Dystonia is a movement disorder that causes involuntary twisting and repetitive movements, which can impede the patient so much that they are unable to lead independent lives or even communicate clearly with the people around them. In recent decades, exogenous electrical stimulation, including deep brain stimulation (DBS) and peripheral nerve stimulation (PNS), has shown promising results in the treatment of movement disorders caused by abnormal neural activity. However, as with any tool, exogenous electrical stimulation is only as useful as its operator is skilled, and for optimal use, the operator must both know what to do, and how to do so. By studying the abnormal signal flow that causes dystonia, we can understand what needs to be fixed, and by studying the effects of electrical stimulation on the dystonic brain, we can learn how to control the response pattern to generate the desired effect for each individual patient.

I aimed to contribute to these topics by studying neural recordings from stereo-electroencephalography (sEEG) electrodes in thalamic nuclei and basal ganglia of pediatric patients with dystonia during intracranial and peripheral electrical stimulation. My results were multifold, highlighting the complexity of the brain’s response to exogenous stimulation.

I found that the initial transient neural response to exogenous stimulations differs from long-term steady state responses to constant stimulation, and that DBS evoked potentials (EPs) can be affected, in a highly heterogeneous way, by the intake of medications. I discovered novel, intricate, yet highly consistent EPs, and unearthed trends in how DBS EPs and their delay, amplitude, and even shape depends on the stimulation frequency. I helped generate models to describe the observed neural responses and even discover connections between invasive neurophysiological recordings and non-invasive imaging methods.

These results were made possible by my extensive work put into developing methods to accurately process the data, remove noise and artifacts, and automate processes wherever possible to reduce bias and save time for further analyses. Through these methods alone, I hope to have contributed to the field of engineering for an extended time to come.

While we may still just be scratching the surface, I am confident that my dissertation research has at least made a solid dent in the casing that holds the secret to using exogenous stimulation to elicit the optimal clinical effect for children with dystonia and other movement disorders.

Neuroplasticity can be defined as the ability of the nervous system to respond to intrinsic or extrinsic stimuli by reorganizing its structure, function and connections. Major advances in the understanding of neuroplasticity have to date yielded few established interventions. To advance the translation of neuroplasticity research towards clinical applications, the National Institutes of Health Blueprint for Neuroscience Research sponsored a workshop in 2009. Basic and clinical researchers in disciplines from central nervous system injury/stroke, mental/addictive disorders, paediatric/developmental disorders and neurodegeneration/ageing identified cardinal examples of neuroplasticity, underlying mechanisms, therapeutic implications and common denominators. Promising therapies that may enhance training-induced cognitive and motor learning, such as brain stimulation and neuropharmacological interventions, were identified, along with questions of how best to use this body of information to reduce human disability. Improved understanding of adaptive mechanisms at every level, from molecules to synapses, to networks, to behaviour, can be gained from iterative collaborations between basic and clinical researchers. Lessons can be gleaned from studying fields related to plasticity, such as development, critical periods, learning and response to disease. Improved means of assessing neuroplasticity in humans, including biomarkers for predicting and monitoring treatment response, are needed. Neuroplasticity occurs with many variations, in many forms, and in many contexts. However, common themes in plasticity that emerge across diverse central nervous system conditions include experience dependence, time sensitivity and the importance of motivation and attention. Integration of information across disciplines should enhance opportunities for the translation of neuroplasticity and circuit retraining research into effective clinical therapies.