Modeling sex-differences in trauma-related neural organization conferring resilience against addiction

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ABSTRACT While childhood adversity is a recognized risk factor for the development of drug use and other psychiatric disorders, many individuals are resilient against the negative consequences of childhood trauma. Searches for the mechanisms of resilient adaptation have largely sought to characterize psychological and psychosocial protective factors. However, inhibitory motor control and its inferior frontal cortex (IFC) mechanisms represent risk and protective factors for drug use disorders. The motivation for the proposed exploratory/developmental project is our fMRI demonstration that – for women without drug use or other psychiatric disorders – an increasing severity of childhood maltreatment was associated with increasing negative modulation of dorsal anterior cingulate cortex (dACC) activity by the left IFC (LIFC). Furthermore, this LIFC to dACC influence predicted both better response inhibition for a Stop Signal task and less impaired attention/impulsivity, suggesting it may be a construct encoding resilience to trauma. Our finding stands in contrast of existing literature implicating right IFC function in inhibitory control among healthy individuals. The proposed project would use further characterize the role of IFC-dACC connectivity in encoding sex-differences in resiliency against trauma. Aim 1 would use fMRI to independently replicate this adaptive response for motor control (Stop Signal task) by comparing task responses for men and women without drug use or other disorders and with (“resilient”) and without (“control”) childhood maltreatment histories. Aim 2 would assess the generalization of this neural pathway to cognitive conflict for emotionally distracting stimuli (the emotional Stroop task). Aim 3 would explore neurodevelopment of resilience through re-enrollment of female adolescents with trauma histories whom previously underwent the Stop Signal fMRI task to associate longitudinal changes in the neural mechanisms of inhibitory control to post-trauma clinical and drug use trajectories. The proposed model-based and hypothesis-driven research plan would explore further the role of a hypothetical neural network response related to behavioral control as a mechanism of adaptive cognitive resilience and develop potential biomarkers of resilience and neurobehavioral targets for intervention in at-risk individuals.