Identifying Networks Underlying Compulsivity in Anorexia Nervosa for Targeting With Neuromodulation

Transcranial Magnetic Stimulation (TMS) is approved by the Food and Drug Administration (FDA) for the treatment of refractory Major Depressive Disorder (MDD) and obsessive-compulsive disorder (OCD). Anorexia nervosa (AN) is characterized by restrictive eating leading to low weight and associated complications. There is an emerging understanding that the symptoms of OCD and AN overlap as AN can be characterized by obsessive thought patterns around food and compulsive restricting and weight loss behaviors. Both conditions are characterized by a propensity toward cognitive inflexibility and the conditions may share neural substrates that maintain maladaptive habitual behaviors and cognitive rigidity. An evidence-based repetitive transcranial magnetic stimulation (rTMS) target for OCD is the orbitofrontal cortex (OFC). The investigators intend to determine if the OFC is also a potential rTMS target for AN and to determine if there is a characteristic pattern of functional network reorganization as characterized by functional magnetic resonance imaging (fMRI) in TMS responders.

To determine if accelerated theta burst rTMS can treat symptoms of AN and normalize abnormal network connectivity, the investigators will enroll 20 patients with AN (aged 18-45) to receive five treatments of inhibitory continuous theta burst rTMS to the right orbitofrontal cortex (R OFC) lasting three minutes delivered every hour over the course of 10 days (2 weeks) for a total of 50 treatments, with follow-up immediately post-treatment, and at 1 month. Clinical symptom change will be determined with weight gain from percent expected body weight (%EBW) and clinical interview with the Eating Disorders Examination (EDE) as well as validated self-report. For Hypothesis 1: At 1-month post-rTMS, the investigators expect increased %EBW, and meaningful reductions in AN compulsive symptoms per the EDE. For Hypothesis 2: The investigators intend to identify changes in the default mode network comparing before and after TMS that are associated with an improvement in AN compulsive symptoms.

Eligibility Criteria:
Inclusion Criteria:

* outpatients
* ages 18 - 45 for Aim 2
* meets Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for AN
* stable on chronic psychotropic medications for 4 weeks prior to the study and agreeable to continue throughout the study
* participants may continue to take medications and record daily usage throughout the study
* capacity to provide informed consent
* ability to tolerate clinical study procedures
* successfully complete the screening forms without any contraindications

Exclusion Criteria:

* Psychiatric: schizophrenia, bipolar disorder, prior psychosurgery, prior electroconvulsive therapy (ECT)
* Neurologic: severe neurocognitive disorder, seizure disorder, certain structural brain lesions (e.g., intracranial mass lesions, hydrocephalus, sequelae of meningitis)
* TMS contraindications: implanted device; presence of metal in the head, including eyes and ears (excluding dental implants); certain tics; medications or systemic illness that predispose seizure risk
* Subjects with an unstable physical, systemic, or metabolic disorder (e.g., unstable hypertension)
* Females who are pregnant or nursing
* Inability to complete the research study