Impulse control disorders in Parkinson’s disease are common neuropsychiatric complications associated with dopamine replacement therapy. Some patients treated with dopamine agonists develop pathological behaviours, such as gambling, compulsive eating, shopping, or disinhibited sexual behaviours, which can have a severe impact on their lives and that of their families. In this study we investigated whether hypersensitivity to reward might contribute to these pathological behaviours and how this is influenced by dopaminergic medication. We asked participants to shift their gaze to a visual target as quickly as possible, in order to obtain reward. Critically, the reward incentive on offer varied over trials. Motivational effects were indexed by pupillometry and saccadic velocity, and patients were tested ON and OFF dopaminergic medication, allowing us to measure the effect of dopaminergic medication changes on reward sensitivity. Twenty-three Parkinson’s disease patients with a history of impulse control disorders were compared to 26 patients without such behaviours, and 31 elderly healthy controls. Intriguingly, behavioural apathy was reported alongside impulsivity in the majority of patients with impulse control disorders. Individuals with impulse control disorders also exhibited heightened sensitivity to exogenous monetary rewards cues both ON and OFF (overnight withdrawal) dopamine medication, as indexed by pupillary dilation in anticipation of reward. Being OFF dopaminergic medication overnight did not modulate pupillary reward sensitivity in impulse control disorder patients, whereas in control patients reward sensitivity was significantly reduced when OFF dopamine. These effects were independent of cognitive impairment or total levodopa equivalent dose. Although dopamine agonist dose did modulate pupillary responses to reward, the pattern of results was replicated even when patients with impulse control disorders on dopamine agonists were excluded from the analysis. The findings suggest that hypersensitivity to rewards might be a contributing factor to the development of impulse control disorders in Parkinson’s disease. However, there was no difference in reward sensitivity between patient groups when ON dopamine medication, suggesting that impulse control disorders may not emerge simply because of a direct effect of dopaminergic drug level on reward sensitivity. The pupillary reward sensitivity measure described here provides a means to differentiate, using a physiological measure, Parkinson’s disease patients with impulse control disorder from those who do not experience such symptoms. Moreover, follow-up of control patients indicated that increased pupillary modulation by reward can be predictive of the risk of future emergence of impulse control disorders and may thereby provide the potential for early identification of patients who are more likely to develop these symptoms.
The claustrum is the most densely interconnected region in the human brain. Despite the accumulating data from clinical and experimental studies, the functional role of the claustrum remains unknown. Here, we systematically review claustrum lesion studies and discuss their functional implications. Claustral lesions are associated with an array of signs and symptoms, including changes in cognitive, perceptual and motor abilities; electrical activity; mental state; and sleep. The wide range of symptoms observed following claustral lesions do not provide compelling evidence to support prominent current theories of claustrum function such as multisensory integration or salience computation. Conversely, the lesions studies support the hypothesis that the claustrum regulates cortical excitability. We argue that the claustrum is connected to, or part of, multiple brain networks that perform both fundamental and higher cognitive functions. As a multifunctional node in numerous networks, this may explain the manifold effects of claustrum damage on brain and behaviour.
Apathy and impulsivity are debilitating conditions associated with many neuropsychiatric conditions, and expressed to variable degrees in healthy people. While some theories suggest that they lie at different ends of a continuum, others suggest their possible co-existence. Surprisingly little is known, however, about their empirical association in the general population. Here, gathering data from six large studies ($$n = 3755$$ n = 3755 ), we investigated the relationship between measures of apathy and impulsivity in young adults. The questionnaires included commonly used self-assessment tools—Apathy Evaluation Scale, Barratt Impulsiveness Scale (BIS-11) and UPPS-P Scale—as well as a more recent addition, the Apathy Motivation Index (AMI). Remarkably, across datasets and assessment tools, global measures of apathy and impulsivity correlated positively. However, analysis of sub-scale scores revealed a more complex relationship. Although most dimensions correlated positively with one another, there were two important exceptions revealed using the AMI scale. Social apathy was mostly negatively correlated with impulsive behaviour, and emotional apathy was orthogonal to all other sub-domains. These results suggest that at a global level, apathy and impulsivity do not exist at distinct ends of a continuum. Instead, paradoxically, they most often co-exist in young adults. Processes underlying social and emotional apathy, however, appear to be different and dissociable from behavioural apathy and impulsivity.
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