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Our understanding of the adaptive processes that shape sensorimotor behavior is largely derived from studying isolated movements. Studies of visuomotor adaptation, in which participants adapt cursor movements to rotations of the cursor's screen position, have led to prominent theories of motor control. In response to changes in visual feedback of movements, explicit (cognitive) and implicit (automatic) learning processes adapt movements to counter errors. However, movements rarely occur in isolation. The extent to which explicit and implicit processes drive sensorimotor adaptation when multiple movements occur simultaneously, as in the real world, remains unclear. Here we address this problem in the context of speech and hand movements. Participants spoke in-time with rapid, hand-driven cursor movements. Using real-time alterations of vowel sound feedback, and visual rotations of the cursor's screen position, we induced sensorimotor adaptation in one or both movements simultaneously. Across three experiments (n = 60, n = 48 and n = 76, respectively), we demonstrate that visuomotor adaptation is markedly impaired by simultaneous speech adaptation, and the impairment is specific to the explicit learning process in visuomotor adaptation. In contrast, visuomotor adaptation had no impact on speech adaptation. The results demonstrate that the explicit learning process in visuomotor adaptation is sensitive to movements in other motor domains. They suggest that some forms of speech adaptation may lack an explicit learning process altogether.

The multi-sensory nature of episodic memories indicates that communication between a multitude of brain areas is required for their effective creation and recollection. Previous studies have suggested that the effectiveness of memory processes depends on theta synchronization (4 Hz) of sensory areas relevant to the memory. This study aimed to manipulate theta synchronization between different sensory areas in order to further test this hypothesis. We intend to entrain visual cortex with 4 Hz alternating current stimulation (tACS), while simultaneously entraining auditory cortex with 4 Hz amplitude-modulated sounds. By entraining these different sensory areas, which pertain to learned audio–visual memory associations, we expect to find that when theta is synchronized across the different sensory areas, the memory performance would be enhanced compared to when theta is not synchronized across the sensory areas. We found no evidence for such an effect in this study. It is unclear whether this is due to an inability of 4 Hz tACS to entrain the visual cortex reliably, or whether sensory entrainment is not the underlying mechanism required for episodic memory.

The dysregulation of endogenous rhythms within brain networks have been implicated in a broad range of motor and non-motor pathologies. Essential tremor (ET), classically the purview of a single aberrant pacemaker, has recently become associated with network-level dysfunction across multiple brain regions. Specifically, it has been suggested that motor cortex constitutes an important node in a tremor-generating network involving the cerebellum. Yet the mechanisms by which these regions relate to tremor remain a matter of considerable debate. We sought to discriminate the contributions of cerebral and cerebellar dysregulation by combining high-density electroencephalography with subject-specific structural MRI. For that, we contrasted ET with voluntary (mimicked) tremor before and after ingestion of alcohol to regulate the tremorgenic networks. Our results demonstrate distinct loci of cortical tremor coherence, most pronounced over the sensorimotor cortices in healthy controls, but more frontal motor areas in ET-patients consistent with a heightened involvement of the supplementary motor area. We further demonstrate that the reduction in tremor amplitude associated with alcohol intake is reflected in altered cerebellar - but not cerebral - coupling with movement. Taken together, these findings implicate tremor emergence as principally associated with increases in activity within frontal motor regions, whereas modulation of the amplitude of established tremor relates to changes in cerebellar activity. These findings progress a mechanistic understanding of ET and implicate network-level vulnerabilities in the rhythmic nature of communication throughout the brain.

People with Parkinson’s disease (PD) experience motor symptoms that are affected by sensory information in the environment. Sensory attenuation describes the modulation of sensory input caused by motor intent. This appears to be altered in PD and may index important sensorimotor processes underpinning PD symptoms. We review recent findings investigating sensory attenuation and reconcile seemingly disparate results with an emphasis on task-relevance in the modulation of sensory input. Sensory attenuation paradigms, across different sensory modalities, capture how two identical stimuli can elicit markedly different perceptual experiences depending on our predictions of the event, but also the context in which the event occurs. In particular, it appears as though contextual information may be used to suppress or facilitate a response to a stimulus on the basis of task-relevance. We support this viewpoint by considering the role of the basal ganglia in task-relevant sensory filtering and the use of contextual signals in complex environments to shape action and perception. This perspective highlights the dual effect of basal ganglia dysfunction in PD, whereby a reduced capacity to filter task-relevant signals harms the ability to integrate contextual cues, just when such cues are required to effectively navigate and interact with our environment. Finally, we suggest how this framework might be used to establish principles for effective rehabilitation in the treatment of PD.

Key points Healthy ageing in man is associated with a decline in motor adaptation. Transcranial direct current stimulation (TDCS) over the primary motor cortex (M1) or the lateral cerebellum can improve motor adaptation in young and older adults, but as yet no direct comparisons of TDCS effects exist between the two age groups and the two stimulation sites. TDCS over M1 enhanced the motor adaptation in both age groups by ∼30% relative to their respective non-stimulated groups and improved the performance of older adults to the extent that it compared with that of young adults without stimulation. The study suggests that the plastic mechanisms activated by TDCS that underpin improvements in motor behaviour in young adults remain available in older adults. The results indicate that TDCS may be a useful tool to help combat the normal decline in motor performance seen in normal healthy ageing. Abstract Healthy ageing is characterised by deterioration of motor performance. In normal circumstances motor adaptation corrects for movements’ inaccuracies and as such, it is critical in maintaining optimal motor control. However, motor adaptation performance is also known to decline with age. Anodal transcranial direct current stimulation (TDCS) of the cerebellum and the primary motor cortex (M1) have been found to improve visuomotor adaptation in healthy young and older adults. However, no study has directly compared the effect of TDCS on motor adaptation between the two age populations. The aim of our study was to investigate whether the application of anodal TDCS over the lateral cerebellum and M1 affected motor adaptation in young and older adults similarly. Young and older participants performed a visuomotor rotation task and concurrently received TDCS over the left M1, the right cerebellum or received sham stimulation. Our results replicated the finding that older adults are impaired compared to the young adults in visuomotor adaptation. At the end of the adaptation session, older adults displayed a larger error (−17 deg) than the young adults (−10 deg). The stimulation of the lateral cerebellum did not change the adaptation in both age groups. In contrast, anodal TDCS over M1 improved initial adaptation in both age groups by around 30% compared to sham and this improvement lasted up to 40 min after the end of the stimulation. These results demonstrate that TDCS of M1 can enhance visuomotor adaptation, via mechanisms that remain available in the ageing population.

BACKGROUND: Classically, studies adopting non-invasive transcranial electrical stimulation have placed greater importance on the position of the primary "stimulating" electrode than the secondary "reference" electrode. However, recent current density modeling suggests that ascribing a neutral role to the reference electrode may prove an inappropriate oversimplification. HYPOTHESIS: We set out to test the hypothesis that the behavioral effects of transcranial electrical stimulation are critically dependent on the position of the return ("reference") electrode. METHODS: We examined the effect of transcranial alternating current stimulation (sinusoidal waveform with no direct current offset at a peak-to-peak amplitude of 2000 μA and a frequency matched to each participant's peak tremor frequency) on physiological tremor in a group of healthy volunteers (N = 12). We implemented a sham-controlled experimental protocol where the position of the stimulating electrode remained fixed, overlying primary motor cortex, whilst the position of the return electrode varied between two cephalic (fronto-orbital and contralateral primary motor cortex) and two extracephalic (ipsilateral and contralateral shoulder) locations. We additionally controlled for the role of phosphenes in influencing motor output by assessing the response of tremor to photic stimulation, through self-reported phosphene ratings. RESULTS: Altering only the position of the return electrode had a profound behavioral effect: only the montage with extracephalic return contralateral to the primary stimulating electrode significantly entrained physiological tremor (15.9% ± 6.1% increase in phase stability, 1 S.E.M.). Photic stimulation also entrained tremor (11.7% ± 5.1% increase in phase stability). Furthermore, the effects of electrical stimulation are distinct from those produced from direct phosphene induction, in that the latter were only seen with the fronto-orbital montage that did not affect the tremor. CONCLUSION: The behavioral effects of transcranial alternating current stimulation appear to be critically dependent on the position of the reference electrode, highlighting the importance of electrode montage when designing experimental and therapeutic protocols.

Non-invasive transcranial brain stimulation (NTBS) techniques have a wide range of applications but also suffer from a number of limitations mainly related to poor specificity of intervention and variable effect size. These limitations motivated recent efforts to focus on the temporal dimension of NTBS with respect to the ongoing brain activity. Temporal patterns of ongoing neuronal activity, in particular brain oscillations and their fluctuations, can be traced with electro- or magnetoencephalography (EEG/MEG), to guide the timing as well as the stimulation settings of NTBS. These novel, online and offline EEG/MEG-guided NTBS-approaches are tailored to specifically interact with the underlying brain activity. Online EEG/MEG has been used to guide the timing of NTBS (i.e., when to stimulate): by taking into account instantaneous phase or power of oscillatory brain activity, NTBS can be aligned to fluctuations in excitability states. Moreover, offline EEG/MEG recordings prior to interventions can inform researchers and clinicians how to stimulate: by frequency-tuning NTBS to the oscillation of interest, intrinsic brain oscillations can be up- or down-regulated. In this paper, we provide an overview of existing approaches and ideas of EEG/MEG-guided interventions, and their promises and caveats. We point out potential future lines of research to address challenges.

Parkinson's disease (PD) and essential tremor (ET) are the two most common movement disorders. Both have been associated with similar patterns of network activation leading to the suggestion that they may result from similar network dysfunction, specifically involving the cerebellum. Here, we demonstrate that parkinsonian tremors and ETs result from distinct patterns of interactions between neural oscillators. These patterns are reflected in the tremors' derived frequency tolerance, a novel measure readily attainable from bedside accelerometry. Frequency tolerance characterizes the temporal evolution of tremor by quantifying the range of frequencies over which the tremor may be considered stable. We found that patients with PD (N= 24) and ET (N= 21) were separable based on their frequency tolerance, with PD associated with a broad range of stable frequencies whereas ET displayed characteristics consistent with a more finely tuned oscillatory drive. Furthermore, tremor was selectively entrained by transcranial alternating current stimulation applied over cerebellum. Narrow frequency tolerances predicted stronger entrainment of tremor by stimulation, providing good evidence that the cerebellum plays an important role in pacing those tremors. The different patterns of frequency tolerance could be captured with a simple model based on a broadly coupled set of neural oscillators for PD, but a more finely tuned set of oscillators in ET. Together, these results reveal a potential organizational principle of the human motor system, whose disruption in PD and ET dictates how patients respond to empirical, and potentially therapeutic, interventions that interact with their underlying pathophysiology.

Tremor represents one of the most prominent examples of aberrant synchronisation within the human motor system, and Essential Tremor (ET) is by far the most common tremor disorder. Yet, even within ET there is considerable variation, and patients may have contrasting amounts of postural and intention tremor. Recently, Pedrosa et al. (2013) challenged tremor circuits in a cohort of patients presenting with ET, by applying low-frequency deep brain stimulation within thalamus. This interventional approach provided strong evidence that distinct (yet possibly overlapping) neural substrates are responsible for postural and intention tremor in ET. Intention tremor, and not postural tremor, was exacerbated by low frequency stimulation, and the effect was localised in the region of the ventrolateral thalamus in such a way as to implicate cerebello-thalamic pathways. These results, taken in conjunction with the contemporary literature, reveal that pathological changes exaggerate oscillatory synchrony in selective components of an extensive and distributed motor network, and that synchronisation within these networks is further regulated according to motor state. Through a combination of pathological and more dynamic physiological factors, activity then spills out into the periphery in the form of tremor. The findings of Pedrosa et al. (2013) are timely as they coincide with an emerging notion that tremor may result through selective dysregulation within a broader tremorgenic network.

Oscillatory activity in the beta (13-30 Hz) frequency band is widespread in cortico-basal ganglia circuits, and becomes prominent in Parkinson's disease (PD). Here we develop the hypothesis that the degree of synchronization in this frequency band is a critical factor in gating computation across a population of neurons, with increases in beta band synchrony entailing a loss of information-coding space and hence computational capacity. Task and context drive this dynamic gating, so that for each state there will be an optimal level of network synchrony, and levels lower or higher than this will impair behavioural performance. Thus, both the pathological exaggeration of synchrony, as observed in PD, and the ability of interventions like deep brain stimulation (DBS) to excessively suppress synchrony can potentially lead to impairments in behavioural performance. Indeed, under physiological conditions, the manipulation of computational capacity by beta activity may itself present a mechanism of action selection and maintenance. © 2014 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley and Sons Ltd.

Oscillations form a ubiquitous feature of the central nervous system. Evidence is accruing from cortical and sub-cortical recordings that these rhythms may be functionally important, although the precise details of their roles remain unclear. The basal ganglia share this predilection for rhythmic activity which, as we see in Parkinson's disease, becomes further enhanced in the dopamine depleted state. While certain cortical rhythms appear to penetrate the basal ganglia, others are transformed or blocked. Here, we discuss the functional association of oscillations in the basal ganglia and their relationship with cortical activity. We further explore the neural underpinnings of such oscillatory activity, including the important balance to be struck between facilitating information transmission and limiting information coding capacity. Finally, we introduce the notion that synchronised oscillatory activity can be broadly categorised as immutability promoting rhythms that reinforce incumbent processes, and mutability promoting rhythms that favour novel processing. © 2013 Elsevier Inc.

Gait freezing is an episodic arrest of locomotion due to an inability to take normal steps. Pedunculopontine nucleus stimulation is an emerging therapy proposed to improve gait freezing, even where refractory to medication. However, the efficacy and precise effects of pedunculopontine nucleus stimulation on Parkinsonian gait disturbance are not established. The clinical application of this new therapy is controversial and it is unknown if bilateral stimulation is more effective than unilateral. Here, in a double-blinded study using objective spatiotemporal gait analysis, we assessed the impact of unilateral and bilateral pedunculopontine nucleus stimulation on triggered episodes of gait freezing and on background deficits of unconstrained gait in Parkinson's disease. Under experimental conditions, while OFF medication, Parkinsonian patients with severe gait freezing implanted with pedunculopontine nucleus stimulators below the pontomesencephalic junction were assessed during three conditions; off stimulation, unilateral stimulation and bilateral stimulation. Results were compared to Parkinsonian patients without gait freezing matched for disease severity and healthy controls. Pedunculopontine nucleus stimulation improved objective measures of gait freezing, with bilateral stimulation more effective than unilateral. During unconstrained walking, Parkinsonian patients who experience gait freezing had reduced step length and increased step length variability compared to patients without gait freezing; however, these deficits were unchanged by pedunculopontine nucleus stimulation. Chronic pedunculopontine nucleus stimulation improved Freezing of Gait Questionnaire scores, reflecting a reduction of the freezing encountered in patients' usual environments and medication states. This study provides objective, double-blinded evidence that in a specific subgroup of Parkinsonian patients, stimulation of a caudal pedunculopontine nucleus region selectively improves gait freezing but not background deficits in step length. Bilateral stimulation was more effective than unilateral. © 2012 The Author.

The mechanisms by which neural signals are encoded to produce conscious sensations remain a central question in neuroscience. Invasive recordings from human brain structures in vivo give us the opportunity to study neural correlates of these sensations. Pain is a sensation fundamental to survival and its subjective nature in the clinical setting makes it difficult to quantify. It remains without direct objective neuronal correlates. Here we describe an 8–14 Hz, spindle-shaped neural signal present in both the sensory thalamus and periaqueductal gray area (PAG) in humans that directly correlates to the subjective reporting of pain intensity. Local field potentials (LFPs) recorded by deep brain macroelectrodes reveal the ensemble activity of neuronal groups in particular brain regions.1 The oscillatory amplitude of such ensembles is proportionate to the degree of synchrony with which they oscillate.2 Properties of oscillations including their synchrony, frequency, and corresponding power spectra vary both between brain structures and dynamically, depending upon the activity performed.3 ### Methods. Twelve patients (11 male, 1 female) underwent deep brain stimulation for treatment of chronic neuropathic pain. Etiology was as follows; poststroke pain (4), phantom limb pain (3), facial pain of various causes (4), and brachial plexus injury (1). Nuclei targeted were periaqueductal gray (PAG) alone in 3 patients, ventroposterolateral/medial nucleus of the thalamus (VPL/VPM) in 6 patients, and both in 3 patients. This was decided upon based on clinical grounds (in general, sensory thalamus was avoided if the patient had had a thalamic stroke). Three patients …

highlights Beta oscillatory activity in the subthalamic nucleus is differentially modulated by rate of finger tapping. Beta desynchronization occurs to the same level regardless of rate of tapping, and thus is independent of motor parameters. Beta resynchronization is markedly suppressed at the high tapping rate, implicating persistent beta suppression with continuous movement sequences. abstract Objective: The function of synchronous oscillatory activity at beta band (15-30 Hz) frequencies within the basal ganglia is unclear. Here we sought support for the hypothesis that beta activity has a global function within the basal ganglia and is not directly involved in the coding of specific biomechanical parameters of movement. Methods: We recorded local field potential activity from the subthalamic nuclei of 11 patients with Par- kinson's disease during a synchronized tapping task at three different externally cued rates. Results: Beta activity was suppressed during tapping, reaching a minimum that differed little across the different tapping rates despite an increase in velocity of finger movements. Thus beta power suppression was independent of specific motor parameters. Moreover, although beta oscillations remained sup- pressed during all tapping rates, periods of resynchronization between taps were markedly attenuated during high rate tapping. As such, a beta rebound above baseline between taps at the lower rates was absent at the high rate. Conclusion: Our results demonstrate that beta desynchronization in the region of the subthalamic nucleus is independent of motor parameters and that the beta resynchronization is differentially modu- lated by rate of finger tapping, Significance: These findings implicate consistent beta suppression in the facilitation of continuous move- ment sequences.

Surprising events markedly affect behaviour and cognition, yet the underlying mechanism is unclear. Surprise recruits a brain mechanism that globally suppresses motor activity, ostensibly via the subthalamic nucleus (STN) of the basal ganglia. Here, we tested whether this suppressive mechanism extends beyond skeletomotor suppression and also affects cognition (here, verbal working memory, WM). We recorded scalp-EEG (electrophysiology) in healthy participants and STN local field potentials in Parkinson's patients during a task in which surprise disrupted WM. For scalp-EEG, surprising events engage the same independent neural signal component that indexes action stopping in a stop-signal task. Importantly, the degree of this recruitment mediates surprise-related WM decrements. Intracranially, STN activity is also increased post surprise, especially when WM is interrupted. These results suggest that surprise interrupts cognition via the same fronto-basal ganglia mechanism that interrupts action. This motivates a new neural theory of how cognition is interrupted, and how distraction arises after surprising events., Surprising events affect ongoing behaviour and cognitive processing, yet the underlying neural mechanisms remain unclear. Wessel and colleagues show that surprise recruits a motor suppression mechanism which may be implemented via the sub-thalamic nucleus and interrupts working memory performance.

We measured reaction times during a stop-signal task while patients with Parkinson's disease were on and off unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN). While reaction times to a “go” stimulus improved, there was no change in reaction times to the “stop” stimulus (SSRTs). However, changes in SSRTs induced by DBS were highly dependent on baseline SSRTs (measured off stimulation), with the greatest improvements being achieved by those with particularly slow reaction times. We therefore selected only those patients whose baseline SSRTs were within the limits of a control sample (N = 10). In this group, SSRTs became slower when DBS was on. This finding suggests a role for the STN in response inhibition, which can be interrupted by DBS, observable only when more general improvements in Parkinson's function are minimised. We also compared the effects of unilateral left and right sided stimulation. We found a greater increase in SSRTs after DBS of the left STN.

The subthalamic nucleus (STN) is thought to play a central role in modulating responses during conflict. Computational models have suggested that the location of the STN in the basal ganglia, as well as its numerous connections to conflict-related cortical structures, allows it to be ideally situated to act as a global inhibitor during conflict. Additionally, recent behavioral experiments have shown that deep brain stimulation to the STN results in impulsivity during high-conflict situations. However, the precise mechanisms that mediate the “hold-your-horses” function of the STN remain unclear. We recorded from deep brain stimulation electrodes implanted bilaterally in the STN of 13 human subjects with Parkinson's disease while they performed a flanker task. The incongruent trials with the shortest reaction times showed no behavioral or electrophysiological differences from congruent trials, suggesting that the distracter stimuli were successfully ignored. In these trials, cue-locked STN theta band activity demonstrated phase alignment across trials and was followed by a periresponse increase in theta power. In contrast, incongruent trials with longer reaction times demonstrated a relative reduction in theta phase alignment followed by higher theta power. Theta phase alignment negatively correlated with subject reaction time, and theta power positively correlated with trial reaction time. Thus, when conflicting stimuli are not properly ignored, disruption of STN theta phase alignment may help operationalize the hold-your-horses role of the nucleus, whereas later increases in the amplitude of theta oscillations may help overcome this function.

Brain-derived neurotrophic factor (BDNF) plays an important role in learning, memory, and brain plasticity. Humans with a val66met polymorphism in the BDNF gene have reduced levels of BDNF and alterations in motor learning and short-term cortical plasticity. In the current study, we sought to further explore the role of BDNF in motor learning by testing human subjects on a visuomotor adaptation task. In experiment 1, 21 subjects with the polymorphism (val/met) and 21 matched controls (val/val) were tested during learning, short-term retention (45 min), long-term retention (24 h), and de-adaptation of a 60° visuomotor deviation. We measured both mean error as well as rate of adaptation during each session. There was no difference in mean error between groups; however, val/met subjects had a reduced rate of adaptation during learning as well as during long-term retention, but not short-term retention or de-adaptation. In experiment 2, 12 val/met and 12 val/val subjects were tested on a larger 80° deviation, revealing a more pronounced difference in mean error during adaptation than the 60° deviation. These results suggest that BDNF may play an important role in visuomotor adaptive processes in the human. © 2012 Springer-Verlag.

The subthalamic nucleus (STN) is a key node in the network that supports response inhibition. It is suggested that the STN rapidly inhibits basal ganglia activity, to pause motor output during conflict until an appropriate motor plan is ready. Here, we recorded neural activity during a Stroop task from deep brain stimulation electrodes implanted in the human STN. We intended to determine whether cognitive psychological phenomena such as the Stroop effect can be explained via mechanisms of response inhibition involving the STN, or whether higher cognitive centers are alone responsible. We show stimulus-driven desychronization in the beta band (15–35 Hz) that lasts throughout the verbal response, in keeping with the idea that beta-band synchrony decreases to allow motor output to occur. During incongruent trials—in which response times were elongated due to the Stroop effect—a resynchronization was seen in the beta band before response. Crucially, in the incongruent trials during which the participant was unable to withhold the prepotent response, this resynchronization occurred after response onset. We suggest that this beta-band resynchronization pauses the motor system until conflict can be resolved.

Oscillatory activities in the brain within the beta (15–30 Hz) and gamma (70–90 Hz) ranges have been implicated in the generation of voluntary movement. However, their roles remain unclear. Here, we record local field potential activity from the region of the subthalamic nucleus during movement of the contralateral limb in 11 patients with Parkinson's disease. Patients were on their normal dopaminergic medication and were cued to perform arm-reaching movements after a delay period at three different speeds: ‘slow’, ‘normal’, and ‘fast’. Beta activity desynchronized earlier in response to the cue indicating an upcoming fast reach than to the cues for slow or normal speed movement. There was no difference in the degree of beta desynchronization between reaching speeds and beta desynchronization was established prior to movement onset in all cases. In contrast, synchronization in the gamma range developed during the reaching movement, and was especially pronounced during fast reaching. Thus the timing of suppression in the beta band depended on task demands, whereas the degree of increase in gamma oscillations depended on movement speed. These findings point to functionally segregated roles for different oscillatory frequencies in motor preparation and performance.

Timing is central to all motor behavior, especially repetitive or rhythmic movements. Such complex programs are underpinned by a network of motor structures, including the cerebellum, motor cortex, and basal ganglia. Patients with Parkinson's disease (PD) are impaired in some aspects of timing behavior, presumably as a result of the disruption to basal ganglia function. However, direct evidence that this deficit is specifically due to basal ganglia dysfunction is limited. Here, we sought to further understand the role of the basal ganglia in motor timing by studying PD patients with implanted subthalamic nucleus (STN) electrodes. Patients performed a synchronization-continuation tapping task at 500 ms and 2000 ms intervals both off and on therapeutic high frequency stimulation of the STN. Our results show that the mean tap interval was not affected by STN stimulation. However, in the un-stimulated state variability of tapping was abnormally high relative to controls, and this deficit was significantly improved, even normalized, with stimulation. Moreover, when partitioning the variance into central and peripheral motor components according to the Wing and Kristofferson model (1973), a selective reduction of central, but not motor, variance was revealed. The effect of stimulation on central variance was dependent on off-stimulation performance. These results demonstrate that STN stimulation can improve rhythmic movement performance in PD through an effect on central timing. Our experimental approach strongly implicates the STN, and more generally the basal ganglia, in the control of timing stability.

Response inhibition as measured during a stop-signal task refers to the ability to halt an action that has already been set in motion. Cortical and sub-cortical structures, such as the subthalamic nucleus (STN), that are active during attempts to inhibit action are thought to contribute to a ‘stop-process’ that must gain dominance over a ‘go-process’ if inhibition is to be successful. We recorded local field potential activity from the STN of Parkinson's disease patients with implanted deep brain stimulation electrodes during a stop-signal task. In particular we measured activity in the STN that has traditionally been associated with motor action (gamma-band, 60–100 Hz) and inhibition (beta-band, 10–30 Hz). Our data support the idea that beta activity in the STN is related to the inhibition of motor action. Further, we report that gamma oscillatory activity responds robustly to stop-signals as well as go-signals. This unexpected finding might suggest that gamma activity supports a go-process that not only responds to go-signals, but is also sensitive to stimuli that signal stopping.

We report a case of induced oscillopsia caused by deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN). Recent reports have described involuntary oscillopsia during DBS of the PPN that patients have described as trembling vision. Here we substantiate this observation using infra-red eye tracking. It has been suggested that this phenomenon might be used as an indicator of accurate targeting of the PPN with DBS. Our observations suggest that this phenomenon may not be related to a constricted anatomical structure and therefore such practise may be unwise. Scrutiny has led us to believe that the oscillopsia in our patient is not caused by direct stimulation of the oculomotor nerve as suggested in a previous report, but by stimulation of fibres in the uncinate fasciculus of the cerebellum and the superior cerebellar peduncle, which in turn stimulate the saccadic pre-motor neurones in the brainstem.

Parkinson's disease is treated pharmacologically with dopamine replacement medication and, more recently, by stimulating basal-ganglia nuclei such as the subthalamic nucleus (STN). Depth recordings after this procedure have revealed excessive activity at frequencies between 8 and 35 Hz (Brown et al., 2001; Kuhn et al., 2004; Priori et al., 2004) that are reduced by dopamine therapy in tandem with improvements in bradykinesia/rigidity, but not tremor (Kuhn et al., 2006). It has also been shown that improvements in motor symptoms after dopamine correlate with single unit activity in the beta range (Weinberger et al., 2006). We recorded local field potentials (LFPs) from the subthalamic nucleus of patients with Parkinson's disease (PD) after surgery to implant deep brain stimulating electrodes while they were on and off dopaminergic medication. As well as replicating Kuhn et al., using the same patients we were able to extend Weinberger et al. to show that LFP beta oscillatory activity correlated with the degree of improvement in bradykinesia/rigidity, but not tremor, after dopamine medication. We also found that the power of beta oscillatory activity uniquely predicted improvements in bradykinesia/rigidity, but again not tremor, after stimulation of the STN in a regression analysis. However improvements after STN stimulation related inversely to beta power, possibly reflecting the accuracy of the electrode placement and/or the limits of STN stimulation in patients with the greatest levels of beta oscillatory activity.