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Transl Psychiatry. 2016 Nov 8;6(11):e944. doi: 10.1038/tp.2016.218.

You say 'prefrontal cortex' and I say 'anterior cingulate': meta-analysis of spatial overlap in amygdala-to-prefrontal connectivity and internalizing symptomology.

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Department of Pharmacy Practice, Wayne State University, Detroit, MI, USA.
Merrill Palmer Skillman Institute for Child and Family Development, Wayne State University, Detroit, MI, USA.
Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI, USA.
Unit on Perinatal Neural Connectivity, Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD, USA.
Behavioral Neuroscience, Boston University, Boston, MA, USA.


Connections between the amygdala and medial prefrontal cortex (mPFC) are considered critical for the expression and regulation of emotional behavior. Abnormalities in frontoamygdala circuitry are reported across several internalizing conditions and associated risk factors (for example, childhood trauma), which may underlie the strong phenotypic overlap and co-occurrence of internalizing conditions. However, it is unclear if these findings converge on the same localized areas of mPFC or adjacent anterior cingulate cortex (ACC). Examining 46 resting-state functional connectivity magnetic resonance imaging studies of internalizing conditions or risk factors (for example, early adversity and family history), we conducted an activation likelihood estimation meta-analysis of frontoamygdala circuitry. We included all reported amygdala to frontal coordinate locations that fell within a liberal anatomically defined frontal mask. Peak effects across studies were centered in two focal subareas of the ACC: pregenual (pgACC) and subgenual (sgACC). Using publicly available maps and databases of healthy individuals, we found that observed subareas have unique connectivity profiles, patterns of neural co-activation across a range of neuropsychological tasks, and distribution of tasks spanning various behavioral domains within peak regions, also known as 'functional fingerprints'. These results suggest disruptions in unique amygdala-ACC subcircuits across internalizing, genetic and environmental risk studies. Based on functional characterizations and the studies contributing to each peak, observed amygdala-ACC subcircuits may reflect separate transdiagnostic neural signatures. In particular, they may reflect common neurobiological substrates involved in developmental risk (sgACC), or the broad expression of emotional psychopathology (pgACC) across disease boundaries.

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