Supervisor: Angela Roberts
Understanding the contribution of higher-order prefrontal cortex in the regulation of positive and negative emotion
The aim of this project will be to identify the interaction between the lateral prefrontal cortex (PFC) and the ventromedial PFC in the regulation of anhedonia and anxiety. The lateral PFC, in particular area 46, has been implicated in depression, a role hypothesised to involve cognitive regulation of emotional responses. Imaging studies investigating the cognitive regulation of emotion identify changes in activity in this region during successful implementation of cognitive regulation strategies. In addition, transcranial magnetic stimulation (TMS) of area 46 can be successful in ameliorating symptoms in patients with treatment resistant depression in which pharmaco- and behavioural therapies have failed. In both cases, activation of area 46 is seen to dampen hyperactivity of vmPFC cortex during the regulation of emotion. Indeed, it has been proposed that ketamine, a drug that has had some success in treating treatment-resistance patients with depression may have, in part, some of its effects in area 46. Thus, the proposed programme of work will test the hypothesis that area 46 can act to regulate positive and negative emotions and does so through its connectivity (probably indirect) with vmPFC. This project will use new world monkeys to investigate the role of area 46 in regulating behavioural and cardiovascular reactivity to uncertain threat and to determine how it interacts with regions of ventromedial PFC to have its effects. The project will involve the use of viral mediated strategies to perturb area 46 activity and to target pathways between area 46 and other prefrontal regions in order to investigate its role in emotion regulation.
Relevant references:
1. Arnsten AF1, Murray JD2, Seo H3, Lee D3. Ketamine's Antidepressant Actions: Potential Mechanisms in the Primate Medial Prefrontal Circuits That Represent Aversive Experience. Biol Psychiatry. 2016 May 1;79(9):713-5. doi: 10.1016/j.biopsych.2016.02.014.
2. Alexander L, Clarke HF, Roberts AC. A Focus on the Functions of Area 25. Brain Sci. 2019 3;9(6). pii: E129. doi: 10.3390/brainsci9060129. Review.
3. Datta D1, Arnsten AFT2. Loss of Prefrontal Cortical Higher Cognition with Uncontrollable Stress: Molecular Mechanisms, Changes with Age, and Relevance to Treatment Brain Sci. 2019 May 17;9(5). pii: E113. doi: 10.3390/brainsci9050113.