Abstract

Stroke is a leading cause of worldwide disability, and up to 75% of survivors suffer from some degree of arm paresis. Recently, rehabilitation of stroke patients has focused on recovering motor skills by taking advantage of use-dependent neuroplasticity, where high-repetition of goal-oriented movement is at times combined with non-invasive brain stimulation, such as transcranial direct current stimulation (tDCS). Merging the two approaches is thought to provide outlasting clinical gains, by enhancing synaptic plasticity and motor relearning in the motor cortex primary area. However, this general approach has shown mixed results across the stroke population. In particular, stroke location has been found to correlate with the likelihood of success, which suggests that different patients might require different protocols. Understanding how motor rehabilitation and stimulation interact with ongoing neural dynamics is crucial to optimize rehabilitation strategies, but it requires theoretical and computational models to consider the multiple levels at which this complex phenomenon operate. In this work, we argue that biophysical models of cortical dynamics are uniquely suited to address this problem. Specifically, biophysical models can predict treatment efficacy by introducing explicit variables and dynamics for damaged connections, changes in neural excitability, neurotransmitters, neuromodulators, plasticity mechanisms, and repetitive movement, which together can represent brain state, effect of incoming stimulus, and movement-induced activity. In this work, we hypothesize that effects of tDCS depend on ongoing neural activity and that tDCS effects on plasticity may be also related to enhancing inhibitory processes. We propose a model design for each step of this complex system, and highlight strengths and limitations of the different modeling choices within our approach. Our theoretical framework proposes a change in paradigm, where biophysical models can contribute to the future design of novel protocols, in which combined tDCS and motor rehabilitation strategies are tailored to the ongoing dynamics that they interact with, by considering the known biophysical factors recruited by such protocols and their interaction.

Highlights

  • Specialty section: This article was submitted to Stroke, a section of the journal Frontiers in Neurology

  • Rehabilitation of stroke patients has focused on recovering motor skills by taking advantage of use-dependent neuroplasticity, where high-repetition of goal-oriented movement is at times combined with non-invasive brain stimulation, such as transcranial direct current stimulation

  • Our theoretical framework proposes a change in paradigm, where biophysical models can contribute to the future design of novel protocols, in which combined transcranial direct current stimulation (tDCS) and motor rehabilitation strategies are tailored to the ongoing dynamics that they interact with, by considering the known biophysical factors recruited by such protocols and their interaction

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Summary

Cortical Activity after a Stroke

Due to the interruption of blood supply to the brain determining an acute neurologic condition [1], is a major cause of disability worldwide, often resulting in limited motor recovery in the paretic upper limb. A stroke initiates a large amount of changes in cortical excitability, connectivity (i.e., the synaptic wiring within and across brain regions), and coding (i.e., the specific neural spiking patterns that encode for movement are likely different after stroke) These changes, not completely understood, occur on different time scales: some immediately after the injury and some are slowly established on the course of months (the chronic phase). FMRI studies show that bilateral activation in both the ipsilesional (affected) and controlesional (unaffected) hemispheres occurs, revealing the development of early cortical reorganization processes [14, 15] These findings suggest that a damaged brain is still plastic and possibly amenable to be influenced by experiences. Though a rebalance between hemispheres is considered a sign of good recovery in chronic phase, whether such bilateral activation is adaptive or maladaptive is still on debate [19, 20]

Recovery Depends on Network State
Motor Recovery
MODELING HOW BRAIN DYNAMICS INTERACTS WITH STIMULATION AND NEUROREHABILITATION
Understanding the Effect of tDCS on Stroke Brain Dynamics
Representing Different tDCS Stimulations in a Model
Findings
Modeling How Synaptic Plasticity
Full Text
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