Impaired emotion regulation contributes to the development and severity of substance use disorders (substance disorders). This review summarizes the literature on alterations in emotion regulation ...neural circuitry in substance disorders, particularly in relation to disorders of negative affect (without substance disorder), and it presents promising areas of future research. Emotion regulation paradigms during functional magnetic resonance imaging are conceptualized into four dimensions: affect intensity and reactivity, affective modulation, cognitive modulation, and behavioral control. The neural circuitry associated with impaired emotion regulation is compared in individuals with and without substance disorders, with a focus on amygdala, insula, and prefrontal cortex activation and their functional and structural connectivity. Hypoactivation of the rostral anterior cingulate cortex/ventromedial prefrontal cortex (rACC/vmPFC) is the most consistent finding across studies, dimensions, and clinical populations (individuals with and without substance disorders). The same pattern is evident for regions in the cognitive control network (anterior cingulate and dorsal and ventrolateral prefrontal cortices) during cognitive modulation and behavioral control. These congruent findings are possibly related to attenuated functional and/or structural connectivity between the amygdala and insula and between the rACC/vmPFC and cognitive control network. Although increased amygdala and insula activation is associated with impaired emotion regulation in individuals without substance disorders, it is not consistently observed in substance disorders. Emotion regulation disturbances in substance disorders may therefore stem from impairments in prefrontal functioning, rather than excessive reactivity to emotional stimuli. Treatments for emotion regulation in individuals without substance disorders that normalize prefrontal functioning may offer greater efficacy for substance disorders than treatments that dampen reactivity.
Several lines of evidence suggest that classic (5HT2A agonist) hallucinogens have clinically relevant effects in alcohol and drug addiction. Although recent studies have investigated the effects of ...psilocybin in various populations, there have been no studies on the efficacy of psilocybin for alcohol dependence. We conducted a single-group proof-of-concept study to quantify acute effects of psilocybin in alcohol-dependent participants and to provide preliminary outcome and safety data. Ten volunteers with DSM-IV alcohol dependence received orally administered psilocybin in one or two supervised sessions in addition to Motivational Enhancement Therapy and therapy sessions devoted to preparation for and debriefing from the psilocybin sessions. Participants’ responses to psilocybin were qualitatively similar to those described in other populations. Abstinence did not increase significantly in the first 4 weeks of treatment (when participants had not yet received psilocybin), but increased significantly following psilocybin administration (p < 0.05). Gains were largely maintained at follow-up to 36 weeks. The intensity of effects in the first psilocybin session (at week 4) strongly predicted change in drinking during weeks 5–8 (r = 0.76 to r = 0.89) and also predicted decreases in craving and increases in abstinence self-efficacy during week 5. There were no significant treatment-related adverse events. These preliminary findings provide a strong rationale for controlled trials with larger samples to investigate efficacy and mechanisms.
TRIAL REGISTRATION: NCT02061293
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Substance use disorders (SUD) are diseases of the brain, characterized by aberrant functioning in the neural circuitry of the brain. Resting state functional connectivity (rsFC) can illuminate these ...functional changes by measuring the temporal coherence of low-frequency fluctuations of the blood oxygenation level-dependent magnetic resonance imaging signal in contiguous or non-contiguous regions of the brain. Because this data is easy to obtain and analyze, and therefore fairly inexpensive, it holds promise for defining biological treatment targets in SUD, which could help maximize the efficacy of existing clinical interventions and develop new ones. In an effort to identify the most likely “treatment targets” obtainable with rsFC we summarize existing research in SUD focused on 1) the relationships between rsFC and functionality within important psychological domains which are believed to underlie relapse vulnerability 2) changes in rsFC from satiety to deprived or abstinent states 3) baseline rsFC correlates of treatment outcome and 4) changes in rsFC induced by treatment interventions which improve clinical outcomes and reduce relapse risk. Converging evidence indicates that likely “treatment target” candidates, emerging consistently in all four sections, are reduced connectivity within executive control network (ECN) and between ECN and salience network (SN). Other potential treatment targets also show promise, but the literature is sparse and more research is needed. Future research directions include data-driven prediction analyses and rsFC analyses with longitudinal datasets that incorporate time since last use into analysis to account for drug withdrawal. Once the most reliable biological markers are identified, they can be used for treatment matching, during preliminary testing of new pharmacological compounds to establish clinical potential (“target engagement”) prior to carrying out costly clinical trials, and for generating hypotheses for medication repurposing.
•Resting state functional connectivity (rsFC) is altered in substance use disorder•Reduced rsFC within executive control network (ECN) may be a treatment target•Reduced rsFC between ECN and salience network (SN) may be a treatment target•Withdrawal state profoundly affects rsFC and needs to be controlled for in research•More research using data-driven longitudinal prediction analyses are needed
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ
Abstract Objective measures of drug use are very important in treatment outcome studies of persons with substance use disorders, but obtaining and interpreting them can be challenging and not always ...practical. Thus, it is important to determine if, and when, drug-use self-reports are valid. To this end we explored the relationships between urine drug screen results and self-reported substance use among adolescents and young adults with opioid dependence participating in a clinical trial of buprenorphine–naloxone. In this study, 152 individuals seeking treatment for opioid dependence were randomized to a 2-week detoxification with buprenorphine–naloxone (DETOX) or 12 weeks of buprenorphine–naloxone (BUP), each with weekly individual and group drug counseling. Urine drug screens and self-reported frequency of drug use were obtained weekly, and patients were paid $5 for completing weekly assessments. At weeks 4, 8, and 12, more extensive assessments were done, and participants were reimbursed $75. Self-report data were dichotomized (positive vs. negative), and for each major drug class we computed the kappa statistic and the sensitivity, specificity, positive predictive value, and negative predictive value of self-report using urine drug screens as the “gold standard”. Generalized linear mixed models were used to explore the effect of treatment group assignment, compensation amounts, and participant characteristics on self-report. In general, findings supported the validity of self-reported drug use. However, those in the BUP group were more likely to under-report cocaine and opioid use. Therefore, if used alone, self-report would have magnified the treatment effect of the BUP condition.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Objective
Previous work suggests that the perception of pain is subjective and dependent on individual differences in physiological, emotional, and cognitive states. Functional magnetic resonance ...imaging (FMRI) studies have used both stimulus‐related (nociceptive properties) and percept‐related (subjective experience of pain) models to identify the brain networks associated with pain. Our objective was to identify the network involved in processing subjective pain during cold stimuli.
Methods
The current FMRI study directly contrasted a stimulus‐related model with a percept‐related model during blocks of cold pain stimuli in healthy adults. Specifically, neuronal activation was modelled as a function of changes in stimulus intensity vs as a function of increasing/decreasing levels of subjective pain corresponding to changes in pain ratings. In addition, functional connectivity analyses were conducted to examine intrinsic correlations between three proposed subnetworks (sensory/discriminative, affective/motivational, and cognitive/evaluative) involved in pain processing.
Results
The percept‐related model captured more extensive activation than the stimulus‐related model and demonstrated an association between higher subjective pain and activation in expected cortical (dorsolateral prefrontal cortex, ventrolateral prefrontal cortex, insula, dorsal anterior cingulate cortex dACC extending into pre‐supplementary motor area) and subcortical (thalamus, striatum) areas. Moreover, connectivity results supported the posited roles of dACC and insula as key relay sites during neural processing of subjective pain. In particular, anterior insula appeared to link sensory/discriminative regions with regions in the other subnetworks, and dACC appeared to serve as a hub for affective/motivational, cognitive/evaluative, and motor subnetworks.
Conclusions
Using a percept‐related model, brain regions involved in the processing of subjective pain during the application of cold stimuli were identified. Connectivity analyses identified linkages between key subnetworks involved in processing subjective pain.
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BFBNIB, DOBA, FSPLJ, FZAB, GIS, IJS, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Abstract Chronic cocaine use is associated with enhanced cue reactivity to drug stimuli. However, it may also alter functional connectivity (fcMRI) in regions involved in processing drug stimuli. Our ...aims were to evaluate the neural regions involved in subjective craving and how fcMRI may be altered in chronic cocaine users. Fourteen patients with a confirmed diagnosis of cocaine abuse or dependence (CCA) and 16 gender, age, and education-matched healthy controls (HC) completed a cue reactivity task and a resting state scan while undergoing functional magnetic resonance imaging. CCA showed increased activation compared to HC in left dorsolateral prefrontal and bilateral occipital cortex in response to cocaine cues but not to appetitive control stimuli. Moreover, CCA also showed increased activation within the orbital frontal cortex (OFC) for cocaine cues relative to the appetitive stimuli during a hierarchical regression analysis. A negative association between subjective craving and activity in medial posterior cingulate gyrus (PCC) was also observed for CCA. CCA exhibited increased resting state correlation (positive) between cue-processing seed regions (OFC and ventral striatum), and negative connectivity between cue-processing regions and PCC/precuneus. These alterations in fcMRI may partially explain the neural basis of increased drug cue salience in CCA.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Cognitive control refers to the internal representation, maintenance, and updating of context information in the service of exerting control over thoughts and behavior. Deficits in cognitive control ...likely contribute to difficulty in maintaining abstinence in individuals with alcohol use disorders (AUD). In this article, we define three cognitive control processes in detail (response inhibition, distractor interference control, and working memory), review the tasks measuring performance in these areas, and summarize the brain networks involved in carrying out these processes. Next, we review evidence of deficits in these processes in AUD, including both metrics of task performance and functional neuroimaging. Finally, we explore the clinical relevance of these deficits by identifying predictors of clinical outcome and markers that appear to change (improve) with treatment. We observe that individuals with AUD experience deficits in some, but not all, metrics of cognitive control. Deficits in cognitive control may predict clinical outcome in AUD, but more work is necessary to replicate findings. It is likely that performance on tasks requiring cognitive control improves with abstinence, and with some psychosocial and medication treatments. Future work should clarify which aspects of cognitive control are most important to target during treatment of AUD.
A series of model oligomers consisting of combinations of a traditional strong donor unit (3,4-ethylenedioxythiophene), a traditional strong acceptor unit (benzo
c
1,2,5thiadiazole), and the ...ambipolar unit thieno3,4-
b
pyrazine were synthesized
via
cross-coupling methods. The prepared oligomers include all six possible dimeric combinations in order to characterize the extent and nature of donor-acceptor effects commonly used in the design of conjugated materials, with particular focus on understanding how the inclusion of ambipolar units influences donor-acceptor frameworks. The full oligomeric series was thoroughly investigated
via
photophysical and electrochemical studies, in parallel with density functional theory (DFT) calculations, in order to correlate the nature and extent of donor-acceptor effects on both frontier orbital energies and the desired narrowing of the HOMO-LUMO energy gap. The corresponding relationships revealed should then provide a deeper understanding of donor-acceptor interactions and their application to conjugated materials.
Model dimers consisting of a traditional strong donor, a traditional strong acceptor, and ambipolar thieno3,4-
b
pyrazine were studied to provide a deeper understanding of donor-acceptor interactions and their application to conjugated materials.
Background: Depression may contribute to increased drinking in individuals with alcohol use disorder. Although Alcoholics Anonymous (AA) attendance predicts drinking reductions, there is conflicting ...information regarding the intermediary role played by reductions in depression. Objectives: We explored whether AA attendance reduces depressive symptoms, the degree to which improvement in depression results in reductions in drinking, and in which subgroups these effects occur. Methods: 253 early AA affiliates (63% male) were recruited and assessed at baseline 3, 6, 9, 12, 18, and 24 months. Depression was measured using the Beck Depression Inventory (BDI) and was administered at baseline 3, 6, 12, 18, and 24 months. AA attendance and alcohol use outcomes were obtained with the Form 90. Mediation analyses were performed at early (3, 6, and 9 months) and late (12, 18, and 24 months) follow-up to investigate the degree to which reductions in depression mediated the effect of AA attendance on drinking, controlling for concurrent drinking. In addition, a series of moderated mediation analyses were performed using baseline depression severity as a moderator. Results: At early follow-up, reductions in depression (6 months) mediated the effects of AA attendance (3 months) on later drinking (drinks per drinking day) (9 months) (b = −0.02, boot CI −0.055, −0.0004), controlling for drinking at 6 months. Baseline depression severity did not moderate the degree to which BDI mediated the effects of AA attendance on alcohol use (ps > .05). Conclusion: These findings provide further evidence that depression reduction is a mechanism by which AA attendance leads to reductions in alcohol use. Improving depression may help reduce alcohol use in individuals with AUD, and AA attendance may be an effective way to achieve that goal.
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DOBA, FSPLJ, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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