Contributions of orbitofrontal subregions to socioemotional processing in Rhesus macaques Público
Murphy, Lauren (Spring 2018)
Abstract
The orbitofrontal cortex (OFC) is a heteromodal association area within the prefrontal cortex responsible for understanding and maintaining the flexible relationship between a stimulus and a subsequent outcome. As such, damage to the OFC impairs behaviors ranging from complex social interactions to Pavlovian fear conditioning. Despite extensive research to understand the complexities of the whole OFC, few studies have attempted the dissociate the separable contributions of OFC subregions to socioemotional processing and flexible behavioral modulation. Understanding the functional dissociation and organization of OFC subregions in the context of emotional processing will help elucidate the mechanisms underlying emotional dysregulation present in many mood disorders. Thus, this dissertation describes two studies comparing the effects of restricted cortical lesions to subregions of the OFC (Brodmann Areas BA12, BA13, and BA14) on emotional processing. In Study 1, data demonstrated that OFC areas 12 and 13, part of the lateral orbital network of the OFC, but not BA14, part of the medial OFC network, critically support attention to salient social cues and regulate arousal in socioemotional contexts. In Study 2, the results showed that this same lateral orbital OFC network, but not the medial OFC network, support the modulation of emotional behaviors in the presence of conflicting cues, though differences occurred in the magnitude of the impairment. Thus, while damage to BA12 yields impairments only in the modulation of fear response in the presence of a safe cue, damage to BA13 causes impairments in both the expression fear and safe associations and modulation of fear responses. Together, the two studies provide additional support to the view that the lateral orbital network of the OFC, but not the medial OFC network, is critical for emotional regulation in primates and suggest that emotional dysregulation may stem from impairments in flexibly maintaining and updating stimulus-outcome associations.
Table of Contents
Table of Contents
General Introduction.............................................................................. 1
Features of the Orbitofrontal Cortex.......................................................... 2
Functions of the Orbitofrontal Cortex........................................................ 5
Summary............................................................................................... 15
Impacts of orbitofrontal lesions on social attention and arousal in rhesus macaques................................................................................. 20
Abstract................................................................................................. 21
Introduction........................................................................................... 22
Methods................................................................................................. 26
Data Analyses........................................................................................ 33
Results................................................................................................... 34
Discussion............................................................................................. 41
Impacts of orbitofrontal lesions on fear retention and expression in rhesus macaques.................................................................................... 62
Abstract................................................................................................. 63
Introduction........................................................................................... 64
Materials & Methods.............................................................................. 69
Results................................................................................................... 78
Discussion............................................................................................. 85
General Discussion.............................................................................. 109
The specialized role of the lateral OFC in the processing of negative stimuli................................................................................................. 110
The role of the OFC BA13 in emotional behavior and stimulus-outcome associations.......................................................................................... 113
The role of the medial OFC and the ventromedial PFC in regulating arousal................................................................................................. 116
Implications for understanding the role of OFC-amygdala connectivity in
emotional regulation............................................................................. 119
Limitations and future directions........................................................... 122
General conclusions and the contributions of the orbital and medial networks of the OFC........................................................................................... 124
References............................................................................................ 126
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