Reduced GO/NOGO ACC-sensitive activity in a case of Parkinson's disease with impulse control disorders

Abstract

Introduction

The incidence of impulse control disorders (ICDs) in Parkinson’s disease is as high as 20%. Dopamine agonists can induce alterations in those frontostriatal networks that manage reward and mediate impulse monitoring and control. Indeed, tonic stimulation of dopamine receptors may damage inhibitory control mechanisms and reward processing, while promoting compulsive repetition of behavior. The neurocognitive approach considers two measurable executive-functions from which ICDs can be detected: 1) response-inhibition, which neural substrate is located in the inferior portion of the prefrontal cortex; 2) integration of reward/punishment contingencies in individual choices, which neural substrate is located in the orbital-prefrontal cortex.

Case description

A 51-year-old man with a 12-year story of Parkinson’s disease, presenting motor fluctuations, and stable on 375 mg/day of levodopa was admitted to the hospital for the ascertainment of requirements for DBS surgery (MDS-UPDRS-III OFF=56; Hoehn-Yahr=2). In 2014, the patient developed an impulse-control disorder, including compulsive intake of sugary and high-fat food, and video-games dependence. Grazing behavior and hyper-focus on in-game achievements interfered with the patient’s everyday life. During neuroimaging data acquisition, the subject was asked to perform a response-inhibition ACC-sensitive task in which the subject had to respond to GO stimuli inhibiting the response to infrequent NOGO stimuli.

Results and conclusions

Examination findings included the following: bilateral bradykinesia and tremor of the upper limbs. The remaining neurological examination was negative. The neuropsychiatric assessment revealed significant levels of anxiety. Although the patient exhibited a normal global cognitive profile, reaching normative scores on the screening tests, abnormalities were detected for the performance on conceptualizing and response-inhibition tasks. The MRI showed no alterations in the brain parenchyma signal. The patient showed no response-inhibition abilities as measured by the GO/NOGO task and action-monitoring deficits (error awareness). Moreover, fMRI acquisition revealed absent task-sensitive recruitment of cingulo-frontal regions for the contrast NOGO vs GO.

Take-home message

In our experience, fMRI response-inhibition task may be useful in PD for better characterizing the clinical profile evaluating treatment options. A frontostriatal – cingulofrontal dysfunction may reflect impairment in metacognitive-executive abilities (such as response-inhibition, action monitoring and error awareness). Interestingly, impaired response-inhibition is an example of the motor/behavioral aspect of impulse control. Its assessment is supposed to be particularly useful in the PD post-diagnostic phase, to better identify individuals at risk of developing ICDs with dopaminergic medication. Theoretical models will be more effective if they integrate fMRI and neuropsychological data according to a neurocognitive approach to Parkinson's disease and ICDs.