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Repetitive transcranial magnetic stimulation targeting the insular cortex for reduction of heavy drinking in treatment-seeking alcohol-dependent subjects: a randomized controlled trial
Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience.ORCID iD: 0000-0002-5972-0913
Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.ORCID iD: 0000-0002-1107-5644
Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Psykiatriska kliniken i Linköping.
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2020 (English)In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 45, no 5, p. 842-850Article in journal (Refereed) Published
Abstract [en]

Insula responses to drug cues are correlated with cravings, and lesions in this area reduce nicotine seeking. Here, we investigated the potential efficacy of repetitive transcranial magnetic stimulation (rTMS) targeting the insula in alcohol addiction. Treatment-seeking alcohol-dependent patients (Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition; N = 56) participated in this double-blind, sham-controlled, randomized trial. Participants received 10 Hz rTMS or sham using an H8 coil, 5 days a week for 3 weeks. Stimulation targeted insular cortex and overlaying regions bilaterally, while excluding anterior prefrontal areas. Craving and self-reported as well as biomarker-based drinking measures were collected at baseline, during treatment, and through 12 weeks. Resting-state magnetic resonance imaging (rsMRI) data were collected before and after treatment. Task-based MRI was used to probe brain correlates of reward processing, affective responses, and alcohol following completion of treatment. A marked overall decrease in craving and drinking measures was observed during treatment, but did not differ between rTMS or sham stimulation. Both groups equally increased their alcohol use following completion of treatment and through the 12-week follow-up. Analysis using seeds in the insula identified differences in resting-state connectivity between active and sham groups at completion of treatment, potentially indicating an ability of treatment to modify insula function. However, while each task robustly replicated brain responses established in the literature, no effects of rTMS were found. Collectively, this study does not support efficacy of rTMS targeting the insula in alcohol addiction. 

Place, publisher, year, edition, pages
Springer Nature, 2020. Vol. 45, no 5, p. 842-850
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:liu:diva-200130DOI: 10.1038/s41386-019-0565-7ISI: 000519980000016OAI: oai:DiVA.org:liu-200130DiVA, id: diva2:1825800
Funder
Swedish Research Council, 2013-07434EU, Horizon 2020, 668863-SyBil-AAAvailable from: 2024-01-10 Created: 2024-01-10 Last updated: 2024-05-16
In thesis
1. From social drinking to alcohol addiction: Decision making and its neural substrates along a spectrum from social drinking to alcohol addiction
Open this publication in new window or tab >>From social drinking to alcohol addiction: Decision making and its neural substrates along a spectrum from social drinking to alcohol addiction
2024 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

For a minority of alcohol users, the initial sip of alcohol marks the start of a life-threatening process. This thesis studies cognitive mechanisms pertinent to alcohol addiction and its development, using a spectrum of individuals that range from healthy social drinkers, through people with hazardous use, to those suffering from alcohol addiction. 

Decision making can be altered in addiction, but less is known on the direct pharmacodynamic effects of alcohol intake in healthy people. Study 1 addressed decision making under the effects of moderate alcohol intoxication in healthy social drinkers using established behavioral economics tasks. The investigated processes encompassed both personal and social aspects of decision making. Within the personal domain, impulsivity and risk taking were investigated, while in the social domain, prosocial attitudes along with moral judgment were assessed. Moderate alcohol intoxication was found to impact only the social domain, leading to increased prosocial and utilitarian behaviors, but did not affect measures of impulsivity. 

Choosing alcohol over other natural rewards despite negative consequences is a central phenomenon of alcohol addiction. Two studies of this thesis investigated choice preference for alcohol compared to snack, using a cost manipulation paradigm, in light and heavy drinkers. Study 2 was a laboratory experiment whereas Study 3 was an imaging experiment for characterization of neural substrates. Cost was an important predictor of choice, as in both groups, alcohol choice was sensitive to cost in a parametric manner. This was mirrored in the brain by activity in value-based and salience regions, including orbitofrontal cortex and insula. In Study 2 we found that heavy drinkers showed generally higher alcohol choice preference and attenuated cost sensitivity. Failure to replicate this finding in Study 3, was possibly due to the artificial scanner environment. 

Craving is a key component in the cycle of addiction and a determinant of relapse, making it an important target for treatment interventions. Study 4 was a randomized sham-controlled trial using repetitive transcranial magnetic stimulation (rTMS) targeting the insula as a method to reduce craving and alcohol use in people suffering from alcohol addiction. An overall decrease in alcohol consumption and craving were seen, but did not differ between sham stimulation and rTMS targeting the insula. 

In summary, this thesis provides some insights into cognitive mechanisms related to alcohol addiction and processes that may be implicated in its development. During a moderate acute alcohol intoxication in healthy social drinkers, social decision-making is influenced, leading to increased utilitarian and altruistic behaviors. Thus, deficits in prosocial behaviors in people with alcohol addiction are unlikely to result from direct pharmacodynamic effects of alcohol, but are rather likely to reflect a selection of vulnerable individuals, consequences of the addictive process, or both. In individuals at risk of developing alcohol addiction, the sensitivity to the costs associated with choosing alcohol over an alternative reward is largely preserved, though it might be reduced compared to light, non-problem drinkers. Modulation of the insula cortex with TMS was not successful in decreasing alcohol use in individuals with alcohol addiction. 

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2024. p. 61
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1884
Keywords
alcohol, heavy drinking, alcohol addiction, decision making, alcohol choice, fMRI, rTMS
National Category
Substance Abuse Neurosciences
Identifiers
urn:nbn:se:liu:diva-200129 (URN)10.3384/9789180754088 (DOI)9789180754071 (ISBN)9789180754088 (ISBN)
Public defence
2024-01-26, Storö, Tinnerbäckshuset, Campus US, Linköping, 13:00
Opponent
Supervisors
Available from: 2024-01-10 Created: 2024-01-10 Last updated: 2024-01-10Bibliographically approved

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Perini, IreneKämpe, RobinKarlsson, HannaLöfberg, AndreasPietrzak, MichalHeilig, Markus

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Faculty of Medicine and Health SciencesCenter for Social and Affective NeuroscienceCenter for Social and Affective NeurosciencePsykiatriska kliniken i LinköpingCenter for Medical Image Science and Visualization (CMIV)
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