Amygdalar interhemispheric functional connectivity differs between the non-depressed and depressed human brain

The amygdalae are important, if not critical, brain regions for many affective, attentional and memorial processes, and dysfunction of the amygdalae has been a consistent finding in the study of clinical depression. Theoretical models of the functional neuroanatomy of both normal and psychopathological affective processes which posit cortical hemispheric specialization of functions have been supported by both lesion and functional neuroimaging studies in humans. Results from human neuroimaging studies in support of amygdalar hemispheric specialization are inconsistent. However, recent results from human lesion studies are consistent with hemispheric specialization. An important, yet largely ignored, feature of the amygdalae in the primate brain--derived from both neuroanatomical and electrophysiological data--is that there are virtually no direct interhemispheric connections via the anterior commissure (AC). This feature stands in stark contrast to that of the rodent brain wherein virtually all amygdalar nuclei have direct interhemispheric connections. We propose this feature of the primate brain, in particular the human brain, is a result of influences from frontocortical hemispheric specialization which have developed over the course of primate brain evolution. Results consistent with this notion were obtained by examining the nature of human amygdalar interhemispheric connectivity using both functional magnetic resonance imaging (FMRI) and positron emission tomography (PET). We found modest evidence of amygdalar interhemispheric functional connectivity in the non-depressed brain, whereas there was strong evidence of functional connectivity in the depressed brain. We interpret and discuss the nature of this connectivity in the depressed brain in the context of dysfunctional frontocortical-amygdalar interactions which accompany clinical depression.