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Plastic Changes in Human Motor Cortical Output Induced by Random but not Closed-Loop Peripheral Stimulation: the Curse of Causality

Lookup NU author(s): Kenneth Brown, Dr Elizabeth Williams, Felipe De Carvalho, Professor Stuart BakerORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Previous work showed that repetitive peripheral nerve stimulation can induce plastic changes in motor cortical output. Triggering electrical stimulation of central structures from natural activity can also generate plasticity. In this study, we tested whether triggering peripheral nerve stimulation from muscle activity would likewise induce changes in motor output. We developed a wearable electronic device capable of recording electromyogram (EMG) and delivering electrical stimulation under closed-loop control. This allowed paired stimuli to be delivered over longer periods than standard laboratory-based protocols. We tested this device in healthy human volunteers. Motor cortical output in relaxed thenar muscles was first assessed via the recruitment curve of responses to contralateral transcranial magnetic stimulation. The wearable device was then configured to record thenar EMG and stimulate the median nerve at the wrist (intensity around motor threshold, rate similar to 0.66 Hz). Subjects carried out normal daily activities for 4-7 h, before returning to the laboratory for repeated recruitment curve assessment. Four stimulation protocols were tested (9-14 subjects each): No Stim, no stimuli delivered; Activity, stimuli triggered by EMG activity above threshold; Saved, stimuli timed according to a previous Activity session in the same subject; Rest, stimuli given when EMG was silent. As expected, No Stim did not modify the recruitment curve. Activity and Rest conditions produced no significant effects across subjects, although there were changes in some individuals. Saved produced a significant and substantial increase, with average responses 2.14 times larger at 30% stimulator intensity above threshold. We argue that unavoidable delays in the closed loop feedback, due mainly to central and peripheral conduction times, mean that stimuli in the Activity paradigm arrived too late after cortical activation to generate consistent plastic changes. By contrast, stimuli delivered essentially at random during the Saved paradigm may have caused a generalized increase in cortical excitability akin to stochastic resonance, leading to plastic changes in corticospinal output. Our study demonstrates that non-invasive closed loop stimulation may be critically limited by conduction delays and the unavoidable constraint of causality.

Publication metadata

Author(s): Brown KI, Williams ER, de Carvalho F, Baker SN

Publication type: Article

Publication status: Published

Journal: Frontiers in Human Neuroscience

Year: 2016

Volume: 10

Online publication date: 15/11/2016

Acceptance date: 04/11/2016

Date deposited: 26/01/2017

ISSN (electronic): 1662-5161

Publisher: Frontiers Research Foundation


DOI: 10.3389/fnhum.2016.00590


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Funder referenceFunder name
101002Wellcome Trust
G0801705Medical Research Council