Increased ventral anterior insular connectivity to sports betting availability indexes problem gambling.

With the advent of digital technologies, online sports betting is spurring a fast-growing expansion. In this study, we examined how sports betting availability modulates the brain connectivity of frequent sports bettors with [problem bettors (PB)] or without [non-problem bettors (NPB)] problematic sports betting. We conducted functional connectivity analyses centred on the ventral anterior insular cortex (vAI), a brain region playing a key role in the dynamic interplay between reward-based processes. We re-analysed a dataset on sports betting availability undertaken in PB (n = 30) and NPB (n = 35). Across all participants, we observed that sports betting availability elicited positive vAI coupling with extended clusters of brain activation (encompassing the putamen, cerebellum, occipital, temporal, precentral and central operculum regions) and negative vAI coupling with the orbitofrontal cortex. Between-group analyses showed increased positive vAI coupling in the PB group, as compared with the NPB group, in the left lateral occipital cortex, extending to the left inferior frontal gyrus, the anterior cingulate gyrus and the right frontal pole. Taken together, these results are in line with the central assumptions of triadic models of addictions, which posit that the insular cortex plays a pivotal role in promoting the drive and motivation to get a reward by 'hijacking' goal-oriented processes toward addiction-related cues. Taken together, these findings showed that vAI functional connectivity is sensitive not only to gambling availability but also to the status of problematic sport betting.

Physical Exercise to Redynamize Interoception in Substance use Disorders.

Physical exercise is considered a promising medication-free and cost-effective adjunct treatment for substance use disorders (SUD). Nevertheless, evidence regarding the effectiveness of these interventions is currently limited, thereby signaling the need to better understand the mechanisms underlying their impact on SUD, in order to reframe and optimize them. Here we advance that physical exercise could be re-conceptualized as an "interoception booster", namely as a way to help people with SUD to better decode and interpret bodily-related signals associated with transient states of homeostatic imbalances that usually trigger consumption. We first discuss how mismatches between current and desired bodily states influence the formation of reward-seeking states in SUD, in light of the insular cortex brain networks. Next, we detail effort perception during physical exercise and discuss how it can be used as a relevant framework for re-dynamizing interoception in SUD. We conclude by providing perspectives and methodological considerations for applying the proposed approach to mixed-design neurocognitive research on SUD.

Brain modular connectivity interactions can predict proactive inhibition in smokers when facing smoking cues.

Proactive inhibition is a critical ability for smokers who seek to moderate or quit smoking. It allows them to pre-emptively refrain from seeking and using nicotine products, especially when facing salient smoking cues in daily life. Nevertheless, there is limited knowledge on the impact of salient cues on behavioural and neural aspects of proactive inhibition, especially in smokers with nicotine withdrawal. Here, we seek to bridge this gap. To this end, we recruited 26 smokers to complete a stop-signal anticipant task (SSAT) in two separate sessions: once in the neutral cue condition and once in the smoking cue condition. We used graph-based modularity analysis to identify the modular structures of proactive inhibition-related network during the SSAT and further investigated how the interactions within and between these modules could be modulated by different proactive inhibition demands and salient smoking cues. Findings pointed to three stable brain modules involved in the dynamical processes of proactive inhibition: the sensorimotor network (SMN), cognitive control network (CCN) and default-mode network (DMN). With the increase in demands, functional connectivity increased within the SMN, CCN and between SMN-CCN and decreased within the DMN and between SMN-DMN and CCN-DMN. Salient smoking cues disturbed the effective dynamic interactions of brain modules. The profiles for those functional interactions successfully predicted the behavioural performance of proactive inhibition in abstinent smokers. These findings advance our understanding of the neural mechanisms of proactive inhibition from a large-scale network perspective. They can shed light on developing specific interventions for abstinent smokers.

How distinct functional insular subdivisions mediate interacting neurocognitive systems.

Recent neurocognitive models propose that the insula serves as a hub of interoceptive awareness system, modulating 2 interplaying neurocognitive systems: The posterior insula (PI) receives and integrates various interoceptive signals; these signals are then transmitted to the anterior insula for processing higher-order representations into awareness, where the dorsal anterior insula (dAI) modulates the prefrontal self-control system and the ventral anterior insula (vAI) modulates the amygdala (AMG)-striatal reward-seeking circuit. We sought to test this view using a multimodal approach. We first used a resting-state functional magnetic resonance imaging (fMRI) approach with a sample of 120 undergraduate students. Then, we unpacked the neuro-cognitive association between insular connectivity and cognitive performance during an Iowa gambling fMRI task. Lastly, an independent Open Southwest University Longitudinal Imaging Multimodal dataset was used to validate the results. Findings suggested that the dAI was predominantly connected to the prefrontal regions; the vAI was primarily connected to the AMG-ventral-striatum system; and the PI was mainly connected to the visceral-sensorimotor system. Moreover, cognitive scores were positively correlated with FC between dAI and the self-control process of ventrolateral prefrontal cortex and were negatively correlated with FC between vAI and the reward-seeking process of orbitofrontal cortex and subgenual anterior cingulate cortex. The findings highlight the roles of our theorized subinsular functionality in the overall operation of the neural cognitive systems.

The modulation of acute stress on model-free and model-based reinforcement learning in gambling disorder.

Background and aims: Experiencing acute stress is common in behavioral addictions such as gambling disorder. Additionally, like most substance-induced addictions, aberrant decision-making wherein a reactive habit-induced response (conceptualized as a Model-free [MF] in reinforcement learning) suppresses a flexible goal-directed response (conceptualized as a Model-based [MB]) is also common in gambling disorder. In the current study we investigated the influence of acute stress on the balance between habitual response and the goal-directed system. Methods: A sample of N = 116 problem gamblers (PG) and healthy controls (HC) performed an acute stress task - the Socially Evaluated Cold pressure task (SECPT) - or a control task. Self-reported stress and salivary cortisol were collected as measures of acute stress. Following the SECPT, participants performed the Two-Step Markov Task to account for the relative contribution of MB and MF strategies. Additionally, verbal working memory and IQ measures were collected to account for their mediating effects on the orchestration between MB/MF and the impact of stress. Results: Both groups had comparable baseline and stress-induced cortisol response to the SECPT. Non-stressed PG displayed lower MB learning than HC. MANOVA and regression analyses showed a deleterious effect of stress-induced cortisol response on the orchestration between MB and MF learning in HC but not in PG. These effects remained when controlling for working memory and IQ. Discussion and Conclusions: We found an abnormal pattern of modulation of stress on the orchestration between MB and MF learning among PG. Several interpretations and future research directions are discussed.

Maladaptive changes in delay discounting in males during the COVID-19 pandemic: the predictive role of functional connectome.

The Coronavirus disease of 2019 (COVID-19) and measures to curb it created population-level changes in male-dominant impulsive and risky behaviors such as violent crimes and gambling. One possible explanation for this is that the pandemic has been stressful, and males, more so than females, tend to respond to stress by altering their focus on immediate versus delayed rewards, as reflected in their delay discounting rates. Delay discounting rates from healthy undergraduate students were collected twice during the pandemic. Discounting rates of males (n=190) but not of females (n=493) increased during the pandemic. Using machine learning, we show that prepandemic functional connectome predict increased discounting rates in males (n=88). Moreover, considering that delay discounting is associated with multiple psychiatric disorders, we found the same neural pattern that predicted increased discounting rates in this study, in secondary datasets of patients with major depression and schizophrenia. The findings point to sex-based differences in maladaptive delay discounting under real-world stress events, and to connectome-based neuromarkers of such effects. They can explain why there was a population-level increase in several impulsive and risky behaviors during the pandemic and point to intriguing questions about the shared underlying mechanisms of stress responses, psychiatric disorders and delay discounting.

Auricular transcutaneous vagus nerve stimulation modulates the heart-evoked potential.

BACKGROUND: There is active interest in biomarker discovery for transcutaneous auricular vagus nerve stimulation (taVNS). However, greater understanding of the neurobiological mechanisms is needed to identify candidate markers. Accumulating evidence suggests that taVNS influences activity in solitary and parabrachial nuclei, the primary brainstem relays for the transmission of visceral sensory afferents to the insula. The insula mediates interoception, which concerns the representation and regulation of homeostatic bodily states. Consequently, interoceptive pathways may be relevant to taVNS mechanisms of action. HYPOTHESES: We hypothesized that taVNS would modulate an EEG-derived marker of interoceptive processing known as the heart-evoked potential (HEP). We also hypothesized that taVNS-induced HEP effects would be localizable to the insula. METHODS: Using a within-subject, sham-controlled design, we recorded EEG and ECG concurrent to taVNS in 43 healthy adults. Using ECG and EEG data, we extracted HEPs. Estimation of the cortical sources of the taVNS-dependent HEP responses observed at the scalp were computed using the Boundary Element Method and weighted Minimum Norm Estimation. Statistics were calculated using cluster-based permutation methods. RESULTS: taVNS altered HEP amplitudes at frontocentral and centroparietal electrode sites at various latencies. The taVNS-dependent HEP effect was localized to the insula, operculum, somatosensory cortex, and orbital and ventromedial prefrontal regions. CONCLUSION: The results support the hypothesis that taVNS can access the insula as well as functionally and anatomically connected brain regions. HEPs may serve as an objective, non-invasive outcome parameter for the cortical effects of taVNS.

Structural brain differences associated with extensive massively-multiplayer video gaming.

Video gaming can be associated with inter-individual differences in brain morphology. Much of this literature has focused on non-professional/occasional gamers who barely play, on the one extreme; or Internet Gaming Disorder (IGD) cases who typically play more than 5 h/day, on the other extreme. We sought to extend this literature and focus on extensive gamers, who play about 3 h/day, which is typically more than non-professional gamers, but less than IGD cases. Findings regarding this sector of gamers can inform research on risk factors or markers for IGD development, even before addiction symptoms emerge. We predicted that extensive gamers have smaller prefrontal regions that presumably reflect weaker inhibition abilities, and larger visuomotor regions that presumably reflect stronger motor skills in response to visual stimuli. We tested these assertions with a between-subject brain morphology comparison of 26 extensive League of Legends (LOL) and matched 26 non-gamers, using voxel based morphometry, deformation based morphometry, and cortical thickness and sulcus depth analyses. Findings largely supported our predictions by pointing to morphological alterations in extensive gamers in the bilateral ventromedial prefrontal cortex and left dorsolateral prefrontal cortex, as well is in the left superior parietal lobule. These findings suggest that extensive gamers, at least of Massive-Multiplayer battle arena games, present brain alterations that are consistent with presumed loss of control (as mediated by the prefrontal cortex), but also improved attention and visoumotor skills (as mediated by superior parietal lobule). Implications for research and practice are discussed.

The role of the insula in internet gaming disorder.

Internet gaming disorder (IGD) is a concerning issue that requires further research. Here, we seek to examine its neural etiology with an emphasis on the role of the insula. To do so, we relied on the tripartite neurocognitive model of addictive behaviors as applied to IGD. We hypothesized that (a) video game cues will elicit stronger reward system activation and weaker prefrontal activation in gamers vs controls, (b) the IGD scores of gamers will be positively associated with activation of the reward system and negatively with activation of prefrontal regions, (c) deprivation from video gaming will result in increased activation of the insula, when gamers are exposed to video game cues vs to neutral cues, and (d) in deprivation conditions, there will be positive and negative coupling, respectively, between activation of the insula and the reward and prefrontal regions in gamers. We tested these hypotheses with a design with one between-subjects factor (gamers vs controls) and two within-subjects factors: stimuli (gaming vs neutral; for all participants) and session (deprivation vs satiety; only for gamers). Findings based on functional magnetic resonance imaging (fMRI; applied to all 52 subjects, 26 gamers, and 26 controls) and psychophysiological interaction (PPI; applied to the 26 gamers) engaged in a video reactivity task supported our assertions. The IGD score positively correlated with activity in the right ventral striatum and negatively with activity in the right dorsolateral prefrontal cortex (DLPFC). Left insular cortex activity was the highest when observing video gaming cues under deprivation. Lastly, there was an increased coupling between the left insula and left ventral striatum and a decreased coupling with left DLPFC when observing video gaming cues compared with when watching control videos in the deprivation condition.

Increased brain reactivity to gambling unavailability as a marker of problem gambling.

The unprecedented development and ubiquity of sports betting constitute an emerging public health concern. It is crucial to provide markers that could help to better identify people experiencing sports betting-related harms. The current study investigated whether problem gambling status, sports betting passion, and trait-self-control modulate brain reactivity to sports betting cues. Sixty-five frequent sports bettors (35 "nonproblem bettors" and 30 "problem bettors") were exposed to cues representing real upcoming sport events (with varying levels of winning confidence) that were made available or blocked for betting, during functional magnetic resonance imaging (fMRI) recording. Sports betting passion and trait-self-control were assessed using self-report scales. Sport events nonavailable for betting elicited higher insular and striatal activation in problem bettors, as compared with nonproblem bettors. Within a large cluster encompassing the ventral striatum, hippocampus, and amygdala, lower trait-self-control was associated with increased brain reactivity to sport events with high levels of winning confidence that were nonavailable for betting. No significant effect of sports betting passion was observed. These findings suggest that sports bettors' brain reactivity to gambling unavailability might be a relevant marker of sports betting-related harms, as well as of blunted trait-self-control.

Patients on the psychosis spectrum employ an alternate brain network to engage in complex decision-making.

Brain reward processing mechanisms that underlie complex decision-making are compromised in psychosis. The goal of this research was to advance our understanding of the underlying (1) neural mechanisms and (2) discrete neuro-economic/motivational processes that may be altered in complex decision-making in euthymic patients on the psychosis spectrum (PPS). Utilizing a functional magnetic resonance neuroimaging (fmri) paradigm of a well-validated laboratory measure of complex decision-making (Iowa Gambling Task-IGT), the brain activation patterns of a target group of PPS were compared to a demographically matched healthy comparison group (HMC). These two groups were also evaluated on real-life decision outcomes on day of scan. PPS primarily activate the Dorsal Attentional Network (DAN) in real-life decision outcomes and in achieving similar levels of performance on the IGT as the HMC, in-spite of dysregulated dopamine-based brain-reward circuit and salience network fmri activation patterns. However, PPS report more significant negative outcomes of their decision-making in real-life, compared to HMC. The differential engagement of brain networks by PPS on the IGT appear to be moderated by antipsychotic, dopamine antagonist, medication lifetime/daily dose levels. These findings may also be mediated by extent of dysregulation in brain reward circuitry and salience network associated with psychosis severity in the target PPS group. This is also evident in case studies of unmedicated PPS. We conclude by suggesting that the brain may adapt to this dysregulation by co-opting the DAN network, which is implicated in the related function of problem-solving, towards complex decision-making. The extent of utilization of the DAN network in complex decision-making may be moderated by psychosis severity.

Smoking cues impair monitoring but not stopping during response inhibition in abstinent male smokers.

The attenuated inhibitory control of smokers is a stumbling block for treating nicotine dependence. Unfortunately, smokers are often exposed to cigarette-related salient cues, which may violate homeostasis, override self-control, and lead to relapse. To understand the mechanisms underlying these associations, we investigate the cognitive and neural processes of inhibitory control (including proactive and reactive inhibition) of smoking cues in abstinent smokers. Twenty-six smokers completed cue-reactivity and stop signal tasks during functional magnetic resonance imaging scans, on two separate sessions, 2-3 weeks apart: one involved a neutral cue reactivity task, and the other a smoking cue reactivity task. Findings pointed to no significant subjective craving changes, or behavioral influences of smoking cues on proactive and reactive inhibition. However, abstinent smokers exhibited hyperactive brain reactivity in response to smoking versus neutral stimuli, in regions including the insula, amygdala, anterior cingulate cortex (ACC), and putamen. They also had hypoactive bilateral rostral ACC (rACC) and hyperactive right pre-supplementary motor area during reactive inhibition in smoking versus neutral conditions. Support vector regression analysis showed that activation of these regions predicted and correlated with reactive inhibition index (i.e., SSRT), alluding to the possibility of their involvement in the reactive inhibition. Subjective craving scores were predicted by and correlated with activation of bilateral dorsal and rostral ACC, supporting the ideas of their possible involvement in subjective craving. These findings suggest that smoking cues evoke hyperactive brain reactivity; this may interfere with normal performance monitoring and rapid reactive inhibition. These findings have important implication for treating smoking dependence.

Theta-burst stimulation and frontotemporal regulation of cardiovascular autonomic outputs: The role of state anxiety.

Dysregulation of autonomic cardiovascular homeostasis is an important cardiological and neurological risk factor. Cortical regions including the prefrontal and insular cortices exert tonic control over cardiovascular autonomic functions. Transcranial Magnetic Stimulation (TMS) may be a suitable approach for studying top-down control of visceromotor processes. However, there is inconsistent evidence as to whether TMS can modify cardiovascular autonomic states. One reason for the inconsistency may arise from the lack of studies accounting for the acute affective states of participants with respect to the stimulation procedures. To gain more insights into these processes, we evaluated the effects of intermittent and continuous theta-burst stimulation (TBS) to the right frontotemporal cortex on state anxiety and cardiovascular responses in a preliminary study. State anxiety significantly increased for both intermittent and continuous TBS relative to sham. Intermittent TBS also significantly increased heart-rate variability (HRV) at natural and slow-paced breathing rates. The effect of intermittent TBS on vagally-mediated HRV was attenuated after accounting for stimulation-induced anxiety, suggesting that increased HRV after stimulation may reflect a response to a transient stressor (i.e., the stimulation itself), rather than TBS effects on visceromotor networks. In contrast, continuous TBS increased pulse transit time latency across breathing rates, an effect that was enhanced after accounting for state anxiety. TMS is a promising approach to study cortical involvement in cardiovascular autonomic regulation. The findings show that TBS induces effects on visceromotor networks, and that analysis of state covariates such as anxiety can be important for increasing the precision of these estimates. Future non-invasive brain stimulation studies of top-down neurocardiac regulation should account for the potential influence of non-specific arousal or anxiety responses to stimulation.

White matter integrity alternations associated with cocaine dependence and long-term abstinence: Preliminary findings.

Cocaine dependence has been associated with deficits in white matter (WM) integrity. Nevertheless, what happens to WM integrity after long-term abstinence is not fully understood. To bridge this gap, changes in WM integrity were examined with diffusion tensor imaging (DTI) applied to 39 participants: 12 participants who used cocaine in the last year (CURRENT USERS), 20 who were at different stages of cocaine abstinence (ABSTINENCE) [five with 1-5 years of abstinence (ABS1), five with 6-10 years of abstinence (ABS2), and 10 with over 10 years of abstinence (ABS3)], and 7 healthy controls (CONTROLS). The CONTROL group had higher fractional anisotropy (FA) compared to CURRENT USERS in frontal cortex tracts, including the bilateral corpus callosum, bilateral superior longitudinal fasciculus, bilateral inferior fronto-occipital fasciculus, left internal capsule, left middle cingulum, and left ventral and dorsal medial frontal regions. The ABSTINENCE group also had higher FA compared to CURRENT USERS in frontal cortex tracts, such as the bilateral corpus callosum, bilateral superior longitudinal fasciculus, left inferior longitudinal fasciculus, left uncinate fasciculus, left inferior fronto-occipital fasciculus, and the left ventral and dorsal medial frontal regions. Tractography analysis showed (1) deficits in terms of number of fibers and fiber length in these regions, and that (2) while there was some recovery of white matter in dorsolateral regions during abstinence, duration of abstinence was not associated with such recovery. The results identified WM differences among cocaine users, cocaine abstinent participants, and controls. These preliminary findings point to WM tracts that recover, and some that do not, after long-term abstinence from cocaine.

Reduced model-based decision-making in gambling disorder.

Compulsive behaviors (e.g., addiction) can be viewed as an aberrant decision process where inflexible reactions automatically evoked by stimuli (habit) take control over decision making to the detriment of a more flexible (goal-oriented) behavioral learning system. These behaviors are thought to arise from learning algorithms known as "model-based" and "model-free" reinforcement learning. Gambling disorder, a form of addiction without the confound of neurotoxic effects of drugs, showed impaired goal-directed control but the way in which problem gamblers (PG) orchestrate model-based and model-free strategies has not been evaluated. Forty-nine PG and 33 healthy participants (CP) completed a two-step sequential choice task for which model-based and model-free learning have distinct and identifiable trial-by-trial learning signatures. The influence of common psychopathological comorbidities on those two forms of learning were investigated. PG showed impaired model-based learning, particularly after unrewarded outcomes. In addition, PG exhibited faster reaction times than CP following unrewarded decisions. Troubled mood, higher impulsivity (i.e., positive and negative urgency) and current and chronic stress reported via questionnaires did not account for those results. These findings demonstrate specific reinforcement learning and decision-making deficits in behavioral addiction that advances our understanding and may be important dimensions for designing effective interventions.

A Neurobehavioral Approach to Addiction: Implications for the Opioid Epidemic and the Psychology of Addiction.

Two major questions about addictive behaviors need to be explained by any worthwhile neurobiological theory. First, why do people seek drugs in the first place? Second, why do some people who use drugs seem to eventually become unable to resist drug temptation and so become "addicted"? We will review the theories of addiction that address negative-reinforcement views of drug use (i.e., taking opioids to alleviate distress or withdrawal), positive-reinforcement views (i.e., taking drugs for euphoria), habit views (i.e., growth of automatic drug-use routines), incentive-sensitization views (i.e., growth of excessive "wanting" to take drugs as a result of dopamine-related sensitization), and cognitive-dysfunction views (i.e., impaired prefrontal top-down control), including those involving competing neurobehavioral decision systems (CNDS), and the role of the insula in modulating addictive drug craving. In the special case of opioids, particular attention is paid to whether their analgesic effects overlap with their reinforcing effects and whether the perceived low risk of taking legal medicinal opioids, which are often prescribed by a health professional, could play a role in the decision to use. Specifically, we will address the issue of predisposition or vulnerability to becoming addicted to drugs (i.e., the question of why some people who experiment with drugs develop an addiction, while others do not). Finally, we review attempts to develop novel therapeutic strategies and policy ideas that could help prevent opioid and other substance abuse.

Double dissociation of HIV and substance use disorder effects on neurocognitive tasks dependent on striatal integrity.

OBJECTIVE: Substance use is common among individuals infected with HIV, yet whether neurocognitive effects of HIV can be distinguished from more nonspecific effects of drug dependence and associated comorbidities is not known. DESIGN: Cross-sectional observational study of neurocognitive function among HIV-infected and uninfected individuals with and without substance use disorders (SUDs). METHODS: We compared the performance of 458 (31% HIV-infected) substance-dependent individuals (SDIs) and 90 individuals (23% HIV-infected) with no history of SUDs on measures of delay discounting and probability learning, tasks, which are differentially sensitive to addictive processes and HIV serostatus, respectively. RESULTS: In factorial analyses of covariance adjusted for age, years of education, and sex, we found that SDIs showed significantly higher rates of delay discounting, regardless of HIV serostatus (P < 0.05). Conversely, HIV-infected individuals performed significantly more poorly on probability learning compared with uninfected groups, regardless of SUD history (P < 0.05). CONCLUSION: Theory-driven cognitive neuropsychological tasks may have the capacity to detect neurocognitive effects of HIV not attributable solely to substance use; evidence from functional neuroimaging studies with more selective neurocognitive probes will be critical for hypothesis testing and mapping underlying brain systems more precisely.