Author ORCID Identifier
Date of Graduation
Doctor of Philosophy (PhD)
Adolescence is a dynamic period of social, cognitive, and biological changes. In particular, working memory, the ability to actively encode and maintain information over a short period of time, develops early in childhood and gradually increases in capacity and stability during adolescence. The precise neurophysiological mechanism by which working memory capacity increases during adolescence is unclear. The objective of this investigation was to evaluate the role of cortical gamma-band (> 30 Hz) oscillations—which are associated with working memory in adults—for the development of working memory capacity in adolescents, and to identify the extent to which the temporal profile of gamma-aminobutyric acid (GABA)-mediated cortical inhibition underlies these changes. I hypothesized that cortical gamma-band rhythms would become faster during adolescence in a manner that supports improved working memory capacity, and that the kinetics of cortical inhibition would also become faster to support these faster rhythms.
To this end, I recruited two cohorts of typically developing children (10 – 12 years) and adolescents (15 – 17 years) for a combined electrophysiology (EEG) and transcranial magnetic stimulation (TMS) study. First, I investigated the endogenous rhythmic activity generated by children and adolescence when performing a serially presented working memory task of varying set size. I found evidence of maturation in the generation of gamma-band rhythms which differed in power between groups, but identified no effects of a change in the central frequency of gamma-band activity. Next, I used TMS to exogenously evoke oscillatory activity in the left prefrontal cortex to identify the cortical natural (i.e., resonant) frequency. Using this measure, I found that adolescents exhibit higher median natural frequencies (MdCHILD = 16 Hz; MdADO = 24 Hz, Z = 2.35, p = 0.009), but that sex may play a mediating role when this change emerges. While this measure positively correlated with working memory capacity (rs = 0.47, p = 0.007), this effect disappeared when controlling for age and sex (rs = 0.29, p = 0.128).
Finally, I investigated the role of inhibitory timing as a potential mechanism for improved cognition and increased natural frequency using classic paired pulse TMS techniques. Six inter-pulse intervals (IPI) in the range of short- and long-intracortical inhibition (SICI, LICI) were tested to assess the temporal characteristics of GABA type-A and type-B receptor-mediated inhibition (GABAAR, GABABR, respectively). For SICI, I found alpha-band (9-14 Hz) facilitation in children and suppression in adolescents. For LICI, adolescents demonstrated greater suppression of gamma-band power compared to children, and equal suppression to children in the beta-band (15-30 Hz). I found no evidence for a change in timing of SICI- or LICI-induced modulations though LICI suppression of gamma- and beta-band power correlated with working memory capacity.
The overall hypothesis that the prefrontal cortex can produce faster rhythms during adolescent development was supported, but the hypothesized relationships between those rhythms, working memory capacity, and the timing of GABA-mediated inhibition were not. Rather, I observed several developmental differences in oscillatory power that suggest excitation-inhibition balance underlies the developmental increases in working memory capacity and gamma-band synchrony.
Adolescence, Transcranial Magnetic Stimulation, TMS, Electroencephalography, EEG, Development, Working Memory, Cognition