A cognitive neuroscience hypothesis of mood and depression

Abstract

Although mood has a direct impact on mental and physical health, our understanding of the mechanisms underlying mood regulation is limited. Here, I propose that there is a direct reciprocal relation between the cortical activation of associations and mood regulation, whereby positive mood promotes associative processing, and associative processing promotes positive mood. This relation might stem from an evolutionary pressure for learning and predicting. Along these lines, one can think of mood as a reward mechanism that guides individuals to use their brains in the most productive manner. The proposed framework has many implications, most notably for diagnosing and treating mood disorders such as depression; for elucidating the role of inhibition in the regulation of mood; for contextualizing adult hippocampal neurogenesis; and for a general, non-invasive improvement of well-being.

Figure 1. – Rumination versus broadly associative thinking

(a) Thought pattern typical of mood disorder involves rumination around a narrow focus. Even if this thought pattern is associative, it is limited in scope. Such constrained thought is proposed here to stem from hyper-inhibition from the medial prefrontal cortex (MPFC) to the medial temporal lobe (MTL). (b) The thought pattern in the brain of individuals without mood disorders is characterized by a broadly associative activation, which although is still affected by inhibition signals (for functional guidance), can seamlessly disengage from one focus and advance to another.

Figure 2. - Converging activations in MPFC

The same MPFC region that is stimulated by deep brain stimulation (DBS) to treat severe depression, and where activation is most indicative of successful treatment (a), is strongly active in our studies of context-based associative predictions (b). Panel a. is modified from [71] with permission. (c) Anatomical support to the direct and extensive connection between BA25 and the MPFC region activated by contextual associations has been reported previously [72], as well as using population maps of probabilistic tractography of strongly interconnected MPFC regions [73] (reproduced with permission). (d) The same region shows reduced gray matter in depression patients [46] (reproduced with permission). (e) The default network [74], which shows a striking overlap with the same network that mediates contextual associations and predictions [4] (reproduced with permission). Recruiting this MPFC region by cognitive means, as in (b), could potentially regulate inhibition and retrain the natural tendency to engage in broad associative activation, which is compromised in mood disorders.