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Saturday, September 10, 2022

Applied neuroscience updates:

Deep brain stimulation tx for opioids addiction; Neurotrainer partners up with LG.

My latest issue of Harper's just arrived.

Fascinating article therein by fine young Chicago-based writer Zachary Siegel.

On a bright summer day in July 2021, James Fisher rested nervously, with a newly shaved head, in a hospital bed surrounded by blinding white lights and surgeons shuffling about in blue scrubs. He was being prepped for an experimental brain surgery at West Virginia University’s Rockefeller Neuroscience Institute, a hulking research facility that overlooks the rolling peaks and cliffs of coal country around Morgantown. The hours-long procedure required impeccable precision, “down to the millimeter,” Fisher’s neurosurgeon, Ali Rezai, told me.

Prior to operating, Rezai and his team of neuroscientists created a digital rendering of Fisher’s brain, a neural map that would help them place what looked like a pair of long metal chopsticks roughly six centimeters deep into his nucleus accumbens, a structure in the center of the brain. The nucleus accumbens, according to the latest research, is associated with processing reinforcement, motivation, and desire. It’s also where the most famous neurotransmitter, dopamine, gets released when we anticipate rewards from behaviors like sex, drug use, or gambling. Rezai, who thinks as much like a neural engineer as like a surgeon, described the nucleus accumbens as the brain’s Grand Central Station, a junction for “addictions and anxiety and obsessions.”

Once Fisher was anesthetized, Rezai bored two holes about the size of nickels into the top of his skull. Then he slowly inserted the long metal probes into Fisher’s brain, as if sticking a dull knife into a mold of opaque Jell-O. The probes were lined with four tiny round electrodes, each just over a millimeter in diameter, that were to deliver continuous electrical impulses to Fisher’s nucleus accumbens. The surgery is known, fittingly, as deep brain stimulation, or DBS.

The probes were connected to wires that ran under Fisher’s skin, beneath his scalp, behind his ear and down his neck, then into a pulse generator sewn into his chest below his collarbone. Imagine a pacemaker, but for the brain. Once the generator’s battery was switched on, low-voltage electricity began traveling up the wires and out of the electrodes resting in the nucleus accumbens. Rezai, the executive chair of the institute and the head of its DBS experiments, hypothesized that stimulating this region of Fisher’s brain would reduce his cravings and help him recover from a severe addiction to opioids and anti-anxiety pills that had persisted despite numerous treatments and life-threatening consequences, including multiple overdoses.

For decades, addiction and overdose deaths have been skyrocketing across the United States—and particularly in West Virginia, which has been dubbed the epicenter of the overdose crisis and consistently has one of the highest death rates in the nation. Patients like Fisher have been deemed “treatment-resistant,” meaning conventional approaches have failed to bring about lasting recovery. Medication, therapy, inpatient and outpatient care—Fisher has tried it all. Deep brain stimulation, which before this trial had never been tested in the United States to treat addiction, was a last resort...
"What kinds of treatments work? How do you properly address a catastrophe like the one in which the United States finds itself, where overdose deaths now kill more than a hundred thousand people each year?"

Yeah. Recall my citing of this book several years ago.

Back to Zachary:
Neuroscientists, as is their wont, generally understand addiction as a disorder of the brain. Drugs are said to hijack neural circuits and scramble the brain’s most critical reward pathway. Years of neuroimaging studies purport to show hot spots in the brains of addicted people; experts like Nora Volkow claim this is empirical evidence of physiological abnormalities. Volkow, the director of the National Institute on Drug Abuse, the federal agency funding WVU’s phase 1 DBS trial, has called addiction “a disease of free will.” The addicted brain, after years of exposure to drugs, Volkow argues, loses capacity to make “free determinations.” Thus people like Fisher, despite their best, clear-eyed intentions to quit, return to drugs again and again. This research suggests that one should not shame or blame a person who is struggling, because they are not in complete control of their own decision-making. We don’t punish and criminalize people who are sick; yet for decades, addiction has existed in a kind of limbo between criminalization and medicalization...
...James Mahoney, a neuropsychologist who directs addiction research at the WVU neuroscience institute, said that he and his team are constantly asking: “Why here?” How did West Virginia come to be the center of the overdose epidemic? “It’s so multifaceted,” Mahoney told me. “It’s not just biological, obviously. Substance use is so self-reinforcing because it works really well. It’s able to remove people mentally and psychologically from stress.” He went on to list a few of the factors at play: “economic despair, health literacy, educational attainment, all of that going back through Appalachian history.”...
As one wrassling with my annoying Parkinson's dx for a number of years now, I found the following quite interesting.
The first time I met Rezai at the neuroscience institute in Morgantown, he had just finished a brain implant procedure on a patient with Parkinson’s disease. As soon as the battery was switched on and the brain received its first electrical impulses, the patient’s debilitating tremors and shaking improved. In such cases, it’s clear that the stimulation, in some sense, has worked. Testing the effects of DBS in patients who struggle with drug addiction, meanwhile, is a much thornier endeavor...
DBS for Parkinson's is a more mature technological tx than I'd realized. Not sure I'm sufficiently addled yet for that kind of full "bore" intervention. I recently conferred with a doc at Hopkins regarding their new "MRgFUS" tx (Magnetic Resonance-Guided Focused Ultrasound). I cited it in a post back in March. It's now FDA-approved, but no one covers it, so I'd be looking at about $15k cash out-of-pocket.

Back to Zachary...
“Most contemporary accounts of DBS therapy give the impression that it is the inevitable consequence of scientific discovery and medical progress,” John Gardner, a sociologist, wrote in the journal Social Studies of Science. “The history of DBS is, in fact, complex.” Gardner’s history shows that DBS continues to be tested by medical device companies seeking new use cases—that is, new markets—for their own technologies, despite the treatment’s spotty track record. What’s driving this expanding search? When I reached Gardner by phone in Australia, he told me that our “neuro-obsessed” culture offered fertile ground for testing brain-stimulation technology, as “we like to think of behaviors and social problems in terms of their neural correlates.” Gardner points to a murky nexus of “entrepreneurial” neurosurgeons aligned with medical device companies that lobby government agencies responsible for deciding whether all this hardware is safe to put inside human beings.

The biggest and most profitable of the device companies, Medtronic, trademarked the term “deep brain stimulation” decades ago while marketing its device as a treatment for pain, says Gardner, who notes that DBS has been a genuine medical breakthrough for movement disorders. But medical breakthroughs must also be profitable. “DBS for [Parkinson’s], then, has proven highly lucrative for Medtronic,” Gardner wrote. “The company is attempting to replicate some of this success by developing DBS as a treatment for other conditions.” This includes addiction. Medtronic is listed as a “collaborator” on WVU’s phase 1 trial. A spokesperson for Medtronic told me that this role means the company provides the hardware for the trial and not much else. This year, incidentally, Medtronic posted $435 million in second-quarter earnings from its neuromodulation division, which sells the DBS hardware...

And, what happens if your implant vendor goes belly-up? Surgically remove the DBS hardware?

Back to Zachary. He is to be commended for his candor:
At one point during my tour of the neuroscience institute, Rezai invited me into a windowless room where I donned a pair of VR goggles that placed me in what looked like a college kid’s messy apartment. I saw old boxes of pizza and drug paraphernalia strewn about the room, as well as crushed beer cans and lines of white powder splayed on a wooden coffee table. “There’s a Mountain Dew,” Rezai said, chuckling.

Alongside DBS, virtual reality is one of the many technologies used at the Morgantown lab to try and grasp how addiction works at the physiological level. A type of exposure therapy, virtual reality has been used to help combat veterans struggling with post-traumatic stress disorder relive the horrors of war in a controlled clinical setting. VR simulations for addiction attempt something similar. Instead of a Humvee, the scene is a seedy apartment.

“We immerse somebody with addiction into a virtual environment, and then we’re testing the networks in the brain,” Rezai said. If somebody’s drug of choice was alcohol, Rezai explained, they could be transported to a bar where they’d hear the unmistakable sound of ice clinking against a glass. Any changes in a person’s heart or respiratory rate, eye movements, skin tone, or sweat glands could be an indication of the virtual experience triggering a reaction, maybe even a craving.

In this case, the test subject was me. Almost ten years ago, I turned twenty-three inside a treatment facility in Minnesota, where I was treated for an opioid addiction that had spiraled out of control. By now, the story of how I got addicted is boilerplate for a millennial: Pharmaceutical opioids like OxyContin were in abundant supply by the time I graduated from high school in Chicago’s north suburbs. I had experimented with the usual drugs that teenagers in affluent communities tend to, like Adderall and marijuana. It wasn’t until I tried an opioid at age seventeen that the proverbial clouds parted. The harsh, judgmental, self-effacing critic in my head finally quieted, and in the absence of that unrelenting mental cacophony, I was left with a feeling of soothing warmth and clarity like I had never felt before. It wasn’t that I loved the high, per se—I remember thinking, this must be what it’s like to feel normal.

Before flying out to West Virginia, I had mentioned to Rezai that I had my own experience with addiction, hence my sincere interest in his lab’s research. With the VR headset on, I looked up, down, and from side to side. The simulated drug den certainly resembled the dingy apartments I inhabited while using—there was a familiar sort of austerity that tends to accompany opioid addiction. I never needed much to be comfortable, mostly because opioids make you comfortable wherever you are, in whatever condition. That’s more or less the point...
This article is a fairly long read. Likely subscriber-paywalled. Well worth it, IMO. I've been a Harper's subscriber for decades.
NOTE: Some prior posts going to neural stuff—"Livewired"
"VR goggles?"

My wife showed me a news item last night about NeuroTrainer. We could not be more thrilled.
SAN FRANCISCO, Sept. 7, 2022 /PRNewswire/ -- The LG Electronics North American Innovation Center, LG NOVA, has selected the Finalist companies for its Mission for the Future global challenge program. Representing multiple potential business paths in three industries, the companies will be working with the LG NOVA team to collaborate on new business ventures, alongside continuing to grow and scale their companies, qualifying for potential investment from LG and other investors within LG NOVA ecosystem to develop impactful solutions for people, communities and the planet.*

"This inaugural year of our challenge demonstrated how effective and powerful collaboration between technology startups and established corporations can help accelerate the innovation process," said LG Electronics Senior Vice President of Innovation Dr. Sokwoo Rhee and head of LG NOVA. "Congratulations to the Finalists and all the companies that participated in the Mission for the Future challenge. We look forward to the journey with these companies innovating for a brighter, more technologically advanced future."

The finalists were selected from an initial pool of approximately 1,300 applicants. They secured the top spot after working closely with the LG NOVA Entrepreneur-In-Residence team over a six- to nine-month period to build and test the proposals. Throughout the process, the companies had opportunities to meet with LG business teams and other investors within the LG NOVA ecosystem. Finalists were presented to LG Electronics Global CEO William Cho…

NeuroTrainer is a brain training and optimization platform deployed in VR to create immersive environments and training protocols that utilizes the scientific principles of neuroplasticity to enhance focus and cognitive performance. Expanding upon iQ3 capabilities, LG and NeuroTrainer will work together to add platform capabilities and enhancements designed to further refine NeuroTrainer as a powerful tool for corporate wellness and mental resiliency.
NeuroTrainer is the brain"child" of Dr. Jeff Nyquist (neuropsychology PhD, Vanderbilt). Husband of my niece April. He's been working on this project for years. Cited them on this blog multiple times.


Interesting that they've broadened their target market scope. "Out of the lab and into the living room." "A powerful tool for corporate wellness."
Cool. As long as the underlying science is bulletproof. Knowing Jeff—one of the smartest, most humane, ethical guys I know—I'd bank on it. (Full disclosure: I have zero financial interest at stake. Not "Talking my Book" here.)
I've had a permanent right-hand column blog link for NeuroTrainer for years (It's down there somewhere, LOL)..

Train from the neck up.

Hope this all bears significant fruit.



This caught my eye w/respect to the LG Nova Top Ten announcement. Notwithstanding that I am now retired and out of the Health IT fray (with tech views of rapidly abating utility relevance), nonetheless, I am a (cranky) Medicare bene currently with Kaiser-Permanente, and not a big fan of KP's telehealth visits. They're largely a waste of time.
See my old rants related to the "SOAPe Note."

Sounds good. We shall see.


I've repeatedly watched the "Friday Night Lights" movie (I have the DVD), as well as its slapstick knock-off cousin "Varsity Blues." I recently got around to binge-watching the Netflix TV version "Friday Night Lights" series. I thought "Dude, you've never read the book."

Rectified that. One of the best books I've ever read. Talk about evocative writing. And, both the movie and the TV series have done it great credit, in differing ways.

A wonderful diversion from the enervating Donald Trump and Vladimir Putin Follies.

And, Roll Tide today (wife's alma mater). They barely survived Texas, 20-19. As did my TN Vols vs Pitt, 34-27.

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