In each hemisphere of the mammalianbrain the insular cortex (often called insula, insulary cortex or insular lobe) is a portion of the cerebral cortex folded deep within the lateral sulcus (the fissure separating the temporal lobe from the parietal and frontal lobes).
The insulae are believed to be involved in consciousness and play a role in diverse functions usually linked to emotion or the regulation of the body's homeostasis. These functions include perception, motor control, self-awareness, cognitive functioning, and interpersonal experience. In relation to these it is involved in psychopathology.
The insular cortex is divided into two parts: the larger anterior insula and the smaller posterior insula in which more than a dozen field areas have been identified. The cortical area overlying the insula towards the lateral surface of the brain is the operculum (meaning "lid"). The opercula are formed from parts of the enclosing frontal, temporal and parietal lobes.
The insula was first described by Johann Christian Reil while describing cranial and spinal nerves and plexi.Henry Gray in Gray's Anatomy is responsible for it being known as the Island of Reil.
The right anterior insula aids interoceptive awareness of body states, such as the ability to time one's own heart beat. Moreover, greater right anterior insular gray matter volume correlates with increased accuracy in this subjective sense of the inner body, and with negative emotional experience. It is also involved in the control of blood pressure, particularly during and after exercise, and its activity varies with the amount of effort a person believes they are exerting.
The insular cortex also is where the sensation of pain is judged as to its degree. Further, the insula is where a person imagines pain when looking at images of painful events while thinking about them happening to one's own body. Those with irritable bowel syndrome have abnormal processing of visceral pain in the insular cortex related to dysfunctional inhibition of pain within the brain.
Another perception of the right anterior insula is the degree of nonpainful warmth or nonpainful coldness of a skin sensation. Other internal sensations processed by the insula include stomach or gastric distension. A full bladder also activates the insular cortex.
One brain imaging study suggest that the unpleasantness of subjectively perceived dyspnea is processed in the right human anterior insula and amygdala.
The cerebral cortex processing vestibular sensations extends into the insula with small lesions in the anterior insular cortex being able to cause loss of balance and vertigo.
Other noninteroceptive perceptions include passive listening to music, laughter and crying, empathy and compassion, and language.
In motor control it contributes to hand and eye motor movement, swallowing, gastric motility, and speech articulation. It has been identified as a "central command” centre that ensures that heart rate and blood pressure increase at the onset of exercise. Research upon conversation links it to the capacity for long and complex spoken sentences. It is also involved in motor learning and has been identified as playing a role in the motor recovery from stroke.
In homeostasis it controls autonomic functions through the regulation of the sympathetic and parasympathetic systems. It has a role in regulating the immune system.
It has been identified as playing a role in the experience of bodily self-awareness, sense of agency and sense body ownership.
The anterior insular processes a person's sense of disgust both to smells and to the sight of contamination and mutilation — even when just imagining the experience. This associates with a mirror neuron like link between external and internal experience.
In social experience it is involved in the processing of norm violations, emotional processing, empathy, and orgasms.
The insular cortex, in particular its most anterior portion, is considered a limbic-related cortex. The insula has increasingly become the focus of attention for its role in body representation and subjective emotional experience. In particular, Antonio Damasio has proposed that this region plays a role in mapping visceral states that are associated with emotional experience, giving rise to conscious feelings. This is in essence a neurobiological formulation of the ideas of William James, who first proposed that subjective emotional experience (i.e. feelings) arise from our brain's interpretation of bodily states that are elicited by emotional events. This is an example of embodied cognition.
Functionally speaking, the insula is believed to process convergent information to produce an emotionally relevant context for sensory experience. More specifically, the anterior insula is related more to olfactory, gustatory, vicero-autonomic, and limbic function, while the posterior insula is related more to auditory-somesthetic-skeletomotor function. Functional imaging experiments have revealed that the insula has an important role in pain experience and the experience of a number of basic emotions, including anger, fear, disgust, happiness and sadness.
Specifically, the anterior insular cortex (AIC) is believed to be responsible for emotional feelings, including maternal and romantic love, anger, fear, sadness, happiness, sexual arousal, disgust, aversion, unfairness, inequity, indignation, uncertainty, disbelief, social exclusion, trust, empathy, sculptural beauty, a ‘state of union with God’, and hallucinogenic state. 
Functional imaging studies have also implicated the insula in conscious desires, such as food craving and drug craving. What is common to all of these emotional states is that they each change the body in some way and are associated with highly salient subjective qualities. The insula is well situated for the integration of information relating to bodily states into higher-order cognitive and emotional processes. The insula receives information from "homeostatic afferent" sensory pathways via the thalamus and sends output to a number of other limbic-related structures, such as the amygdala, the ventral striatum and the orbitofrontal cortex, as well as to motor cortices.
A study using magnetic resonance imaging found that the right anterior insula was significantly thicker in people who meditate.
Another study using voxel-based morphometry and MRI on experienced Vipassana meditators was done to extend the findings of Lazar et al., which found increased grey matter concentrations in this and other areas of the brain in experienced meditators.
Functional imaging research suggests the insula is involved in two types of salience. Interoceptive information processing that links interoception with emotional salience to generate a subjective representation of the body. This involves the anterior insular cortex with the pregenual anterior cingulate cortex (Brodmann area 33) and the anterior and posterior mid-cingulate cortices. Second, a general salience system concerned with environmental monitoring, response selection, and skeletomotor body orientation that involves all of the insular cortex and the mid-cingulate cortex.
An alternative or perhaps complementary proposal is that right anterior insular regulates the interaction between the salience of the selective attention created to achieve a task (the dorsal attention system) and the salience of arousal created to keep focused upon the relevant part of the environment (ventral attention system). This regulation of salience might be particularly important during challenging tasks where attention might fatigue and so cause careless mistakes but if there is too much arousal it risks creating poor performance by turning into anxiety.
The anterior insula receives a direct projection from the basal part of the ventral medial nucleus (VMb) of the thalamus and a particularly large input from the central nucleus of the amygdala. Additionally, the anterior insula itself projects to the amygdala.
One study on rhesus monkeys revealed widespread reciprocal connections between the insular cortex and almost all subnuclei of the amygdaloid complex. The posterior insula projects predominantly to the dorsal aspect of the lateral and to the central amygdaloid nuclei. In contrast, the anterior insula projects to the anterior amygdaloid area as well as the medial, the cortical, the accessory basal magnocellular, the medial basal and the lateral amygdaloid nuclei.
The posterior insula connects reciprocally with the secondary somatosensory cortex (S2) and receives input from spinothalamically activated ventral posterior inferior (VPI) thalamic nuclei. More recent work by Bud Craig and his colleagues has shown that this region receives inputs from the ventromedial nucleus (posterior part) of the thalamus that are highly specialized to convey emotional/homeostatic information such as pain, temperature, itch, local oxygen status and sensual touch.
A human neuroimaging study using diffusion tensor imaging revealed that the anterior insula is interconnected to regions in the temporal and occipital lobe, opercular and orbitofrontal cortex, triangular and opercular parts of the inferior frontal gyrus. The same study revealed differences in the anatomical connection patterns between the left and right hemisphere.
The insular cortex has regions of variable cell structure or cytoarchitecture, changing from granular in the posterior portion to agranular in the anterior portion. The insula also receives differential cortical and thalamic input along its length.
The insular cortex is considered a separate lobe of the telencephalon by some authorities. Other sources see the insula as a part of the temporal lobe. It is also sometimes grouped with limbic structures deep in the brain into a limbic lobe.
As a paralimbic cortex, the insular cortex is considered to be a relatively old structure. It plays a role in a variety of highly conserved functions that are related to basic survival needs, such as taste, visceral sensation and autonomic control (so-called homeostatic functions). There is evidence that in addition to its more conserved functions, the insula may play a role in certain "higher" functions that operate only in humans and other great apes. John Allman and his colleagues have shown that the anterior insular cortex contains a population of neurons, called spindle neurons. These neurons are also found in the anterior cingulate cortex, which is another region that has reached a high level of specialization in great apes. Spindle neurons are found at a higher density in the right insular cortex. It has been speculated that these neurons are involved in cognitive-emotional processes that are specific to great apes, such as empathy and self-aware emotional feelings. This is supported by functional imaging results showing that the structure and function of the right anterior insula are correlated with the ability to feel one's own heartbeat, or to empathize with the pain of others. It is thought that these functions are not distinct from the "lower" functions of the insula, but rather arise as a consequence of the role of the insula in conveying homeostatic information to consciousness.
Progressive non-fluent aphasia
Progressive non-fluent aphasia is the deterioration of normal language function which causes individuals to lose the ability to communicate fluently while being still being able to comprehend single words and intact other non-linguistic cognition. It is found in a variety of degenerative neurological conditions including Pick's disease, motor neuron disease, corticobasal degeneration, frontotemporal dementia and Alzheimer's disease. It is associated with hypometabolism and atrophy of the left anterior insular cortex.
A number of functional brain imaging studies have shown that the insular cortex is activated when drug abusers are exposed to environmental cues that trigger cravings. This has been shown for a variety of drugs, including cocaine, alcohol, opiates and nicotine. Despite these findings, the insula has been ignored within the drug addiction literature, perhaps because it is not known to be a direct target of the mesotelencephalic dopamine system which is central to current dopamine reward theories of addiction. Recent research has shown that cigarette smokers who suffer damage to the insular cortex, from a stroke for instance, have their addiction to cigarettes practically eliminated. However, the study was conducted on average eight years after the strokes, and the author admits recall bias could affect the results.
These individuals were found to be up to 136 times more likely to undergo a disruption of smoking addiction than smokers with damage in other areas. Disruption of addiction was evidenced by self-reported behavior changes such as quitting smoking less than one day after the brain injury, quitting smoking with great ease, not smoking again after quitting, and having no urge to resume smoking since quitting. This suggests a significant role for the insular cortex in the neurological mechanisms underlying addiction to nicotine and other drugs, and would make this area of the brain a possible target for novel anti-addiction medication. In addition, this finding suggests that functions mediated by the insula, especially conscious feelings, may be particularly important for maintaining drug addiction, although this view is not represented in any modern research or reviews of the subject.
A recent study in rats by Contreras et al. corroborates these findings by showing that reversible inactivation of the insula disrupts amphetamine conditioned place preference, an animal model of cue-induced drug craving. In this study, insula inactivation also disrupted "malaise" responses to lithium chloride injection, suggesting that the representation of negative interoceptive states by the insula plays a role in addiction. However, in this same study, the conditioned place preference took place immediately after the injection of amphetamine, suggesting that it was the immediate, pleasurable interoceptive effects of amphetamine administration, rather than the delayed, aversive effects of amphetamine withdrawal that are represented within the insula.
A model proposed by Naqvi et al. (see above) is that the insula stores a representation of the pleasurable interoceptive effects of drug use (e.g. the airway sensory effects of nicotine, the cardiovascular effects of amphetamine), and that this representation is activated by exposure to cues that have previously been associated with drug use. A number of functional imaging studies have shown the insula to be activated during the administration of drugs of abuse. Several functional imaging studies have also shown that the insula is activated when drug users are exposed to drug cues, and that this activity is correlated with subjective urges. In the cue-exposure studies, insula activity is elicited when there is no actual change in the level of drug in the body. Therefore, rather than merely representing the interoceptive effects of drug use as it occurs, the insula may play a role in memory for the pleasurable interoceptive effects of past drug use, anticipation of these effects in the future, or both. Such a representation may give rise to conscious urges that feel as if they arise from within the body. This may make addicts feel as if their bodies need to use a drug, and may result in persons with lesions in the insula reporting that their bodies have forgotten the urge to use, according to this study.
Other clinical conditions
The insular cortex has been suggested to have a role in anxiety disorders, and emotion dysregulation.
Coronal section of brain through intermediate mass of third ventricle.
Coronal section through anterior cornua of lateral ventricles.
Coronal section of brain through anterior commissure.
Orbital surface of left frontal lobe.
Section of brain showing upper surface of temporal lobe.
Horizontal section of left cerebral hemisphere.
Human brain frontal (coronal) section
Human brain view on transverse temporal and insular gyri
- ^ abBinder DK, Schaller K, Clusmann H (November 2007). "The seminal contributions of Johann-Christian Reil to anatomy, physiology, and psychiatry". Neurosurgery61 (5): 1091–6; discussion 1096. doi:10.1227/01.neu.0000303205.15489.23. PMID 18091285.
- ^Critchley HD, Wiens S, Rotshtein P, Ohman A, Dolan RJ (February 2004). "Neural systems supporting interoceptive awareness". Nat. Neurosci.7 (2): 189–95. doi:10.1038/nn1176. PMID 14730305.
- ^ abLamb K, Gallagher K, McColl R, Mathews D, Querry R, Williamson JW (April 2007). "Exercise-induced decrease in insular cortex rCBF during postexercise hypotension". Med Sci Sports Exerc39 (4): 672–9. doi:10.1249/mss.0b013e31802f04e0. PMID 17414805.
- ^Williamson JW, McColl R, Mathews D, Mitchell JH, Raven PB, Morgan WP (April 2001). "Hypnotic manipulation of effort sense during dynamic exercise: cardiovascular responses and brain activation". J. Appl. Physiol.90 (4): 1392–9. PMID 11247939.
- ^Williamson JW, McColl R, Mathews D, Ginsburg M, Mitchell JH (September 1999). "Activation of the insular cortex is affected by the intensity of exercise". J. Appl. Physiol.87 (3): 1213–9. PMID 10484598.
- ^Baliki MN, Geha PY, Apkarian AV (February 2009). "Parsing pain perception between nociceptive representation and magnitude estimation". J. Neurophysiol.101 (2): 875–87. doi:10.1152/jn.91100.2008. PMID 19073802.
- ^Ogino Y, Nemoto H, Inui K, Saito S, Kakigi R, Goto F (May 2007). "Inner experience of pain: imagination of pain while viewing images showing painful events forms subjective pain representation in human brain". Cereb. Cortex17 (5): 1139–46. doi:10.1093/cercor/bhl023. PMID 16855007.
- ^Song GH, Venkatraman V, Ho KY, Chee MW, Yeoh KG, Wilder-Smith CH (December 2006). "Cortical effects of anticipation and endogenous modulation of visceral pain assessed by functional brain MRI in irritable bowel syndrome patients and healthy controls". Pain126 (1-3): 79–90. doi:10.1016/j.pain.2006.06.017. PMID 16846694.
- ^Olausson H, Charron J, Marchand S, Villemure C, Strigo IA, Bushnell MC (November 2005). "Feelings of warmth correlate with neural activity in right anterior insular cortex". Neurosci. Lett.389 (1): 1–5. doi:10.1016/j.neulet.2005.06.065. PMID 16051437.
- ^Craig AD, Chen K, Bandy D, Reiman EM (February 2000). "Thermosensory activation of insular cortex". Nat. Neurosci.3 (2): 184–90. doi:10.1038/72131. PMID 10649575.
- ^Ladabaum U, Minoshima S, Hasler WL, Cross D, Chey WD, Owyang C (February 2001). "Gastric distention correlates with activation of multiple cortical and subcortical regions". Gastroenterology120 (2): 369–76. doi:10.1053/gast.2001.21201. PMID 11159877.
- ^Hamaguchi T, Kano M, Rikimaru H, et al. (June 2004). "Brain activity during distention of the descending colon in humans". Neurogastroenterol. Motil.16 (3): 299–309. doi:10.1111/j.1365-2982.2004.00498.x. PMID 15198652.
- ^Matsuura S, Kakizaki H, Mitsui T, Shiga T, Tamaki N, Koyanagi T (November 2002). "Human brain region response to distention or cold stimulation of the bladder: a positron emission tomography study". J. Urol.168 (5): 2035–9. doi:10.1097/01.ju.0000027600.26331.11. PMID 12394703.
- ^von Leupoldt, A.; Sommer, T., Kegat, S., Baumann, H. J., Klose, H., Dahme, B., Buchel, C. (24 January 2008). "The Unpleasantness of Perceived Dyspnea Is Processed in the Anterior Insula and Amygdala". American Journal of Respiratory and Critical Care Medicine177 (9): 1026–1032. doi:10.1164/rccm.200712-1821OC.
- ^Kikuchi M, Naito Y, Senda M, et al. (April 2009). "Cortical activation during optokinetic stimulation — an fMRI study". Acta Otolaryngol.129 (4): 440–3. doi:10.1080/00016480802610226. PMID 19116795.
- ^Papathanasiou ES, Papacostas SS, Charalambous M, Eracleous E, Thodi C, Pantzaris M (2006). "Vertigo and imbalance caused by a small lesion in the anterior insula". Electromyogr Clin Neurophysiol46 (3): 185–92. PMID 16918202.
- ^Brown S, Martinez MJ, Parsons LM (September 2004). "Passive music listening spontaneously engages limbic and paralimbic systems". NeuroReport15 (13): 2033–7. doi:10.1097/00001756-200409150-00008. PMID 15486477.
- ^Sander K, Scheich H (October 2005). "Left auditory cortex and amygdala, but right insula dominance for human laughing and crying". J Cogn Neurosci17 (10): 1519–31. doi:10.1162/089892905774597227. PMID 16269094.
- ^Bamiou DE, Musiek FE, Luxon LM (May 2003). "The insula (Island of Reil) and its role in auditory processing. Literature review". Brain Res. Brain Res. Rev.42 (2): 143–54. doi:10.1016/S0165-0173(03)00172-3. PMID 12738055.
- ^Anderson TJ, Jenkins IH, Brooks DJ, Hawken MB, Frackowiak RS, Kennard C (October 1994). "Cortical control of saccades and fixation in man. A PET study". Brain117 (Pt 5): 1073–84. doi:10.1093/brain/117.5.1073. PMID 7953589.
- ^Fink GR, Frackowiak RS, Pietrzyk U, Passingham RE (April 1997). "Multiple nonprimary motor areas in the human cortex". J. Neurophysiol.77 (4): 2164–74. PMID 9114263.
- ^Sörös P, Inamoto Y, Martin RE (August 2009). "Functional brain imaging of swallowing: an activation likelihood estimation meta-analysis". Hum Brain Mapp30 (8): 2426–39. doi:10.1002/hbm.20680. PMID 19107749.
- ^Penfield W, Faulk ME (1955). "The insula; further observations on its function". Brain78 (4): 445–70. PMID 13293263.
- ^Dronkers NF (November 1996). "A new brain region for coordinating speech articulation". Nature384 (6605): 159–61. doi:10.1038/384159a0. PMID 8906789.
- ^Ackermann H, Riecker A (May 2004). "The contribution of the insula to motor aspects of speech production: a review and a hypothesis". Brain Lang89 (2): 320–8. doi:10.1016/S0093-934X(03)00347-X. PMID 15068914.
- ^Nowak M, Holm S, Biering-Sørensen F, Secher NH, Friberg L (June 2005). ""Central command" and insular activation during attempted foot lifting in paraplegic humans". Hum Brain Mapp25 (2): 259–65. doi:10.1002/hbm.20097. PMID 15849712.
- ^Borovsky A, Saygin AP, Bates E, Dronkers N (June 2007). "Lesion correlates of conversational speech production deficits". Neuropsychologia45 (11): 2525–33. doi:10.1016/j.neuropsychologia.2007.03.023. PMID 17499317.
- ^Mutschler I, Schulze-Bonhage A, Glauche V, Demandt E, Speck O, Ball T (2007). "A rapid sound-action association effect in human insular cortex". In Fitch, Tecumseh. PLoS ONE2 (2): e259. doi:10.1371/journal.pone.0000259. PMC 1800344. PMID 17327919.
- ^Weiller C, Ramsay SC, Wise RJ, Friston KJ, Frackowiak RS (February 1993). "Individual patterns of functional reorganization in the human cerebral cortex after capsular infarction". Ann. Neurol.33 (2): 181–9. doi:10.1002/ana.410330208. PMID 8434880.
- ^Oppenheimer SM, Gelb A, Girvin JP, Hachinski VC (September 1992). "Cardiovascular effects of human insular cortex stimulation". Neurology42 (9): 1727–32. PMID 1513461.
- ^Critchley HD (December 2005). "Neural mechanisms of autonomic, affective, and cognitive integration". J. Comp. Neurol.493 (1): 154–66. doi:10.1002/cne.20749. PMID 16254997.
- ^Pacheco-López G, Niemi MB, Kou W, Härting M, Fandrey J, Schedlowski M (March 2005). "Neural substrates for behaviorally conditioned immunosuppression in the rat". J. Neurosci.25 (9): 2330–7. doi:10.1523/JNEUROSCI.4230-04.2005. PMID 15745959.
- ^Ramírez-Amaya V, Alvarez-Borda B, Ormsby CE, Martínez RD, Pérez-Montfort R, Bermúdez-Rattoni F (June 1996). "Insular cortex lesions impair the acquisition of conditioned immunosuppression". Brain Behav. Immun.10 (2): 103–14. doi:10.1006/brbi.1996.0011. PMID 8811934.
- ^Ramírez-Amaya V, Bermúdez-Rattoni F (March 1999). "Conditioned enhancement of antibody production is disrupted by insular cortex and amygdala but not hippocampal lesions". Brain Behav. Immun.13 (1): 46–60. doi:10.1006/brbi.1998.0547. PMID 10371677.
- ^Karnath HO, Baier B, Nägele T (August 2005). "Awareness of the functioning of one's own limbs mediated by the insular cortex?". J. Neurosci.25 (31): 7134–8. doi:10.1523/JNEUROSCI.1590-05.2005. PMID 16079395.
- ^Craig AD (January 2009). "How do you feel—now? The anterior insula and human awareness". Nat. Rev. Neurosci.10 (1): 59–70. doi:10.1038/nrn2555. PMID 19096369.
- ^Farrer C, Frith CD (March 2002). "Experiencing oneself vs another person as being the cause of an action: the neural correlates of the experience of agency". Neuroimage15 (3): 596–603. doi:10.1006/nimg.2001.1009. PMID 11848702.
- ^Tsakiris M, Hesse MD, Boy C, Haggard P, Fink GR (October 2007). "Neural signatures of body ownership: a sensory network for bodily self-consciousness". Cereb. Cortex17 (10): 2235–44. doi:10.1093/cercor/bhl131. PMID 17138596.
- ^Wicker B, Keysers C, Plailly J, Royet JP, Gallese V, Rizzolatti G (October 2003). "Both of us disgusted in My insula: the common neural basis of seeing and feeling disgust". Neuron40 (3): 655–64. doi:10.1016/S0896-6273(03)00679-2. PMID 14642287.
- ^Wright P, He G, Shapira NA, Goodman WK, Liu Y (October 2004). "Disgust and the insula: fMRI responses to pictures of mutilation and contamination". NeuroReport15 (15): 2347–51. doi:10.1097/00001756-200410250-00009. PMID 15640753.
- ^Jabbi M, Bastiaansen J, Keysers C (2008). "A common anterior insula representation of disgust observation, experience and imagination shows divergent functional connectivity pathways". In Lauwereyns, Jan. PLoS ONE3 (8): e2939. doi:10.1371/journal.pone.0002939. PMC 2491556. PMID 18698355.
- ^Sanfey AG, Rilling JK, Aronson JA, Nystrom LE, Cohen JD (June 2003). "The neural basis of economic decision-making in the Ultimatum Game". Science300 (5626): 1755–8. doi:10.1126/science.1082976. PMID 12805551.
- ^Phan KL, Wager T, Taylor SF, Liberzon I (June 2002). "Functional neuroanatomy of emotion: a meta-analysis of emotion activation studies in PET and fMRI". Neuroimage16 (2): 331–48. doi:10.1006/nimg.2002.1087. PMID 12030820.
- ^Singer T (2006). "The neuronal basis and ontogeny of empathy and mind reading: review of literature and implications for future research". Neurosci Biobehav Rev30 (6): 855–63. doi:10.1016/j.neubiorev.2006.06.011. PMID 16904182.
- ^Ortigue S, Grafton ST, Bianchi-Demicheli F (August 2007). "Correlation between insula activation and self-reported quality of orgasm in women". Neuroimage37 (2): 551–60. doi:10.1016/j.neuroimage.2007.05.026. PMID 17601749.
- ^Craig, A. D. (Bud) (2009). "How do you feel — now? The anterior insula and human awareness". Nature Reviews Neuroscience10: 59–70.
- ^Craig, A. D. (Bud) (2002). "A new view of pain as a homeostatic emotion". Trends in Neuroscience26 (6): 303–307.
- ^Sara W. Lazar, Catherine E. Kerr, Rachel H. Wasserman, Jeremy R. Gray, Douglas N. Greve, Michael T. Treadway, Metta McGarvey, Brian T. Quinn, Jeffery A. Dusek, Herbert Benson, Scott L. Rauch, Christopher I. Moore, and Bruce Fischl (2005). "Meditation experience is associated with increased cortical thickness". NeuroReport16 (17): 1893–7. doi:10.1097/01.wnr.0000186598.66243.19. PMC 1361002. PMID 16272874.
- ^Taylor KS, Seminowicz DA, Davis KD (September 2009). "Two systems of resting state connectivity between the insula and cingulate cortex". Hum Brain Mapp30 (9): 2731–45. doi:10.1002/hbm.20705. PMID 19072897.
- ^ abEckert MA, Menon V, Walczak A, Ahlstrom J, Denslow S, Horwitz A, Dubno JR. (2009). At the heart of the ventral attention system: the right anterior insula. Hum Brain Mapp. 30(8):2530-41. doi:10.1002/hbm.20688PMID 19072895
- ^MUFSON, E; MESULAM, M, PANDYA, D (1 July 1981). "Insular interconnections with the amygdala in the rhesus monkey". Neuroscience6 (7): 1231–1248. doi:10.1016/0306-4522(81)90184-6.
- ^JAKAB, A; MOLNAR, P, BOGNER,P,BERES,M,BERENYI, E (1 oct2011). "Connectivity-based parcellation reveals interhemispheric differences in the insula". Brain Topography. doi:10.1007/s10548-011-0205-y.
- ^Brain, MSN Encarta. Archived 2009-10-31.
- ^Kolb, Bryan; Whishaw, Ian Q. (2003). Fundamentals of human neuropsychology (5th ed.). [New York]: Worth. ISBN 0-7167-5300-6.
- ^Benedetto De Martino, Dharshan Kumaran, Ben Seymour, and Raymond J. Dolan (August 2006). "Frames, Biases, and Rational Decision-Making in the Human Brain". Science313 (6): 684–687. doi:10.1126/science.1128356. PMC 2631940. PMID 16888142.
- ^Gui Xue, Zhonglin Lu, Irwin P. Levin d, Antoine Bechara (2010). "The impact of prior risk experiences on subsequent risky decision-making: The role of the insula". NeuroImage50: 709–716.
- ^Nestor PJ, Graham NL, Fryer TD, Williams GB, Patterson K, Hodges JR (November 2003). "Progressive non-fluent aphasia is associated with hypometabolism centred on the left anterior insula". Brain126 (Pt 11): 2406–18. doi:10.1093/brain/awg240. PMID 12902311.
- ^Gorno-Tempini ML, Dronkers NF, Rankin KP, et al. (March 2004). "Cognition and anatomy in three variants of primary progressive aphasia". Ann. Neurol.55 (3): 335–46. doi:10.1002/ana.10825. PMC 2362399. PMID 14991811.
- ^Nasir H. Naqvi, David Rudrauf, Hanna Damasio, Antoine Bechara. (January 2007). "Damage to the Insula Disrupts Addiction to Cigarette Smoking" (abstract). Science315 (5811): 531–4. doi:10.1126/science.1135926. PMID 17255515.
- ^Vorel SR, Bisaga A, McKhann G, Kleber HD (July 2007). "Insula damage and quitting smoking". Science317 (5836): 318–9; author reply 318–9. doi:10.1126/science.317.5836.318c. PMID 17641181.
- ^Hyman, Steven E. (2005-08-01). "Addiction: A Disease of Learning and Memory" (abstract). Am J Psychiatry162 (8): 1414–22. doi:10.1176/appi.ajp.162.8.1414. PMID 16055762.
- ^Marco Contreras, Francisco Ceric, Fernando Torrealba (January 2007). "Inactivation of the Interoceptive Insula Disrupts Drug Craving and Malaise Induced by Lithium" (abstract). Science318 (5850): 655–8. doi:10.1126/science.1145590. PMID 17962567.
- ^Paulus MP, Stein MB (August 2006). "An insular view of anxiety". Biol. Psychiatry60 (4): 383–7. doi:10.1016/j.biopsych.2006.03.042. PMID 16780813.
- ^Thayer JF, Lane RD (December 2000). "A model of neurovisceral integration in emotion regulation and dysregulation". J Affect Disord61 (3): 201–16. doi:10.1016/S0165-0327(00)00338-4. PMID 11163422.