A theory of the neural mechanisms underlying negative cognitive bias in major depression

The widely acknowledged cognitive theory of depression, developed by Aaron Beck, focused on biased information processing that emphasizes the negative aspects of affective and conceptual information. Current attempts to discover the neurological mechanism underlying such cognitive and affective bias have successfully identified various brain regions associated with severally biased functions such as emotion, attention, rumination, and inhibition control. However, the neurobiological mechanisms of how individuals in depression develop this selective processing toward negative is still under question. This paper introduces a neurological framework centered around the frontal-limbic circuit, specifically analyzing and synthesizing the activity and functional connectivity within the amygdala, hippocampus, and medial prefrontal cortex. Firstly, a possible explanation of how the positive feedback loop contributes to the persistent hyperactivity of the amygdala in depression at an automatic level is established. Building upon this, two hypotheses are presented: hypothesis 1 revolves around the bidirectional amygdalohippocampal projection facilitating the amplification of negative emotions and memories while concurrently contributing to the impediment of the retrieval of opposing information in the hippocampus attractor network. Hypothesis 2 highlights the involvement of the ventromedial prefrontal cortex in the establishment of a negative cognitive framework through the generalization of conceptual and emotional information in conjunction with the amygdala and hippocampus. The primary objective of this study is to improve and complement existing pathological models of depression, pushing the frontiers of current understanding in neuroscience of affective disorders, and eventually contributing to successful recovery from the debilitating affective disorders.