Iowa Gambling Task in patients with early-onset Parkinson's disease: strategy analysis.

The aim of our study was to analyse decision making in early-onset Parkinson's disease (PD) patients performing the Iowa Gambling Task (IGT). We compared 19 patients with early-onset PD (≤ 45 years) on dopaminergic medication (no evidence of depression, dementia, executive dysfunction according to the Tower of London test and the Stroop test, or pathological gambling) with 20 age-matched controls. A computer version of the IGT was employed. The PD patients achieved slightly lower IGT scores than the control group. A detailed analysis based on 'shift frequencies' between the individual decks showed that the patients tended to change their preferences for the decks more frequently, with a higher preference for the 'disadvantageous' deck B. Control subjects seemed to develop a more effective strategy. These differences could be caused by the poorer ability of the patients to develop any strategy at all. We observed changes in decision making during IGT performance in patients with early-onset PD, although they had no executive dysfunction as measured by established neuropsychological tests. The more detailed analysis employed in the present study could lead to a more accurate study of IGT performance and application of IGT in clinical practice.

Predictive motor timing performance dissociates between early diseases of the cerebellum and Parkinson's disease.

There is evidence that both the basal ganglia and the cerebellum play a role in the neural representation of time in a variety of behaviours, but whether one of them is more important is not yet clear. To address this question in the context of predictive motor timing, we tested patients with various movement disorders implicating these two structures in a motor-timing task. Specifically, we investigated four different groups: (1) patients with early Parkinson's disease (PD); (2) patients with sporadic spinocerebellar ataxia (SCA); (3) patients with familial essential tremor (ET); and (4) matched healthy controls. We used a predictive motor-timing task that involved mediated interception of a moving target, and we assessed the effect of movement type (acceleration, deceleration and constant), speed (slow, medium and fast) and angle (0 degrees , 15 degrees and 30 degrees) on performance (hit, early error and late error). The main results showed that PD group and arm ET subgroup did not significantly differ from the control group. SCA and head ET subjects (severe and mild cerebellar damage, respectively) were significantly worse at interception than the other two groups. Our findings support the idea that the basal ganglia play a less significant role in predictive motor timing than the cerebellum. The fact that SCA and ET subjects seemed to have a fundamental problem with predictive motor timing suggests that the cerebellum plays an essential role in integrating incoming visual information with the motor output in a timely manner, and that ET is a heterogeneous entity that deserves increased attention from clinicians.

Functional imaging of the cerebellum and basal ganglia during predictive motor timing in early Parkinson's disease.

BACKGROUND AND PURPOSE: The basal ganglia and the cerebellum have both emerged as important structures involved in the processing of temporal information. METHODS: We examined the roles of the cerebellum and striatum in predictive motor timing during a target interception task in healthy individuals (HC group; n = 21) and in patients with early Parkinson's disease (early stage PD group; n = 20) using functional magnetic resonance imaging. RESULTS: Despite having similar hit ratios, the PD failed more often than the HC to postpone their actions until the right moment and to adapt their behavior from one trial to the next. We found more activation in the right cerebellar lobule VI in HC than in early stage PD during successful trials. Successful trial-by-trial adjustments were associated with higher activity in the right putamen and lobule VI of the cerebellum in HC. CONCLUSIONS: We conclude that both the cerebellum and striatum are involved in predictive motor timing tasks. The cerebellar activity is associated exclusively with the postponement of action until the right moment, whereas both the cerebellum and striatum are needed for successful adaptation of motor actions from one trial to the next. We found a general ''hypoactivation'' of basal ganglia and cerebellum in early stage PD relative to HC, indicating that even in early stages of the PD there could be functional perturbations in the motor system beyond striatum.

Similar circuits but different connectivity patterns between the cerebellum, basal ganglia, and supplementary motor area in early Parkinson's disease patients and controls during predictive motor timing.

BACKGROUND AND PURPOSE: The cerebellum, basal ganglia (BG), and other cortical regions, such as supplementary motor area (SMA) have emerged as important structures dealing with various aspects of timing, yet the modulation of functional connectivity between them during motor timing tasks remains unexplored. METHODS: We used dynamic causal modeling to investigate the differences in effective connectivity (EC) between these regions and its modulation by behavioral outcome during a motor timing prediction task in a group of 16 patients with early Parkinson's disease (PD) and 17 healthy controls. Behavioral events (hits and errors) constituted the driving input connected to the cerebellum, and the modulation in connectivity was assessed relative to the hit condition (successful interception of target). RESULTS: The driving input elicited response in the target area, while modulatory input changed the specific connection strength. The neuroimaging data revealed similar structure of intrinsic connectivity in both groups with unidirectional connections from cerebellum to both sides of the BG, from BG to the SMA, and then from SMA to the cerebellum. However, the type of intrinsic connection was different between two groups. In the PD group, the connection between the SMA and cerebellum was inhibitory in comparison to the HC group, where the connection was activated. Furthermore, the modulation of connectivity by the performance in the task was different between the two groups, with decreased connectivity between the cerebellum and left BG and SMA and a more pronounced symmetry of these connections in controls. In the same time, there was an increased EC between the cerebellum and both sides of BG with more pronounced asymmetry (stronger connection with left BG) in patients. In addition, in the PD group the modulatory input strengthened inhibitory connectivity between the SMA and the cerebellum, while in the HC group the excitatory connection was slightly strengthened. CONCLUSIONS: Our findings indicate that although early PD subjects and controls use similar functional circuits to maintain a successful outcome in predictive motor timing behavior, the type and strength of EC and its modulation by behavioral performance differ between these two groups. These functional differences might represent the first step of cortical reorganization aimed at maintaining a normal performance in the brain affected by early Parkinson's disease and may have implications for the neuro-rehabilitation field.

Essential tremor, the cerebellum, and motor timing: towards integrating them into one complex entity.

Essential tremor (ET) is the most common movement disorder in humans. It is characterized by a postural and kinetic tremor most commonly affecting the forearms and hands. Isolated head tremor has been found in 1-10% of patients, suggesting that ET may be a composite of several phenotypes. The exact pathophysiology of ET is still unknown. ET has been repeatedly shown as a disorder of mild cerebellar degeneration, particularly in postmortem studies. Clinical observations, electrophysiological, volumetric and functional imaging studies all reinforce the fact that the cerebellum is involved in the generation of ET. However, crucial debate exists as to whether ET is a neurodegenerative disease. Data suggesting that it is neurodegenerative include postmortem findings of pathological abnormalities in the brainstem and cerebellum, white matter changes on diffusion tensor imaging, and clinical studies demonstrating an association with cognitive and gait changes. There is also conflicting evidence against ET as a neurodegenerative disease: the improvement of gait abnormalities with ethanol administration, lack of gray matter volume loss on voxel-based morphometry, failure to confirm the prominent presence of Lewy bodies in the locus ceruleus, and other pathological findings. To clarify this issue, future research is needed to describe the mechanism of cellular changes in the ET brain and to understand the order in which they occur. The cerebellum has been shown to be involved in the timing of movement and sensation, acting as an internal timing system that provides the temporal representation of salient events spanning hundreds of milliseconds. It has been reported that cerebellar timing function is altered in patients with ET, showing an increased variability of rhythmic hand movements as well as diminished performance during predictive motor timing task. Based on current knowledge and observations, we argue that ET is essentially linked with cerebellar degeneration, or at least cerebellar dysfunction, together with disturbance of motor timing. We explain the context of our current understanding on this topic, highlighting possible clinical consequences for patients suffering from ET and future research directions.