Executive processes in Parkinson's disease: FDG‐PET and network analysis

Abstract

It is assumed widely that the clinical expression of Parkinson's Disease (PD), both motor and cognitive, is subtended by topographically distributed brain networks. However, little is known about the functional neuroanatomy of executive dysfunction in PD. Our objective was to validate further in a PD group the use of network analysis to assess the relationship between executive processes and pathological disorganization of frontostriatal networks. We studied 15 patients with idiopathic PD, and 7 age-matched normal controls, using resting [(18)F]fluorodeoxyglucose (FDG) and high-resolution positron emission tomography (PET). We carried out network analysis on regional metabolic data to identify specific covariation patterns associated with motor and executive dysfunction. We detected two independent patterns relating respectively to the two clinical abnormalities. The first pattern (principal component 1) was topographically similar to that described previously in other PD populations. Subject scores for this pattern discriminated patients from controls and correlated significantly with bradykinesia ratings (P = 0.013, r = 0.655) in PD patients. The second pattern (principal component 2) was characterized by relative ventromedial frontal, hippocampal, and striatal hypometabolism, associated with mediodorsal thalamic hypermetabolism. In the PD group, scores from this pattern correlated with scores on the conditional associative learning (CAL; P = 0.01, r = 0.690) and the Brown Peterson paradigm (BPP; P = 0.017, r = -0.651) tests, respectively assessing strategy and planning, and working memory. According to these findings, the networks subserving bradykinesia and executive dysfunction in PD seems to be topographically distinct and to involve different aspects of subcortico-cortical processing.

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

“…However, it is important to note that although treatment-mediated changes in PDRP expression correlate significantly with improvement in UPDRS ratings, the metabolic and clinical disease descriptors are not interchangeable. Indeed, intersubject differences in these measures generally have less than 50% of their variability in common, as observed in correlations between PDRP scores and motor UPDRS ratings obtained at baseline or during therapy (e.g., Feigin et al, 2002;Lozza et al, 2004;Trošt et al, 2006). Thus, it is likely that the objective imaging-based network measure may provide unique information about disease severity or the Test-retest reliability of Parkinson's disease-related brain network Y Ma et al treatment response that is not captured by the simpler and more accessible clinical rating scales.…”

“…We have found that this disease is associated with a specific spatial covariance pattern involving metabolic abnormalities in basal ganglia thalamocortical functional/anatomic pathways (Eidelberg et al, 1994(Eidelberg et al, , 1997. Indeed, this PD-related covariance pattern (PDRP) has been detected in multiple independent patient populations scanned in the resting condition (Moeller et al, 1999;Feigin et al, 2002;Lozza et al, 2004;Asanuma et al, 2005).…”

Striatal dopamine release during performance of executive functions: A [11C] raclopride PET study

“…Some neuroimaging studies have proposed that changes in striatal dopamine levels can modulate certain cognitive processes and that level of cognitive impairment may be dependent on the level of dopamine depletion (Cropley et al, 2006). Consistent with this hypothesis, positron emission tomography (PET) studies performed both in healthy subjects (Mehta et al, 2005), following tyrosine and phenylalanine-induced depletion, and patients with Parkinson's disease (PD) (Marie et al, 1999;Lozza et al, 2004) have shown significant correlation between executive task performances and striatal dopamine denervation.…”

Neuroimaging and therapeutics in movement disorders

“…This characteristic pattern (FIG. 1A) 1) has been validated in multiple populations of unmedicated PD patients 4,36,43 ; 2) can be detected early in the disease course 34 ; and 3) correlates consistently with disease severity and duration. 3,44 We also found that PDRP activity correlates with nigrostriatal dopamine deficiency as determined by [ 18 F]-fluorodopa PET 34,45 and with internal pallidal (GPi) single unit activity recorded during surgery.…”