Bayesian optimization of peripheral intraneural stimulation protocols to evoke distal limb movements

Objective. Motor neuroprostheses require the identification of stimulation protocols that effectively produce desired movements. Manual search for these protocols can be very time-consuming and often leads to suboptimal solutions, as several stimulation parameters must be personalized for each subject for a variety of target movements. Here, we present an algorithm that efficiently tunes peripheral intraneural stimulation protocols to elicit functionally relevant distal limb movements. Approach. We developed the algorithm using Bayesian Optimization and defined multi-objective functions based on the coordinated recruitment of multiple muscles. We implemented different multi-output Gaussian Processes to model our system and compared their functioning by applying the algorithm offline to data acquired in rats for walking control and in monkeys for hand grasping control. We then performed a preliminary online test in a monkey to experimentally validate the functionality of our method. Main results. Offline, optimal intraneural stimulation protocols for various target motor functions were rapidly identified in both experimental scenarios. Using the model that performed best, the algorithm converged to stimuli that evoked functionally consistent movements with an average number of actions equal to 20% (13% unique) and 20% (16% unique) of the search space size in rats and monkeys, respectively. Online, the algorithm quickly guided the observations to stimuli that elicited functional hand gestures, although more selective motor outputs could have been achieved by refining the objective function used. Significance. These results demonstrate that Bayesian Optimization can reliably and efficiently automate the tuning of peripheral neurostimulation protocols, establishing a translational framework to configure peripheral motor neuroprostheses in clinical applications. The proposed method can potentially be applied to optimize motor functions using other stimulation modalities.

Theoretical Perspective on an Ideomotor Brain-Computer Interface: Toward a Naturalistic and Non-invasive Brain-Computer Interface Paradigm Based on Action-Effect Representation

Recent years have been marked by the fulgurant expansion of non-invasive Brain-Computer Interface (BCI) devices and applications in various contexts (medical, industrial etc.). This technology allows agents “to directly act with thoughts,” bypassing the peripheral motor system. Interestingly, it is worth noting that typical non-invasive BCI paradigms remain distant from neuroscientific models of human voluntary action. Notably, bidirectional links between action and perception are constantly ignored in BCI experiments. In the current perspective article, we proposed an innovative BCI paradigm that is directly inspired by the ideomotor principle, which postulates that voluntary actions are driven by the anticipated representation of forthcoming perceptual effects. We believe that (1) adapting BCI paradigms could allow simple action-effect bindings and consequently action-effect predictions and (2) using neural underpinnings of those action-effect predictions as features of interest in AI methods, could lead to more accurate and naturalistic BCI-mediated actions.

Clinical, Neurophysiological, and MRI Markers of Fampridine Responsiveness in Multiple Sclerosis—An Explorative Study

Objective: Persons with multiple sclerosis (PwMS), already established as responders or non-responders to Fampridine treatment, were compared in terms of disability measures, physical and cognitive performance tests, neurophysiology, and magnetic resonance imaging (MRI) outcomes in a 1-year explorative longitudinal study.Materials and Methods: Data from a 1-year longitudinal study were analyzed. Examinations consisted of the timed 25-foot walk test (T25FW), six spot step test (SSST), nine-hole peg test (9-HPT), five times sit-to-stand test (5-STS), symbol digit modalities test (SDMT), transcranial magnetic stimulation (TMS) elicited motor evoked potentials (MEP) examining central motor conduction times (CMCT), peripheral motor conduction times (PMCT) and their amplitudes, electroneuronography (ENG) of the lower extremities, and brain structural MRI measures.Results: Forty-one responders and eight non-responders to Fampridine treatment were examined. There were no intergroup differences except for the PMCT, where non-responders had prolonged conduction times compared to responders to Fampridine. Six spot step test was associated with CMCT throughout the study. After 1 year, CMCT was further prolonged and cortical MEP amplitudes decreased in both groups, while PMCT and ENG did not change. Throughout the study, CMCT was associated with the expanded disability status scale (EDSS) and 12-item multiple sclerosis walking scale (MSWS-12), while SDMT was associated with number of T2-weighted lesions, lesion load, and lesion load normalized to brain volume.Conclusions: Peripheral motor conduction time is prolonged in non-responders to Fampridine when compared to responders. Transcranial magnetic stimulation-elicited MEPs and SDMT can be used as markers of disability progression and lesion activity visualized by MRI, respectively.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT03401307.

Zoster-associated limb paralysis mimicking acute stroke: a case report

Background Varicella zoster virus is a Deoxyribonucleic acid (DNA) virus exclusively affecting humans. Reactivation of varicella zoster virus causes herpes zoster with vesicular eruptions in a restricted dermatomal distribution. Peripheral motor neuropathy is a very rare complication of varicella zoster virus. Case presentation A 57-year-old previously well Sri Lankan female presented with acute onset painful weakness of the left upper limb with a preceding history of a febrile illness. Subsequently she developed vesicular eruptions in the dermatomal distribution of cervical 5, 6, and 7. Electromyography was suggestive of acute denervation of cervical 5, 6, and 7 myotomes. Diagnosis of zoster-associated brachial plexopathy was made, and the patient was treated with acyclovir, steroids, and analgesics. She made a good recovery. Conclusion Brachial plexus neuritis due to varicella zoster infection should be considered in an acute monoparesis of a limb as it is a treatable and reversible condition

Spontaneous Production Rates in Music and Speech

Individuals typically produce auditory sequences, such as speech or music, at a consistent spontaneous rate or tempo. We addressed whether spontaneous rates would show patterns of convergence across the domains of music and language production when the same participants spoke sentences and performed melodic phrases on a piano. Although timing plays a critical role in both domains, different communicative and motor constraints apply in each case and so it is not clear whether music and speech would display similar timing mechanisms. We report the results of two experiments in which adult participants produced sequences from memory at a comfortable spontaneous (uncued) rate. In Experiment 1, monolingual pianists in Buffalo, New York engaged in three production tasks: speaking sentences from memory, performing short melodies from memory, and tapping isochronously. In Experiment 2, English-French bilingual pianists in Montréal, Canada produced melodies on a piano as in Experiment 1, and spoke short rhythmically-structured phrases repeatedly. Both experiments led to the same pattern of results. Participants exhibited consistent spontaneous rates within each task. People who produced one spoken phrase rapidly were likely to produce another spoken phrase rapidly. This consistency across stimuli was also found for performance of different musical melodies. In general, spontaneous rates across speech and music tasks were not correlated, whereas rates of tapping and music were correlated. Speech rates (for syllables) were faster than music rates (for tones) and speech showed a smaller range of spontaneous rates across individuals than did music or tapping rates. Taken together, these results suggest that spontaneous rate reflects cumulative influences of endogenous rhythms (in consistent self-generated rates within domain), peripheral motor constraints (in finger movements across tapping and music), and communicative goals based on the cultural transmission of auditory information (slower rates for to-be-synchronized music than for speech).

Spinal cord precursors utilize neural crest cell mechanisms to generate hybrid peripheral myelinating glia

During development, oligodendrocytes and Schwann cells myelinate central and peripheral nervous system axons, respectively, while motor exit point (MEP) glia are neural tube-derived, peripheral glia that myelinate axonal territory between these populations at MEP transition zones. From which specific neural tube precursors MEP glia are specified, and how they exit the neural tube to migrate onto peripheral motor axons, remain largely unknown. Here, using zebrafish, we found that MEP glia arise from lateral floor plate precursors and require foxd3 to delaminate and exit the spinal cord. Additionally, we show that similar to Schwann cells, MEP glial development depends on axonally derived neuregulin1. Finally, our data demonstrate that overexpressing axonal cues is sufficient to generate additional MEP glia in the spinal cord. Overall, these studies provide new insight into how a novel population of hybrid, peripheral myelinating glia are generated from neural tube precursors and migrate into the periphery.