Psychiatry Research Neuroimaging 114 (2002) 39–50 0925-4927/01/$ - see front matter  2002 Elsevier Science Ireland Ltd. All rights reserved. PII:S0925-4927 Ž 01 . 00130-5 Changes in brain functional homogeneity in subjects with Alzheimer’s disease Nora D. Volkow *, Wei Zhu , Christoph A. Felder , Klaus Mueller , Tomihisa F. Welsh , a,b, c a d d Gene-Jack Wang , Mony J. de Leon a e,f Medical Department, Bldg. 490, Brookhaven National Laboratory, P.O. Box 5000, Upton, NY 11973-5000, USA a Department of Psychiatry, State University of New York, Stony Brook, NY 11794, USA b Department of Applied Mathematics and Statistics, State University of New York, Stony Brook, NY 11794, USA c Department of Computer Science, State University of New York, Stony Brook, NY 11794, USA d Department of Psychiatry, New York University, New York, NY 10016, USA e Nathan Kline Institute, Orangeburg, NY 10962, USA f Received 9 April 2001; received in revised form 14 November 2001; accepted 28 November 2001 Abstract Imaging studies have reported marked reductions in brain glucose metabolism in Alzheimer’s Disease (AD). However, less is known about disruptions in the patterns of brain metabolic activity. Here we questioned whether AD affects the patterns of homogeneity y heterogeneity in brain metabolism. PET images of 35 AD subjects were compared with those of 35 controls. A template was applied to extract a cortical rim, which was partitioned into 990 contiguous regions. Estimates of metabolic homogeneity were obtained using the coefficient of variation (CV). The CV of the entire cortex was found to be significantly larger in AD, suggesting increased heterogeneity at the whole brain level. In contrast, regional CV was significantly lower in AD in temporal and parietal cortices, which were the regions that along with the precuneus had the largest metabolic decrements, though the precuneus had increased CV. The enhanced heterogeneity for the global cortical pattern most likely reflects variability in the degree of pathology among brain regions as well as neuroanatomical disconnection. The enhanced homogeneity in parietal and temporal cortices is likely to reflect loss of regional differentiation (i.e. macrocolumnar disorganization). The enhanced CV in precuneus, despite its marked reductions in metabolism, suggests that increases in regional homogeneity in parietal and temporal cortices are not a mere reflection of the decrement in metabolism.  2002 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Coefficient of variation (CV); FDG; Discriminant analysis; Heterogeneity; Laterality; Positron emission tomography 1. Introduction Imaging studies of patients with Alzheimer’s Disease (AD) have consistently shown significant * Corresponding author. Tel.: q1-631-344-3335; fax: q1- 631-344-5260. E-mail address: volkow@bnl.gov (N.D. Volkow). reductions in brain glucose metabolism, which are most accentuated in the parietotemporal cortex (Foster et al., 1984; Jagust et al., 1997; Kogure et al., 2000). The decrements in brain glucose metab- olism are believed to reflect in part neuronal loss (Foster et al., 1984; Herholz, 1995). In addition to neuronal loss, histopathological studies in sub-