Subthalamic stimulation affects homophone meaning generation in Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) in individuals with Parkinson's disease (PD) has often been associated with reduced verbal fluency performance. This study aimed to directly assess semantic switching as a function of STN stimulation in PD participants with the Homophone Meaning Generation Test (HMGT). Seventeen participants with PD who had received STN DBS completed the HMGT in on and off stimulation conditions. Twenty-one non-neurologically impaired participants acted as controls. PD participants (in both on and off stimulation conditions) generated significantly fewer meanings than control participants and consistent with the previous reports of verbal fluency impairment, PD participants produced fewer definitions in the on stimulation condition. PD participants (in both on and off stimulation conditions) also had greater difficulty generating definitions for nonhomographic homophones compared with homographic homographs. The results of this study indicate that STN stimulation exacerbates impairment in semantic switching.

Estimation of neuronal firing rates with the three-state biological point process model.

In the subcortex of the human brain, neuronal firing events are stochastic and the inter-arrival times of action potentials (APs) are highly irregular. It has been shown that stimulation of the subthalamic nucleus (STN), a small subcortical structure located within the basal ganglia, can help ameliorate the motor symptoms associated with Parkinson's disease (PD). However, success of image guided stereotactic surgery is reliant upon the refinement of the anatomic target (in this case the STN) based on micro-electrode recordings (MERs) of background activity and firing rate. In practice MERs must be analysed on-line and in real-time. Currently, the most common method of performing on-line MER analysis is a manual thresholding procedure. However, this is subjective in nature and often complicated by the presence of variable amounts of background noise. Therefore, in this paper, we present an automated adaptive thresholding technique, based on a modified 'top-hat' operator, which detects APs exceeding the local background activity. We then go on to model these inter-arrival times using a coupled Poisson process that provides improved estimates of both inter-burst and intra-burst neuronal firing activity in the STN.

Lexical-semantic inhibitory mechanisms in Parkinson's disease as a function of subthalamic stimulation.

Inhibitory control may be affected by Parkinson's disease (PD) due to impairment within the non-motor basal ganglia-thalamocortical circuits. The present study aimed to identify the effects of chronic stimulation of the subthalamic nucleus (STN) on lexical-semantic inhibitory control. Eighteen participants with PD who had undergone surgery for deep brain stimulation (DBS) of the STN, completed a picture-word interference (PWI) task and the Hayling test in on and off stimulation conditions. The results of PD participants were compared with 21 non-neurologically impaired control participants. PD participants performed no differently from controls on the PWI task, and no significant differences between on and off stimulation conditions were revealed, therefore suggesting that PD participants are not impaired in lexical-semantic interference control. In contrast, in the off stimulation condition, PD participants had significantly delayed reaction times and increased errors on the inhibition section of the Hayling test compared with the STN stimulation condition and control participants. These results suggest that PD patients are impaired in aspects of inhibitory control that are dependent on behavioural inhibition (such as the suppression of prepotent responses) and selection from competing alternatives without the presence of external cues. Furthermore, STN stimulation acts to restore these behavioural inhibitory processes.

Semantic and affective priming as a function of stimulation of the subthalamic nucleus in Parkinson's disease.

Lexical-semantic and emotional processing deficits have been associated with Parkinson's disease. This study investigated automatic and controlled lexical-semantic processing, the automatic activation of emotional evaluations, and the processing of words conveying negative and neutral emotional connotations in a combined affective and semantic priming paradigm. Eighteen participants with Parkinson's disease who had undergone surgery for deep brain stimulation (DBS) of the subthalamic nucleus (STN) completed a lexical decision task at short and long stimulus onset asynchronies (SOAs), during on and off stimulation conditions. Nineteen non-neurologically impaired participants acted as controls. The results indicated that automatic lexical-semantic and emotional evaluative processes are unimpaired in Parkinson's disease as reflected in the presence of comparable semantic and affective priming effects at the short SOA in on and off stimulation conditions compared with healthy controls. In contrast, participants with Parkinson's disease in the off stimulation condition showed a pattern of aberrant controlled lexical-semantic processing as evidenced by a lack of semantic priming effects at the long SOA condition. Controlled semantic priming was present, however, when the participants with Parkinson's disease were receiving stimulation of the STN, suggesting that STN stimulation modulates basal ganglia-thalamocortical circuits involved in such processes. Finally, delayed reaction times for negatively valenced targets compared with neutrally valenced targets was evident in participants with Parkinson's disease in the on stimulation condition and control participants, but not for participants with Parkinson's disease in the off stimulation condition, suggesting that the incidental evaluation of negatively versus neutrally valenced words in Parkinson's disease is modulated by basal ganglia-thalamocortical circuits.