Johnson, Kara A., Duffley, Gordon ORCID: 0000-0003-0966-0294, Anderson, Daria Nesterovich, Ostrem, Jill L., Welter, Marie-Laure, Baldermann, Juan Carlos, Kuhn, Jens, Huys, Daniel ORCID: 0000-0002-9124-4128, Visser-Vandewalle, Veerle, Foltynie, Thomas, Zrinzo, Ludvic, Hariz, Marwan, Leentjens, Albert F. G., Mogilner, Alon Y., Pourfar, Michael H., Almeida, Leonardo, Gunduz, Aysegul ORCID: 0000-0001-7925-0747, Foote, Kelly D., Okun, Michael S. and Butson, Christopher R. (2020). Structural connectivity predicts clinical outcomes of deep brain stimulation for Tourette syndrome. Brain, 143. S. 2607 - 2624. OXFORD: OXFORD UNIV PRESS. ISSN 1460-2156

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Abstract

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Johnson, Kara A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Duffley, GordonUNSPECIFIEDorcid.org/0000-0003-0966-0294UNSPECIFIED
Anderson, Daria NesterovichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ostrem, Jill L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Welter, Marie-LaureUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baldermann, Juan CarlosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kuhn, JensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Huys, DanielUNSPECIFIEDorcid.org/0000-0002-9124-4128UNSPECIFIED
Visser-Vandewalle, VeerleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Foltynie, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zrinzo, LudvicUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hariz, MarwanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leentjens, Albert F. G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mogilner, Alon Y.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pourfar, Michael H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Almeida, LeonardoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gunduz, AysegulUNSPECIFIEDorcid.org/0000-0001-7925-0747UNSPECIFIED
Foote, Kelly D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Okun, Michael S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Butson, Christopher R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-324327
DOI: 10.1093/brain/awaa188
Journal or Publication Title: Brain
Volume: 143
Page Range: S. 2607 - 2624
Date: 2020
Publisher: OXFORD UNIV PRESS
Place of Publication: OXFORD
ISSN: 1460-2156
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
DOUBLE-BLIND; TIC SUPPRESSION; THALAMIC-STIMULATION; NEURONAL-ACTIVITY; NETWORK ACTIVITY; BASAL GANGLIA; TRACTOGRAPHY; MODULATION; SEVERITY; MODELSMultiple languages
Clinical Neurology; NeurosciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/32432

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