NANS Neuromodulation Journal Club

Scheduled

Presented Article: Structural connectivity predicts clinical outcomes of deep brain stimulation for Tourette syndrome
Date: Tuesday, April 13, 2021
Time: 3 pm CDT / 4 pm EDT

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 < 0.017). For centromedial thalamus, connectivity to sensorimotor networks, parietal-temporal-occipital networks, putamen, and cerebellum was positively correlated with tic improvement; the model predicted clinical improvement scores (P = 0.012) and was robust to cross-validation. Regions in the anterior/lateral centromedial thalamus exhibited higher connectivity to the positively correlated networks, but volume of tissue activated overlap with this map did not predict 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), but the model was not robust to cross-validation. Collectively, the results demonstrate that the structural connectivity of the site of stimulation are likely important for mediating symptom improvement, and the networks involved in tic improvement may differ across surgical targets. These networks provide important insight on potential mechanisms and could be used to guide lead placement and stimulation parameter selection, as well as refine targets for neuromodulation therapies for Tourette syndrome.

Target Audience: Neuroscientists, Biomedical Engineers, and Clinicians. NANS invites all faculty, students and post docs to attend!

Presenter and Co-Author
Christopher R. Butson, PhD
Professor of Neurology
Fixel Endowed Chair of Neurotherapeutics
Norman Fixel Institute for Neurological Diseases
University of Florida

Presenter and Co-Author
Kara A. Johnson, PhD
Postdoctoral Fellow | de Hemptinne Lab
Norman Fixel Institute for Neurological Diseases
University of Florida

Moderator
Irina Duff, MD PhD
Postdoctoral Fellow
Department of Psychiatry and Behavioral Sciences
The Johns Hopkins University

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Past Webinars

March Article: Refining Deep Brain Stimulation to Emulate Optogenetic Treatment of Synaptic Pathology
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Meaghan C. Creed, PhD
Irina Duff, MD PhD

February Article: Learning to Control the Brain through Adaptive Closed-Loop Patterned Stimulation
Tafazoli S, MacDowell CJ, Che Z, Letai KC, Steinhardt C, Buschman TJ. Learning to Control the Brain through Adaptive Closed-Loop Patterned Stimulation. 2020 Jan 1. 

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Ilknur Telkes, PhD MSc

December Article: Multiple Stimulation Parameters Influence Efficacy of Deep Brain Stimulation in Parkinsonian Mice
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Jonathan S. Schor, PhD
Irina Duff, MD PhD

November Article: Continuous Theta-Burst Stimulation in Children With High-Functioning Autism Spectrum Disorder and Typically Developing Children
Frontiers in Integrative Neuroscience
Ali Jannati, Gabrielle Block, Mary A. Ryan, Harper L. Kaye, Fae B. Kayarian, Shahid Bashir, Lindsay M. Oberman, Alvaro Pascual-Leone, and Alexander Rotenberg

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October Article: Patient‐Specific Analysis of Neural Activation during Spinal Cord Stimulation for Pain
Neuromodulation: Technology at the Neural Interface 2020 Jul;23(5):572-81
Scott F. Lempka, PhD; Hans J. Zander, MSE; Carlos J. Anaya, BS; Alexandria Wyant, BA; John G. Ozinga IV, PA-C; Andre G. Machado, PhD

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Faculty
Hans J. Zander, MSE
Ilknur Telkes, PhD MSc