MRC TS Award: Dynamic Neuromodulation

Brief neural rhythms, coordinated across multiple brain regions, control our everyday actions from reaching for a glass of water to making decisions. Dysfunction of this fundamental neural property has been linked to common conditions such as Parkinson's disease, Essential Tremor, and Dystonia, which impact more than one million people across the UK. Understanding the role of neural coordination in health and disease is key for the development of effective therapies.

My research programme uses brain stimulation to establish the role of neural coordination in Parkinson's disease and Essential Tremor.

During my Career Development Award, I worked towards:

Theme 1: Establishing how the current state of a disease circuit influences the most effective stimulation strategy.
Theme 2: Determining how selectively modulating neural coordination impacts goal-directed behaviour.
Theme 3: Establishing the mechanisms through which our brains naturally control neural coordination.
Theme 4: Determining whether it is possible to regulate neural coordination with brain stimulation by mimicking mechanisms through which our brains naturally control coordination.

We have made good progress with Themes 1-3 and (a) implemented experimental tasks to better understand the link between symptom severity and movement, (b) built realistic computational models that capture the mechanisms underlying Essential Tremor and Parkinson's disease and (c) developed invasive and non-invasive stimulation strategies to reduce tremor and influence goal-directed behaviour.

Due to several mitigating circumstances, we are still at the beginning stages of Theme 4 and require additional time. The Transition Support Award will be used to support this important body of work and consolidate my intermediate fellowship by supporting a key member of my team and protecting my research time.

My research programme leverages brain stimulation to establish the functional role of neural synchrony in goal-directed behaviour, and its pathological role in Parkinson's disease and Essential Tremor.

During my Career Development Award, I

[Theme 1] established that the dynamic state of a disease circuit influences the most effective stimulation strategy. Building on our computational and experimental observations, we developed a time-varying stimulation controller that could maintain optimal stimulation performance in the face of fluctuating physiological demands as expected from factors such as disease progression, medication, or circadian rhythms.

[Theme 2] determined the effect of non-invasive brain stimulation on goal-directed behaviour using different stimulation patterns such as random noise and alternating current stimulation.

[Theme 3] explored the mechanisms through which our brains naturally control neural synchrony using biophysical computational models and experimental recordings that leverage cutting edge neuroimaging techniques such as optically pumped magnetometers.

Due to several mitigating circumstances, we are still at the beginning stages of Theme 4 and require additional time to develop this important translational element of the programme. With the funding provided by the Transition Support award, I aim to complete key experimental work, and determine whether it is possible to selectively modulate neural synchrony for therapeutic gain using brain stimulation. To this end, I will use non-invasive brain stimulation to mimic spatiotemporal signatures associated with spontaneous tremor suppression. This work will consolidate our outputs from Themes 1-3 and provide the necessary momentum to enable me to take my next career step.