Kahan, J;
Mancini, L;
Urner, M;
Friston, K;
Hariz, M;
Holl, E;
White, M;
... Foltynie, T; + view all
(2012)
Therapeutic subthalamic nucleus deep brain stimulation reverses cortico-thalamic coupling during voluntary movements in Parkinson's disease.
PLoS One
, 7
(12)
, Article e50270. 10.1371/journal.pone.0050270.
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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.
| Type: | Article |
|---|---|
| Title: | Therapeutic subthalamic nucleus deep brain stimulation reverses cortico-thalamic coupling during voluntary movements in Parkinson's disease. |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0050270 |
| Publisher version: | http://dx.doi.org/10.1371/journal.pone.0050270 |
| Language: | English |
| Additional information: | © 2012 Kahan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This study was funded by the Brain Research trust (www.brt.org.uk). Josh Kahan receives funding from The Astor Foundation, The Rosetrees Trust, and the MHMS General Charitable Trust. Karl Friston receives funding from the Wellcome Trust. The Unit of Functional Neurosurgery is funded by the Parkinson's Appeal and the Monument trust. The work was undertaken by UCL/UCLH, who receive a proportion of funding from the UK Department of Health's NIHR Biomedical Research Centres funding scheme. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. TF, LZ, MH, and PL report that they have received honoraria from industry for invited talks. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials. The authors report that they have no other financial disclosures or conflicts of interest related to the topics addressed in the study. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Brain Repair and Rehabilitation UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Imaging Neuroscience UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/1382711 |
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