Deep Brain Stimulation (DBS)

This developing scientific theme is within the Human Threshold Research Group and Testing Facility in association with the Bioelectromagnetics (BEMS) Group. It has the objective of accelerating the development of innovative therapeutic approaches in Parkinson’s disease (PD) and other movement disorders. Specifically, the groups intends to improve an existing therapy called ‘deep brain stimulation’ (DBS). DBS involves supplying a continuous pulsed electrical stimulation to brain structures delivered by electrodes implanted within the brain. This provides significant benefits to patients, but the mechanisms are poorly understood and clinical settings are applied as a ‘best-guess’ by physicians.

Example of closed-loop stimulation therapy being developed for Parkinson’s disease treatment: neuronal activity is monitored by a multi-electrode matrix, processed, and a controller determines if stimulation needs to be applied to brain tissue. This results in real-time optimization of the stimulation, personalized for each patient.

Despite its clinical effectiveness and the fact that over 80,000 patients worldwide benefit from DBS, it is still only accessible to a minority of patients, is costly, very invasive (deep brain surgery and implantation of permanent electrodes is involved), and commonly induces side effects (e.g., trouble with speech). Therefore, understanding the mechanisms by which DBS improves motor symptoms of PD patients is a precursor to improving this technique and providing the understanding required to produce new technology.

The original approach consisted of a close integration of experimental recordings performed in PD patients (electroencephalography, EEG; electromyography, EMG; finger tremor recordings) and mathematical modeling. Indeed, it is now a validated approach to use specific mathematical equations to describe and predict how brain activity evolves depending on specific factors (e.g., changes in neurotransmitters concentration, neuro- stimulation by DBS). By comparing experimental data from PD patients using DBS, to results from a corresponding mathematical model simulating EEG with/without DBS, it becomes possible to deepen insights into DBS effects on brain activity and the underlying mechanisms.

The integrated approach, using experimental recordings in parallel with mathematical models of brain activity, is connected to the Human Threshold Research Group studying the effects of specific high levels of electromagnetic stimuli on human neurophysiology and behaviour. The common objective is the use of such experimental, theoretical, and integrated approaches to understand biological mechanisms of interaction between electric and magnetic stimuli and human brain activity (physiological and pathological). The ultimate objective is knowledge translation towards therapeutic application.

The group is strengthening its efforts to identify biological mechanisms by which DBS regulates brain activity in a manner that results in symptom relief in PD patients. In these aspects, they are conducting an experiment in collaboration with neurologists from the Clinical Neurological Sciences department from Western University (Drs. Mandar Jog, Mary Jenkins, Christopher Hyson and Andrew Parrent).

They also currently are directing efforts in the technology transfer of a major improvement of deep brain stimulation, which is closed-loop stimulation. This consists in moving away from existing devices which provides the exact same stimulation signal 24/7, towards “smart” brain pacemakers able to adapt in real-time their settings to control optimally patients symptoms. This would not only be a major step towards personalized therapy, but would also extend device’s battery life (which needs to be replaced surgically).

Investigators
Alexandre Legros, PhD, BEMS, Kinesiology
Julien Modolo, PhD, Computational Neurosciences
Robert Stodilka, PhD, Nuclear Medicine Physics
Alex Thomas, PhD, BEMS Group leader

Collaborators
Frank Prato, PhD, Imaging Director/Physicist Chief
Anne Beuter, PhD, Neuroscience
Mary Jenkins, MD, FRCPC, Neurologist
Mandar Jog, MD, FRCPC, Neurologist, Director, Movement Disorders Program, University Hospital
Christopher Hyson, MD, FRCPC, Neurologist, University Hospital
Andrew Parrent, MD, FRCPC, Neurosurgeon, University Hospita
Jean Théberge, PhD, Magnetic Resonance Physics Terry Thompson, PhD, Magnetic Resonance Spectroscopy