Sensory attenuation in sport and rehabilitation:perspective from research in Parkinson's disease

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

Single-trial multiwavelet coherence in application to neurophysiological time series

A method of single-trial coherence analysis is presented, through the application of continuous muldwavelets. Multiwavelets allow the construction of spectra and bivariate statistics such as coherence within single trials. Spectral estimates are made consistent through optimal time-frequency localization and smoothing. The use of multiwavelets is considered along with an alternative single-trial method prevalent in the literature, with the focus being on statistical, interpretive and computational aspects. The multiwavelet approach is shown to possess many desirable properties, including optimal conditioning, statistical descriptions and computational efficiency. The methods. are then applied to bivariate surrogate and neurophysiological data for calibration and comparative study. Neurophysiological data were recorded intracellularly from two spinal motoneurones innervating the posterior,biceps muscle during fictive locomotion in the decerebrated cat

Modulation of Long-Range Connectivity Patterns via Frequency-Specific Stimulation of Human Cortex

There is increasing interest in how the phase of local oscillatory activity within a brain area determines the long-range functional connectivity of that area. For example, increasing convergent evidence from a range of methodologies suggests that beta (20 Hz) oscillations may play a vital role in the function of the motor system [1-5]. The "communication through coherence" hypothesis posits that the precise phase of coherent oscillations in network nodes is a determinant of successful communication between them [6, 7]. Here we set out to determine whether oscillatory activity in the beta band serves to support this theory within the cortical motor network in vivo. We combined non-invasive transcranial alternating-current stimulation (tACS) [8-12] with resting-state functional MRI (fMRI) [13] to follow both changes in local activity and long-range connectivity, determined by inter-areal blood-oxygen-level-dependent (BOLD) signal correlation, as a proxy for communication in the human cortex. Twelve healthy subjects participated in three fMRI scans with 20 Hz, 5 Hz, or sham tACS applied separately on each scan. Transcranial magnetic stimulation (TMS) at beta frequency has previously been shown to increase local activity in the beta band [14] and to modulate long-range connectivity within the default mode network [15]. We demonstrated that beta-frequency tACS significantly changed the connectivity pattern of the stimulated primary motor cortex (M1), without changing overall local activity or network connectivity. This finding is supported by a simple phase-precession model, which demonstrates the plausibility of the results and provides emergent predictions that are consistent with our empirical findings. These findings therefore inform our understanding of how local oscillatory activity may underpin network connectivity

Montage Matters: The Influence of Transcranial Alternating Current Stimulation on Human Physiological Tremor

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

A functional micro-electrode mapping of ventral thalamus in Essential Tremor

Deep brain stimulation enables the delivery of therapeutic interventions to otherwise inaccessible areas of the brain while, at the same time, offering the unique opportunity to record from these same regions in awake patients. The posterior ventrolateral thalamus has become a reliable deep brain stimulation target for medically-refractory patients suffering from essential tremor. However, the contribution of the thalamus in essential tremor, and even whether posterior ventrolateral thalamus is the optimal target, remains a matter of ongoing debate. There are several lines of evidence supporting clusters of activity within the posterior ventrolateral thalamus that are important for tremor emergence. In this study we sought to map the functional properties of these clusters through microelectrode recordings during deep brain stimulation surgery. Data were obtained from 10 severely affected patients with essential tremor (12 hemispheres) undergoing deep brain stimulation surgery. Our results demonstrate power and coherence maxima located in the inferior posterior ventrolateral thalamus and immediate ventral region. Moreover, we identified distinct yet overlapping clusters of predominantly efferent (driving) and afferent (feedback) activity, with a preference for more efferent contributors, consistent with a net role in the driving of tremor output. Finally, we demonstrate that resolvable thalamic spiking activity directly relates to background activity and that the strength of tremor may be dictated by phase relationships between efferent and afferent pockets in the posterior ventrolateral thalamus. Taken together, these results provide important evidence for the role of the inferior posterior ventrolateral thalamus and its border region in essential tremor pathophysiology. Such results progress our mechanistic understanding and promote the adoption of next-generation therapies such as high resolution segregated deep brain stimulation electrodes

Gain-of-Function Mutations in the K_ATP Channel (KCNJ11) Impair Coordinated Hand-Eye Tracking

Background: Gain-of-function mutations in the ATP-sensitive potassium channel can cause permanent neonatal diabetes mellitus (PNDM) or neonatal diabetes accompanied by a constellation of neurological symptoms (iDEND syndrome). Studies of a mouse model of iDEND syndrome revealed that cerebellar Purkinje cell electrical activity was impaired and that the mice exhibited poor motor coordination. In this study, we probed the hand-eye coordination of PNDM and iDEND patients using visual tracking tasks to see if poor motor coordination is also a feature of the human disease.Methods: Control participants (n = 14), patients with iDEND syndrome (n = 6 or 7), and patients with PNDM (n = 7) completed three computer-based tasks in which a moving target was tracked with a joystick-controlled cursor. Patients with PNDM and iDEND were being treated with sulphonylurea drugs at the time of testing.Results: No differences were seen between PNDM patients and controls. Patients with iDEND syndrome were significantly less accurate than controls in two of the three tasks. The greatest differences were seen when iDEND patients tracked blanked targets, i.e. when predictive tracking was required. In this task, iDEND patients incurred more discrepancy errors (p = 0.009) and more velocity errors (p  = 0.009) than controls.Conclusions: These results identify impaired hand-eye coordination as a new clinical feature of iDEND. The aetiology of this feature is likely to involve cerebellar dysfunction. The data further suggest that sulphonylurea doses that control the diabetes of these patients may be insufficient to fully correct their neurological symptoms.</p