Biology & Treatments for Compulsive Eating & Behaviors | Dr. Casey Halpern

Biology & Treatments for Compulsive Eating & Behaviors

Summary

Dr. Casey Halpern, Chief of Stereotactic and Functional Neurosurgery at the University of Pennsylvania, discusses the neuroscience underlying compulsive behaviors including binge eating disorder, OCD, and addiction. His laboratory develops and applies engineered devices — particularly deep brain stimulation (DBS) — to directly modulate brain circuits responsible for loss-of-control behaviors. The conversation covers the role of the nucleus accumbens, current treatment approaches, and a groundbreaking first-in-human trial using responsive DBS for compulsive eating.

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Key Takeaways

• The nucleus accumbens is a central hub of reward circuitry that becomes dysregulated after repeated exposure to highly palatable foods, drugs, or other powerful rewards — potentially within as little as two weeks in animal models.
• Binge eating disorder is the most common eating disorder, affecting an estimated 3–5% of the population, and is likely underdiagnosed in people with obesity.
• A defining feature of binge eating disorder, OCD, and addiction is loss of control — pursuing a reward despite known risks — which Dr. Halpern views as a common neurological denominator across these conditions.
• Responsive (intermittent) DBS — triggered only when a craving signal is detected — appears more effective and durable than continuous stimulation, which loses efficacy over time due to the brain’s homeostatic regulation.
• Obesity is a phenotype, not a uniform diagnosis; roughly 20% of people with obesity have a binge eating component, but not all obesity is behaviorally driven.
• High-fat and highly refined foods can hijack normal nucleus accumbens function within weeks, predisposing continued compulsive eating behavior.
• A “two-hit hypothesis” is proposed for developing binge eating disorder: a biological/genetic predisposition combined with a recurring environmental stressor.
• Anorexia and obesity-related compulsive overeating may be more neurologically similar than different, both involving compulsive behavior driven by societal pressures and brain circuit vulnerabilities.
• Deep brain stimulation for OCD achieves a responder rate of roughly 50%, and even responders remain symptomatic — motivating more targeted, disease-specific approaches.
• Social stigma around obesity and eating disorders worsens outcomes by causing shame, discouraging treatment-seeking, and reinforcing the cycle of disordered behavior.

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Detailed Notes

What Neurosurgeons Do vs. Other Brain Specialists

• Neurosurgery covers the entire central and peripheral nervous system — tumors, aneurysms, spinal disorders, and functional/movement disorders.
• Stereotactic and functional neurosurgery is a subspecialty focused on precise, physiology-driven interventions rather than purely structural ones.
• DBS involves implanting a thin insulated wire into a target brain region, connected to a subcutaneous pulse generator (similar to a cardiac pacemaker). The electrical stimulation itself — not the wire placement — is the therapy.
• Focused ultrasound (transcranial) is an FDA-approved, non-invasive ablation method currently approved for essential tremor.

Deep Brain Stimulation: How It Works

• In Parkinson’s disease, DBS targets the subthalamic nucleus; electrical activity from tremor cells is converted to audio and matched to the patient’s tremor frequency — allowing real-time confirmation of correct electrode placement.
• Patients are often awake during surgery for precise mapping; stimulation effects (e.g., tremor relief, mood elevation, laughter) can be observed in real time.
• Incidental findings: Parkinson’s patients receiving DBS for tremor sometimes report improvements in depression, OCD symptoms, or gambling behavior, pointing to overlapping limbic-motor circuits.

OCD: Neurobiology and Treatment

• Brain areas involved: Orbital frontal cortex (OFC), prefrontal cortex, dorsal striatum (caudate/putamen), and ventral striatum including the nucleus accumbens.
• These regions form a cortical-subcortical loop; in OCD, they appear dysregulated rather than simply hypo- or hyperactive.
• OCD exists on a spectrum — from subclinical obsessive tendencies (common in high-achieving individuals) to severe, treatment-refractory disorder.
• Treatment hierarchy:
  1. SSRIs (first-line pharmacotherapy)
  2. Tricyclic antidepressants
  3. Exposure and Response Prevention (ERP) — considered among the most effective non-surgical options; developed in part by Dr. Edna Foa at Penn
  4. DBS or capsulotomy (ablation) for treatment-refractory cases
• Approximately 30% of OCD patients do not respond adequately to medication and behavioral therapy.
• DBS for OCD achieves roughly a 50% responder rate; even responders remain symptomatic, highlighting the need for improved targeting.
• Capsulotomy (thermal ablation of a small brain region) can be effective with minimal detectable side effects; some regions appear safe to ablate — described as “appendix-like” in terms of necessity.

Nucleus Accumbens and Reward Circuitry

• The nucleus accumbens is nearly 1 centimeter in size — larger than many DBS targets — and contains functionally distinct subregions.
• It gates reward-seeking behavior; when perturbed, it promotes compulsive pursuit of rewards despite negative consequences (analogous to a rat seeking food despite receiving foot shocks).
• In mice exposed to 60% high-fat diet, nucleus accumbens function changes within two weeks — showing both hyperactive and hypoactive regions — predisposing continued compulsive eating.
• A craving/anticipatory signal in the nucleus accumbens appears to precede binge behavior and can be detected with local field potential (LFP) recordings.

Binge Eating Disorder: Definition and Neurobiology

• Prevalence: 3–5% of the general population; likely higher among people with obesity (obesity affects ~35% of the U.S. population).
• A binge is defined by: (1) eating an unusually large amount of food in a brief period, and (2) a subjective sense of loss of control — not simply overeating at a meal.
• Severe binge eating disorder: approximately once daily; moderate: ~3–4 times per week.
• Loss-of-control eating (without meeting full binge criteria) can occur dozens of times per week.
• A pre-meal negative affect — feeling stressed, anxious, or low — commonly precedes binge episodes; eating temporarily relieves this state, reinforcing the cycle.
• Binge eating disorder is strongly linked to obesity but not identical — not all patients with binge eating disorder are obese, and not all obese individuals binge eat.

The Penn DBS Trial for Loss-of-Control Eating

• Study design: NIH-funded, FDA-approved first-in-human pilot study; targeting patients who have failed gastric bypass surgery, presumed due to binge eating disorder.
• Target: Nucleus accumbens — specifically the region connected to the prefrontal cortex via tractography-mapped circuits (connectomics).
• Intraoperative protocol:
  • Patients are awake and fasted
  • Shown personally selected high-craving food images to provoke craving
  • Single-unit and multi-unit neural recordings identify “craving cells”
  • Stimulation is delivered to assess safety and mood elevation
  • Real-time intraoperative CT imaging confirms electrode placement to within ~0.5 mm accuracy
• Stimulation parameters: Brief, episodic bursts of 5–10 seconds, triggered only when the craving signal is detected (responsive/closed-loop stimulation).
• Rationale for intermittent stimulation: Mouse data (published in PNAS) showed that continuous stimulation loses efficacy over time; intermittent, signal-triggered stimulation produces more durable binge-blocking effects.
• The positive affect transiently induced by stimulation is hypothesized to interrupt the craving-to-binge cycle.
• Six patients planned at Penn; two have been treated at time of recording.

Anorexia and the Shared Circuit Hypothesis

• Anorexia nervosa has the **highest mortality of all psychiatric conditions