Humans are able to use knowledge of previous events to estimate the probability of future actions. Consequently, an unexpected event will elicit a prediction error as the prepared action has to be ...replaced by an unprepared option in a process known as "action reprogramming" (AR). Here we show that people with Parkinson's disease (PD) have a dopamine-sensitive deficit in AR that is proportional to the size of the prediction error. Participants performed a probabilistic reaction time (RT) task in the context of either a predictable or unpredictable environment. For an overall predictable sequence, PD patients, on and off dopamine medication, and healthy controls showed similar improvements in RT. However, in the context of a generally predictable sequence, PD patients off medication were impaired in reacting to unexpected events that elicit large prediction errors and require AR. Critically, this deficit in AR was modulated by the prediction error associated with the upcoming event. The prolongation of RT was not observed during an overall unpredictable sequence, in which relatively unexpected events evoke little prediction error and the requirement for AR should be minimal, given the context. The data are compatible with recent theoretical accounts suggesting that levels of dopamine encode the reliability, i.e., precision, of sensory information. In this scheme, PD patients off medication have low dopamine levels and may therefore be less confident about incoming sensory information and more reliant on top-down predictions. Consequently, when these internal predictions are incorrect, PD patients take longer to respond appropriately to unexpected sensory information.
From observation of human behavior, we know that speed of movement initiation and execution can be influenced by motivational factors, for example we walk faster when in a hurry (sense of urgency) or ...write faster during an exam (potential reward of good results). However, there is scant experimental evidence for the motivational modulation of movement in man. Experiments in non-human primates have demonstrated shortening of reaction times in response to reward. However, it is not clear how reward might affect performance of reaction time (RT) tasks in humans, and specifically whether warned and unwarned simple and uncued and precued choice RTs are similarly or differentially affected by reward. The effect of monetary incentive on total time (TT, (RT + MT)) was assessed in 16 healthy participants using four paradigms: warned simple RT (wSRT), unwarned simple RT (uSRT), uncued choice RT (uCRT), and precued choice RT (pCRT). wSRT, uSRT, and pCRT tasks all allow advance preparation and preprogramming of the movement, whereas uCRT does not. We found a significant effect of monetary incentive in shortening TTs in wSRT, uSRT, and pCRT tasks, but no effect on the uCRT task. These results demonstrate that monetary incentive can speed up movement initiation and execution in human participants, but only in tasks where preprogramming of the response is possible. This suggests that in reaction time tasks such as these, monetary incentive is having its effect by enhancing preparation of preprogrammed movement, but has little effect when movements cannot be specified in advance. These “RT and reward” tasks provide a useful paradigm for investigation into the effects of monetary incentive on reaction times in man and to study motivational modulation of movement speed in health and disease.
Paradoxical kinesis has been observed in bradykinetic people with Parkinson's disease. Paradoxical kinesis occurs in situations where an individual is strongly motivated or influenced by relevant ...external cues. Our aim was to induce paradoxical kinesis in the laboratory. We tested whether the motivation of avoiding a mild electric shock was sufficient to induce paradoxical kinesis in externally-triggered and self-initiated conditions in people with Parkinson's disease tested on medication and in age-matched controls.
Participants completed a shock avoidance behavioural paradigm in which half of the trials could result in a mild electric shock if the participant did not move fast enough. Half of the trials of each type were self-initiated and half were externally-triggered. The criterion for avoiding shock was a maximum movement time, adjusted according to each participant's performance on previous trials using a staircase tracking procedure.
On trials with threat of shock, both patients with Parkinson's disease and controls had faster movement times compared to no potential shock trials, in both self-initiated and externally-triggered conditions. The magnitude of improvement of movement time from no potential shock to potential shock trials was positively correlated with anxiety ratings.
When motivated to avoid mild electric shock, patients with Parkinson's disease, similar to healthy controls, showed significant speeding of movement execution. This was observed in both self-initiated and externally-triggered versions of the task. Nevertheless, in the ET condition the improvement of reaction times induced by motivation to avoid shocks was greater for the PD patients than controls, highlighting the value of external cues for movement initiation in PD patients. The magnitude of improvement from the no potential shock to the potential shock trials was associated with the threat-induced anxiety. This demonstration of paradoxical kinesis in the laboratory under both self-initiated and externally-triggered conditions has implications for motivational and attentional enhancement of movement speed in Parkinson's disease.
As part of the first randomized double-blind trial of deep brain stimulation (DBS) of the globus pallidus (GPi) in Tourette syndrome, we examined the effect of stimulation on response initiation and ...inhibition. A total of 14 patients with severe Tourette syndrome were recruited and tested on the stop signal task prior to and after GPi-DBS surgery and compared to eight age-matched healthy controls. Tics were significantly improved following GPi-DBS. The main measure of reactive inhibition, the stop signal reaction time did not change from before to after surgery and did not differ from that of healthy controls either before or after GPi-DBS surgery. This suggests that patients with Tourette syndrome have normal reactive inhibition which is not significantly altered by GPi-DBS.
Parkinson's disease (PD) is characterized by a range of motor symptoms. Besides the cardinal symptoms (tremor, bradykinesia/akinesia, and rigidity), PD patients also show other motor deficits, ...including gait disturbance, speech deficits, and impaired handwriting. However, along with these key motor symptoms, PD patients also experience cognitive deficits in attention, executive function, working memory, and learning. Recent evidence suggests that these motor and cognitive deficits of PD are not completely dissociable, as aspects of cognitive dysfunction can impact motor performance in PD. In this article, we provide a review of behavioral and neural studies on the associations between motor symptoms and cognitive deficits in PD, specifically akinesia/bradykinesia, tremor, gait, handwriting, precision grip, and speech production. This review paves the way for providing a framework for understanding how treatment of cognitive dysfunction, for example cognitive rehabilitation programs, may in turn influence the motor symptoms of PD.
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for Parkinson's disease (PD). Varying the frequency DBS has differential effects on axial and distal limb ...functions, suggesting differing modulation of relevant pathways. The STN is also a critical node in oculomotor and associative networks, but the effect of stimulation frequency on these networks remains unknown. This study aimed to investigate the effects of 80 hz vs. 130 Hz frequency STN-DBS on eye movements and executive control. Twenty-one STN-DBS PD patients receiving 130 Hz vs. 80 Hz stimulation were compared to a healthy control group (n = 16). All participants were tested twice in a double-blind manner. We examined prosaccades (latency and gain) and antisaccades (latency of correct and incorrect antisaccades, error rate and gain of the correct antisaccades). Executive function was tested with the Stroop task. The motor condition was assessed using Unified Parkinson's Disease Rating Scale part III. The antisaccadic error rate was higher in patients (p = 0.0113), more so in patients on 80 Hz compared to 130 Hz (p = 0.001) stimulation. The differences between patients and controls and between frequencies for all other eye-movements or cognitive measures were not statistically significant. We show that 80 Hz STN-DBS in PD reduces the ability to maintain stable fixation but does not alter inhibition, resulting in a higher antisaccade error rate presumably due to less efficient fixation, without altering the motor state. This provides a wider range of stimulation parameters that can reduce specific DBS-related effects without affecting motor outcomes.
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