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  1. Cue & Play, Vol.1
  2. Open Text: Vol. 1
  3. Systems & Techniques
  4. Open Text: Vol. 1 – CUE Books
  5. Systems & Techniques

The PACS alcohol craving scores at T1 reached trend level significance, after accounting for baseline craving and duration between the scans. NC contrast. Specifically, whereas the subjects in the baclofen group showed significantly greater activation of bilateral DLPFC and right ACC after baclofen treatment relative to baseline, the subjects in the control group showed no such activation Table 2 and Fig.

Additionally, there was reduction of right insular cortex activity after baclofen treatment relative to baseline uncorrected p 0.

Cue & Play, Vol.1

We found that baclofen-treatment related effects at ACC and IC significantly predicted time to relapse. NC condition increased the likelihood of early lapse by 1. As shown in Fig. This study investigated the brain CR changes associated with baclofen treatment in AUD individuals and its relationship with relapse outcomes.

Baclofen treatment was associated with significantly greater activity in bilateral DLPFC and right ACC, critical regions that are involved in decision-making and executive control.

Open Text: Vol. 1

More importantly, greater activation of ACC and deactivation of insula following treatment with baclofen predicted longer time to first alcohol relapse. Several meta-analyses have attempted to build upon traditional concepts of drug dependence which stress on mesolimbic response to pleasure and reward, to a more complex meso-cortical syndrome of impaired response inhibition and salience attribution iRISA. Here, the IC is postulated to store pleasurable interoceptive effects of previous alcohol use, and anticipate these rewarding effects in future 44 and the ACC is believed to be involved in control and inhibition of prepotent maladaptive responses 47 including craving.

Thus, upon exposure to such salient stimulus, AUD individuals, who undergo treatment and intend to stay abstinent, may be able to mobilize coping skills, including attempts to inhibit craving. While two resting state perfusion fMRI based studies in humans have revealed that both acute and chronic administration of baclofen 52 , 53 blunts the cerebral blood flow to ventral anterior insula, it would be further interesting to examine in future studies if higher doses of baclofen can induce more profound deactivation of insula.

The current study results are largely consistent with studies that have evaluated the impact of other pharmacological treatment protocols on brain CR, albeit with some key differences. For example, fMRI CR studies conducted on non-treatment seeking AUD subjects have noted a reduction in VS activity with drugs such as naltrexone, ondansetron, 20 and aripiprazole 54 compared to a placebo arm.

However, another fMRI study in treatment seeking AUD subjects that evaluated the effects of long-acting naltrexone on brain CR 22 found no difference in subcortical activity. This discrepancy is explained by a series of studies that have demonstrated that even direct intravenous alcohol infusion induces robust activation of the VS only in healthy social drinkers, 55 , 56 and not in heavy drinking AUD subjects. Further, there are also some differences noted in the prefrontal CR changes with treatment.

For example, the fMRI study that examined long-acting naltrexone on brain CR 22 found reduced activity in orbital gyri, inferior and middle frontal gyrus, and cingulate gyrus for visual cues. Also an fMRI study with acamprosate found no significant difference in brain CR compared with placebo. Although longitudinal fMRI studies are crucial to model the dynamic changes in brain CR over the treatment course in AUDs, very few studies have employed such design 22 , 59 and none have examined the predictive value of treatment related CR change for relapse outcomes.

However, studies that either have utilized a pre- or post-treatment fMRI CR have reported interesting results congruent to the present study using baclofen. For example, subject with higher baseline VS CR responded better to naltrexone with longer time to relapse.

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This study represents one of the first attempts to examine baclofen treatment-related fMRI cue-reactivity in AUD individuals, but has certain limitations that need to be considered when interpreting the results. While this study may have the limitations of a non-randomized trial, several non-treatment related confounding factors like baseline characteristics and treatment setting were controlled.

Despite the group difference in the time interval between the fMRI scans, we employed mixed effects modelling that provides flexibility in allowing for unequal time intervals, missing values, and imbalanced data. The present study did not specifically control for placebo-effect; however, true effects related to baclofen are still likely because both groups received standard treatment protocols that included comparable detoxification regimes with benzodiazepines, thrice a week group therapy for relapse prevention, oral thiamine supplementation, with only the addition of baclofen in the baclofen-treatment arm.

The encouraging observations of the present study, make a case for further, randomized double-blind, placebo controlled longitudinal fMRI studies of baclofen treatment, preferably following longer periods of administration of baclofen.

While we explored the relationship of ACC-IC cue-reactivity with relapse outcomes, further examination with neuro-cognitive tests of response inhibition and reward functions are warranted. Also, the study results may be biased as we included only male participants, but that reflects the strong preponderance of males in treatment centres and indeed the extreme male preponderance of drinking prevalence in India.

Despite these limitations, this study provides both novel and valuable preliminary neurobiological evidence for baclofen response in AUD and its relationship with relapse outcomes. Baclofen appears produce its clinical effects in AUD through modulation of critical brain regions within the incentive-salience network, with activation of regions involved in cognitive control like ACC; and deactivation of regions involved in reward anticipation like insula. Brain regions that showed significant group-by-time interaction with significantly greater activation in baclofen group relative to control group for the contrast alcohol-neutral cues.

Cox proportional hazard regression models of baclofen treatment-related BOLD signal change predicting time to relapse. Results indicate that greater activation of ACC and deactivation of insula following baclofen treatment, predicted longer time to first alcohol relapse.

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Title Author Keyword Volume Vol. Methods Twenty-three inpatients with AUD underwent a functional magnetic resonance imaging cue-reactivity task before beginning medication with baclofen and 2 weeks later. Results Whole-brain linear mixed effects analysis revealed a significant group-by-time interaction with greater activation of the bilateral dorsolateral pre-frontal cortex and right anterior cingulate cortex ACC following baclofen treatment in comparison with the control group.

Conclusion This study provides preliminary evidence for the neural predictors of baclofen treatment response in AUD. Keywords : Baclofen, Functional magnetic resonance imaging, Cue-reactivity, Relapse prediction. Participants and Procedures Thirty-five male subjects seeking in-patient treatment for alcohol dependence, aged between 23 and 50 years, participated in this naturalistic, observational study. A The visual image induced craving for ethanol VICE functional magnetic resonance imaging paradigm was presented in a block design, consisting of four second epochs.

The resting control block R was a blank screen with fixation cross-hair. B Changes in the in-scanner craving responses mean and standard error averaged across subjects for different ARC exposure blocks for the baseline solid lines and 2nd week dashed lines scans shown for baclofen and control groups separately. For illustration each ARC block liquor storefront, alcohol bottles, pouring and sipping alcohol was scored 1 if the subjects experienced craving for alcohol indicated by means of button presses for at least two of the five cues in the block. Brain regions depicting significant group-by-time interactions for alcohol vs.

The results indicate significant activation of bilateral dorsolateral prefrontal cortex DLPFC and right anterior cingulate cortex ACC following baclofen treatment compared to the control group.

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Color-bar is indicative of z-values. L, left; R, right. C Accuracy of relapse prediction as computed by the receiver operating characteristic analysis curves. All regions are significant at cluster p family-wise error. Drug dependence, a chronic medical illness: implications for treatment, insurance, and outcomes evaluation. World Health Organization Global status report on alcohol and health Geneva: World Health Organization. Swift, RM Drug therapy for alcohol dependence.

N Engl J Med. Pharmacotherapy of alcohol use disorders: seventy-five years of progress. J Stud Alcohol Drugs Suppl. Soyka, M Nalmefene for the treatment of alcohol dependence: a current update. Int J Neuropsychopharmacol. Baclofen: a new drug for the treatment of alcohol dependence. Int J Clin Pract. Nat Neurosci. Eur Neuropsychopharmacol. Baclofen efficacy in reducing alcohol craving and intake: a preliminary double-blind randomized controlled study. Alcohol Alcohol. Effectiveness and safety of baclofen for maintenance of alcohol abstinence in alcohol-dependent patients with liver cirrhosis: randomised, double-blind controlled study.

Efficacy and safety of baclofen for alcohol dependence: a randomized, double-blind, placebo-controlled trial. Alcohol Clin Exp Res.

Systems & Techniques

Baclofen as add-on to standard psychosocial treatment for alcohol dependence: a randomized, double-blind, placebo-controlled trial with 1 year follow-up. J Subst Abuse Treat. Efficacy and safety of high-dose baclofen for the treatment of alcohol dependence: A multicentre, randomised, double-blind controlled trial. Dose-response effect of baclofen in reducing daily alcohol intake in alcohol dependence: secondary analysis of a randomized, double-blind, placebo-controlled trial.

Correlates of baclofen effectiveness in alcohol dependence. Indian J Psychol Med.

Open Text: Vol. 1 – CUE Books

Effectiveness and safety of baclofen in the treatment of alcohol dependent patients. A human laboratory pilot study with baclofen in alcoholic individuals. Pharmacol Biochem Behav.

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Liu, J, and Wang, L Baclofen for alcohol withdrawal. Baclofen for the treatment of alcohol dependence and possible role of comorbid anxiety. Effect of naltrexone and ondansetron on alcohol cue-induced activation of the ventral striatum in alcohol-dependent people. Arch Gen Psychiatry. Alcohol-associated stimuli activate the ventral striatum in abstinent alcoholics.

J Neural Transm Vienna. Alcohol-related olfactory cues activate the nucleus accumbens and ventral tegmental area in high-risk drinkers: preliminary findings. Subcortical correlates of craving in recently abstinent alcoholic patients. Am J Psychiatry. Activation of prefrontal cortex and anterior thalamus in alcoholic subjects on exposure to alcohol-specific cues. Differential brain activity in alcoholics and social drinkers to alcohol cues: relationship to craving.

Effect of brain structure, brain function, and brain connectivity on relapse in alcohol-dependent patients. Cue reactivity is associated with duration and severity of alcohol dependence: an FMRI study. PLoS One. Neural substrates of cue reactivity: association with treatment outcomes and relapse. Addict Biol. Functional neuroimaging studies of alcohol cue reactivity: a quantitative meta-analysis and systematic review. Network traffic reduction is obtained as the final result in the use of Green Ajax.

Systems & Techniques

What's New. May 14, News! Frequency: Monthly DOI: Steve Thatcher Executive Editor: Ms. Nancy Y. E-mail: ijiet ejournal. The journal publishes good-quality papers which focous on the advanced researches in the field of information and education technology. International Journal of Information and Education Technology.