Neuroplasticity in an Extended Amygdala Network as a Target Mechanism for Attention Bias Modification Outcome

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Abstract Northern Michigan University (NMU) is a rural primarily undergraduate university with approximately 8,000 students located in Michigan's sparsely populated and economically depressed Upper Peninsula. The proposed research will meet the objectives of the AREA grant by providing students with significant hands-on experience in clinically relevant human neuroimaging research and by strengthening the research environment of NMU. Anxiety disorders are one of the most common psychological disorders. Underlying anxiety is an increased attentional bias to threat, which has been identified as a causal contributor in the development of anxiety. Given this causal relationship, attention bias modification was introduced as a treatment option where anxiety is reduced by training individuals to direct their attention away from threat and thereby decreasing anxiety. Over a decade of research using this approach, called attention bias modification (ABM), suggests that overall the approach is effective in reducing anxiety. Although ABM appears to be a very promising treatment option for anxiety, there are several factors limiting the effectiveness of ABM. These include the recognition of individual-level needs and a known underlying mechanism of action by which ABM is effective. Neuroimaging evidence suggests that attentional bias to visual threat is associated with a network of brain regions including the amygdala, anterior cingulate cortex, and visual cortex. In human participants, experience- dependent neuroplasticity is visible in the voxel-based morphometry based measures of gray matter volume following training. Recently, voxel-based morphometry measures of gray matter volume have been linked to dendritic spine density—a known cellular mechanism for learning-related neuroplasticity. Thus, voxel-based morphometry measures are ideally suited to measure learning-related neuroplasticity following attention bias modification. In this proposal participants' level of attentional bias, anxiety, and gray matter volume will be measured before and after completing six weeks of attention bias modification training (N = 50) or attention control training (N= 50). The proposal aims to (1) establish that pre-treatment bias predicts variability in the gray matter volume in the extended amygdala and anterior cingulate cortex, (2) assess the extent to which reduced extended amygdala and anterior cingulate cortex gray matter volume following ABM underlies reductions in attentional bias and anxiety, and (3) Establish pre-treatment bias as a predictor of successful ABM as measured by reduced bias, reduced anxiety, and reduced gray matter volume in the extended amygdala and anterior cingulate cortex. Consistent with the objectives of the AREA grant and NIMH's focus on identifying and validating new targets for treatment development that underlie disease mechanisms, the current proposal plans to involve students at a rural primarily undergraduate university in a research project aimed at establishing neuroplasticity in the extended amygdala and anterior cingulate cortex as a target mechanism for ABM training outcome, which could be used to objectively track training-related outcomes in anxiety treatment.