Structural connectivity predicts clinical outcomes of deep brain stimulation for Tourette syndrome

• Published in: Brain (London, England : 1878) England : 1878), 2020-08, Vol.143 (8), p.2607-2623
• Main Authors: Johnson, Kara A, Duffley, Gordon, Anderson, Daria Nesterovich, Ostrem, Jill L, Welter, Marie-Laure, Baldermann, Juan Carlos, Kuhn, Jens, Huys, Daniel, Visser-Vandewalle, Veerle, Foltynie, Thomas, Zrinzo, Ludvic, Hariz, Marwan, Leentjens, Albert F G, Mogilner, Alon Y, Pourfar, Michael H, Almeida, Leonardo, Gunduz, Aysegul, Foote, Kelly D, Okun, Michael S, Butson, Christopher R
• Format: Article
• Language: English
• Subjects: Adult; Brain - diagnostic imaging; Brain - physiopathology; cortico-striato-thalamo-cortical networks; Deep Brain Stimulation - methods; Diffusion Tensor Imaging; Female; Human health and pathology; Humans; Image Interpretation, Computer-Assisted; Life Sciences; Male; Middle Aged; Nerve Net - diagnostic imaging; Nerve Net - physiopathology; neuromodulation; obsessive-compulsive behaviour; Original; Retrospective Studies; tics; Tourette Syndrome - diagnostic imaging; Tourette Syndrome - physiopathology; Tourette Syndrome - therapy; tractography; Treatment Outcome
• ISSN: 0006-8950; 1460-2156; 1460-2156
• DOI: 10.1093/brain/awaa188

Deep brain stimulation may be an effective therapy for select cases of severe, treatment-refractory Tourette syndrome; however, patient responses are variable, and there are no reliable methods to predict clinical outcomes. The objectives of this retrospective study were to identify the stimulation-dependent structural networks associated with improvements in tics and comorbid obsessive-compulsive behaviour, compare the networks across surgical targets, and determine if connectivity could be used to predict clinical outcomes. Volumes of tissue activated for a large multisite cohort of patients (n = 66) implanted bilaterally in globus pallidus internus (n = 34) or centromedial thalamus (n = 32) were used to generate probabilistic tractography to form a normative structural connectome. The tractography maps were used to identify networks that were correlated with improvement in tics or comorbid obsessive-compulsive behaviour and to predict clinical outcomes across the cohort. The correlated networks were then used to generate 'reverse' tractography to parcellate the total volume of stimulation across all patients to identify local regions to target or avoid. The results showed that for globus pallidus internus, connectivity to limbic networks, associative networks, caudate, thalamus, and cerebellum was positively correlated with improvement in tics; the model predicted clinical improvement scores (P = 0.003) and was robust to cross-validation. Regions near the anteromedial pallidum exhibited higher connectivity to the positively correlated networks than posteroventral pallidum, and volume of tissue activated overlap with this map was significantly correlated with tic improvement (P  0.23). For obsessive-compulsive behaviour, both targets showed that connectivity to the prefrontal cortex, orbitofrontal cortex, and cingulate cortex was positively correlated with improvement; however, only the centromedial thalamus maps predicted clinical outcomes across the cohort (P = 0.034), bu