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ABSTRACT ObjectiveNeighborhood perceptions are associated with physical and mental health outcomes; however, the biological associates of this relationship remain to be fully understood. Here, we evaluate the relationship between neighborhood perceptions and amygdala activity and connectivity with salience network (i.e., insula, anterior cingulate, thalamus) nodes. MethodsForty-eight older adults (mean age = 68 [7] years, 52% female, 47% non-Hispanic Black, 2% Hispanic) without dementia or depression completed the Perceptions of Neighborhood Environment Scale. Lower scores indicated less favorable perceptions of aesthetic quality, walking environment, availability of healthy food, safety, violence (i.e., more perceived violence), social cohesion, and participation in activities with neighbors. Participants separately underwent resting-state functional magnetic resonance imaging. ResultsLess favorable perceived safety (β= −0.33,p_FDR= .04) and participation in activities with neighbors (β= −0.35,p_FDR= .02) were associated with higher left amygdala activity, independent of covariates including psychosocial factors. Less favorable safety perceptions were also associated with enhanced left amygdala functional connectivity with the bilateral insular cortices and the left anterior insula (β= −0.34,p_FDR= .04). Less favorable perceived social cohesion was associated with enhanced left amygdala functional connectivity with the right thalamus (β =−0.42,p_FDR= .04), and less favorable perceptions about healthy food availability were associated with enhanced left amygdala functional connectivity with the bilateral anterior insula (right:β= −0.39,p_FDR= .04; left:β= −0.42,p_FDR= .02) and anterior cingulate gyrus (β= −0.37,p_FDR= .04). ConclusionsTaken together, our findings document relationships between select neighborhood perceptions and amygdala activity as well as connectivity with salience network nodes; if confirmed, targeted community-level interventions and existing community strengths may promote brain-behavior relationships.