The Most Effective Depression Treatment Ever is an FDA Breakthrough
Neuroscience Has (Finally) Paid Off!
The Frontier Psychiatrists newsletter and his written by one psychiatrist. The Royal We. That kind of plural. Every once in a while I write an article to explain something to myself, and also explain it to the rest of the world in the process. This is one of those articles. This is the story of the most effective depression treatment, ever.
The most important thing for the general public to understand about brain scans is they are very convincing. If you put a picture of a brain next to text, it makes it more believable.1
We do know a movie of the blood flow in the brain shot with functional magnetic resonance imaging (fMRI) can show differences in brain activity.
In the case of depression treatment, we now know enough to use one of these brain activity movies to improve outcomes dramatically.
Magnetic Resonance Imaging Scanners are Heavy and Expensive
I'm going to get through what an MRI is without getting far into the weeds— frankly, it's complicated. And I don't understand it well enough to not be made fun2 of. I'm going to quote from a piece in scientific American to make my life easier and limit mockery for myself:
The scanner is a large electromagnetic cylinder constructed from superconducting wire cooled by helium that generates powerful magnetic fields. The levels of these fields are 25,000 to 80,000 times the strength of the earth’s magnetic field. They are so powerful that subjects must remove all metal items before entering the shielded area. Patients with pacemakers or metal implants cannot even go into the room, which itself is heavily fortified with steel and uses soundproofing technologies to muffle the bone-shaking noise produced when the magnets work their magic.
It is a lot of structural work3 to get one installed— solid metal walls, reinforcing the floors, it's heavy, it's expensive. Steel I beams, liquid helium cooling.
Any medical scanner is making a picture by capturing photons. These wave-particle duality quanta you may vaguely remember from physics. They what make up light—but also other radiation! This includes gamma rays, x-rays, and, in MRIs, radio waves. That's right. Tune in —to your MRI4. The difference between a photon of visual light and a photon of an x-ray is the frequency at which it vibrates. Scanners are capturing photons generated somehow, and doing a lot of math to turn those photons into a picture. Physicians, in turn, use those to guide healing.
Low energy photons are safe for humans!
The higher the energy of a photon, the more likely it is to do damage to the human body.
Radio waves travel harmlessly through our bodies5. X-rays can cause damage to our DNA. The real magic of the magnetic resonance imaging machine is not just that it's capable of creating extremely high resolution images.
The magic is MRI gets your body to launch the photons instead of bombarding you with radiation!
Photons can be absorbed by electrons! Photons can also be re-emitted by electrons. Specifically, it's the electrons around an atom that can store the potential energy of a photon, and then release that potential energy as a new photon:
The wavy red line is a photon. The electron (e) is moving up to a higher energy level after absorbing a photon. Next, it emits a brand new photon, then it drops down to the lower energy level again.
Magnetic resonance imaging6 excites electrons then captures emitted photons. Electrons get excited, and then they relax. When they do, they had emit a photon. That photon is captured by fancy radio antennas7. Instead of music, MRI jostles the body with magnetic fields, gets photons emitted, and these are captured to recreates a picture8 of our body.
The difference between a photograph and a movie is the difference between a structural MRI and a functional MRI.
The structural images, that we get with additional “lighting up” is a little bit of a post processing trick—basically overlaying information from the movie onto the structural picture:
Functional brain scans— movies of blood flow over time— take advantage of changes in how much oxygen is used to power metabolically active brain. The more a neuron and its supporting glial cells have to work, the more oxygen it needs. This means the blood, which carries four oxygen molecules on each hemoglobin at maximum, has to give up some oxygen so that the brain has the energy to run. This change, oxygen being pulled off of hemoglobin, this is what we're measuring on a functional brain scan with fMRI. The science term is BOLD signal change.
fMRI takes a movie of the brain.
In the work I do, we take that movie three times in a row, just to make sure we got it. In that movie, we are seeing the brain’s metabolism in close to real time. More active brain pulls off more oxygen from the blood. And the MRI can see that as a differential change in BOLD signal.
This is no longer of “academic interest.” It is the change in BOLD signal—and the relationship of this change in one part of the brain to another part of the brain—that lets us know where to target brain simulation treatment!
Bringing it all together as a remarkable treatment!
We're able to do something useful with a brain scan. It's able to guide treatment. Right now. It is not divorced of clinical judgment—we can get a series of targets from these brain scans, but which one to utilize is based on a physician speaking with a patient. Next, that human physician puts together the information from the story, into a presumptive diagnosis that identifies the circuit in the brain involved. What we know from the story plus clinical exam is paired with information we have from the brain scans as follows:
We take that “movie data” using fMRI:
And overlay it on structural MRI to generate a target derived from fMRI approach pictured above:
And this allows positioning In the real world using similar technology to motion capture circa Lord of The Rings Gollum:
We bring that into the office—now using the same “motion capture” approach to map an area on his skull onto the on the brain. A computer makes sure that we figure out the right place in physical space for treatment using our overlapping brain scans:
And boom: we are targeting a stimulator at the correct brain region for YOUR depression or YOUR anxiety.
And when we target a precise spot, and give a gentle stimulation, spaced out once an hour, 10 times a day, for 5 days, we get remission rates that go from underwhelming, in drug studies9…
To the outcome of the SAINT fMRI guided Neuromodulation study…
A New Era
As my colleague Joshua Bess, M.D. is fond of saying (which is a quote, off the cuff originally, of a certain author of a certain newsletter):
“it F$@ing works.”
And it does. Reliably.
And, thanks to the efforts of the public including my readers…even Medicare (in hospital settings) has agreed this is a treatment worth paying for.
So please approach this with caution and with your skepticism intact !
My readership is area data but kind of fierce? Some of them understand MRI a lot better than I do!
Building structure, not brain structure
Can’t be worse than Seven Mary Three
These are low frequency and low energy as a result.
which was a sassy rebrand of the original basic science term nuclear magnetic resonance (NMR). Yes, I was an award winning physics teacher. this is how low the bar for that is.
Radio is an “scanner” that turns radio waves (photons at radio wave frequency) into the music we hear.
Photons are coming from electrons around hydrogen atoms. The hydrogen atoms are on almost everything—particularly water—H2O!
The structural images that we get of the brain are not with this article is about. I'm gonna ask you to accept that the structural images exist. That shouldn't be hard. They're very convincing.
in part due to poor selection of the sample enriched with a lot of people who are likely to respond to placebo):
Hi Owen, interesting article, I am curious about footnote nine and have a question if you have time to answer it. How do you select people who aren't likely to respond to placebo?