Fronto-striatal changes along the menstrual cycle during working memory: Effect of sex hormones on activation and connectivity patterns

Frontal and striatal areas are the neuroanatomical basis for working memory (WM), as well as targets for sex steroids. However, up to date little is known regarding menstrual cycle (MC) effects on brain activation and connectivity patterns during verbal WM. To the best of our knowledge, this is the first longitudinal dataset to study dorsolateral prefrontal cortex, putamen and caudate activation and connectivity patterns during a verbal WM task along the natural MC. Thirty-nine naturally cycling healthy women were scanned three times locked to their MC (menses, pre-ovulatory and luteal phase). They performed an N-back task with two trial types, targets and lures, assessing (i) updating and (ii) inhibitory process respectively. Distinct patterns of fronto-striatal activation and connectivity changes were observed for each process. (i) For targets, we observed decreased connectivity between left striatum- and inferior frontal and parietal areas, the circuit underlying phonological WM, in response to elevated progesterone during the luteal phase. Simultaneously, we observed an alleviation of inhibition from fronto-striatal areas on areas related to higher cognitive effort and the salience network. (ii) For lures, negative inter-hemispheric connectivity between fronto-parietal areas during the pre-ovulatory phase, as well as increased connectivity between bilateral dorsolateral prefrontal cortex and posteromedial structures during the luteal phase. Overall, we corroborated a hormone mediated inter-hemispheric decoupling, enhanced frontal activity and disinhibition of the salience brain network and striatum during the luteal phase. In summary, we interpret these results in relation to a differential top-down regulation in higher hormone levels phases and hyperactive bottom-up network during the luteal phase, which could explain the vulnerability of this phase to MC associated disorders.