Editing Insular cortex (section)

== Clinical significance ==

=== Progressive expressive aphasia ===
Progressive [[expressive aphasia]] is the deterioration of normal [[language function]] that causes individuals to lose the ability to communicate fluently while 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<ref>{{cite journal |vauthors=Nestor PJ, Graham NL, Fryer TD, Williams GB, Patterson K, Hodges JR |title=Progressive non-fluent aphasia is associated with hypometabolism centred on the left anterior insula |journal=Brain |volume=126 |issue=Pt 11 |pages=2406–18 |date=November 2003 |pmid=12902311 |doi=10.1093/brain/awg240 |doi-access=free }}</ref> and atrophy of the left anterior insular cortex.<ref>{{cite journal  |vauthors=Gorno-Tempini ML, Dronkers NF, Rankin KP, etal |title=Cognition and anatomy in three variants of primary progressive aphasia |journal=Annals of Neurology |volume=55 |issue=3 |pages=335–46 |date=March 2004 |pmid=14991811 |pmc=2362399 |doi=10.1002/ana.10825}}</ref>

=== Addiction ===
A number of functional brain imaging studies have shown that the insular cortex is activated when drug users are exposed to environmental cues that trigger cravings. This has been shown for a variety of drugs, including [[cocaine]], [[alcohol (drug)|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 mesocortical [[dopamine]] system, which is central to current dopamine reward theories of addiction. Research published in 2007<ref>{{Cite journal
|author1=Nasir H. Naqvi |author2=David Rudrauf |author3=Hanna Damasio |author4=Antoine Bechara. | title   = Damage to the Insula Disrupts Addiction to Cigarette Smoking
| journal = [[Science (journal)|Science]]
| date    = January 2007
| volume  = 315
| issue   = 5811
| pages   = 531–4
| doi     = 10.1126/science.1135926
| pmid    = 17255515
| pmc     = 3698854
|bibcode=2007Sci...315..531N }}</ref> has shown that [[cigarette]] smokers suffering damage to the insular cortex, from a [[stroke]] for instance, have their addiction to cigarettes practically eliminated. 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. The study was conducted on average eight years after the strokes, which opens up the possibility that [[recall bias]] could have affected the results.<ref>{{cite journal |vauthors=Vorel SR, Bisaga A, McKhann G, Kleber HD |title=Insula damage and quitting smoking |journal=Science |volume=317 |issue=5836 |pages=318–9; author reply 318–9 |date=July 2007 |pmid=17641181 |doi=10.1126/science.317.5836.318c |s2cid=8917168 }}</ref>  More recent prospective studies, which overcome this limitation, have corroborated these findings<ref>{{cite journal|doi=10.1161/STROKEAHA.111.630004 | pmid=22052507 | title=Smoking Cessation 1 Year Poststroke and Damage to the Insular Cortex | journal=Stroke | date=2011 | volume=43 | issue=1 | pages=131–136 | first=R. | last=Suner-Soler| doi-access=free }}</ref><ref>{{cite journal|doi=10.1093/ntr/ntt172 | pmid=24169814 | title=Basal Ganglia Plus Insula Damage Yields Stronger Disruption of Smoking Addiction Than Basal Ganglia Damage Alone | journal=Nicotine | date=2013 | volume=16 | issue=4 | pages=445–453 | first=N. | last=Gaznick| pmc=3954424 }}</ref>  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.<ref>{{Cite journal
| doi     = 10.1176/appi.ajp.162.8.1414
| volume  = 162
| issue   = 8
| pages   = 1414–22
| last    = Hyman
| first   = Steven E.
| title   = Addiction: A Disease of Learning and Memory
| journal = Am J Psychiatry
| date    = 2005-08-01
| pmid    = 16055762
}}</ref>

A recent study in rats by Contreras et al.<ref>{{Cite journal
|author1=Marco Contreras |author2=Francisco Ceric |author3=Fernando Torrealba | title   = Inactivation of the Interoceptive Insula Disrupts Drug Craving and Malaise Induced by Lithium
| journal = [[Science (journal)|Science]]
| date    = January 2007
| volume  = 318
| issue   = 5850
| pages   = 655–8
| doi     = 10.1126/science.1145590
| pmid    = 17962567
|bibcode=2007Sci...318..655C |s2cid=23499558 | hdl= 10533/135157
| hdl-access= free
}}</ref> 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 is 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 addictive psychoactive drugs. 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.

===Subjective certainty in ecstatic seizures===
{{Main|Ecstatic seizures}}

A common quality in mystical experiences is a strong feeling of certainty which [[ineffability|cannot be expressed in words]]. Fabienne Picard proposes a neurological explanation for this subjective certainty, based on clinical research of epilepsy.<ref>{{Citation | last =Picard | first =Fabienne |title =State of belief, subjective certainty and bliss as a product of cortical dysfuntion | journal =Cortex |volume=49 | issue =9 |year=2013 |pages=2494–2500| pmid =23415878 | doi =10.1016/j.cortex.2013.01.006 | s2cid =206984751 }}</ref><ref>{{Citation | last1 =Gschwind | first1 =Markus | last2 =Picard | first2 =Fabienne | year =2016 | title =Ecstatic Epileptic Seizures: a glimpse into the multiple roles of the insula | journal =Frontiers in Behavioral Neuroscience | volume =10 | page =21 | doi=10.3389/fnbeh.2016.00021 | pmid=26924970 | pmc=4756129| doi-access =free }}</ref>
According to Picard, this feeling of certainty may be caused by a dysfunction of the anterior insula, a part of the brain which is involved in [[interoception]], self-reflection, and in avoiding uncertainty about the internal representations of the world by "anticipation of resolution of uncertainty or risk". This avoidance of uncertainty functions through the comparison between predicted states and actual states, that is, "signaling that we do not understand, i.e., that there is ambiguity."<ref>Picard 2013, p.2496-2498</ref> Picard notes that  "the concept of insight is very close to that of certainty," and refers to Archimedes' "Eureka!"<ref>Picard 2013, p.2497-2498</ref><ref>See also [[satori]] in Japanese Zen</ref> Picard hypothesizes that during ecstatic seizures the comparison between predicted states and actual states no longer functions, and that mismatches between predicted state and actual state are no longer processed, blocking "[[negative emotion]]s and negative arousal arising from predictive uncertainty," which will be experienced as emotional confidence.<ref name="Picard 2013, p.2498">Picard 2013, p.2498</ref> Picard concludes that "[t]his could lead to a spiritual interpretation in some individuals."<ref name="Picard 2013, p.2498"/>

===Other clinical conditions===
The insular cortex has been suggested to have a role in anxiety disorders,<ref>{{cite journal |vauthors=Paulus MP, Stein MB |title=An insular view of anxiety |journal=Biol. Psychiatry |volume=60 |issue=4 |pages=383–7 |date=August 2006 |pmid=16780813 |doi=10.1016/j.biopsych.2006.03.042 |s2cid=17889111 }}</ref>  emotion dysregulation,<ref>{{cite journal |vauthors=Thayer JF, Lane RD |title=A model of neurovisceral integration in emotion regulation and dysregulation |journal=J Affect Disord |volume=61 |issue=3 |pages=201–16 |date=December 2000 |pmid=11163422 |doi=10.1016/S0165-0327(00)00338-4|url=https://zenodo.org/record/1259859 }}</ref> and [[anorexia nervosa]].<ref name="Gaudio2016">{{cite journal |vauthors=Gaudio S, Wiemerslage L, Brooks SJ, Schiöth HB | title = A systematic review of resting-state functional-MRI studies in anorexia nervosa: Evidence for functional connectivity impairment in cognitive control and visuospatial and body-signal integration. | journal = Neurosci Biobehav Rev | year = 2016 | pmid = 27725172 | doi = 10.1016/j.neubiorev.2016.09.032 | volume=71 | pages=578–589| s2cid = 16526824 | url = http://researchonline.ljmu.ac.uk/9236/1/A%20systematic%20review%20of%20resting-state%20functional-MRI%20studies%20in%20anorexia%20nervosa%20Evidence%20for%20functional%20connectivity%20impairment%20in%20cognitive%20control%20and%20visuospatial%20and%20body-signal%20integration..pdf | doi-access = free }}</ref>