FV 1 Segregating the prefrontal cortex by means of deep brain stimulation. (May 2022) - Hollunder, B.
Abstract : Introduction: Neurocircuits are involved in the motor, cognitive, and affective dysfunctions of multiple brain disorders. Functional segregation into these domains has been widely defined on a fronto- cortical basis. However, despite considerable interaction, these functional domains remain partitioned to some extent at (sub)thalamic levels (1). To map the functional organization of the the frontal cortex (FC), we employ optimal connectivity profiles from successful deep brain stimulation (DBS) electrodes to the same target, which receives input from the entire FC, in four different disorders. Specifically, we identify cortical projection sites that, on a group level, associate with maximal improvements following subthalamic nucleus (STN) DBS in dystonia (DYT), Parkinson's disease (PD), Tourette syndrome (TS) or obsessive-compulsive disorder (OCD). Patients and Methods: Using Lead-DBS (2), stimulation volumes were estimated for six patient cohorts from six centers, each implanted with DBS to the STN for treatment of either DYT (N = 62), PD (N = 51), TS (N = 14), or OCD (N = 19). Via DBS Network Mapping (3) we derived disease-specific structural connections between cortex and STN from a normative connectome (4) that relate to optimal clinical outcomes. Results: Functional organization in the STN and FC was reflected along a caudo-rostral gradient (Fig. 1). Beneficial DBS networks for DYT predominantly projected to the primary motor cortex, while in PD, electrode connectivity to pre- and supplementary motor areas, in TS to the dorsomedial preFC, and in OCD to ventromedial, dorsal anterior cingulate and dorsolateral preFC emerged. Conclusion: Our findings demonstrate the usefulness of DBS to investigate the organizational gradient of frontal network (dys)function. As such, they bear both interest for cognitive neurosciences as well as clinical-translational value for circuit-guided DBS. References 1. Haynes WIA, Haber SN (2013): The organization of prefrontal-subthalamic inputs in primates provides an anatomical substrate for both functional specificity and integration: Implications for basal ganglia models and deep brain stimulation. J Neurosci 33: 4804–4814. 2. Horn A, Li N, Dembek TA, Kappel A, Boulay C, Ewert S, et al. (2019): Lead-DBS v2: Towards a comprehensive pipeline for deep brain stimulation imaging. Neuroimage 184: 293–316. 3. Horn A, Reich M, Vorwerk J, Li N, Wenzel G, Fang Q, et al. (2017): Connectivity predicts deep brain stimulation outcome in Parkinson disease. Ann Neurol 82: 67–78. 4. Wang F, Dong Z, Tian Q, Liao C, Fan Q, Hoge WS, et al. (2021): In vivo human whole-brain Connectom diffusion MRI dataset at 760 µm isotropic resolution. Sci Data 8: 122. Figure Legend: