title: Abnormal network topographies and changes in global activity: absence of a causal relationship.
abstract: Changes in regional brain activity can be observed following global normalization procedures to reduce variability in the data. In particular, spurious regional differences may appear when scans from patients with low global activity are compared to those from healthy subjects. It has thus been suggested that the consistent increases in subcortical activity that characterize the abnormal Parkinson's disease-related metabolic covariance pattern (PDRP) are artifacts of global normalization, and that similar topographies can be identified in scans from healthy subjects with varying global activity. To address this issue, we examined the effects of experimental reductions in global metabolic activity on PDRP expression. Ten healthy subjects underwent ¹⁸F-fluorodeoxyglucose PET in wakefulness and following sleep induction. In all subjects, the global metabolic rate (GMR) declined with sleep (mean -34%, range: -17 to -56%), exceeding the test-retest differences of the measure (p<0.001). By contrast, sleep-wake differences in PDRP expression did not differ from test-retest differences, and did not correlate (R²=0.04) with concurrent declines in global metabolic activity. Indeed, despite significant GMR reductions in sleep, PDRP values remained within the normal range. Likewise, voxel weights on the principal component patterns resulting from combined analysis of the sleep and wake scans did not correlate (R²<0.07) with the corresponding regional loadings on the PDRP topography. In aggregate, the data demonstrate that abnormal PDRP expression is not induced by reductions in global activity. Moreover, significant declines in GMR are not associated with the appearance of PDRP-like spatial topographies.
authors.affiliation: Center for Neurosciences, The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY 11030, USA. dhawan@nshs.edu
authors.forename: Vijay
authors.initials: V
authors.lastname: Dhawan
authors.forename: Chris C
authors.initials: CC
authors.lastname: Tang
authors.forename: Yilong
authors.initials: Y
authors.lastname: Ma
authors.forename: Phoebe
authors.initials: P
authors.lastname: Spetsieris
authors.forename: David
authors.initials: D
authors.lastname: Eidelberg
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology*; D001923:Brain Chemistry / Q000502:physiology; D015984:Causality; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D003627:Data Interpretation, Statistical; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D049268:Positron-Emission Tomography; D025341:Principal Component Analysis; D019275:Radiopharmaceuticals; D012890:Sleep / Q000502:physiology; D013788:Thalamus / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18