Functional and structural MRI studies of cognitive change in Parkinson's disease.

摘要

The main goal of this thesis was to increase our understanding of the relationship between the pathological and cognitive changes that occur in Parkinson's disease (PD). This goal was accomplished by combining structural and functional magnetic resonance imaging (MRI) and neuropsychological measurements. Three experiments were completed. In the first two experiments, functional MRI was used to examine the role of the frontal lobe-basal ganglia circuits during semantic event sequencing in young healthy adults, and the functional integrity of these circuits was examined in patients with PD. The third study examined the relationship between brain atrophy and cognitive deficits in PD using structural MRI and neuropsychological measurements.; Experiment #1 examined the role of frontal lobe-basal ganglia circuits during a semantic event sequencing task in healthy, young adults. The results of this experiment indicate that the dorsolateral prefrontal cortex and globus pallidus internal part, specifically in the left hemisphere, are critical for semantic event sequencing.; Experiment #2 assessed the functional integrity of frontal lobe-basal ganglia circuits in nondemented and medicated PD patients using the semantic event sequencing task developed in Experiment #1. The findings of this experiment demonstrate that the functional integrity of the left frontostriatal circuits is compromised in patients with PD, and that the right frontostriatal circuits show compensatory hyperactivation in the PD group compared to matched controls.; Experiment #3 examined the relationship between structural and cognitive changes in nondemented, early-stage PD patients. The structural results demonstrate focal atrophy in the putamen, and in frontal, parietal, and occipital lobes, and the correlation with the neuropsychological measurements indicate that these changes may partly explain the higher depression-anxiety scores and psychomotor slowing in PD.; In conclusion, these experiments implicate a specific role for frontal lobe-basal ganglia circuits in semantic event sequencing, and demonstrate compromised functional integrity within these circuits in patients with PD. These results are consistent with previous studies that have documented deficits in the temporal organization of behavior in patients with PD. Furthermore, the results demonstrate that PD patients have focal brain atrophy even at relatively early stages of the disease course that may be related to their impairment in cognition and emotion.