Connectivity Predicts deep brain stimulation outcome in Parkinson disease

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Deep brain stimulation (DBS) is a well‐established treatment for Parkinson disease (PD), yielding improvements in motor symptoms and quality of life.1 The most common DBS target is the subthalamic nucleus (STN), identified based on stereotactic coordinates and preoperative magnetic resonance imaging (MRI). However, the therapeutic benefit of DBS may depend on modulation of remote brain regions connected to the stimulation site.2 These remote effects of DBS have been measured with both electrophysiology5 and brain imaging.3 Furthermore, they can correlate with clinical response.11 As such, connectivity of the stimulation site to a network of other brain regions may be an important mediator of DBS response. If so, one could potentially predict response based on connectivity with the stimulation site and even optimize the DBS target based on connectivity.
Motivated by these findings, researchers have worked to determine which connections with the DBS site are most important. For example, the hyperdirect pathway connecting STN to cortex is thought to play a key role.8 However, identifying connectivity noninvasively in humans is not straightforward. Two MRI‐based connectivity measures appear promising. Diffusion tractography, a noninvasive metric of anatomical connectivity, can identify white matter tracts near the DBS electrode.9 Functional connectivity, a measure of the correlation in spontaneous activity, can link DBS sites to cortical regions including targets of noninvasive brain stimulation.2 Despite these efforts, the connectivity profile of clinically effective STN stimulation for PD remains unclear.
Here, we use high‐quality connectome datasets of both diffusion tractography and functional connectivity to compute the connectivity profile of effective STN stimulation for PD. Most analyses used connectome data from normal subjects (n = 1,030), but we ensured results were reproducible using a connectome from PD patients (n = 90). Although group connectome data have not previously been used to study DBS outcomes, it has proven valuable in similar contexts.2 We studied 2 large cohorts of PD patients with STN DBS (n = 51 and n = 44) to test the hypotheses that connectivity profiles predict clinical outcome across independent datasets.

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