248 research outputs found
Subthalamic nucleus deep brain stimulation induces impulsive action when patients with Parkinson's disease act under speed pressure
The subthalamic nucleus (STN) is proposed to modulate response thresholds and speed-accuracy trade-offs. In situations of conflict, the STN is considered to raise response thresholds, allowing time for the accumulation of information to occur before a response is selected. Conversely, speed pressure is thought to reduce the activity of the STN and lower response thresholds, resulting in fast, errorful responses. In Parkinson's disease (PD), subthalamic nucleus deep brain stimulation (STN-DBS) reduces the activity of the nucleus and improves motor symptoms. We predicted that the combined effects of STN stimulation and speed pressure would lower STN activity and lead to fast, errorful responses, hence resulting in impulsive action. We used the motion discrimination 'moving-dots' task to assess speed-accuracy trade-offs, under both speed and accuracy instructions. We assessed 12 patients with PD and bilateral STN-DBS and 12 age-matched healthy controls. Participants completed the task twice, and the patients completed it once with STN-DBS on and once with STN-DBS off, with order counterbalanced. We found that STN stimulation was associated with significantly faster reaction times but more errors under speed instructions. Application of the drift diffusion model showed that stimulation resulted in lower response thresholds when acting under speed pressure. These findings support the involvement of the STN in the modulation of speed-accuracy trade-offs and establish for the first time that speed pressure alone, even in the absence of conflict, can result in STN stimulation inducing impulsive action in PD
Effects of deep brain stimulation of the subthalamic nucleus and the pedunculopontine nucleus on cognitive function in Parkinson's disease
The general aim of this thesis was to investigate the cognitive effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN) or the pedunclopontine nucleus (PPN) in Parkinson’s disease (PD). In Study 1, acute STN stimulation did not induce impulsivity on a probabilistic decisionmaking task, suggesting STN-DBS induced impulsivity may occur in tasks involving conflict, reward or time pressure. This study has clarified that the inhibitory deficits associated with STN-DBS are situation and task specific, which makes it clear why new cases of post-operative impulse control disorders are only reported in some patients. In Study 2, the STN-DBS induced decline in verbal fluency (VF), greater for semantic than phonemic fluency, was found to be a surgical rather than an acute stimulation effect, mainly due to reduced switching but no change in cluster size. Therefore, future work in identifying the mechanisms of the STN-DBS induced VF decline should focus on surgical rather than stimulation effects. In Study 3, patients failed to benefit from corrective feedback to enhance their learning relative to a trial-and-error version when performing visual conditional associative learning tasks (VCLT) with STN-DBS on versus off. STN-DBS seemed to influence proactive interference resolution on the VCLTs. These results have implications for the use of adjunct interventions such as speech therapy or physiotherapy following STN-DBS surgery. In Study 4, PPN-DBS surgery did not have an impact on most aspects of cognition assessed and the only consistent decline was in switching category VF. For the two patients who developed dementia after PPN-DBS surgery, resuming low frequency stimulation improved working memory and attention. The findings from these studies provide further evidence and clarity regarding the cognitive sequel of STN-DBS and PPN-DBS for PD and confirm that the former can be a good treatment of choice for mid to late-stage Parkinson’s disease without the risk of major cognitive adverse effects
Deep Brain Stimulation of the Subthalamic Nucleus Induces Impulsive Responses to Bursts of Sensory Evidence
Decisions are made through the integration of external and internal inputs until a threshold is reached, triggering a response. The subthalamic nucleus (STN) has been implicated in adjusting the decision bound to prevent impulsivity during difficult decisions. We combine model-based and model-free approaches to test the theory that the STN raises the decision bound, a process impaired by deep brain stimulation (DBS). Eight male and female human subjects receiving treatment for Parkinson's disease with bilateral DBS of the STN performed an auditory two-alternative forced choice task. By ending trials unpredictably, we collected reaction time (RT) trials in which subjects reached their decision bound and non-RT trials in which subjects were forced to make a decision with less evidence. A decreased decision bound would cause worse performance on RT trials, and we found this to be the case on left-sided RT trials. Drift diffusion modeling showed a negative drift rate. This implies that in the absence of new evidence, the amount of evidence accumulated tends to drift toward zero. If evidence is accumulated at a constant rate this results in the evidence accumulated reaching an asymptote, the distance of which from the bound was decreased by DBS (p = 0.0079, random shuffle test), preventing subjects from controlling impulsivity. Subjects were more impulsive to bursts of stimuli associated with conflict (p < 0.001, cluster mass test). In addition, DBS lowered the decision bound specifically after error trials, decreasing the probability of switching to a non-RT trial after an error compared to correct response (28% vs. 38%, p = 0.005, Fisher exact test). The STN appears to function in decision-making by modulating the decision bound and drift rate to allow the suppression of impulsive responses
Effects of deep brain stimulation of the subthalamic nucleus on inhibitory and executive control over prepotent responses in Parkinson's disease.
Inhibition of inappropriate, habitual or prepotent responses is an essential component of executive control and a cornerstone of self-control. Via the hyperdirect pathway, the subthalamic nucleus (STN) receives inputs from frontal areas involved in inhibition and executive control. Evidence is reviewed from our own work and the literature suggesting that in Parkinson's disease (PD), deep brain stimulation (DBS) of the STN has an impact on executive control during attention-demanding tasks or in situations of conflict when habitual or prepotent responses have to be inhibited. These results support a role for the STN in an inter-related set of processes: switching from automatic to controlled processing, inhibitory and executive control, adjusting response thresholds and influencing speed-accuracy trade-offs. Such STN DBS-induced deficits in inhibitory and executive control may contribute to some of the psychiatric problems experienced by a proportion of operated cases after STN DBS surgery in PD. However, as no direct evidence for such a link is currently available, there is a need to provide direct evidence for such a link between STN DBS-induced deficits in inhibitory and executive control and post-surgical psychiatric complications experienced by operated patients
The acute effects of dopaminergic medication and deep brain stimulation of subthalamic nucleus on basic executive functions including shifting, updating and inhibition in Parkinson’s disease patients
The general aim of the present PhD thesis is to investigate the effects of two common treatments of Parkinson’s disease (PD), dopamine medication and deep brain stimulation (DBS) of the subthalamic nucleus (STN), on executive functions (EFs) including the abilities of shifting, updating and inhibition in patients relative to age-matched healthy controls. The thesis consisted of four studies. Study 1 examined the acute effect of dopamine medication on PD patients who had been previously diagnosed with impulsive control disorders (ICDs) using a moving dots paradigm to assess their abilities of context monitoring. Study 2 created predictive models using behavioural data from the previous studies to build classification predictive models, to demonstrate that behavioural patterns on a moving dots task could potentially be used as a screening tool in predicting vulnerability to develop ICDs in PD patients. Study 3 examined the acute effects of STN DBS on task switching using a moving dots paradigm in PD patients. Study 4 investigated the acute effects of STN DBS on reprogramming actions when encountering surprising events, using a probabilistic reaction time (RT) task. It was hypothesised that for both treatments, being ON states would induce impaired executive functions that lead to faster RTs and more incorrect responses in PD patients, due to the ‘dopamine overdose hypothesis’ and the DBS interrupting the role of the STN in inhibitory control. In summary, the acute manipulation of both treatments did not render significantly negative effects on PD patients behaviourally. However, PD patients still showed certain difference on task performance compared to age-matched healthy controls, which may shed lights on the role of basal ganglia in basic abilities of EFs. Furthermore, the behavioural patterns on tasks involving core aspects of EFs may potentially be used to predict the onset of ICDs, which provides benefits to clinical purpose
Doctor of Philosophy
dissertationParkinson's Disease (PD) motor symptoms, characterized most commonly by bradykinesia, akinesia, rigidity, and tremor, are brought about through the degeneration of dopaminergic neurons in the substantia nigra pars compacta, which leads to changes in electrophysiological activity throughout the basal ganglia. These symptoms are often effectively treated in the early stages of the disease by dopamine replacement therapies. However, as the disease progresses, the therapeutic window of pharmacological approaches reduces and patients develop significant side effects, even under minimally effective doses. When the disease reaches this stage, surgical therapies, such as high-frequency deep brain stimulation (DBS), are considered. DBS of the subthalamic nucleus partially treats the motor symptoms of PD and has been implemented to treat PD over 50,000 times worldwide, but its mechanisms are unclear. In this work, we set out to advance the understanding of the mechanisms, function, and malfunction of DBS as a treatment for PD, keeping in mind the idea that DBS treats PD symptoms without restoring basal ganglia neural activity to that seen under healthy conditions. First, we demonstrated that neuronal information directed from the basal ganglia to the thalamus is pathologically increased in the parkinsonian condition and reduced by DBS in a standard 6-OHDA rat model of PD. Next, we developed a rodent model of DBSs role in the exacerbation of hypokinetic dysarthria, providing a framework for the study of this poorly understood side effect of DBS. Finally, we found that DBS creates action suppression deficits independently from a parkinsonian state, and that PD creates apathy that is not rescued by DBS. Our specific results led to the interpretation that DBS, in its current form, might inherently create side effects that are largely unavoidable. Our work fits into the following overarching idea. DBS successfully treats some motor symptoms of PD through the reduction of pathological information transmission. However, the fact that reducing pathological information does not restore neural activity to that present under healthy conditions underlies some of its failures to improve certain symptoms, as well as its exacerbations and side effects
- …