Distinct neural networks predict cocaine versus cannabis treatment outcomes.

Treatment outcomes for individuals with substance use disorders (SUDs) are variable and more individualized approaches may be needed. Cross-validated, machine-learning methods are well-suited for probing neural mechanisms of treatment outcomes. Our prior work applied one such approach, connectome-based predictive modeling (CPM), to identify dissociable and substance-specific neural networks of cocaine and opioid abstinence. In Study 1, we aimed to replicate and extend prior work by testing the predictive ability of the cocaine network in an independent sample of 43 participants from a trial of cognitive-behavioral therapy for SUD, and evaluating its ability to predict cannabis abstinence. In Study 2, CPM was applied to identify an independent cannabis abstinence network. Additional participants were identified for a combined sample of 33 with cannabis-use disorder. Participants underwent fMRI scanning before and after treatment. Additional samples of 53 individuals with co-occurring cocaine and opioid-use disorders and 38 comparison subjects were used to assess substance specificity and network strength relative to participants without SUDs. Results demonstrated a second external replication of the cocaine network predicting future cocaine abstinence, however it did not generalize to cannabis abstinence. An independent CPM identified a novel cannabis abstinence network, which was (i) anatomically distinct from the cocaine network, (ii) specific for predicting cannabis abstinence, and for which (iii) network strength was significantly stronger in treatment responders relative to control particpants. Results provide further evidence for substance specificity of neural predictors of abstinence and provide insight into neural mechanisms of successful cannabis treatment, thereby identifying novel treatment targets. Clinical trials registation: "Computer-based training in cognitive-behavioral therapy web-based (Man VS Machine)", registration number: NCT01442597 . "Maximizing the Efficacy of Cognitive Behavior Therapy and Contingency Management", registration number: NCT00350649 . "Computer-Based Training in Cognitive Behavior Therapy (CBT4CBT)", registration number: NCT01406899 .

Connectome-based prediction of craving in gambling disorder and cocaine use disorder.

INTRODUCTION: Craving, involving intense and urgent desires to engage in specific behaviours, is a feature of addictions. Multiple studies implicate regions of salience/limbic networks and basal ganglia, fronto-parietal, medial frontal regions in craving in addictions. However, prior studies have not identified common neural networks that reliably predict craving across substance and behavioural addictions. METHODS: Functional magnetic resonance imaging during an audiovisual cue-reactivity task and connectome-based predictive modelling (CPM), a data-driven method for generating brain-behavioural models, were used to study individuals with cocaine-use disorder and gambling disorder. Functions of nodes and networks relevant to craving were identified and interpreted based on meta-analytic data. RESULTS: Craving was predicted by neural connectivity across disorders. The highest degree nodes were mostly located in the prefrontal cortex. Overall, the prediction model included complex networks including motor/sensory, fronto-parietal, and default-mode networks. The decoding revealed high functional associations with components of memory, valence ratings, physiological responses, and finger movement/motor imagery. CONCLUSIONS: Craving could be predicted across substance and behavioural addictions. The model may reflect general neural mechanisms of craving despite specificities of individual disorders. Prefrontal regions associated with working memory and autobiographical memory seem important in predicting craving. For further validation, the model should be tested in diverse samples and contexts.

Differential responses to infant faces in relation to maternal substance use: An exploratory study.

BACKGROUND: Maternal substance use and addiction has been associated with negative consequences for parenting and may increase addiction vulnerability in the developing child. Neuroimaging research suggests that substance use may decrease the reward of caring for infants and heighten stress reactivity to affective infant cues. METHODS: Thirty-two substance-using mothers and twenty-two non-substance-using mothers were presented with emotional face and cry stimuli generated from their own and a demographically matched unknown infant during fMRI scanning. Between-group differences in neural activity during task performance were assessed using whole-brain, mixed-effects models corrected for multiple comparisons (voxel-level p < 0.001, pFWE<0.05). RESULTS: Relative to non-substance-using mothers, substance-using mothers exhibited greater activation when viewing their own infant's face as compared to an unknown infant's face across multiple brain regions, including superior medial frontal, inferior parietal, and middle temporal regions. Substance-using mothers also had a decreased response to sad infant faces in the ventral striatum relative to the non-substance-using mothers. Neural responses to own vs. unknown infant cries did not significantly differ between substance-using and non-substance-using mothers. CONCLUSIONS: Findings suggest overlapping cortical and subcortical brain regions implicated in responding to infant faces, with activation differences related to infant familiarity, emotional expression, and maternal substance use. While prior work has focused on attenuated neural responses to infant cues, greater attention is needed toward understanding the increased reactivity to affective infant cues observed in substance-using mothers.

Altered functional connectivity to stressful stimuli in prenatally cocaine-exposed adolescents.

BACKGROUND: Prenatal cocaine exposure (PCE) is linked to addiction and obesity vulnerability. Neural responses to stressful and appetitive cues in adolescents with PCE versus those without have been differentially linked to substance-use initiation. However, no prior studies have assessed cue-reactivity responses among PCE adolescents using a connectivity-based approach. METHODS: Twenty-two PCE and 22 non-prenatally drug-exposed (NDE) age-, sex-, IQ- and BMI-matched adolescents participated in individualized guided imagery with appetitive (favorite-food), stressful and neutral-relaxing cue scripts during functional magnetic resonance imaging. Subjective favorite-food craving scores were collected before and after script exposure. A data-driven voxel-wise intrinsic connectivity distribution analysis was used to identify between-group differences and examine relationships with craving scores. RESULTS: A group-by-cue interaction effect identified a parietal lobe cluster where PCE versus NDE adolescents showed less connectivity during stressful and more connectivity during neutral-relaxing conditions. Follow-up seed-based connectivity analyses revealed that, among PCE adolescents, the parietal seed was positively connected to inferior parietal and sensory areas and negatively connected to corticolimbic during both stress and neutral-relaxing conditions. For NDE, greater parietal connectivity to parietal, cingulate and sensory areas and lesser parietal connectivity to medial prefrontal areas were found during stress compared to neutral-relaxing cueing. Craving scores inversely correlated with corticolimbic connectivity in PCE, but not NDE adolescents, during the favorite-food condition. CONCLUSIONS: Findings from this first data-driven intrinsic connectivity analysis of PCE influences on adolescent brain function indicate differences relating to PCE status and craving. These findings provide insight into the developmental impact of in utero drug exposure.

Prenatal cocaine exposure, illicit-substance use and stress and craving processes during adolescence.

BACKGROUND: Prenatal cocaine exposure (PCE) is associated with increased rates of illicit-substance use during adolescence. In addition, both PCE and illicit-substance use are associated with alterations in cortico-striato-limbic neurocircuitry, development of which is ongoing throughout adolescence. However, the relationship between illicit-substance use, PCE and functional neural responses has not previously been assessed concurrently. METHODS: Sixty-eight adolescents were recruited from an ongoing longitudinal study of childhood and adolescent development. All participants had been followed since birth. Functional magnetic resonance imaging (fMRI) data were acquired during presentation of personalized stressful, favorite-food and neutral/relaxing imagery scripts and compared between 46 PCE and 22 non-prenatally-drug-exposed (NDE) adolescents with and without lifetime illicit-substance use initiation. Data were analyzed using multi-level ANOVAs (pFWE<.05). RESULTS: There was a significant three-way interaction between illicit-substance use, PCE status and cue condition on neural responses within primarily cortical brain regions, including regions of the left and right insula. Among PCE versus NDE adolescents, illicit-substance use was associated with decreased subcortical and increased cortical activity during the favorite-food condition, whereas the opposite pattern of activation was observed during the neutral/relaxing condition. Among PCE versus NDE adolescents, illicit-substance use during stress processing was associated with decreased activity in cortical and subcortical regions including amygdala, hippocampus and prefrontal cortex. Neural activity within cortico-striato-limbic regions was significantly negatively associated with subjective ratings of anxiety and craving among illicit-substance users, but not among non-users. CONCLUSIONS: These findings suggest different neural substrates of experimentation with illicit drugs between adolescents with and without in utero cocaine exposure.

Pretreatment measures of brain structure and reward-processing brain function in cannabis dependence: an exploratory study of relationships with abstinence during behavioral treatment.

BACKGROUND: Cannabis is widely abused, and efficacies of therapeutics for cannabis dependence remain suboptimal. Magnetic resonance imaging (MRI) may aid in the identification of biological markers for successful treatment outcomes (i.e., abstinence). METHODS: Twenty men with cannabis dependence and twenty non-substance-using healthy comparison (HC) men underwent MRI scanning. Cannabis-dependent individuals then participated in a 12-week randomized clinical trial of behavioral treatments (contingency management (CM), cognitive behavioral therapy (CBT) or both). Pretreatment functional and structural data were compared between the cannabis-dependent and HC participants. In addition, individuals with cannabis dependence were subdivided based on the successful achievement of 21 days of consecutive abstinence during treatment to assess whether abstinent versus non-abstinent cannabis-dependent participants displayed different pretreatment functional and structural characteristics when compared to HC participants. RESULTS: In comparison to HC participants, cannabis-dependent participants demonstrated greater ventral striatal activation during the receipt of losing outcomes and smaller putamenal volumes. Cannabis-dependent participants who did not subsequently achieve 21 days of consecutive abstinence had increased activity within the striatum during the receipt of losing outcomes, relative to HC participants. Cannabis-dependent participants who did not achieve 21 days of abstinence had decreased bilateral putamen volumes prior to treatment, relative to HC participants. CONCLUSIONS: Individual differences in pretreatment striatal function and structure may relate to individual differences in treatment responses for cannabis dependence. While mechanisms underlying these associations require further exploration, the striatum might mediate treatment responses via its role in associative reward-learning (e.g., through skills training in CBT or reinforcement of abstinence in CM).