The aim of this study was to examine possible neuropsychological changes in patients with advanced idiopathic Parkinson's disease treated with bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN). Eleven patients (age = 67 +/- 8 years, years with Parkinson's disease = 15 +/- 3, verbal IQ = 114 +/- 12) were evaluated (in their best 'on state') with tests assessing processes reliant on the functional integrity of frontal striatal circuitry, prior to the procedure (n = 11), at 3-6 months (n = 11) and at 9-12 months (n =10) post-operatively. Six of these patients were older than 69 years. Despite clinical motor benefits at 3-6 months post-operative, significant declines were noted in working memory, speed of mental processing, bimanual motor speed and co-ordination, set switching, phonemic fluency, long-term consolidation of verbal material and the encoding of visuospatial material. Declines were more consistently observed in patients who were older than 69 years, leading to a mental state comparable with progressive supranuclear palsy. 'Frontal' behavioural dyscontrol without the benefit of insight was also reported by half (three of six) of the caregivers of the elderly subgroup. At 9-12 months postoperative, only learning based on multiple trials had recovered. Tasks reliant on the integrity of frontal striatal circuitry either did not recover or gradually worsened over time. Bilateral STN DBS can have a negative impact on various aspects of frontal executive functioning, especially in patients older than 69 years. Future studies will evaluate a larger group of patients and examine the possible reversibility of these effects by turning the DBS off.

The subthalamic nucleus (STN) is part of the cortico-basal ganglia (BG)-thalamocortical circuit, whereas the ventral lateral nucleus of the thalamus (VL) is a relay nucleus in the cerebello-dentato-thalamocortical (CTC) pathway. Both pathways have been implicated in movement preparation. We compared the involvement of the STN and VL in movement preparation in humans by recording local field potentials (LFPs) from seven patients with Parkinson's disease with deep-brain stimulation (DBS) electrodes in the STN and five patients with tremor and electrodes in VL. LFPs were recorded from DBS electrodes and scalp electrodes simultaneously while the patients performed self-paced and externally cued (ready, go/no-go) movements. For the self-paced movement, a premovement-related potential was observed in all patients from scalp, STN (phase reversal, five of six patients), and VL (phase reversal, five of five patients) electrodes. The onset times of the potentials were similar in the cortex, STN, and VL, ranging from 1.5 to 2 s before electromyogram onset. For the externally cued movement, an expectancy potential was observed in all patients in cortical and STN electrodes (phase reversal, six of six patients). The expectancy potential was recorded from the thalamic electrodes in four of five patients. However, phase reversal occurred only in one case, and magnetic resonance imaging showed that this contact was outside the VL. The cortico-BG-thalamocortical circuit is involved in the preparation of both self-paced and externally cued movements. The CTC pathway is involved in the preparation of self-paced but not externally cued movements, although the pathway may still be involved in the execution of these movements.