The hidden island of addiction: the insula
Open accessAbstract
Most prior research on the neurobiology of addiction has focused on the role of subcortical systems, such as the amygdala, the ventral striatum and mesolimbic dopamine system, in promoting the motivation to seek drugs. Recent evidence indicates that a largely overlooked structure, the insula, plays a crucial part in conscious urges to take drugs. The insula has been highlighted as a region that integrates interoceptive (i.e. bodily) states into conscious feelings and into decision-making processes that involve uncertain risk and reward. Here, we propose a model in which the processing of the interoceptive effects of drug use by the insula contributes to conscious drug urges and to decision-making processes that precipitate relapse.
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Imaging studies report differential activation of the insula during craving, possibly reflecting interoceptive cues and hypothesised to involve CRF activation.
“Consistent with this hypothesis, imaging studies have reported differential activation of the insula during craving, possibly reflecting interoceptive cues and hypothesised to involve CRF activation (table 2, circuit 18).54,117,118”
From Neurobiology of addiction: a neurocircuitry analysis (2016) · cites this paper as [54]
The Evidence for the role of the insula in addiction section reports imaging activation of the insula during drug urges, and the Proposed role section links those urges to interoceptive representations. The Anatomy and function section notes CRF receptors in the insula and a possible role in stress-related motivation to take drugs, but it does not link the reported imaging activation during craving to CRF activation. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe insula has long been implicated in drug cravings, the maintenance of drug-seeking behavior, and the regulation of distress during withdrawal.
“The insula has long been implicated in drug cravings, the maintenance of drug-seeking behavior, and the regulation of distress during withdrawal [1,6,71].”
From The Insular Cortex: An Interface Between Sensation, Emotion and Cognition (2024) · cites this paper as [6]
The 'Evidence for the role of the insula in addiction' section links insula activity to drug urges and relapse or continued use. The 'Proposed role for the insula in addiction' section suggests that the insula might translate withdrawal-related bodily signals into dysphoria, but does not establish that it regulates distress during withdrawal. (LLM, conf=0.84)
Experimental — accuracy not yet measuredDysfunction of interoception is increasingly recognized as an important component of anxiety disorders, mood disorders, eating disorders, addictive disorders, and somatic symptom disorders.
“Dysfunction of interoception is increasingly recognized as an important component of different mental health conditions, including anxiety disorders, mood disorders, eating disorders, addictive disorders, and somatic symptom disorders.”
From Interoception and Mental Health: A Roadmap. (2018) · cites this paper as [102]
The sections on interoception and addiction link interoceptive processes and insula dysfunction to drug addiction. The paper does not establish dysfunctional interoception as an important component of anxiety, mood, eating, or somatic symptom disorders; its discussion of fear, sadness, and hunger concerns experiences, not those diagnoses. Page numbers are not available in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredDrug addiction is marked by interoceptive disturbances, with overlapping neural circuitry and abnormal responses to interoceptive cues.
“Drug addiction, another condition marked by interoceptive disturbances, has an overlapping neural circuitry and abnormal responses to interoceptive cues (101–104).”
From Interoception and Mental Health: A Roadmap. (2018) · cites this paper as [102]
In “Proposed role for the insula in addiction” (page unavailable), the paper describes a hypothesized shift in how drug-related bodily sensations are valued and links interoceptive effects to the insula and related regions. This supports altered responses to interoceptive signals in addiction, but the paper presents much of the mechanism as a model rather than an established finding and does not establish neural-circuit overlap with another condition. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThe insula appears to have an interoceptive function integrating autonomic and visceral information with emotion and motivation, providing conscious awareness of urges.
“The insula appears to have an interoceptive function that integrates autonomic and visceral information with emotion and motivation, thus providing conscious awareness of these urges.54”
From Neurobiology of addiction: a neurocircuitry analysis (2016) · cites this paper as [54]
The AI, dACC and dlPFC activate synchronously in response to uncertainty in the environment, and these regions overlap with areas implicated in negative mood states.
“For one, the AI, dACC and dlPFC activate synchronously in response to uncertainty in the environment; these regions overlap with areas implicated in negative mood states (Feinstein et al., 2006; Naqvi and Bechara, 2009; Davis and Hasson, 2016).”
From Cortico-striatal-thalamic loop circuits of the salience network: A central pathway in psychiatric disease and treatment (2016) · cites this paper as Naqvi and Bechara, 2009
The anterior insula has been associated with depression, anxiety or substance abuse.
“It has also been associated with depression, anxiety or substance abuse (for reviews cf. Craig, 2009; Naqvi and Bechara, 2009).”
From Cognitive flexibility in adolescence: Neural and behavioral mechanisms of reward prediction error processing in adaptive decision making during development (2015) · cites this paper as Naqvi and Bechara, 2009
The insula, particularly its anterior regions, is reciprocally connected to several limbic regions including ventromedial prefrontal cortex, amygdala, and ventral striatum.
“The insula, particularly its more anterior regions, is reciprocally connected to several limbic regions (e.g. ventromedial prefrontal cortex, amygdala, and ventral striatum) and appears to have an interoceptive function, integrating the autonomic and visceral information with emotion and motivation, thus providing conscious awareness of these urges (135).”
From Obesity and addiction: Neurobiological overlaps (2013) · cites this paper as [135]
The insula appears to have an interoceptive function, integrating autonomic and visceral information with emotion and motivation, thus providing conscious awareness of urges.
“The insula, particularly its more anterior regions, is reciprocally connected to several limbic regions (e.g. ventromedial prefrontal cortex, amygdala, and ventral striatum) and appears to have an interoceptive function, integrating the autonomic and visceral information with emotion and motivation, thus providing conscious awareness of these urges (135).”
From Obesity and addiction: Neurobiological overlaps (2013) · cites this paper as [135]
Many imaging studies show differential activation of the insula during craving.
“Consistent with this hypothesis, many imaging studies show differential activation of the insula during craving (135).”
From Obesity and addiction: Neurobiological overlaps (2013) · cites this paper as [135]
Many imaging studies show differential activation of the insula during craving.
“Consistent with this hypothesis, many imaging studies show differential activation of the insula during craving (95).”
From The Addictive Dimensionality of Obesity (2013) · cites this paper as [95]
The insula, especially anterior regions, is reciprocally connected to limbic regions and supports interoceptive functions, integrating autonomic/visceral information with emotion and motivation and providing conscious awareness of urges.
“The insula, particularly its more anterior regions, is reciprocally connected to several limbic regions and supports interoceptive functions, integrating the autonomic and visceral information with emotion and motivation and providing conscious awareness of these urges (95).”
From The Addictive Dimensionality of Obesity (2013) · cites this paper as [95]
Many imaging studies show differential activation in the insula during craving.
“Consistent with this hypothesis, many imaging studies show differential activation in the insula during craving (Naqvi and Bechara 2009).”
From Food and Drug Reward: Overlapping Circuits in Human Obesity and Addiction (2011) · cites this paper as Naqvi and Bechara 2009
The insula, particularly its more anterior regions, is reciprocally connected to several limbic regions and appears to have an interoceptive function, integrating autonomic and visceral information with emotion and motivation, thus providing conscious awareness of urges.
“The insula, particularly its more anterior regions, is reciprocally connected to several limbic regions (e.g., ventromedial prefrontal cortex, amygdala, and ventral striatum) and appears to have an interoceptive function, integrating the autonomic and visceral information with emotion and motivation, thus providing conscious awareness of these urges (Naqvi and Bechara 2009).”
From Food and Drug Reward: Overlapping Circuits in Human Obesity and Addiction (2011) · cites this paper as Naqvi and Bechara 2009
The insula integrates emotional information to and from limbic and cortical areas and is involved in the representation of interoceptive responses to emotionally salient and rewarding stimuli, such as drug craving, urgency, and impulsivity.
“Moreover, the insula integrates emotional information to and from limbic and cortical areas and is involved in the representation of interoceptive responses to emotionally salient and rewarding stimuli, such as drug craving, urgency, and impulsivity (Bonson et al., 2002; Naqvi and Bechara, 2009; Villafuerte et al., 2011).”
From The effects of poor quality sleep on brain function and risk taking in adolescence (2013) · cites this paper as Naqvi and Bechara, 2009
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- [92]Everitt BJ 1999 Associative processes in addiction and reward: the role of amygdala and ventral striatal subsystems Ann N Y Acad Sci 877 412 438 10415662
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Koob, G. F., & Volkow, N. D. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2009.110 · Cited by 5,340 · see citing works
“Our understanding of the neurobiological substrates for the reinforcing effects of drugs of abuse can be traced to early work on the identification of a reward system in the brain with the discovery of electrical brain stimulation reward or intracranial self-stimulation by Olds and Milner (1954). Brain stimulation rew…”
BackgroundResultInfluentialLarge-scale brain networks and psychopathology: a unifying triple network model
Menon, V. (2011) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2011.08.003 · Cited by 4,168 · see citing works
Neurobiology of addiction: a neurocircuitry analysis
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“The anterior insula encodes the subjective value of rewards [97] and representations of interoceptive effects of rewards (reviewed in [98]).”
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Cognitive neuroscience of self-regulation failure
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The Neuroscience of Drug Reward and Addiction
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“The relevance of the insula to addiction first emerged with a seminal study that showed that smokers with insular lesions (due to stroke) were able to quit smoking with remarkable ease, without cravings or relapse (243).”
Gogolla, N. (2017) · Current Biology · doi:10.1016/j.cub.2017.05.010 · Cited by 851 · see citing works
Sescousse, G., Caldú, X., Segura, B., & Dreher, J.-C. (2013) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.02.002 · Cited by 782 · see citing works
“This situation enables the anterior insula to integrate autonomic and visceral information with emotional and motivational processes, in line with its proposed role in interoception (Naqvi and Bechara, 2009).”
InfluentialObesity and addiction: Neurobiological overlaps
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“ventromedial prefrontal cortex, amygdala, and ventral striatum) and appears to have an interoceptive function, integrating the autonomic and visceral information with emotion and motivation, thus providing conscious awareness of these urges (135).”
BackgroundResultReward mechanisms in obesity: new insights and future directions
Kenny, P. J. (2011) · Neuron · doi:10.1016/j.neuron.2011.02.016 · Cited by 748 · see citing works
“, prefrontal cortex) and in interoceptive processing (insular cortex) have been heavily implicated in drug addiction (Everitt et al., 2008; Fineberg et al., 2010; Koob and Volkow, 2010; Naqvi and Bechara, 2009), yet little is known of their precise role in compulsive eating and obesity, e.”
BackgroundPeters, S. K., Dunlop, K., & Downar, J. (2016) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2016.00104 · Cited by 611 · see citing works
“Functional abnormalities of single SN nodes have been related to SUD behaviors; the AI is considered critical to conscious drug-seeking motivation (Naqvi and Bechara, 2009).”
BackgroundNieuwenhuys, R. (2012) · Progress in Brain Research · doi:10.1016/b978-0-444-53860-4.00007-6 · Cited by 580 · see citing works
Mindfulness meditation training alters cortical representations of interoceptive attention
Farb, N. A. S., Segal, Z. V., & Anderson, A. K. (2013) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nss066 · Cited by 566 · see citing works
“, 2009) and maladaptive biases such as addiction (Naqvi and Bechara, 2009).”
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The changing opioid crisis: development, challenges and opportunities
Volkow, N. D., & Blanco, C. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-0661-4 · Cited by 564 · see citing works
Food and Drug Reward: Overlapping Circuits in Human Obesity and Addiction
Volkow, N. D., Wang, G. J., Fowler, J. S., Tomasi, D., & Baler, R. (2011) · Current Topics in Behavioral Neurosciences · doi:10.1007/7854_2011_169 · Cited by 525 · see citing works
“motivation, thus providing conscious awareness of these urges (Naqvi and Bechara 2009).”
BackgroundResultResting state functional connectivity in addiction: Lessons learned and a road ahead
Sutherland, M. T., McHugh, M. J., Pariyadath, V., & Stein, E. A. (2012) · NeuroImage · doi:10.1016/j.neuroimage.2012.01.117 · Cited by 495 · see citing works
“Multiple studies of cigarette-cue reactivity have noted positive associations between insula responses and subjective use-urges (Naqvi and Bechara, 2009).”
BackgroundInfluentialThe insula: an underestimated brain area in clinical neuroscience, psychiatry, and neurology
Namkung, H., Kim, S.-H., & Sawa, A. (2017) · Trends in Neurosciences · doi:10.1016/j.tins.2017.02.002 · Cited by 462 · see citing works
Nicotine addiction and nicotinic receptors: lessons from genetically modified mice
Changeux, J.-P. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2849 · Cited by 453 · see citing works
Internet and Gaming Addiction: A Systematic Literature Review of Neuroimaging Studies
Kuss, D. J., & Griffiths, M. D. (2012) · Brain Sciences · doi:10.3390/brainsci2030347 · Cited by 437 · see citing works
“Insula dysfunction may explain neurological activities indicative of relapse [60].”
BackgroundThe von Economo neurons in frontoinsular and anterior cingulate cortex in great apes and humans
Allman, J., Tetreault, N. A., Hakeem, A. Y., Manaye, K., Semendeferi, K., Erwin, J., Park, S. Q., Goubert, V., & Hof, P. (2010) · Brain Structure and Function · doi:10.1007/s00429-010-0254-0 · Cited by 429 · see citing works
“Disruption of this feedback could also underlie the recently recognized role of the insula in the feelings of craving associated with addiction to food or drugs (Naqvi and Bechara 2009).”
BackgroundA neurocognitive approach to understanding the neurobiology of addiction
Noël, X., Brevers, D., & Bechara, A. (2013) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2013.01.018 · Cited by 436 · see citing works
“The insula is viewed as a ‘gate’ system that responds to homeostatic perturbations [5], which in turn modulate activities of the dual systems [6].”
BackgroundSelf-citationJanes, A. C., Pizzagalli, D. A., Richardt, S., Frederick, B. D., Chuzi, S., Pachas, G., Culhane, M. A., Holmes, A. J., Fava, M., Evins, A. E., et al. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.12.034 · Cited by 416 · see citing works
“focus because it is reactive to smoking-related cues (19), may”
Contributions of the insula to cognition and emotion
Gasquoine, P. G. (2014) · Neuropsychology Review · doi:10.1007/s11065-014-9246-9 · Cited by 400 · see citing works
“Hyper - and Hypo - Neuroimaged Activity in the Insula Several functional neuroimaging studies have shown increased activity within the insula in either hemisphere during conscious urges to take drugs of all types ( see Naqvi and Bechara 2008 for review ) .”
BackgroundNeural substrates of smoking cue reactivity: A meta-analysis of fMRI studies
Engelmann, J. M., Versace, F., Robinson, J. D., Minnix, J. A., Lam, C. Y., Cui, Y., Brown, V. L., & Cinciripini, P. M. (2012) · NeuroImage · doi:10.1016/j.neuroimage.2011.12.024 · Cited by 394 · see citing works
“The insula has been shown to be important in interoception (Craig, 2002) and taste perception (Pritchard et al., 1999), and may thus be involved in perception of cue-evoked conditioned responses, resulting in a subjective craving for cigarettes (Naqvi & Bechara, 2009; Naqvi & Bechara, 2010).”
Alterations in brain structure and functional connectivity in prescription opioid-dependent patients
Upadhyay, J., Maleki, N., Potter, J. S., Elman, I., Rudrauf, D., Knudsen, J., Wallin, D. J., Pendse, G., McDonald, L., Griffin, M. L., et al. (2010) · Brain · doi:10.1093/brain/awq138 · Cited by 394 · see citing works
“The structure has been implicated in craving for multiple drugs of abuse (Naqvi et al., 2007; Naqvi and Bechara, 2009).”
BackgroundThe Addictive Dimensionality of Obesity
Volkow, N. D., Wang, G.-J., Tomasi, D., & Baler, R. D. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.12.020 · Cited by 380 · see citing works
“The insula, particularly its more anterior regions, is reciprocally connected to several limbic regions and supports interoceptive functions, integrating the autonomic and visceral information with emotion and motivation and providing conscious awareness of these urges (95).”
BackgroundResultA convergent functional architecture of the insula emerges across imaging modalities
Kelly, C., Toro, R., Di Martino, A., Cox, C. L., Bellec, P., Castellanos, F. X., & Milham, M. P. (2012) · NeuroImage · doi:10.1016/j.neuroimage.2012.03.021 · Cited by 374 · see citing works
“Given the implication of the insula across several clinical and psychiatric disorders, including autism and addiction (Di Martino et al., 2009a; Naqvi and Bechara, 2009), delineating these connectivity-based functional building blocks of the insula will inform investigations of the role of this…”
InfluentialBrain default-mode network dysfunction in addiction
Zhang, R., & Volkow, N. D. (2019) · NeuroImage · doi:10.1016/j.neuroimage.2019.06.036 · Cited by 365 · see citing works
The insula: a critical neural substrate for craving and drug seeking under conflict and risk
Naqvi, N. H., Gaznick, N., Tranel, D., & Bechara, A. (2014) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12415 · Cited by 336 · see citing works
Self-citationRevisiting the role of the insula in addiction
Droutman, V., Read, S. J., & Bechara, A. (2015) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2015.05.005 · Cited by 317 · see citing works
Self-citationChase, H. W., Eickhoff, S. B., Laird, A. R., & Hogarth, L. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.05.025 · Cited by 316 · see citing works
“Previous reviews (29,30) have treated activations of a given reion as a binary variable.”
InfluentialGray matter abnormalities in internet addiction: a voxel-based morphometry study
Zhou, Y., Lin, F.-C., Du, Y.-S., Qin, L.-D., Zhao, Z.-M., Xu, J.-R., & Lei, H. (2011) · European Journal of Radiology · doi:10.1016/j.ejrad.2009.10.025 · Cited by 301 · see citing works
Balodis, I. M., Kober, H., Worhunsky, P. D., Stevens, M. C., Pearlson, G. D., & Potenza, M. N. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.01.006 · Cited by 305 · see citing works
“Altogether, the role for the insula in signaling aversive value has led to the proposal of this area as an important therapeutic target in both PG and substance dependence (54,58).”
BackgroundHoudé, O., Rossi, S., Lubin, A., & Joliot, M. (2010) · Developmental Science · doi:10.1111/j.1467-7687.2009.00938.x · Cited by 306 · see citing works
Aversive state processing in the posterior insular cortex
Gehrlach, D. A., Dolensek, N., Klein, A. S., Roy Chowdhury, R., Matthys, A., Junghänel, M., Gaitanos, T. N., Podgornik, A., Black, T. D., Reddy Vaka, N., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0469-1 · Cited by 303 · see citing works
The effects of poor quality sleep on brain function and risk taking in adolescence
Telzer, E. H., Fuligni, A. J., Lieberman, M. D., & Galván, A. (2013) · NeuroImage · doi:10.1016/j.neuroimage.2013.01.025 · Cited by 296 · see citing works
“Moreover, the insula integrates emotional information to and from limbic and cortical areas and is involved in the representation of interoceptive responses to emotionally salient and rewarding stimuli, such as drug craving, urgency, and impulsivity (Bonson et al., 2002; Naqvi and Bechara, 2009; Villafuerte et al., 20…”
Cognitive control of drug craving inhibits brain reward regions in cocaine abusers
Volkow, N. D., Fowler, J. S., Wang, G.-J., Telang, F., Logan, J., Jayne, M., Ma, Y., Pradhan, K., Wong, C., & Swanson, J. M. (2010) · NeuroImage · doi:10.1016/j.neuroimage.2009.10.088 · Cited by 283 · see citing works
“…involved with salience attribution) (Hare et al., 2008) and right insula, (region involved with interoception including awareness of craving) (Naqvi and Bechara, 2009) with CI, suggests that both the alteration in salience to the cues and in interoceptive awareness were involved in the…”
BackgroundPotenza, M. N., Hong, K., Lacadie, C., Fulbright, R. K., Tuit, K. L., & Sinha, R. (2012) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2011.11020289 · Cited by 288 · see citing works
Ruíz, S., Lee, S., Soekadar, S. R., Carìa, A., Veit, R., Kircher, T. T. J., Birbaumer, N., & Sitaram, R. (2011) · Human Brain Mapping · doi:10.1002/hbm.21427 · Cited by 284 · see citing works
“VC 2011 Wiley Periodicals, Inc. Keywords: real-time fMRI; schizophrenia; insula; face emotion recognition; self-regulation; neurofeedback r r”
BackgroundFood Addiction in the Light of DSM-5
Meule, A., & Gearhardt, A. N. (2014) · Nutrients · doi:10.3390/nu6093653 · Cited by 277 · see citing works
“Similarly, activation patterns of neuronal structures underlying craving experiences largely overlap across different substances, including food [15,59–61].”
BackgroundNeural Basis of Video Gaming: A Systematic Review
Palaus, M., Marrón, E. M., Viejo-Sobera, R., & Redolar-Ripoll, E. (2017) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2017.00248 · Cited by 281 · see citing works
“Striatal volumes, particularly the ventral striatum, responsible for a key role in reward prediction, were reduced in people with excessive internet gaming compared to healthy controls (Hou et al., 2012 ∗ ) and in the insula, with its role in conscious urges to abuse drugs (Naqvi and Bechara, 2009).”
BackgroundReimann, M., Castaño, R., Zaichkowsky, J. L., & Bechara, A. (2011) · Journal of Consumer Psychology · doi:10.1016/j.jcps.2011.11.003 · Cited by 280 · see citing works
“Recently, Reimann and Aron (2009) suggested that these ideas of relationships may be relevant to consumers' close relationships with brands as people also form a similar type of relationship with objects (Belk, 1988).”
BackgroundSelf-citationThe role of interoception in addiction: A critical review
Verdejo‐García, A., Clark, L., & Dunn, B. D. (2012) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2012.05.007 · Cited by 270 · see citing works
Breese, G. R., Sinha, R., & Heilig, M. A. (2010) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2010.09.007 · Cited by 262 · see citing works
“This latter structure is of particular interest because it is reciprocally interconnected with the amygdala, encodes aversive interoceptive states, and has been implicated in mechanisms of craving and relapse (see review by Naqvi and Bechara, 2009).”
BackgroundThe impact of prior risk experiences on subsequent risky decision-making: The role of the insula
Xue, G., Lu, Z., Levin, I. P., & Bechara, A. (2010) · NeuroImage · doi:10.1016/j.neuroimage.2009.12.097 · Cited by 249 · see citing works
“Mounting evidence has suggested that the insula plays an important role in signaling the awareness of the urge for drug addictions (Naqvi and Bechara, 2009).”
InfluentialSelf-citationIdentifying Neurobiological Phenotypes Associated with Alcohol Use Disorder Severity
Claus, E. D., Ewing, S. W. F., Filbey, F. M., Sabbineni, A., & Hutchison, K. E. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2011.99 · Cited by 249 · see citing works
“The correlations of the insula with AUD severity measures suggests a potential increase in processing of interoceptive cues triggered by cue presentation (Bechara 2005; Critchley, 2005; Goldstein et al, 2009; Gray and Critchley, 2007; Lovero et al, 2009; Naqvi and Bechara, 2009; Paulus, 2007).”
BackgroundCritical Roles for Anterior Insula and Dorsal Striatum in Punishment-Based Avoidance Learning
Palminteri, S., Justo, D., Jauffret, C., Pavlicek, B., Dauta, A., Delmaire, C., Czernecki, V., Karachi, C., Capelle, L., Dürr, A., et al. (2012) · Neuron · doi:10.1016/j.neuron.2012.10.017 · Cited by 244 · see citing works
“This is in line with theories proposing that brain areas involved in somatic affective representations are causally responsible for making a choice (Jones et al., 2010; Naqvi and Bechara, 2009; Craig, 2003).”
Neural systems underlying approach and avoidance in anxiety disorders
Robin L., A., & Martin, P. P. (2010) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2010.12.4/raupperle · Cited by 227 · see citing works
Hogarth, L., & Chase, H. W. (2011) · Journal of Experimental Psychology: Animal Behavior Processes · doi:10.1037/a0022913 · Cited by 225 · see citing works
Deep brain stimulation in addiction: a review of potential brain targets
Luigjes, J., van den Brink, W., Feenstra, M. G. P., van den Munckhof, P., Schuurman, P. R., Schippers, R., Mazaheri, A., Vries, T. J. D., & Denys, D. A. J. P. (2011) · Molecular Psychiatry · doi:10.1038/mp.2011.114 · Cited by 222 · see citing works
Hauser, T. U., Iannaccone, R., Walitza, S., Brandeis, D., & Brem, S. (2015) · NeuroImage · doi:10.1016/j.neuroimage.2014.09.018 · Cited by 203 · see citing works
“It has also been associated with depression, anxiety or substance abuse (for reviews cf. Craig, 2009; Naqvi and Bechara, 2009).”
BackgroundNummenmaa, L., Hirvonen, J., Hannukainen, J. C., Immonen, H., Lindroos, M. M., Salminen, P., & Nuutila, P. (2012) · PLoS ONE · doi:10.1371/journal.pone.0031089 · Cited by 220 · see citing works
“The anterior insula integrates autonomic and visceral signals into motivational and emotional functions, whereas the posterior insula is thought to underlie somatosensory, vestibular and motor integration as well as monitoring bodily states [53].”
BackgroundClinical effects of insular damage in humans
Ibañez, A., Gleichgerrcht, E., & Manes, F. (2010) · Brain Structure and Function · doi:10.1007/s00429-010-0256-y · Cited by 217 · see citing works
“Naqvi and Bechara (2009) proposed that the insula is a region able to integrate bodily states into conscious feelings and into decision-making processes.”
BackgroundInfluentialUnbalanced neuronal circuits in addiction
Volkow, N. D., Wang, G.-J., Tomasi, D. G., & Baler, R. (2013) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2013.01.002 · Cited by 219 · see citing works
“In fact, many imaging studies show differential activation of the insula during craving [56], which has been suggested to serve as a biomarker to predict relapse [57 ].”
Smoking, nicotine and neuropsychiatric disorders
Döme, P., Lazáry, J., Kalapos, M. P., & Rihmer, Z. (2009) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2009.07.013 · Cited by 215 · see citing works
“associated with impaired amphetamine-conditioned place-preference (Contreras et al., 2007; Naqvi and Bechara, 2009).”
BackgroundNeuroscience of Behavioral and Pharmacological Treatments for Addictions
Potenza, M. N., Sofuoglu, M., Carroll, K. M., & Rounsaville, B. J. (2011) · Neuron · doi:10.1016/j.neuron.2011.02.009 · Cited by 214 · see citing works
“Other brain regions and circuits contribute importantly to motivational behaviors, with regions like the amygdala providing important affective information, the hippocampus important contextual memory information, the hypothalamus and septum important homeostatic information, and the insula important information relat…”
Translational and reverse translational research on the role of stress in drug craving and relapse
Sinha, R., Shaham, Y., & Heilig, M. A. (2011) · Psychopharmacology · doi:10.1007/s00213-011-2263-y · Cited by 208 · see citing works
“These data suggest that guanfacine’s positive effects may include reversing the previously documented hypofrontality and insula deficits in drug addicts (Goldstein and Volkow 2002; Naqvi and Bechara 2009).”
Resting-State Functional Connectivity of the Medial Superior Frontal Cortex
Zhang, S., Ide, J. S., & Li, C.-S. R. (2011) · Cerebral Cortex · doi:10.1093/cercor/bhr088 · Cited by 206 · see citing works
“We also examined the connectivity between the medial SFC and insula, which is implicated in many psychological processes such as emotion, somatomotor integration, and cognitive control (Naqvi and Bechara 2009; Taylor et al. 2009; Menon and Uddin 2010; Nelson et al. 2010).”
BackgroundA Triadic Neurocognitive Approach to Addiction for Clinical Interventions
Noël, X., Brevers, D., & Bechara, A. (2013) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2013.00179 · Cited by 193 · see citing works
“The insular cortex has recently emerged as a key neural structure that plays a key role in the formation of interoceptive representation, which is crucial for subjective emotional feelings (5, 13, 91).”
BackgroundInfluentialSelf-citationRegulation of nausea and vomiting by cannabinoids and the endocannabinoid system
Sharkey, K. A., Darmani, N. A., & Parker, L. A. (2013) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2013.09.068 · Cited by 195 · see citing works
“(2007) suggested that this region of the insular cortex (which is also involved in craving for drugs; Naqvi and Bechara, 2009; Forget et al., 2010) may be responsible for sensing strong deviations from a “well-being state” (e.”
BackgroundAddiction science: Uncovering neurobiological complexity
Volkow, N. D., & Baler, R. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.05.007 · Cited by 194 · see citing works
“Consistent with this hypothesis, imaging studies show differential activation of the insula during craving (Brody et al., 2009; Goudriaan et al., 2010; Naqvi and Bechara, 2009; Wang et al.,1999).”
BackgroundResultAltered prefrontal and insular cortical thickness in adolescent marijuana users
Lopez-Larson, M. P., Bogorodzki, P., Rogowska, J., McGlade, E., King, J. B., Terry, J., & Yurgelun-Todd, D. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2011.02.001 · Cited by 187 · see citing works
“Moreover, numerous functional imaging studies have found both prefrontal and insular activation during conscious drug urges [38–42].”
BackgroundResultA neurocomputational account of how inflammation enhances sensitivity to punishments versus rewards
Harrison, N. A., Voon, V., Cercignani, M., Cooper, E. A., Pessiglione, M., & Critchley, H. D. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.07.018 · Cited by 185 · see citing works
Subcortical structural connectivity of insular subregions
Ghaziri, J., Tucholka, A., Girard, G., Boucher, O., Houde, J., Descoteaux, M., Obaïd, S., Gilbert, G., Rouleau, I., & Nguyen, D. K. (2018) · Scientific Reports · doi:10.1038/s41598-018-26995-0 · Cited by 190 · see citing works
Nature's clocks and human mood: the circadian system modulates reward motivation
Murray, G., Nicholas, C. L., Kleiman, J., Dwyer, R., Carrington, M. J., Allen, N. B., & Trinder, J. (2009) · Emotion · doi:10.1037/a0017080 · Cited by 185 · see citing works
“There is no agreed multilevel measure of human reward activation (e.g., Carlezon & Thomas, 2009; Naqvi & Bechara, 2009), but measurement of left frontal asymmetry would address concerns about the reward specificity of the objective findings here (e.g., Amodio, Master, Yee, & Taylor, 2008).”
BackgroundPando-Naude, V., Toxto, S., Fernandez-Lozano, S., Parsons, C. E., Alcauter, S., & Garza-Villarreal, E. (2020) · bioRxiv · doi:10.1038/s41398-020-01128-2 · Cited by 118 · see citing works
Garavan, H. (2010) · Brain Structure and Function · doi:10.1007/s00429-010-0259-8 · Cited by 181 · see citing works
Is Our Self Nothing but Reward?
Northoff, G., & Hayes, D. J. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.12.014 · Cited by 185 · see citing works
Atypical interoception as a common risk factor for psychopathology: A review
Brewer, R., Murphy, J., & Bird, G. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.07.036 · Cited by 180 · see citing works
Andrews, M. M., Meda, S. A., Thomas, A. D., Potenza, M. N., Krystal, J. H., Worhunsky, P., Stevens, M. C., O'Malley, S., Book, G. A., Reynolds, B., et al. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.09.049 · Cited by 181 · see citing works
Villafuerte, S., Heitzeg, M. M., Foley, S., Yau, W.-Y. W., Majczenko, K., Zubieta, J., Zucker, R. A., & Burmeister, M. (2011) · Molecular Psychiatry · doi:10.1038/mp.2011.33 · Cited by 182 · see citing works
Perry, J. L., Joseph, J. E., Jiang, Y., Zimmerman, R. S., Kelly, T. H., Darna, M., Huettl, P., Dwoskin, L. P., & Bardo, M. T. (2011) · Brain Research Reviews · doi:10.1016/j.brainresrev.2010.09.001 · Cited by 180 · see citing works
Waiting to perceive: Reward or punishment?
Brunia, C. H. M., Hackley, S. A., van Boxtel, G. J. M., Kotani, Y., & Ohgami, Y. (2011) · Clinical Neurophysiology · doi:10.1016/j.clinph.2010.12.039 · Cited by 176 · see citing works
“Naqvi and Bechara (2009) argue, for example, that the insula has a role in the generation of conscious feeling of drug urge.”
BackgroundCho, Y. T., Fromm, S., Guyer, A. E., Detloff, A., Pine, D. S., Fudge, J. L., & Ernst, M. (2013) · NeuroImage · doi:10.1016/j.neuroimage.2012.10.013 · Cited by 173 · see citing works
“Therefore, the projections from the insula to theNAc are expected to critically influencemotivated behavior, particularly decision-making (Clark et al., 2008; Damasio, 1999; Naqvi and Bechara, 2009).”
Schwartz, D. L., Mitchell, A. D., Lahna, D. L., Luber, H. S., Huckans, M. S., Mitchell, S. H., & Hoffman, W. F. (2010) · NeuroImage · doi:10.1016/j.neuroimage.2010.01.056 · Cited by 171 · see citing works
“The INS may mediate withdrawal phenomena through translation of physiological symptoms into conscious dysphoria (Naqvi and Bechara, 2009).”
BackgroundInfluentialSocial touch modulates endogenous μ-opioid system activity in humans
Nummenmaa, L., Tuominen, L. J., Dunbar, R., Hirvonen, J., Manninen, S., Arponen, E., Machin, A., Hari, R., Jääskeläinen, I. P., & Sams, M. E. (2016) · NeuroImage · doi:10.1016/j.neuroimage.2016.05.063 · Cited by 170 · see citing works
“Given the proposed lateralization of affective processing and anterior–posterior organization of emotional versus somatosensory and interoceptive processing in the insula (Duerden et al. 2013; Naqvi and Bechara 2009), we also analyzed the insular responses using hemisphere-specific anterior and posterior insular ROIs.”
MethodThe role of interoception and alliesthesia in addiction
Paulus, M. P., Tapert, S. F., & Schulteis, G. (2009) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2009.08.005 · Cited by 168 · see citing works
“However, we (Paulus, 2007), Craig (Craig, 2007), and Naqvi and Bechara (Naqvi and Bechara, 2008) argue that both approach behaviors to positive hedonic stimuli and avoidance of negative hedonic stimuli are regulated by interoceptive input provided by the insula, and our model allows for both…”
BackgroundInfluentialLee, W., & Reeve, J. (2012) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nss029 · Cited by 164 · see citing works
“, 2004), cravings from bodily addictions (Naqvi et al., 2007; Goldstein et al., 2009; Naqvi and Bechara, 2009), and so on.”
BackgroundAnterior insula degeneration in frontotemporal dementia
Seeley, W. W. (2010) · Brain Structure and Function · doi:10.1007/s00429-010-0263-z · Cited by 162 · see citing works
“These approaches could, in turn, elucidate key aspects of other common neuropsychiatric disorders, such as schizophrenia, anxiety states, autism, eating disorders, and substance abuse (to name a few) whose pathophysiologies seem embedded within the insula and its core network affiliates (Di Martino et al. 2009; Fornit…”
BackgroundOn the functional anatomy of the urge-for-action
Jackson, S. R., Parkinson, A., Kim, S. Y., Schüermann, M., & Eickhoff, S. B. (2011) · Cognitive Neuroscience · doi:10.1080/17588928.2011.604717 · Cited by 158 · see citing works
“The proposal that the insular and cingulate cortices are associated with the uncomfortable feelings associated with the urge to tic in TS is consistent with the putative role of these areas in the neural representation of bodily states more generally (interoception), and the initiation of behaviors associated with the…”
ResultDual role of nicotine in addiction and cognition: A review of neuroimaging studies in humans
Jasinska, A. J., Zorick, T. S., Brody, A. L., & Stein, E. A. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.02.015 · Cited by 163 · see citing works
“In addition, smokers showed higher gray matter density in left insular cortex (Zhang et al., 2011), consistent with previous evidence of the role of the insula in supporting tobacco dependence (Naqvi and Bechara, 2009; Naqvi et al., 2007).”
Current smoking and reduced gray matter volume - a voxel-based morphometry study
Fritz, H.-C., Wittfeld, K., Schmidt, C. O., Domin, M., Grabe, H. J., Hegenscheid, K., Hosten, N., & Lotze, M. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.112 · Cited by 160 · see citing works
The Insular Cortex: An Interface Between Sensation, Emotion and Cognition
Zhang, R., Deng, H., & Xiao, X. (2024) · Neuroscience Bulletin · doi:10.1007/s12264-024-01211-4 · Cited by 158 · see citing works
“The insula has long been implicated in drug cravings, the maintenance of drug-seeking behavior, and the regulation of distress during withdrawal [1, 6, 71].”
Gray matter and white matter abnormalities in online game addiction
Weng, C.-B., Qian, R.-B., Fu, X.-M., Lin, B., Han, X.-P., Niu, C.-S., & Wang, Y.-H. (2013) · European Journal of Radiology · doi:10.1016/j.ejrad.2013.01.031 · Cited by 158 · see citing works
Dopaminergic Modulation of Risky Decision-Making
Simon, N. W., Montgomery, K. S., Beas, B. S., Mitchell, M. R., LaSarge, C. L., Mendez, I. A., Bañuelos, C., Vokes, C. M., Taylor, A. B., Haberman, R. P., et al. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.3772-11.2011 · Cited by 157 · see citing works
“These data suggest that D1 receptors within this system (Reynolds and Zahm, 2005) may be involved in valuation of risky versus safe outcomes (or perhaps valuation of differing reward magnitudes), consistent with a role for this system in cost-benefit decision-making (Cardinal, 2006; Naqvi and Bechara, 2009).”
MethodResultIdentifying the neural substrates of intrinsic motivation during task performance
Lee, W., & Reeve, J. (2017) · Cognitive Affective & Behavioral Neuroscience · doi:10.3758/s13415-017-0524-x · Cited by 159 · see citing works
A review of gambling disorder and substance use disorders
Rash, C. J., Weinstock, J., & Patten, R. V. (2016) · Substance Abuse and Rehabilitation · doi:10.2147/sar.s83460 · Cited by 154 · see citing works
Granular insular cortex inactivation as a novel therapeutic strategy for nicotine addiction
Forget, B., Pushparaj, A., & Le Foll, B. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.01.029 · Cited by 153 · see citing works
The neuropsychological impact of insular cortex lesions
Jones, C. L., Ward, J., & Critchley, H. D. (2010) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.2009.193672 · Cited by 158 · see citing works
“This finding is also in line with a Somatic Marker model of addictive behaviour in which exposure to or recollection of an experience associated with a drug can reactivate this ‘interoceptive memory ’ state.(7) Future patient studies will establish how general the effects of insula lesions are on other forms of addict…”
ResultNestor, L. J., Ghahremani, D. G., Monterosso, J. R., & London, E. D. (2011) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2011.04.010 · Cited by 150 · see citing works
“Research suggests that the insular cortex and interoceptive awareness are critical to drug craving and dependence (Gray and Critchley, 2007; Naqvi et al., 2007; Paulus, 2007; Naqvi and Bechara, 2009) whereby this region monitors interoceptive “urges” for rewarding stimuli such as drugs.”
BackgroundZhu, X., Cortes, C. R., Mathur, K., Tomasi, D. G., & Momenan, R. (2015) · Addiction Biology · doi:10.1111/adb.12272 · Cited by 152 · see citing works
“Thus, insula causes a severe imbalance between the impulsive and reflective systems (Naqvi & Bechara 2009; Noel et al. 2013; Lu & Stein 2014).”
BackgroundDevoto, F., Zapparoli, L., Bonandrini, R., Berlingeri, M., Ferrulli, A., Luzi, L., Banfi, G., & Paulesu, E. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.07.017 · Cited by 140 · see citing works
“…et al., 1997; Bonson et al., 2002) and even for air (Liotti et al., 2001); more importantly, lesions to the insula disrupt addiction to cigarettes smoking (Naqvi et al., 2007; Naqvi and Bechara, 2009), thus suggesting that the region plays a pivotal role in craving and in addiction-like behaviors.”
Jia, Z., Worhunsky, P. D., Carroll, K. M., Rounsaville, B. J., Stevens, M. C., Pearlson, G. D., & Potenza, M. N. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.05.008 · Cited by 147 · see citing works
A Motivational Model of Alcohol Use: Determinants of Use and Change
Cox, W. M., & Klinger, E. (2011) · Wiley eBooks · doi:10.1002/9780470979952.ch6 · Cited by 145 · see citing works
Food cravings in food addiction: The distinct role of positive reinforcement
Meule, A., & Kübler, A. (2012) · Eating Behaviors · doi:10.1016/j.eatbeh.2012.02.001 · Cited by 144 · see citing works
“This area has also been recognized as a crucial part in urges to take drugs (Naqvi & Bechara, 2009).”
Background
- Authors
- Naqvi, N. H., & Bechara, A.
- Affiliations
- New York State Psychiatric Institute (US)
- University of Southern California (US)
- Corresponding author
- Bechara, Antoine
- ORCID
- Bechara, Antoine
- Venue
- Trends in Neurosciences
- Publisher
- Elsevier BV
- Published
- 2009-01
- Volume
- 32
- Issue
- 1
- Pages
- 56-67
- ISSN
- 0166-2236 (ISSN-L)
- PMC
- PMC3698860
- OpenAlex
- W2036074427
- Semantic Scholar
- 2c3d49d333514ca29ffa128dca631e5f5cfbfe5b
- Cited by
- 833
- References
- 148
- Citations by year
- 2026: 29 · 2025: 26 · 2024: 32 · 2023: 45 · 2022: 58 · 2021: 44 · 2020: 107 · 2019: 38 · 2018: 37 · 2017: 42 · 2016: 53 · 2015: 48 · 2014: 49 · 2013: 60 · 2012: 52
- FWCI
- 3.11
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Trends in Neurosciences (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Drug Abuse (R01DA023051)
- National Institute of General Medical Sciences (T32GM007337)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- insula, addiction, drug craving, interoception, relapse, decision-making, risk and reward, neurobiology of addiction
- MeSH terms
- Animals, Cerebral Cortex, Humans, Models, Biological, Neural Pathways, Substance-Related Disorders
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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