Sex steroids and connectivity in the human brain: A review of neuroimaging studies
ABSTRACT Our brain operates by the way of interconnected networks. Connections between brain regions have been extensively studied at a functional and structural level, and impaired connectivity has been postulated as an important pathophysiological mechanism underlying several neuropsychiatric disorders. Yet the neurobiological mechanisms contributing to the development of functional and structural brain connections remain to be poorly understood. Interestingly, animal research has convincingly shown that sex steroid hormones (estrogens, progesterone and testosterone) are critically involved in myelination, forming the basis of white matter connectivity in the central nervous system. To get insights, we reviewed studies into the relation between sex steroid hormones, white matter and functional connectivity in the human brain, measured with neuroimaging. Results suggest that sex hormones organize structural connections, and activate the brain areas they connect. These processes could underlie a better integration of structural and functional communication between brain regions with age. Specifically, ovarian hormones (estradiol and progesterone) may enhance both cortico-cortical and subcortico-cortical functional connectivity, whereas androgens (testosterone) may decrease subcortico-cortical functional connectivity but increase functional connectivity between subcortical brain areas. Therefore, when examining healthy brain development and aging or when investigating possible biological mechanisms of 'brain connectivity' diseases, the contribution of sex steroids should not be ignored.
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- "The present sample was mostly female (Table 1). Myelination of the CC is an on-going process until adulthood and is influenced by hormonal status (Peper et al. 2011). However, controls were matched for sex and PDS scores, and these variables were used as covariates in between-group comparisons. "
ABSTRACT: Resilience is the capacity of individuals to resist mental disorders despite exposure to stress. Little is known about its neural underpinnings. The putative variation of white-matter microstructure with resilience in adolescence, a critical period for brain maturation and onset of high-prevalence mental disorders, has not been assessed by diffusion tensor imaging (DTI). Lower fractional anisotropy (FA) though, has been reported in the corpus callosum (CC), the brain's largest white-matter structure, in psychiatric and stress-related conditions. We hypothesized that higher FA in the CC would characterize stress-resilient adolescents. Three groups of adolescents recruited from the community were compared: resilient with low risk of mental disorder despite high exposure to lifetime stress (n = 55), at-risk of mental disorder exposed to the same level of stress (n = 68), and controls (n = 123). Personality was assessed by the NEO-Five Factor Inventory (NEO-FFI). Voxelwise statistics of DTI values in CC were obtained using tract-based spatial statistics. Regional projections were identified by probabilistic tractography. Higher FA values were detected in the anterior CC of resilient compared to both non-resilient and control adolescents. FA values varied according to resilience capacity. Seed regional changes in anterior CC projected onto anterior cingulate and frontal cortex. Neuroticism and three other NEO-FFI factor scores differentiated non-resilient participants from the other two groups. High FA was detected in resilient adolescents in an anterior CC region projecting to frontal areas subserving cognitive resources. Psychiatric risk was associated with personality characteristics. Resilience in adolescence may be related to white-matter microstructure.Psychological Medicine 03/2015; 45(11):1-10. DOI:10.1017/S0033291715000239 · 5.43 Impact Factor
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- "Finally, there is evidence that hormonal changes that occur during puberty can affect both structural and functional connectivity (Peper et al. 2011). Hormonal changes, in particular, may help to explain the timing of the changes that we observed here. "
ABSTRACT: The goal of this fMRI study was to examine how well developmental improvements in reasoning ability can be explained by changes in functional connectivity between specific nodes in prefrontal and parietal cortices. To this end, we examined connectivity within the lateral fronto-parietal network (LFPN) and its relation to reasoning ability in 132 children and adolescents aged 6-18 years, 56 of whom were scanned twice over the course of 1.5 years. Developmental changes in strength of connections within the LFPN were most prominent in late childhood and early adolescence. Reasoning ability was related to functional connectivity between left rostrolateral prefrontal cortex (RLPFC) and inferior parietal lobule (IPL), but only among 12-18-year olds. For 9-11-year olds, reasoning ability was most strongly related to connectivity between left and right RLPFC; this relationship was mediated by working memory. For 6-8-year olds, significant relationships between connectivity and performance were not observed; in this group, processing speed was the primary mediator of improvement in reasoning ability. We conclude that different connections best support reasoning at different points in development and that RLPFC-IPL connectivity becomes an important predictor of reasoning during adolescence. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: firstname.lastname@example.org.Cerebral Cortex 10/2014; DOI:10.1093/cercor/bhv050 · 8.67 Impact Factor
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- "In addition to these structural effects, the amount of circulating ovarian hormones influenced functional abilities in humans, specifically, verbal memory (Peper et al., 2011) and explicit memory recall (Gooren, 2007). Moreover, estrogen administration was found to protect against neurodegeneration only in cognitively intact women for whom degeneration had not yet started (Siegfried, 2007). "
ABSTRACT: Aging is associated with well-recognized alterations in brain function, some of which are reflected in cognitive decline. While less appreciated, there is also considerable evidence of socioemotional changes later in life, some of which are beneficial. In this review, we examine age-related changes and individual differences in four neuroendocrine systems-cortisol, estrogen, testosterone, and oxytocin-as "difference makers" in these processes. This suite of interrelated hormonal systems actively coordinates regulatory processes in brain and behavior throughout development, and their level and function fluctuate during the aging process. Despite these facts, their specific impact in cognitive and socioemotional aging has received relatively limited study. It is known that chronically elevated levels of the stress hormone cortisol exert neurotoxic effects on the aging brain with negative impacts on cognition and socioemotional functioning. In contrast, the sex hormones estrogen and testosterone appear to have neuroprotective effects in cognitive aging, but may decrease prosociality. Higher levels of the neuropeptide oxytocin benefit socioemotional functioning, but little is known about the effects of oxytocin on cognition or about age-related changes in the oxytocin system. In this paper, we will review the role of these hormones in the context of cognitive and socioemotional aging. In particular, we address the aforementioned gap in the literature by: (1) examining both singular actions and interrelations of these four hormonal systems; (2) exploring their correlations and causal relationships with aspects of cognitive and socioemotional aging; and (3) considering multilevel internal and external influences on these hormone systems within the framework of explanatory pluralism. We conclude with a discussion of promising future research directions.Frontiers in Psychology 01/2014; 5:1595. DOI:10.3389/fpsyg.2014.01595 · 2.80 Impact Factor
Jiska S Peper