Relationship of GABA Levels in Motor Cortex to Executive Function in Older Adults

Research Objectives To investigate the relationship of metabolite levels to cognitive performance in older adults. Design The present study involves baseline measures of older adults (60+ years) enrolled in an exercise intervention. In this report, we measured the sensitivity of cortical excitability using neuro metabolite (specifically GABA in primary motor cortex [M1]) levels measured with functional magnetic resonance spectroscopy (fMRS) to predict performance on cognitive assessments. Data acquisition was completed over two separate 120-minute sessions: 1) Cognitive testing; 2) fMRS involving motor learning at 3) Tesla. Setting The study was completed with community-dwelling older adults in a climate-controlled medical facility. Participants Participants in the present study included 22 older adults who were: over 60 years of age, cognitively intact (assessed by the MoCA), free from neurological or psychological impairment, able to complete a 12-week exercise program, and reportedly sedentary (less than 75 minutes of weekly voluntary exercise). Interventions The present study had two 12-week interventional arms involving physical activity: Balance/Stretching or High-Intensity Interval Training (HIIT) Aerobic Exercise. However, the data presented here are from baseline assessments. Main Outcome Measures The outcome measures are the correlation of resting GABA and magnitude of change in GABA (assessed using Gannet 3.3.1) during a motor learning task with functional MRS to levels to executive function (working memory, processing speed, verbal learning, verbal fluency). We hypothesize that higher levels of resting GABA and greater change in GABA levels during functional MRS will indicate greater dynamic range of GABA, which will predict higher executive function. Results Data quality was high (< 5% fit error, >12.5 SNR) for fMRS across runs. Baseline resting GABA levels significantly (p<.05) predicted digit symbol lookup (R^2=.23), while GABA change predicted HVLT Delay (R^2=.18), and COWA (R^2=.21). Resting GABA levels significantly predict motor learning accuracy during the fMRS session (R^2=.29) in addition to GABA change (R^2=.41). Conclusions We conclude that baseline and change measures of GABA have selective sensitivity to component executive functions in older adults. Additionally, resting GABA levels predict GABA change during motor learning. Author(s) Disclosures None.