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While current neural models of major depressive disorder have been important in both understanding and treating this disorder (6), they are equivocal with respect to the primary neural mechanisms of the illness and do not integrate contemporary knowledge of major neuroanatomical pathways and functional subdivisions of the brain. In formulating a more mechanistic and neuroanatomically viable model of major depression, it is important that we first identify and address issues concerning the data that inform neural theories of the disorder. In this context, it is noteworthy that even the neural findings that are considered most foundational in the neuroscience of depression, such as higher than normal baseline activity in the subgenual anterior cingulate cortex (6) and low activation in the dorsolateral prefrontal cortex (7), have not gone unchallenged (8–10). Further, region-of-interest analytic approaches, which are widely used in clinical neuroimaging (in reference 11, for instance) both to bolster statistical power and to test specific neural models of depression, (Am J P sych ia try Ham ilton e t a l.; A iA :1–11 ) Functiona l Neu ro im ag ing o f M a jo r D ep re ssive D iso rde r: A M e ta -A na ly sis and New In te g ra tion o f Base line A c tiv a tion and Neu ra l R e spon se D a ta