Measurements and models of current flow in the brain during transcranial Direct Current Stimulation (tDCS) indicate stimulation of regions in-between electrodes. Moreover, the folded cortex results in local fluctuations in current flow intensity and direction, and animal studies suggest current flow direction relative to cortical columns determines response to tDCS. Here we test this idea by using Transcranial Magnetic Stimulation Motor Evoked Potentials (TMS-MEP) to measure changes in corticospinal excitability following tDCS applied with electrodes aligned orthogonal (across) or parallel to M1 in the central sulcus. Current flow models predicted that the orthogonal electrode montage produces consistently oriented current across the hand region of M1 that flows along cortical columns, while the parallel electrode montage produces non-uniform current directions across the M1 cortical surface. We find that orthogonal, but not parallel, orientated tDCS modulates TMS-MEPs. We also show modulation is sensitive to the orientation of the TMS coil (PA or AP), which is thought to select different afferent pathways to M1. Our results are consistent with tDCS producing directionally specific neuromodulation in brain regions in-between electrodes, but shows nuanced changes in excitability that are presumably current direction relative to column and axon pathway specific. We suggest that the direction of current flow through cortical target regions should be considered for targeting and dose-control of tDCS.

Biphasic pulses produced by most commercially available TMS machines have a cosine waveform, which makes it difficult to study the interaction between the two phases of stimulation. We used a controllable pulse TMS (cTMS) device delivering quasi-rectangular pulse outputs to investigate whether monophasic are more effective than biphasic pulses. Temporally symmetric ("biphasic") or highly asymmetric ("monophasic") charge-balanced biphasic stimuli were used to target the hand area of motor cortex in the anterior-posterior (AP) or posterior-anterior (PA) initial current direction. We observed the lowest motor thresholds and shortest motor evoked potential (MEP) latencies with initial PA pulses, and highest thresholds and longest latencies with AP pulses. Increasing pulse symmetry tended to increase threshold with a PA direction whereas it lowered thresholds and shortened latencies with an AP direction. Furthermore, it steepened the MEP input-output curve with both directions. "Biphasic" TMS pulses can be viewed as two monophasic pulses of opposite directions, each stimulating a different set of interneurons with different thresholds (PA < AP). At threshold, the reverse phase of an initially PA pulse increases threshold compared with "monophasic" stimulation. At higher intensities, the reverse phase begins to activate AP-sensitive neurones and increase the effectiveness of stimulation above that of a "monophasic" PA pulse. "Biphasic" stimulation with initially AP pulses is dominated at threshold by activation produced by the lower threshold reverse (PA) phase. The effects of biphasic stimulation are best understood as the summed output of two independent sets of directionally selective neural populations.

Falls in extrapyramidal disorders, particularly Parkinson's disease (PD), multisystem atrophy (MSA), and progressive supranuclear palsy (PSP), are key milestones affecting patients' quality of life, incurring increased morbidity/mortality and high healthcare costs. Unfortunately, gait and balance in parkinsonisms respond poorly to currently available treatments. A serendipitous observation of improved gait and balance in patients with PD receiving spinal cord stimulation (SCS) for back pain kindled an interest in using SCS to treat gait disorders in parkinsonisms. We reviewed preclinical and clinical studies of SCS to treat gait dysfunction in parkinsonisms, covering its putative mechanisms and efficacies. Preclinical studies in animal models of PD and clinical studies in patients with PD, PSP, and MSA who received SCS for gait disorders were included. The main outcome assessed was clinical improvement in gait, together with outcome measures used and possible mechanism of actions. We identified 500 references, and 45 met the selection criteria and have been included in this study for analysis. Despite positive results in animal models, the outcomes in human studies are inconsistent. The lack of blind and statistically powered studies, the heterogeneity in patient selection and study outcomes, and the poor understanding of the underlying mechanisms of action of SCS are some of the limiting factors in the field. Addressing these limitations will allow us to draw more reliable conclusions on the effects of SCS on gait and balance in extrapyramidal disorders.

We control a biped robot moving in a crowd with a Model Predictive Control (MPC) scheme that generates stable walking motions, with automatic footstep placement. Most walking strategies propose to re-plan the walking motion to adapt to changing environments only once at every footstep. This is because a footstep is planted on the ground, it usually stays there at a constant position until the next footstep is initiated, what naturally constrains the capacity for the robot to react and adapt its motion in between footsteps. The objective of this paper is to measure if re-planning the walking motion more often than once at every footstep can lead to an improvement in collision avoidance when navigating in a crowd. Our result is that re-planning twice (or more) during each footstep leads to a significant reduction of the number of collisions when walking in a crowd, but depends on the density of the crowd.

Background: Postural imbalance with falls affects 80% of patients with Parkinson’s disease (PD) at 10 years. Standard PD therapies (e.g., levodopa and/or deep brain stimulation—DBS) are poor at improving postural imbalance. Additionally, the mechanistic complexity of interpreting postural control is a major barrier to improving our understanding of treatment effects. In this paper, we review the effects of DBS on balance as measured using posturography. We also critically appraise the quantitative measures and analyses used in these studies. Methods: A literature search was performed independently by 2 researchers using the PUBMED database. Thirty-eight studies are included in this review, with DBS at the subthalamic nucleus (STN-) (n = 25), globus pallidus internus (GPi-) (n = 6), ventral intermediate nucleus (VIM)/thalamus (n = 2), and pedunculopontine nucleus (PPN) (n = 5). Results: STN- and GPi-DBS reduce static sway in PD and mitigate the increased sway from levodopa. STN-DBS impairs automatic responses to perturbations, whilst GPi-DBS has a more neutral effect. STN-DBS may promote protective strategies following external perturbations but does not improve adaptation. The evidence regarding the effects on gait initiation is less clear. Insufficient evidence exists to make conclusions regarding VIM- and PPN-DBS. Conclusions: STN- and GPi-DBS have differing effects on posturography, which suggests site-specific and possibly non-dopaminergic mechanisms. Posturography tests should be utilised to answer specific questions regarding the mechanisms of and effects on postural control following DBS. We recommend standardising posturography measures and test conditions by expert consensus and greater long-term data collection, utilising ongoing DBS registries.

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.