Addiction | Neuro Adx Lab

Neural Markers of Reward Dysregulation in Alcoholism Relapse Prediction

Sun, 31 May 2026 00:00:00 +0100

Project Overview

Neural Markers of Reward Dysregulation in Alcoholism Relapse Prediction

RELAPSE-PREDICT: FCT Exploratory R&D Grant Project (2024.13959.PEX)

This project aims to identify neurobiological and cognitive-behavioral markers of alcohol use disorder (AUD) and evaluate their utility for predicting relapse after treatment. The project applies a multi-method clinical and translational approach that combines neural, cognitive-behavioral, and physiological measures with a prospective follow-up clinical design. By identifying markers of relapse vulnerability, this project aims to inform more specific targets for prevention and intervention.

Research Aims

Identify neurobiological markers of reward dysregulation in AUD
Characterize cognitive-behavioral markers associated with relapse risk
Evaluate whether multimodal markers predict relapse after treatment
Inform targeted prevention and intervention strategies for AUD

Methods

Neural measures of reward dysregulation and alcohol cue reactivity
Cognitive-behavioral assessment of relapse risk
Physiological markers relevant to relapse risk
Prospective clinical follow-up after treatment

Funding

This work is financed by national funds through FCT – Fundação para a Ciência e a Tecnologia, I.P., under the project 2024.13959.PEX

Total funding: 60,000€

Project DOI:

Research Team

Jorge Martins, PI (ISPA-Instituto Universitário)
Rajita Sinha, Co-PI (Yale University)
Bruce Bartholow (University of Iowa)
Francesco Versace (The University of Texas MD Anderson Cancer Center)

Social Context, Drinking Motives, and Alcohol Motivation

Sat, 30 May 2026 00:00:00 +0000

Project Overview

This project examines how alcohol-related motivational tendencies are shaped by the interaction between individual drinking motives and social-emotional context. Specifically, the study investigates whether experiences of social exclusion versus social inclusion differentially influence neural reactivity, implicit approach tendencies, and drinking behavior among individuals who drink primarily for coping motives versus enhancement motives. The project focuses on the distinction between alcohol use motivated by the regulation of negative affect and alcohol use motivated by the amplification of positive affect. By combining an experimental social-context manipulation, EEG/ERP measures of alcohol cue reactivity, behavioral indices of alcohol approach tendencies, a laboratory Alcohol Taste Test, and 15-day ecological follow-up, the study aims to clarify how emotional and interpersonal contexts influence alcohol motivation in daily life.

Background

Alcohol use is shaped by distinct motivational pathways, particularly coping motives, involving drinking to reduce negative affect, and enhancement motives, involving drinking to amplify positive affect or pleasure. Coping motives are linked to negative reinforcement processes and greater risk for problematic alcohol use, whereas enhancement motives reflect positive reinforcement processes. Social context may determine when these pathways are activated: social exclusion may increase alcohol motivation among coping drinkers by inducing negative affect, while social inclusion may enhance alcohol motivation among enhancement drinkers by activating positive social reward. However, it remains unclear whether these contexts differentially influence neural alcohol cue reactivity, implicit approach tendencies, and subsequent drinking behavior.

Research Aims

Examine whether social exclusion versus social inclusion influences neural reactivity to alcohol-related cues.
Test whether coping motives moderate the effect of social exclusion on alcohol cue reactivity, implicit alcohol approach tendencies, and alcohol consumption.
Test whether enhancement motives moderate the effect of social inclusion on alcohol cue reactivity, implicit alcohol approach tendencies, and alcohol consumption.
Assess whether ERP indices of alcohol cue reactivity are associated with behavioral measures of implicit alcohol motivation.

Methods

Self-Report Measures

Participants complete questionnaires assessing drinking motives, with a focus on: (1) drinking driven by coping motives and (2) drinking driven by enhancement motives.

Experimental Paradigm

Participants are randomly assigned to one of two Cyberball conditions: (1) social exclusion, in which participants are excluded during the computerized ball-tossing game; and (2) social inclusion, in which participants are included during the game.

Alcohol Cue-Reactivity Task

Participants complete a picture-viewing oddball task while EEG is recorded.
Event-related potentials are used to assess neural reactivity to alcohol-related cues.

Alcohol Approach-Avoidance Task

Participants complete an Alcohol Approach-Avoidance Task to assess implicit motivational tendencies toward alcohol.
Approach bias scores are used as behavioral indices of implicit alcohol motivation.

Alcohol Taste Test

At the end of the laboratory session, participants complete an Alcohol Taste Test that provides a behavioral measure of implicit motivation to consume alcohol in the laboratory.

Ecological Follow-Up

After the laboratory session, participants are followed for 15 days using a smartphone app.
Participants complete brief daily surveys assessing alcohol consumption during the follow-up period.
These data allow the study to examine whether experimentally induced motivational processes predict real-world drinking behavior.

Significance

This study examines why some individuals are more motivated to drink in negative emotional contexts, whereas others are more responsive to positive or socially rewarding contexts. By integrating experimentally manipulated social contexts with EEG/ERP measures, implicit behavioral tasks, laboratory alcohol consumption, and daily follow-up, the project provides a multi-level assessment of alcohol motivation. Findings may clarify when and for whom social exclusion or inclusion increases alcohol motivation, helping to identify motive-specific risk pathways and inform more personalized interventions.

Developing and Validating a Scale to Assess Differential Valuation of Substance-Related Rewards Versus Natural and Other Non-Drug Rewards in Addiction

Wed, 22 Apr 2026 00:00:00 +0000

Project Overview

Several influential models and theories of substance use and addiction propose that individuals with substance use disorders show an increased motivational valuation of drug-related rewards, at the expense of natural rewards and other rewarding activities. This project builds on these theoretical frameworks by integrating qualitative methods, quantitative psychometric approaches, expert consensus procedures, and recent advances in artificial intelligence (AI) and large language models to develop and validate a new psychological assessment scale. This scale will be designed to measure the differential valuation of substance-related rewards versus natural rewards and other non-drug rewarding activities. By doing so, the project aims to provide a theoretically grounded, clinically relevant, and psychometrically robust instrument for assessing reward-processing dysregulation in addiction.

Background

The chronic use of alcohol and other drugs leads to changes in motivational and reward-processing systems, whereby substance-related rewards and cues acquire excessive motivational value while natural rewards and other meaningful non-drug activities are devalued. This motivational imbalance is central to several influential models of addiction and is thought to contribute to craving, compulsive substance use, reduced engagement with alternative sources of reinforcement, and promote relapse risk. Despite its theoretical and clinical importance, there is currently a lack of psychometrically validated self-report instruments specifically designed to assess the differential valuation of substance-related rewards relative to natural rewards and other rewarding activities. This project addresses this gap by developing and validating a new theoretically grounded scale that captures this reward-valuation imbalance across different patterns of alcohol and other drug use.

Research Objectives

Identify psychologically and clinically relevant content domains related to reward valuation in substance use
Generate and refine candidate items using qualitative data, expert input, and AI-assisted psychometric methods
Evaluate the content validity, clarity, relevance, and theoretical adequacy of the items
Test the factor structure, reliability, and validity of the final scale
Examine whether the scale can distinguish between individuals with different levels of substance use involvement and addiction-related risk

Methodology

The study adopts a multi-method design that integrates qualitative, computational, expert-based, and quantitative procedures:

Semi-structured interviews will be conducted with individuals with different histories and patterns of alcohol and other drug use
Qualitative data will be analyzed using both traditional content-analytic procedures and AI-assisted approaches based on large language models
AI-assisted psychometric development procedures, including AI-GENIE — Automatic Item Generation and Validation with Network-Integrated Evaluation — to support the generation, refinement, and preliminary evaluation of candidate items
Delphi methodology will be used to obtain structured feedback from experts in addiction, clinical psychology, psychometrics, and reward processing
Quantitative validation studies will be conducted to assess the psychometric properties of the scale (i.e., dimensional structure, internal consistency, test-retest reliability, convergent and discriminant validity, criterion validity, and ability to differentiate between groups with distinct patterns of substance use)

Significance

This project aims to make a significant contribution to the addiction literature by developing and validating a theoretically informed, clinically useful, and psychometrically robust self-report instrument for assessing reward-processing dysregulation in substance use. The resulting scale is expected to provide a rapid, reliable, low-cost, and scalable method for assessing the extent to which substance-related rewards are overvalued relative to natural rewards and other rewarding activities. This is clinically important because such motivational imbalance is thought to play a central role in the development, maintenance, and relapse of substance use disorders.

Stress, Sleep, and Autonomic Dysregulation in Alcohol Use Disorder

Wed, 22 Apr 2026 00:00:00 +0000

Project Overview

This project investigates the role of Autonomic Nervous System (ANS) regulation in shaping sleep quality across the spectrum of alcohol use, from moderate consumption to Alcohol Use Disorder (AUD). Specifically, it examines how dynamic interactions between sympathetic activation and parasympathetic recovery influence stress responsivity and downstream sleep disruption. By integrating psychophysiological indices with experimentally induced stress, the project aims to identify mechanistic pathways linking autonomic dysregulation to impaired sleep in AUD.

Background

AUD is characterized by a self-reinforcing cycle involving stress, alcohol use, and sleep disturbance. Heightened stress reactivity promotes alcohol consumption as a maladaptive regulatory strategy; alcohol, in turn, disrupts sleep architecture and circadian regulation; impaired sleep further sensitizes individuals to stress, perpetuating the cycle. The ANS is a central mediator of this process. Dysregulation within the balance of sympathetic (arousal-related) and parasympathetic (restorative) activity compromises adaptive stress recovery and has been consistently associated with both poor sleep quality and substance use pathology. In particular, reduced autonomic activity—indexed via Heart Rate Variability—is linked to impaired emotional regulation, exaggerated stress responses, and vulnerability to relapse. Despite this, the temporal and mechanistic relationships between ANS functioning, stress reactivity, and sleep disturbances in AUD remain insufficiently characterized. This project addresses this gap using controlled experimental stress induction and high-resolution physiological measurement.

Research Aims

Assess individual differences in autonomic responses to acute stress, focusing on both reactivity (sympathetic activation) and recovery (parasympathetic rebound).
Compare autonomic profiles between moderate drinkers and individuals with AUD to identify markers of dysregulation.
Test whether impaired autonomic recovery predicts subjective and/or objective sleep disturbances.
Evaluate whether ANS indices mediate the relationship between alcohol use severity and sleep impairment.

Methods

Acute stress will be elicited using the Trier Social Stress Test.
Continuous electrocardiographic activity will be recorded using the MindWare BioLab system.
Behavioral and self-report measures: Sleep quality, alcohol consumption patterns and severity, craving, and psychological stress.

Significance

This project advances a mechanistic account of AUD by positioning autonomic dysregulation as a core process linking stress vulnerability and sleep disturbance. By identifying physiological markers of impaired regulation—particularly deficits in parasympathetic recovery—it provides targets for intervention (e.g., biofeedback, neuromodulation, or behavioral treatments aimed at restoring autonomic balance). More broadly, the findings have the potential to refine theoretical models of addiction by integrating stress physiology and sleep disruption into a unified framework, with direct implications for relapse prevention and treatment optimization.

The Role of Reward Deficits in Vulnerability to Alcohol Addiction

Wed, 22 Apr 2026 00:00:00 +0000

Project Overview

This project investigates whether individual differences in reward processing deficits contribute to vulnerability to alcohol addiction by increasing the susceptibility to develop enhanced motivational value attributed to alcohol cues. Specifically, it examines whether reduced reward sensitivity makes individuals more likely to assign incentive salience to initially neutral stimuli—such as simple geometric shapes—after these stimuli are paired with alcohol-related images and odors. By integrating Pavlovian conditioning, olfactory and visual alcohol cues, EEG/ERP indices, and attentional capture measures, the project aims to clarify how reward deficits may shape cue-driven motivational processes that increase risk for alcohol misuse.

Background

Alcohol addiction is characterized by heightened reactivity to alcohol-related cues, including exaggerated craving, attentional capture, and neural responses to alcohol-associated stimuli. Incentive Sensitization Theory of addiction proposes that repeated alcohol use can sensitize mesocorticolimbic reward circuits, causing alcohol cues to acquire excessive motivational salience. As a result, these cues may come to automatically attract attention, elicit craving, and bias behavior toward alcohol seeking.

At the same time, the Reward Deficiency hypothesis of addiction suggests that some individuals may have blunted responsiveness to natural rewards, potentially reflecting reduced tonic dopaminergic function. These reward deficits may create vulnerability to compensatory reward-seeking and may increase susceptibility to the motivational impact of alcohol cues. Within this integrated framework, reduced baseline reward sensitivity may amplify the acquisition of incentive salience when neutral cues become associated with alcohol.

Despite strong theoretical links between reward deficiency and incentive sensitization, the mechanisms connecting these processes remain insufficiently characterized in humans. This project addresses this gap by testing whether individual differences in reward deficits predict neural and behavioral responses to conditioned alcohol-paired cues.

Research Aims

Assess whether reward processing deficits predict stronger acquisition of incentive salience to alcohol-paired conditioned cues
Examine whether alcohol-paired geometric shapes elicit enhanced neural responses
Test whether alcohol-paired conditioned cues produce greater attentional capture

Methods

Participants complete a laboratory-based conditioning protocol involving initially neutral geometric shapes
Neutral colored shapes are paired with beverage-related image–odor combinations: beer, orange juice, or water
Pavlovian conditioning is used to establish associations between shapes and alcohol or non-alcohol cues
EEG is recorded during a picture-viewing ‘oddball task’ to quantify neural responses to conditioned shapes

Significance

This project advances a mechanistic account of vulnerability to alcohol addiction by integrating Reward Deficiency hypothesis and Incentive Sensitization Theory of addiction. Rather than treating reward deficits and alcohol cue-reactivity as separate processes, the project tests whether reduced reward sensitivity may increase the likelihood that alcohol-associated cues acquire motivational significance. By identifying neural and behavioral markers of enhanced incentive salience attribution, the study may help clarify why some individuals are especially vulnerable to alcohol-related motivational biases. More broadly, the findings have the potential to refine etiological models of addiction by showing how blunted reward processing may interact with associative learning to promote cue-driven alcohol motivation. This could inform prevention strategies aimed at identifying individuals at elevated risk before severe alcohol-related problems emerge.

TMS in Modulating Brain Reward Circuity

Wed, 22 Apr 2026 00:00:00 +0000

Project Overview

This project is a proof-of-concept study examining whether transcranial magnetic stimulation (TMS) can modulate neural responses underlying reward processing in individuals with problematic alcohol use. Specifically, the study investigates whether TMS can reduce the overvaluation of alcohol-related rewards while enhancing neural responses to alternative "natural" rewards, and whether such modulation translates into changes in craving and alcohol consumption behavior.

Background

Alcohol use disorder (AUD) is characterized by a maladaptive shift in reward processing, whereby alcohol-related cues acquire heightened motivational salience at the expense of non-drug rewards. This imbalance is reflected in neurophysiological markers, including increased brain responses to alcohol cues and diminished responses to natural rewards. Such reward dysregulation is strongly implicated in craving, compulsive use, and relapse.

Emerging evidence suggests that these neural biases are not fixed and may be reversible. Studies using neuroimaging and electrophysiology have shown normalization of reward-related brain responses following sustained abstinence. More recently, non-invasive brain stimulation techniques, such as TMS, have demonstrated the capacity to directly modulate these processes by altering activity in prefrontal–striatal circuits. This raises the possibility that TMS could serve as a translational intervention targeting core neurocognitive mechanisms of addiction.

Research Aims

Evaluate whether TMS can reverse biased neural responses to alcohol versus natural reward stimuli
Examine changes in electrophysiological markers of reward processing (P3 amplitude) following TMS
Assess whether TMS-induced neural modulation is associated with changes in craving
Determine whether these effects extend to behavioral indices of alcohol consumption in laboratory and real-world contexts

Methods

Experimental Paradigm

Passive image-viewing task with simultaneous EEG recording
Stimuli categories: alcohol-related, non-alcoholic beverages, neutral objects, and natural rewards
Behavioral ratings of stimulus valence (pleasant vs. neutral)
Pre- and post-TMS assessment of neural responses (P3 component)

TMS Protocol

Target region: left dorsolateral prefrontal cortex (DLPFC)
Excitatory stimulation (10 Hz) paired with natural reward stimuli
Inhibitory stimulation (1 Hz) paired with alcohol-related stimuli
Active vs. sham-controlled quasi-experimental design
Counterbalanced stimulation order across participants

Behavioral and Clinical Measures

Craving assessment using visual analogue scales
Alcohol Taste Task to measure implicit drinking motivation
Daily ecological monitoring of alcohol consumption

Sample and Design

Non-treatment-seeking individuals with problematic alcohol use
Inclusion based on drinking patterns and health criteria
Quasi-experimental, translational design bridging lab-based neuroscience and clinical relevance

Significance

This study targets a central mechanism in addiction—reward dysregulation—using a mechanistically informed neuromodulation approach. By directly testing whether TMS can recalibrate the balance between drug-related and non-drug rewards, the project advances a translational framework linking neural processes to behavior. If successful, the findings will provide preliminary evidence supporting TMS as a scalable and biologically grounded intervention for reducing craving and relapse risk in alcohol use disorder.

ADDICT-RESPONSE: Neural and Cognitive Mechanisms of Response Inhibition in Addiction

Mon, 01 Jan 2024 00:00:00 +0000

Project Overview

ADDICT-RESPONSE is an FCT-funded research project examining how impairments in response inhibition — the ability to stop or override prepotent behavioral responses — contribute to the development and maintenance of addictive behaviors. Using a multimodal approach combining neuroimaging, psychophysiology, and behavioral paradigms, the project aims to characterize the neurocognitive profile of inhibitory control deficits in addiction and their role in treatment outcomes.

Research Questions

How do deficits in response inhibition differ across substance use disorders?
What are the neural correlates of impaired inhibitory control in individuals with alcohol use disorder?
Do inhibitory control deficits predict relapse following treatment?
Can targeted cognitive training improve inhibitory control and treatment outcomes?

Methodology

Neuroimaging

fMRI: Task-based imaging during Go/No-Go and Stop-Signal paradigms
Resting-state fMRI: Functional connectivity analyses of inhibitory control networks
EEG: High temporal resolution measures of neural inhibitory processes

Behavioral Assessment

Stop-Signal Task and Go/No-Go paradigms
Alcohol and substance cue-reactivity protocols
Ecological momentary assessment of craving and inhibitory failures

Clinical Sample

Adults with alcohol use disorder in outpatient treatment
Matched healthy control participants
Longitudinal follow-up at 3, 6, and 12 months post-treatment

Funding

Funded by the Portuguese Foundation for Science and Technology (FCT), this project supports research activities at the William James Center for Research, ISPA–Instituto Universitário.