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Deep brain stimulation (DBS) is an established treatment for advanced Parkinson's disease, medically refractory tremor, dystonia and obsessive compulsive disorder. Several hypotheses driven DBS trials are underway to study modulation of circuit dysfunction in other neurological and psychiatric disorders like epilepsy, Alzheimer's disease and depression. Recent reports suggest profound effects of DBS on the anatomy and function of downstream areas in the brain. For example electrical stimulation of limbic circuits is associated with increase in hippocampal neurogenesis. Similarly, stimulation of subthalamic nucleus (STN) or globus pallidus (GPi) results in activation of cortical motor circuits. Non-invasive imaging modalities are increasingly being employed in these investigations to better understand the effects of DBS on the structure and function of the brain.
There have been important advances in MRI and we now have MRI which provides higher resolution and higher quality brain images. More specifically, the investigators propose to use MRI to perform functional magnetic resonance imaging (i.e. fMRI) to assess the effects of deep brain stimulation on brain function and to assess whether fMRI can be used as an adjunct to improve clinical practice in these patients.
This is a prospective cohort study that will enroll patients who are about to or have already undergone DBS electrode placement for a variety of disorders including, but not limited to Parkinson's disease, essential tremor, dystonia, depression, epilepsy, neuropathic pain and Alzheimer's disease. This eligible patient population is broad but unified by the fact that they will all undergo DBS to treat specific circuit dysfunctions. Pre-operative DBS patients and patients with externalized leads or internalized IPG may be included.
We propose to study patients with externalized leads or internalized IPG programmed at either 'switched off' (IPG at 0 volt and off state) and 'switched on' settings We have already performed phantom safety testing for these experimental conditions and found it to be safe. We propose to perform the following scans:
Further, we propose to assess whether the aforementioned scans can be used as an adjunct to improve current DBS post-operative follow up.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| fMRI-based programming | Experimental | DBS patients will undergo fMRI scanning while on different stimulation settings. The results will be fed to the programming clinician (movement disorder neurologist) to aid the conventional programming process at the clinician's discretion. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| fMRI | Other | DBS patients will undergo fMRI scanning. For each patient, scans will be performed using a selection of DBS settings. fMRI responses will be analysed to evaluate brain responses on different DBS settings. These results will be provided to the programming clinician to guide them choose the optimal setting for each patient at the clinician's discretion. |
| Measure | Description | Time Frame |
|---|---|---|
| Brain areas engaged with deep brain stimulation | The primary outcome of interest is safety of 3T structural and functional brain MRI scans in patients with implanted DBS. | 3 months before DBS implant to 1 year after DBS implant. |
| Measure | Description | Time Frame |
|---|---|---|
| Structural connectivity using 1.5T or 3T MRI | • to study volume changes (mm3) associated with DBS therapy in patients with movement disorders, psychiatric illness, epilepsy, and pain | 3 months before DBS implant to 1 year after DBS implant. |
| Functional connectivity using 1.5T or 3T MRI |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Alexandre Boutet, MD/MSc | Contact | (647) 463-5513 | alexandre.boutet@mail.utoronto.ca | |
| Tasnuva Hoque, BHA | Contact | 4166035800 | 2797 | tasnuva.hoque@uhn.ca |
| Name | Affiliation | Role |
|---|---|---|
| Andres Lozano | University Health Network, Toronto | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Toronto Western Hospital | Recruiting | Toronto | Ontario | M5T2S8 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34031407 | Background | Boutet A, Madhavan R, Elias GJB, Joel SE, Gramer R, Ranjan M, Paramanandam V, Xu D, Germann J, Loh A, Kalia SK, Hodaie M, Li B, Prasad S, Coblentz A, Munhoz RP, Ashe J, Kucharczyk W, Fasano A, Lozano AM. Predicting optimal deep brain stimulation parameters for Parkinson's disease using functional MRI and machine learning. Nat Commun. 2021 May 24;12(1):3043. doi: 10.1038/s41467-021-23311-9. |
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• To study the mechanisms underlying the therapeutic effects of DBS as measured by changes in functional and anatomical connectivity of the motor, sensory, memory and cognition circuits. |
| 3 months before DBS implant to 1 year after DBS implant. |
| Clinical outcome | • number of clinic visits required until optimization | 3 months before DBS implant to 1 year after DBS implant. |