Lesions of Ventrolateral Prefrontal or Anterior Orbitofrontal Cortex in Primates Heighten Negative Emotion

Agustín-Pavón, Carmen; Braesicke, Katrin; Shiba, Yoshiro; Santangelo, Andrea Mariana; Mikheenko, Yevheniia; Cockroft, Gemma; Asma, Faaiza; Clarke, Hannah F.; Man, Mei-See; Roberts, Angela

doi:10.1016/j.biopsych.2012.03.007

Cited by 82 publications

(110 citation statements)

References 45 publications

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“…1B). Thus, it would appear that in the control condition, the animals still find the reward "worth" responding for, despite the occasional punishment it incurs (14). Following implantation of intracerebral cannulae targeting either the antOFC (area 11) or vlPFC (area 12; Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Such insight will allow the development of more precise diagnostics and individually tailored therapeutic approaches. absence of reward, this loud noise, when paired with a neutral cue, has been shown to induce Pavlovian conditioned cardiovascular arousal and behavioral vigilance (14), indicative of its aversive properties. By combining the aversive noise with a reward, this task measures the extent of avoidance of the punished schedule when this conflicts with a competing approach response for a reward.…”

Section: Resultsmentioning

confidence: 99%

“…[10][11][12][13]. However, we showed previously that selective excitotoxic lesions of either anterior OFC (antOFC; area 11) or vlPFC (area 12) heighten anxiety and Pavlovian fear responses in marmoset monkeys, demonstrating that both regions contribute independently to the regulation of negative emotion (14), but their differential contribution and their involvement in modulating the impact of anxiety on decision making remains unknown. To address this, we developed an approach-avoidance conflict task suitable for marmoset monkeys and used anatomically specific intracerebral infusions and anxiolytic drug treatment to determine how temporary inactivation of these regions affected cost-benefit decision making.…”

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confidence: 95%

“…Given that permanent lesions of both these prefrontal regions enhance anxiety (14), it was possible that these inactivation-induced biases were due to an increase in anxiety-related behavior. We therefore determined whether these biases away from punishment could be blocked by a known anxiolytic drug.…”

Section: An Anxiolytic Abolished the Antofc And Vlpfc Inactivation-inmentioning

confidence: 99%

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Regional inactivations of primate ventral prefrontal cortex reveal two distinct mechanisms underlying negative bias in decision making

Clarke

Horst

Roberts

2015

Proc. Natl. Acad. Sci. U.S.A.

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Dysregulation of the orbitofrontal and ventrolateral prefrontal cortices is implicated in anxiety and mood disorders, but the specific contributions of each region are unknown, including how they gate the impact of threat on decision making. To address this, the effects of GABAergic inactivation of these regions were studied in marmoset monkeys performing an instrumental approach–avoidance decision-making task that is sensitive to changes in anxiety. Inactivation of either region induced a negative bias away from punishment that could be ameliorated with anxiolytic treatment. However, whereas the effects of ventrolateral prefrontal cortex inactivation on punishment avoidance were seen immediately, those of orbitofrontal cortex inactivation were delayed and their expression was dependent upon an amygdala–anterior hippocampal circuit. We propose that these negative biases result from deficits in attentional control and punishment prediction, respectively, and that they provide the basis for understanding how distinct regional prefrontal dysregulation contributes to the heterogeneity of anxiety disorders with implications for cognitive-behavioral treatment strategies.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 95%

Section: An Anxiolytic Abolished the Antofc And Vlpfc Inactivation-inmentioning

confidence: 99%

See 2 more Smart Citations

Regional inactivations of primate ventral prefrontal cortex reveal two distinct mechanisms underlying negative bias in decision making

Clarke

Horst

Roberts

2015

Proc. Natl. Acad. Sci. U.S.A.

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“…Lesions to the ventrolateral prefrontal cortex have been associated with increased anxiety in nonhuman primates (Agustín-Pavón et al, 2012). It has been proposed that the amygdala is hyper-responsive to threatening stimuli, whereas the response of the ventromedial prefrontal cortex is a blunted in patients with anxiety disorders, resulting in inadequate regulation of their responses to anxiety-inducing stimuli (Kent and Rauch, 2003;Rauch et al, 2003).…”

Section: Neural Systems and The Neurochemical Basis Of Anxietymentioning

confidence: 99%

Targeting the Modulation of Neural Circuitry for the Treatment of Anxiety Disorders

Farb

Ratner

2014

Pharmacol Rev

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Noninvasive cardiac psychophysiology as a tool for translational science with marmosets

Murphy

Ross

Bliss‐Moreau

2019

American J Primatol

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The importance of marmosets for comparative and translational science has grown in recent years because of their relatively rapid development, birth cohorts of twins, family social structure, and genetic tractability. Despite this, they remain understudied in investigations of affective processes. In this methodological note, we establish the validity of using noninvasive commercially available equipment to record cardiac physiology and compute indices of autonomic nervous system activity -a major component of affective processes. Specifically, we recorded electrocardiogram and impedance cardiogram, from which we derived heart rate, respiration rate, measures of high-frequency heart rate variability (indices of parasympathetic autonomic nervous system activity), and ventricular contractility (an index of sympathetic autonomic nervous system activity). Our methods produced physiologically plausible data, and further, animals with increased heart rates during testing were also more reactive to isolation from their social partner and presentation of novel objects, though no relationship was observed between reactivity and specific indices of parasympathetic or sympathetic nervous system activity. K E Y W O R D S affect, autonomic nervous system, heart rate variability, respiratory sinus arrhythmia, ventricular contractility Ashley M. Murphy

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Lesions of Ventrolateral Prefrontal or Anterior Orbitofrontal Cortex in Primates Heighten Negative Emotion

Cited by 82 publications

References 45 publications

Regional inactivations of primate ventral prefrontal cortex reveal two distinct mechanisms underlying negative bias in decision making

Regional inactivations of primate ventral prefrontal cortex reveal two distinct mechanisms underlying negative bias in decision making

Targeting the Modulation of Neural Circuitry for the Treatment of Anxiety Disorders

Noninvasive cardiac psychophysiology as a tool for translational science with marmosets

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