Studies of Parkinson's disease (PD) suggest that cognitive deficits accompany the classically recognized motor symptoms, and that these cognitive deficits may result from damage to frontal–basal ganglia circuits. PD patients are impaired on ordering events and action components into coherent sequences. In this study, we examined early-stage, nondemented, medicated PD subjects and matched control subjects during a semantic event sequencing task using functional MRI (fMRI). The task required subjects to examine four pictures of meaningful events, determine the correct temporal relationship between each picture, and re-order the pictures into a coherent sequence. There were two main findings. First, we found abnormal activation within the prefrontal cortex (PFC) and the “default” network in the PD group. Distinct areas of the PFC showed both hypoactivation and hyperactivation, whereas the “default” network showed reduced levels of resting activation in PD. Secondly, we observed left caudate hyperactivation in the PD group. The findings are discussed in relationship to how more activation may be compensatory, but does not necessarily mean efficient and correlated brain function.
Parkinson's disease (PD) is an aging-related neurodegenerative disorder characterized by the classical motor symptoms of bradykinesia, rigidity, tremor, postural instability, and gait disturbances. A growing body of neuropsychological and neuroimaging evidence suggests that patients with PD also have diverse cognitive problems affecting spatial, memory, and executive abilities, even at relatively early stages of the disease (Amick et al., 2006, Cronin-Golomb and Amick, 2001 and Dubois and Pillon, 1997). Behavioral research on PD has demonstrated deficits in strategic control, attention shifting, planning, working memory, and perceptuomotor temporal sequencing. Yet, most neuroimaging studies focus on motor symptoms and few on cognitive problems, and so relatively little is known about the brain basis of high-level cognitive dysfunction in PD (Carbon and Marie, 2003). The present functional magnetic resonance imaging (fMRI) study sought to examine the functional integrity of frontal–basal ganglia circuits in early-stage, nondemented, medicated PD participants during a semantic event sequencing task, an executive function that is known to be impaired in PD and is central to many high-level activities of daily living, such as following a recipe to prepare a meal or organizing a daily schedule.
Neuropsychological findings suggest that damage to the fronto-striatal system in PD results in problems with sequencing meaningful events. PD patients have been shown to be impaired on picture arrangement tests in which scrambled picture sets must be re-ordered to tell a story (Beatty and Monson, 1990, Cooper et al., 1991 and Sullivan et al., 1989) and on related tasks entailing ordering and organizing script information that is presented as action sequence components in a scrambled order (Godbout and Doyon, 2000 and Zalla et al., 1998).
We designed a semantic event sequencing task that is an fMRI variant (Tinaz et al., 2006) of the Picture Arrangement subtest of the Wechsler Adult Intelligence Scale-III (WAIS-III) (Wechsler, 1997). Similarly, our picture sequencing task required subjects to examine four pictures of meaningful events, determine the correct temporal relationship, and, finally, re-order the pictures into a coherent sequence (Groth-Marnat, 1999 and Lezak, 1995). In a previous fMRI study using this sequencing task with young healthy subjects, we demonstrated that this task engages a distributed network of occipitotemporal, parietal, frontal and basal ganglia regions (Tinaz et al., 2006). More important, we found that the crucial components of this network for accomplishing semantic event sequencing are the dorsolateral prefrontal cortex (DLPFC) and the globus pallidus internal part (GPi), especially in the left hemisphere.
The goal in the present study was to examine the functional integrity of these frontal–basal ganglia circuits in patients with PD. We predicted that PD patients would show abnormal brain activity relative to a matched control group, specifically in the prefrontal cortex and the basal ganglia.
