The Aversive Lens: Stress effects on the prefrontal-cingulate cortical pathways that regulate emotion. (February 2023)

• Record Type: Journal Article
• Authors: Arnsten, Amy F.T.; Joyce, Mary Kate P.; Roberts, Angela C.
• Is Part Of: Neuroscience and biobehavioral reviews. Volume 145(2023)
• Publication Date: 2023-02
• Subjects: Anhedonia BA25 depression dopamine ketamine major depressive disorder norepinephrine prefrontal cortex primate rTMS serotonin SSRIs stress threat working memory; Psychophysiology -- Periodicals; Human behavior -- Periodicals; Animal behavior -- Periodicals; Neurology -- Periodicals; Behavior -- Periodicals; Ethology -- Periodicals; Neurology -- Periodicals; Psychophysiologie -- Périodiques; Comportement humain -- Périodiques; Animaux -- Mœurs et comportement -- Périodiques; Neurologie -- Périodiques; Animal behavior; Human behavior; Neurology; Psychophysiology; Periodicals; Electronic journals; 573.8
• DOI: 10.1016/j.neubiorev.2022.105000
• Languages: English
• ISSNs: 0149-7634

Abstract

Abstract: ARNSTEN, A.F.T., M.K.P. Joyce and A.C. Roberts. The Aversive Lens: Stress effects on the prefrontal-cingulate cortical pathways that regulate emotion. NEUROSCI BIOBEHAV REV XXX-XXX, 2022. The symptoms of major-depressive-disorder include psychic pain and anhedonia, i.e. seeing the world through an "aversive lens". The neurobiology underlying this shift in worldview is emerging. Here these data are reviewed, focusing on how activation of subgenual cingulate (BA25) induces an "aversive lens", and how higher prefrontal cortical (PFC) areas (BA46/10/32) provide top-down regulation of BA25 but are weakened by excessive dopamine and norepinephrine release during stress exposure, and dendritic spine loss with chronic stress exposure. These changes may generate an attractor state, which maintains the brain under the control of BA25, requiring medication or neuromodulatory treatments to return connectivity to a more flexible state. In line with this hypothesis, effective anti-depressant treatments reduce the activity of BA25 and restore top-down regulation by higher circuits, e.g. as seen with SSRI medications, ketamine, deep brain stimulation of BA25, or rTMS to strengthen dorsolateral PFC. This research has special relevance in an era of chronic stress caused by the COVID19 pandemic, political unrest and threat of climate change. Graphical Abstract: Graphical illustration of how overactivity of BA25 alters brain state to create an "Aversive Lens", e.g. where a neutral face is seen as sad. A. Under nonstressful conditions, higher PFC areas (BA46, BA10, BA32) provide top-down control of BA25, allowing accurate assessments of the world. B. Exposure to uncontrollable stress weakens the function of higher PFC areas, decreasing top-down regulation of BA25, creating an "Aversive Lens", e.g. with heightened response to threat and anhedonia (see text). Faces are from (Ekman and Friesen (1976) ). ga1 Highlights: The brain circuits that generate a depressive state are being illuminated in primates. New data show that activating BA25 can induce anhedonia and increased threat response. This brain state may be maintained when stress weakens prefrontal top-down regulation. These data are particularly timely due to the chronic stress of a global pandemic.