Testosterone effects on functional amygdala lateralization: A study in adolescent transgender boys and cisgender boys and girls.

The influence of testosterone on the development of human brain lateralization has been subject of debate for a long time, partly because studies investigating this are necessarily mostly correlational. In the present study we used a quasi-experimental approach by assessing functional brain lateralization in trans boys (female sex assigned at birth, diagnosed with Gender Dysphoria, n = 21) before and after testosterone treatment, and compared these results to the functional lateralization of age-matched control groups of cisgender boys (n = 20) and girls (n = 21) around 16 years of age. The lateralization index of the amygdala was determined with functional magnetic resonance imaging (fMRI) during an emotional face matching task with angry and fearful faces, as the literature indicates that boys show more activation in the right amygdala than girls during the perception of emotional faces. As expected, the lateralization index in trans boys shifted towards the right amygdala after testosterone treatment, and the cumulative dose of testosterone treatment correlated significantly with amygdala lateralization after treatment. However, we did not find any significant group differences in lateralization and endogenous testosterone concentrations predicted rightward amygdala lateralization only in the cis boys, but not in cis girls or trans boys. These inconsistencies may be due to sex differences in sensitivity to testosterone or its metabolites, which would be a worthwhile course for future studies.

Cortisol during adolescence organises personality traits and behavioural syndromes.

Despite the growing evidence for the importance of developmental experiences shaping consistent individual differences in behaviour and physiology, the role of endocrine factors underlying the development and maintenance of such differences across multiple traits, remains poorly understood. Here, we investigated how an experimental manipulation of circulating glucocorticoids during early adolescence affects behavioural and physiological variation and covariation later in life in the precocial cavy (Cavia aperea). Plasma cortisol concentrations were experimentally elevated by administering cortisol via food for 3 weeks. Struggle docility, escape latency, boldness, exploration and social behaviour were then tested three times after individuals attained sexual maturity. In addition, blood samples were taken repeatedly to monitor circulating cortisol concentrations. Exogenous cortisol affected mean trait expression of plasma cortisol levels, struggle docility and escape latency. Repeatability of cortisol and escape latency was increased and repeatability of struggle docility tended to be higher (approaching significance) in treated individuals. Increased repeatability was mainly caused by an increase of among-individual variance. Correlations among docility, escape latency and cortisol were stronger in treated animals compared to control animals. These results suggest that exposure to elevated levels of cortisol during adolescence can alter animal personality traits as well as behavioural syndromes. Social and risk-taking traits showed no correlation with cortisol levels and were unaffected by the experimental manipulation, indicating behavioural modularity. Taken together, our data highlight that cortisol can have organising effects during adolescence on the development of personality traits and behavioural syndromes, adding to the increasing evidence that not only early life but also adolescence is an important sensitive period for behavioural development.

Driving performance during word generation--testing the function of human brain lateralization using fTCD in an ecologically relevant context.

It has been hypothesized that cerebral lateralization of function enhances cognitive performance. Evidence was found in birds and fish. However, recent research in humans did not support this hypothesis. We aimed to replicate and extend these findings for single- and dual-task performance in an ecologically relevant task. We combined a word generation task which is assumed to be primarily processed in the left hemisphere with a driving task which is assumed to be primarily processed in the right hemisphere. For each task the individual strength and direction of hemispheric lateralization was assessed by using functional transcranial Doppler sonography (fTCD). For each subject (36 right-handed, 35 nonright-handed) performance was measured in the two single-tasks and in the dual-task condition. On average, subjects showed a left hemisphere bias for the word generation task, a right hemisphere bias for the driving task and dual-task interference. Within subjects, lateralization of language and driving were statistically independent. In accordance with earlier studies, the results show no indication of a positive effect of strength of lateralization on performance in single-tasks or dual-task efficiency. We also found no advantage of a typical compared to an atypical or a contralateral compared to an ipsilateral lateralization pattern. In right-handers, but not in nonright-handers, we even found a negative relationship between strength of lateralization and dual-task efficiency for atypically lateralized subjects. This further supports the suggestion that lateralization does not enhance cognitive performance in humans.

Functional cerebral lateralization and dual-task efficiency-testing the function of human brain lateralization using fTCD.

It has been hypothesized that functional cerebral lateralization enhances cognitive performance. Evidence was found in birds and fish. Our study aimed to test this hypothesis by analyzing the relationship between cerebral lateralization and both single-task performance and dual-task efficiency in humans. We combined a dynamic Landmark task which is assumed to be primarily processed in the right hemisphere and a frequently used word generation task which is assumed to be primarily processed in the left hemisphere. For each task individual strength and direction of hemispheric lateralization was assessed using functional transcranial Doppler sonography (fTCD). For each subject (15 women, 11 men), performance was measured in the two single-tasks and in the dual-task condition. Performance was not related to strength or direction of lateralization in single-tasks. With regard to dual-task efficiency, we found the expected advantage of having a typical lateralization pattern. Moreover, the results showed a slight negative, rather than a positive, relationship between strength of lateralization and dual-task efficiency. Further analysis showed that this negative relationship may only be present in subjects showing non-significant lateralization for one or both tasks. Therefore, the hypothesis that cerebral lateralization enhances human cognitive performance is too general: having two functions significantly lateralized to different hemispheres enhances dual-task efficiency, in this group strength of lateralized does not matter. However, if one or both functions are not significantly lateralized overall performance is worse and in this group, performance is negatively related to increased strength of lateralization.

Sex specific effect of prenatal testosterone on language lateralization in children.

Brain lateralization refers to the division of labour between the two hemispheres in controlling a wide array of functions and is remarkably well developed in humans. Based on sex differences in lateralization of handedness and language, several hypotheses have postulated an effect of prenatal exposure to testosterone on human lateralization development, the topic of a long-standing and unresolved debate. Here we demonstrate a clear relationship between prenatal levels of testosterone as assessed from amniotic fluid of healthy pregnant mothers and language lateralization of their offspring at the age of 6 years. Using focused attention conditions in the dichotic listening task, in which the child is instructed to report information from the left ear or the right ear, we were able to differentiate between potential effects of early testosterone on the left hemisphere and effects on inter-hemispheric connectivity. This provides a new method to distinguish between the claims of the different hypotheses. The results suggest that in girls higher prenatal testosterone exposure facilitates left hemisphere language processing, whereas in boys it reduces the information transfer via the corpus callosum.