[Abstract Title]. - Society for Neuroscience

Disclosures: M. Lin, None; R. Sundararajan, None; P.M. Greenwood, None; R.
Parasuraman, None; K.J. Fryxell, None.
Poster
288. Working Memory: Disorders, Genes and Connectivity
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 288.8/RR15
Topic: F.01.f. Working memory
Title: Brain-derived neurotrophic factor val 66 met polymorphism differentially affects regional
cerebral blood flow during working memory and rest
Authors: *S.-M. WEI, A. PADMANABHAN, K. V. ROE, P. D. KOHN, B. S. KOLACHANA,
D. R. WEINBERGER, K. F. BERMAN;
NIH, Bethesda, MD
Abstract: The Val 66 Met single nucleotide polymorphism (SNP) in the human brain-derived
neurotrophic factor (BDNF) gene influences hippocampal function, with the met allele being
associated with abnormal hippocampal recruitment during episodic and working memory 1,2 . To
further investigate the effects of this BDNF SNP on hippocampal and cortical function, we used
H2 15 O positron emission tomography to assess regional cerebral blood flow (rCBF) as a function
of BDNF genotype during rest as well as during a working memory task and a matched
sensorimotor control.
Seventy-one healthy right-handed Caucasians (44 val/val, 27 val/met, 5 met/met) performed a 0-
and 2-back working memory task (7 scans of each task, 10 mCi oxygen-15 water/scan). Sixtynine
of these participants (49 val/val , 20 val/met) also underwent eyes-closed resting PET scans
(two scans each). Genotype groups were matched for age, sex, and performance. For the working
memory paradigm, 2-back vs. 0-back contrast maps were generated for each participant and
entered into a second-level random effects analysis to compare val homozygotes to met carriers.
Additionally, rCBF values extracted from a sphere centered on the between-groups difference in
the right hippocampus were entered into a whole-brain cross-correlation analysis to assess
hippocampal connectivity. For the resting rCBF data, we used an a priori anatomical mask
(bilateral hippocampus and parahippocampal cortices) to perform a small volume correction at
p=0.01 to assess group differences.
During rest, BDNF met carriers showed increased rCBF in bilateral hippocampal and
parahippocampal regions compared to val homozygotes (p