Activity In Anterior Insula Research Articles

Aggression differentially modulates neural correlates of social intention attribution to benevolent, tickling and taunting laughter: An fMRI study in children and adolescents

ABSTRACT Human laughter is a powerful means of communicating social intention, ranging from welcoming and friendly to hostile and ridiculing. To be communicated accurately, the recipient must correctly identify the laugher’s underlying social intention. Regular misattribution of the social intention of others has been associated with maladaptive psychosocial development, in particular with aggressive behavior. We investigated the relationship between self-reported aggressive behavior and the neural correlates of social intention attributions to different audiovisual laughter types in 50 healthy children and adolescents (29 female, 10–18 years, M 15.5, SD 2.2) using functional magnetic resonance imaging. Trial-by-trial associations of neural response and behavioral attributions were distinctly modulated by aggression for benevolent versus taunting and tickling laughter. With increasing aggression, hostile misattributions of benevolent laughter were associated with decreased dorsolateral prefrontal and anterior insular cortex activation. In contrast, hostile attributions of taunting and tickling laughter were associated with increased superior frontal, superior temporal, medial prefrontal, supplementary motor, and anterior and mid-cingulate cortex activation. We argue that aggression may be associated with down-regulated emotional saliency of benevolent laughter, whereas up-regulated neural responses to taunting laughter may underlie a heightened sensitivity to hostility or acceptance of taunting behavior in more aggressive individuals.

The neural correlates of delay discounting in obesity and binge eating disorder.

Background and aimsIncreased delay discounting is associated with obesity and binge eating disorder (BED). Although BED and obesity frequently co-occur, the neural mechanisms underlying delay discounting in these conditions remain poorly understood.MethodsThirtyfive women with obesity, including 10 participants with obesity and BED and 31 controls completed a monetary delay discounting task during functional magnetic resonance imaging.ResultsWe identified that increased discounting rates were associated with decreased activity in the left anterior insula in participants with obesity compared to controls when choosing immediate rewards over delayed rewards (P FWE < 0.05). An exploratory analysis comparing the BED subsample to the other groups did not detect significant differences.Discussion and conclusionsOur findings suggest decreased activity in the anterior insula may underlie heightened delay discounting in individuals with obesity, contributing the probability of choosing immediate rewards over delayed rewards based on emotional states. Future studies including larger, more diverse samples are required to confirm these effects.

Dysregulation of threat neurocircuitry during fear extinction: the role of anhedonia

Dimensional models of anxiety and depression highlight common and distinct symptom clusters that are thought to reflect disruptions in underlying functional processes. The current study investigated how functioning of threat neurocircuitry relates to symptom dimensions of anxiety and depression. Participants were aged 18–19 years (n = 229, 158 female) and were selected to ensure a range of scores on symptom measures. Symptom dimensions of “General Distress” (common to anxiety disorders and depression), “Fears” (more specific to anxiety disorders), and “Anhedonia-apprehension” (more specific to depression) were evaluated. Participants underwent functional magnetic resonance imaging during a Pavlovian fear conditioning paradigm. Multilevel modeling analyses estimated relationships between symptom dimensions and activation in threat neural circuitry. Exploratory whole brain analyses were also conducted. Threat-related neural activity was not associated with General Distress or Fears. Anhedonia-apprehension was associated with activation of bilateral amygdala, anterior insula and dACC during late extinction. We found no evidence to support an association between symptom dimensions of General Distress or Fears with threat circuitry activation in a large sample of young adults. We did, however, find that the symptom dimension of Anhedonia-apprehension was significantly associated with threat-related neural activation during fear extinction. This effect requires replication in future work but may reflect anhedonic impairments in learning when contingencies are altered, possibly linked to the rewarding relief of an unexpectedly absent threat.

Brain Activity Foreshadows Stock Price Dynamics.

Successful investing is challenging since stock prices are difficult to consistently forecast. Recent neuroimaging evidence suggests, however, that activity in brain regions associated with anticipatory affect may not only predict individual choice, but also forecast aggregate behavior out-of-sample. Thus, in two experiments, we specifically tested whether anticipatory affective brain activity in healthy humans could forecast aggregate changes in stock prices. Using functional magnetic resonance imaging, we found in a first experiment (n = 34, 6 females; 140 trials/subject) that nucleus accumbens activity forecast stock price direction, whereas anterior insula (AIns) activity forecast stock price inflections. In a second preregistered replication experiment (n = 39, 7 females) that included different subjects and stocks, AIns activity still forecast stock price inflections. Importantly, AIns activity forecast stock price movement even when choice behavior and conventional stock indicators did not (e.g., previous stock price movements), and classifier analysis indicated that forecasts based on brain activity should generalize to other markets. By demonstrating that AIns activity might serve as a leading indicator of stock price inflections, these findings imply that neural activity associated with anticipatory affect may extend to forecasting aggregate choice in dynamic and competitive environments such as stock markets.SIGNIFICANCE STATEMENT Many try but fail to consistently forecast changes in stock prices. New evidence, however, suggests that anticipatory affective brain activity may not only predict individual choice, but also may forecast aggregate choice. Assuming that stock prices index collective choice, we tested whether brain activity sampled during the assessment of stock prices could forecast subsequent changes in the prices of those stocks. In two neuroimaging experiments, a combination of previous stock price movements and brain activity in a region implicated in processing uncertainty and arousal forecast next-day stock price changes—even when behavior did not. These findings challenge traditional assumptions of market efficiency by implying that neuroimaging data might reveal “hidden information” capable of foreshadowing stock price dynamics.

Establishing Evidence for Clinical Utility of a Neuroimaging Biomarker in Major Depressive Disorder: Prospective Testing and Implementation Challenges

BackgroundAlthough a number of neuroimaging biomarkers for response have been proposed, none have been tested prospectively for direct effects on treatment outcomes. To the best of our knowledge, this is the first prospective test of the clinical utility of the use of an imaging biomarker to select treatment for patients with major depressive disorder. MethodsEligible participants (n = 60) had a primary diagnosis of major depressive disorder and were assigned to either escitalopram or cognitive behavioral therapy based on fluorodeoxyglucose positron emission tomography activity in the right anterior insula. The overall study remission rate after 12 weeks of treatment, based on the end point Hamilton Depression Rating Scale score, was then examined for futility and benefit of the strategy. ResultsRemission rates demonstrated lack of futility at the end of stage 1 (37%, 10/27), and the study proceeded to stage 2. After adjustment for the change in stage 2 sample size, the complete remission rate did not demonstrate evidence of benefit (37.7%, 95% confidence interval, 26.3%–51.4%, p = .38). However, total remission rates (complete and partial remission) did reach significance in post hoc analysis (49.1%, 95% confidence interval, 37.6%–60.7%, p = .020). ConclusionsThe study shows some evidence for a role of the right anterior insula in the clinical choice of major depressive disorder monotherapy. The effect size, however, is insufficient for the use of insula activity as a sole predictive biomarker of remission. The study also demonstrates the logistical difficulties in establishing clinical utility of biomarkers.

The neural basis of ideological differences in race categorization

Multiracial individuals are often categorized as members of their 'socially subordinate' racial group-a form of social discrimination termed hypodescent-with political conservatives more likely than liberals to show this bias. Although hypodescent has been linked to racial hierarchy preservation motives, it remains unclear how political ideology influences categorization: Do conservatives and liberals see, feel or think about mixed-race faces differently? Do they differ in sensitivity to Black prototypicality (i.e. skin tone darkness and Afrocentric features) or racial ambiguity (i.e. categorization difficulty) of Black/White mixed-race faces? To help answer these questions, we collected a politically diverse sample of White participants and had them categorize mixed-race faces as Black or White during functional neuroimaging. We found that conservatism was related to greater anterior insula activity to racially ambiguous faces, and this pattern of brain activation mediated conservatives' use of hypodescent. This demonstrates that conservatives' greater sensitivity to racial ambiguity (rather than Black prototypicality) gives rise to greater categorization of mixed-race individuals into the socially subordinate group and tentatively suggests that conservatives may differ from liberals in their affective reactions to mixed-race faces. Implications for the study of race categorization and political psychology are discussed. This article is part of the theme issue 'The political brain: neurocognitive and computational mechanisms'.

Processing of emotionally ambiguous stimuli in eating disorders: an fMRI pilot study.

People with eating disorders (EDs) have difficulties understanding their own emotions and recognizing the emotions of others, especially in ambiguous settings. We examined the neuronal mechanisms underlying the emotion processing of ambiguous interpersonal stimuli in EDs and healthy controls (HCs). The fMRI data were acquired by a blocked experimental design with 28 women (14 EDs) during the visual presentation of a modified Thematic Apperception Test. EDs showed very strong associations between experienced and inferred emotions evoked by the stimuli; no such relationship was found in HCs. HCs displayed elevated left anterior insula activity during the mentalizing condition; EDs showed increased activity in the right supramarginal gyrus and medial prefrontal cortex. The two groups seem to apply different strategies for judging emotionally ambiguous stimuli, albeit resulting in equivalent judgments. We assume that activity in the supramarginal gyrus and insula in EDs is linked with suppressing their own perspective while considering emotional states, probably due to alexithymia and the lack of awareness of their own mental states. We hypothesize that the strong correlation between experienced and inferred emotions in EDs could reflect their tendency to use others as a reference point for perceiving themselves and gaining information about their affective state. No level of evidence, this is a basic science study.

Brain imaging of executive function with the computerised multiple elements test.

The Computerised Multiple Elements Test (CMET) is a novel executive task to assess goal management and maintenance suitable for use within the fMRI environment. Unlike classical executive paradigms, it resembles neuropsychological multi-elements tests that capture goal management in a more ecological way, by requiring the participant to switch between four simple games within a specified time period. The present study aims to evaluate an fMRI version of the CMET and examine its brain correlates. Thirty-one healthy participants performed the task during fMRI scanning. During each block, they were required to play four simple games, with the transition between games being made either voluntarily (executive condition) or automatically (control condition). The executive condition was associated with increased activity in fronto-parietal and cingulo-opercular regions, with anterior insula activity linked to better task performance. In an additional analysis, the activated regions showed to form functional networks during resting-state and to overlap the executive fronto-parietal and cingulo-opercular networks identified in resting-state with independently defined seeds. These results show the ability of the CMET to elicit activity in well-known executive networks, becoming a potential tool for the study of executive impairment in neurological and neuropsychiatric populations in a more ecological way than classical paradigms.

Shared and unique neural circuitry underlying temporally unpredictable threat and reward processing

Temporally unpredictable stimuli influence behavior across species, as previously demonstrated for sequences of simple threats and rewards with fixed or variable onset. Neuroimaging studies have identified a specific frontolimbic circuit that may become engaged during the anticipation of temporally unpredictable threat (U-threat). However, the neural mechanisms underlying processing of temporally unpredictable reward (U-reward) are incompletely understood. It is also unclear whether these processes are mediated by overlapping or distinct neural systems. These knowledge gaps are noteworthy given that disruptions within these neural systems may lead to maladaptive response to uncertainty. Here, using functional magnetic resonance imaging data from a sample of 159 young adults, we showed that anticipation of both U-threat and U-reward elicited activation in the right anterior insula, right ventral anterior nucleus of the thalamus and right inferior frontal gyrus. U-threat also activated the right posterior insula and dorsal anterior cingulate cortex, relative to U-reward. In contrast, U-reward elicited activation in the right fusiform and left middle occipital gyrus, relative to U-threat. Although there is some overlap in the neural circuitry underlying anticipation of U-threat and U-reward, these processes appear to be largely mediated by distinct circuits. Future studies are needed to corroborate and extend these preliminary findings.

Roles of the MPFC and insula in impression management under social observation.

People often engage in impression management by presenting themselves and others as socially desirable. However, specific behavioral manifestations and underlying neural mechanisms of impression management remain unknown. In this study, we investigated the neural mechanism of impression management during self- and friend-evaluation. Only participants assigned to the observation (OBS) group, not the control (CON) group, were informed that their responses would be monitored. They answered how well positive and negative trait adjectives described themselves or their friends. The behavioral results showed that the OBS group was more likely to reject negative traits for self-evaluation and to accept positive traits for friend-evaluation. An independent study revealed that demoting negative traits for oneself and promoting positive traits for a friend helps manage one’s impression. In parallel with the behavioral results, in the OBS vs the CON group, the rostromedial prefrontal cortex (rmPFC) and anterior insula (AI) activity showed a greater increase as the negativity of negatively valenced adjectives increased during self-evaluation and also showed a greater increase as the positivity of positively valenced adjectives increased during friend-evaluation. The present study suggests that rmPFC and AI are critically involved in impression management, promoting socially desirable target evaluations under social observation.

Modifications in fMRI Representation of Mental Rotation Following a 6 Week Graded Motor Imagery Training in Chronic CRPS Patients

Complex regional pain syndrome (CRPS) is a neuropathic pain condition that is difficult to treat. For behavioral interventions, graded motor imagery (GMI) showed relevant effects, but underlying neural substrates in patient groups have not been investigated yet. A previous study investigating differences in the representation of a left/right hand judgment task demonstrated less recruitment of subcortical structures, such as the putamen, in CRPS patients than in healthy controls. In healthy volunteers, the putamen activity increased after a hand judgment task training. In order to test for longitudinal effects of GMI training, we investigated 20 CRPS patients in a wait-list crossover design with 3 evaluation time points. Patients underwent a 6 week GMI treatment and a 6 week waiting period in a randomized group assignment and treatment groups were evaluated by a blinded rater. When compared to healthy matched controls at baseline, CRPS patients showed less functional activation in areas processing visual input, left sensorimotor cortex, and right putamen. Only GMI treatment, but not the waiting period showed an effect on movement pain and hand judgment task performance. Regression analyses revealed positive associations of movement pain with left anterior insula activation at baseline. Right intraparietal sulcus activation change during GMI was associated with a gain in performance of the hand judgment task. The design used here is reliable for investigating the functional representation of the hand judgment task in an intervention study. PerspectiveTwenty chronic CRPS patients underwent a 6 week GMI intervention in a randomized wait-list crossover design. functional MRI was tested pre and post for the hand lateralization task which improved over GMI but not over WAITING. Performance gain was positively related to right parietal functional MRI activation.

White-matter tract connecting anterior insula to nucleus accumbens predicts greater future motivation in adolescents

The motivation to approach or avoid incentives can change during adolescence. Advances in neuroimaging allow researchers to characterize specific brain circuits that underlie these developmental changes. Whereas activity in the nucleus accumbens (NAcc) can predict approach toward incentive gain, activity in anterior insula (AIns) is associated with avoidance of incentive loss. Recent research characterized the structural white-matter tract connecting the two brain regions, but the tract has neither been characterized in adolescence nor linked to functional activity during incentive anticipation. In this study, we collected diffusion MRI and characterized the tract connecting the AIns to the NAcc for the first time in early adolescents. We then measured NAcc functional activity during a monetary incentive delay task and found that structural coherence of the AIns-NAcc tract is correlated with decreased functional activity at the NAcc terminal of the tract during anticipation of no incentives. In adolescents who completed an assessment 2 years later, we found that AIns-NAcc tract coherence could predict greater future self-reported motivation, and that NAcc functional activity could statistically mediate this association. Together, the findings establish links from brain structure to function to future motivation and provide targets to study the reciprocal development of brain structure and function.

Retrospective Valuation of Experienced Outcome Encoded in Distinct Reward Representations in the Anterior Insula and Amygdala.

Our ability to evaluate an experience retrospectively is important because it allows us to summarize its total value, and this summary value can then later be used as a guide in deciding whether the experience merits repeating, or whether instead it should rather be avoided. However, when an experience unfolds over time, humans tend to assign disproportionate weight to the later part of the experience, and this can lead to poor choice in repeating, or avoiding experience. Using model-based computational analyses of fMRI recordings in 27 male volunteers, we show that the human brain encodes the summary value of an extended sequence of outcomes in two distinct reward representations. We find that the overall experienced value is encoded accurately in the amygdala, but its merit is excessively marked down by disincentive anterior insula activity if the sequence of experienced outcomes declines temporarily. Moreover, the statistical strength of this neural code can separate efficient decision-makers from suboptimal decision-makers. Optimal decision-makers encode overall value more strongly, and suboptimal decision-makers encode the disincentive markdown (DM) more strongly. The separate neural implementation of the two distinct reward representations confirms that suboptimal choice for temporally extended outcomes can be the result of robust neural representation of a displeasing aspect of the experience such as temporary decline.SIGNIFICANCE STATEMENT One of the numerous foibles that prompt us to make poor decisions is known as the "Banker's fallacy," the tendency to focus on short-term growth at the expense of long-term value. This effect leads to unwarranted preference for happy endings. Here, we show that the anterior insula in the human brain marks down the overall value of an experience as it unfolds over time if the experience entails a sequence of predominantly negative temporal contrasts. By contrast, the amygdala encodes overall value accurately. These results provide neural indices for the dichotomy of decision utility and experienced utility popularized as Thinking fast and slow by Daniel Kahneman.

Reward function as an outcome predictor in youth with mood and anxiety symptoms

BackgroundAdolescent depression varies considerably in its course. However, there remain no biobehavioral predictors of illness trajectory, and follow-up studies in depressed youth are sparse. Here, we sought to examine whether reward function would predict future clinical outcomes in adolescents with depressive symptoms. We utilized the reward flanker fMRI task to assess brain function during distinct reward processes of anticipation, attainment, and positive prediction error (PPE, i.e. receiving uncertain rewards). MethodsSubjects were 29 psychotropic-medication-free adolescents with mood and anxiety symptoms and 14 healthy controls (HC). All had psychiatric evaluations at baseline and approximately 24-month follow-up. Thirty-two participants (10 HC) had usable fMRI data. Correlation and hierarchical regression models examined baseline symptom severity measures as predictors of follow-up clinical outcomes. Whole-brain analyses examined relationships between neural reward processes and follow-up outcomes. ResultsClinically, anhedonia, but not irritability, predicted future depression and suicidal ideation. Among reward processes, only baseline neural activation during PPE correlated with follow-up depression and anhedonia severity. Specifically, activation in the left angular gyrus—a component of the default mode network—was associated with future depression, while activation in the dorsal anterior cingulate, operculum, and left insula—key salience and pain network regions—was associated with future anhedonia, even when controlling for baseline anhedonia. LimitationsThe small sample size and variable follow-up intervals limit the generalizability of conclusions. ConclusionsThis research suggests that reward dysfunction, indexed by anhedonia, may predict worse clinical trajectories in depressed youth. Adolescents presenting with significant anhedonia should be carefully monitored for illness progression.

Sex Differences in Neural Responses to the Perception of Social Interactions.

Social interaction is critical to emotional well-being. Previous studies have suggested sex differences in the perception of social interaction. However, the findings depend on the nature of interactions and whether it involves facial emotions. Here, we explored sex differences in neural responses to the perception of social interaction using the Human Connectome Project data. Participants (n = 969, 505 women) were engaged in a social cognition task with geometric objects moving and colliding to simulate social interaction. Behaviorally, men relative to women demonstrated higher accuracy in perceiving social vs. random interactions. Men vs. women showed higher activation in the right superior temporal gyrus, bilateral occipital and posterior cingulate cortex and precuneus, and women vs. men showed higher activation in the right inferior frontal cortex, during exposure to social vs. random interactions. In whole-brain regressions, the differences in accuracy rate in identifying social vs. random interactions (ARSOC – ARRAN) were associated with higher activation in the paracentral lobule (PCL) and lower activation in bilateral anterior insula (AI), pre-supplementary motor area (preSMA), and left middle frontal gyrus (MFG) in men and women combined, lower activation in bilateral AI, preSMA and left MFG in men alone, and higher activation in the PCL and the medial orbitofrontal cortex in women alone. The latter sex differences were confirmed by slope tests. Further, the PCL activity mediated the correlation between an internalizing syndromal score, as assessed by the Achenbach Self-Report, and (ARSOC – ARRAN) across all subjects. These findings highlighted sex differences in the behavioral and neural processes underlying the perception of social interaction, as well as the influence of internalizing traits on these processes.

Regional Activity in the Rat Anterior Cingulate Cortex and Insula during Persistence and Quitting in a Physical-Effort Task.

As animals carry out behaviors, particularly costly ones, they must constantly assess whether or not to persist in the behavior or quit. The anterior cingulate cortex (ACC) has been shown to assess the value of behaviors and to be especially sensitive to physical effort costs. Complimentary to these functions, the insula is thought to represent the internal state of the animal including factors such as hunger, thirst, and fatigue. Using a novel weight-lifting task for rats, we characterized the local field potential (LFP) activity of the ACC and anterior insula (AI) during effort expenditure. In the task, male rats are challenged to work for sucrose reward, which costs progressively more effort over time to obtain. Rats are able to quit the task at any point. We found modest shifts in LFP theta (7–9 Hz) activity as the task got progressively more difficult in terms of absolute effort expenditure. However, when the LFP data were analyzed based on the relative progress of the rat toward quitting the task, substantial shifts in LFP power in the theta and gamma (55–100 Hz) frequency bands were observed in ACC and AI. Both ACC and AI theta power decreased as the rats got closer to quitting, while ACC and AI gamma power increased. Furthermore, coherency between ACC and AI in the delta (2–4 Hz) range shifted alongside the performance state of the rat. Overall, we show that ACC and AI LFP activity changes correlate to the relative performance state of rats in an effort-based task.

Oxytocin increases the pleasantness of affective touch and orbitofrontal cortex activity independent of valence

Touch plays a crucial role in affiliative behavior and social communication. The neuropeptide oxytocin is released in response to touch and may act to facilitate the rewarding effects of social touch. However, no studies to date have determined whether oxytocin facilitates behavioral or neural responses to non-socially administered affective touch and possible differential effects of touch valence. In a functional MRI experiment using a randomized placebo-controlled, within-subject design in 40 male subjects we investigated the effects of intranasal oxytocin (24IU) on behavioral and neural responses to positive, neutral and negative valence touch administered to the arm via different types of materials at a frequency aimed to optimally stimulate C-fibers. Results showed that oxytocin significantly increased both the perceived pleasantness of touch and activation of the orbitofrontal cortex independent of touch valence. The effects of OT on touch-evoked orbitofrontal activation were also positively associated with basal oxytocin concentrations in blood. Additionally, anterior insula activity and the functional connectivity between the amygdala and right anterior insula were enhanced only in response to negative valence touch. Overall, the present study provides the first evidence that oxytocin may facilitate the rewarding effects of all types of touch, irrespective of valence.

Impaired error awareness in healthy older adults: an age group comparison study

Aging is associated with reduced conscious error detection but the brain regions mediating these changes have yet to be clarified. The present study examined the neural correlates of error awareness in healthy older adults. Sixteen older participants (mean age = 75.5 years) and sixteen younger controls (mean age = 27.9 years) were administered the error awareness task, a go/no-go response inhibition paradigm, in which participants were required to signal commission errors. Compared with young adults, older adults were significantly poorer at consciously detecting performance errors, despite both groups being matched for overall accuracy. This age-related behavioral effect was associated with differences in error-related dorsal anterior cingulate cortex and insula activation, with younger adults showing significant differences between errors made with versus without awareness compared with older adults. By contrast, an age-specific modulation in right inferior parietal lobule activation emerged, with increased right inferior parietal lobule activity occurring in older adults during errors made with awareness compared with younger adults. These findings are consistent with theories of age-related deterioration in error processing mechanisms.

Global reward state affects learning and activity in raphe nucleus and anterior insula in monkeys

People and other animals learn the values of choices by observing the contingencies between them and their outcomes. However, decisions are not guided by choice-linked reward associations alone; macaques also maintain a memory of the general, average reward rate – the global reward state – in an environment. Remarkably, global reward state affects the way that each choice outcome is valued and influences future decisions so that the impact of both choice success and failure is different in rich and poor environments. Successful choices are more likely to be repeated but this is especially the case in rich environments. Unsuccessful choices are more likely to be abandoned but this is especially likely in poor environments. Functional magnetic resonance imaging (fMRI) revealed two distinct patterns of activity, one in anterior insula and one in the dorsal raphe nucleus, that track global reward state as well as specific outcome events.

Temporal Dynamics of Large-Scale Networks Predict Neural Cue Reactivity and Cue-Induced Craving

BackgroundCue reactivity, a core characteristic of substance use disorders, commonly recruits brain regions that are key nodes in neurocognitive networks, including the default mode network (DMN) and salience network (SN). Whether resting-state temporal dynamic properties of these networks relate to subsequent cue reactivity and cue-induced craving is unknown. MethodsThe resting-state data of 46 nicotine-dependent participants were assessed to define temporal dynamic properties of DMN and SN states. Temporal dynamics focused on the total time across the scan session that brain activity resides in these specific states. Using regression models, we examined how the total time in each state related to neural reactivity to smoking cues within key DMN (posterior cingulate cortex, medial prefrontal cortex) or SN (anterior insula, dorsal anterior cingulate cortex) nodes. Mediation analyses were subsequently conducted to study how neural cue reactivity mediates the relationship between total time in state at rest and subjective cue-induced craving. ResultsIncreased time spent in the DMN state and decreased time spent in the SN state predicted subsequent cue-induced increases in the anterior insula and dorsal anterior cingulate cortex, respectively. Cue-induced anterior insula and dorsal anterior cingulate cortex activity significantly mediated the relationship between time spent in DMN/SN and cue-induced subjective craving. ConclusionsOur findings showed a significant relationship between resting-state dynamics of the DMN/SN and task-activated SN nodes that together predicted cue-induced craving changes in nicotine-dependent individuals. These findings propose a neurobiological pathway for cue-induced craving that begins with resting-state temporal dynamics, suggesting that brain responding to external stimuli is driven by resting temporal dynamics.