Disturbed frontal regulation of attention in Parkinson's disease

Abstract

Parkinson's disease is characterized not only by tremor, akinesia and rigidity, but also by frontal cognitive dysfunction, that can be understood as a disturbance in the 'Supervisory Attentional System' (SAS). This concept refers to a system, located in the frontal cortex, that regulates attentional processes under novel, non-routine conditions. The hypothesis that cognitive dysfunction in Parkinson's disease results from a disturbance in the SAS was investigated by recording 'processing negativity' in 33 parkinsonian patients and 17 controls. Processing negativity is an event-related potential that reflects neuronal activity during selective attention. The contribution of the frontal cortex to selective attention can be studied directly using processing negativity. Parkinsonian patients were also scored for clinical symptoms and subjected to a neuropsychological test battery. Processing negativity was clearly disturbed in the parkinsonian patients. Moreover, parkinsonian patients with the lowest scores on 'frontal' neuropsychological tests such as Stroop, Trail Making and Word Fluency, also had the lowest processing negativity. Our results support the hypothesis that cognitive dysfunction in Parkinson's disease might be understood as a disturbance in the frontal regulation of attentional processes. Degeneration of the dopaminergic mesocortical innervation of the frontal cortex in Parkinson's disease is a possible neurochemical substrate of these frontal attentional disturbances.

Increased dopamine turnover in the prefrontal cortex impairs spatial working memory performance in rats and monkeys.

“…The cognitive changes of Parkinson disease, as well as the hallmark motor impairments, have been linked to dopaminedepleted circuits (37,40,41). However, in L-dopa-treated Parkinsonian patients, apomorphine can induce cognitive deficits (42).…”

6-Hydroxydopamine lesion of the rat prefrontal cortex impairs motor initiation but not motor execution

“…An involvement of prefrontal DA may be also relevant for increased RT measured in patients with Parkinson's disease (Evarts et al 1981). In advanced stages of Parkinson's disease there is not only an impaired DA innervation of the CP but, additionally, a reduced DAergic and NAergic innervation of the cerebral cortex, which may play a role in motor (Scatton et al 1983) and attentional processes (Stam et al 1993). …”

Mismatch Negativity in Aging and in Alzheimer’s and Parkinson’s Diseases

“…In three of these studies [Stam et al, 1993;Vieregge et al, 1994;Karayanidis et al, 1995], the main interest was attention and its effects on ERPs, and thus a dichotic paradigm was employed. However, this paradigm yields also information about the processing of ignored deviant sounds.…”