Functional Inhibitory Control Dynamics in Impulse Control Disorders in Parkinson's Disease

Abstract

A BS TRACT: Background: Impulse control disorders related to alterations in the mesocorticolimbic dopamine network occur in Parkinson's disease (PD). Our objective was to investigate the functional neural substrates of reward processing and inhibitory control in these patients. Methods: Eighteen PD patients with impulse control disorders, 17 without this complication, and 18 healthy controls performed a version of the Iowa Gambling Task during functional magnetic resonance scanning under 3 conditions: positive, negative, and mixed feedback. Whole-brain contrasts, regions of interest, time courses, functional connectivity analyses, and brain-behavior associations were examined. Results: PD patients with impulse control disorders exhibited hyperactivation in subcortical and cortical regions typically associated with reward processing and inhibitory control compared with their PD and healthy control counterparts. Time-course analyses revealed that only PD patients with impulse control disorders exhibited stronger signal intensity during the initial versus final periods of the negative-feedback condition in bilateral insula, and right ventral striatum. Interestingly, hyperactivation of all the examined right-lateralized frontostriatal areas during negative feedback was positively associated with impulse control disorder severity. Importantly, positive associations between impulse control disorder severity and regional activations in the right insula and right inferior frontal gyrus, but not the right subthalamic nucleus, were mediated by functional connectivity with the right ventral striatum. Conclusions: During a reward-based task, PD patients with impulse control disorders showed hyperactivation in a right-lateralized network of regions including the subthalamic nucleus that was strongly associated with impulse control disorder severity. In these patients, the right ventral striatum in particular played a critical role in modulating the functional dynamics of right-lateralized inhibitory-control frontal regions when facing penalties.

Linking brain activity during sequential gambling to impulse control in Parkinson's disease

“…5 ). Beyond some studies implicating differences in the activity of response-control regions such as the ACC in ICD ( van Eimeren et al, 2010 , Hammes et al, 2019 ), this finding indicates a reduced engagement of both the inhibitory control network (i.e., right STN and right IFG) and reward processing network (i.e., right and left VS), in sequential gambling in PD patients with ICD, showing that both processes are altered in PD patients with ICD ( Mosley et al, 2019 , Paz-Alonso et al, 2020 ).…”

“…The emergence of ICD during dopamine replacement therapy on patients with PD has been attributed to two neurocognitive mechanisms ( Mosley et al, 2019 , Paz-Alonso et al, 2020 , Cilia and van Eimeren, 2011 ). The first mechanism consists of functional alterations in the reward system, especially the ventral striatum (VS), which may alter reward valuation.…”

“…Functional alterations in the inhibitory network constitute a second neurocognitive mechanism, which may contribute to abnormal impulsivity ( Mosley et al, 2019 , Paz-Alonso et al, 2020 ). Impulsivity is broadly seen as a failure of inhibition and is commonly divided into a “motor” subtype related to the failure to inhibit inappropriate actions and a “cognitive” subtype related to e.g.…”

“…Patients with ICD are unimpaired in tasks testing motor impulsivity such as the stop-signal or Simon task ( Wylie et al, 2012 , Claassen et al, 2015 ), but impaired in tasks testing impulsivity in more cognitively demanding contexts such as temporal discounting ( Housden et al, 2010 , Voon et al, 2011 ), information sampling ( Djamshidian et al, 2012 ), perceptual decision-making ( Djamshidian et al, 2014 ), and novelty-seeking ( Djamshidian et al, 2011 ). The functional brain alterations that underpin faulty cognitive inhibition in ICD have been associated with changes in a fronto-subthalamic network ( Mosley et al, 2019 , Paz-Alonso et al, 2020 ). This network consists of the pre-supplementary motor area (pre-SMA) and inferior frontal gyrus (IFG), which directly project to the subthalamic nucleus (STN) via so-called hyper-direct pathways, mediating the inhibitory control of action and cognition ( Djamshidian et al, 2012 , Djamshidian et al, 2014 , Djamshidian et al, 2011 , Aron et al, 2007 , Jahfari et al, 2009 , Neubert et al, 20107 , Rae et al, 2015 ).…”

Response to the paper “unraveling functional Neurology: an overview of all published documents by FR Carrick, including a critical review of research articles on its effect or benefit.” by Marine Demortier and Charlotte Leboeuf-Yde

“…There is an abundance of evidence-based literature reporting diagnostic and treatment modalities under a FN paradigm. Functional connectivity (FC) [2,[12][13][14], functional neuroanatomy of sequence learning [15], functional neural substrates of reward processing and inhibitory control [16], functional brain network connectivity [17], functional neurological characterization of disease [18], functional exercise capacity [19], utilization of functional magnetic resonance imaging (fMRI) scanning of cognitive tasks [20] are all components of a FN paradigm and the list goes on and on. While physical exercise is an evidence-based application within the paradigm of FN, it would not and should not be classified as a FN treatment.…”