Driving Oscillatory Dynamics: Neuromodulation for Recovery After Stroke

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Driving Oscillatory Dynamics: Neuromodulation for Recovery After Stroke

Sven Storch^†, Montana Samantzis^† and Matilde Balbi^*

• Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia

Stroke is a leading cause of death and disability worldwide, with limited treatments being available. However, advances in optic methods in neuroscience are providing new insights into the damaged brain and potential avenues for recovery. Direct brain stimulation has revealed close associations between mental states and neuroprotective processes in health and disease, and activity-dependent calcium indicators are being used to decode brain dynamics to understand the mechanisms underlying these associations. Evoked neural oscillations have recently shown the ability to restore and maintain intrinsic homeostatic processes in the brain and could be rapidly deployed during emergency care or shortly after admission into the clinic, making them a promising, non-invasive therapeutic option. We present an overview of the most relevant descriptions of brain injury after stroke, with a focus on disruptions to neural oscillations. We discuss the optical technologies that are currently used and lay out a roadmap for future studies needed to inform the next generation of strategies to promote functional recovery after stroke.

Introduction

Stroke is a debilitating neurological condition that constitutes a major cause of adult disability, affecting 10 million patients annually. Recent advances in treatment have improved the prognosis of stroke survivors, but few treatment options are available for most patients. Tissue plasminogen activator (tPA), the gold standard treatment for ischemic stroke, can break up the clot if administered within a narrow therapeutic window of <4.5 h (Cheatwood et al., 2008). However, <5% of patients are eligible to be treated with tPA (Henninger and Fisher, 2016), requiring a new strategic approach to guide translational interventions.

Following stroke changes occur at the molecular, circuit, and behavioural levels. These include activation of inflammatory pathways and increased oxidative stress (Moskowitz et al., 2010). On a circuit and interhemispheric level, there is an imbalance of inhibitory and excitatory neuronal activity, and disruption of neural networks (Aronowski and Zhao, 2011). Ultimately, these changes lead to neuronal death and loss of synaptic connections that, depending on which part of the brain is affected, result in behavioural deficits such as weakness, limb hemiparesis, and loss of coordination (Hatem et al., 2016; Lodha et al., 2017), as well as speech and cognitive impairments (Sun et al., 2014). This loss of function can be partly recovered due to neuroplastic processes, including the rewiring of neural connections and compensation from other brain regions (Alia et al., 2017). The peri-infarct area is the major region where this plasticity occurs, through the expression of both growth-promoting and growth-inhibitory proteins that induce key neural plasticity processes including spinogenesis, and intense rewiring of neuronal circuits (Carmichael, 2006; Overman et al., 2012; Clarkson et al., 2013; Silasi and Murphy, 2014). Researchers have harnessed these neuroplastic processes to promote recovery in stroke survivors by using neuromodulatory pharmaceuticals and stimulation techniques including exercise, GABA_A receptor antagonists, and brain stimulation (Boddington and Reynolds, 2017; Caglayan et al., 2019; Inoue et al., 2020).

Brain stimulation methods are currently used in the treatment of many disorders, including obsessive compulsive disorder, depression, and epilepsy (Johnson et al., 2013). Invasive and non-invasive stimulation has led to promising motor recovery in several disorders such as Parkinson's disease (PD), tremors, and spinal cord injuries (Johnson et al., 2013). Deep brain stimulation (DBS) is a method of invasive stimulation used to treat stroke (Elias et al., 2018), while non-invasive approaches include transcranial magnetic stimulation (TMS) (Smith and Stinear, 2016), transcranial direct current stimulation (tDCS) (Sawan et al., 2020), and transcranial alternating current stimulation (tACS) (Solomons and Shanmugasundaram, 2019). These techniques rely on different electromagnetic principles to modulate brain activity, and their effects which range from the molecular to the behavioural level, are still poorly understood. Changes to resting oscillatory brain activity are key features in several neurological disorders (Başar et al., 2016; Assenza et al., 2017), leading Krawinkel et al. to suggest that brain stimulation tools could be used to modulate abnormal oscillatory activity and guide behavioural recovery (Krawinkel et al., 2015). This type of targeted neuromodulation has since shown promising effects in the treatment of PD, Alzheimer's disease (AD) and epilepsy, among other neurological disorders (Andrade et al., 2016; Mably and Colgin, 2018).

In this review we focus our attention on the recent advances in stroke recovery related to changes in brain oscillations. We present an overview on how brain stimulation techniques drive neural oscillations and lay out a roadmap for future studies that are needed to inform the next generation of strategies to promote functional recovery after stroke.

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