Insular Cortex Lesions Research Articles

Conditioned taste aversion and latent inhibition following extensive taste preexposure in rats with insular cortex lesions

Lesions of the insular cortex (IC) attenuate acquisition of conditioned taste aversions (CTAs). We have suggested that this impairment is the expected consequence of a failure of IC-lesioned (ICX) rats to recognize unfamiliar taste stimuli as novel. That is, ICX rats treat novel taste stimuli as if they are familiar and as a result show a latent inhibition-like retardation of learning. This account anticipates that ICX rats should acquire CTAs at the same slow rate as normal rats that are familiar with the taste stimulus. The present experiment confirmed this hypothesis in a design that compared CTA acquisition in normal and ICX rats following either extensive taste familiarization or no taste familiarization prior to conditioning.

Insular cortex lesions and morphine-induced suppression of conditioned stimulus intake in the rat.

The present experiment examined the influence of insular cortex (IC) lesions on the intake of a taste stimulus in a consummatory procedure that used morphine as the unconditioned stimulus. In normal rats, morphine caused a rapid reduction in saccharin intake when the taste was novel but not when it was familiar. Irrespective of stimulus novelty, morphine had little influence on the saccharin consumption of IC-lesioned rats. The results are discussed in terms of a lesion-induced disruption of (i) a reward comparison mechanism and (ii) the perception of taste novelty.

Establishing aversive, but not safe, taste memories requires lateralized pontine–cortical connections

Aversive and safe taste memory processing is dramatically disrupted by bilateral lesions of the pontine parabrachial nucleus (PBN). To determine how such lesions affect patterns of neuronal activation in forebrain, lesions were combined with assessment of cFos-like immunoreactivity (FLI) in insular cortex (IC) and amygdala after conditioned taste aversion (CTA) training. Increases in FLI in amygdala and IC, which are normally seen following novel (versus familiar) CS–US pairing, were eliminated after PBN lesions. This suggests that PBN lesions prevent transmission of critical CS and US information to forebrain regions for the processing of both aversive and safe taste memories. Unilateral asymmetrical lesions of PBN and IC blocked CTA acquisition as well as normal patterns of FLI in amygdala after novel CS–US pairing, an effect not seen when unilateral lesions were confined to a single hemisphere. The crossed-disconnection experiments provide compelling evidence that functional interactions between PBN and IC are required for CTA acquisition, but not for safe taste memory formation and retrieval. The dissociation between effects of the different types of lesions on safe and aversive taste memories supports emerging evidence that the neural underpinnings of the two types of taste learning differ.

Reduced Perception of Dyspnea and Pain after Right Insular Cortex Lesions

The perception of dyspnea and pain show many similarities. Initial imaging studies suggested an important role of the insular cortex for the perception of both sensations. However, little is known about the cortical processing of dyspnea. This study investigated the influence of lesions of the insular cortex on the perception of dyspnea and pain. Dyspnea was induced by resistive loaded breathing in four patients with right-hemispheric insular cortex lesions, as assessed with computer tomography or magnetic resonance imaging, and four matched healthy control subjects. Pain was induced by a cold-pressor test. Perceived intensity and unpleasantness of both sensations were rated on visual analog scales. In contrast to healthy control subjects, patients with lesions demonstrated reduced perceptual sensitivity for dyspnea, in particular for the unpleasantness of dyspnea (P < 0.05). This was paralleled by reduced sensitivity for pain in patients with lesions, as reflected by smaller ratings of intensity and unpleasantness, higher sensory pain-thresholds, and, in particular, higher affect-related pain tolerance times (P < 0.05). The results suggest that lesions of the right insular cortex are associated with reduced sensitivity for the perception of dyspnea and pain, in particular for their perceived unpleasantness. This underlines the importance of the insular cortex for the perception of both sensations.

Stroke-Induced Sudden-Autonomic Death

See related article, pages 2425–2431. Stroke is the third leading cause of death.1,2 Fatal outcome has been primarily related to acute or chronic complications of stroke-induced executive deficits, such as muscle weakness, swallowing disorders, respiratory dysfunction with pneumonia, or cardiac complications.3,4 Only during the last 10 or 15 years has there been an increasing interest in and knowledge of associations between cerebral lesions and altered influences of the central autonomic nervous system on cardiovascular and respiratory function.5–7 Oppenheimer et al8–10 suggested a role of the insular cortex in the pathophysiology of sudden death. The group extensively assessed topographically distinct interactions of the left and the right insular cortex with heart rate and blood pressure control.11 There was agreement that insular cortex lesions essentially contribute to clinically relevant alterations of cardiovascular control.8 In this issue of Stroke , Rincon and coworkers present an analysis of associations between ischemic stroke location and fatal cardiac outcome, based on the epidemiological data of the Northern Manhattan Stroke study (NOMAS).12,13 Considering neurological syndromes and neuroimaging findings, the authors analyzed outcome during a 5-year follow-up period. Mortality rates or nonfatal myocardial infarctions, and particularly sudden unexpected or unwitnessed death, were associated with the location of brain infarctions. Apart from age, male gender, the National Institutes of Health Stroke Scale (NIHSS), and a history of coronary artery disease, the authors identified infarct locations in the frontal, parietal, temporal lobe, and …

Differential effects of insular and ventromedial prefrontal cortex lesions on risky decision-making

The ventromedial prefrontal cortex (vmPFC) and insular cortex are implicated in distributed neural circuitry that supports emotional decision-making. Previous studies of patients with vmPFC lesions have focused primarily on decision-making under uncertainty, when outcome probabilities are ambiguous (e.g. the Iowa Gambling Task). It remains unclear whether vmPFC is also necessary for decision-making under risk, when outcome probabilities are explicit. It is not known whether the effect of insular damage is analogous to the effect of vmPFC damage, or whether these regions contribute differentially to choice behaviour. Four groups of participants were compared on the Cambridge Gamble Task, a well-characterized measure of risky decision-making where outcome probabilities are presented explicitly, thus minimizing additional learning and working memory demands. Patients with focal, stable lesions to the vmPFC (n = 20) and the insular cortex (n = 13) were compared against healthy subjects (n = 41) and a group of lesion controls (n = 12) with damage predominantly affecting the dorsal and lateral frontal cortex. The vmPFC and insular cortex patients showed selective and distinctive disruptions of betting behaviour. VmPFC damage was associated with increased betting regardless of the odds of winning, consistent with a role of vmPFC in biasing healthy individuals towards conservative options under risk. In contrast, patients with insular cortex lesions failed to adjust their bets by the odds of winning, consistent with a role of the insular cortex in signalling the probability of aversive outcomes. The insular group attained a lower point score on the task and experienced more ‘bankruptcies’. There were no group differences in probability judgement. These data confirm the necessary role of the vmPFC and insular regions in decision-making under risk. Poor decision-making in clinical populations can arise via multiple routes, with functionally dissociable effects of vmPFC and insular cortex damage.

Gustatory insular cortex lesions disrupt drug-induced, but not lithium chloride-induced, suppression of conditioned stimulus intake.

Rats suppress intake of a normally preferred 0.15% saccharin conditioned stimulus (CS) when it is paired with an aversive agent like lithium chloride (LiCl) or a preferred substance such as sucrose or a drug of abuse. The reward comparison hypothesis suggests that rats avoid intake of a saccharin cue following pairings with a drug of abuse because the rats are anticipating the availability of the rewarding properties of the drug. The present study used bilateral ibotenic acid lesions to examine the role of the gustatory cortex in the suppression of CS intake induced by cocaine, morphine, and LiCl. The results show that bilateral lesions of the insular gustatory cortex (1) fully prevent the suppressive effects of both a 15 and a 30 mg/kg dose of morphine, (2) attenuate the suppressive effect of a 10 mg/kg dose of cocaine, but (3) are overridden by a 20 mg/kg dose of the drug. Finally, these same cortical lesions had no impact on LiCl-induced conditioned taste aversion. The current data show that the insular taste cortex plays an integral role in drug-induced avoidance of a gustatory CS.

Effects of insular cortex lesions on conditioned taste aversion and latent inhibition in the rat

The present study tested the hypothesis that lesions of the insular cortex of the rat retard the acquisition of conditioned taste aversions (CTAs) because of an impairment in the detection of the novelty of taste stimuli. Demonstrating the expected latent inhibition effect, nonlesioned control subjects acquired CTAs more rapidly when the conditioned stimulus (0.15% sodium saccharin) was novel rather than familiar (achieved by pre-exposure to the to-be-conditioned taste cue). However, rats with insular cortex lesions acquired taste aversions at the same slow rate regardless of whether the saccharin was novel or familiar. The pattern of behavioural deficits obtained cannot be interpreted as disruptions of taste detection or stimulus intensity, but is consistent with the view that insular cortex lesions disrupt taste neophobia, a dysfunction that consequently retards CTA acquisition because of a latent inhibition-like effect.

Insular cortex lesions fail to block flavor and taste preference learning in rats

The role of the insular cortex (IC) in learning to associate orosensory cues with the oral and post-oral properties of carbohydrate was examined. Rats with either small (gustatory region) or large (gustatory and visceral regions) ibotenic acid lesions of the IC learned to prefer flavors (Experiments 1 and 3) and taste mixtures (Experiments 2 and 4) paired with intragastric infusions of maltodextrin. The rats with large IC lesions also learned a preference for a flavor cue paired with the sweet taste of fructose (Experiment 5). In fact, they showed enhanced conditioning and retarded extinction compared with controls. Collectively, these data provided no evidence that IC is essential for flavor preference learning based on associations between the orosensory cues and the oral and post-oral reinforcing properties of nutrients.

Lesions of the gustatory thalamocortical loop block drug-induced devaluation of a natural saccharin reward cue, while leaving instrumental responding for the drug intact.

Asymmetric ibotenic acid lesions of the taste nuclei in the thalamus and cortex (THCx) selectively disrupt avoidance of a taste cue when paired with a rewarding sucrose solution or morphine, but not when paired with the aversive agent, LiCl (Geddes et al., submitted). The present study used similar THCx lesions to examine the role of this thalamocortical loop in drug-induced suppression of intake of the taste cue, drug-seeking (runway) and drug-taking (self-administration) behavior. Using predetermined coordinates (cortex) and electrophysiological guidance (thalamus), 22 rats received unilateral lesions of the VPMpc and contralateral lesions of the gustatory insular cortex (THCx). The remaining 22 control (Cntl) rats received ipsilateral lesions (different nuclei, same hemisphere). In Experiment 1, half of the Cntl and THCx rats were water-deprived and given 5 min access to saccharin in the start box followed by an ip injection of morphine (15 mg/kg) in the goal box for 6 trials in a runway. In Experiment 2, the remaining half of the rats were water-deprived and given 5 min access to the saccharin CS followed by 1.5 h to self-administer cocaine over 14 trials in an operant chamber. Collectively, the results showed that the THCx lesion blocked both morphine- and cocaine-induced suppression of intake of the saccharin CS, but had no effect on instrumental responding for the drug. Thus, while this thalamocortical loop is essential for drug-induced devaluation of CS intake, it is not involved in responding, instrumentally, to the reinforcing properties of the drugs. This research was supported by DA12473 and DA017416.

The role of the agranular insular cortex in anticipation of reward contrast

Sixteen male Long–Evans rats were tested on a modified version of Flaherty et al.’s [Flaherty, C. F., Turovsky, J., & Krauss, K. L. (1994). Relative hedonic value modulates anticipatory contrast. Physiology and Behavior, 55, 1047–1054.] anticipatory contrast paradigm to assess memory for the anticipation of reward. Prior to testing each rat received either a control or quinolinic acid induced lesion of the agranular insular cortex. In the home cage, each rat was allowed to drink a water solution containing 2% sucrose for 3 min followed by a water solution containing 32% sucrose for 3 min. Across 10 days of testing, the control rats showed significantly increased anticipatory discriminability as a function of days. In contrast, rats with agranular insular cortex lesions failed to show anticipatory discriminability. The results of a preference task revealed that both groups could perceptually discriminate between a 2% and a 32% sucrose solution. The data suggest that the agranular insular cortex may be involved in the anticipation of reward.

Neural Substrates for Behaviorally Conditioned Immunosuppression in the Rat

We have previously demonstrated behaviorally conditioned immunosuppression using cyclosporin A as an unconditioned stimulus and saccharin as a conditioned stimulus. In the current study, we examined the central processing of this phenomenon generating excitotoxic lesions before and after acquisition to discriminate between learning and memory processes. Three different brain areas were analyzed: insular cortex (IC), amygdala (Am), and ventromedial nucleus of the hypothalamus (VMH). The results demonstrate that IC lesions performed before and after acquisition disrupted the behavioral component of the conditioned response (taste aversion). In contrast, Am and VMH lesions did not affect conditioned taste aversion. The behaviorally conditioned suppression of splenocyte proliferation and cytokine production (interleukin-2 and interferon-gamma) was differentially affected by the excitotoxic lesions, showing that the IC is essential to acquire and evoke this conditioned response of the immune system. In contrast, the Am seems to mediate the input of visceral information necessary at the acquisition time, whereas the VMH appears to participate within the output pathway to the immune system necessary to evoke the behavioral conditioned immune response. The present data reveal relevant neural mechanisms underlying the learning and memory processes of behaviorally conditioned immunosuppression.

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

The insular gustatory cortex may be essential for the evaluation of saliency and representation of the incentive values of tastes. Gustatory cortex lesions should interfere with conditioned taste avoidance according to these factors, which depend on the conditioned taste avoidance protocol used. The present study was aimed at investigating the effects of bilateral lesions of the gustatory cortex—focusing on electrolytic and excitotoxic lesions. Lesioned and sham-operated male Long–Evans rats were intoxicated using LiCl after drinking sucrose from a tube (SD) or having the same amount of sucrose fed directly into their mouths through a chronically implanted intra-oral (IO) cannula. Every aspect of the experiment was carefully counterbalanced between the experimental groups. In the control groups, the acquired avoidance towards sucrose was strongly preserved over eight extinction test days in SD rats but not in IO rats, in which a progressive decline was recorded. Electrolytic gustatory cortex lesions impaired but did not suppress conditioned taste avoidance in both protocols. Excitotoxic lesions tend to impair CTA also, but differentially according to the SD or IO protocols. Extinction of CTA was selectively impaired in the SD protocol by small lesions destroying the anterior insular cortex.

Unconditioned stimulus pathways to the amygdala: effects of posterior thalamic and cortical lesions on fear conditioning

Plasticity in the lateral nucleus of the amygdala is thought to be critical for the acquisition of Pavlovian fear conditioning. The pathways that transmit auditory conditioned stimulus information originate in auditory processing regions of the thalamus and cortex, but the pathways mediating transmission of unconditioned stimuli to the amygdala are poorly understood. Recent studies suggest that somatosensory (footshock) unconditioned stimulus information is also relayed in parallel to the lateral nucleus of the amygdala from the thalamus (the posterior intralaminar thalamic complex, PIT) and the cortex (parietal insular cortex). In the present study we reexamined this issue. Our results showed that bilateral electrolytic lesions of the PIT alone blocked fear conditioning, whereas bilateral excitotoxic PIT lesions had no effect. These electrolytic PIT lesions did not affect fear conditioning using a loud noise as unconditioned stimulus, defining the effects of PIT lesions as a disruption of somatosensory as opposed to auditory processing. Finally, we performed combined bilateral excitotoxic lesions of the PIT nuclei and electrolytic lesions of the parietal insular cortex. These, like excitotoxic lesions of PIT alone, had no effect on the acquisition of fear conditioning. Thus, somatosensory regions of the thalamus and cortex may well be important routes of unconditioned stimulus transmission to the amygdala in fear conditioning, but information about the unconditioned somatosensory stimulus is also transmitted from other sources that send fibers through, but do not form essential synapses in, the thalamus en route to the amygdala.

Fear conditioning to tone, but not to context, is attenuated by lesions of the insular cortex and posterior extension of the intralaminar complex in rats.

Fear conditioning to tone, but not to context, is attenuated by lesions of the insular cortex and posterior extension of the intralaminar complex in rats.

Insular cortex lesions and taste aversion learning: effects of conditioning method and timing of lesion

The specific role of insular cortex in acquisition and expression of a conditioned taste aversion was assessed using two different conditioning methods, which vary mode of taste delivery. Involvement of insular cortex in the induction of c-Fos-immunoreactivity in the nucleus of the solitary tract, a cellular correlate of the behavioral expression of a conditioned taste aversion, was also assessed. Electrolytic lesions of insular cortex blocked behavioral expression of a conditioned taste aversion and this was evident not only when lesions were placed prior to conditioning, but also when they were made after conditioning but before testing. In contrast to the effects on behavior, lesions did not completely block the c-Fos-immunoreactivity which accompanies re-exposure to the aversive taste. In addition, the blocking of behavioral evidence of aversion conditioning by cortical lesions was seen both in animals trained under an intraoral acquisition procedure and those trained with bottle-conditioning. This contrasts with previous work with amygdala lesions which showed that amygdala was absolutely necessary for taste aversions conditioned with the intraoral method but not for those conditioned using bottle presentation of the taste. Overall, these findings imply that the details of the neural circuitry involved in taste aversion learning, including its anatomical distribution, complexity and degree of redundancy, vary with the type of conditioning method employed.

Abstracts of literature

Abstracts of literature

Pain Pathways Involved in Fear Conditioning Measured with Fear-Potentiated Startle: Lesion Studies

It is well established that the basolateral amygdala is critically involved in the association between an unconditioned stimulus (US), such as a foot shock, and a conditioned stimulus (CS), such as a light, during classic fear conditioning. However, little is known about how the US (pain) inputs are relayed to the basolateral amygdala. The present studies were designed to define potential US pathways to the amygdala using lesion methods. Electrolytic lesions before or after training were placed in caudal granular/dysgranular insular cortex (IC) alone or in conjunction with the posterior intralaminar nuclei of the thalamus (PoT/PIL), and the effects on fear conditioning were examined. Pretraining lesions of both IC and PoT/PIL, but not lesions of IC alone, blocked the acquisition of fear-potentiated startle. However, post-training combined lesions of IC and PoT/PIL did not prevent expression of conditioned fear. Given that previous studies have shown that lesions of PoT/PIL alone had no effect on acquisition of conditioned fear, these results suggest that two parallel cortical (insula-amygdala) and subcortical (PoT/PIL-amygdala) pathways are involved in relaying shock information to the basolateral amygdala during fear conditioning.

Taste perception in patients with insular cortex lesions.

Taste perception in patients with insular cortex lesions.

Taste perception in patients with insular cortex lesions.

Research on nonhuman primates suggests that the primary taste cortex in humans is located in the rostrodorsal insula. Qualitative and quantitative assessment of taste perception was performed on 6 patients with unilateral damage to the insula, 3 patients with brain damage outside the insula, and 11 age-matched, normal subjects. Each subject identified the quality and intensity of the gustatory stimuli applied separately to the left and right sides of the anterior tongue. Damage to the right insula produced ipsilateral taste recognition and intensity deficits. Damage to the left insula caused an ipsilateral deficit in taste intensity but a bilateral deficit in taste recognition. The unexpected deficit in the left-hemispheric stroke patients for taste recognition on the right side of the tongue suggests that taste information from both sides of the tongue passes through the left insula.