit.Patients with clinically asymmetric PD represent a valuable model to study compensatory reorganization within the motor system since functional changes that prevent motor symptom progression are likely to be more evident on the less affected side. A previous [ 18 F]-fluorodeo...

Primary dystonia is thought to be a disorder of the basal ganglia because the symptoms resemble those of patients who have anatomical lesions in the same regions of the brain (secondary dystonia). However, these two groups of patients respond differently to therapy suggesting differences in pathophysiological mechanisms. Pathophysiological deficits in primary dystonia are well characterized and include reduced inhibition at many levels of the motor system and increased plasticity, while emerging evidence suggests additional cerebellar deficits. We compared electrophysiological features of primary and secondary dystonia, using transcranial magnetic stimulation of motor cortex and eye blink classical conditioning paradigm, to test whether dystonia symptoms share the same underlying mechanism. Eleven patients with hemidystonia caused by basal ganglia or thalamic lesions were tested over both hemispheres, corresponding to affected and non-affected side and compared with 10 patients with primary segmental dystonia with arm involvement and 10 healthy participants of similar age. We measured resting motor threshold, active motor threshold, input/output curve, short interval intracortical inhibition and cortical silent period. Plasticity was probed using an excitatory paired associative stimulation protocol. In secondary dystonia cerebellar-dependent conditioning was measured using delayed eye blink classical conditioning paradigm and results were compared with the data of patients with primary dystonia obtained previously. We found no difference in motor thresholds, input/output curves or cortical silent period between patients with secondary and primary dystonia or healthy controls. In secondary dystonia short interval intracortical inhibition was reduced on the affected side, whereas it was normal on the non-affected side. Patients with secondary dystonia had a normal response to the plasticity protocol on both the affected and non-affected side and normal eye blink classical conditioning that was not different from healthy participants. In contrast, patients with primary dystonia showed increased cortical plasticity and reduced eye blink classical conditioning. Normal motor cortex plasticity in secondary dystonia demonstrates that abnormally enhanced cortical plasticity is not required for clinical expression of dystonia, and normal eye blink conditioning suggests an absence of functional cerebellar involvement in this form of dystonia. Reduced short interval intracortical inhibition on the side of the lesion may result from abnormal basal ganglia output or may be a consequence of maintaining an abnormal dystonic posture. Dystonia appears to be a motor symptom that can reflect different pathophysiological states triggered by a variety of insults.

Tremor in inflammatory neuropathies is common, adds to disability and yet does not often respond to treatment of the underlying neuropathy. When present, tremor severity is associated with F wave latency.

We assessed the duration and severity of tremor in a real-life ambulatory setting in patients with psychogenic and organic tremor by actigraphy, and compared this with self-reports of tremor over the same period. Ten participants with psychogenic tremor and eight with organic tremor, diagnosed using standardized clinical criteria, were studied. In an explicit design, participants were asked to wear a small actigraph capable of continuously monitoring tremor duration and intensity for 5 days while keeping a diary of their estimates of tremor duration during the same period. Eight patients with psychogenic tremor and all patients with organic tremor completed the study. Psychogenic patients reported significantly more of the waking day with tremor compared with patients with organic tremor (83.5 ± 14.0% of the waking day versus 58.0 ± 19.0% of the waking day; P < 0.01), despite having almost no tremor recorded by actigraphy (3.9 ± 3.7% of the waking day versus 24.8 ± 7.7% of the waking day; P = 0.001). Patients with organic tremor reported 28% more tremor than actigraphy recordings, whereas patients with psychogenic tremor reported 65% more tremor than actigraphy. These data demonstrate that patients with psychogenic tremor fail to accurately perceive that they do not have tremor most of the day. The explicit study design we employed does not support the hypothesis that these patients are malingering. We discuss how these data can be understood within models of active inference in the brain to provide a neurobiological framework for understanding the mechanism of psychogenic tremor.

Background The natural fluctuation of motor symptoms of Parkinson's disease (PD) makes judgement of any change challenging and the use of clinical scales such as the International Parkinson and Movement Disorder Society (MDS)‐UPDRS imperative. Recently developed commodity mobile communication devices, such as smartphones, could possibly be used to assess motor symptoms in PD patients in a convenient way with low cost. We provide the first report on the development and testing of stand‐alone software for mobile devices that could be used to assess both tremor and bradykinesia of PD patients. Methods We assessed motor symptoms with a custom‐made smartphone application in 14 patients and compared the results with their MDS‐UPDRS scores. Results We found significant correlation between five subscores of MDS‐UPDRS (rest tremor, postural tremor, pronation‐supination, leg agility, and finger tapping) and eight parameters of the data collected with the smartphone. Conclusions These results provide evidence as a proof of principle that smartphones could be a useful tool to objectively assess motor symptoms in PD in clinical and experimental settings.

HighlightsAn electrophysiological study of tremor can be helpful for the diagnosis.A study of hand tremor can be done with surface EMG and an accelerometer.Analysis in the frequency domain allows separating the different tremor components.Coherence analysis shows whether there are one or more oscillators.

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