Effects of endogenous testosterone on oscillatory activity during verbal working memory in youth

• Published in: Human brain mapping 2024-07, Vol.45 (10), p.e26774-n/a
• Main Authors: Killanin, Abraham D., Ward, Thomas W., Embury, Christine M., Calhoun, Vince D., Wang, Yu‐Ping, Stephen, Julia M., Picci, Giorgia, Heinrichs‐Graham, Elizabeth, Wilson, Tony W.
• Format: Article
• Language: English
• Subjects: Adolescent; alpha; Brain - physiology; Brain Mapping; Child; development; Female; Humans; Magnetoencephalography; Male; MEG; Memory, Short-Term - physiology; neural oscillations; pubertal hormones; puberty; Saliva - chemistry; Saliva - metabolism; Sex Characteristics; sex differences; Testosterone; theta
• ISSN: 1065-9471; 1097-0193; 1097-0193
• DOI: 10.1002/hbm.26774

Testosterone levels sharply rise during the transition from childhood to adolescence and these changes are known to be associated with changes in human brain structure. During this same developmental window, there are also robust changes in the neural oscillatory dynamics serving verbal working memory processing. Surprisingly, whereas many studies have investigated the effects of chronological age on the neural oscillations supporting verbal working memory, none have probed the impact of endogenous testosterone levels during this developmental period. Using a sample of 89 youth aged 6–14 years‐old, we collected salivary testosterone samples and recorded magnetoencephalography during a modified Sternberg verbal working memory task. Significant oscillatory responses were identified and imaged using a beamforming approach and the resulting maps were subjected to whole‐brain ANCOVAs examining the effects of testosterone and sex, controlling for age, during verbal working memory encoding and maintenance. Our primary results indicated robust testosterone‐related effects in theta (4–7 Hz) and alpha (8–14 Hz) oscillatory activity, controlling for age. During encoding, females exhibited weaker theta oscillations than males in right cerebellar cortices and stronger alpha oscillations in left temporal cortices. During maintenance, youth with greater testosterone exhibited weaker alpha oscillations in right parahippocampal and cerebellar cortices, as well as regions across the left‐lateralized language network. These results extend the existing literature on the development of verbal working memory processing by showing region and sex‐specific effects of testosterone, and are the first results to link endogenous testosterone levels to the neural oscillatory activity serving verbal working memory, above and beyond the effects of chronological age. During puberty, endogenous testosterone levels rise. We examined whether these increases in testosterone are associated with developmental changes, controlling for age, in the neural oscillatory dynamics serving verbal working memory. Results showed that alpha and theta oscillatory responses were modulated by testosterone levels across multiple regions critical for task performance.