What Brain Stimulation is Teaching Us about Anorexia Nervosa

What is TMS?

Transcranial magnetic stimulation (TMS) is a noninvasive form of brain stimulation that uses magnetic fields to stimulate specific regions of the brain. During a TMS session, a pulse is sent through a coil that rests on the head over a specific region of the brain. This pulse stimulates the brain region and connected areas of the brain.

Repetitive TMS is a form of TMS that involves the administration of multiple pulses over a short period of time. With multiple sessions, repetitive TMS may promote longer-term changes in brain activity.

Repetitive TMS appears especially promising as a potential treatment for several psychiatric disorders. In fact, several devices that deliver repetitive TMS are now approved by the Federal Drug Administration (FDA) – the regulatory body in the U.S. that oversees the safety and efficacy of new medicines and medical devices – for use in the treatment of depression and obsessive-compulsive disorder.

In addition to its use as a treatment, repetitive TMS can also be used as a direct way to learn about the function of brain regions. Single sessions of repetitive TMS can be used to stimulate a specific area of the brain so that subsequent changes in behavior can be observed. If similar behavioral changes are observed when the same part of the brain is stimulated among many participants, it provides initial evidence that the brain region may be involved in that behavior.

What is known about anorexia nervosa and the brain?

Anorexia nervosa is a serious psychiatric disorder and perhaps its key defining feature is the persistent restriction of food intake (i.e., not eating enough to maintain an appropriate weight). Using a computer task in which we ask people to make a series of food ratings and decisions, we have previously found that patients with anorexia nervosa consistently demonstrate a striking avoidance of high-fat foods. This is similar to what we (and others) have found in laboratory eating studies.

Research by our team has also found that people with anorexia nervosa – unlike individuals without an eating disorder – use a specific brain region, the dorsal striatum, when making decisions about what to eat. Findings from this research study also indicate that the dorsal striatum’s connections to another brain region, the dorsolateral prefrontal cortex, may also underlie restrictive food choices in anorexia nervosa.

Together, this research suggests that connections between these brain regions may influence the restriction of food intake and may therefore be good targets for treatment for people with anorexia nervosa.

Using repetitive TMS to test the brain basis of anorexia nervosa.

Based on our findings of altered brain activity and connectivity in anorexia nervosa, we designed an experiment involving a single session of repetitive TMS to test whether stimulating the dorsolateral prefrontal cortex could influence food choice among patients. Our hypothesis was that repetitive TMS to this brain region would reduce restrictive food choices in patients with AN.

Study Methods

Ten adult females with anorexia nervosa receiving treatment in our inpatient program participated in this study. Participants completed the computerized food choice task twice: once while receiving a session of repetitive TMS, and once while receiving a session of “sham” repetitive TMS.

The sham session is designed to look and sound like repetitive TMS but, as the name implies, it is a sham and does not change brain activity at all! In this study, participants did not know which session was “true” TMS and which was the sham.

We compared participants’ food choices after the session of repetitive TMS with their food choices after the sham procedure to determine whether real repetitive TMS impacted behavior.

Findings, and what it all means.

In this small, initial study, participants chose a greater proportion of high fat foods while receiving the real repetitive TMS procedure compared to the sham condition. There was also a pattern suggesting participants made decisions more consistent with their taste preferences (rather than their ideas about how healthy foods were) when receiving the real versus sham procedure – we will need a larger sample of participants to see if this pattern holds up.

These findings provide preliminary evidence that this area of the brain (the dorsolateral prefrontal cortex) may function as a good repetitive TMS target for the treatment of anorexia nervosa.

To read more about the study described above, check out:

Muratore AF, Bershad M, Steinglass JE, Foerde KE, Gianini L, Broft A, Attia E. Use of high-frequency repetitive transcranial magnetic stimulation to probe the neural circuitry of food choice in anorexia nervosa: A proof-of-concept study. Int J Eat Disord. 2021 Nov;54(11):2031-2036. doi: 10.1002/eat.23597. Epub 2021 Aug 20. PMID: 34415081; PMCID: PMC9126092.

What’s next?

With funding from the National Institute of Mental Health and the National Eating Disorder Association, a larger study is in the works!

This next study investigates the effects of repetitive TMS to the same area of the brain we looked at before – the dorsolateral prefrontal cortex – to see how repetitive TMS impacts both brain and behavior among female inpatients with anorexia nervosa.

Participation takes place over the course of two days, scheduled about a week apart. On the first day, participants will undergo an MRI brain scan while completing the food choice computer task, so that we can measure brain activity while decisions are being made about what to eat. On the second day, participants will receive either a single session of real repetitive TMS or sham repetitive TMS. During the session, neither the researcher nor the participant will know if they are receiving the real or sham procedure (this ensures that neither the participant’s nor the researcher’s behavior is affected by their knowledge that the procedure is real or sham).  Immediately following the repetitive TMS procedure, participants will again undergo an MRI brain scan while completing the food choice task.

This study will allow us to more definitively test whether repetitive TMS can change brain activity in the areas we think it does, and whether changes in brain activity are also associated with changes in food choice behavior.

Findings from this research will further our understanding of the brain regions involved in restrictive eating symptoms and, help us continue to explore new treatment options for this challenging disorder.

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