Functional anatomy of ventromedial prefrontal cortex: implications for mood and anxiety disorders

Abstract

In recent years, an increasing number of neuroimaging studies have sought to identify the brain anomalies associated with mood and anxiety disorders. The results of such studies could have significant implications for the development of novel treatments for these disorders. A challenge currently facing the field is to assimilate the large and growing corpus of imaging data to inform a systems-level model of the neural circuitry underlying the disorders. One prominent theoretical perspective highlights the top-down inhibition of amygdala by ventromedial prefrontal cortex (vmPFC) as a crucial neural mechanism that may be defective in certain mood and anxiety disorders, such as major depression and post-traumatic stress disorder. In this article we provide a critical review of animal and human data related to this model. In particular, we emphasize the considerable body of research that challenges the veracity (or at least completeness) of the predominant model. We propose a framework for constructing a more comprehensive model of vmPFC function, with the goal of fostering further progress in understanding the neuropathophysiological basis of mood and anxiety disorders.

Optogenetic stimulation of infralimbic PFC reproduces ketamine’s rapid and sustained antidepressant actions

“…Connections between IL-PFC and amygdala have been implicated in fear memory, extinction, and anxiety and could thereby contribute to the behavioral responses observed in the present study (36,37). In addition, previous studies demonstrate that mPFC connections with the dorsal raphe or mesolimbic dopamine system, including the nucleus accumbens, could contribute to the antidepressant responses to ketamine and optogenetic stimulation (32,35,38,39).…”

Dissociable relations between amygdala subregional networks and psychopathy trait dimensions in conduct‐disordered juvenile offenders

“…While these regions clearly serve myriad of functions, the interconnections and temporal dynamics they share are increasingly surmised reflective of an integrated neural circuitry serving salience processing, affective responding, and associative learning [Bressler and Menon, 2010; Etkin et al, 2011; Habas et al, 2009; Menon, 2011; Pessoa, 2011; Seeley et al, 2007]. Within this putative circuitry, the periaqueductal gray, cerebellum, and CMA seemingly convey visceromotor and affective salience to ventral segments of the anterior cingulate and medial prefrontal cortices, where it is represented as expected value information [Arnsten and Rubia, 2012; Etkin et al, 2011; Myers‐Schulz and Koenigs, 2012; Pessoa, 2011; Roy et al, 2014; Sah et al, 2003; Seeley et al, 2007]. These computations are then fed to dorsal segments within the anterior cingulate/medial prefrontal region for higher‐order processing that presumably aids adaptive selection and appropriate action [Arnsten and Rubia, 2012; Etkin et al, 2011; Myers‐Schulz and Koenigs, 2012; Pessoa, 2011; Roy et al, 2014; Sah et al, 2003; Seeley et al, 2007].…”

“…Within this putative circuitry, the periaqueductal gray, cerebellum, and CMA seemingly convey visceromotor and affective salience to ventral segments of the anterior cingulate and medial prefrontal cortices, where it is represented as expected value information [Arnsten and Rubia, 2012; Etkin et al, 2011; Myers‐Schulz and Koenigs, 2012; Pessoa, 2011; Roy et al, 2014; Sah et al, 2003; Seeley et al, 2007]. These computations are then fed to dorsal segments within the anterior cingulate/medial prefrontal region for higher‐order processing that presumably aids adaptive selection and appropriate action [Arnsten and Rubia, 2012; Etkin et al, 2011; Myers‐Schulz and Koenigs, 2012; Pessoa, 2011; Roy et al, 2014; Sah et al, 2003; Seeley et al, 2007]. It is noteworthy to mention that feedforward and feedback loops within this integrated circuitry not only allow for bottom‐up signaling but also top‐down regulatory modulation [Arnsten and Rubia, 2012; Bienkowski and Rinaman, 2013; Keifer et al, 2015; Pessoa, 2011; Roy et al, 2014; Sah et al, 2003].…”

Reducing future fears by suppressing the brain mechanisms underlying episodic simulation

“…Importantly, there is notable evidence for functional specialization within this region (see ref. 69), suggesting that it is particularly the posterior vmPFC that is involved in negative mood and anticipatory anxiety, whereas more anterior parts may support positive affect and fear extinction. Although parts of the cluster observed in the current study appear to cover the posterior vmPFC, direct comparisons are necessary to determine the extent to which the regions affected by future suppression colocalize with those involved in anticipatory anxiety or extinction.…”