Response inhibition in Parkinson’s disease: a meta-analysis of dopaminergic medication and disease duration effects

Abstract

Parkinson’s disease is a neurodegenerative disorder involving the basal ganglia that results in a host of motor and cognitive deficits. Dopamine-replacement therapy ameliorates some of the hallmark motor symptoms of Parkinson’s disease, but whether these medications improve deficits in response inhibition, a critical executive function for behavioral control, has been questioned. Several studies of Parkinson’s disease patients “on” and “off” (12-h withdrawal) dopaminergic medications suggested that dopamine-replacement therapy did not provide significant response inhibition benefits. However, these studies tended to include patients with moderate-to-advanced Parkinson’s disease, when the efficacy of dopaminergic drugs is reduced compared to early-stage Parkinson’s disease. In contrast, a few recent studies in early-stage Parkinson’s disease report that dopaminergic drugs do improve response inhibition deficits. Based on these findings, we hypothesized that Parkinson’s disease duration interacts with medication status to produce changes in cognitive function. To investigate this issue, we conducted a meta-analysis of studies comparing patients with Parkinson’s disease and healthy controls on tests of response inhibition (50 comparisons from 42 studies). The findings supported the hypothesis; medication benefited response inhibition in patients with shorter disease duration, whereas “off” medication, moderate deficits were present that were relatively unaffected by disease duration. These findings support the role of dopamine in response inhibition and suggest the need to consider disease duration in research of the efficacy of dopamine-replacement therapy on cognitive function in Parkinson’s disease.

Corrigendum to “On the integrity of functional brain networks in schizophrenia, Parkinson's disease, and advanced age: Evidence from connectivity‐based single‐subject classification.”

“…Also, we found a decrease in the performance of the network subserving cognitive action control for SCZ classification (Acc. Nevertheless, this is in line with dysfunctional emotion regulation as a well-established characteristic of SCZ [Khoury and Lecomte, 2012;van der Meer et al, 2014] and is well mirrored in the degree of SCZ-related information that is contained in the cognitive emotion regulation network. While this network still showed a classification performance for SCZ vs. HC that was significantly above chance, the decrease in accuracy combined with an increase in PD-classification accuracy now renders this network similarly discriminative for both disorders, which actually matches the clinical deficits in cognitive action control in patients with either PD and SCZ [Lesh et al, 2011;Manza et al, 2017].…”

“…Moreover, the cognitive emotion regulation network now comes out as more specific for SCZ classification, which is, however, not attributable to a significant increase in SCZ classification accuracy, but rather to a decrease in classification accuracy for PD. Nevertheless, this is in line with dysfunctional emotion regulation as a well-established characteristic of SCZ [Khoury and Lecomte, 2012;van der Meer et al, 2014] and is well mirrored in the degree of SCZ-related information that is contained in the cognitive emotion regulation network.…”

“…= 64%; AUC = 0.67). While this network still showed a classification performance for SCZ vs. HC that was significantly above chance, the decrease in accuracy combined with an increase in PD-classification accuracy now renders this network similarly discriminative for both disorders, which actually matches the clinical deficits in cognitive action control in patients with either PD and SCZ [Lesh et al, 2011;Manza et al, 2017]. Interestingly, the reanalysis now shows the highest accuracy with respect to SCZ vs. HC classification for the reward processing network.…”

Action Control Deficits in Patients With Essential Tremor

“…Parkinson’s Disease, Tourette’s and ADHD; Manza et al, 2017; Alderson, Rapport & Kofler, 2007; Wylie et al, 2016). The underlying neuropathology in ET is less clearly understood; it includes degradation of cerebellar gray and white matter along with abnormal signaling in cerebellar-thalamic-cortical circuitries (Cerasa & Quattrone, 2016).…”

Functional connectivity alterations in Parkinson’s disease during the stop-signal task

“…Although the sample from Ye et al and ours are quite comparable with respect to motor symptom severity and disease stage, patients in our sample had a much shorter disease duration (2.8 versus 10.8 years), were slightly younger and had a lower LEDD. As dopaminergic medication loses its potency with progression of the disease [21] and loses some of its beneficial effect on behavioral performance of response inhibition tasks [22], it is possible that dopaminergic medication normalized task-related activity in our sample but not that of Ye et al 2014.…”