8372 Evidence of dACC Glutamate Modulation During Top-down Inhibitory Control Predicting Weight Loss Ability in Individuals with Obesity Using1H fMRS

Abstract

Abstract Disclosure: J.M. Eichstaedt: None. R. Sochocki: None. D. Khatib: None. N. Miller: None. V.A. Diwadkar: None. P. Burghardt: None. A.E. Rothberg: None. J.A. Stanley: None. Poor weight loss maintenance (WLM) following dietary intervention has been associated with poor top-down inhibitory control. The neurobiological mechanisms are not fully understood; it is not clear if changes to inhibitory control are specific to the presence of appetitive food cues. The dorsal anterior cingulate cortex (dACC) is central to inhibitory control and can be conceptualized selectively withholding ‘prepotent’ motor responses. This is driven by highly integrated glutamatergic and GABAergic neurotransmission. Temporal changes in glutamate, reflecting shifts in glutamate neurotransmission, can be detected under distinct processes or task conditions using [1]H fMRS. We investigated differences in dACC glutamate under task conditions with or without inhibitory motor control, utilizing neutral Squares and Food/Non-food stimuli, and their association with weight loss. Data were acquired from 13 individuals with obesity following dietary intervention resulting in 10% weight loss (5F; mean age: 50.1±5.2yrs). A visually-guided motor tapping task was used requiring participants to respond to stimuli under two modes, “Non-Selective” (motor responses to 100% of trials) and “Selective” (withholding responses on 20% of trials - involving both motor control and inhibition), and under two stimuli types (Squares and appetitive Food/Non-Food cues). Glutamate modulation changes (relative to the total signal) were assessed across stimuli type (independent of task mode) using repeated measures generalizing estimating equations (GEE) approach (SAS GENMOD). The correlation between glutamate during the Selective mode with food/non-food stimuli and percentage of weight lost during the dietary intervention was also assessed. The stimuli model term was not significant (χ2=3.50, p=0.174), but post hoc analysis indicated significantly increased glutamate during the Squares (z=-1.99, p=0.046), but not the Food/Non-food (z=-1.39, p=0.163) relative to baseline. A trending correlation between decreasing dACC glutamate modulation (Selective mode, Food/Non-Food) and decreasing percentage of weight lost during the intervention was observed (R2=0.274, F(1,11)=4.15, p=0.07). This suggests that the presence of appetitive food cues leads to a non-significant change in the dACC glutamate modulation independent of inhibitory or motor alone responses. The potential correlation between dACC glutamate modulation and weight loss provides preliminary support that appetitive food cues influence inhibitory control and the extent of the influences may be related to one’s ability to maintain weight loss. These results could provide greater understanding of the neurobiological mechanisms underlying top-down inhibitory processes influenced by affect and difficulties with weight loss and maintenance, potentially fueling better treatment for successful long-term WLM in obesity. Presentation: 6/1/2024