Recruitment of orbitofrontal cortex during unpredictable threat among adults at risk for affective disorders

Kirlić, Namik; Aupperle, Robin L.; Misaki, Masaya; Kuplicki, Rayus; Alvarez, Ruben P.

doi:10.1002/brb3.757

Cited by 11 publications

(6 citation statements)

References 55 publications

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“…Human functional magnetic resonance imaging (fMRI) studies have reported BNST activation to uncertain threat anticipation [27][28][29][30][31][32] , yet evidence that the BNST encodes subjective anticipatory experience remains controversial. Previous fMRI studies comparing conditions of uncertain threat versus safe anticipation (overview see 33 ) have revealed increased activity in a broad range of brain regions such as BNST 30,31,34,35 , amygdala [36][37][38] , periaqueductal gray (PAG) 29,34,39 , anterior insula (aINS) [27][28][29]40,41 , anterior cingulate cortex (ACC) 28,29,40,42,43 and lateral and medial frontal regions 41,[44][45][46] . However, the comparison does not allow to specifically isolate the subjective feeling of uncertain threat anticipation given that the conditions may differ in several other mental processes (e.g., defensive responses or arousal), and the identified regions are involved in fundamental cognitive processes including salience or arousal 13 .…”

Section: Introductionmentioning

confidence: 99%

A neural signature for the subjective experience of threat anticipation under uncertainty

Liu,

Jiao,

Zhou

et al. 2023

Preprint

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Uncertainty about potential future threats and the associated anxious anticipation represents a key feature of anxiety. However, the neural systems that underlie the subjective experience of threat anticipation under uncertainty remain unclear. Combining a novel uncertain shock anticipation paradigm that allows precise modulation of the level of momentary anxious arousal during functional magnetic resonance imaging (fMRI) with multivariate predictive modeling, we trained a brain model that accurately predicted the intensity of subjective experience of anxious arousal on the population and individual level. In a series of analyses utilizing available fMRI datasets, we further demonstrate that the signature specifically predicted anxious anticipation and was not sensitive in predicting pain, general anticipation or unspecific arousal. The signature was functionally and spatially distinguishable from representations of subjective fear or negative affect. We developed a sensitive, generalizable, and specific neuromarker for subjective anxious arousal experienced during uncertain threat anticipation that can facilitate model development and clinical translation.

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Section: Introductionmentioning

confidence: 99%

A neural signature for the subjective experience of threat anticipation under uncertainty

Liu,

Jiao,

Zhou

et al. 2023

Preprint

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“…The OFC chiefly influences purposeful actions via the rewarding aspects of reinforcers and correlates with subjective emotional experiences; when OFC is impaired, patients use the inability to perceive changes in physical state as a warning cue to control unwanted behavior, while ceasing to perform in response to incentive or punishment predictions and reducing purposeful actions ( Rudebeck and Rich, 2018 ; Rolls, 2019 ). Abnormalities within the OFC are observed in a range of mental diseases, such as bipolar condition ( Ferguson and Gao, 2018 ), depression ( Lai, 2021 ), anxiety conditions ( Kirlic et al, 2017 ), obsessive-compulsive syndrome ( Nakao et al, 2014 ), social interaction problems ( Evans et al, 2004 ), and conditions involving drug misuse Stoeckel et al (2015) demonstrated a correlation between the OFC and the habituation of breathlessness perception in asthma patients. Herigstad et al (2017) also found that the OFC played a part in the heightened sensitivity of dyspnea in patients with COPD who were participating in breathing therapy.…”

Section: Discussionmentioning

confidence: 99%

Investigation of altered spontaneous brain activity in patients with bronchial asthma using the percent amplitude of fluctuation method: a resting-state functional MRI study

Wang,

Huang,

Dai

et al. 2023

Front. Hum. Neurosci.

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PurposeTo explore the regions of aberrant spontaneous brain activity in asthma patients and their potential impacts using the Percent amplitude of fluctuation (PerAF) analysis method.Patients and methodsIn this study, a total of 31 bronchial asthma (BA) patients were ultimately included, comprising 17 males and 14 females. Subsequently, 31 healthy control subjects (HCS) were recruited, consisting of 17 males and 14 females, and they were matched with the BA group based on age, sex, and educational status. The PerAF analysis technique was employed to study the differences in spontaneous brain activity between the two groups. The SPM12 toolkit was used to carry out a two sample t-test on the collected fMRI data, in order to examine the differences in PerAF values between the asthma patients and the healthy controls. We employed the Montreal Cognitive Assessment (MoCA) scale and the Hamilton Depression Scale (HAMD) to evaluate the cognitive and emotional states of the two groups. Pearson correlation analysis was utilized to ascertain the relationship between changes in the PerAF values within specific brain regions and cognitive as well as emotional conditions.ResultsCompared with the healthy control group, areas of the brain with reduced PerAF in asthma patients included the inferior cerebellum, fusiform gyrus, right inferior orbital frontal gyrus, left middle orbital frontal gyrus, left/right middle frontal gyrus (MFG), dorsal lateral superior frontal gyrus (SFGdl), left superior temporal gyrus (STG), precuneus, right inferior parietal lobule (IPL), and left/right angular gyrus. BA patients exhibit mild cognitive impairments and a propensity for emotional disturbances. Furthermore, the perAF values of the SFGdl region are significantly positively correlated with the results of the MoCA cognitive assessment, while negatively correlated with the HAMD evaluation.ConclusionThrough the application of PerAF analysis methods, we discovered that several brain regions in asthma patients that control the amplitude of respiration, vision, memory, language, attention, and emotional control display abnormal changes in intrinsic brain activity. This helps characterize the neural mechanisms behind cognitive, sensory, and motor function impairments in asthma patients, providing valuable insights for potential therapeutic targets and disease management strategies.

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“…An example for such an anxiety-induction procedure is the threat of shock paradigm, which induces sustained anxiety by informing participants that they will receive unpleasant electrical stimuli during the experiment (e.g., 64 – 68 ). For example, Kirlic, et al (2017) 69 demonstrated that participants with high risk for affective disorder display less exploratory behavior in response to a threat of shock. Using this paradigm in the OFT would offer the possibility to investigate the effects of state anxiety on thigmotaxis as a defensive behavior.…”

Section: Discussionmentioning

confidence: 99%

Thigmotaxis in a virtual human open field test

Gromer

Kiser

Pauli

2021

Sci Rep

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Animal models are used to study neurobiological mechanisms in mental disorders. Although there has been significant progress in the understanding of neurobiological underpinnings of threat-related behaviors and anxiety, little progress was made with regard to new or improved treatments for mental disorders. A possible reason for this lack of success is the unknown predictive and cross-species translational validity of animal models used in preclinical studies. Re-translational approaches, therefore, seek to establish cross-species translational validity by identifying behavioral operations shared across species. To this end, we implemented a human open field test in virtual reality and measured behavioral indices derived from animal studies in three experiments ($$\textit{N}=31$$ N = 31 , $$\textit{N}=30$$ N = 30 , and $$\textit{N}=80$$ N = 80 ). In addition, we investigated the associations between anxious traits and such behaviors. Results indicated a strong similarity in behavior across species, i.e., participants in our study—like rodents in animal studies—preferred to stay in the outer region of the open field, as indexed by multiple behavioral parameters. However, correlational analyses did not clearly indicate that these behaviors were a function of anxious traits of participants. We conclude that the realized virtual open field test is able to elicit thigmotaxis and thus demonstrates cross-species validity of this aspect of the test. Modulatory effects of anxiety on human open field behavior should be examined further by incorporating possible threats in the virtual scenario and/or by examining participants with higher anxiety levels or anxiety disorder patients.

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Recruitment of orbitofrontal cortex during unpredictable threat among adults at risk for affective disorders

Abstract: Background: Mood and anxiety disorders are characterized by altered prefrontal-

Cited by 11 publications

References 55 publications

A neural signature for the subjective experience of threat anticipation under uncertainty

A neural signature for the subjective experience of threat anticipation under uncertainty

Investigation of altered spontaneous brain activity in patients with bronchial asthma using the percent amplitude of fluctuation method: a resting-state functional MRI study

Thigmotaxis in a virtual human open field test

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