The neuromodulatory properties of gonadal steroid hormones with regard to individual differences in cognition and brain organisation.

Abstract

Sex hormones exert powerful modulatory effects throughout the nervous system and influence various aspects of behaviour. For example, estrogen and progesterone have been shown to influence sex-sensitive cognitive abilities, such as verbal and visuo-spatial abilities (Hampson, 1990a, 1990b). More recently it has been suggested that estradiol can influence executive functioning abilities, such as cognitive control, working memory and selective attention (Colzato et al., 2012; Hampson, 1990a, 1990b; Hampson & Morley, 2013; Hjelmervik et al., 2012; Rosenberg & Park, 2002). Sex hormones have also been shown to affect functional brain organisation, in particular, cerebral lateralisation. Cerebral lateralisation is a fundamental principle of functional brain organisation, referring to the asymmetrical representation of a specific cognitive process in a particular cerebral hemisphere. For example, the left hemisphere is typically dominant for language, while the right hemisphere is dominant for visuo-spatial processes in the healthy brain (Broca, 1861; Hellige, 1993; Kimura, 1967). While men typically demonstrate pronounced, stable patterns of lateralisation, women are assumed to be less lateralised and demonstrate a higher level of intra- and inter-individual variation in the degree of lateralisation (e.g., Bibawi et al, 1995; Cowell et al., 2011; Hampson, 1990a, 1990b; Hausmann et al., 2002; Hausmann & Güntürkün, 2000; Hjelmervik et al., 2012; Wadnerkar et al., 2008; Weis et al., 2008).
The present thesis focuses on the influence of estrogen (particularly estradiol) and progesterone on cerebral lateralisation, functional connectivity, and cognition in naturally cycling women. Young, naturally cycling women, free of hormonal contraceptives, were tested during specific phases of their menstrual cycles across a series of behavioural studies and a resting state functional magnetic resonance imaging study. Hormone levels (estradiol and progesterone) were directly measured in each study.
The results showed that while both cerebral lateralisation and executive functioning could be modulated by sex hormones, such effects may be smaller and more specific than previously suggested. Firstly, while estradiol (and progesterone) influenced language lateralisation, this effect was dependent on the degree of asymmetry produced by the task used. Specifically, a task that yields a large degree of asymmetry (presumably due to strong bottom-up effects) is likely to mask any sex hormonal effect on other processes underpinning lateralisation, such as interhemispheric inhibition. Secondly, and similarly, the effects of estradiol on executive function and cognitive control were smaller and more specific than previously demonstrated. As such, it was argued that estradiol effects on cognition are likely dependent upon individual differences in neurophysiology, such as those that underpin different levels of schizotypy. Finally, the rs-fMRI findings demonstrate that functional connectivity in the DMN fluctuates according to different phases of the menstrual cycle, while connectivity in the auditory network is stable. Taken together, the findings presented here highlight the extensive effects of sex hormones on the brain, and on behaviours beyond those related to sexual reproduction. Furthermore, they suggest that sex hormonal effects are more complex than previously hypothesised, underpinned by their capacity to interact with task demands, other hormones, and individual differences in neurophysiology.