Sexual dimorphism in cortical theta rhythms relates to elevated internalizing symptoms during adolescence

Abstract Psychiatric disorders frequently emerge during adolescence, with girls at nearly twice the risk compared to boys. These sex differences have been linked to structural brain differences in association regions, which undergo profound development during childhood and adolescence. However, the relationship between functional activity in these cortical regions and the emergence of psychiatric disorders more broadly remains poorly understood. Herein, we investigated whether differences in internalizing and externalizing symptoms among youth are related to multispectral spontaneous neural activity. Spontaneous cortical activity was recorded using magnetoencephalography (MEG) in 105 typically-developing youth (9-15 years-old; 54 female) during eyes-closed rest. The strength of spontaneous neural activity within canonical frequency bands was estimated at each cortical vertex. The resulting functional maps were submitted to vertex-wise regressions to identify spatially specific effects whereby sex moderated the relationship between externalizing and internalizing symptoms, age, and spontaneous neural activity. The interaction between sex, age, and internalizing symptoms was significant in the theta frequency band, wherein theta activity was weaker for older relative to younger girls (but not boys) with greater internalizing symptoms. This relationship was strongest in the temporoparietal junction, with areas of the cingulate cortex exhibiting a similar relationship. The moderating role of sex in the relationship between age, internalizing symptoms, and spontaneous theta activity predominantly implicated association cortices. The negative relationship between theta and internalizing symptoms may reflect negative rumination with anxiety and depression. The specificity of this effect to older girls may reflect the selective emergence of psychiatric symptoms during adolescence in this subgroup.