Role of the Insula
Functional imaging studies of the brain have shown that activation of the insula in response to drug cues is positively correlated with cravings. High insula activity during a simple decision-making task is associated with relapse to drug use. This is consistent with the notion that disrupted insula function contributes to impaired decision making, resulting in continued drug use despite negative consequences.
For example, chronic cocaine users have been shown to have grey matter loss in the insula. Similar reductions in insular volume and cortical thickness have been reported in alcoholics. Modulation of insula activity may therefore represent a novel therapeutic approach in addiction.
Irene Perini is one of the researchers in the project. She has a background in neuropsychology and neurophysiology research with MRI as the primary tool.
-We are interested in the insula because it has been shown that lesions in this area reduce craving for drugs. The insula is involved in processing the internal states of the body. It is processing the way we feel, Irene explains.
Neuromodulation to Reduce Cravings
However, non-invasive methods to modulate the activity of this structure have until recently not been available.
A small pilot study has suggested that repetitive transcranial magnetic stimulation (rTMS), a non-invasive tool for neuromodulation, can reduce craving and cue reactivity in cocaine and opiate users.
- The idea is to alter the activity in the insula to see how this is going to impact their behavior. With rTMS you can excite the brain activity or inhibit the activity depending on the frequency you use, Irene says.
In these studies, rTMS has typically been applied to a superficial structure of the brain. However, the insula is located deeper into the brain and no study has therefore to date evaluated whether modulation of insula activity using rTMS would reduce alcohol craving and use. The present study uses a novel coil, designed to allow “deep TMS”, to examine whether stimulation of the insula offers a novel alcoholism treatment.
-The objectives of the project are to investigate the effects of repetitive transcranial magnetic stimulation (rTMS) targeting the insula on alcohol use and neural responses in alcohol-dependent patients, Irene continues.
The project is part of a bigger international consortium with 11 other partners. In Israel one of the partners are doing the same study but with another brain area.
The study population consists of treatment seeking alcohol dependent subjects who have first completed standard alcohol withdrawal treatment if needed. The participants first undergo an MRI scan to collect resting state, DTI and structural data, and then receive one of two treatments: Active (10Hz) rTMS; or sham stimulation, both targeting the insula bilaterally. rTMS sessions will be conducted five times per week, for 3 weeks, for a total of 15 sessions. A second MRI scan is obtained at the end of the treatment phase to assess changes in resting state connectivity, and to evaluate insula activity in tasks known to activate this structure.
The primary outcome measures are alcohol consumption during the follow-up phase and insula fMRI responses during tasks known to induce insula activation. A number of secondary and exploratory measures are also assessed, including objective biomarkers of alcohol consumption.
-Coming from basic research, I have never worked with clinicians before. Now we work with clinicians in every project. That has been an insight for me. Thanks to this relationship between research and clinic work we get access to and help with recruiting the patients. It is very motivating to work with research that is directly aimed at helping the patients, Irene concludes.