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Background: There is a current discord between the foundational theories underpinning motor learning and how we currently apply transcranial direct current stimulation (TDCS): the former is dependent on tight coupling of events while the latter is conducted with very low temporal resolution. Objective: Here we aimed to investigate the temporal specificity of stimulation by applying TDCS in short epochs, and coincidentally with movement, during a motor adaptation task. Methods: Participants simultaneously adapted a reaching movement to two opposing velocity-dependent force-fields (clockwise and counter-clockwise), distinguished by a contextual leftward or rightward shift in the task display and cursor location respectively. Brief bouts (

Abstract Adaptation of movements involving the proximal and distal upper-limb can be differentially facilitated by anodal transcranial direct current stimulation (TDCS) over the cerebellum and primary motor cortex (M1). Here, we build on this evidence by demonstrating that cathodal TDCS impairs motor adaptation with a differentiation of the proximal and distal upper-limbs, relative to the site of stimulation. Healthy young adults received M1 or cerebellar cathodal TDCS while making fast ‘shooting’ movements towards targets under 60° rotated visual feedback conditions, using either whole-arm reaching or fine hand and finger movements. As predicted, we found that cathodal cerebellar TDCS resulted in impairment of adaptation of movements with the whole arm compared to M1 and sham groups, which proved significantly different during late adaptation. However, cathodal cerebellar TDCS also significantly enhanced adaptation of hand movements, which may reflect changes in the excitability of the pathway between the cerebellum and M1. We found no evidence for change of adaptation rates using arm or finger movements following cathodal TDCS directly over M1. These results are further evidence to support movement specific effects of TDCS, and highlight how the connectivity and functional organisation of the cerebellum and M1 must be considered when designing TDCS-based therapies.

Background: The cerebellum and primary motor cortex (M1) are crucial to coordinated and accurate movements of the upper limbs. There is also appreciable evidence that these two structures exert somewhat divergent influences upon proximal versus distal upper limb control. Here, we aimed to differentially regulate the contribution of the cerebellum and M1 to proximal and distal effectors during motor adaptation, with transcranial direct current stimulation (tDCS). For this, we employed tasks that promote similar motor demands, but isolate whole arm from hand/finger movements, in order to functionally segregate the hierarchy of upper limb control. Methods: Both young and older adults took part in a visuomotor rotation task; where they adapted to a 60° visuomotor rotation using either a hand-held joystick (requiring finger/hand movements) or a 2D robotic manipulandum (requiring whole-arm reaching movements), while M1, cerebellar or sham tDCS was applied. Results: We found that cerebellar stimulation improved adaptation performance when arm movements were required to complete the task, while in contrast stimulation of M1 enhanced adaptation during hand and finger movements only. This double-dissociation was replicated in an independent group of older adults, demonstrating that the behaviour remains intact in ageing. Conclusions: These results suggest that stimulation of distinct motor areas can selectively improve motor adaptation in the proximal and distal upper limb. This also highlights new ways in which tDCS might be best applied to achieve reliable rehabilitation of upper limb motor deficits.

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.

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.

Optimal decision-making requires balancing fast but error-prone and more accurate but slower decisions through adjustments of decision thresholds. Here, we demonstrate two distinct correlates of such speed-accuracy adjustments by recording subthalamic nucleus (STN) activity and electroencephalography in 11 Parkinson’s disease patients during a perceptual decision-making task; STN low-frequency oscillatory (LFO) activity (2–8 Hz), coupled to activity at prefrontal electrode Fz, and STN beta activity (13–30 Hz) coupled to electrodes C3/C4 close to motor cortex. These two correlates differed not only in their cortical topography and spectral characteristics but also in the relative timing of recruitment and in their precise relationship with decision thresholds. Increases of STN LFO power preceding the response predicted increased thresholds only after accuracy instructions, while cue-induced reductions of STN beta power decreased thresholds irrespective of instructions. These findings indicate that distinct neural mechanisms determine whether a decision will be made in haste or with caution.

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.

Abstract Objective Respiratory abnormalities such as upper airway obstruction are common in Parkinson's disease (PD) and are an important cause of mortality and morbidity. We tested the effect of pedunculopontine region (PPNr) stimulation on respiratory maneuvers in human participants with PD, and separately recorded PPNr neural activity reflected in the local field potential (LFP) during these maneuvers. Methods Nine patients with deep brain stimulation electrodes in PPNr, and seven in globus pallidus interna (GPi) were studied during trials of maximal inspiration followed by forced expiration with stimulation OFF and ON. Local field potentials (LFPs) were recorded in the unstimulated condition. Results PEFR increased from 6.41 ± 0.63 L/sec in the OFF stimulation state to 7.5 L ± 0.65 L/sec in the ON stimulation state (z = −2.666, df = 8, P = 0.024). Percentage improvement in PEFR was strongly correlated with proximity of the stimulated electrode contact to the mesencephalic locomotor region in the rostral PPN (r = 0.814, n = 9, P = 0.008). Mean PPNr LFP power increased within the alpha band (7–11 Hz) during forced respiratory maneuvers (1.63 ± 0.16 μV2/Hz) compared to resting breathing (0.77 ± 0.16 μV2/Hz; z = −2.197, df = 6, P = 0.028). No changes in alpha activity or spirometric indices were seen with GPi recording or stimulation. Percentage improvement in PEFR was strongly positively correlated with increase in alpha power (r = 0.653, n = 14 (7 PPNr patients recorded bilaterally), P = 0.0096). Interpretation PPNr stimulation in PD improves indices of upper airway function. Increased alpha‐band activity is seen within the PPNr during forced respiratory maneuvers. Our findings suggest a link between the PPNr and respiratory performance in PD.