The Insular Cortex Dynamically Maps Changes in Cardiorespiratory Interoception

Hassanpour, Mahlega S.; Simmons, W. Kyle; Feinstein, Justin S.; Luo, Qing; Lapidus, Rachel C.; Bodurka, Jerzy; Paulus, Martin P.; Khalsa, Sahib S.

doi:10.1038/npp.2017.154

Cited by 98 publications

(94 citation statements)

References 49 publications

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“…Taken together, increased DLPFC and MOFC response to high-conflict trials in the emotional conflict Stroop at 1 week post-psilocybin task may reflect greater top-down control of emotionally conflicting information and IFG has been implicated in supporting a domain-general interference resolution process 69 . Activity in the anterior insula is understood to contribute to interoceptive mapping 70 , and both IFG and insula may be involved in the appraisal of social emotional stimuli 71 . The fusiform gyrus contains a number of functionally-defined sub-regions dedicated to stimulus-specific object recognition [72][73][74] , with specialized regions that respond to facial stimuli 75,76 .…”

Section: Discussionmentioning

confidence: 99%

Emotions and brain function are altered up to one month after a single high dose of psilocybin

Barrett

Doss

Sepeda

et al. 2020

Sci Rep

255

218

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Psilocybin is a classic psychedelic compound that may have efficacy for the treatment of mood and substance use disorders. Acute psilocybin effects include reduced negative mood, increased positive mood, and reduced amygdala response to negative affective stimuli. However, no study has investigated the long-term, enduring impact of psilocybin on negative affect and associated brain function. Twelve healthy volunteers (7F/5M) completed an open-label pilot study including assessments 1-day before, 1-week after, and 1-month after receiving a 25 mg/70 kg dose of psilocybin to test the hypothesis that psilocybin administration leads to enduring changes in affect and neural correlates of affect. One-week post-psilocybin, negative affect and amygdala response to facial affect stimuli were reduced, whereas positive affect and dorsal lateral prefrontal and medial orbitofrontal cortex responses to emotionally-conflicting stimuli were increased. One-month post-psilocybin, negative affective and amygdala response to facial affect stimuli returned to baseline levels while positive affect remained elevated, and trait anxiety was reduced. Finally, the number of significant resting-state functional connections across the brain increased from baseline to 1-week and 1-month post-psilocybin. These preliminary findings suggest that psilocybin may increase emotional and brain plasticity, and the reported findings support the hypothesis that negative affect may be a therapeutic target for psilocybin. Studies suggest that psilocybin, a classic psychedelic drug (serotonin 2A or 5-HT 2A receptor partial agonist), may have efficacy for the treatment of depression and anxiety 1-3 , tobacco use disorder 4,5 , and alcohol use disorder 6,7. Reduction of clinical symptoms has been shown to last up to 3 3 , 6 1,2 , and 12 8 months after 1 to 3 psilocybin administrations. Despite these promising advances, the neural and psychological mechanisms underlying the enduring therapeutic effects of psychedelic drugs are not well-understood. Two possibly interactive trans-diagnostic targets that may be affected by psilocybin are negative affect and brain network plasticity. Increased negative affect, reduced positive affect, and hypersensitivity to negatively biased information are hallmarks of mood disorders 9-11. Negative affect is also a core component of the cycle of addiction in which craving and withdrawal symptoms experienced after intoxication lead to preoccupation, anticipation, and re-administration of drugs of abuse 12. The amygdala has been shown in clinical and preclinical models to track the salience of stimuli in the environment 13,14 and is highly responsive to negative emotional stimuli 15-17. Abnormally high amygdala reactivity to negative affective stimuli has been implicated in the pathophysiology of depression 18. Areas within the anterior cingulate cortex (ACC) are understood to monitor cognitive conflict 19-22 , are involved in the appraisal and expression of negative emotion 22 , respond to distress levels associated with pain 23 ...

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Section: Discussionmentioning

confidence: 99%

Emotions and brain function are altered up to one month after a single high dose of psilocybin

Barrett

Doss

Sepeda

et al. 2020

Sci Rep

255

218

View full text Add to dashboard Cite

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“…It has recently been shown that a discrete population of neurons in the posterior IC responded to both electric footshocks and tone during threat learning and the 24-h memory test (Berret et al, 2019). Also, imaging studies have shown that changes in the cardiorespiratory state are represented in the insula (Hassanpour et al, 2017), fear processing is modulated by cardiac activity (Garfinkel et al, 2014), and human fear-related disorders such as anxiety are associated with altered interoceptive processing in the insular cortex (Paulus and Stein, 2010;Simmons et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Interoceptive Insular Cortex Mediates Both Innate Fear and Contextual Threat Conditioning to Predator Odor

Rodríguez

Cerić

Murgas

et al. 2020

Front. Behav. Neurosci.

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The insular cortex (IC), among other brain regions, becomes active when humans experience fear or anxiety. However, few experimental studies in rats have implicated the IC in threat responses. We have recently reported that inactivation of the primary interoceptive cortex (pIC) during pre-training, or the intra-pIC blockade of protein synthesis immediately after training, impaired the consolidation of auditory fear conditioning. The present study was designed to investigate the role of the pIC in innate and learned defensive responses to predator odor. Freezing behavior was elicited by single or repetitive exposures to a collar that had been worn by a domestic cat. Sessions were video-recorded and later scored by video observation. We found that muscimol inactivation of the pIC reduced the expression of freezing reaction in response to a single or repeated exposure to cat odor. We also found that pIC inactivation with muscimol impaired conditioning of fear to the context in which rats were exposed to cat odor. Furthermore, neosaxitoxin inactivation of the pIC resulted in a prolonged and robust reduction in freezing response in subsequent re-exposures to cat odor. In addition, freezing behavior significantly correlated with the neural activity of the IC. The present results suggest that the IC is involved in the expression of both innate and learned fear responses to predator odor.

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“…The prelimbic and ventral orbital regions of PFC, where we observed the greatest OxA-elicited neuronal activation, have been implicated in attentional shifting and reversal learning, respectively (Dalley et al 2004). We also observed robust activation in the agranular insular cortex, part of an area described as putative 'interoceptive cortex' because of its role in sensing the organism's physiological status (Craig and Craig 2002;Avery et al 2017;Hassanpour et al 2017). Given the role of orexin neurons in responding to peripheral cues indicative of physiological status, intranasal OxA may facilitate interoceptive processing within the insular region.…”

Section: Effects Of Intranasal Oxa On C-fos Expressionmentioning

confidence: 52%

“…; Hassanpour et al . ). Given the role of orexin neurons in responding to peripheral cues indicative of physiological status, intranasal OxA may facilitate interoceptive processing within the insular region.…”

Section: Discussionmentioning

confidence: 97%

Increased acetylcholine and glutamate efflux in the prefrontal cortex following intranasal orexin‐A (hypocretin‐1)

Calva

Fayyaz

Fadel

2018

Journal of Neurochemistry

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Orexin/hypocretin neurons of the lateral hypothalamus and perifornical area are integrators of physiological function. Previous work from our laboratory and others has shown the importance of orexin transmission in cognition. Age-related reductions in markers of orexin function further suggest that this neuropeptide may be a useful target for the treatment of age-related cognitive dysfunction. Intranasal administration of orexin-A (OxA) has shown promise as a therapeutic option for cognitive dysfunction. However, the neurochemical mechanisms of intranasal OxA administration are not fully understood. Here, we use immunohistochemistry and in vivo microdialysis to define the effects of acute intranasal OxA administration on: (i) activation of neuronal populations in the cortex, basal forebrain, and brainstem and (ii) acetylcholine (ACh) and glutamate efflux in the prefrontal cortex (PFC) of Fischer 344/Brown Norway F1 rats. Acute intranasal administration of OxA significantly increased c-Fos expression, a marker for neuronal activation, in the PFC and in subpopulations of basal forebrain cholinergic neurons. Subsequently, we investigated the effects of acute intranasal OxA on neurotransmitter efflux in the PFC and found that intranasal OxA significantly increased both ACh and glutamate efflux in this region. These findings were independent from any changes in c-Fos expression in orexin neurons, suggesting that these effects are not resultant from direct activation of orexin neurons. In total, these data indicate that intranasal OxA may enhance cognition through activation of distinct neuronal populations in the cortex and basal forebrain and through increased neurotransmission of ACh and glutamate in the PFC.

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The Insular Cortex Dynamically Maps Changes in Cardiorespiratory Interoception

Cited by 98 publications

References 49 publications

Emotions and brain function are altered up to one month after a single high dose of psilocybin

Emotions and brain function are altered up to one month after a single high dose of psilocybin

Interoceptive Insular Cortex Mediates Both Innate Fear and Contextual Threat Conditioning to Predator Odor

Increased acetylcholine and glutamate efflux in the prefrontal cortex following intranasal orexin‐A (hypocretin‐1)

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