P1-242 ALTERED HIPPOCAMPUS FUNCTIONAL CONNECTIVITY IN THE RECOGNITION MEMORY NETWORK CORRECTED FOR GREY MATTER ATROPHY IN MILD COGNITIVE IMPAIRMENT Michael Ewers 1,2 , Arun L. W. Bokde 1,2 , Stefan J. Teipel 2,3 , Sebastian Beil 2 , Christine Born 4 , Maximilian Reiser 4 , Harald Hampel 1,5 , 1 Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience (TCIN), Trinity College, University of Dublin, The Adelaide and Meath Hospital incorporating The National Children’s Hospital (AMiNCH), Dublin, Ireland; 2 Dementia and Neuroimaging Research Section, Alzheimer Memorial Center and Geriatric Psychiatry Branch, Department of Psychiatry, Ludwig- Maximilian University, Munich, Germany; 3 Department of Psychiatry, Neurological Center, University of Rostock, Rostock, Germany; 4 Department of Radiology, Clinical Center Grosshadern, Ludwig- Maximilian University, Munich, Germany; 5 Dementia and Neuroimaging Research Section, Alzheimer Memorial Center and Geriatric Psychiatry Branch, Department of Psychiatry, Ludwig-Maximilian University, Munich, Munich, Germany. Contact e-mail: ewersm@tcd.ie Background: Mild cognitive impairment (MCI) has been associated with increased risk to develop Alzheimer’s disease (AD), with episodic memory impairment being of the earliest symptoms preceding dementia. Hippocam- pus has been shown to be involved in episodic memory and is altered in MCI. Recent studies have shown that functional connectivity 1 of hip- pocampus activity within a larger cortical default network is altered in MCI and AD. Here we investigated to what extent hippocampus functional connectivity as assessed during episodic memory retrieval is altered. Since hippocampus has been found to be reduced in MCI we investigated in addition to what extent grey matter volume changes may influence func- tional connectivity changes of hippocampus. Methods: Functional MRI was acquired during delayed forced-choice word recognition task in healthy controls (HC, n = 10) and MCI (n = 8) subjects. Hippocampus volume was manually outlined on T1 weighted volumetric MRI scans according to an established volumetric protocol and used as mask to extract the average positive hippocampus activity during trials of successful re- trieval. Hippocampus connectivity was assessed voxel-based by regression of hippocampus volume onto brain activity in the rest of the brain voxel- by-voxel controlling for age and, optionally, hippocampus volume differ- ences. Results: Functional hippocampus connectivity during a forced- choice visual verbal recognition memory task was found to be bilaterally dramatically reduced in spatial extent in MCI subjects when compared to HC. HC showed increased hippocampus connectivity within large-scale neuronal network including prefrontal, lateral temporal, posterior parietal, occipital, cerebellar brain areas. Notably, whereas HC showed only posi- tive hippocampus correlations, MCI patients showed only negative hip- pocampus correlations primarily confined to medial and anterior prefrontal cortex. Hippocampus connectivity in MCI within right dorso-lateral pre- frontal cortex and middle anterior cingulate gyrus was no longer different from HC when hippocampus volume was controlled for. Conclusions: The current findings show that hippocampus related network is markedly al- tered in MCI, partially dependent upon hippocampus volume deficits, that may underly episodic memory deficits in MCI. References Bokde AL, Lopez-Bayo P, Meindl T, et al. Functional connec- tivity of the fusiform gyrus during a face-matching task in subjects with MCI. Brain 2006;129:1113-1124. P1-243 QUANTIFYING METABOLIC ASYMMETRY IN ALZHEIMER’S DISEASE USING BOTH MR AND PET IMAGING P. Thomas Fletcher, Angela Y. Wang, Norman L. Foster, Sarang C. Joshi, University of Utah, Salt Lake City, UT, USA. Contact e-mail: fletcher@sci.utah.edu Background: Some of the earliest studies of FDG-PET in Alzheimer’s disease (AD) noticed that patients sometimes had predominant left or right hemisphere hypometabolism. Currently, asymmetry in clinical brain scans is interpreted using only visual inspection. Quantifying metabolic asymmetry is difficult because mirroring values about the midsagittal plane does not neces- sarily align homologous structures in the left and right hemispheres. The objective of this research is to automatically quantify statistically significant areas of metabolic asymmetry in AD, while removing the confounding effects of structural asymmetry. Methods: We constructed an atlas of normative metabolic asymmetry from 10 normal control subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and quantified the metabolic asym- metry of an AD subject compared to the normative atlas. A symmetric structural image for each subject was computed using an unbiased average image from the original MRI and the MRI mirrored about the midsagittal plane. The PET image was mapped onto this structurally symmetric image, and an asymmetry image was computed as the difference of the left minus the right side. Since this is done in structurally symmetric coordinates, metabolism was compared across homologous structures of each hemisphere. Next, we built a structurally symmetric atlas of the 10 control subjects from an unbiased average of their symmetric MR images. The mean and standard deviation of the population’s metabolic asymmetry was computed in the symmetric atlas coordinates. Finally, we registered the asymmetry image from an AD subject to the normal atlas and computed a pixel-by-pixel z-score of metabolic asym- metry. Results: Average normal asymmetry was in the range -0.15 to 0.15 relative to pons, with a maximal standard deviation of 0.35. The asymmetry z-score map of the AD patient shown in the figure showed significant (z  3) asymmetry, which verifies and quantifies the asymmetry found by visual inspection. Conclusions: Structurally symmetric image coordinates are an effective approach to locating and quantifying asymmetry of glucose metab- olism in AD. Acknowledgements: Supported in part by the Center for Alz- heimer’s Care, Imaging and Research and NIH grant AG024904. References: Fletcher, et al., IPMI 2007, pp. 346-358. P1-244 FREQUENCY OF HEMISPHERIC METABOLIC ASYMMETRY IN PROBABLE ALZHEIMER’S DISEASE Norman L. Foster 1 , Angela Y. Wang 1 , James A. Levy 1 , Robert A. Koeppe 2 , William J. Jagust 3 , Kewei Chen 4 , Eric M. Reiman 4 , Michael W. Weiner 5 , 1 University of Utah, Salt Lake City, UT, USA; 2 University of Michigan, Ann Arbor, MI, USA; 3 University of California, Berkeley, Berkeley, CA, USA; 4 Banner Alzheimer’s Institute, Phoenix, AZ, USA; 5 University of California, San Francisco, San Francisco, CA, USA. Contact e-mail: norman.foster@hsc.utah.edu Background: Alzheimer’s disease (AD) causes, on average, a symmetric pattern of glucose hypometabolism. However, some patients have hypome- tabolism predominantly affecting either the left or right hemisphere. These patients may have atypical presentations that could cause them to be system- atically excluded from clinical drug trials. It is unknown whether the left or T286 Poster Presentations P1