Opportunities for Guided Multichannel Non-invasive Transcranial Current Stimulation in Poststroke Rehabilitation

I'm sure the mechanical and electrical engineers in your stroke department can make sense of this.
http://journal.frontiersin.org/article/10.3389/fneur.2016.00021/full?

Begonya Otal¹, Anirban Dutta², Águida Foerster³, Oscar Ripolles¹, Amy Kuceyeski⁴, Pedro C. Miranda⁵, Dylan J. Edwards⁶, Tihomir V. Ilić⁷, Michael A. Nitsche^8,9 and Giulio Ruffini^1,10*

• ¹Neuroelectrics Barcelona, Barcelona, Spain
• ²INRIA (Sophia Antipolis), Université Montpellier, Montpellier, France
• ³University of Medicine Göttingen, Göttingen, Germany
• ⁴Department of Radiology, Brain and Mind Research Institute, Weill Cornell Medical College, New York, NY, USA
• ⁵Institute of Biophysics and Biomedical Engineering (IBEB), Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal
• ⁶Non-Invasive Brain Stimulation and Human Motor Control Laboratory, Burke-Cornell Medical Research Institute, White Plains, NY, USA
• ⁷Department of Clinical Neurophysiology, Medical Faculty of Military Medical Academy, University of Defense, Belgrade, Serbia
• ⁸Leibniz Research Centre for Working Environment and Human Factors, Technical University of Dortmund, Dortmund, Germany
• ⁹Department of Neurology, University Medical Hospital Bergmannsheil, Bochum, Germany
• ¹⁰Starlab Barcelona, Barcelona, Spain

Stroke is a leading cause of serious long-term disability worldwide. Functional outcome depends on stroke location, severity, and early intervention. Conventional rehabilitation strategies have limited effectiveness, and new treatments still fail to keep pace, in part due to a lack of understanding of the different stages in brain recovery and the vast heterogeneity in the poststroke population. Innovative methodologies for restorative neurorehabilitation are required to reduce long-term disability and socioeconomic burden. Neuroplasticity is involved in poststroke functional disturbances and also during rehabilitation. Tackling poststroke neuroplasticity by non-invasive brain stimulation is regarded as promising, but efficacy might be limited because of rather uniform application across patients despite individual heterogeneity of lesions, symptoms, and other factors. Transcranial direct current stimulation (tDCS) induces and modulates neuroplasticity, and has been shown to be able to improve motor and cognitive functions. tDCS is suited to improve poststroke rehabilitation outcomes, but effect sizes are often moderate and suffer from variability. Indeed, the location, extent, and pattern of functional network connectivity disruption should be considered when determining the optimal location sites for tDCS therapies. Here, we present potential opportunities for neuroimaging-guided tDCS-based rehabilitation strategies after stroke that could be personalized. We introduce innovative multimodal intervention protocols based on multichannel tDCS montages, neuroimaging methods, and real-time closed-loop systems to guide therapy. This might help to overcome current treatment limitations in poststroke rehabilitation and increase our general understanding of adaptive neuroplasticity leading to neural reorganization after stroke.

Introduction

Although spontaneous poststroke recovery occurs, between 15% and 30% of stroke survivors are left permanently disabled (1). Poststroke rehabilitation helps relearn skills that are lost when part of the brain is damaged. As an adjunct therapy, non-invasive brain stimulation (NIBS) techniques, including repetitive transcranial magnetic stimulation (rTMS) and transcranial current stimulation (tCS) – particularly direct current stimulation (tDCS) – are promising approaches to enhance the effects of standardized rehabilitation treatments in selected poststroke patients. Like rTMS, tDCS can alter cortical excitability in predictable ways. tDCS is characterized as neuromodulatory rather than neurostimulatory, since the currents delivered during tDCS are not sufficient to directly generate action potentials. tDCS-induced excitability alterations depend on the duration, current density, and direction of the current flow. Generally, anodal tDCS (a-tDCS) enhances excitability, while cathodal tDCS (c-tDCS) reduces it (2–4). Whereas after-effects of single stimulation sessions are in the time range of early-phase long-term potentiation and long-term depression (~1 h), repetitive stimulations with certain intervals can induce late-phase effects lasting longer than 24 h after intervention (3–6). tDCS is a well-tolerated technique, easily applied over cortical targets leading to adaptive neural reorganization and the reduction in maladaptive plasticity during behavioral treatment. Further, tDCS is less expensive and likely to be better accepted by patients than rTMS (7, 8), making it potentially well poised for home therapy.

Currently, the need to target not an isolated cortical region, but several functionally correlated cortical hubs involved in larger scale intrinsic brain networks is becoming increasingly recognized (9, 10). Advances in neuroimaging technology, such as functional magnetic resonance imaging (fMRI), diffusion tensor imaging, electroencephalography (EEG), and functional near-infrared spectroscopy (fNIRS), are allowing us to non-invasively visualize and quantify brain network connectivity in humans with increasing accuracy. Recently, we showed how the optimal electrode configuration of a multichannel tDCS system can be determined by using neuroimaging data to specify a target map on the cortical surface for excitatory or inhibitory stimulation (11). Multichannel tDCS is a new approach highly capable of efficiently targeting distributed brain networks to facilitate beneficial neuroplasticity and functional connectivity leading to poststroke recovery.

Portable neuroimaging solutions, such as EEG and fNIRS, can objectively capture individual brain states poststroke, which can be used to customize and adapt NIBS in real time to facilitate training (12, 13). An EEG–fNIRS-based method (14) was recently proposed for screening and monitoring of neurovascular coupling functionality in combination with tDCS. In this system, neuronal and hemodynamic responses were abstractly represented as feedback for tDCS effects. Such innovative portable EEG–fNIRS neuroimaging systems could be used to objectively guide and quantify the progress of a tDCS treatment regime in conjunction with neurorehabilitation. Moreover, system identification and parameter estimation techniques using neuronal and hemodynamic responses to tDCS can be used to track the effects, e.g., on corticospinal excitability, for closed-loop control of tDCS. Poststroke integrity of task-specific ipsilesional and/or contralesional neural pathways can be determined with EEG–fNIRS neuroimaging during task performance, which can be leveraged toward the optimization of subject-specific tDCS. The goal may be to correlate functional outcome with regard to EEG–fNIRS brain activation patterns as a marker of the underlying task-specific residual activation such that those residual brain activation patterns are facilitated with individualized brain state-dependent multichannel tDCS as an adjunct treatment during stroke rehabilitation.

Here, we introduce the potential of these two methods (11, 14) to optimize future multichannel tDCS systems for modulation of excitability of brain networks, represented by spatially extended cortical targets. Combining both models closely addresses the individual determinants of patterns of neuroplastic changes both to guide tDCS treatment and to assess functional recovery. We present potential novel application opportunities based on guided multichannel tDCS in poststroke rehabilitation. Likewise, we show how multimodal approaches pairing neuroimaging and electrophysiological measures with therapeutic tDCS can extend its potential in aiding customized and personalized long-term rehabilitation strategies, including post-acute rehabilitation after stroke.

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