Functional connectivity of amygdala subnuclei in PTSD: a narrative review

While the amygdala is often implicated in the neurobiology of posttraumatic stress disorder (PTSD), the pattern of results remains mixed. One reason for this may be the heterogeneity of amygdala subnuclei and their functional connections. This review used PRISMA guidelines to synthesize research exploring the functional connectivity of three primary amygdala subnuclei, basolateral (BLA), centromedial (CMA), and superficial nuclei (SFA), in PTSD (N = 331) relative to trauma-exposed (N = 155) and non-trauma-exposed controls (N = 210). Although studies were limited (N = 11), preliminary evidence suggests that in PTSD compared to trauma-exposed controls, the BLA shows greater connectivity with the dorsal anterior cingulate, an area involved in salience detection. In PTSD compared to non-trauma-exposed controls, the BLA shows greater connectivity with the middle frontal gyrus, an area involved in attention. No other connections were replicated across studies. A secondary aim of this review was to outline the limitations of this field to better shape future research. Importantly, the results from this review indicate the need to consider potential mediators of amygdala subnuclei connectivity, such as trauma type and sex, when conducting such studies. They also highlight the need to be aware of the limited inferences we can make with such small samples that investigate small subcortical structures on low field strength magnetic resonance imaging scanners. Collectively, this review demonstrates the importance of exploring the differential connectivity of amygdala subnuclei to understand the pathophysiology of PTSD and stresses the need for future research to harness the strength of ultra-high field imaging to gain a more sensitive picture of the neural connectivity underlying PTSD.