Therapeutic Brain Stimulation

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Figure Caption: Figure Caption: Illustration of DBS therapy, involving a pacemaker delivering electrical stimuli transferred to the stimulation electrodes placed in deep brain regions. Source: http://www.wired.com/wiredscience/2007/10/parkinsons-impl/.
Future Directions

We are strengthening our 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, we are currently 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 - http://www.cnsuwo.ca/faculty/neurologists/). A specific focus will consist in the technology transfer and clinical translation of our research results, to propose innovative, less invasive, more efficient and safe neuromodulation therapies for PD.

To achieve these objectives, we take advantage from the Human Threshold Testing Facility, and more specifically of the 64- and 128-channel fixed-lead EEG/EMG, and also of the 3T mMR/PET/EEG/EMG hybrid imaging facility. These platforms offer an exceptional environment to test and improve our mathematical models, and knowledge of physio-pathological mechanisms, which in turn will lead to improved therapies.   

This developing scientific theme within the Human Threshold Research Group has the objective of accelerating the development of innovative therapeutic approaches in Parkinson’s disease (PD) and other movement disorders. Specifically, we intent to improve an existing therapy called ‘deep brain stimulation’ (DBS). DBS consists of a supplying a continuous pulsed electrical stimulation to brain structures delivered by electrodes implanted in 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. 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, 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 improve this technique and provide the understanding required to produce new technology.

Our original approach consists 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, neurostimulation by DBS). By comparing experimental data from PD patients with DBS on one hand; and results from a corresponding mathematical model simulating EEG with/without DBS on the other hand, it becomes possible to deepen insights into DBS effects on brain activity and the underlying mechanisms.

Our integrated approach, consisting of using experimental recordings in parallel with mathematical models of brain activity, is connected to our Human Threshold Testing theme studying the effects of specific 50 and 60 Hz electromagnetic stimuli on human neurophysiology and behaviour. The common objective is the use of such experimental, theoretical, and integrated approaches to understanding biological mechanisms of interaction between electric and magnetic stimuli and human brain activity (physiological and pathological). Knowledge translation towards therapeutic application is the ultimate objective.

 

Researchers
A. Legros
BEMS, Kinesiology, Neurosciences
J. Modolo
Computational Neurosciences
A.W. Thomas
Director, BEMS Group, Neuromodulation


Technologies
3T PET/MR
Bioelectromagnetics
Human Threshold Testing Facility
Prototype Facility

Collaborators
A. Beuter
Neuroscience
R.Z. Stodilka
Nuclear medicine physics
J. Théberge
Magnetic resonance physicist
R.T. Thompson
Director, MR Spectroscopy
F.S. Prato
Lawson Imaging Program Leader, MR and Nuclear Medicine Phsyics
Key Accomplishments

A mathematical model of brain activity during DBS “on” and/or “off” has been developed, and it has already led to predictions that have been experimentally validated. For instance, the model accurately predicts that DBS mimics the role of dopamine on the regulation of the pathway between the motor cortex and the subthalamic nucleus, as experimentally demonstrated (Eusebio et al., Brain, 2009). Also, an improvement of brain stimulation, targeting the cortex instead of deep brain regions, and functioning in a “closed-loop” (i.e., sensing brain activity and stimulating the brain depending on measured ongoing brain activity), has been implemented and patented (Modolo and Beuter, WO2010/130538 A1). An international collaboration with academic and clinical partners in both Canada and Europe is currently being setup to turn this new concept into a reality for patients in the near future.

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