Essentials: Compulsive Behaviors & Deep Brain Stimulation | Dr. Casey Halpern
In a Nutshell
Dr. Casey Halpern, a neurosurgeon specializing in deep brain stimulation (DBS) and focused ultrasound, treats severe, treatment-resistant OCD and compulsive behaviors like binge eating by targeting brain circuits in the prefrontal cortex, basal ganglia, ventral striatum, and nucleus accumbens, which drive urges despite risks. DBS and ablations offer ~50% response rates for refractory cases failing SSRIs, ERP therapy, and medications, with intraoperative recordings identifying "craving cells" to optimize placement. Enhancing pre-craving awareness via lab-induced signals, AI-monitored physiology (e.g., voice patterns), and scalable non-invasive tools like TMS could prevent compulsions, impulsivity, and epidemics like obesity and suicidality affecting millions.
These notes were generated by AI and may contain inaccuracies.
Welcome to Huberman Lab Essentials, revisiting past episodes for science-based tools for mental health, physical health, and performance. Andrew Huberman, professor of neurobiology and ophthalmology at Stanford School of Medicine, introduces Dr. Casey Halpern, a neurosurgeon considered the astronauts of neuroscience.
Neurosurgeons handle a broad scope: removing brain tumors, clipping aneurysms, treating traumatic brain injury, concussion, spine surgeries (90% of neurosurgeons do herniated discs and lumbar fusions), carpal tunnel syndrome, and nerve disorders across the central and peripheral nervous system. Specialization is now common; Dr. Halpern is chief of stereotactic functional neurosurgery at Penn Medicine, focusing on deep brain stimulation (DBS) surgery and complementary focused ultrasound (non-invasive ablation, FDA-approved for tremor).
DBS places a thin insulated wire into brain areas involved in conditions like Parkinson's disease. The therapy delivers electrical stimulation through multiple contacts at the wire's tip into a small brain region, like implanting a tool to deliver electricity as medication. Electrodes can cause temporary side effects (e.g., laughter, panic) in nearby regions, which can be shut off but may also be therapeutic.
In Parkinson's patients with psychiatric comorbidities like depression or obsessive-compulsive disorder (OCD), DBS for tremor often improves compulsivity, impulsivity, gambling, or mood. Stimulation affects not just motor circuits but limbic circuits involved in emotion. Immediate tremor relief in 20-year sufferers inspires development of therapies for other symptoms.
OCD involves obsessions and compulsions. Dr. Halpern treats 3-5 severe cases yearly with DBS, focusing research on improving outcomes. OCD is a spectrum disorder; mild traits (e.g., obsessiveness in surgeons, scientists, CEOs) can be assets if controlled, but severe cases fail medications.
First-line: SSRIs and tricyclics (target serotonin system, interacting with noradrenergic and dopamine systems). Exposure response prevention (ERP) therapy (cognitive behavioral therapy variant, e.g., Edna Foa's clinic at Penn) helps habituate to stressors; effective for many but 30% of patients (moderate to severe) remain symptomatic.
Deep brain stimulation and capsulotomy (ablation by heating tissue, 3-4 mm size) balance risks/benefits. Ablations can be effective without obvious side effects post-recovery, but transformative effects are low (~50% responder rate, responders still symptomatic). Goal: disease- or symptom-specific delivery.
Disorder of cortex (hyperfunctioning prefrontal cortex, orbitofrontal cortex) and subcortex (basal ganglia, caudate-putamen, dorsal striatum, ventral striatum including nucleus accumbens). Ventral striatum gates reward-seeking; perturbation gates compulsive behavior (e.g., pursuing reward despite punishment like foot shock).
Examples: checking home safety until 3 a.m., hand-washing for hours, cleaning dropped toothbrush, eating disorders (bingeing, purging despite risks), addiction (drug-seeking despite risks). Common denominator: urge despite risk. Nucleus accumbens and cortical projections are key circuits.
Part of reward circuits, interconnects broadly. Manages urges for risky rewards (e.g., heroin despite lethality, OCD checking despite sleep loss). Repeated strong rewards (drugs, binges) hijack function. Tailored treatment can alleviate.
In operating room, leverage Parkinson's technique: audible electrical signals from tremor cells (frequency matches hand shaking). Probe with fine wires to find and disrupt via stimulation.
Craving (relatable term for binge eating disorder, obesity; patients affirm craving even if denying loss of control). In OCD patient, identified obsession-related cells (single case study) to optimize electrode placement. Patients awake for first-in-human trials to establish targets.
Transcranial magnetic stimulation (TMS): FDA-approved for depression, OCD, nicotine addiction; defines circuits for temporary improvement, guiding invasive studies. Limited precision currently, but improvable. Potential TMS targets for anorexia, obesity.
MRI-guided focused ultrasound: FDA-approved for tremor (non-invasive ablation, no incision; effective for one side, e.g., dominant hand). Used routinely for Parkinson's/essential tremor. Trials for modulation (drive/inhibit activity), opening blood-brain barrier for drugs. For OCD, could target capsulotomy site but needs new targets for compulsion.
Invasive electrodes (<1 mm diameter) throughout brain for epilepsy (map seizures, stimulate for symptoms; low complication rate, well-tolerated). Interest in OCD, depression (e.g., Baylor, UCSF studies). Could define ultrasound/TMS targets. Reversible (shut off/remove electrodes).
Developed from mouse models (better modeled than depression/OCD). Human validation via disease-specific invasive recordings leads to non-invasive (TMS modulation, ultrasound lesion).
If people can be made to feel or make themselves feel just a little bit better, a little less anxious just prior to a craving episode or a binge episode, or become better at detecting their own internal states when veering toward a binge, using a drug, or suicidal thinking, that awareness is among the best tools they could develop.
I've always thought that if we can improve awareness, we can improve outcomes. I think that's probably true for many of these patients.
The problem is that some patients are so treatment-resistant. The patients surgeons see have tried cognitive behavioral therapy, medications, and behavioral management; they are as aware as possible but still lose control.
Patients with implanted devices are brought to the laboratory to provoke electrographic signals detectable by the device for home stimulation. Before initiating stimulation, researchers confirm if the device can detect the craving signal, which differs from single-cell intraoperative recordings. These electrodes are about a millimeter in diameter (versus a tenth of a millimeter in the operating room), detecting thousands of cells' responses.
A validated mood provocation method induces moods related to each patient's self-described binge episodes, similar to provoking seizures in an epilepsy monitoring unit but in a psychiatric or food monitoring unit. A psychiatrist and eating disorder specialist induce the mood to evoke the negative behavior.
Video is synchronized to brain signal recordings. Patients wear an eye tracker to monitor eating and gaze with high temporal resolution, understanding events right before the bite. Under video surveillance through a one-way mirror in a lab setting, patients aware they are being studied still binge because they cannot control it; they are the most severe cases.
Improving patient awareness around their problem, beyond societal awareness, could powerfully help many, as in cognitive behavioral therapy—a wonderful treatment, though limited because stopping it leads many patients back to old behaviors. It is not always lasting without continued therapy. For less severe patients, improving awareness is key, but for refractory patients, despite awareness, they cannot control themselves; the goal is to restore that control.
Laboratories at the University of Washington use voice signature patterns to help suicidally depressed people detect episodes before conscious awareness, raising issues of free will and machines being smarter than humans. Search algorithms like Google may know preferences better than users.
These devices listen to speech all day, monitor breathing patterns, sleep quality, and integrate cues, signaling with a yellow light: > "You're headed into a depressive episode." The person might feel fine (baseline), but the device indicates patterns preceding a prior deep episode.
Such devices could help with compulsions and impulsivity. To understand brain signals, get in the brain first; then identify non-invasive signals. Machine learning and bot tech can anticipate high impulsivity.
Suicide is the most dangerous impulse. The lab focuses on impulsivity: going after something without waiting, modeled in mice as taking a food reward without the paired tone cue.
I've been that mouse. We can all relate to a certain extent. It's a spectrum.
Use the body's physiology to anticipate impulses; solutions are just scratching the surface but needed for epidemic problems: obesity, opiate crisis, depression, suicidality—affecting a third of the country or more. Scalable solutions are essential.
Neurosurgeons treat only the most severe; ~200,000 deep brain stimulation surgeries ever performed, but the problem affects 50 million Americans. Surgeons cannot address it alone but can inspire rigorous initiatives. Avoid wasteful wearables; need real therapies. Machine learning is used in the lab; the neurosurgeon develops hypotheses and fundraises.
Hearing this conversation may spark interest in medicine or neurosurgery, requiring physician training first. Neurosurgery residencies may end in some cases.
Thank you for sharing on the cutting edge of brain function and repair.
Keep Andrew Huberman in your library
Save the videos and channels worth coming back to, and find them again in one place.
