Essentials: Psychedelics & Neurostimulation for Brain Rewiring | Dr. Nolan Williams

**Andrew Huberman** (0:00)
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.
I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. And now for my discussion with Dr. Nolan Williams. Thanks for joining today. I'm really excited to have this conversation. I have a lot of questions about different compounds, psychedelics in particular. But before we get into that discussion, I want to ask you about depression, broadly speaking.
I heard you say in a wonderful talk that you gave that depression is perhaps the most debilitating condition worldwide, yet in contrast to other medical conditions like cancer, we actually have a fairly limited number of tools to approach depression. And yet the number of tools and the potency of those tools is growing.

**Nolan Williams** (0:56)
Depression is the most disabling condition worldwide. What's interesting about depression is it's both a risk factor for other illnesses and it makes other medical and psychiatric illnesses worse, right? So recently the American Heart Association added depression as the fourth major risk factor for coronary artery disease, right? So alongside the risk factors that we know, hypertension, high blood pressure, hyperlipidemia, high cholesterol, and diabetes, high blood sugar, those three have been on the list for a long time and depression ended up being added to the list as the fourth one. A lot of what we're doing in the lab actually is measuring kind of brain-heart connections and we can actually, with transcranial magnetic stimulation, a form of brain stimulation, we can actually decellerate the heart rate. We can capture that heart rate decelleration over the mood regulatory regions. So actually a direct probe of that connection. We've been very interested in a very particular clinical set of problems around the most severe and the most high acuity settings that folks with depression end up being in, and that's in emergency settings where they go into inpatient units. The field really hasn't developed a way of consistently being able to treat that problem, and folks end up getting the same standard oral antidepressants that they've been getting outpatient.
And I came to this because I've, you know, dual trained as a neurologist and psychiatrist, went back and forth between neurology and psychiatry, saw that in neurology we have all these ways of treating acute brain-based problems, and really wanted to emulate that in psychiatry and find ways to develop and engineer new, you know, brain-based solutions.

**Andrew Huberman** (2:44)
Many people out there probably think of the relationship between the heart and the mind as kind of woo or kind of a soft biology, but here you're talking about an actual physical connection. What area of the brain is it?

**Nolan Williams** (2:57)
You know, the first place where the stimulation goes is called the dorsolateral prefrontal cortex. It's kind of the sense of control, kind of governor of the brain.
And then what we know is that when you use a magnet, kind of what we call Faraday's law, this idea of using a magnetic pulse to induce an electrical current in electrically conducting substances. So in this case, brain tissue, but not skull or scalp or any of that or hair, you avoid all that, just the brain tissue. Then you have a direct depolarization of cortical neurons, you know, the surface of the brain's neurons in this dorsolateral prefrontal. And if you do that in the actual scanner, which we can do, you can see that that distributes down into the intersingulate and the insula and the amygdala. And ultimately, the tract goes into something called the nucleus tractus solitarius, and ultimately into the vagus nerve and to the heart. So the heart very consistently seems to be the end organ of the dorsolateral prefrontal cortex. And if you do that over visual cortex, you don't get that, or motor cortex, you don't get any of those findings. It's really specific to this kind of control region of the brain. And so, yeah, it seems to, you know, it's our work, other folks work, Martin Arnz in Europe, the Netherlands work showing the same connections. I think it's been replicated like four or five times. Where I think TMS is really interesting, actually, we had a lot of patients who've told me, like, my therapist told me that I wasn't trying hard enough in therapy. These are, you know, moderate to pretty severe depressed patients. And as soon as we get them well with the TMS approaches, you know, kind of rapid, you know, five-day approach, and the next week we come in and see them, and they'll say, you know what I did all weekend is I looked at my therapy books, and now I can understand it.