Blond BN, Fredericks CA, Blumberg HP. Functional neuroanatomy of bipolar disorder: structure, function, and connectivity in an amygdala–anterior paralimbic neural system. 
Bipolar Disord 2012: 14: 340–355. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S.

Objectives:  In past decades, neuroimaging research in bipolar disorder has demonstrated a convergence of findings in an amygdala–anterior paralimbic cortex neural system. This paper reviews behavioral neurology literature that first suggested a central role for this neural system in the disorder and the neuroimaging evidence that supports it.

Methods:  Relevant articles are reviewed to provide an amygdala–anterior paralimbic cortex neural system model of bipolar disorder, including articles from the fields of behavioral neurology and neuroanatomy, and neuroimaging.

Results:  The literature is highly supportive of key roles for the amygdala, anterior paralimbic cortices, and connections among these structures in the emotional dysregulation of bipolar disorder. The functions subserved by their more widely distributed connection sites suggest that broader system dysfunction could account for the range of functions—from neurovegetative to cognitive—disrupted in the disorder. Abnormalities in some components of this neural system are apparent by adolescence, while others, such as those in rostral prefrontal regions, appear to progress over adolescence and young adulthood, suggesting a neurodevelopmental model of the disorder. However, some findings conflict, which may reflect the small sample sizes of some studies, and clinical heterogeneity and methodological differences across studies.

Conclusions:  Consistent with models derived from early behavioral neurology studies, neuroimaging studies support a central role for an amygdala–anterior paralimbic neural system in bipolar disorder, and implicate abnormalities in the development of this system in the disorder. This system will be an important focus of future studies on the developmental pathophysiology, detection, treatment, and prevention of the disorder.