Somatosensory input in the context of transcranial magnetic stimulation coupled with electroencephalography: An evidence-based overview.

The transcranial evoked potential (TEP) is a powerful technique to investigate brain dynamics, but some methodological issues limit its interpretation. A possible contamination of the TEP by electroencephalographic (EEG) responses evoked by the somatosensory input generated by transcranial magnetic stimulation (TMS) has been postulated; nonetheless, a characterization of these responses is lacking. The aim of this work was to review current evidence about possible somatosensory evoked potentials (SEP) induced by sources of somatosensory input in the craniofacial region. Among these, only contraction of craniofacial muscle and stimulation of free cutaneous nerve endings may be able to induce EEG responses, but direct evidence is lacking due to experimental difficulties in isolating these inputs. Notably, EEG evoked activity in this context is represented by a N100/P200 complex, reflecting a saliency-related multimodal response, rather than specific activation of the primary somatosensory cortex. Strategies to minimize or remove these responses by EEG processing still yield uncertain results; therefore, data inspection is of paramount importance to judge a possible contamination of the TEP by multimodal potentials caused by somatosensory input.

Only the Fastest Corticospinal Fibers Contribute to ß Corticomuscular Coherence.

Human corticospinal transmission is commonly studied using brain stimulation. However, this approach is biased to activity in the fastest conducting axons. It is unclear whether conclusions obtained in this context are representative of volitional activity in mild-to-moderate contractions. An alternative to overcome this limitation may be to study the corticospinal transmission of endogenously generated brain activity. Here, we investigate in humans (N = 19; of either sex), the transmission speeds of cortical ß rhythms (∼20 Hz) traveling to arm (first dorsal interosseous) and leg (tibialis anterior; TA) muscles during tonic mild contractions. For this purpose, we propose two improvements for the estimation of corticomuscular ß transmission delays. First, we show that the cumulant density (cross-covariance) is more accurate than the commonly-used directed coherence to estimate transmission delays in bidirectional systems transmitting band-limited signals. Second, we show that when spiking motor unit activity is used instead of interference electromyography, corticomuscular transmission delay estimates are unaffected by the shapes of the motor unit action potentials (MUAPs). Applying these improvements, we show that descending corticomuscular ß transmission is only 1-2 ms slower than expected from the fastest corticospinal pathways. In the last part of our work, we show results from simulations using estimated distributions of the conduction velocities for descending axons projecting to lower motoneurons (from macaque histologic measurements) to suggest two scenarios that can explain fast corticomuscular transmission: either only the fastest corticospinal axons selectively transmit ß activity, or else the entire pool does. The implications of these two scenarios for our understanding of corticomuscular interactions are discussed.SIGNIFICANCE STATEMENT We present and validate an improved methodology to measure the delay in the transmission of cortical ß activity to tonically-active muscles. The estimated corticomuscular ß transmission delays obtained with this approach are remarkably similar to those expected from transmission in the fastest corticospinal axons. A simulation of ß transmission along a pool of corticospinal axons using an estimated distribution of fiber diameters suggests two possible mechanisms by which fast corticomuscular transmission is achieved: either a very small fraction of the fastest descending axons transmits ß activity to the muscles or, alternatively, the entire population does and natural cancellation of slow channels occurs because of the distribution of axon diameters in the corticospinal tract.

Premovement Suppression of Corticospinal Excitability may be a Necessary Part of Movement Preparation.

In reaction time (RT) tasks corticospinal excitability (CSE) rises just prior to movement. This is preceded by a paradoxical reduction in CSE, when the time of the imperative ("GO") stimulus is relatively predictable. Because RT tasks emphasise speed of response, it is impossible to distinguish whether reduced CSE reflects a mechanism for withholding prepared actions, or whether it is an inherent part of movement preparation. To address this question, we used transcranial magnetic stimulation (TMS) to estimate CSE changes preceding 1) RT movements; 2) movements synchronized with a predictable signal (predictive timing or PT movements); and 3) self-paced movements. Results show that CSE decreases with a similar temporal profile in all three cases, suggesting that it reflects a previously unrecognised state in the transition between rest and movement. Although TMS revealed reduced CSE in all movements, the TMS pulse itself had different effects on movement times. TMS given ~200 ms before the times to move speeded the onset of RT and self-paced movements, suggesting that their initiation depends on a form of trigger that can be conditioned by external events. On the contrary, PT movements did not show this effect, suggesting the use of a different triggering strategy prioritizing internal events.

Vestibulo masseteric reflex and acoustic masseteric Reflex. Normative data and effects of age and gender.

OBJECTIVE: To provide normative data for the Vestibulo-Masseteric Reflex (VMR) and Acoustic-Masseteric Reflex (AMR) in healthy subjects, stratified for age and gender. METHODS: A total of 82 healthy subjects (M:F 43:39, mean age 39.3 ±â€¯18.4 years, range 13-79 years) underwent recording of click-evoked VMR and AMR (0.1 ms duration, 5 Hz frequency) from active masseter muscles. Masseter responses to uni- and bilateral stimulation were recorded in a zygomatic and a mandibular configuration, according to the position of the reference electrode. Stimulation intensity curves were recorded for each reflex in ten subjects (mean age 20.7 ±â€¯8.1 years). Gender effect was investigated in 62 subjects and age effect was analyzed in six 10-subject groups aged from <25 to >65 years. Onset and peak latencies, interpeak intervals, raw and corrected amplitudes, latency and amplitude asymmetries were analyzed. RESULTS: VMR had a higher elicitation rate than AMR. For both reflexes, rates of elicitation, and corrected amplitudes were higher in the zygomatic configuration, and bilateral stimulation elicited larger responses. Best acoustic ranges of elicitation were 98-113 dB for AMR and 128-138 dB for VMR. Reflex latencies were shorter in females than males. Frequency and amplitude of VMR and AMR decreased substantially over 55 year olds. CONCLUSIONS: VMR and AMR can be easily performed in any clinical neurophysiology laboratory. SIGNIFICANCE: These reflexes can find application in the investigation of brainstem function in central neurological disorders.

Tremor in motor neuron disease may be central rather than peripheral in origin.

BACKGROUND AND PURPOSE: Motor neuron disease (MND) refers to a spectrum of degenerative diseases affecting motor neurons. Recent clinical and post-mortem observations have revealed considerable variability in the phenotype. Rhythmic involuntary oscillations of the hands during action, resembling tremor, can occur in MND, but their pathophysiology has not yet been investigated. METHODS: A total of 120 consecutive patients with MND were screened for tremor. Twelve patients with action tremor and no other movement disorders were found. Ten took part in the study. Tremor was recorded bilaterally using surface electromyography (EMG) and triaxial accelerometer, with and without a variable weight load. Power spectra of rectified EMG and accelerometric signal were calculated. To investigate a possible cerebellar involvement, eyeblink classic conditioning was performed in five patients. RESULTS: Action tremor was present in about 10% of our population. All patients showed distal postural tremor of low amplitude and constant frequency, bilateral with a small degree of asymmetry. Two also showed simple kinetic tremor. A peak at the EMG and accelerometric recordings ranging from 4 to 12 Hz was found in all patients. Loading did not change peak frequency in either the electromyographic or accelerometric power spectra. Compared with healthy volunteers, patients had a smaller number of conditioned responses during eyeblink classic conditioning. CONCLUSIONS: Our data suggest that patients with MND can present with action tremor of a central origin, possibly due to a cerebellar dysfunction. This evidence supports the novel idea of MND as a multisystem neurodegenerative disease and that action tremor can be part of this condition.

A qualitative study exploring views and experiences of people with stroke undergoing transcranial direct current stimulation and upper limb robot therapy.

Background Neurorehabilitation technologies used mainly in research such as robot therapy (RT) and transcranial direct current stimulation (tDCS) can promote upper limb motor recovery after stroke. Understanding the feasibility and efficacy of stroke rehabilitation technologies for upper limb impairments is crucial for effective implementation in practice. Small studies have explored views of RT by people with stroke; however experiences of people receiving tDCS in combination with RT have never been explored. Objective To explore views and experiences of people with sub-acute and chronic stroke that had previously taken part in a randomised controlled trial involving tDCS and RT for their impaired upper limb. Methods An interview study includes open and closed questions. Face-to-face interviews were audio recorded. Open-ended question responses were transcribed and analyzed using thematic analysis; closed questions were analyzed using descriptive analysis. Results Participants felt that RT was enjoyable (90%) and beneficial for their affected arm (100%). From the open question data, it was found that the intervention was effective for the impaired arm especially in the sub-acute stage. Main reported concerns were that tDCS caused painful, itching and burning sensations and RT was sometimes tiring and difficult. Participants recommended that future research should focus on designing a more comfortable method of tDCS and develop a robot that promotes hand movements. Conclusions This study provides new knowledge about the benefits and barriers associated with these technologies which are crucial to the future effective implementation of these tools in practice.

Effects of pulse width, waveform and current direction in the cortex: A combined cTMS-EEG study.

BACKGROUND: the influence of pulse width, pulse waveform and current direction on transcranial magnetic stimulation (TMS) outcomes is of critical importance. However, their effects have only been investigated indirectly with motor-evoked potentials (MEP). By combining TMS and EEG it is possible to examine how these factors affect evoked activity from the cortex and compare that with the effects on MEP. OBJECTIVE: we used a new controllable TMS device (cTMS) to vary systematically pulse width, pulse waveform and current direction and explore their effects on global and local TMS-evoked EEG response. METHODS: In 19 healthy volunteers we measured (1) resting motor threshold (RMT) as an estimate of corticospinal excitability; (2) global mean field power (GMFP) as an estimate of global cortical excitability; and (3) local mean field power (LMFP) as an estimate of local cortical excitability. RESULTS: RMT was lower with monophasic posterior-to-anterior (PA) pulses that have a longer pulse width (p < 0.001). After adjusting for the individual motor threshold of each pulse type we found that (a) GMFP was higher with monophasic pulses (p < 0.001); (b) LMFP was higher with longer pulse width (p = 0.015); (c) early TEP polarity was modulated depending on the current direction (p = 0.01). CONCLUSIONS: Despite normalizing stimulus intensity to RMT, we found that local and global responses to TMS vary depending on pulse parameters. Since EEG responses can vary independently of the MEP, titrating parameters of TMS in relation to MEP threshold is not a useful way of ensuring that a constant set of neurons is activated within a cortical area.

Past, present, and future of Parkinson's disease: A special essay on the 200th Anniversary of the Shaking Palsy.

This article reviews and summarizes 200 years of Parkinson's disease. It comprises a relevant history of Dr. James Parkinson's himself and what he described accurately and what he missed from today's perspective. Parkinson's disease today is understood as a multietiological condition with uncertain etiopathogenesis. Many advances have occurred regarding pathophysiology and symptomatic treatments, but critically important issues are still pending resolution. Among the latter, the need to modify disease progression is undoubtedly a priority. In sum, this multiple-author article, prepared to commemorate the bicentenary of the shaking palsy, provides a historical state-of-the-art account of what has been achieved, the current situation, and how to progress toward resolving Parkinson's disease. © 2017 International Parkinson and Movement Disorder Society.

The associative brain at work: Evidence from paired associative stimulation studies in humans.

The original protocol of Paired Associative Stimulation (PAS) in humans implies repetitive cortical and peripheral nerve stimuli, delivered at specific inter-stimulus intervals, able to elicit non-invasively long-term potentiation (LTP)- and long-term depression (LTD)-like plasticity in the human motor cortex. PAS has been designed to drive cortical LTP/LTD according to the Hebbian rule of associative plasticity. Over the last two decades, a growing number of researchers have increasingly used the PAS technique to assess cortical associative plasticity in healthy humans and in patients with movement disorders and other neuropsychiatric diseases. The present review covers the physiology, pharmacology, pathology and motor effects of PAS. Further sections of the review focus on new protocols of "modified PAS" and possible future application of PAS in neuromorphic circuits designed for brain-computer interface.

Time-dependent functional role of the contralesional motor cortex after stroke.

After stroke, movements of the paretic hand rely on altered motor network dynamics typically including additional activation of the contralesional primary motor cortex (M1). The functional implications of contralesional M1 recruitment to date remain a matter of debate. We here assessed the role of contralesional M1 in 12 patients recovering from a first-ever stroke using online transcranial magnetic stimulation (TMS): Short bursts of TMS were administered over contralesional M1 or a control site (occipital vertex) while patients performed different motor tasks with their stroke-affected hand. In the early subacute phase (1-2 weeks post-stroke), we observed significant improvements in maximum finger tapping frequency when interfering with contralesional M1, while maximum grip strength and speeded movement initiation remained unaffected. After > 3 months of motor recovery, disruption of contralesional M1 activity did not interfere with performance in any of the three tasks, similar to what we observed in healthy controls. In patients with mild to moderate motor deficits, contralesional M1 has a task- and time-specific negative influence on motor performance of the stroke-affected hand. Our results help to explain previous contradicting findings on the role of contralesional M1 in recovery of function.

The reliability of commonly used electrophysiology measures.

BACKGROUND: Electrophysiological measures can help understand brain function both in healthy individuals and in the context of a disease. Given the amount of information that can be extracted from these measures and their frequent use, it is essential to know more about their inherent reliability. OBJECTIVE/HYPOTHESIS: To understand the reliability of electrophysiology measures in healthy individuals. We hypothesized that measures of threshold and latency would be the most reliable and least susceptible to methodological differences between study sites. METHODS: Somatosensory evoked potentials from 112 control participants; long-latency reflexes, transcranial magnetic stimulation with resting and active motor thresholds, motor evoked potential latencies, input/output curves, and short-latency sensory afferent inhibition and facilitation from 84 controls were collected at 3 visits over 24 months at 4 Track-On HD study sites. Reliability was assessed using intra-class correlation coefficients for absolute agreement, and the effects of reliability on statistical power are demonstrated for different sample sizes and study designs. RESULTS: Measures quantifying latencies, thresholds, and evoked responses at high stimulator intensities had the highest reliability, and required the smallest sample sizes to adequately power a study. Very few between-site differences were detected. CONCLUSIONS: Reliability and susceptibility to between-site differences should be evaluated for electrophysiological measures before including them in study designs. Levels of reliability vary substantially across electrophysiological measures, though there are few between-site differences. To address this, reliability should be used in conjunction with theoretical calculations to inform sample size and ensure studies are adequately powered to detect true change in measures of interest.

Mind the gap: temporal discrimination and dystonia.

BACKGROUND AND PURPOSE: One of the most widely studied perceptual measures of sensory dysfunction in dystonia is the temporal discrimination threshold (TDT) (the shortest interval at which subjects can perceive that there are two stimuli rather than one). However the elevated thresholds described may be due to a number of potential mechanisms as current paradigms test not only temporal discrimination but also extraneous sensory and decision-making parameters. In this study two paradigms designed to better quantify temporal processing are presented and a decision-making model is used to assess the influence of decision strategy. METHODS: 22 patients with cervical dystonia and 22 age-matched controls completed two tasks (i) temporal resolution (a randomized, automated version of existing TDT paradigms) and (ii) interval discrimination (rating the length of two consecutive intervals). RESULTS: In the temporal resolution task patients had delayed (P = 0.021) and more variable (P = 0.013) response times but equivalent discrimination thresholds. Modelling these effects suggested this was due to an increased perceptual decision boundary in dystonia with patients requiring greater evidence before committing to decisions (P = 0.020). Patient performance on the interval discrimination task was normal. CONCLUSIONS: Our work suggests that previously observed abnormalities in TDT may not be due to a selective sensory deficit of temporal processing as decision-making itself is abnormal in cervical dystonia.

No evidence of neural adaptations following chronic unilateral isometric training of the intrinsic muscles of the hand: a randomized controlled study.

PURPOSE: To test whether long-term cortical adaptations occur bilaterally following chronic unilateral training with a simple motor task. METHODS: Participants (n = 34) were randomly allocated to a training or control groups. Only the former completed a 4-week maximal-intensity isometric training of the right first dorsal interosseus muscle through key pinching. Maximal strength was assessed bilaterally in four different movements progressively less similar to the training task: key, tip and tripod pinches, and handgrip. Transcranial magnetic stimulation was used to probe, in the left and right primary hand motor cortices, a number of standard tests of cortical excitability, including thresholds, intra-cortical inhibition and facilitation, transcallosal inhibition, and sensory-motor integration. RESULTS: Training increased strength in the trained hand, but only for the tasks specifically involving the trained muscle (key +8.5 %; p < 0.0005; tip +7.2 %; p = 0.02). However, the effect size was small and below the cutoff for meaningful change. Handgrip and tripod pinch were instead unaffected. There was a similar improvement in strength in the untrained hand, i.e., a cross-education effect (key +6.4 %; p = 0.02; tip +4.7 %; p = 0.007). Despite these changes in strength, no significant variation was observed in any of the neurophysiological parameters describing cortico-spinal and intra-cortical excitability, inter-hemispheric inhibition, and cortical sensory-motor integration. CONCLUSIONS: A 4-week maximal-intensity unilateral training induced bilaterally spatial- and task-specific strength gains, which were not associated to direct or crossed cortical adaptations. The observed long-term stability of neurophysiological parameters might result from homeostatic plasticity phenomena, aimed at restoring the physiological inter-hemispheric balance of neural activity levels perturbed by the exercise. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier NCT02010398.

Ten Years of Theta Burst Stimulation in Humans: Established Knowledge, Unknowns and Prospects.

BACKGROUND/OBJECTIVES: Over the last ten years, an increasing number of authors have used the theta burst stimulation (TBS) protocol to investigate long-term potentiation (LTP) and long-term depression (LTD)-like plasticity non-invasively in the primary motor cortex (M1) in healthy humans and in patients with various types of movement disorders. We here provide a comprehensive review of the LTP/LTD-like plasticity induced by TBS in the human M1. METHODS: A workgroup of researchers expert in this research field review and discuss critically ten years of experimental evidence from TBS studies in humans and in animal models. The review also includes the discussion of studies assessing responses to TBS in patients with movement disorders. MAIN FINDINGS/DISCUSSION: We discuss experimental studies applying TBS over the M1 or in other cortical regions functionally connected to M1 in healthy subjects and in patients with various types of movement disorders. We also review experimental evidence coming from TBS studies in animals. Finally, we clarify the status of TBS as a possible new non-invasive therapy aimed at improving symptoms in various neurological disorders.

Abnormal movement-related suppression of sensory evoked potentials in upper limb dystonia.

BACKGROUND: Gating of sensory evoked potentials (SEPs) around the onset of a voluntary movement is a physiological phenomenon with centripetal and central components, and may reflect sensorimotor integration required for normal movement control. OBJECTIVE: Our objective was the investigation of SEP suppression at the onset of movement and the interaction between SEP suppression and vibration of the limb. METHODS: Fourteen patients with primary focal/segmental dystonia and 17 age-matched healthy volunteers were studied. SEPs were elicited after electrical stimulation of the median nerve at the wrist. Electroencephalograms (EEGs) were recorded over the scalp at three sites according to the International 10-20 System (F3, C3 and P3). SEPs were recorded in four conditions: at rest, at the onset of movement (a self-paced abduction movement of the right thumb), both in the absence and in the presence of vibration of the limb. RESULTS: Repeated measures anova revealed that there was a significant main effect of group [F(1, 11.1) = 0.471, P = 0.002]. Post hoc exploration of this effect revealed it to be due to an absence of SEP suppression at movement onset in patients (mean ratio SEP movement onset/rest 1.15 at F3, 1.13 at C3, 1.01 at P3) compared to controls, who had SEP suppression at movement onset (mean ratio SEP movement onset/rest 0.79 at F3, 0.78 at C3, 0.77 at P3). With vibration, SEP suppression reduced in both patients and controls to a similar extent. CONCLUSION: These results demonstrate abnormal SEP suppression at the onset of movement in patients with primary dystonia, and in addition that vibration of the limb reduces SEP suppression in patients and controls.

Multiple sessions of transcranial direct current stimulation and upper extremity rehabilitation in stroke: A review and meta-analysis.

OBJECTIVE: To systematically review the methodology in particular treatment options and outcomes and the effect of multiple sessions of transcranial direct current stimulation (tDCS) with rehabilitation programmes for upper extremity recovery post stroke. METHODS: A search was conducted for randomised controlled trials involving tDCS and rehabilitation for the upper extremity in stroke. Quality of included studies was analysed using the Modified Downs and Black form. The extent of, and effect of variation in treatment parameters such as anodal, cathodal and bi-hemispheric tDCS on upper extremity outcome measures of impairment and activity were analysed using meta-analysis. RESULTS: Nine studies (371 participants with acute, sub-acute and chronic stroke) were included. Different methodologies of tDCS and upper extremity intervention, outcome measures and timing of assessments were identified. Real tDCS combined with rehabilitation had a small non-significant effect of +0.11 (p=0.44) and +0.24 (p=0.11) on upper extremity impairments and activities at post-intervention respectively. CONCLUSION: Various tDCS methods have been used in stroke rehabilitation. The evidence so far is not statistically significant, but is suggestive of, at best, a small beneficial effect on upper extremity impairment. SIGNIFICANCE: Future research should focus on which patients and rehabilitation programmes are likely to respond to different tDCS regimes.

Post-stroke fatigue: a problem of altered corticomotor control?

OBJECTIVES: We recently showed that diminished motor cortical excitability is associated with high levels of post-stroke fatigue. Motor cortex excitability impacts movement parameters such as reaction and movement times. We predicted that one or both would be influenced by the presence of post-stroke fatigue. METHODS: 41 first-time stroke survivors (high fatigue n=21, Fatigue Severity Scale 7 (FSS-7) score >5; low fatigue n=20, FSS-7 score <3) participated in the study. Movement times, choice and simple reaction times were measured in all participants. RESULTS: A three way ANOVA with fatigue (high and low), task (movement time, simple reaction time and choice reaction time) and hand (affected and unaffected) as the three factors, revealed a significant difference between affected (but not unaffected) hand movement times in the high compared to low fatigue groups. Reaction times, however, were not different between the high-fatigue and low-fatigue groups in either the affected or unaffected hand. CONCLUSIONS: Previously, we showed that motor cortex excitability is lower in patients with high post-stroke fatigue. Our current findings suggest that post-stroke fatigue (1) is a problem of movement speed (possibly a consequence of diminished motor cortex excitability) and not movement preparation, and (2) may have a focal origin confined to the lesioned hemisphere. We suggest that low motor cortex excitability in the lesioned hemisphere is a viable therapeutic target in post-stroke fatigue.

Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: Basic principles and procedures for routine clinical and research application. An updated report from an I.F.C.N. Committee.

These guidelines provide an up-date of previous IFCN report on "Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application" (Rossini et al., 1994). A new Committee, composed of international experts, some of whom were in the panel of the 1994 "Report", was selected to produce a current state-of-the-art review of non-invasive stimulation both for clinical application and research in neuroscience. Since 1994, the international scientific community has seen a rapid increase in non-invasive brain stimulation in studying cognition, brain-behavior relationship and pathophysiology of various neurologic and psychiatric disorders. New paradigms of stimulation and new techniques have been developed. Furthermore, a large number of studies and clinical trials have demonstrated potential therapeutic applications of non-invasive brain stimulation, especially for TMS. Recent guidelines can be found in the literature covering specific aspects of non-invasive brain stimulation, such as safety (Rossi et al., 2009), methodology (Groppa et al., 2012) and therapeutic applications (Lefaucheur et al., 2014). This up-dated review covers theoretical, physiological and practical aspects of non-invasive stimulation of brain, spinal cord, nerve roots and peripheral nerves in the light of more updated knowledge, and include some recent extensions and developments.

All in the blink of an eye: new insight into cerebellar and brainstem function in DYT1 and DYT6 dystonia.

BACKGROUND AND PURPOSE: Traditionally dystonia has been considered a disorder of basal ganglia dysfunction. However, recent research has advocated a more complex neuroanatomical network. In particular, there is increasing interest in the pathophysiological role of the cerebellum. Patients with cervical and focal hand dystonia have impaired cerebellar associative learning using the paradigm eyeblink conditioning. This is perhaps the most direct evidence to date that the cerebellum is implicated in patients. METHODS: Eleven patients with DYT1 dystonia and five patients with DYT6 dystonia were examined and rates of eyeblink conditioning were compared with age-matched controls. A marker of brainstem excitability, the blink reflex recovery, was also studied in the same groups. RESULTS: Patients with DYT1 and DYT6 dystonia have a normal ability to acquire conditioned responses. Blink reflex recovery was enhanced in DYT1 but this effect was not seen in DYT6. CONCLUSIONS: If the cerebellum is an important driver in DYT1 and DYT6 dystonia our data suggest that there is specific cerebellar dysfunction such that the circuits essential for conditioning function normally. Our data are contrary to observations in focal dystonia and suggest that the cerebellum may have a distinct role in different subsets of dystonia. Evidence of enhanced blink reflex recovery in all patients with dystonia was not found and recent studies calling for the blink recovery reflex to be used as a diagnostic test for dystonic tremor may require further corroboration.

Domain-specific suppression of auditory mismatch negativity with transcranial direct current stimulation.

OBJECTIVE: To evaluate the influence of frontal transcranial direct current stimulation (tDCS) on auditory mismatch negativity (MMN). METHODS: MMN is an event related potential calculated by subtracting the amplitude of the evoked potentials in response to a "standard" stimulus from the evoked potentials produced by a rare "oddball" stimulus. Here we assessed the influence of anodal tDCS, cathodal tDCS or sham stimulation delivered over the right inferior frontal cortex on MMN in response to duration and frequency auditory deviants in 10 healthy subjects. RESULTS: MMN to frequency deviants was significantly reduced after anodal tDCS compared with sham or cathodal stimulation which did not change MMN to frequency deviants. Neither anodal nor cathodal tDCS had any effect on MMN to duration deviants. CONCLUSIONS: Non-invasive brain stimulation with tDCS can influence MMN. The differing networks known to be activated by duration and frequency deviants could account for the differential effect of tDCS on duration and frequency MMN. SIGNIFICANCE: Non-invasive brain stimulation could be a useful method to manipulate MMN for experimental purposes.