TY - JOUR
T1 - Evaluation of prefrontal-hippocampal effective connectivity following 24 hours of estrogen infusion
T2 - An FDG-PET study
AU - Ottowitz, William E.
AU - Siedlecki, Karen L.
AU - Lindquist, Martin A.
AU - Dougherty, Darin D.
AU - Fischman, Alan J.
AU - Hall, Janet E.
N1 - Funding Information:
Funding for this study was supplied by NIH and NIMH. Neither of these had any role in the study design, in the collection, analysis or interpretation of data, nor submission of the manuscript.
Funding Information:
The authors gratefully acknowledge support from NIH and NIMH for Grants R01 AG13241, K24HD01290, M01 RR01066, and T32MH020004-09. We also thank Steve Weiss for his technical assistance regarding scan acquisition.
PY - 2008/11
Y1 - 2008/11
N2 - Although several functional neuroimaging studies have addressed the relevance of hormones to cerebral function, none have evaluated the effects of hormones on network effective connectivity. Since estrogen enhances synaptic connectivity and has been shown to drive activity across neural systems, and because the hippocampus and prefrontal cortex (PFC) are putative targets for the effects of estrogen, we hypothesized that effective connectivity between these regions would be enhanced by an estrogen challenge. In order to test this hypothesis, FDG-PET scans were collected in eleven postmenopausal women at baseline and 24 h after a graded estrogen infusion. Subtraction analysis (SA) was conducted to identify sites of increased cerebral glucose uptake (CMRglc) during estrogen infusion. The lateral PFC and hippocampus were a priori sites for activation; SA identified the right superior frontal gyrus (RSFG; MNI coordinates 18, 60, 28) (SPM2, Wellcome Dept. of Cognitive Neurology, London, UK) as a site of increased CMRglc during estrogen infusion relative to baseline. Omnibus covariate analysis conducted relative to the RSFG identified the right hippocampus (MNI coordinates: 32, -32, -6) and right middle frontal gyrus (RMFG; MNI coordinates: 40, 22, 52) as sites of covariance. Path analysis (Amos 5.0 software) revealed that the path coefficient for the RSFG to RHIP path differed from zero only during E2 infusion (p < 0.05); moreover, the magnitude of the path coefficient for the RHIP to RMFG path showed a significant further increase during the estrogen infusion condition relative to baseline [Δχ2 = 4.05, Δd.f. = 1, p = 0.044]. These findings are consistent with E2 imparting a stimulatory effect on effective connectivity within prefrontal-hippocampal circuitry. This holds mechanistic significance for resting state network interactions and may hold implications for mood and cognition.
AB - Although several functional neuroimaging studies have addressed the relevance of hormones to cerebral function, none have evaluated the effects of hormones on network effective connectivity. Since estrogen enhances synaptic connectivity and has been shown to drive activity across neural systems, and because the hippocampus and prefrontal cortex (PFC) are putative targets for the effects of estrogen, we hypothesized that effective connectivity between these regions would be enhanced by an estrogen challenge. In order to test this hypothesis, FDG-PET scans were collected in eleven postmenopausal women at baseline and 24 h after a graded estrogen infusion. Subtraction analysis (SA) was conducted to identify sites of increased cerebral glucose uptake (CMRglc) during estrogen infusion. The lateral PFC and hippocampus were a priori sites for activation; SA identified the right superior frontal gyrus (RSFG; MNI coordinates 18, 60, 28) (SPM2, Wellcome Dept. of Cognitive Neurology, London, UK) as a site of increased CMRglc during estrogen infusion relative to baseline. Omnibus covariate analysis conducted relative to the RSFG identified the right hippocampus (MNI coordinates: 32, -32, -6) and right middle frontal gyrus (RMFG; MNI coordinates: 40, 22, 52) as sites of covariance. Path analysis (Amos 5.0 software) revealed that the path coefficient for the RSFG to RHIP path differed from zero only during E2 infusion (p < 0.05); moreover, the magnitude of the path coefficient for the RHIP to RMFG path showed a significant further increase during the estrogen infusion condition relative to baseline [Δχ2 = 4.05, Δd.f. = 1, p = 0.044]. These findings are consistent with E2 imparting a stimulatory effect on effective connectivity within prefrontal-hippocampal circuitry. This holds mechanistic significance for resting state network interactions and may hold implications for mood and cognition.
KW - Depression
KW - Effective connectivity
KW - Estradiol
KW - Neural networks
KW - Postmenopausal women
KW - Verbal memory
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U2 - 10.1016/j.psyneuen.2008.09.013
DO - 10.1016/j.psyneuen.2008.09.013
M3 - Article
C2 - 18977091
AN - SCOPUS:56249138633
SN - 0306-4530
VL - 33
SP - 1419
EP - 1425
JO - Psychoneuroendocrinology
JF - Psychoneuroendocrinology
IS - 10
ER -