Dopamine-Related Reduction of Semantic Spreading Activation in Patients With Parkinson’s Disease

Abstract

Impaired performance in verbal fluency (VF) tasks is a frequent observation in Parkinson’s disease (PD). As to the nature of the underlying cognitive deficit, it is commonly attributed to a frontal-type dysexecutive syndrome due to nigrostriatal dopamine depletion. Whereas dopaminergic medication typically improves VF performance in PD, e.g., by ameliorating impaired lexical switching, its effect on semantic network activation is unclear. Data from priming studies suggest that dopamine causes a faster decay of semantic activation spread. The aim of the current study was to examine the impact of dopaminergic medication on the dynamic change of word frequency during VF performance as a measure of semantic spreading activation. To this end, we performed a median split analysis of word frequency during phonemic and semantic VF task performance in a PD group tested while receiving dopaminergic medication (ON) as well as after drug withdrawal (i.e., OFF), and in a sample of age-matched healthy volunteers (both groups n = 26). Dopaminergic medication in the PD group significantly affected phonemic VF with improved word production as well as increased error-rates. The expected decrease of word frequency during VF task performance was significantly smaller in the PD group ON medication than in healthy volunteers across semantic and phonemic VF. No significant group-difference emerged between controls and the PD group in the OFF condition. The comparison between both treatment conditions within the PD group did not reach statistical significance. The observed pattern of results indicates a faster decay of semantic network activation during lexical access in PD patients on dopaminergic medication. In view of improved word generation, this finding is consistent with a concept of more focused neural activity by an increased signal-to-noise ratio due to dopaminergic neuromodulation. However, the effect of dopaminergic stimulation on VF output suggests a trade-off between these beneficial effects and increased error-rates.

Reward-related regions play a role in natural story comprehension

“…Semantic processing and the reward system have also been linked through the finding of the spread of semantic priming activation, mainly using patients with Parkinson’s disease that display abnormal activation. 40 , 41 However, it has yet to be exemplified that the reward system is activated during normal comprehension of a natural story. The ability to consistently differentiate test participants at an above-chance level between conditions based on activity in the reward areas suggests that the processing of a natural story is to the very least supported by these regions.…”

DRD3 Predicts Cognitive Impairment and Anxiety in Parkinson’s Disease: Susceptibility and Protective Effects

“…Ropinirole has been shown to selectively reduce proactive inhibition (i.e., slowing of motor activity in anticipation of stopping), but not reactive inhibition (i.e., response to sudden sensory cues and serves to abruptly stop motor activity) in healthy adults [36]. A reduction in proactive inhibition could potentially favor semantic fluency in PD patients [37]. There is evidence that pramipexole, another agonist with D3 affinity used in our cohort, may have negative effects on multiple cognitive functions, including semantic fluency [33,38].…”