Probing responses to deep brain stimulation with functional magnetic resonance imaging

Abstract

Background: Deep brain stimulation (DBS) is an established treatment for certain movement disorders and has additionally shown promise for various psychiatric, cognitive, and seizure disorders. However, the mechanisms through which stimulation exerts therapeutic effects are incompletely understood. A technique that may help to address this knowledge gap is functional magnetic resonance imaging (fMRI). This is a non-invasive imaging tool which permits the observation of DBS effects in vivo.

Objective: The objective of this review was to provide a comprehensive overview of studies in which fMRI during active DBS was performed, including studied disorders, stimulated brain regions, experimental designs, and the insights gleaned from stimulation-evoked fMRI responses.

Methods: We conducted a systematic review of published human studies in which fMRI was performed during active stimulation in DBS patients. The search was conducted using PubMED and MEDLINE.

Results: The rate of fMRI DBS studies is increasing over time, with 37 studies identified overall. The median number of DBS patients per study was 10 (range = 1-67, interquartile range = 11). Studies examined fMRI responses in various disease cohorts, including Parkinson's disease (24 studies), essential tremor (3 studies), epilepsy (3 studies), obsessive-compulsive disorder (2 studies), pain (2 studies), Tourette syndrome (1 study), major depressive disorder, anorexia, and bipolar disorder (1 study), and dementia with Lewy bodies (1 study). The most commonly stimulated brain region was the subthalamic nucleus (24 studies). Studies showed that DBS modulates large-scale brain networks, and that stimulation-evoked fMRI responses are related to the site of stimulation, stimulation parameters, patient characteristics, and therapeutic outcomes. Finally, a number of studies proposed fMRI-based biomarkers for DBS treatment, highlighting ways in which fMRI could be used to confirm circuit engagement and refine DBS therapy.

Conclusion: A review of the literature reflects an exciting and expanding field, showing that the combination of DBS and fMRI represents a uniquely powerful tool for simultaneously manipulating and observing neural circuitry. Future work should focus on relatively understudied disease cohorts and stimulated regions, while focusing on the prospective validation of putative fMRI-based biomarkers.

Keywords: Deep brain stimulation; Functional imaging; Movement disorders; Neuromodulation; fMRI.