Distal Functional Connectivity of Known and Emerging Cortical Targets for Therapeutic Noninvasive Stimulation.

Noninvasive stimulation is an emerging modality for the treatment of psychiatric disorders, including addiction. A crucial element in effective cortical target selection is its distal influence. We approached this question by examining resting-state functional connectivity patterns in known and potential stimulation targets in 145 healthy adults. We compared connectivity patterns with distant regions of particular relevance in the development and maintenance of addiction. We used stringent Bonferroni-correction for multiple comparisons. We show how the anterior insula, dorsal anterior cingulate, and ventromedial prefrontal cortex had opposing functional connectivity with striatum compared to the dorsomedial prefrontal cortex. However, the dorsolateral prefrontal cortex, the currently preferred target, and the presupplementary motor area had strongest negative connections to amygdala and hippocampus. Our findings highlight differential and opposing influences as a function of cortical site, underscoring the relevance of careful cortical target selection dependent on the desired effect on subcortical structures. We show the relevance of dorsal anterior cingulate and ventromedial prefrontal cortex as emerging cortical targets, and further emphasize the anterior insula as a potential promising target in addiction treatment, given its strong connections to ventral striatum, putamen, and substantia nigra

Addictions NeuroImaging Assessment (ANIA): Towards an integrative framework for alcohol use disorder.

Alcohol misuse and addiction are major international public health issues. Addiction can be characterized as a disorder of aberrant neurocircuitry interacting with environmental, genetic and social factors. Neuroimaging in alcohol misuse can thus provide a critical window into underlying neural mechanisms, highlighting possible treatment targets and acting as clinical biomarkers for predicting risk and treatment outcomes. This neuroimaging review on alcohol misuse in humans follows the Addictions Neuroclinical Assessment (ANA) that proposes incorporating three functional neuroscience domains integral to the neurocircuitry of addiction: incentive salience and habits, negative emotional states, and executive function within the context of the addiction cycle. Here we review and integrate multiple imaging modalities focusing on underlying cognitive processes such as reward anticipation, negative emotionality, cue reactivity, impulsivity, compulsivity and executive function. We highlight limitations in the literature and propose a model forward in the use of neuroimaging as a tool to understanding underlying mechanisms and potential clinical applicability for phenotyping of heterogeneity and predicting risk and treatment outcomes

Instrumental and Pavlovian Mechanisms in Alcohol Use Disorder

Purpose of Review: Current theories of alcohol use disorders (AUD) highlight the importance of Pavlovian and instrumental learning processes mainly based on preclinical animal studies. Here, we summarize available evidence for alterations of those processes in human participants with AUD with a focus on habitual versus goal-directed instrumental learning, Pavlovian conditioning, and Pavlovian-to-instrumental transfer (PIT) paradigms. Recent Findings: The balance between habitual and goal-directed control in AUD participants has been studied using outcome devaluation or sequential decision-making procedures, which have found some evidence of reduced goal-directed/model-based control, but little evidence for stronger habitual responding. The employed Pavlovian learning and PIT paradigms have shown considerable differences regarding experimental procedures, e.g., alcohol-related or conventional reinforcers or stimuli. Summary: While studies of basic learning processes in human participants with AUD support a role of Pavlovian and instrumental learning mechanisms in the development and maintenance of drug addiction, current studies are characterized by large variability regarding methodology, sample characteristics, and results, and translation from animal paradigms to human research remains challenging. Longitudinal approaches with reliable and ecologically valid paradigms of Pavlovian and instrumental processes, including alcohol-related cues and outcomes, are warranted and should be combined with state-of-the-art imaging techniques, computational approaches, and ecological momentary assessment methods

Goal-directed and habitual control in human substance use: state of the art and future directions.

Theories of addiction posit a deficit in goal-directed behavior and an increased propensity toward habitual actions in individuals with substance use disorders. Control over drug intake is assumed to shift from goal-directed to automatic or habitual motivation as the disorder progresses. Several diagnostic criteria reflect the inability to pursue goals regarding reducing or controlling drug use and performing social or occupational functions. The current review gives an overview of the mechanisms underlying the goal-directed and habitual systems in humans, and the existing paradigms that aim to evaluate them. We further summarize the current state of research on habitual and goal-directed functioning in individuals with substance use disorders. Current evidence of alterations in addiction and substance use are mixed and need further investigation. Increased habitual responding has been observed in more severely affected groups with contingency degradation and some outcome devaluation tasks. Reduced model-based behavior has been mainly observed in alcohol use disorder and related to treatment outcomes. Motor sequence learning tasks might provide a promising new approach to examine the development of habitual behavior. In the final part of the review, we discuss possible implications and further developments regarding the influence of contextual factors, such as state and trait variations, and recent advances in task design

Distraction towards contextual alcohol cues and craving are associated with levels of alcohol use among youth

Abstract Background Controlling drinking behaviour requires the ability to block out distracting alcohol cues in situations in which drinking is inappropriate or harmful. However, at present few studies have investigated whether distraction and response inhibition to contextual alcohol cues are related to alcohol use in adolescents and young adults. We aimed to investigate whether tendencies towards distraction and failures of response inhibition in the presence of contextual alcohol cues, and alcohol craving were associated with higher levels of alcohol consumption, beyond what could be explained by demographic variables. Methods To test this, 108 participants (Mean age = 21.7, range = 16–27), whom were both drinkers and non-drinkers performed a modified Go/NoGo task tailored to measure distraction and response inhibition in the presence of alcohol cues relative to neutral stimuli. Alcohol craving was assessed using a visual analogue scale of craving for different types of alcohol cues. Levels of alcohol use and problematic alcohol use were assessed using a self-report measure of number of drinking days in the previous month and the Alcohol Use Disorders Identification Test. Data were analysed using sequential multiple regression using a zero-inflated negative binomial distribution model. Results Drinking days correlated with distraction but not response inhibition to contextual alcohol cues. Sequential regression analyses revealed that the inclusion of distraction bias accounted for 11% additional variance (significant) in alcohol use, in addition to that explained by demographics alone (17%). Craving for alcohol explained an additional 30% variance (significant) in alcohol use. Conclusions The results reported here support the idea that both biased distraction towards alcohol cues and alcohol craving are associated with preceding drinking days, but not necessarily drinking status. Further studies are warranted that address whether cognitive distraction to alcohol-related cues cause or is an effect of alcohol use among youth

The effect of frontoparietal paired associative stimulation on decision-making and working memory.

Previous single-site neurostimulation experiments have unsuccessfully attempted to shift decision-making away from habitual control, a fast, inflexible cognitive strategy, towards goal-directed control, a flexible, though computationally expensive strategy. We employed a dual-target neurostimulation approach in 30 healthy participants, using cortico-cortical paired associative stimulation (ccPAS) to target two key nodes: lateral prefrontal cortex (LPFC) and intraparietal sulcus (IPS), to test whether decision-making can be artificially shifted from habitual toward goal-directed control. Participants received three active stimulations, delivered at least six days apart (each involving 100 paired pulses over the IPS and LPFC, varying the interstimulus interval): two interventional, time-relevant ccPAS (10 msec interval) and one control, non-time-relevant ccPAS (100 msec interval). Following stimulation, participants completed a sequential learning task, measuring goal-directed/habitual control, and a working memory task. IPS→LPFC ccPAS (stimulating IPS, then LPFC with a 10 msec interval) shifted decision-making from habitual toward goal-directed control, compared to control ccPAS. There was no effect of LPFC→IPS ccPAS, nor an effect of any PAS condition on working memory. Previous studies have shown ccPAS effects outside the motor domain targeting prefrontal regions on response inhibition, attentional bias, and alpha asymmetry. The present study measures the behavioural effects of parietal-prefrontal PAS, focusing on a highly complex decision-making task and working memory. If confirmed in larger studies, this would be the first instance of neurostimulation successfully shifting decision-making from habitual to goal-directed control, putatively via inducing long-term potentiation between the IPS and LPFC. However, we found no effect in the other direction (LPFC→IPS ccPAS), and no effect on working memory overall. PAS is a relatively new neuromodulatory technique in the cognitive arsenal, and this study could help guide future approaches in healthy and disordered decision-making