Metabolic brain networks associated with cognitive function in Parkinson's disease

Abstract

The motor manifestations of Parkinson's disease (PD) have been linked to an abnormal spatial covariance pattern involving basal ganglia thalamocortical pathways. By contrast, little is known about the functional networks that underlie cognitive dysfunction in this disorder. To identify such patterns, we studied 15 non-demented PD patients using FDG PET and a voxel-based network modeling approach. We detected a significant covariance pattern that correlated (p< 0.01) with performance on tests of memory and executive functioning. This PD-related cognitive pattern (PDCP) was characterized by metabolic reductions in frontal and parietal association areas and relative increases in the cerebellar vermis and dentate nuclei. To validate this pattern, we analyzed data from 32 subsequent PD patients of similar age, disease duration and severity. Prospective measurements of PDCP activity predicted memory performance (p<0.005), visuospatial function (p<0.01), and perceptual motor speed (p<0.005) in this validation sample. PDCP scores additionally exhibited an excellent degree of test-retest reliability (intraclass correlation coefficient, ICC=0.89) in patients undergoing repeat FDG PET at an 8-week interval. Unlike the PD-related motor pattern, PDCP expression was not significantly altered by antiparkinsonian treatment with either intravenous levodopa or deep brain stimulation (DBS). These findings substantiate the PDCP as a reproducible imaging marker of cognitive function in PD. Because PDCP expression is not altered by routine antiparkinsonian treatment, this measure of network activity may prove useful in clinical trials targeting the progression of non-motor manifestations of this disorder.

Prefrontal D1 dopamine signaling is required for temporal control

“…One such disease, Parkinson disease, involves cognitive dysfunction (37) that can manifest as a dysexecutive syndrome (38) with impaired temporal control (9). Although temporal processing and executive function in Parkinson disease can be heterogeneous (37,39), impairment in these processes in Parkinson disease is likely related to dysfunctional mesocortical networks (12,18,40). The present study provides data demonstrating that prefrontal dopamine is crucial to timing, and that stimulation of D1 systems in prefrontal cortex can facilitate temporal control.…”

“…A brain region that organizes goal-directed behavior is the medial prefrontal cortex (10,11). In metabolic imaging studies, hypoactivity in this area is correlated with impaired executive function in Parkinson disease (12). Medial prefrontal regions are activated during human brain imaging of fixed-interval timing tasks (13).…”

Abnormal Metabolic Network Activity in Parkinson'S Disease: Test—Retest Reproducibility

“…We have also noted that network expression increases linearly with disease progression (Huang et al, , 2006. However, such findings can be difficult to interpret in the absence of information concerning the reliability of these measurements within and between imaging sessions.…”

Assessment of functional development in normal infant brain using arterial spin labeled perfusion MRI

“…This approach is useful for correlating regional variations in brain function with variations in task performance across a cohort of patients with performance deficits, or for measuring regional brain function with behavioral changes over time. Such an approach carried out by metabolic mapping using positron emission tomography (PET) scanning with fluorodeoxyglucose (FDG) has been used to identify patterns of changing brain function associated with development (Chugani et al, 1987) and cognitive disorders such as Alzheimer's disease (Hoffman et al, 1989, Kadir et al, 2006) and Parkinson's disease (Huang et al, 2007).…”