Essentials: Compulsive Behaviors & Deep Brain Stimulation | Dr. Casey Halpern | Edited Transcript
A copyedited transcript of Andrew Huberman's conversation with Dr. Casey Halpern on compulsive behavior, OCD, deep brain stimulation, reward circuits, and neuromodulation.
This is a professionally copyedited transcript of Essentials: Compulsive Behaviors & Deep Brain Stimulation | Dr. Casey Halpern. It has been edited for readability and lightly formatted while preserving the substance of the discussion.
Episode Guide
00:00:00 Casey Halpern
00:00:20 Neurosurgery, Deep Brain Stimulation
00:04:19 Obsessive-Compulsive Disorder (OCD) & Treatments
00:10:11 OCD Brain Areas, Addiction
00:12:34 Nucleus Accumbens, Risk & Rewards; Binge Eating Disorder
00:16:50 Non-Invasive Brain Stimulation, Transcranial Magnetic Stimulation
00:24:33 Awareness of Cravings, Severe Binge Eating Disorder
00:28:38 Artificial Intelligence/Machine Learning & Predicting Impulsive Behavior
00:32:44 Acknowledgements
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Full video:
In this Huberman Lab Essentials episode, my guest is Dr. Casey Halpern, MD, a professor of neurosurgery at the Perelman School of Medicine at the University of Pennsylvania. We discuss how deep brain stimulation and other neuromodulation approaches are being used to treat Parkinson’s disease, obsessive-compulsive disorder (OCD), binge eating disorder and depression-related symptoms. We also explore the brain circuits that drive compulsions, cravings and impulsivity, as well as emerging non-invasive tools for predicting and treating harmful behaviors.
Transcript
00:02-00:04
Andrew Huberman: Welcome to Huberman Lab Essentials, where we revisit past episodes for the most potent and actionable science-based tools for mental health, physical health, and performance.
00:04-00:13
Andrew Huberman: I’m Andrew Huberman, a professor of neurobiology and ophthalmology at Stanford School of Medicine. Today, I’m joined by Dr. Casey Halpern for a conversation.
00:20-00:24
Andrew Huberman: Casey—well, Dr. Halpern—welcome.
00:24-00:26
Casey Halpern: Thank you. Great to be here.
00:26-00:32
Andrew Huberman: You’re a neurosurgeon, which I like to think of as the astronauts of neuroscience. For those who aren’t familiar with the differences between neurosurgery, neurology, and psychiatry, could you explain what a neurosurgeon does and how you view the brain?
00:32-01:07
Casey Halpern: Sure, neurosurgery covers a pretty broad range. We remove brain tumors, clip brain aneurysms, and treat traumatic brain injuries—like concussions. We also do a lot of spine surgeries—about 90% of neurosurgery in the country involves things like herniated discs and lumbar fusions. So really, our scope covers the entire central nervous system plus the peripheral nervous system. We treat things like carpal tunnel syndrome and nerve disorders. Historically, neurosurgeons handled a wide range of conditions, but nowadays, we tend to specialize. I’m fortunate to be at Penn Medicine, where I focus specifically on one area: stereotactic functional neurosurgery. Basically, I do deep brain stimulation surgery.
01:07-01:37
Casey Halpern: That’s what I do—implanting tiny wires deep into specific parts of the brain, like regions involved in Parkinson’s disease. But actually, just implanting the wire isn’t the therapy. The therapy comes from delivering electrical stimulation through the tiny contacts at the tip of the wire. Think of it like implanting a tool that delivers medication, except instead of drugs, it’s electricity. The stimulations affect a very specific small region in the brain. I feel very privileged to work this closely with the human brain. The goal is always to provide meaningful therapy for patients.
01:37-02:41
Casey Halpern: When we deliver electrical stimulation, the electrodes sit in a very small area, but even millimeters away are regions that, if stimulated, can cause brief side effects—a sudden laugh, a moment of panic, things like that. Usually, we just turn off those contacts, but interestingly, some of these side effects can actually be therapeutic. This discovery is how deep brain stimulation has expanded beyond movement disorders like Parkinson’s to psychiatric conditions. Some Parkinson’s patients who also have depression or obsessive-compulsive disorder—a lot of these folks are highly compulsive and impulsive—sometimes see their symptoms improve as we treat their tremor. They might tell us their gambling problems have lessened or their mood has lifted.
02:41-03:53
Casey Halpern: Why does this happen? Well, there are probably several reasons. Sure, improving their tremor can boost someone’s mood, but we often see moments of laughter or other emotional responses in the clinic when stimulating certain brain areas. That’s because we’re targeting not only motor circuits but also what we call limbic circuits—areas involved in emotion. If we learn how to modulate those emotional areas properly, we can develop therapies for other conditions like depression. For example, one of the most impressive and consistent effects I’ve seen is when a patient with a 20-year history of tremor gets immediate relief as soon as we start stimulating the electrode in the clinic.
04:07-04:57
Dr. Casey Halpern: I’ve seen immediate tremor relief from deep brain stimulation—that effect actually inspired me to become a neurosurgeon back in college. I’ve never really wanted to do anything else except help develop similar therapies for other kinds of symptoms. I’d love to share more about OCD with you. Maybe I can start by explaining what OCD is, which brain areas are involved, the current treatments, and the difference between someone who’s just obsessive and someone who truly has OCD.
From my perspective as a neurosurgeon, it might differ a bit from a psychiatrist who treats OCD daily. I probably only see three to five patients per year for deep brain stimulation targeting obsessive-compulsive disorder. So, I’m not seeing OCD patients routinely, but my lab is focused on improving outcomes of deep brain stimulation for OCD. I feel I have some expertise and a perspective worth sharing.
I also feel it’s my obligation, as a neurosurgeon, to understand where obsessions arise in the brain and how we can interrupt those circuits to stop the compulsions that go along with them better than we currently can. I’ve been leading a project with collaborators across the country aiming to better understand these brain circuits in humans, studying them invasively with electrode-based surgery—similar to how epilepsy patients are studied to pinpoint seizure origins. We want to pinpoint where obsessions come from.
But we’re also working with imaging experts and geneticists to understand OCD on a broader level. I think of OCD as somewhat of a spectrum disorder. I realize that might be controversial to some, but I use it to describe people who have obsessions and maybe some compulsions but don’t quite meet full diagnostic criteria for OCD.
As a neurosurgeon, I’m very “obsessive” about safety and “compulsive” about my surgical procedures. So, in some ways, a bit of OCD helps people. There are plenty of famous CEOs, surgeons, and scientists who probably have some level of OCD. If it’s controlled, it can be an asset. But when it gets out of control and unmanageable, that’s when it becomes obsessive-compulsive disorder.
I tend to treat the most severe cases—the patients who have failed multiple medications. There are several effective medications for OCD worth trying.
04:58-06:30
Interviewer: Which neurotransmitter systems do these medications typically target?
Dr. Casey Halpern: SSRIs are usually the first line of treatment for OCD. Tricyclic antidepressants can also be helpful. Both primarily affect the serotonin system. But of course, serotonin interacts with other systems, like the dopaminergic system, so it’s hard to isolate one system. That’s also why it’s tricky to predict exactly how these medications will work for any individual patient.
Exposure and response prevention therapy, a form of cognitive behavioral therapy, is probably the most effective behavioral treatment. It’s different from traditional CBT and usually offered by psychologists. At my institution, Penn, there’s a dedicated clinic run by experts like Edna Foa focusing on these therapies. Patients are gradually exposed to what triggers their anxiety or obsessions and taught to habituate to those stressors without performing their usual compulsions. This helps them regain control and improve daily functioning.
These treatments are incredibly helpful for many patients, but about 30% still struggle with OCD symptoms, sometimes severe or moderate to severe. Those are the patients I’m most motivated to help.
Right now, the treatments available for these patients are worth pursuing but far from optimal.
08:35-10:05
Dr. Casey Halpern: These approaches are definitely worth exploring, but they aren’t perfect. As researchers, we have to balance hope with reality. When you see patients who are struggling like this, you want to do everything you can to help. It’s important to educate them about the risks and benefits—not just of deep brain stimulation surgery but also of capsulotomy. Capsulotomy is more of an ablation method. Instead of sending electrical stimulation through an electrode, it heats and destroys a small area of brain tissue.
Some say this part of the brain is fairly safe to destroy—kind of like removing an appendix. Others argue it’s safer to modulate that area rather than destroy it. I’ve seen patients benefit significantly from these ablations. What amazes me about the brain is sometimes how little effect you get from traversing certain areas—you might not see any deficits in the patients’ functions that you can test. At the same time, you can actually destroy tiny spots, maybe three or four millimeters, and see real improvements for patients without obvious side effects, at least after a brief recovery.
Still, despite how safe these procedures can be, they are surgeries. Patients are understandably hesitant, especially when the chance of achieving a transformative effect is relatively low. Generally, we get about a 50% responder rate, and even those responders still have symptoms of OCD. That’s why I’m really motivated to find ways to deliver these therapies in ways tailored to specific diseases or symptoms.
10:05-11:00
Interviewer: If a patient came to your clinic for ablation or stimulation treatment, where would you start probing in the brain?
Dr. Casey Halpern: OCD is a disorder involving both the cortex and subcortex. In the cortex, areas like the prefrontal cortex and orbitofrontal cortex don’t function normally—they tend to be overactive. We want to find ways to normalize that activity. Then you have projections down to the subcortex, specifically to the basal ganglia, including the caudate and dorsal striatum, which are connected to the ventral striatum.
I focus a lot of my energy on the ventral striatum, which includes the nucleus accumbens. This area is involved in gating reward-seeking behavior. When it’s disrupted, it can drive compulsive actions—like a rat going after a reward despite getting shocked. That’s similar to an OCD patient who might check their home repeatedly until 3 a.m., unable to sleep because the urge overrides their judgment, even when the behavior puts them at risk.
11:00-12:33
Dr. Casey Halpern: In OCD, you might see contamination fears where patients wash their hands for hours or compulsively clean their toothbrush if it falls on the floor. Those are common behaviors patients report or that we observe. The same kind of compulsive drive appears in eating disorders. For example, someone with binge eating disorder might overeat, and in bulimia, a person might purge despite knowing the risks. Addiction follows a similar pattern—an addict will find ways to get drugs even when it’s dangerous.
This urge that drives behavior despite risk is something I’ve long been fascinated by. It’s a key factor across these conditions, which are among the most common in society today. I believe the nucleus accumbens and related cortical areas, which send projections to these circuits, are at the heart of these problems. These circuits are likely central to compulsive behaviors and impulsivity seen across disorders.
12:34-14:03
Dr. Casey Halpern: So, what exactly is the nucleus accumbens and what role does it play in normal brain function and in disorders? Well, the nucleus accumbens is a part of the brain involved in our reward circuits. It has many functions and connects with multiple brain areas. When I first became interested in reward and what I could do as a surgeon to help regulate reward processing, I focused on this area. Having urges for rewards is a normal thing—that’s not what we’re trying to eliminate. The problem is when the urge for a reward puts you or others in danger, that’s when it becomes pathological and probably a reward you shouldn’t seek.
For example, if you’re struggling with drug addiction and using heroin or other opiates, those drugs might temporarily help you feel better because life is stressful, but the risks are extremely high—potentially deadly. In obsessive-compulsive disorder (OCD), if you can’t sleep because you’re so anxious about whether you locked the door, and you’ve checked it 30 times, that’s an urge we need to address. Eating disorders work the same way. These problems can be relieved or managed better with a deeper understanding and targeted treatment of the nucleus accumbens.
Repeated exposure to a strong reward like drugs or other compelling stimuli can hijack the normal function of the nucleus accumbens. The goal, then, is to disrupt these habitual or recurring problematic urges. Take binge eating disorder, for example: many folks with severe cases binge about once a day. So, we decided to apply a tool we frequently use in surgery, specifically for patients with Parkinson’s disease.
14:03-15:28
Dr. Casey Halpern: With Parkinson’s, many patients suffer from tremors. When we place an electrode into the relevant motor structures to help reduce those tremors, we actually listen to the electrical signals those cells produce by converting them to sound. The tremor’s frequency corresponds to the frequency of the electrical signal we pick up from the brain cells. We probe carefully, one fine wire at a time, listening for cells firing at the tremor frequency. Once identified, we can stimulate or silence those cells to see if the tremor stops—and it often does.
15:28-16:18
Interviewer: What’s the equivalent of tremor when it comes to appetite and the urge to binge?
Dr. Casey Halpern: The closest analogy is craving. There might be other terms we could use, but craving is effective and relatable. People with binge eating disorder or obesity often acknowledge they experience cravings. Interestingly, if you ask them if they feel out of control or if they binge, they might not fully recognize it or admit to losing control, even if they do. But craving is a familiar concept, so we used that term.
We set out to see if we could identify “craving cells” in the brain. In a patient with OCD, which involves circuits similar to those targeted for binge eating, we tried to pinpoint cells linked with obsessions. In a single case study, we aimed to optimize electrode placement and were able to evoke the patient’s specific symptom during surgery, assuming the patient was awake. Not every patient needs to be awake during these procedures, but for early human trials where we need to establish precise brain targets, it’s crucial. I believe this type of approach is key for advancing treatment.
16:18-16:55
Interviewer: What is the current status of non-invasive brain stimulation, ablation, and blocking activity in the brain? My understanding is...
16:56-17:44
Interviewer: So, I understand that transcranial magnetic stimulation is being used non-invasively to treat depression and other brain disorders. Since it doesn’t involve drilling into the skull, the spatial precision isn’t that great, right? I’ve also been hearing a lot about ultrasound lately. From what I gather, ultrasound can allow clinicians and researchers to stimulate specific brain areas. What are your thoughts on these non-invasive brain stimulation methods—things that don’t require opening the skull or directly implanting devices to stimulate or block brain activity?
17:44-18:27
Dr. Casey Halpern: We definitely need to embrace non-invasive approaches, though some of them feel a bit fuzzy since we don’t fully understand how they work. Even with deep brain stimulation, our mechanistic knowledge is incomplete. Because of that, these methods aren’t yet as precise as we’d hope, but I think improving that precision is totally doable and is already underway. For example, transcranial magnetic stimulation, or TMS, is FDA-approved for depression, OCD, and even nicotine addiction. We think we can use TMS to identify brain circuits that, when modulated, temporarily improve OCD symptoms. For patients whose relief is temporary, invasive procedures might be the next step. This is something we’re actively researching. I’ve always believed neurosurgeons should be involved in discussions on non-invasive methods—we don’t have to perform surgery every time—but we can help make these approaches more targeted and purposeful.
18:27-19:01
Dr. Casey Halpern: Maybe one day, there’ll be a TMS target specifically for disorders like anorexia and obesity. Right now, we’re just scratching the surface with invasive methods for these problems, and non-invasive brain stimulation has been even less explored in areas like eating disorders. So, there’s a lot of work ahead. Regarding ultrasound, particularly MRI-guided focused ultrasound, this FDA-approved technique is used to deliver brain ablations non-invasively. Researchers—including myself—are investigating whether it can modulate brain activity, not just ablate. We’re still figuring out how to use it to either stimulate or inhibit neurons. There are also trials exploring whether ultrasound can open the blood-brain barrier to deliver medications directly to brain regions, which could help treat conditions like brain tumors.
19:01-20:18
Dr. Casey Halpern: This field is really exciting. Focused ultrasound is FDA-approved to treat tremor, and I regularly use it for patients with Parkinson’s disease or essential tremor. It’s almost miraculous because there’s no incision or electrode placement, yet the results are similar. It usually targets one side, often the patient’s dominant or worse hand, and works incredibly well. This shows it’s possible to non-invasively ablate a brain region that’s linked to the specific problem, effectively. Could the same approach help with psychiatric disorders, obesity, or eating disorders? Potentially. The challenge is that we don’t yet know the right target areas for these conditions. There’s a trial we’re interested in doing for OCD where focused ultrasound would deliver ablations to the same brain area that’s been targeted for years in surgical capsulotomies for OCD, which do help but only somewhat. It’s a good method because it’s non-invasive, but we really need to find new targets for these conditions.
20:18-21:13
Dr. Casey Halpern: Since many of these disorders share a common thread—the compulsive urge despite knowing the risks—it’s possible that similar brain circuits are involved. But honestly, I don’t know if it’s exactly the same target. What I do believe is that we need to carry out these kinds of modulatory experiments—either with...
21:15-23:32
Dr. Casey Halpern: We’re using modulatory experiments—either with devices or invasive recordings—to better understand where these problems originate, so we can pinpoint where treatments like ultrasound should be applied. This approach has sparked a revolution in the U.S., though it actually started earlier in Europe. We use stereoencephalography, which is essentially like doing an EEG with invasive electrodes in epilepsy patients. We place tiny wires, less than a millimeter in diameter, all throughout the brain in areas we suspect are involved in seizures. Then, we admit patients to the hospital and figure out exactly where the seizures start and spread.
We can stimulate these electrodes to see if particular symptoms arise, helping us identify regions that could be surgically removed, ablated with a laser, or treated with a stimulator. This has become standard practice for epilepsy and works extremely well and safely. Of course, it’s still brain surgery, but complication rates are surprisingly low, especially given how many electrodes we place. Most patients leave the hospital without even feeling like they had surgery.
Because of this, there’s growing interest in using this technology to study mental health disorders. We’re currently trying this with patients who have obsessive-compulsive disorder and are awaiting FDA approval. I actually credit our colleagues at Baylor and UCSF who have been pioneers in combining epilepsy techniques with psychiatric expertise to better target electrodes for depression. If they can find a consistent target in depression, this could lead to an ultrasound treatment option. For now, the electrode-based approach is more flexible since we can turn it off or even remove it if it’s not in the right spot.
Eventually, with enough cases, they might gather enough data to develop a reliable ultrasound target for depression—that would be fantastic and probably a long-term goal.
You might wonder why we’re not using this for obesity yet. In our study, we’ve developed a target for obesity and binge eating disorder based on mouse models. We believe this is relevant to humans because binge eating can be more accurately modeled in mice than depression or OCD. So, we feel more confident relying on preclinical studies for those.
But for more complex mental health issues that are harder to model in animals, we really need to study them directly in humans. We can start by studying epileptic patients with electrodes, possibly triggering depressive states or studying those who have comorbid depression. This will help validate the approach.
Ultimately, it’s about getting into the human brain in the specific disease state. That’s what will pave the way for non-invasive approaches—either lesion-type treatments or neuromodulation. Lesions might be created with ultrasound, while modulation could be done with techniques like transcranial magnetic stimulation (TMS).
If people could learn to feel even slightly better or less anxious just before a craving or binge episode, or become better at recognizing their internal states before slipping into binge eating, drug use, or even suicidal thoughts, that awareness could be one of the most powerful tools they develop.
24:44-25:25
Andrew Huberman: Yes, I’ve always believed that boosting awareness can improve outcomes. That probably holds true for many patients. The challenge is that some patients are incredibly resistant to treatment. The ones we see as surgeons are usually those who have already tried cognitive behavioral therapy and medications, along with behavioral interventions.
25:27-26:10
Dr. Casey Halpern: Patients have tried medications and behavioral management, and they’re as aware as they possibly can be—they still lose control. We’ve studied this in the lab by bringing patients in with these implanted devices to try and provoke an electrical brain signal that the device can detect. This same device is what will later stimulate them at home. But before we begin stimulation, we want to see if the device can pick up this craving signal. It’s different from the signals we see in the operating room since there we’re recording from single cells, but the implanted electrodes used for at-home therapy are about a millimeter in diameter, detecting the activity of thousands of cells.
26:10-27:05
Dr. Casey Halpern: We have a method to provoke binges called mood provocation. It’s well validated, kind of like provoking seizures in epilepsy monitoring, but in a psychiatric or food monitoring setting. A psychiatrist and an eating disorder specialist come in and induce a mood that relates to each patient’s self-described binge episode. So the psychiatrist provokes a feeling that can trigger the negative behavior. We video-record and synchronize this with brain signal recordings. Patients wear eye trackers so we can see exactly what they’re looking at and eating. This lets us pinpoint what’s happening right before a bite.
27:05-27:45
Dr. Casey Halpern: Even though patients know they’re being studied and are aware of what’s happening, many still binge. We believe this happens because these are the most severe cases; despite that awareness, they can’t control their behavior. Improving awareness—not just societal awareness, but the patient’s own—could be a powerful way to help many of them. This is genuinely the goal of cognitive behavioral therapy (CBT).
27:45-28:18
Dr. Casey Halpern: The limitation of CBT is that if people stop it, many relapse back into their old behaviors—maybe habits, maybe something deeper. Some do benefit long-term, but some don’t. In less severe patients, boosting awareness is key. But in these really refractory cases, the disease persists despite awareness, and they just can’t control themselves. What we’re trying to restore is their ability to control their behavior better.
28:38-29:36
Andrew Huberman: Do you think machines and artificial intelligence have a role here?
Dr. Casey Halpern: Absolutely. There are labs, like at the University of Washington, working on analyzing voice patterns to help predict when people with suicidal depression might be heading toward an episode—even before the person consciously realizes it. This raises interesting questions about free will and whether machines can be smarter than us. You could argue that search algorithms from Google or others might actually know our preferences better than we do.
These devices essentially listen to people all day, tracking their speech, breathing patterns, sleep quality, and other cues. They then integrate this huge amount of data and can give a signal—like a yellow light—warning someone they might be heading into a depressive episode, even if the person feels fine or thinks they’re just at their baseline.
29:38-30:44
Dr. Casey Halpern: People tell me, “Hey, that’s where you were right before the last episode you did, the one that dragged you down a really deep, dark hole—and it took you months to climb out of it.” And I wonder if some of these devices could actually help with the kinds of issues we’re talking about today.
I’ve always believed we need to get inside the brain to understand it before we can get out of these problems. If we can identify what these brain signals look like internally, then maybe we can detect them non-invasively. I think it’s becoming scientifically feasible to use machine learning and this sort of bot-tech approach to predict when someone might become highly impulsive.
You know, suicide is the most dangerous impulse someone can have. It’s a major focus in our lab—impulsivity. We’ve talked mostly about compulsion, which is pursuing a reward or urge despite the risks. Impulsivity is similar but a bit different. It’s more about going after something without thinking or waiting.
If you model impulsivity in a mouse, for example, it’s like going after a food reward without waiting for the cue that signals they’re supposed to wait. The mouse stops waiting and just grabs the food, which I think many of us can relate to on some level. It’s a spectrum.
In any case, I think there’s definitely potential to use our body’s own physiology to anticipate when these impulses are coming online. We’re just scratching the surface on how to do that best, but these types of solutions are what we need.
30:44-32:05
Dr. Casey Halpern: These problems are epidemic in scale—obesity, the opioid crisis, depression, suicidality—they impact a huge portion of the population. We need solutions that can scale. The problem is, as a neurosurgeon, I can really only treat the most severe cases. Deep brain stimulation has only been done about 200,000 times worldwide, but we’re talking about tens of millions of people in the U.S. alone.
There’s no way surgery alone can solve these issues at that scale. But hopefully, we can inspire initiatives to tackle these problems more rigorously. The last thing anyone needs is some flashy wearable device that just wastes money and time. We need real therapies that work. The devices we’re discussing have a lot of promise. We use machine learning a lot in the lab.
I’m not an electrical engineer or computational neuroscientist who builds these tools; I focus on developing the hypotheses and helping raise funds. I definitely believe there’s a future here, but we’re just at the beginning of figuring out how to make it work best.
32:05-33:12
Andrew Huberman: I really appreciate you sharing these tools. I’m guessing a lot of people watching might be inspired to become neurosurgeons. After today’s conversation, I’m confident you’ve sparked interest in medicine or neurosurgery for many folks.
Dr. Halpern: I hope so. Of course, you have to be a physician before you can specialize in neurosurgery. That would be wonderful, and I predict it will happen in time as a result of conversations like this.
Andrew Huberman: Thank you so much for taking the time out of your incredibly busy and important schedule. The work you’re doing is truly at the cutting edge—and I hesitate to say “bleeding edge” because of the context—but you’re definitely at the forefront of what we know about the human brain and how to repair it. On behalf of everyone and myself, thank you very much.
Dr. Halpern: Thank you. I’m honored to be here.
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