I. Mechanisms of action of deep brain stimulation
II. Clinical trials of surgery for movement, pain and psychiatric disorders
III. Neural prostheses
IV. Human systems physiology
I Mechanisms of action of deep brain stimulation
Our research aim is to understand how therapeutic deep brain stimulation (DBS) works. DBS electrodes are placed in various deep brain nuclei for the treatment of movement disorders (essential tremor, Parkinson’s disease, dystonia), pain, epilepsy, depression, and obsessive-compulsive disorder. The clinical benefits of DBS are well recognized, however its mechanism of action is unknown. Using a combined approach of direct examination of beneficial effects of DBS in patients, intra-operative microelectrode recording/stimulation, applying DBS to brain slices, and in behaving animal models, we hope to understand its mode of action. With a better understanding of how it works at the cellular level, and then the brain circuit level, DBS may be applied to other brain nuclei to treat other conditions.
II Clinical trials of surgery for movement, pain and psychiatric disorders
While DBS seems to help several neurological and psychiatric conditions, in order to prove benefit well-designed and controlled clinical trials are essential. Our group was the first to perform a multicentre clinical trial for DBS in Canada (see publications for details). At present we are leading a multicentre randomized controlled double blind trial of hippocampal DBS for epilepsy (the METTLE study). We are also performing a small pilot study to determine the effects of DBS for refractory depression, we are involved in a multicentre cross-over trial of motor cortex stimulation for various chronic pain syndromes and a small prospective trial of occipital and peripheral nerve region stimulation for chronic facial pain and headache syndromes.
Thanks in large part to the Hotchkiss Brain Institute Clinical Research Unit, we have access to a large-scale database server (capable of coordinating large multicentre clinical trials), clinical trialists, data analysists, database designers, and biostatisticians.
III Smart neural prostheses to restore lost function
Smart prosthetics are in their infancy, but they are one of the newest fields of neuroscience. In 2006-2007 the US National Academies (Science, Engineering and Institute of Medicine) focused on Smart Prosthetics. Cochlear implants were science fiction 30 years ago and now >30,000 people have had them implanted to restore hearing. The Artificial Retina is rapidly advancing with several patients having had the first generation (16 electrodes), and second generation ( 64 electrode) systems implanted. Four patients have had their motor cortex implanted with a microelectrode array, that has proven the principle that motor cortical neuronal firing can be de-coded fast enough with today’s computing power, to allow brain control of a computer mouse . Functional electrical stimulation to restore continence, standing and walking in spinal cord injured patients are also advancing significantly http://fescenter.case.edu/. A new myoelectric arm, which allows patients to feel by capitalizing on nervous system plasticity, is revolutionary for a limb prosthetic. With an aging population and young people surviving for long periods after injury, functional restoration and rehabilitation science are where the medical device industry is putting its bets for growth in the next decade.
The major challenges faced in this arena include: (i) sustainable electrode-tissue interfaces, (ii) MRI compatibility, (iii) sensory restoration of touch and kinesthesis, (iv) fine motor control restoration. We have just received funding from AHFMR to explore these challenges with an interdisciplinary team grant in Neural Prostheses in collaboration with University of Alberta investigators. See team website for details
IV Human systems physiology
While smart prosthetics are exciting and novel, we still do not understand how the nervous system works well enough to interact with it in a meaningful manner.
We have been recording single and multiple neuronal firing in the human thalamus, pallidum, striatum and subthalamic regions with microelectrodes for the past decade, as part of routine surgery to determine the optimal spot for DBS electrode placement. This provides a unique opportunity to study the firing rates, patterns and receptive fields of the neurons we encounter, thereby helping us understand the function of these nuclei and the sensorimotor system as a whole.