FDG-PET analysis of amygdalar-cortical network covariance during pre- versus post-menopausal estrogen levels: potential relevance to resting state networks, mood, and cognition

Abstract

Objectives: 1.) Expand the scope of neuroendocrine applications of functional neuroimaging techniques. 2.) Compare the covariance of amygdalar activity with that of the rest of the brain during pre- and post-menopausal levels of estrogen (E2). Based on the distribution of cortical E2 receptors and the neocortical regions where E2 has been shown to preferentially accumulate, we predict that E2 infusion will increase covariance of amygdalar activity with that of the temporal and frontal cortices.

Design: This basic physiology study employed a within-subject design. All participants were post-menopausal women (n =7). Analysis of covariance between whole brain and amygdalar regional cerebral glucose consumption (CMRglc) was conducted in a voxel-wise manner by means of the basic regression option in SPM2 and was applied to FDG-PET scans acquired at baseline and after a 24 hour graded E2 infusion.

Setting: An academic medical center; Massachusetts General Hospital, Boston, Massachusetts.

Results: E2 levels (mean +/- sem) were significantly greater at 24 hours (257.9 pg/mL +/- 29.7) than at 0 hours (28.1 pg/mL +/- 3.4). Right amygdalar CMRglc showed a significant covariance with activity of three different regions of the temporal cortex during E2 infusion, but none at baseline. In addition, right amygdalar CMRglc covaried with that of the right medial and superior frontal gyri only during E2 infusion.

Conclusions: In addition to suggesting changes in amygdalar-cortical network connectivity as a result of short-term E2 exposure, these analyses provide evidence that basic neuroendocrine research may benefit from further use of FDG-PET and other functional neuroimaging modalities for network level analyses.

Figures

Figure 1. Sites of covariance of right amygdalar and temporal lobe CMRglc during estrogen infusion

Left Panel: Transverse structural MRI section of the brain, imaged at the level of the midbrain and temporal lobe showing spherical amygdalar regions of interest (ROIs) shaded in red. To facilitate anatomical placement, ROIs were drawn on each subject’s high resolution MRI scan, which was co-registered to their PET scans; the right sided panels include examples of PET images. Panels on Right: Regions in the temporal lobe showing covariance with the right amygdala included the left middle temporal gyrus at MNI coordinates -52, -32, -2 (top right), and the anterior and posterior aspects of the right superior temporal gyrus at MNI coordinates 58, 8, -4, (middle right), and 68, -34, 8, (bottom right), respectively. These covariances were significant only during estrogen infusion. Both the MRI and PET images are positioned in neurological convention, i.e. the right hemisphere is located on the right side of the image. (CMRglc = regional cerebral glucose consumption).

Figure 2. Sites of covariance of CMRglc between each amygdala and the prefrontal cortex during estrogen infusion

Left Panel: Transverse structural MRI section of the brain, imaged at the level of the midbrain and temporal lobe showing spherical amygdalar regions of interest (ROIs) shaded in red. Right Panel: Prefrontal sites of covariance with the right amygdala included the right superior frontal gyrus (MNI coordinates 8, 48, 48; identified by the yellow crosshairs) and the right ventrolateral prefrontal cortex (VLPFC), (MNI coordinates 54, 28, 0 at 0 hours, and 54, 22, 0 at 24 hours). The dashed blue arrow indicates a significant covariance that was present during both baseline scanning and scanning after 24 hours of estrogen infusion, whereas the solid red arrows indicate a significant covariance that was present only after 24 hours of estrogen infusion. The top red arrow indicates a significant covariance present between the right amygdala and right medial frontal gyrus/superior frontal gyrus (MNI coordinates 8, 48, 48), whereas the bottom red arrow indicates a significant covariance between the left amygdala and right VLPFC (MNI coordinates 54, 22, 0). Both the MRI and PET images are positioned in neurological convention, i.e. the right hemisphere is located on the right side of the image. (CMRglc = regional cerebral glucose consumption).