title: Therapeutic subthalamic nucleus deep brain stimulation reverses cortico-thalamic coupling during voluntary movements in Parkinson's disease.
abstract: Deep brain stimulation of the subthalamic nucleus (STN DBS) has become an accepted treatment for patients experiencing the motor complications of Parkinson's disease (PD). While its successes are becoming increasingly apparent, the mechanisms underlying its action remain unclear. Multiple studies using radiotracer-based imaging have investigated DBS-induced regional changes in neural activity. However, little is known about the effect of DBS on connectivity within neural networks; in other words, whether DBS impacts upon functional integration of specialized regions of cortex. In this work, we report the first findings of fMRI in 10 subjects with PD and fully implanted DBS hardware receiving efficacious stimulation. Despite the technical demands associated with the safe acquisition of fMRI data from patients with implanted hardware, robust activation changes were identified in the insula cortex and thalamus in response to therapeutic STN DBS. We then quantified the neuromodulatory effects of DBS and compared sixteen dynamic causal models of effective connectivity between the two identified nodes. Using Bayesian model comparison, we found unequivocal evidence for the modulation of extrinsic (between region), i.e. cortico-thalamic and thalamo-cortical connections. Using Bayesian model parameter averaging we found that during voluntary movements, DBS reversed the effective connectivity between regions of the cortex and thalamus. This casts the therapeutic effects of DBS in a fundamentally new light, emphasising a role in changing distributed cortico-subcortical interactions. We conclude that STN DBS does impact upon the effective connectivity between the cortex and thalamus by changing their sensitivities to extrinsic afferents. Furthermore, we confirm that fMRI is both feasible and is tolerated well by these patients provided strict safety measures are adhered to.
authors.affiliation: Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London, United Kingdom. joshua.kahan@ucl.ac.uk
authors.forename: Josh
authors.initials: J
authors.lastname: Kahan
authors.forename: Laura
authors.initials: L
authors.lastname: Mancini
authors.forename: Maren
authors.initials: M
authors.lastname: Urner
authors.forename: Karl
authors.initials: K
authors.lastname: Friston
authors.forename: Marwan
authors.initials: M
authors.lastname: Hariz
authors.forename: Etienne
authors.initials: E
authors.lastname: Holl
authors.forename: Mark
authors.initials: M
authors.lastname: White
authors.forename: Diane
authors.initials: D
authors.lastname: Ruge
authors.forename: Marjan
authors.initials: M
authors.lastname: Jahanshahi
authors.forename: Tessel
authors.initials: T
authors.lastname: Boertien
authors.forename: Tarek
authors.initials: T
authors.lastname: Yousry
authors.forename: John S
authors.initials: JS
authors.lastname: Thornton
authors.forename: Patricia
authors.initials: P
authors.lastname: Limousin
authors.forename: Ludvic
authors.initials: L
authors.lastname: Zrinzo
authors.forename: Tom
authors.initials: T
authors.lastname: Foltynie
mesh_terms: D000328:Adult; D000368:Aged; D001499:Bayes Theorem; D046690:Deep Brain Stimulation; D004599:Electric Stimulation Therapy; D006801:Humans; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D009044:Motor Cortex / Q000502:physiology*; D010300:Parkinson Disease / Q000473:pathology / Q000628:therapy*; D020531:Subthalamic Nucleus / Q000502:physiology*