[@hubermanlab] Essentials: Compulsive Behaviors & Deep Brain Stimulation | Dr. Casey Halpern

Link: https://youtu.be/aKDzF_fMMrc

Duration: 33 min

Transcript: Download plain text

Short Summary

Dr. Casey Halpern, a neurosurgeon and chief of stereotactic functional neurosurgery at Penn Medicine, joins Andrew Huberman to discuss surgical approaches to brain disorders including OCD, eating disorders, and depression. The conversation explores deep brain stimulation, capsulotomy, and future non-invasive treatments like focused ultrasound for epidemic-scale conditions affecting tens of millions of Americans.

Key Quotes

1. "We have to get in the brain before we get out of it. And if we get in the brain and understand what these signals look like, we'll know what those non-invasive signals are." (00:00:29)
2. "Some of these problems are of epidemic proportions. Largest public health problems in this country, in this world, obesity, opiate crisis, depression, suicidality. I mean, that's like a third of our country, maybe more." (00:00:31)
3. "You can also destroy small parts of the brain. We're talking 3 or 4 millimeters in size." (00:00:09)

Detailed Summary

Episode Overview

This Huberman Lab Essentials episode features Dr. Casey Halpern, a neurosurgeon and chief of stereotactic functional neurosurgery at Penn Medicine, discussing the intersection of neurosurgery and psychiatric conditions. The conversation explores surgical approaches to treating brain disorders including obsessive-compulsive disorder (OCD), binge eating disorder, and depression, along with emerging non-invasive treatment technologies that could address these conditions at population scale.

• Dr. Casey Halpern is chief of stereotactic functional neurosurgery at Penn Medicine and focuses on surgical treatments for psychiatric conditions
• The episode covers deep brain stimulation (DBS), capsulotomy ablation procedures, and future non-invasive approaches like focused ultrasound
• Halpern's work spans treating conditions affecting millions of Americans, from OCD to eating disorders to depression

Neurosurgery Scope and DBS Basics

Neurosurgery encompasses a broad range of procedures including brain tumor removal, aneurysm clipping, traumatic brain injury treatment, concussion management, and spine surgeries (which comprise approximately 90% of cases). Deep brain stimulation involves placing thin insulated wires with multiple contacts deep into brain regions involved in specific conditions like Parkinson's disease; critically, the electrical stimulation itself is therapeutic, not the electrode itself.

• Approximately 200,000 DBS surgeries have ever been performed worldwide since the procedure was developed
• Surgeons listen to electrical activity through fine wires to find cells firing at similar frequencies before stimulating or quieting them
• The technique disrupts circuits like the tremor circuit in the subthalamic nucleus for movement disorders
• DBS for movement disorders has been discovered to help psychiatric comorbidities—patients treated for tremor also report improvements in gambling issues and mood
• Spine surgeries constitute about 90% of neurosurgical cases overall

OCD Treatment Landscape

OCD is considered a spectrum disorder where obsessions and compulsions may not always meet formal diagnostic criteria but still significantly impact functioning. First-line treatments include SSRIs and tricyclics targeting the serotonin system, though effects are unpredictable due to complex interactions with noradrenergic and dopamine systems. Exposure response prevention, offered at Penn's clinic founded by Dr. Edna Foa, is described as the most effective therapeutic option for OCD.

• About 30% of OCD patients still suffer from the condition despite first-line treatments, representing the treatment-resistant population that surgical intervention targets
• Halpern treats approximately 3 to 5 patients per year with DBS for OCD
• Surgical interventions (DBS or capsulotomy) achieve an approximately 50% responder rate for OCD
• Dr. Edna Foa founded the exposure response prevention clinic at Penn, which offers the most effective therapeutic option for OCD
• SSRIs and tricyclics target the serotonin system but have unpredictable effects due to interactions with noradrenergic and dopamine systems

Surgical Approaches: DBS vs. Ablation

Capsulotomy is an ablation approach where small brain regions (3-4 millimeters) can be safely heated and destroyed with sometimes no obvious functional side effects. DBS electrodes placed in small brain regions can affect areas within a few millimeters, causing temporary side effects like laughter or panic that can be reversed by shutting off the electrode; sometimes these effects are therapeutic.

• Capsulotomy involves destroying small brain regions (3-4mm) through heating, with sometimes no obvious functional side effects
• DBS electrodes can be tested by causing temporary effects like laughter or panic, which are reversible by shutting off the electrode
• When temporary effects during electrode testing are therapeutic, they often translate to lasting therapeutic benefit
• DBS can be turned off or adjusted post-surgery if side effects emerge, whereas ablation is permanent

Brain Circuits: Compulsion vs. Impulsivity

In OCD patients, the prefrontal and orbital frontal cortex are often hyperfunctioning and need to be normalized. The nucleus accumbens, part of reward circuits, gates reward-seeking behavior; when perturbed, it gates compulsive behavior where patients pursue rewards despite punishment. The distinction between compulsion and impulsivity is clinically important.

• Compulsion involves going after a reward despite risk, while impulsivity involves going after something immediately without waiting
• The nucleus accumbens gates reward-seeking behavior; when perturbed, it gates compulsive behavior where patients pursue rewards despite punishment
• Real-world OCD examples include patients checking their home for safety until 3:00 a.m. without sleeping
• Another example involves compulsive cleaning for hours after dropping a toothbrush on the floor
• The prefrontal and orbital frontal cortex are often hyperfunctioning in OCD patients and need to be normalized through treatment

Binge Eating Disorder Research

People with severe binge eating disorder tend to binge about once a day; researchers use the term "craving" because patients relate to it better than "binge" or "loss of control." The team uses a "mood provocation" technique, validated similarly to seizure provocation in epilepsy monitoring, with an eating disorder psychiatrist to induce states related to each patient's binge episodes.

• Patients are studied under video surveillance with eye trackers and one-way mirrors during research sessions
• Despite awareness of being studied, patients still binge because they cannot control the behavior
• A limitation of cognitive behavioral therapy is that when patients stop it, many revert to their old behaviors
• Halpern's team includes an eating disorder psychiatrist who helps induce states related to each patient's specific binge episodes

Research Collaborations and Methods

Baylor and UCSF researchers are combining epilepsy stereoencephalography techniques with psychiatry expertise to study better electrode targets for depression. Stereoencephalography uses invasive electrodes less than 1mm in diameter placed throughout the brain to study seizures and has surprisingly low complication rates. Researchers identified cells related to obsessions in a single case study with an OCD patient to optimize electrode placement before larger trials.

• Stereoencephalography electrodes are less than 1mm in diameter and have surprisingly low complication rates
• Mouse studies for obesity and binge eating disorder are believed to translate to humans better than depression or OCD models, which are harder to model in mice
• Researchers identified cells related to obsessions in a single case study with an OCD patient before proceeding to larger trials
• The collaboration between Baylor and UCSF combines epilepsy expertise with psychiatry research

Non-Invasive Treatment Frontiers

TMS (transcranial magnetic stimulation) is FDA-approved for depression, OCD, and nicotine addiction. MRI-guided focused ultrasound is FDA-approved for tremor treatment and works without incisions or electrode placement into the brain. Researchers are studying whether focused ultrasound can open the blood-brain barrier to deliver medication to specific brain areas, such as for brain tumors.

• TMS is FDA-approved for depression, OCD, and nicotine addiction
• MRI-guided focused ultrasound is FDA-approved for tremor and requires no incisions or electrode placement
• The long-term goal is to move from invasive recording studies to non-invasive modulatory approaches like TMS
• Researchers are studying focused ultrasound to open the blood-brain barrier for medication delivery to brain tumors
• Ultrasound lesion approaches are being explored for psychiatric conditions and eating disorders

The Scale of the Problem

Approximately 50 million Americans are affected by obesity, opioid crisis, depression, and suicidality—described as the largest public health problems requiring scalable solutions. Surgery cannot address problems affecting tens of millions of people; scalable solutions are urgently needed. University of Washington laboratories are using voice pattern signatures, breathing patterns, and sleep data to help suicidal people detect approaching depressive episodes.

• Approximately 50 million Americans are affected by obesity, opioid crisis, depression, and suicidality combined
• Surgery cannot address problems affecting tens of millions of people; scalable solutions are urgently needed
• The speaker identifies suicide as the most dangerous impulse and a major focus of the lab's research efforts
• University of Washington laboratories use voice pattern signatures, breathing patterns, and sleep data to detect approaching depressive episodes in suicidal patients
• Wearable devices and tools need to be real therapies rather than products that waste people's money and time