This document discusses the potential role of neuromodulation, specifically repetitive transcranial magnetic stimulation (rTMS), in the treatment of anorexia nervosa (AN). AN is characterized by abnormalities in brain regions involved in reward processing, decision making, and interoception. Preliminary evidence suggests rTMS targeting the dorsolateral prefrontal cortex may improve core AN symptoms, mood, and self-regulation. Several small studies and case reports provide initial support that rTMS is a safe, tolerable and may have therapeutic potential for AN, but more rigorous randomized controlled trials are still needed.

1. Role of
Neuromodulation in
Anorexia Nervosa

2. Anorexia Nervosa
• An eating disorder
• Starvation addiction (abnormalites of the food reward pathway)
• Low body weight associated with an intense fear of gaining weight and
distorted cognitions regarding weight, shape, and drive for thinness
• One year prevalence 0.4% (in females)
• Highest mortality rate among all psychiatric disorders
• High relapse rate
• 50-80% heritable Hill et al. 2016
Gorwood et al., 2016

3. Neurobiology of Anorexia Nervosa
Hill et al.J Eat Disord. 2016; 4: 31.
Dorsal cognitive network (dorsal caudate
and dorsal anterior cingulate, lateral prefrontal
cortex and parietal cortex)
• Makes and executes decisions to control
food consumption
Insula
• Plays a pivotal role in anticipation and
processing of interoceptive states (internal
pain, tastes or feelings of fullness)by
conveying information about the internal
milieu of the person or organism
• Perceives the importance or salience of a
food stimulus
Food intake
Short-term outcomes
Long-term outcomes

4. Neurobiology of Anorexia Nervosa
Hill et al.J Eat Disord. 2016; 4: 31.
• The dorsal cognitive network and
Insula interact to
• Weigh the reward value of food and
• Consequence of consuming it
• This information is integrated to the
homeostatic and motivational drives to
guide eating behaviour

5. Neurobiology of Anorexia Nervosa
Hill et al.J Eat Disord. 2016; 4: 31.
Parietal disturbance
….. distorted
perception about
self-image
Motor cortex…
implements overactive
anxiety and body shape
disturbance through
excessive exercise

6. Neurobiology
of Anorexia
Nervosa
Riva G.Front Hum Neurosci.
2016; 10: 600.

7. Neurobiology
of Anorexia
Nervosa

8. Neurobiology
of Anorexia
Nervosa
Riva G.Front Hum Neurosci. 2016; 10: 600.

9. Neurobiology of Anorexia Nervosa
A
Temperament
-Based Model
for Anorexia
Nervosa

10. Scope of Neuromodulation in AN
• Involvement of fronto-striatal circuitary (DLPFC involvement)
• Success of rTMS to the DLPFC in treating other neurocircuit-based
disorders (such as treatment-resistant depression)
• The encouraging preliminary data on its effects on symptoms of AN
• rTMS to the DLPFC can improve performance on self-regulation tasks,
and thus it may have promise in targeting the self-regulation
difficulties in Eds
(McClelland et al., 2013; McClelland et al., 2016)
• AN characterized by - pathologically increased motor and esophageal
cortical excitability (Khedre et al., 2014)

11. Evidences so far….
PubMed search using Keyword:
Transcranial magnetic
stimulation, Anorexia Nervosa
on 10-03-2017
14 articles
• RCT – 1
• Protocol of RCT -1 (TIARA study)
• Pilot study- 1
• Case series/ reports- 3 (1 in BN)
• Review - 8

12. Evidences so far….
• RCT (McClelland et al., 2016)
• 60 patients with AN
• Primary outcome measure – Core AN symptoms
• Secondary measures – Mood, intertemporal choice behavior, Salivary cortisol,
safety, tolerability, acceptability
• True TMS Vs Sham TMS
• Number of sessions: 1, Site: Left DLPFC
• Change in core symptoms of AN in True TMS group Vs Sham TMS group
• Acceptable, Well tolerated, Safe

13. Evidences so far….
• TIARA study (Bartholdy et al., 2015)
• RCT model protocol
• Plan for 20 sessions (Real Vs Sham TMS) for AN > 3 years
• Outcome measures: BMI, AN Psychopathology, Mood, Anxiety, QOL,
Neuropsychology process, Neuroimaging measures, Tolerability, Safety,
Acceptability
• TMS protocol chosen:
20 sessions of high-frequency rTMS (10 Hz) at 110 % of their
individual MT, consisting of twenty 5-second trains with 55-
second inter-train intervals delivered to the left DLPFC

14. Evidences so far….
• Pilot study on 10 patients with AN – Received single session of HF rTMS @
Lt. DLPFC -->> Reduce core symptoms of AN (Van den Eynde et al., 2013)
• Two cases (McClelland et al., 2013)
• 19-20 sessions of HF rTMS (neuro-navigated) over Lt. DLPFC in treatment resistant AN
• Significant improvement in core AN psychopathology
• Case Series (McClelland et al., 2016)
• 5 females with AN
• 20 sessions of HF rTMS (neuro-navigated) over Lt. DLPFC
• Significant improvement in AN symptoms, mood symptoms, Stable BMI
• 6 months F/U in 3 patients: 2 declared recovered from Eating Disorder
• Conclusion: TMS is safe, acceptable and having potential therapeutic role in AN

15. Evidences so far….
• Increases in fronto-striatal connectivity are associated with response
to dorso-medial repetitive transcranial magnetic stimulation in
refractory binge/purge behaviors (Dunlop et al., 2015)
• 28 subjects with anorexia nervosa, binge-purge subtype or bulimia nervosa
underwent 20-30 sessions of 10 Hz dmPFC rTMS

16. Conclusion
How Neurobiological
Findings Relate to Other
Treatment Tools and the
Behavioral Agreement
Hill et al.J Eat Disord. 2016; 4: 31.