Disruption of subthalamic nucleus dynamics in Parkinson’s disease leads to impairments during walking. Here, we aimed to uncover the principles through which the subthalamic nucleus encodes functional and dysfunctional walking in people with Parkinson’s disease. We conceived a neurorobotic platform embedding an isokinetic dynamometric chair that allowed us to deconstruct key components of walking under well-controlled conditions. We exploited this platform in 18 patients with Parkinson’s disease to demonstrate that the subthalamic nucleus encodes the initiation, termination, and amplitude of leg muscle activation. We found that the same fundamental principles determine the encoding of leg muscle synergies during standing and walking. We translated this understanding into a machine learning framework that decoded muscle activation, walking states, locomotor vigor, and freezing of gait. These results expose key principles through which subthalamic nucleus dynamics encode walking, opening the possibility to operate neuroprosthetic systems with these signals to improve walking in people with Parkinson’s disease.
ABSTRACT Disruption of subthalamic nucleus dynamics in Parkinson’s disease leads to impairments during walking. Here, we aimed to uncover the principles through which the subthalamic nucleus encodes functional and dysfunctional walking in people with Parkinson’s disease. We conceived a neurorobotic platform that allowed us to deconstruct the key components of walking under well-controlled conditions. We exploited this platform in 18 patients with Parkinson’s disease, which allowed us to demonstrate that the subthalamic nucleus encodes the initiation, termination, and vigor of leg muscle activation. We found that the same fundamental principles determine the encoding of walking. We translated this understanding into a machine-learning framework that decoded muscle activation, walking states, locomotor vigor, and freezing of gait. These results expose key principles through which subthalamic nucleus dynamics encode walking, opening the possibility to operate neuroprosthetic systems with these signals to improve walking in people with Parkinson’s disease. One Sentence Summary The subthalamic nucleus encodes the initiation, termination, and vigor of muscle activity, which supports real-time decoding of gait in people with Parkinson’s disease.
Ataxia-telangiectasia (A-T) is an autosomal-recessive disorder characterized by cerebellar ataxia, oculocutaneous telangiectasia, immunodeficiency, radiosensitivity, increased prevalence of malignancies, and increased level of alpha-fetoprotein (AFP). 1 The responsible gene A-T mutated (ATM), localized to chromosome 11q22-2, is a serine/threonine protein kinase that is involved in the cellular response to DNA damage.Whereas the classic form, genetically marked by truncating mutations of the ATM, is a severe, fast progressive disease with no residual ATM kinase activity, patients with variant A-T show a milder form of the disease, often presenting with a plethora of different extrapyramidal manifestations-choreoathetosis, resting tremor, and myoclonus-dystonia (M-D) and still have some residual ATM-kinase activity; they are usually carriers of at least one missense or leaky splice site mutation. 1,2We present a case of a variant A-T with mainly M-D presenting features and a favorable outcome after bilateral DBS of the globus pallidus pars interna (GPi-DBS).
Abstract Measurements and models of current flow in the brain during transcranial Direct Current Stimulation (tDCS) indicate stimulation of regions in-between electrodes. Moreover, the cephalic cortex result 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 measuring changes in cortico-spinal excitability by Transcranial Magnetic Stimulation Motor Evoked Potentials (TMS-MEP), 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 none-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 through 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. Highlights Direction of current flow is important for tDCS after-effects. tDCS modulates excitability between two electrodes. tDCS differentially modulates PA and AP inputs into M1. Abbreviations PA postero-anterior AP antero-posterior ML medio-lateral tDCS transcranial direct current stimulation MEP motor evoked potential M1 primary motor cortex TMS transcranial magnetic stimulation; AP-TMS-MEPs motor evoked potentials elicited with anterior-posterior directed TMS; PA-TMS-MEPs motor evoked potentials elicited with posterior-anterior directed TMS Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
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