Salience processing and insular cortical function and dysfunction

Uddin, Lucina Q.

doi:10.1038/nrn3857

Cited by 1,765 publications

(1,536 citation statements)

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“…Salience could be described as the property of a stimulus that makes it differentially relevant from the others within an environment (Uddin, 2015). The attribution of salience to the surrounding environmental stimuli is an essential process for survival that allows individuals to perform adaptive behavioral responses to approach beneficial goals or avoid threatening ones (Borsook et al, 2013).…”

Section: The Cerebellum In Cravingmentioning

confidence: 99%

The cerebellum in drug craving

Moreno-Rius

Miquel

2017

Drug and Alcohol Dependence

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Craving has been considered one of the core features of addiction. It can be defined as the urge or conscious desire to use a drug elicited by the drug itself, drug-associated cues or stressors. Craving plays a major role in relapse, even after prolonged periods of abstinence, as well as in the maintenance of drug seeking in non-abstinent addicts. The circuitry of craving includes medial parts of the prefrontal cortex, ventral striatal zones, ventral tegmental area, ventral pallidum, and limbic regions. Interestingly, the cerebellum shows reciprocal loops with many of these areas. The cerebellum has been linked traditionally to motor functions but increasing evidence indicates that this part of the brain is also involved in functions related to cognition, prediction, learning, and memory. Moreover, the functional neuroimaging studies that have addressed the study of craving in humans repeatedly demonstrate cerebellar activation when craving is elicited by the presentation of drug-related cues. However, the role of cerebellar activity in these craving episodes remains unknown. Therefore, the main goal of this review is to provide a brief update on craving studies and the traditional neural basis of this phenomenon, and then discuss and propose a hypothesis for the function of the cerebellum in craving episodes.

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Section: The Cerebellum In Cravingmentioning

confidence: 99%

The cerebellum in drug craving

Moreno-Rius

Miquel

2017

Drug and Alcohol Dependence

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“…The ECN, including the medial frontal gyrus, superior frontal gyrus, and the anterior cingulate cortex, is engaged during executive function tasks that require cognitive control and working memory (Seeley et al, 2007). The SN, comprised of the anterior insula, the dorsal anterior cingulate cortex (dACC), the amygdala, the substantia nigra/ventral tegmental area, and thalamus (Seeley et al, 2007), segregates internal and external stimuli to guide behavior (Menon and Uddin, 2010;Uddin, 2014) (Some studies have considered the amygdala to be part of the DMN (eg, Sheline et al, 2010). We here consider the amygdala to be part of the SN based on the work of Seely et al (2007) who demonstrated an independent network distinct from the ECN and the DMN that is comprised of the anterior insula, dACC, amygdala, substantia nigra/ventral tegmental area, and thalamus, as well as studies showing anatomical connectivity between the anterior insula and the amygdala (Menon and Uddin, 2010).…”

Section: Introductionmentioning

confidence: 99%

Resting-State Connectivity Predictors of Response to Psychotherapy in Major Depressive Disorder

Crowther

Smoski

Minkel

et al. 2015

Neuropsychopharmacol

119

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Despite the heterogeneous symptom presentation and complex etiology of major depressive disorder (MDD), functional neuroimaging studies have shown with remarkable consistency that dysfunction in mesocorticolimbic brain systems are central to the disorder. Relatively less research has focused on the identification of biological markers of response to antidepressant treatment that would serve to improve the personalized delivery of empirically supported antidepressant interventions. In the present study, we investigated whether resting-state functional brain connectivity (rs-fcMRI) predicted response to Behavioral Activation Treatment for Depression, an empirically validated psychotherapy modality designed to increase engagement with rewarding stimuli and reduce avoidance behaviors. Twenty-three unmedicated outpatients with MDD and 20 matched nondepressed controls completed rs-fcMRI scans after which the MDD group received an average of 12 sessions of psychotherapy. The mean change in Beck Depression Inventory-II scores after psychotherapy was 12.04 points, a clinically meaningful response. Resting-state neuroimaging data were analyzed with a seed-based approach to investigate functional connectivity with four canonical resting-state networks: the default mode network, the dorsal attention network, the executive control network, and the salience network. At baseline, the MDD group was characterized by relative hyperconnectivity of multiple regions with precuneus, anterior insula, dorsal anterior cingulate cortex (dACC), and left dorsolateral prefrontal cortex seeds and by relative hypoconnectivity with intraparietal sulcus, anterior insula, and dACC seeds. Additionally, connectivity of the precuneus with the left middle temporal gyrus and connectivity of the dACC with the parahippocampal gyrus predicted the magnitude of pretreatment MDD symptoms. Hierarchical linear modeling revealed that response to psychotherapy in the MDD group was predicted by pretreatment connectivity of the right insula with the right middle temporal gyrus and the left intraparietal sulcus with the orbital frontal cortex. These results add to the nascent body of literature investigating pretreatment rs-fcMRI predictors of antidepressant treatment response and is the first study to examine rs-fcMRI predictors of response to psychotherapy.

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“…Our results similarly indicate an absence of dACC‐amygdala anti‐correlation in GAD versus HC during DM. In addition, results indicated increased frontal FC in GAD for core areas of the salience network (SN, i.e., dACC‐AI) (Menon & Uddin, 2010; Uddin, 2015), potentially indicating a hypervigilant state in GAD. Sub‐genual ACC is also involved in emotion modulation (Delgado, Nearing, Ledoux, & Phelps, 2008; Diekhof, Geier, Falkai, & Gruber, 2011; Drevets, Savitz, & Trimble, 2008; Glascher et al., 2012; Urry et al., 2006) and evidenced more positive FC with both cognitive control (i.e., dACC) and emotional (i.e., right AI) circuits in GAD.…”

Section: Discussionmentioning

confidence: 98%

“…The frontal regions that showed differential FC between GAD and HCs during high error feedback trials (i.e., dACC, sgACC, AI, DLPFC), are involved in salience identification, error monitoring and emotional control (Botvinick et al., 2004; Menon & Uddin, 2010; Ochsner et al., 2012; Uddin, 2015). Decreased PFC‐amygdala connectivity is perhaps the most consistent FC abnormality reported for these regions in GAD (Hilbert et al., 2014; Mochcovitch et al., 2014; Taylor & Whalen, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…Dorsolateral prefrontal cortex (DLPFC), dorsal, rostral, and subcallosal (including subgenual) ACC (dACC, rACC, sgACC), and orbitofrontal cortex (OFC) are engaged during DM under uncertainty (Krain, Wilson, Arbuckle, Castellanos, & Milham, 2006); dACC, rACC, sgACC, and AI are activated during salience processing and error monitoring (Barch et al., 2001; Botvinick, Cohen, & Carter, 2004; Braver, Barch, Gray, Molfese, & Snyder, 2001; Menon & Uddin, 2010; Uddin, 2015; Ullsperger & von Cramon, 2001); and ACC, AI and amygdala are involved in emotion regulation (Ochsner, Silvers, & Buhle, 2012). Importantly, coupling of these regions comprises proposed neural networks underlying the cognitive‐emotional processes involved in DM (Khani & Rainer, 2016; Rushworth, Kolling, Sallet, & Mars, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Neural functional architecture and modulation during decision making under uncertainty in individuals with generalized anxiety disorder

et al. 2018

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BackgroundRecent evidence suggests that repetitive transcranial magnetic stimulation (rTMS) might be effective in treating generalized anxiety disorder (GAD). Cognitive models of GAD highlight the role of intolerance of uncertainty (IU) in precipitating and maintaining worry, and it has been hypothesized that patients with GAD exhibit decision‐making deficits under uncertain conditions. Improving understanding of the neural mechanisms underlying cognitive deficits associated with IU may lead to the identification of novel rTMS treatment targets and optimization of treatment parameters. The current report describes two interrelated studies designed to identify and verify a potential neural target for rTMS treatment of GAD.MethodsStudy I explored the integrity of prefrontal cortex (PFC) and amygdala neural networks, which underlie decision making under conditions of uncertainty, in GAD. Individuals diagnosed with GAD (n = 31) and healthy controls (n = 20) completed a functional magnetic resonance imaging (fMRI) gambling task that manipulated uncertainty using high versus low error rates. In a subsequent randomized‐controlled trial (Study II), a subset of the GAD sample (n = 16) completed the fMRI gambling task again after 30 sessions of active versus sham rTMS (1 Hz, right dorsolateral prefrontal cortex) to investigate the modulation of functional networks and symptoms.ResultsIn Study I, participants with GAD demonstrated impairments in PFC‐PFC and PFC‐amygdala functional connectivity (FC) mostly during the high uncertainty condition. In Study II, one region of interest pair, dorsal anterior cingulate (ACC) – subgenual ACC, showed “normalization” of FC following active, but not sham, rTMS, and neural changes were associated with improvement in worry symptoms.ConclusionsThese results outline a possible treatment mechanism of rTMS in GAD, and pave the way for future studies of treatment optimization.

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Salience processing and insular cortical function and dysfunction

Cited by 1,765 publications

References 126 publications

The cerebellum in drug craving

The cerebellum in drug craving

Resting-State Connectivity Predictors of Response to Psychotherapy in Major Depressive Disorder

Neural functional architecture and modulation during decision making under uncertainty in individuals with generalized anxiety disorder

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