Characterizing How Age-Related Changes in GABA and Glutamate Underlie Development of Working Memory Through Adolescence
Year: 2021
Type: article
Study design: Observational Study
Abstract: 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.
Author: Maria I. Perica
Language: English
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3203727036