Gender Differences in the Alcohol-Related Alterations in Cortical Activity

Background: Long-term alcohol use is known to harm brain functioning in adolescence. In the central nervous system, the effects of alcohol are particularly mediated by alterations in GABAergic neurotransmission. Combining simultaneous electroencephalogram (EEG) recording with transcranial magnetic stimulation (TMS) enables direct, in vivo exploration of cortical excitability and assessment of effective and functional connectivity. After motor cortex stimulation, the TMS-evoked EEG potentials (TEPs) N45 and N100 are known to reflect GABA-A- and GABA-B-ergic function, respectively. Sexual differentiation of the brain begins in the prenatal and early postnatal periods. Changes in sex steroid secretion in adolescence continue remodeling the brain and facilitating the sexual differentiation, since the sex hormones act directly on the neurons and supporting neural processes. The effects are region- and sex-specific, the female brain developing earlier than the male brain.

Aims: Previously, we have demonstrated that alcohol use in adolescence is associated with altered cortical activity. The aim of the current study was to explore whether long-term alcohol use in adolescence affects the cortical activity of the male and female brain differently. Our hypothesis was that females are more vulnerable to effects of alcohol and that this difference is seen in the GABAergic TEPs N45 and N100.

Methods: In this study, a total of 27 (11 males) young adults with heavy 10-year alcohol use in adolescence and 25 (12 males) controls with little or no alcohol use participated in TMS-EEG measurements. The motor cortex (M1) was stimulated with an intensity of 90% of the resting motor threshold (rMT) of the abductor pollicis brevis muscle and 61-channel EEG was registered. Data analysis was conducted using MATLAB and the EEGLAB toolbox. Statistical analyses were performed for both genders separately using IB M SPSS Statistics, version 22

Results: In the linear mixed model analysis, in both genders, a statistically significant group*AP interaction (group=case/control, AP=anteroposterior location of the EEG channels) was found in the GABA-A-ergic TEP amplitude N45 (females: p=0.003, males: p<0.001). In males, group*AP difference was also encountered in the GABA-B-ergic N100 (p<0.001). Post hoc analysis was performed to determine the statistically significant interaction factors, i.e. regions in which the differences existed. The average peak amplitudes and statistical significance in the between-groups comparison in the post hoc analysis are presented in Table 1. The significant difference in the N45 was located frontally. The N100 was topographically differently distributed in male subjects and controls. In males, the mean N45 and N100 latencies also differed between the groups (Table 1). All reported p-values are Bonferroni corrected for multiple comparisons.

Conclusions: Our results support the hypothesis that alcohol use affects the developing brain differently in males and females. Interestingly, in males, alcohol use was associated with altered GABA-A- and GABA-B-ergic cortical functioning, whereas in females the alterations were found only in the GABA-A-ergic activity. The relationship between sex hormones and neurotransmission should be further studied.