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Normative vs. patient-specific brain connectivity in Deep Brain Stimulation

By Qiang Wang, Harith Akram, Muthuraman Muthuraman, Gabriel Gonzalez-Escamilla, Sameer Sheth, Sergiu Groppa, Nora Vanegas-Arroyave, Ludvic Zrinzo, Ningfei Li, Andrea Kuhn, Andreas Horn

Posted 27 Feb 2020
medRxiv DOI: 10.1101/2020.02.24.20027490

Brain connectivity profiles seeding from deep brain stimulation (DBS) electrodes have emerged as informative tools to estimate outcome variability across DBS patients. Given the limitations of acquiring and processing patient-specific diffusion-weighted imaging data, most studies have employed normative atlases of the human connectome. To date, it remains unclear whether patient-specific connectivity information would strengthen the accuracy of such analyses. Here, we compared similarities and differences between patient-specific, disease-matched and normative structural connectivity data and retrospective estimation of clinical improvement that they may generate. Data from 33 patients suffering from Parkinsons Disease who underwent surgery at three different centers were retrospectively collected. Stimulation-dependent connectivity profiles seeding from active contacts were estimated using three modalities, namely either patient-specific diffusion-MRI data, disease-matched or normative group connectome data (acquired in healthy young subjects). Based on these profiles, models of optimal connectivity were constructed and used to retrospectively estimate the clinical improvement in out of sample data. All three modalities resulted in highly similar optimal connectivity profiles that could largely reproduce findings from prior research based on a novel multi-center cohort. Connectivity estimates seeding from electrodes when using either patient-specific or normative connectomes correlated significantly to primary motor cortex (R = 0.57, p = 0.001, R=0.73, p=0.001), supplementary motor area (R = 0.40, p = 0.005, R = 0.43, p = 0.003), pre-supplementary motor area (R = 0.33, p = 0.022, R = 0.33, p = 0.031), but not to more frontal regions such as the dorsomedial prefrontal cortex (R = 0.21, p = 0.17, R = 0.18, p = 0.17). However, in a data-driven approach that estimated optimal whole-brain connectivity profiles, out-of-sample estimation of clinical improvements were made and ranged within a similar magnitude when applying either of the three modalities (R = 0.43 at p = 0.001 for patient-specific connectivity; R = 0.25, p = 0.048 for the age- and disease-matched group connectome; R = 0.31 at p = 0.028 for healthy-/young connectome). ConclusionsThe use of patient-specific connectivity and normative connectomes lead to identical main conclusions about which brain areas are associated with clinical improvement. Still, although results were not significantly different, they hint at the fact that patient-specific connectivity may bear the potential of estimating slightly more variance when compared to group connectomes. Our findings further support the role of DBS electrode connectivity profiles as a promising method to guide surgical targeting and DBS programming.

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