The structural connectivity of discrete networks underlies impulsivity and gambling in Parkinson’s disease

Abstract

See O’Callaghan (doi:10.1093/brain/awz349) for a scientific commentary on this article. Mosley et al. examine impulsivity and naturalistic gambling behaviours in patients with Parkinson’s disease. They link within-patient differences to the structural connectivity of networks subserving reward evaluation and response inhibition, and reveal pivotal roles for the ventral striatum and subthalamic nucleus within these networks.

Increased large-scale inter-network connectivity in relation to impulsivity in Parkinson’s disease

“…For instance, ICD has been associated with increased connectivity between the left subthalamic nucleus and the left parietal operculum, whereas trait impulsivity has been associated with a weak connectivity between the left putamen and the right inferior temporal gyrus 21 . Other studies investigating cortical thickness, tractography, or functional MRI have also reported inconsistent results [5][6][7][19][20][21][22] . One of the causes is that impulsivity contains multifaceted constructs.…”

“…High impulsivity (HI) is a precursor of ICDs and can also lead to severe ICDs 18,19 . While HI may be within the spectrum of ICDs, the underlying pathophysiological mechanism differs between trait impulsivity and ICDs 20 . For instance, ICD has been associated with increased connectivity between the left subthalamic nucleus and the left parietal operculum, whereas trait impulsivity has been associated with a weak connectivity between the left putamen and the right inferior temporal gyrus 21 .…”

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

“…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 ).…”