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The role of the subthalamic nucleus and its cortical connections in higher motor control as revealed by Parkinson’s disease, its surgical and medical treatments and transcranial magnetic stimulation.

Obeso, I; (2012) The role of the subthalamic nucleus and its cortical connections in higher motor control as revealed by Parkinson’s disease, its surgical and medical treatments and transcranial magnetic stimulation. Doctoral thesis, UCL (University College London).

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Abstract

Imaging studies have shown that response inhibition and conflict resolution, key executive functions essential for adaptive behaviour, are mediated by fronto-striatal circuits, specifically the right inferior frontal gyrus (IFG), pre-supplementary motor area (pre-SMA), and the subthalamic nucleus (STN). Overactivity of the STN and underactivation of the pre-SMA are features of Parkinson's disease (PD). The aim of this thesis was to investigate the hypothesis that the STN is involved in inhibition of action and serves to provide time for reflection and to slow down decision-making under conflict (Frank et al. 2006; 2007). The conditional stop signal reaction time was used. In Study 1, compared to controls, medicated PD patients showed impaired motor inhibition with prolonged stop signal reaction times (SSRTs), problems with conflict resolution, and impairment on tests of cognitive inhibition. In Study 2, PD patients were impaired on motor inhibition and conflict resolution compared to controls both on and off medication. Most importantly, medication status did not influence motor inhibition or conflict resolution in PD. In Study 3, bilateral deep brain stimulation of the STN impaired inhibition as indicated by significantly prolonged SSRTs, but had no significant effect on conflict resolution. However, Study 4, showed that compared to controls and unoperated PD, PD with unilateral subthalamotomies showed faster Go RTs and less conflict-induced slowing but at the expense of greater response selection errors. Finally, Study 5 investigated the contributions of the pre-SMA and IFG to motor inhibition and conflict resolution in healthy controls using transcranial magnetic stimulation. The results confirmed that the contribution of the right pre-SMA to response inhibition is essential. The results are consistent with the proposal that the STN and pre-SMA are involved in reactive inhibition and that the STN together with the pre-SMA influences the response threshold and speed-accuracy trade-offs.

Type:Thesis (Doctoral)
Title:The role of the subthalamic nucleus and its cortical connections in higher motor control as revealed by Parkinson’s disease, its surgical and medical treatments and transcranial magnetic stimulation.
Language:English
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Neurology

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