Physiological variation in estradiol and brain function: A functional magnetic resonance imaging study of verbal memory across the follicular phase of the menstrual cycle Michael C. Craig a,, Paul C. Fletcher b, Eileen M. Daly a, Janice Rymer c, Mick Brammer d, Vincent Giampietro d, Declan G.M. Murphy a A summary by Danica Marining

Background: Estrogen Therapy (ET) modulates the metabolism and function of brain regions sub-serving memory (e.g. hippocampal, frontal, parietal,and temporal regions) (Maki and Resnick, 2000; Resnick et al.,1998; Shaywitz et al., 1999). Acute suppression of ovarian function is associated with decreased activation in the left inferior frontal gyrus (LIFG) (Craig et al., 2007). There is an association between LIFG activation during encoding and subsequent memory success (Bucckner et al., 2000). It appears estrogen may affect verbal memory formation through modulation of the LIFG. BUT, what about the NORMAL variation in estrogen levels during the menstrual cycle and associated brain function during a memory task?

General Research Question: Is physiological variation in plasma estradiol concentration associated with differences in activity of the LIFG during successful verbal encoding? Hypothesis: Higher plasma concentrations of estradiol will be associated with increased brain activity at the LIFG and improved recall performance.

Methods: Subjects We included 16 right-handed young (26–45 years) pre-menopausal women with regular menstrual cycles. Procedure (in fMRI) Encoding task- identify whether words are non-living or living by moving a joystick (100 words total=old words) Recognition task-paticipant decides whether they have seen the word before (old word) or if it is a new word (new word) by moving a joystick. (200 words total, 100 old words, 100 new words)

Results: Estrogen on Recall Higher estradiol levels do not significantly increase recall performance.

Results: Estrogen and Brain Activation Old words that were subsequently recognized were associated with increased activation in the LIFG (left figure) Average fMRI responses (SSQ) at the LIFG were positively correlated with estradiol levels (right figure)

Discussion: As expected the LIFG had increased activation with increased estradiol. But high estradiol didn’t significantly increase verbal recall performance. Why?

Discussion: Papers Thoughts Numerous neurofunctional systems are at work, not a one-to-one relationship between brain and behaviour. Magnitude of this relationship is relatively small. Study was underpowered to detect a significant behavioural effect.

Discussion: My Thoughts Results were confuzing Only looked at folicular phase of the menstrual cycle, when estradiol levels are rising, but what about when estradiol levels are at their highest? Poor method to measuring recognition accuracy. Tasks were confusing (ex. of non-living item was a mountain). No control, only compared between the subjects, who all had slightly different estradiol levels. Not enough activation of LIFG to affect verbal memory. Different types of estrogens during menopause. Past studies that found results didn’t use normal estrogen levels.

Limitations on the Study: fMRI is loud, difficult to remember/recall because distracting. Poorly written paper, very confusing. Presentation of results were not explained well. Discussion poorly explained results. Overall I find studies on estrogens interesting. Perhaps future research should investigate different types of memory.

Questions ?