Abstract
The phenomenon of impulsivity in Parkinson's disease appears as an arduous side effect of dopaminergic therapy with potentially detrimental consequences for the life of the patients. Although conceptualized as a result of non-physiologic chronic dopaminergic stimulation, recent advances speculate on combined disruption of other networks as well. In the search for neuroanatomical correlates of this multifaceted disturbance, this study employs two distinct, well-defined tasks of close association to motor inhibition and decision-making impulsivity, Go/No Go and Delay discounting. The fMRI and functional connectivity analysis in 21 Parkinson's disease patients, including 8 patients suffering from severe impulse control disorder, and 28 healthy controls, revealed in impulsive Parkinson's disease patients not only decreased fMRI activation in the dorsolateral prefrontal cortex and bilateral striatum, but also vast functional connectivity changes of both caudate nuclei as decreased connectivity to the superior parietal cortex and increased connectivity to the insular area, clearly beyond the commonly stated areas, which indicates that orbitofronto-striatal and mesolimbic functional disruptions are not the sole mechanisms underlying impulse control disorder in Parkinson's disease. Ergo, our results present a refinement and synthesis of gradually developing ideas about the nature of impulsive control disorder in Parkinson's disease—an umbrella term encompassing various behavioral deviations related to distinct neuronal networks and presumably neurotransmitter systems, which greatly exceed the previously envisioned dopaminergic pathways as the only culprit.
Highlights
While considered a mere movement disorder in the times past, Parkinson’s disease (PD) is generally seen as a complex dimension of multiple motor, cognitive, and behavioral components, with neuropsychiatric affections as depression, apathy, and impulse control disorders (ICDs) being the most salient of the non-motor symptoms (Cooney and Stacy, 2016)
ICDs are thought to be triggered by the interaction of chronic dopaminergic medication, especially dopamine agonist therapy (Garcia-Ruiz et al, 2014), and pathophysiological vulnerabilities, either pre-existing before the onset of the disease, or associated directly with neurodegeneration in progressing PD (Vriend, 2018), as occurrence of ICDs in treatment-naïve PD patients is very similar to the general population (Weintraub et al, 2013)
analysis of variance (ANOVA) revealed significant differences among the subgroups in both MADRS [F(2, 47) = 6.64, p = 0.003] and Barratt scale [F(2, 47) = 3.57, p = 0.036], with the highest depression scores found in the non-impulsive PD group, and, the highest impulsivity scores, as expected, in the ICD-PD group
Summary
While considered a mere movement disorder in the times past, Parkinson’s disease (PD) is generally seen as a complex dimension of multiple motor, cognitive, and behavioral components, with neuropsychiatric affections as depression, apathy, and impulse control disorders (ICDs) being the most salient of the non-motor symptoms (Cooney and Stacy, 2016). Impulsivity, commonly defined as the lack of behavioral inhibition and/or premature decision making, entails compulsive fMRI Network Disruption in PD-ICD or repetitive engagement in certain activities, closely associated with the inability to foresee or learn from negative outcomes. In PD, a diverse spectrum of maladaptive behaviors is included in ICDs such as pathological gambling, paraphilias, excessive shopping, or binge eating, with the list sometimes extended by closely related phenomena and purposeless, repetitive behaviors as punding, hoarding, and hobbyism (Weintraub et al, 2015). The underlying neuropathology of ICD probably involves the overstimulation of dopaminergic rewardrelated pathways, assigning excessive salience to incentives (Robinson and Berridge, 1993), and the interference in D2-signaling pauses in the ventral striatum (Frank et al, 2004; Vriend, 2018), which impairs the encoding of harmful behavior, i.e., prevents negative-feedback learning, and leaves D1-receptor-facilitated positive reinforcement intact. Dopamine receptor abnormities (Steeves et al, 2009; Vriend et al, 2014) support the hypothesis of PD pathology being a direct predisposition to ICD
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
