McKeon, Shane
(2024)
Underlying Brain Mechanisms of the PFC Excitatory Inhibitory Balance through Adolescent Cognitive Maturation.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Neurocognitive development through adolescence continues to specialize in the prefrontal cortex (PFC), suggesting critical period plasticity. Animal and human postmortem models have identified specific mechanisms that govern critical periods (CPs) of development in sensory cortex. It has recently been proposed that these mechanisms occur in adolescent PFC maturation, providing evidence for changes in excitatory glutamate and inhibitory GABA, reflecting a shift in the excitatory/ inhibitory (E/I) balance. However, there is limited understanding of developmental changes in the PFC E/I balance in vivo during adolescence and its impact on executive function. This thesis aimed to assess CP plasticity in PFC by characterizing CP mechanisms during adolescence using electrophysiological assessments of E/I balance. The first study revealed that with development, power, and number of gamma bursts, which support working memory reinstatement, decrease, providing evidence for continued specialization of PFC circuit function. We the investigated evidence for changes in E/I balance in PFC by characterizing EEG-derived measures of the E/I balance and their association with changes in glutamate and GABA function in PFC. Results showed a significant association between the EEG and MRSI measures both indicating increases in E/I balance in PFC into adulthood. We further tested this model by demonstrating that increases in the E/I balance are associated with EEG indices of cortical signal-to-noise ratio (SNR), driven by changes in spontaneous activity. Lastly, we characterized changes in the power of broadband (1-200 Hz), gamma (30-60 Hz), and high gamma (60-200 Hz), association with population level spiking, by leveraging stereoelectroencephalogeraphy (sEEG). Increases in high gamma and gamma activity were associated with decreases in the aperiodic exponent, suggesting that gamma and high gamma may support E/I balance via changes in GABAergic interneurons and pyramidal neurons. Taken together, the studies presented here provide novel in vivo human evidence of CP plasticity in PFC during adolescence, its contributions to cognitive development, and importantly possible mechanisms that may underlie this transition. Understanding this important stage of neurodevelopment is crucial to understanding normative development and windows of plasticity that could inform abnormal trajectories such as in psychopathology, many of which emerge during adolescence, and possible approaches for intervention.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
6 September 2024 |
| Date Type: |
Publication |
| Defense Date: |
14 June 2024 |
| Approval Date: |
6 September 2024 |
| Submission Date: |
20 June 2024 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
222 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Swanson School of Engineering > Bioengineering |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Adolescence, excitation inhibition, EEG, aperiodic, signal-to-noise ratio |
| Date Deposited: |
06 Sep 2024 19:56 |
| Last Modified: |
06 Sep 2024 19:56 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/46586 |
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