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Characterizing How Age-Related Changes in GABA and Glutamate Underlie Development of Working Memory Through Adolescence

Perica, Maria Ivana (2021) Characterizing How Age-Related Changes in GABA and Glutamate Underlie Development of Working Memory Through Adolescence. Master's Thesis, University of Pittsburgh. (Unpublished)

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Adolescence is a time of significant cognitive development that leads to the establishment of adult modes of operation. Working memory is a core cognitive process that continues to improve into the second decade of life and is impaired across several psychiatric disorders. However, not much is known about the neurobiological mechanisms underlying the transition to adult-like working memory ability. The prefrontal cortex (PFC) supports working memory and undergoes protracted maturation through adolescence. Postmortem human and animal studies indicate changes in PFC Gamma-Aminobutyric Acid (GABA) (inhibition) and glutamate (excitation) during adolescence. These changes may underlie shifts in excitatory/inhibitory (E/I) balance reflecting critical period plasticity initiated by relative decreased excitation and increased inhibition. However, changes in glutamate and GABA through adolescence have not been well characterized in vivo in humans. We used 7T Magnetic Resonance Spectroscopic Imaging to characterize age-related changes in glutamate, GABA, and their balance in a sample of 144 10-30 year old healthy participants. First, we found age-related decreases in glutamate in the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), anterior insula, and a trend-level decrease in medial prefrontal cortex (MPFC). We found decreases in GABA in ACC and anterior insula, trend-level decrease in MPFC, and no change in DLPFC. Second, we found shifts toward excitation (indexed by the ratio of glutamate to GABA) in the ACC and anterior insula. Third, ACC and MPFC glutamate and GABA were more correlated in older age groups, suggesting greater balance. Finally, we examined whether age-related changes in these indices were associated with age-related improvements in the memory-guided saccade (MGS) task. We did not observe associations between neurotransmitter indices and MGS accuracy. However, in the youngest age group, higher correlations among GABA and glutamate within the ACC were associated with better MGS performance. These results may suggest that the balance of glutamate and GABA, not necessarily their individual concentrations, may be more tightly associated with cognitive ability, particularly in early adolescence. Taken together, these results provide a novel account of age-related changes in glutamate and GABA in frontal and association cortices, and their role in supporting age-related improvements in working memory.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Perica, Maria IvanaMIP86@pitt.eduMIP86
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairLuna,
Committee MemberHanson,
Committee MemberManuck,
Date: 3 May 2021
Date Type: Publication
Defense Date: March 2021
Approval Date: 3 May 2021
Submission Date: 18 March 2021
Access Restriction: 1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
Number of Pages: 73
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > Psychology
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: plasticity, critical period, development, neuroimaging
Date Deposited: 03 May 2021 15:43
Last Modified: 03 May 2022 05:15


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