Trauma-Exposed Adolescents Show Reduced Cortical Glutamate Modulation during Inhibitory Control with Negative Emotional Stimuli

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Abstract Background Childhood trauma exposure (TE) may heighten negative emotional responses, overwhelm cognitive control, and increase risk for anxiety disorders. Cognitive control is facilitated by glutamatergic (Glu) excitatory neurotransmission within the dorsal anterior cingulate cortex (dACC). Dynamic changes in dACC Glu levels were investigated using ¹H functional magnetic resonance spectroscopy ( 1 H fMRS) to assess the impact of negative emotional processing on neural mechanisms supporting cognitive control in TE-youth. Methods Fifty adolescents were categorized into two TE-Groups: Higher (Mtrauma =6 ±1events) and Lower (Mtrauma =3 ±1events). 1 H fMRS from the dACC was acquired during an inhibitory motor control task requiring tapping responses to stimuli under two Response Modes, “NonSelective” (100% response) and “Selective” (80% response, 20% inhibition), executed with two Stimuli Conditions, “Squares” (no emotion) and “Faces” (emotion). Glu modulation (relative to basal levels) was tested across TE-Group, Stimuli Condition, and their interaction. Within each Stimuli Condition, Glu modulation was tested across Response Modes by TE-Group. Results We observed a 2-way interaction of TE-Group x Stimuli Condition (χ 2 =4.66, p =0.031). Post-hoc tests revealed significantly lower Glu modulation in Higher TE vs Lower TE ( p =.023) during Faces but not Squares. This Glu modulation did not differ across Response Modes. Within the Higher TE-Group, Glu was significantly reduced during Faces compared to Squares (p<.001). Basal dACC Glu levels did not differ between groups. Conclusions TE-Group differences in adolescent dACC Glu modulation were observed during cognitive control performed with emotional, but not non-emotional, stimuli, highlighting the value of 1 H fMRS for detecting trauma-related differences in task-related excitatory neurochemical dynamics.

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