Still a “hidden island”? The rodent insular cortex in drug seeking, reward, and risk

McGregor, Matthew S.; LaLumiere, Ryan T.

doi:10.1016/j.neubiorev.2023.105334

Cited by 6 publications

(3 citation statements)

References 98 publications

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“…Observed rostro-caudal D1DR and D2DR densities' gradients, as well as the fact that significant differents were found only in the anterior regions are in line with the known anterior and posterior divisions of rodent and human insular cortex [46].…”

Section: Effects Of Specific Epilepsy Typessupporting

confidence: 67%

“…Interestingly, this putatively ASD-related pattern was specifically localized in the lateral aspects of prefrontal cortex. Insular cortex is a place of convergence for interoceptory sensory inflow and emotional processing in limbic circuits [46,49]. In humans, the insular cortex is referred as a structure responsible for "embodied emotions [49].…”

Section: Effects Of Social Phenotypementioning

confidence: 99%

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D1-like and D2-like Dopamine Receptor of Rat Prefrontal Cortex: Impacts of Genetic Generalized Epilepsies and Social Behavioral Deficits

Birioukova,

Van Luijtelaar,

Midzyanovskaya

2023

Preprint

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The involvement of the prefrontal cortical dopaminergic system in psychopathology of epilepsies and comorbid conditions such as autism spectrum disorder (ASD) still needs to be explored. We used autoradiography to study the D1-like (D1DR) and D2-like (D2DR) receptor binding density in the prefrontal cortex of normal Wistar rats and Wistar-derived strains with generalized convulsive and/or nonconvulsive epilepsies. WAG/Rij rats served as a model for non-convulsive absence epilepsy, WAG/Rij-AGS as a model of mixed convulsive/non-convulsive forms, and KM strain was a model for convulsive epilepsy comorbiding with ASD-like behavioral phenotype. Prefrontal cortex of rats with any of epileptic pathology studied, demonstrated profound decreases in binding densities to both D1DR, D2DR; the effects were localized in the primary and secondary anterior cingulate cortexi, and adjacent regions. The local decreased D1DR and D2DR binding densities were independent (not correlated) from each other. The particular group of epileptic rats with ASD-like phenotype (KM strain), displayed changes in the lateral prefrontal cortex and adjacent regions: D1DR were lowered, but those to D2DR elevated, in anterior dysgranular insular cortex and adjacent regions. Thus, epilepsy-related changes in the dopaminergic system of rat archeocortex were localized in the medial regions, whereas ASD-related candidates were seen in the lateral aspects. The findings point to putative local dopaminergic dysfunctions, associated with generalized epilepsies and/or ASD.

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Section: Effects Of Specific Epilepsy Typessupporting

confidence: 67%

Section: Effects Of Social Phenotypementioning

confidence: 99%

D1-like and D2-like Dopamine Receptor of Rat Prefrontal Cortex: Impacts of Genetic Generalized Epilepsies and Social Behavioral Deficits

Birioukova,

Van Luijtelaar,

Midzyanovskaya

2023

Preprint

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“…Lastly, we identified an insula gamma power increase following bet cue that predicted subsequent risky choices. The insula is broadly thought to be implicated in risk related decision making and reward-seeking, 76,77 and decreased insula fMRI activity has been associated with higher levels of risk aversion in patients with obsessive-compulsive disorder. 26 Our study supports the role of insula in risk related decision-making and suggests that insula neural signals can predict risky choices.…”

Section: Discussionmentioning

confidence: 99%

Reward Circuit Local Field Potential Modulations Precede Risk Taking

Hughes,

Qian,

Zargari

et al. 2024

Preprint

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Risk taking behavior is a symptom of multiple neuropsychiatric disorders and often lacks effective treatments. Reward circuitry regions including the amygdala, orbitofrontal cortex, insula, and anterior cingulate have been implicated in risk-taking by neuroimaging studies. Electrophysiological activity associated with risk taking in these regions is not well understood in humans. Further characterizing the neural signalling that underlies risk-taking may provide therapeutic insight into disorders associated with risk-taking.Eleven patients with pharmacoresistant epilepsy who underwent stereotactic electroencephalography with electrodes in the amygdala, orbitofrontal cortex, insula, and/or anterior cingulate participated. Patients participated in a gambling task where they wagered on a visible playing card being higher than a hidden card, betting $5 or $20 on this outcome, while local field potentials were recorded from implanted electrodes. We used cluster-based permutation testing to identify reward prediction error signals by comparing oscillatory power following unexpected and expected rewards. We also used cluster-based permutation testing to compare power preceding high and low bets in high-risk (<50% chance of winning) trials and two-way ANOVA with bet and risk level to identify signals associated with risky, risk averse, and optimized decisions. We used linear mixed effects models to evaluate the relationship between reward prediction error and risky decision signals across trials, and a linear regression model for associations between risky decision signal power and Barratt Impulsiveness Scale scores for each patient.Reward prediction error signals were identified in the amygdala (p=0.0066), anterior cingulate (p=0.0092), and orbitofrontal cortex (p=6.0E-4, p=4.0E-4). Risky decisions were predicted by increased oscillatory power in high-gamma frequency range during card presentation in the orbitofrontal cortex (p=0.0022), and by increased power following bet cue presentation across the theta-to-beta range in the orbitofrontal cortex (p=0.0022), high-gamma in the anterior cingulate (p=0.0004), and high-gamma in the insula (p=0.0014). Risk averse decisions were predicted by decreased orbitofrontal cortex gamma power (p=2.0E-4). Optimized decisions that maximized earnings were preceded by decreases within the theta to beta range in orbitofrontal cortex (p=2.0E-4), broad frequencies in amygdala (p=2.0E-4), and theta to low-gamma in insula (p=4.0E-4). Insula risky decision power was associated with orbitofrontal cortex high-gamma reward prediction error signal (p=0.0048) and with patient impulsivity (p=0.00478).Our findings identify and help characterize reward circuitry activity predictive of risk-taking in humans. These findings may serve as potential biomarkers to inform the development of novel treatment strategies such as closed loop neuromodulation for disorders of risk taking.

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The anterior insula and its projection to amygdala nuclei modulate the abstinence-exacerbated expression of conditioned place preference

Agoitia,

Cruz-Sanchez,

Balderas

et al. 2023

Psychopharmacology

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Rationale Relapse into substance use is often triggered by exposure to drug-related environmental cues. The magnitude of drug seeking depends on the duration of abstinence, a phenomenon known as the incubation of drug craving. Clinical and preclinical research shows that the insular cortex is involved in substance use disorders and cue-induced drug seeking. However, the role of the insula on memory retrieval and motivational integration for cue-elicited drug seeking remains to be determined. Objectives We investigated the role of the anterior insular cortex (aIC) and its glutamatergic projection to amygdala nuclei (aIC-AMY) on the expression of conditioned place preference (CPP) during early and late abstinence. Methods Male adult C57BL/6J mice underwent amphetamine-induced CPP, and their preference was tested following 1 or 14 days of abstinence. aIC and aIC-AMY functional role in CPP expression was assessed at both abstinence periods by employing optogenetic silencing and behavioral pharmacology. Results Compared to a single day, an exacerbated preference for the amphetamine-paired context was observed after 14 days of abstinence. Photoinhibition of either aIC or aIC-AMY projection reduced CPP expression following late but not early abstinence. Similarly, the antagonism of aIC NMDA receptors reduced CPP expression after 14 days of abstinence but not 1 day. Conclusions These results suggest that aIC and its glutamatergic output to amygdala nuclei constitute critical neurobiological substrates mediating enhanced motivational cue reactivity during the incubation of amphetamine craving rather than contextual memory recall. Moreover, cortical NMDA receptor signaling may become sensitized during abstinence, ultimately modulating disproportioned drug seeking.

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Still a “hidden island”? The rodent insular cortex in drug seeking, reward, and risk

Cited by 6 publications

References 98 publications

D1-like and D2-like Dopamine Receptor of Rat Prefrontal Cortex: Impacts of Genetic Generalized Epilepsies and Social Behavioral Deficits

D1-like and D2-like Dopamine Receptor of Rat Prefrontal Cortex: Impacts of Genetic Generalized Epilepsies and Social Behavioral Deficits

Reward Circuit Local Field Potential Modulations Precede Risk Taking

The anterior insula and its projection to amygdala nuclei modulate the abstinence-exacerbated expression of conditioned place preference

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