Dataset Information

Differential Effects of the Inactivation of Anterior and Posterior Orbitofrontal Cortex on Affective Responses to Proximal and Distal Threat, and Reward Anticipation in the Common Marmoset.

ABSTRACT: Structural and functional abnormalities of the orbitofrontal cortex (OFC) have been implicated in affective disorders that manifest anxiety-related symptoms. However, research into the functions of primate OFC has predominantly focused on reward-oriented rather than threat-oriented responses. To redress this imbalance, the present study performed a comprehensive analysis of the independent role of 2 distinct subregions of the central OFC (anterior area 11; aOFC and posterior area 13; pOFC) in the processing of distal and proximal threat. Temporary inactivation of both aOFC and pOFC heightened responses to distal threat in the form of an unknown human, but not to proximal threat assessed in a discriminative Pavlovian conditioning task. Inactivation of the aOFC, however, did unexpectedly blunt conditioned threat responses, although the effect was not valence-specific, as conditioned appetitive responses were similarly blunted and appeared restricted to a discriminative version of the task (when both CS- and CS+ are present within a session). Inactivation of the pOFC did not affect conditioned responses to either proximal threat or reward and basal cardiovascular activity was unaffected by manipulations of activity in either subregion. The results highlight the contribution of aOFC and pOFC to regulation of responses to more distal uncertain but not proximal, certain threat and reveal their opposing contribution to that of the immediately adjacent medial OFC, area 14.

SUBMITTER: Stawicka ZM

PROVIDER: S-EPMC8971078 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Publications

Differential Effects of the Inactivation of Anterior and Posterior Orbitofrontal Cortex on Affective Responses to Proximal and Distal Threat, and Reward Anticipation in the Common Marmoset.

Stawicka Zuzanna M ZM Massoudi Roohollah R Oikonomidis Lydia L McIver Lauren L Mulvihill Kevin K Quah Shaun K L SKL Cockcroft Gemma J GJ Clarke Hannah F HF Horst Nicole K NK Wood Christian M CM Roberts Angela C AC

Cerebral cortex (New York, N.Y. : 1991) 20220301 7

Structural and functional abnormalities of the orbitofrontal cortex (OFC) have been implicated in affective disorders that manifest anxiety-related symptoms. However, research into the functions of primate OFC has predominantly focused on reward-oriented rather than threat-oriented responses. To redress this imbalance, the present study performed a comprehensive analysis of the independent role of 2 distinct subregions of the central OFC (anterior area 11; aOFC and posterior area 13; pOFC) in th ...[more]

PMID: 34494095

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Project description:BACKGROUND:Mood and anxiety disorders are characterized by altered prefrontal-amygdala function and increased behavioral inhibition (BI) in response to potential threat. Whether these alterations constitute a vulnerability or a symptom of illness remains unclear. The medial orbitofrontal cortex (mOFC) is thought to play a central role in estimating probability and cost of threat, in turn informing selection of subsequent behaviors. To better understand the behavioral and neural processes that may be associated with risk for psychopathology, we used a virtual reality paradigm to examine behavioral and neural responses of psychiatrically healthy adults with familial history of affective disorders during anticipation of unpredictable threat. METHODS:Twenty psychiatrically healthy adults with high familial risk for affective disorders and 20 low-risk matched controls underwent functional magnetic resonance imaging concurrent with a paradigm in which they explored virtual contexts associated with the threat of shock or safety from shock. Subjective anxiety ratings, skin conductance, exploratory behavior, and neural responses were examined for threat versus safe conditions. RESULTS:High-risk adults evidenced greater right mOFC activation, as well as greater BI, compared to low-risk adults. There were no significant group differences in subjective ratings or autonomic responses. Individuals exhibiting greater activity in the right mOFC showed greater BI and decreased skin conductance response. CONCLUSIONS:These results suggest that BI and mOFC recruitment during anticipation of aversive outcomes may reflect a vulnerability for affective disorders. However, such a response may also serve as a compensatory response, protecting these high-risk individuals from negative outcomes (i.e., increased physiological arousal). These results suggest that the OFC may play a central role in driving threat-related behaviors and thus may be a target for efforts aimed at early detection or prevention.

Dataset Information

Differential Effects of the Inactivation of Anterior and Posterior Orbitofrontal Cortex on Affective Responses to Proximal and Distal Threat, and Reward Anticipation in the Common Marmoset.

Publications

Differential Effects of the Inactivation of Anterior and Posterior Orbitofrontal Cortex on Affective Responses to Proximal and Distal Threat, and Reward Anticipation in the Common Marmoset.

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