Dynamic Neuromodulation

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It is estimated that 4% of UK's population suffer from essential tremor while approximately 127,000 people live with Parkinson's disease, making long-term treatment of these conditions one of the key challenges facing the healthcare system. Deep brain stimulation is a commonly used therapeutic intervention, which involves electrical stimulation of key brain regions. State of the art stimulation patterns attenuate brain activity that drives disease symptoms and lead to symptom suppression. However, stimulation also suppresses brain activity not linked with motor symptoms of Parkinson's disease and essential tremor, inducing side effects in up to 50 % of the patients treated with deep brain stimulation. I believe developing therapeutic strategies that selectively target brain activity driving disease symptoms could reduce stimulation-induced side effects and significantly improve patients' quality of life. This proposal emerges from a clinical need to improve stimulation specificity in order to reduce side effects experienced by patients, and to expand the use of this powerful therapeutic intervention to other difficult to treat neurological disorders. The first aim of the proposal is to selectively suppress disease related brain activity by carefully timing stimulation. Critically, I aim to achieve state-dependent deep brain stimulation, which adjusts key aspects of the therapy (e.g. how much stimulation is delivered and pattern of stimulation) dynamically according to patients' symptom severity. Neuromodulation can be used not only to suppress brain activities driving disease symptoms but also to enhance neural activity that play a critical role in controlling our every day actions. I aim to develop stimulation techniques in order to selectively enhance neural processes believed to contribute to behaviors such as response inhibition and action selection. The possibility of promoting neural activity to compensate for impairment may play an important role in the future for managing treatment-refractory disorders such as obsessive-compulsive disorder and impulsivity. The second aim of the proposal is to learn from fundamental neural processes in order to design more "natural" therapeutic interventions. Brain activity driving motor symptoms of Parkinson's disease and essential tremor can be spontaneously suppressed. For instance, when patients with tremor make a movement, tremor amplitude reduces significantly. Therapeutic interventions inspired by natural processes that take place in our brains even during disease, may provide an effective method for reducing disease symptoms while sparing brain activity not linked to disease processes. This research programme will generate exciting theoretical and experimental tools, which could be used to understand how different brain regions communicate and control behavior. Critically, the notion of mimicking the way our brains readily control disease related neural activity through stimulation is an innovative path that could lead to the development of new types of therapeutic interventions not only for Parkinson's disease and essential tremor but also for other movement and psychiatric disorders driven by similar types of brain activity.