Review
The hidden island of addiction: the insula

https://doi.org/10.1016/j.tins.2008.09.009Get rights and content

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.

Section snippets

Evidence for the role of the insula in addiction

Addiction to drugs of abuse is a major public health concern. By itself, cigarette smoking, the most common addictive behavior, is the largest preventable cause of morbidity and mortality in the developed world [1]. Drug addiction is a mental disorder characterized by the compulsive use of drugs that persists despite awareness of negative consequences [2]. Underlying addiction is a set of physiological and psychological processes, such as tolerance, withdrawal, learning, incentive motivation,

Anatomy and function of the insula: a historical perspective

The term ‘insula’ was coined by Johann Christian Reil who described an island of cortex (insula is Latin for island) in the depth of the cerebral mantle situated between the banks of the Sylvian fissure. The insula has been divided into various subregions based upon both anatomical connectivity and cytoarchitectonic features 13, 14, 15, 16, 17. The more posterior, granular regions of the insula, which receive inputs from the thalamus, in addition to parietal, occipital and temporal association

The psychology and neurobiology of addiction: a historical perspective

Various models have been applied to the phenomenon of impulsive and compulsive drug use, but most emphasize one of two possibilities. The first attributes drug motivation, especially with drugs that produce physical dependence such as opioids, to the need to alleviate the withdrawal-distress resultant from a previous history of drug use [75]. The other incentive possibility stresses drug-like rather than drug-withdrawal states as the most powerful instigator of drug use and that drug motivation

The role of interoception in addiction

Although the dopamine system clearly has an important role in addiction to drugs of abuse, drug use does more for the addicted individual than merely providing a means of releasing dopamine in the brain. Drug use involves a complex set of rituals imbued with emotional meaning (both positive and negative) for the addicted individual.

Nearly all drug-use rituals have highly salient and distinctive effects on the body that are likely to contribute to their emotional meaning. For example, snorting

Proposed role for the insula in addiction

Evidence points toward a crucial role for the insula in conscious drug urges and in translating interoceptive signals into conscious feelings and behavioral biases during decision making that involves uncertain risk and reward. Although nearly all drugs of abuse exert interoceptive effects that impart distinct subjective qualities to drug-use rituals, very little attention has been paid to the role of the insula in these effects. Thus, the question arises as to whether the insula has a role in

Future directions

Since our initial finding on the effects of insula lesions on smoking addiction, several authors have suggested that the interoceptive functions of the insula might be important for addiction 7, 12, 127, although they have only discussed these functions in general terms. Here, we propose a specific model in which interoceptive (i.e. bodily) effects of drug-use rituals are encoded by the insula and are integrated into explicit motivational processes that promote addiction, such as conscious

Acknowledgements

The research described in this article was supported by a grant from the National Institute on Drug Abuse (NIDA; www.nida.nih.gov) R01 DA023051.

References (143)

  • W.E. DeCoteau

    Short-term memory for food reward magnitude: the role of the prefrontal cortex

    Behav. Brain Res.

    (1997)
  • N. Fresquet

    Insular cortex lesions alter conditioned taste avoidance in rats differentially when using two methods of sucrose delivery

    Behav. Brain Res.

    (2004)
  • K.A. Zito

    The dopamine innervation of the visceral cortex mediates the aversive effects of opiates

    Pharmacol. Biochem. Behav.

    (1988)
  • Z.H. Zhang

    Monkey insular cortex neurons respond to baroreceptive and somatosensory convergent inputs

    Neuroscience

    (1999)
  • U. Ladabaum

    Gastric fundic distension activates fronto-limbic structures but not primary somatosensory cortex: A functional magnetic resonance imaging study

    Neuroimage

    (2007)
  • G.J. Wang

    Gastric distention activates satiety circuitry in the human brain

    Neuroimage

    (2008)
  • J.C.W. Brooks

    fMRI of thermal pain: effects of stimulus laterality and attention

    Neuroimage

    (2002)
  • K.L. Phan

    Functional neuroanatomy of emotion: a meta-analysis of emotion activation studies in PET and fMRI

    Neuroimage

    (2002)
  • M.L. Pelchat

    Images of desire: food-craving activation during fMRI

    Neuroimage

    (2004)
  • G.J. Wang

    Exposure to appetitive food stimuli markedly activates the human brain

    Neuroimage

    (2004)
  • J.D. Berke

    Addiction, dopamine, and the molecular mechanisms of memory

    Neuron

    (2000)
  • N.D. Volkow

    The addicted human brain viewed in the light of imaging studies: brain circuts and treatment strategies

    Neuropharmacology

    (2004)
  • R.A. Wise et al.

    Action of drugs of abuse on brain reward systems: an update with specific attention to opiates

    Pharmacol. Biochem. Behav.

    (1982)
  • K.C. Berridge et al.

    What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience?

    Brain Res. Brain Res. Rev

    (1998)
  • J.M. Stapleton

    Cerebral glucose utilization in polysubstance abuse

    Neuropsychopharmacology

    (1995)
  • Y.R. Kou

    The stimulatory effect of nicotine on vagal pulmonary C-fibers in dogs

    Respir. Physiol.

    (1989)
  • American Psychiatric Association (2001) Diagnostic and Statistical Manual of Mental Disorders (4th edn), American...
  • B.J. Everitt et al.

    Neural systems of reinforcement for drug addiction: from actions to habits to compulsion

    Nat. Neurosci.

    (2005)
  • T. Robinson et al.

    Incentive-sensitization and addicition

    Addiction

    (2001)
  • S.T. Tiffany

    Is craving the source of compulsive drug use?

    J. Psychopharmacol.

    (1998)
  • M.P. Paulus

    Decision-making dysfunctions in psychiatry – altered homeostatic processing?

    Science

    (2007)
  • N.H. Naqvi

    Damage to the insula disrupts addiction to cigarette smoking

    Science

    (2007)
  • M. Contreras

    Inactivation of the interoceptive insula disrupts drug craving and malaise induced by lithium

    Science

    (2007)
  • M. Chikama

    Insular cortical projections to functional regions of the striatum correlate with cortical cytoarchitectonic organization in the primate

    J. Neurosci.

    (1997)
  • M.M. Mesulam

    Insula of the old-world monkey. 1. Architectonics in the insulo-orbito-temporal component of the paralimbic brain

    J. Comp. Neurol.

    (1982)
  • M.M. Mesulam

    Insula of the old-world monkey. 3. Efferent cortical output and comments on function

    J. Comp. Neurol.

    (1982)
  • E.J. Mufson

    Insula of the old-world monkey. 2. Afferent cortical input and comments on the claustrum

    J. Comp. Neurol.

    (1982)
  • L. Stefanacci

    Topographic organization of cortical inputs to the lateral nucleus of the macaque monkey amygdala: A retrograde tracing study

    J. Comp. Neurol.

    (2000)
  • P. Gaspar

    Catecholamine innervation of the human cerebral-cortex as revealed by comparative immunohistochemistry of tyrosine-hydroxylase and dopamine-β-hydroxylase

    J. Comp. Neurol.

    (1989)
  • M.M. Sanchez

    Autoradiographic and in situ hybridization localization of corticotropin-releasing factor 1 and 2 receptors in nonhuman primate brain

    J. Comp. Neurol.

    (1999)
  • K.E. Habib

    Oral administration of a corticotropin-releasing hormone receptor antagonist significantly attenuates behavioral, neuroendocrine, and autonomic responses to stress in primates

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

    (2000)
  • A.C. Hansson

    Region-specific down-regulation of Crhr1 gene expression in alcohol-preferring msP rats following ad lib access to alcohol

    Addict. Biol.

    (2007)
  • W. Penfield

    The insula – further observations on its function

    Brain

    (1955)
  • J. Shuren

    Insula and aphasia

    J. Neurol.

    (1993)
  • J. Isnard

    Clinical manifestations of insular lobe seizures: a stereo-electroencephalographic study

    Epilepsia

    (2004)
  • T.C. Pritchard

    Projections of thalamic gustatory and lingual areas in the monkey, Macaca fascicularis

    J. Comp. Neurol.

    (1986)
  • M. Kadohisa

    Neuronal representations of stimuli in the mouth: the primate insular taste cortex, orbitofrontal cortex and amygdala

    Chem. Senses

    (2005)
  • J.V. Verhagen

    Primate insular/opercular taste cortex: neuronal representations of the viscosity, fat texture, grittiness, temperature, and taste of foods

    J. Neurophysiol.

    (2004)
  • C. Cereda

    Strokes restricted to the insular cortex

    Neurology

    (2002)
  • T.C. Pritchard

    Taste perception in patients with insular cortex lesions

    Behav. Neurosci.

    (1999)
  • Cited by (0)

    View full text