Tremor is the fast involuntary movement of a body part that forms a disabling symptom in countless movement disorders, most commonly Essential Tremor and Parkinson’s disease. It is currently estimated that as many as 3.4 million people are afflicted with some form of tremor in the UK with few viable treatment options. Recently, I demonstrated that rhythmic electrical stimulation applied across the scalp can controllably suppress tremor in Parkinson’s disease by up to 50%. I have continued to pursue this avenue of research and there is now considerable evidence that this effect can be substantially improved. The objective of this proposal is therefore the development of a non-invasive form of electrical stimulation as a realisable therapy for those afflicted with disabling tremors.
Determining the precise form of stimulation, where that stimulation should be delivered, and who would be responsive to such treatment is a major undertaking. Whether this form of stimulation will prove equally effective across pathology is a key question, after all, different tremors are distinct. In Parkinson’s disease tremor typically emerges at rest, while Essential Tremor emerges only during use of the affected muscles. This latter form is considered far more disabling to the patient, severely affecting activities of daily living. But the precise form of tremor can vary even for patients diagnosed with the same disease. Indeed, my previous studies into Parkinson’s disease have shown that not all patients respond equally to stimulation. Instead, those with the most consistent tremors showed greatest benefit. Essential Tremor is one such condition that could benefit greatly from this approach. To understand this dependence, and in-so-doing identify those patients who would benefit most from stimulation, a thorough characterisation of real-world activity is planned that will assess the typical emergence characteristics of tremor over the course of everyday life.
A key objective of this study is the identification of those brain regions responsible for tremor that are also susceptible to stimulation across the scalp. Using mechanistic hypotheses of tremor production, four carefully chosen electrode arrangements will be tested to reveal the gross anatomical regions implicated in the amelioration of tremor by stimulation. Of course, these arrangements can only act as a first approximation since no further optimisation is possible without extensive trialling or, more pragmatically, functional neuroimaging of the brains response to stimulation. This latter option is precisely the approach taken later in the study that will identify the specific anatomical substrates impacted by the most-effective electrode arrangements. This in turn will allow electrical field models to be built, then extended to provide a predictive model describing the optimal electrode arrangement required to focally target the implicated brain regions. This will likely involve multiple small electrodes to permit electric “field steering”. Targeted suppression will optimise therapeutic benefit whilst minimising potential side-effects. In a longer term view these configurations will be adapted into a practical therapeutic application through non-invasive “skin tattoos”, or minimally invasive surgical procedures. Delivery will be driven by intelligent control systems informed by my characterisation of real-world utility.
In summary, this project builds on my unique experience in the field, with assistance from world-renowned international collaborators, to develop a non-invasive form of electrical stimulation as a realisable therapy for those afflicted with disabling tremors. The combined resource of behavioural, functional and modelling data will provide a rich legacy dataset on which mechanistic hypotheses of tremor production and refinements to the delivery system can be built.