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Dysfunction of the human memory systems: role of the dopaminergic transmission

Human memory is currently considered to consist of different subsystems subserved by different anatomofunctional networks. However, the biochemical basis of memory disturbances remains unclear. The present review focuses on data from studies in Parkinson's disease in order to define the role played by the dopaminergic system in episodic memory and procedural learning. The pattern of episodic memory disturbances in Parkinson's disease is very specific: Parkinson's disease patients display a preserved ability to encode, store and consolidate new information but have difficulties in retrieving it. This deficit is particularly observed when patients have to self-initiate remembering strategies, as they are unimpaired when retrieval cues are explicitly presented. This probably reflects executive dysfunction, and is related to the disruption of the associative striato-prefrontal circuit. It is observed with verbal as well as visuospatial material. On procedural learning tasks, Parkinson's disease patients display a lower progressive performance enhancement over trials than healthy controls. However, this impairment mainly concerns the initial learning phase and appears to be highly dependent on the motor demands of the task. The role played by dopamine depletion in these deficits remains a subject of debate as some studies suggest the involvement of the dopaminergic system in cognitive function, although other results do not support it. Other neurotransmission systems are probably involved in the pathophysiology of cognitive dysfunction in Parkinson's disease, and currently it is the cholinergic hypothesis that is the most considered.