Spectral dynamic causal modelling in healthy women reveals brain connectivity changes along the menstrual cycle

Abstract

Longitudinal menstrual cycle studies allow to investigate the effects of ovarian hormones on brain organization. Here, we use spectral dynamic causal modelling (spDCM) in a triple network model to assess effective connectivity changes along the menstrual cycle within and between the default mode, salience and executive control networks (DMN, SN, and ECN). Sixty healthy young women were scanned three times along their menstrual cycle, during early follicular, pre-ovulatory and mid-luteal phase. Related to estradiol, right before ovulation the left insula recruits the ECN, while the right middle frontal gyrus decreases its connectivity to the precuneus and the DMN decouples into anterior/posterior parts. Related to progesterone during the mid-luteal phase, the insulae (SN) engage to each other, while decreasing their connectivity to parietal ECN, which in turn engages the posterior DMN. When including the most confident connections in a leave-one out cross-validation, we find an above-chance prediction of the left-out subjects’ cycle phase. These findings corroborate the plasticity of the female brain in response to acute hormone fluctuations and may help to further understand the neuroendocrine interactions underlying cognitive changes along the menstrual cycle.

Triple network model of brain connectivity changes related to adverse mood effects in an oral contraceptive placebo-controlled trial

“…Although it is out of the scope of this study, connectivity changes experienced by the placebo group along their menstrual cycle in this study did not completely match changes in healthy naturally cycling women reported in our previous work (52). Although the main reason for these discrepancies may be differences in the time window of each appointment, individual variability in functional responsivity to sex hormones could have also contributed (53).…”

“…Therefore, we find it likely that the constant enhanced synthetic progestins effects, alongside the absence of endogenous hormonal cyclicity and estradiol-progesterone interaction may be of high relevance for the mood side effects and related changes in connectivity here described. Although it is out of the scope of this study, connectivity changes experienced by the placebo group along their menstrual cycle in this study did not completely match changes in healthy naturally cycling women reported in our previous work (52). Although the main reason for these discrepancies may be differences in the time window of each appointment, individual variability in functional responsivity to sex hormones could have also contributed (53).…”

Spindle-Shaped Neurons in the Human Posteromedial (Precuneus) Cortex

“…Among the multiple cellular components with an intrinsic connectivity and functional networks in the human cerebral cortex (see further discussion in van den Heuvel et al, 2015 ), some large-scale circuits have been studied for their roles in resting state, attention and task-related activity or cognitive functions ( Ng et al, 2016 ; Deming and Koenigs, 2020 ; Forlim et al, 2020 ; Kolb and Whishaw, 2021 ). High signal coherence within these networks makes the sub-components functionally coupled along varied timeframes ( Ng et al, 2016 and references therein), such as in the DMN, which comprises the PC ( Cavanna and Trimble, 2006 ) and the posterior cingulate cortex, the medial prefrontal cortex, and the bilateral intraparietal cortex/angular gyrus; in the “salience network” (SN), including the bilateral anterior insula and the dorsal ACC; and, in the “executive control network” (ECN) including the “frontoparietal network” (FPN) composed of bilateral middle frontal gyri and supramarginal gyri/inferior parietal lobe ( Hidalgo-Lopez et al, 2021 and references therein), the intraparietal sulcus, and dorsal prefrontal cortex ( Ptak, 2012 ; Deming and Koenigs, 2020 ). The PC was also included in the ECN/frontoparietal control system for moment-to-moment tasks ( Kolb and Whishaw, 2021 ).…”

Unraveling Brain Microcircuits, Dendritic Spines, and Synaptic Processing Using Multiple Complementary Approaches

“…From this perspective, dendritic spines are sexually dimorphic and/or affected by gonadal steroids (Woolley and McEwen, 1993 ; Rasia-Filho et al, 2012 ; Luine and Frankfurt, 2020 ), sexual experience and motherhood (Rasia-Filho et al, 2004 ; Zancan et al, 2018 ). These phenomena are relevant to sexual differentiation in healthy brain connectivity and as a biological variable in neuropsychiatric research (Joel and McCarthy, 2017 ; Rubinow and Schmidt, 2019 ; Arnold, 2020 ; Hidalgo-Lopez et al, 2021 ).…”