Study Discovers Substance Users Cue Reactivity Center in Brain


The uses for Transcranial Magnetic Stimulation (TMS) is continuing to expand. Currently approved by the FDA for treatment of depression and PTSD, this treatment targets specific areas of the brain associated with the issues it is treating, then applying the magnetic coils to the appropriate area.

Patient receiving TMS. Image Credit: Medical University of South Caroline (MUSC)

In order to expand treatment for other ailments and develop the most effective process and procedures, administrators must isolate the areas of the brain to target with the TMS application. Researchers use neuroimaging techniques to to map neuronal circuits. To identify the area to target, various methods are employed, depending on the ailment it is treating.

In an effort to expand TMS treatment to helping individuals suffering from substance abuse, researchers at Medical University of South Carolina (MUSC) have determined which areas of the brain, during neuroimaging, are “hot spots” of increased activity when participants are shown “drug cues.”

cigarette burning in user's hand

They found when patients with dependence on nicotine, alcohol, or cocaine are shown “drug cues” or images related to the substances they were dependent on, the medial prefrontal cortex (mPFC) area of the brain shows increased activity.

The researchers aimed to answer the question, “Which are of the brain is more engaged when patients see a drug cue versus a neutral cue?”

They recruited three type of substance users, cigarette smokers, heavy alcohol users, and chronic cocaine users.

Researchers then utilized functional magnetic resonance imaging (fMRI) to image brain activity while showing patients cues.

doctor presses buttons on fMRI machine
Participants were shown various images while in the fMRI to visualize their brain activity.

Then, participants, were shown images of alcohol, cigarettes, or cocaine cues, alternating with neutral images. Examples of such images include an image of someone holding a cigarette or a cigarette smoker, as the drug cue, matched with a neutral image, like someone holding a pencil, as the neutral cue. This is all based on the physiological reaction to drug cues, or cue-reactivity, is indicative of substance use disorder and often leads to drug use.

hand holding lit cigarette while smoking
This image of a hand holding a lit cigarette Is an example of a "drug cue."
hand writing with a pen on paper
This image of a hand writing with a pen is an example of a "neutral cue."

All three subsets of participants (cigarettes, alcohol, cocaine) displayed “hot spots” in the mPFC when cues were presented.

The team set out to target the area of the brain to target during TMS for substance treatment. The non-invasive treatment is used to modify the neural network, essentially helping to rewire the brain to bring relief from various ailments. When the magnetic field is applied to the appropriate area, TMS will either attenuate or stimulate electrical activity.

Fortunately, the “hot spot” areas were located at a depth of 5 cm or less, making it ideal for for being reached by TMS, therefore making it a possible treatment for substance use disorder.

The are very few side effects associate with TMS, most often used to treat depression. The most common side effect is headache after treatment. There are some people who are susceptible to seizures and they are advised to avoid TMS treatments.

The area identified during this study, the mPFC, is located in the frontal lobe of the brain and is involved in decision making and memory retrieval. It also plays a role in the limbic reward circuit, which the pleasure seeking pathway activated by addictive drugs. This study has lead to clinical trials using low-frequency TMS to reduce excitability, targeting the mPFC.

Further trials are showing that by modulating the mPFC, they may be able to help other forms of substance-dependent populations, without having to start from square one with each substance.

Doctor demonstrates TMS at Medical University of South Carolina (MUSC)
Dr. Colleen Hanlon demonstrates TMS at Medical University of South Carolina (MUSC). Phase 2 clinical trial, which are testing TMS treatment for those with alcohol and concaine problems, is now underway at MUSC. Image Credit: Medical University of South Carolina

Phase 2 clinical trials are underway at MUSC and Ralph H. Johnson VA Medical Center for patients seeking treatment for cocaine and alcohol use. In the first week these patients will undergo fMRI scans and then are randomized to receive 10 days of treatment with TMS or sham therapy. At the end of their inpatient treatment the will receive follow up scans at one and two months post-treatment. The desired outcome is for there to be reduce cue-reactivity and increased sobriety after treatment for patients receiving TMS therapy.

There is an additional clinical trial, “QuitFast,” focused on nicotine dependence. During their first week of quitting smoking, patients will receive multiple sessions of TMS a day to hopefully increase their ability to stay quit. Additional trials at MUSC are assessing chronic pain and opiate use treatment.

It’s an exciting time for research in TMS treatments and uncovering all of the uses!

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