The sentient self

Ad, Craig

doi:10.1007/s00429-010-0248-y

Cited by 555 publications

(450 citation statements)

References 124 publications

(129 reference statements)

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“…We observed alterations in functional connectivity between the placebo and MDMA condition in many clusters overlapping with the HarvardOxford Atlas (Supplementary Information S1), notably including the right insular cortex (Figure 2a). All further analyses used the insula cluster revealed by the ICC as a seed ROI because it was selected by a prior application of the ICC (Martuzzi et al, 2011), decreased right insular connectivity was strikingly absent from previous fMRI analyses applied to this data set (Carhart-Harris et al, 2015;Roseman et al, 2014), and the insula plays a crucial role in both subjective feelings of the body (Craig, 2002;2009;2010;Critchley et al, 2004) and anxiety (Alvarez et al, 2015;Grupe and Nitschke, 2013;Paulus and Stein, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…Seeley et al, 2007, have previously demonstrated increased connectivity in the salience network (dACC and dorsolateral prefrontal cortex) in association with pre-scan anxiety, interpreted as evidence of trait anxiety coded to some degree in the functional architecture of the salience network (2007). Furthermore, alterations in insular functional connectivity following MDMA administration have never been explored despite converging evidence implicating a functional network anchored in the insula in subjective feelings of the body (Craig, 2002;2003;2009;2010; and anxiety (Alvarez et al, 2015;Grupe and Nitschke, 2013;Paulus and Stein, 2006;Seeley et al, 2007). As such, we endeavored to investigate how differences in right insula functional connectivity under MDMA (compared with placebo) might be related to individual differences in trait anxiety.…”

Section: Discussionmentioning

confidence: 99%

“…A right insula cluster (Figure 2a; MNI coordinates +46, +04, +02) was selected from this list as a seed ROI for all subsequent analyses as it allowed us to closely follow a prior application of this method (Martuzzi et al, 2011). Furthermore, alterations in insular functional connectivity following MDMA administration have never been explored despite converging evidence implicating a functional network anchored in the insula in subjective feelings of the body Craig, 2002Craig, , 2003Craig, , 2009Craig, , 2010Craig, , 2011 and anxiety (Alvarez et al, 2015;Grupe and Nitschke, 2013;Paulus and Stein, 2006;Seeley et al, 2007). Therefore, there was a firm rationale for selecting this particular region for subsequent seed-based analyses.…”

Section: Intrinsic Connectivity Contrastmentioning

confidence: 99%

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Altered Insula Connectivity under MDMA

Walpola

Nest

Roseman

et al. 2017

Neuropsychopharmacol

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Recent work with noninvasive human brain imaging has started to investigate the effects of 3,4-methylenedioxymethamphetamine (MDMA) on large-scale patterns of brain activity. MDMA, a potent monoamine-releaser with particularly pronounced serotonin-releasing properties, has unique subjective effects that include: marked positive mood, pleasant/unusual bodily sensations and pro-social, empathic feelings. However, the neurobiological basis for these effects is not properly understood, and the present analysis sought to address this knowledge gap. To do this, we administered MDMA-HCl (100 mg p.o.) and, separately, placebo (ascorbic acid) in a randomized, doubleblind, repeated-measures design with twenty-five healthy volunteers undergoing fMRI scanning. We then employed a measure of global resting-state functional brain connectivity and follow-up seed-to-voxel analysis to the fMRI data we acquired. Results revealed decreased right insula/salience network functional connectivity under MDMA. Furthermore, these decreases in right insula/salience network connectivity correlated with baseline trait anxiety and acute experiences of altered bodily sensations under MDMA. The present findings highlight insular disintegration (ie, compromised salience network membership) as a neurobiological signature of the MDMA experience, and relate this brain effect to trait anxiety and acutely altered bodily sensations-both of which are known to be associated with insular functioning.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Intrinsic Connectivity Contrastmentioning

confidence: 99%

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Altered Insula Connectivity under MDMA

Walpola

Nest

Roseman

et al. 2017

Neuropsychopharmacol

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“…Projections from anterior insular cortex to ventral striato-pallidum and extended amygdala are thought to contribute to learned-and motivation-driven behaviors, especially those requiring emotional processing (28,29). Human imaging studies suggest that the anterior insula provides a rich interoceptive foundation within which emotionally salient activity from forebrain regions, including the orbitofrontal, dorsolateral prefrontal, and anterior cingulate cortices may be integrated (27).…”

Section: Discussionmentioning

confidence: 99%

Dorsolateral caudate nucleus differentiates cocaine from natural reward-associated contextual cues

Liu

Chefer

et al. 2013

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

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Chronic drug administration induces neuroplastic changes within brain circuits regulating cognitive control and/or emotions. Following repeated pairings between drug intake and environmental cues, increased sensitivity to or salience of these contextual cues provoke conscious or unconscious craving and enhance susceptibility to relapse. To explore brain circuits participating in such experienceinduced plasticity, we combined functional MRI with a preclinical drug vs. food self-administration (SA) withdrawal model. Specifically, two groups of rats were trained to associate odor cues with the availability of i.v. cocaine or oral sucrose, respectively. After 20 d of cocaine or sucrose SA followed by prolonged (30 d) forced abstinence, animals were presented with odor cues previously associated with or without (S+/S−) reinforcer (cocaine/sucrose) availability while undergoing functional MRI scans. ANOVA results demonstrate that a learning effect distinguishing S+ from S− was seen in the insula and nucleus accumbens, with the insula response reflecting the individual history of cocaine SA intake. A main effect of group, distinguishing cocaine from sucrose, was seen in the medial prefrontal cortex (infralimbic, prelimbic, and cingulate cortex) and dorsolateral striatum. Critically, only the dorsomedial striatum demonstrated a double dissociation between the two SA groups and learning (S+ vs. S−). These findings demonstrate altered cortico-limbic-striatal reward-related processing to learned, environment reward-associated contextual odor cues, which may serve as potential biomarkers for therapeutic interventions.context cues | neuroplasticity | drug addiction P reventing or reducing the incidence of relapse remains the major challenge for the treatment of addiction, as recidivism rates can range as high as 90%. Both preclinical (1) and human addiction studies (2) have demonstrated that following repeated pairings with drug administration, various contextual and environmental stimuli when subsequently presented alone can elicit drug-seeking and drug-taking behaviors. Further, dysregulation within specific brain circuits regulating cognitive control and/or emotional regulation (3) can amplify the perceived salience of environmental contexts and cues that provoke craving (4) and thereby enhance susceptibility to relapse (2). These observations speak to the important role of reward learning in addictive processes (5). As such, it is critical to better understand the neural mechanisms and circuitry underlying the retrieval of cue-induced memories as an important intermediary in developing more efficacious interventions to decrease recidivism.The amygdala, nucleus accumbens (NAc), and various prefrontal cortical regions respond to drug-associated cues in human cocaine addicts (6, 7). Supporting their critical roles in the neural circuitry of drug-seeking behavior, these regions have also been identified using preclinical reinstatement models (8, 9). For example, NAc neurons exhibit conditioned responses to drugassociated env...

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“…Recent work suggests that the anterior insula is involved in awareness (Ploran et al 2007;Nelson et al 2010;Craig 2010). This connection with awareness was initially suggested in an fMRI experiment by Kikyo and Ohki (2002) in which they observed activity in anterior insula when subjects reported the subjective sense of knowing a word before recalling it in a memory task, which these authors called the ''feeling of knowing''.…”

Section: Introductionmentioning

confidence: 99%

The von Economo neurons in frontoinsular and anterior cingulate cortex in great apes and humans

et al. 2010

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The von Economo neurons (VENs) are large bipolar neurons located in frontoinsular (FI) and anterior cingulate cortex in great apes and humans, but not other primates. We performed stereological counts of the VENs in FI and LA (limbic anterior, a component of anterior cingulate cortex) in great apes and in humans. The VENs are more numerous in humans than in apes, although one gorilla approached the lower end of the human range. We also examined the ontological development of the VENs in FI and LA in humans. The VENs first appear in small numbers in the 36th week post-conception, are rare at birth, and increase in number during the first 8 months after birth. There are significantly more VENs in the right hemisphere than in the left in FI and LA in postnatal brains of apes and humans. This asymmetry in VEN numbers may be related to asymmetries in the autonomic nervous system. The activity of the inferior anterior insula, which contains FI, is related to physiological changes in the body, decisionmaking, error recognition, and awareness. The VENs appear to be projection neurons, although their targets are unknown. We made a preliminary study of the connections of FI cortex based on diffusion tensor imaging in the brain of a gorilla. The VEN-containing regions connect to the frontal pole as well as to other parts of frontal and insular cortex, the septum, and the amygdala. It is likely that the VENs in FI are projecting to some or all of these structures and relaying information related to autonomic control, decision-making, or awareness. The VENs selectively express the bombesin peptides neuromedin B (NMB) and gastrin releasing peptide (GRP) which are also expressed in another population of closely related neurons, the fork cells. NMB and GRP signal satiety. The genes for NMB and GRP are expressed selectively in small populations of neurons in the insular cortex in mice. These populations may be related to the VEN and fork cells and may be involved in the regulation of appetite. The loss of these cells may be related to the loss of satiety signaling in patients with frontotemporal dementia who have damage to FI. The VENs and fork cells may be morphological specializations of an ancient population of neurons involved in the control of appetite present in the insular cortex in all mammals. We found that the protein encoded by the gene DISC1 (disrupted in schizophrenia) is preferentially expressed by the VENs. DISC1 has undergone rapid evolutionary change in the line leading to humans, and since it suppresses dendritic branching it may be involved in the distinctive VEN morphology.

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The sentient self

Cited by 555 publications

References 124 publications

Altered Insula Connectivity under MDMA

Altered Insula Connectivity under MDMA

Dorsolateral caudate nucleus differentiates cocaine from natural reward-associated contextual cues

The von Economo neurons in frontoinsular and anterior cingulate cortex in great apes and humans

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