Tag Archive for: depression

Lifestyle changes for better brain health

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Dr. Gary Small knows all about brain health. As professor and chair of psychiatry at Hackensack University Medical Center, he oversees all professional and administrative activities within the behavioral health care transformation service at Hackensack Meridian Health. Prior to this gig, Dr. Small was a professor of psychiatry and biobehavioral sciences and a Parlow-Solomon professor on aging at the David Geffen School of Medicine at UCLA, director of the Division of Geriatric Psychiatry at the Semel Institute for Neuroscience and Human Behavior, and director of the UCLA Longevity Center. Now 72, Dr. Small is known for his public work in promoting the practice of psychiatry and innovative research on brain health, aging, and Alzheimer’s disease. He is a co-inventor of the first positron emission tomography (PET) scanning method that provides images in living people with Alzheimer’s disease with abnormal brain proteins, amyloid plaques, and tau tangles. Dr. Small has authored more than 500 scientific works and received numerous honors, including the American Psychiatric Association Weinberg Award in Geriatric Psychiatry. What’s more, Scientific American magazine named him one of the world’s top 50 innovators in science and technology. He is the author of 14 popular books, including a bestseller titled, The Memory Bible. (Dr. Small also recently spoke at a NAN workshop; to access the archived event, click here.) Earlier this year, BrainWise Managing Editor Matt Villano sat down with Dr. Small to discuss the most important aspects of brain health, and how aging adults can take better care of themselves for the future. What follows is an edited transcript of their conversation.

BrainWise: If we had to categorize lifestyle activities, what are some of the top things people can do to improve their brain health?

Dr. Gary Small: I would say number one is physical exercise. Mental exercise and challenging the brain is very important, but the scientific evidence is even more compelling that regular aerobic or cardiovascular conditioning protects your brain too. You don’t have to become a triathlete to achieve that. Some studies show that just a half hour of brisk walking each day will lower a person’s risk for Alzheimer’s disease. And it’s not just cardiovascular conditioning, which improves circulation to the brain, it increases levels of endorphins which lift a person’s mood and improves issues with pain. Physical exercise also increases levels of brain-derived neurotrophic factor, which is a protein that helps our brain cells communicate more effectively. Strength training appears to provide additional benefits. It may be that when you’re lifting weights or using resistance bands, it provides an additional cognitive challenge to get your form correct, or it may be that other factors are involved. We know that as people age, they are at risk for developing a condition called sarcopenia, which is loss of lean muscle mass, which is a predictor of shorter life expectancy. So that’s another area that strength training helps us in. A third component of physical exercise would be balance training. Older people are at risk for falls, and if you fall, you can hit your head and head trauma is not good for your brain health. [Literature such as this article, this article, and this article suggest that] people who hit their heads and lose consciousness for an hour or more [may have] greater risk for developing dementia or cognitive decline that interferes with their ability to care for themselves.

Brainwise: How can PET scanning help patients become better acquainted with and better in control of their own health?

Dr. Small: It’s a complicated issue because any test or technology that you’re going to use, you have to ask the questions, ‘How is it going to be helpful? What is the potential harm? What is the potential benefit?’ I have worked in this area for a number of years. In 2004, [PET scans were] used to differentiate Alzheimer’s disease from Frontotemporal Dementia (FTD). Today, PET scans are used for all sorts of other things. A PET scanner is essentially like a Geiger counter, it measures radioactivity. When a patient gets one, we inject the patient with a radioactive chemical marker that is taken up by the brain. The marker enables us to see how the brain cells are using sugar, which gives you a measure of cellular function. Of course, there is the risk that if you get these scans, it’s going to cause anxiety in [some] patients. I’m not really a big fan of telling people to go out and get a scan or get genetic testing [unless it’s medically necessary], because it could have negative effects. I am a big fan of encouraging everyone to live a healthy lifestyle, to see their doctor if they have cognitive concerns and get tested and find out where they are and whether these scans are [necessary] or not.

BrainWise: You mentioned genetic risk. What role do genetics play in all of this?

Dr. Small: I always want to encourage people to not be discouraged by their family history. One thing to keep in mind is that the age at onset of a cognitive decline tends to be consistent within families. So if you have a grandparent who developed dementia at 95, the chances are that’s more age-related, and whatever forgetfulness you’re experiencing in your forties is likely unrelated. Another factor, and we’ve done these studies, others have done these studies, is you find that even if somebody has a genetic risk, even if you’re an identical twin to someone who has dementia, that doesn’t necessarily mean you’re going to develop it, that if you live a healthy lifestyle, you can do better. We’ve done studies of people with that genetic risk for Alzheimer’s disease, and we find that if they exercise more, if they don’t have too much overweight or obesity in midlife, that they have less Alzheimer’s disease in their brain when we do brain PET scans.

BrainWise: Can someone be too cautious about protecting their brain?

Dr. Small: It’s never too early and it’s never too late to start protecting your brain. We see very good results in older adults, and one of the advantages of starting early is that you don’t have to change habits so much. It’s one thing to educate people about what’s good for their brain health, it’s another to get them to change. And we’re not just talking about becoming a weekend warrior and playing basketball once a month on Sundays; we’re talking about daily habits that have an impact. And we know from other research [such as Dr. Wendy Wood’s work; see this and this] that to convert a behavior into a habit takes a bit of time and takes some motivation and some consistency. It’s also important to develop a program that is not overwhelming. Not long ago, my wife (Gigi Vorgan) and I wrote a book called, Two Weeks to a Younger Brain. If we called it, ‘Two Years to a Younger Brain,’ I doubt anyone would read it, but the point was, two weeks is enough time to take baby steps to begin to change your life habits, your lifestyle habits, so that it becomes easy to protect your brain every day.

BrainWise: So how can someone jump-start momentum to make a change?

Dr. Small: It’s incremental. It starts with what we’re doing right now, educating people. If you let people know that ordering broccoli as your side dish rather than French fries is going to be better for your brain, you’re more inclined to do that. And part of that education is not just about physical exercise and mental exercise and healthy diet, but it’s also about how to get enough sleep, how to manage stress better, how to avoid experiences like head trauma that will worsen your brain health. If you have high blood pressure or high cholesterol, just taking the medicines for those illnesses can extend your life expectancy and lower your risk for dementia. Many of the books I’ve written outline these programs in some detail. There are many ways to get there. Sometimes it’s reading a book, sometimes it’s checking out a website. Other times it’s meeting with a [trained] professional [such as a psychologist or a neuropsychologist, a dietician, or a nutritionist, as the case may be]. Also, there are apps. I remember reading an article several years ago, it’s much easier to break into training with an app than with a person who will kind of give you a hard time if you don’t show up.

BrainWise: How much exercise is too much?

Dr. Small: When I see patients, I not only go through the standard medical interview and assessment and find out about their history, medications, illnesses, etc., but I ask about their lifestyle. I specifically ask, ‘How much exercise are you getting? How are you doing it? What holds you back?’ And I work with them to try to design something that makes sense for them. Let’s say somebody’s a very busy executive and they don’t have time to go to the gym. Well, what about parking your car a little bit further from the building and walking briskly to the office? Maybe take a few flights of stairs. We always think of it in terms of starting low and going slow. You don’t want people to injure themselves, but you want them to be able to build up in a gradual way. And if you can get the program going so that they get these endorphin rushes, the so-called endorphin high that elevates your mood, that’s very helpful in solidifying those exercise habits because people look forward to it. They know they feel better after they exercise. They have less pain after they exercise. I had a trainer who would always say, ‘Motion is the lotion,’ because it lowers inflammation. Exercise is really something that’s individualized and tailored to the person’s lifestyle. If you make it too daunting, they’re not going to do it.

In the aerobic area, exercise could be almost anything that gets your heart to pump oxygen nutrients to your brain. It could be swimming, jogging, or walking. Part of what determines a specific type of exercise is what’s convenient for you, what you enjoy, what kind of injuries you’ve experienced. For example, if you have a bad ankle, jogging may not be good for you, but you could probably swim. If you have a bad shoulder, maybe a treadmill might be better for you. I think that those kinds of considerations will come into play as someone tries to evaluate what form of exercise is best.

BrainWise: What about social activity? How can that impact the brain, and how much of that should people be emphasizing?

Dr. Small: It really needs to be individualized. My wife and I wrote a book about that called, Snap! Change Your Personality in 30 Days, and it brings up a couple issues. First, despite the clinical lore, it is possible to change your personality traits in a positive way to improve your health and improve your life. Personality is also important when it comes to brain health. If somebody is an introvert, they are not so keen on being so social. They come home at the end of the day, and they like to wind down by curling up next to a fire and reading a good book. An extrovert wants to talk about their day and kind of deprogram all experiences in that way. And so, an introvert wouldn’t necessarily want to spend so much time or need to spend so much social time. But a certain amount of social interaction, I think, is important for everyone, whether they’re an extrovert or an introvert, and it has several aspects that will affect brain health. If you’re having conversations, that’s a form of mental exercise and mental challenge, and that’s going to be good for your neural circuits. If you have conversations with friends who are supportive, that will lower your stress levels and that’s going to help your brain health. Loners don’t do well as they age. We saw this really impact people during the pandemic, among people of all ages. Isolation can lead to depression, and depression is a risk factor for cognitive decline.

BrainWise: Finally, what about diet? Can that really affect brain health?

Dr. Small: Diet is significant. Watching your calories, particularly in midlife, is key. The fat around the abdomen is inflammatory. Many of us think that heightened inflammation drives brain disease as we age, so watching out for that is important. The average western diet includes too much Omega 6 fat compared to Omega 3, and we want the Omega 3. Consuming at least seven servings of fresh fruits and vegetables, which lower oxidative stress in the brain and the heart, is wise. Processed foods and refined sugars, which can increase the risk for diabetes, [also may increase] your risk for dementia [as outlined in this CNN article about a recent study on this point]. I was just reflecting about diet this morning when I woke up. I got a reasonable night’s sleep and I felt pretty good getting up. And I thought, ‘Well, what did I eat for dinner last night?’ I had Mediterranean food. We hear a lot about the Mediterranean diet, and I felt a lot better than I did the day before. On that day, I had just returned from a business trip to Chicago where a lot of the airplane food, all that salt and more of a Western diet didn’t help me sleep so well and didn’t make me feel so great. People can experience subjective differences depending on diet. And you can talk to a lot of people who have changed their diet and notice subjectively they feel better. I think that’s one of the things I’d like to emphasize about taking these baby steps to improve your lifestyle. If you do it, you’re going to notice it’s not just the long-term effects on your brain health, but you’re going to start feeling better right away, which reinforces the habits.

BrainWise: Five years from now, what do you think we’ll be talking about when we talk about everyday ways that we can improve brain health?

Dr. Small: Well, I’m hoping that we’ll have more incentives for people to live healthier, because I know how hard it is to get people to change. We don’t want to force them to change, but we need carrots, not sticks, to motivate them.

This essay has been factchecked by members of NAN’s Publications Committee. For more about that process, click here.

How TMS treats depression

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Transcranial Magnetic Stimulation (TMS) is a procedure that generates magnetic fields to stimulate nerve cells in the brain. The goal: to improve symptoms of major depression. The approach is considered a “noninvasive” procedure because it’s done without surgery. In research, TMS has shown promise in treating multiple conditions when symptoms don’t respond to other treatments, including migraines, smoking cessation, PTSD, OCD, Tourette’s Generalized Anxiety Disorder, and movement disorders such as Parkinson’s. TMS, which is notably different from Electroconvulsive Therapy (ECT), is now used most often as a treatment for depression when other treatments haven’t been effective. Dr. Zafiris “Jeff” Daskalakis knows all about TMS. Dr. Daskalakis is chair of the University of California San Diego Psychiatry Department and director of the University of California San Diego Health’s Interventional Psychiatry Clinic. He has become an internationally recognized expert in treating severe psychiatric disorders with TMS. As a sidebar to this essay about a patient’s experience with TMS, BrainWise Managing Editor Matt Villano recently sat down with Dr. Daskalakis to understand more about the science behind the treatment. What follows is an edited transcript of their interview.

BrainWise: What is happening during a TMS treatment?

Dr. Zafiris “Jeff” Daskalakis: Basically, we’re causing millions of neurons to fire together, all at once. And when those neurons fire in synchronicity, it results in neuroplasticity. Of course, it’s much more complicated than that. To do TMS, an electric pulse generator, or stimulator, is connected to a magnetic coil connected to the scalp. The coil is about two laptops thick and about half a laptop in width. The machine takes electrical charge from the wall and stores that electrical charge in a large capacitor. When that capacitor triggers, it sends the electrical current through the coil for an instant. It’s less than 50 microseconds in duration. That very brief instant of time translates into a magnetic field, which travels through the coil, across the skull, and activates neurons in the brain. There’s no actual electrical conduction; it’s a magnetic field. The magnetic field is much less painful, much better in terms of tolerance. And the magnetic field generates neuronal change. We’re able to get neurons to fire in a certain rhythmic pattern. Why is this important? The old expression is, ‘When neurons fire together, they wire together.’ These neurons firing together and wiring together creates neuroplasticity. Which leads to change.

BrainWise: To be clear, TMS does not involve an electrical charge going into the brain? It’s only a magnetic charge?

Dr. Daskalakis: That’s correct.

BrainWise: How finely targeted is the directionality of this magnetic charge?

Dr. Daskalakis: The area of activation depends on the size of the coil. The larger coil size, the higher the area of activation, the larger the area of activation. The smaller the coil size, the smaller the area of activation. By and large, the coils’ area of activation is elliptical, around three centimeters in diameter. The depth of the impact also depends on the amount of stimulation charge, but at standard stimulation charges, on average, they get about 2 to 2.5 centimeters deep. It’s really that top layer of the brain that is most affected.

BrainWise: Why is this such a big deal?

Dr. Daskalakis: Whenever we look at the brain, there’s always an outer and an inner shell. The inner shell tends to be a lot paler, and the outer shell tends to be a little darker. That’s because the inner shell is associated with lots of neuronal output connections, and the outer shell is really the cell body; it’s where all the action happens. The outer shell allows us to think and function and navigate and interact with our world, think logically, be future minded, and play instruments. And the outer shell just so happens to be that same area that we target with TMS. By stimulating that outer shell repetitively with magnetic fields, we are causing neurons to align. And when those neurons align, that neuroplastic effect takes place. It doesn’t happen right away, and it doesn’t happen with just one treatment, but it happens when you bring people in repeatedly over the course of days to weeks and aim to improve their symptoms.

BrainWise: Can this work for everyone?

Dr. Daskalakis: Not exactly. A certain proportion respond to psychotherapy and a certain proportion don’t. We think that up to a third, perhaps as many as 40% of patients do not respond to conventional treatments, conventional meaning medications or psychotherapy. Of those, about two or three patients out of 100 not only have depression, but also have the type of depression that doesn’t respond to conventional treatment. [Editor’s note: For more on this, click here or here.] This proportion of the population tends to be labored with suicidal thinking oftentimes, because the longer it takes for you to get better, the worse you are. That’s where TMS comes in. TMS is singularly used for that patient population. And we believe that roughly out of those patients who choose to receive TMS, one out of every two or three will achieve a significant clinical benefit.

BrainWise: To what extent are there negative impacts of this treatment? What are the side effects?

Dr. Daskalakis: Lots of groups have looked at this very closely. We have learned that TMS represents one of the safest treatments that we have. There’s an extremely remote risk of seizures. In fact, the only population that we do not have TMS available to is patients who’ve had a seizure disorder. [Editor’s note: Some sources also point out that TMS can be a bad idea in patients who have metallic implants in the brain or skull.] Outside of that, the major side effect associated with TMS is a bit of a headache and some discomfort at the stimulation site, which isn’t profound. And usually, it’s very well-tolerated.

BrainWise: What’s the next frontier of TMS? What questions will you be asking next?

Dr. Daskalakis: There are several areas that we can advance. One of them is how do we make the treatment more efficient? It’s already an extremely efficient treatment, but the treatment requires people to drive into a clinic to get treatment a certain amount of time for a certain number of days. Can we make people better within a week? Can we make people better within a day? These are all hot topics that we need to continue to explore.

The second piece, which goes hand in hand with the first piece, is how do we make the treatment more effective? How do we enhance the efficacy? That leads to the third piece, which is understanding the brain. We have a treatment, and we are narrowing in on the ways that this treatment works in the brain.

I’ve mentioned one mechanism called neuroplasticity, but there’s other mechanisms that are also being considered. One of those mechanisms is connectivity—how different parts of the brain connect to one another. That’s really about the threads of connections between different parts of the brain that may be responsible for inducing depression. Understanding those brain mechanisms is the third piece of the puzzle.

Finally, the fourth piece of the puzzle, I think, is how do we maintain people’s wellness? What do we need to do to continue to treat people so that once they respond, they stay better for longer periods of time? Relapse rates are high. When you go on a medication, you’re not out of the woods just yet. The chances that you’re going to get depressed again could come up down the road. And, similarly with TMS, if you respond, how do we maintain your wellness so that you don’t relapse? Understanding how it works, understanding how we can make it work better, understanding how to make it more efficient, and understanding how we can make the effects more durable are all key pieces of this treatment that we need to continue to pursue.

For more about TMS, read this essay by a patient who recently completed 37 sessions of the treatment for depression.

This essay has been factchecked by members of NAN’s Publications Committee. For more about that process, click here.

My experience treating depression with magnetic waves

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Editor’s note: Sandra Haney lives in Waynesboro, Virginia, and recently turned to Transcranial Magnetic Stimulation (TMS) to treat chronic depression. BrainWise Managing Editor Matt Villano wrote this story in her voice after an extensive interview with her about the experience. For more on the science of TMS, click here.

Depression is like an old friend at this point; I’m 41 years old, and I’ve been dealing with depressive episodes since I was about 15.

It was episodic early on. Things came and went. I had more prevalent anxiety than I did depression. Pretty severe panic attacks. Really frequent intrusive thoughts of death—not so much suicidal ideation but more thoughts about my eventual demise. Throughout my teens and twenties, I did therapy. I tried tons of different medications. Some worked a little. Most didn’t. There were a lot of side effects. I was about 28 when I found a combo of meds that worked: Paxil and Wellbutrin. I still had lots of side effects.

By the time I was 32, I said, “This is ridiculous.” I was tired all the time. I had gained about 30 pounds. Finally, I did a GeneSight test. It turned out I have a very rare triple copy of an enzyme called CYP2D6. That makes me an ultra-rapid metabolizer, which means roughly 80 percent of medications won’t work on me like they should. I metabolize them too quickly.

It’s not a great thing to have if you’re battling depression like I am.

When I learned about being an ultra-metabolizer, when I realized that meds basically weren’t going to work for me, I started thinking about Transcranial Magnetic Stimulation (TMS). From what providers had told me, this is a type of treatment that can work for people who can’t do meds—people like me. I didn’t know anybody who’d done it TMS. I did some research. I got a packet of literature. That was basically it—at the time, I was deeply depressed and could barely make it to my appointments, much less seriously consider something like that. So, I didn’t pursue it.

Fast-forward to 2022. I started sleeping extremely poorly. I was getting more and more depressed. I had a severe bout of anxiety that lasted for four months. As the anxiety subsided, I started experiencing suicidal ideation. It was becoming more and more severe. It reached a point where things were going south quickly. I talked to my psychiatrist. Together, we decided it was time to give TMS a try.

I started the treatment in August. I finished in October. All told, I did 37 sessions. And it helped. But more on that later.

Understanding the basics

When you get the treatment, a machine sends magnetic waves through your skull into your brain. The idea is to stimulate neurons to change the way they’ve handled things in the past—kind of like rewiring the brain. For more about the science behind it, check out the sidebar that BrainWise published in conjunction with my story.

My TMS sessions started out at 21 minutes long. By the end they were at 31 minutes. It’s kind of boring to sit there while the treatment is happening. The doctors told me I needed to stay fully conscious. They let me talk. There was a TV in the room so I could watch TV. They were clear that they wanted me to keep my brain active.

Every time I went it felt like an electric zap. Like a static shock. There was no sense of pain. It was like tapping against my head. This may just be my own imagination, but I could swear I felt it going through my skull. I know the brain has no pain receptors, so maybe that’s impossible.

During the sessions I didn’t really experience any kind of change in thought processes or perception. I also didn’t experience any emotional effects. Initially there were headaches and a sense of really deep fatigue. That lasted the first two weeks. After that the immediate effects were a little brightening. My mood improved a little bit each time. It wasn’t a long-term thing; I felt better for a little while, and as the day wanes, my mood dropped back down. For me, it was all about the cumulative effect.

Side effects

After 4 treatments I had some interesting effects occur. One night, after cooking an elaborate dinner, I was sitting on the couch and, suddenly, it felt like I could smell everything. It felt like my sense of smell had been dampened that whole time and, suddenly, it had come into focus. It was like until the TMS treatment, I was smelling things at about 25 percent of what they were. The super smell lasted for about an hour each time, and then things went back to baseline. They say a lot of your senses get dampened with depression. I now know that’s real.

Another thing that happened during treatment: I started experiencing these perception switches. I would go from one state of mind to another. The switches occurred every 15 to 30 minutes. The only way I can describe what it felt like was to compare it to when I did acid a few times and ate mushrooms as a kid. The perception shift you get when you’re under the influence of those chemicals—that’s what it felt like for me.

Later in the treatment cycle I started to get very irritable and very angry. I’d have these mini bouts of rage that would last for 30 seconds or so each time. That was disturbing. Everybody in the house was jumpy and avoiding me. The cats were like, “We’re out of here!” I was told by the lead TMS tech that that was a good sign, that my brain was creating new neural connections and that’s what was causing the irritation. Most people experience a depressive episode in the first three weeks, but some people experience anger. That was difficult to deal with.

The suicidal ideation faded in the first week and a half. It faded out quickly. I don’t know if that was what was happening in my brain—something the machine was doing—or if it was the fact that I was getting help and I was actively doing something to improve things. I was looking at living and improving my health and having hope instead of thinking about ending things. That alone was worth everything.

Charting progress

Over the course of my treatment, there were several markers I used to evaluate how it was going.

The first were the markers from the doctor’s notes. Every Friday I did one of the DSM questionnaires about depression and anxiety. The doctor kept those scores. Over the duration of the treatment, the doctor said my scores decreased depression-wise by about half and anxiety-wise by about a little more than half. The reduction in anxiety was the biggest thing I noticed. The other thing is that I found myself to be more motivated, more hopeful and a little more energized. The reduction in anxiety has been fantastic. Suicidal ideation disappearing has been fantastic. Depression has decreased, for sure. They said I would start sleeping better, but I didn’t. I’m a lifelong insomniac.

I have mixed emotions about this progress. I was hoping for more. At the same time, I know my expectations were unrealistically high and the whole time I fought to bring my expectations back to reality. I had to come to terms with the fact that this is something that will improve things so that I can further improve on my own. It’s like the treatment gave me a toehold so I could get moving in the right direction.

My doctor said things would continue to improve for about two months after the last treatment finished. I’ve also read that each TMS treatment cycle lasts about a year, and that after the year it really varies wildly. About a month later I’m still seeing improvement.

I also recognize that I’m lucky to have insurance. This treatment runs anywhere from $12,000 to $16,000. With my copay it was $980. This is what my specific insurance company and specific insurance plan required before approving TMS. I’m sure requirements are different from company to company, and even plan to plan within the same company.

After dealing with depression for most of my life, this feels like having a future. A lot of possibilities are now open that weren’t open before. My husband and I have been planning trips. We’re talking about going to Iceland and Finland. We talked about doing a bunch of different things. I feel much more excited and motivated to do that. I feel more excited to live.

Spreading the word

I kept a journal about my experiences. Once a week, I shared these journal entries with my friend list on Facebook. The entries were straightforward. Here’s what’s going on with me. Here’s what’s happening. Here’s what it’s been like. People were really interested. After my journal entries, I have been contacted by phone and through Facebook by people who are either interested in TMS for themselves or for loved ones.

I would recommend TMS. Even if TMS doesn’t work for someone at all, I encourage people to try something. Depression is not a way to live well, and it can end in your demise. For me, TMS felt like going to the moon, doing something totally unknown and super frightening.  At first, I felt like I was being a coward, but now I see the opposite is true. I can recognize it as being brave. The stigma around mental health is decreasing, which means more people are talking to each other about depression. Hopefully that means more and more people will start talking about TMS to help.

This essay has been factchecked by members of NAN’s Publications Committee. For more about that process, click here.

Three decades of fighting for brain health

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U.S. Representative Bill Pascrell (D-N.J.) has established himself as a champion of brain health. The 86-year-old Army veteran has represented the Ninth Congressional District since 2013 and served in the House since 1997. During this time, he has leveraged his leadership in several ways to protect the brains of Americans. First, in October 2008, after the death of a young boy in his district who returned to playing football without having fully recovered from a concussion sustained earlier in the season, Pascrell introduced the Concussion Treatment and Care Tools Act (ConTACT), which has been endorsed by the National Football League, the National Football League Players Association, and the Brain Injury Association of America. ConTACT brings together a conference of experts to produce a guidelines for the treatment and care of concussions for middle- and high-school students. It also provides funding for schools’ adoption of baseline and post-injury neuropsychological testing technologies. Later in his tenure, in 2013, Rep. Pascrell introduced the Traumatic Brain Injury Reauthorization Act of 2013 (H.R. 1098; 113th Congress), a bill that reauthorized appropriations for Centers for Disease Control and Prevention (CDC) projects to reduce the incidence of traumatic brain injury and projects related to track and monitor traumatic brain injuries. The National Academy of Neuropsychology is honored to celebrate the leadership of Rep. Pascrell at its forthcoming annual conference in Philadelphia. In advance of that event, BrainWise Managing Editor Matt Villano spoke with Rep. Pascrell about his work and his commitment to brain health. What follows is a transcript of that exchange.

BrainWise: Why did you get into politics in the first place?

Rep. Bill Pascrell: A native son of New Jersey, I have built a life of public service around the principles I learned while growing up on the south side of Paterson. My parents and Italian-immigrant grandparents instilled the value of being a bridge builder: one who seeks to bring together the diverse peoples and neighborhoods in our communities to forge a better society. I was proud to serve in the New Jersey State Assembly in the 1980s and became mayor of my hometown Paterson in 1990. I entered Congress in 1997.

BrainWise: Since you became an elected official, you have been a champion of more than 6 million Americans who live with debilitating brain injuries. What sparked your interest in fighting for these issues, and how did you come to recognize this important group of citizens?

Rep. Pascrell: It bothered me that these Americans were too often being forgotten. Traumatic brain injury is a devastating debilitation that impacts not just its victims, but also their families and friends. I felt these Americans needed a champion in Washington and I have tried to be that champion. I founded the Congressional Brain Injury Task Force in 2001 to increase awareness of brain injury in the United States. [The organization also] supports research initiatives for rehabilitation and potential cures, and strives to address the effects such injuries have on families, children, education, and the workforce.

BrainWise: What inspired you to create this task force? What is the work of this group?

Rep. Pascrell: In 1998, I met a Clifton, New Jersey, constituent named Dennis Benigno, whose 15-year-old son had suffered a severe traumatic brain injury from an automobile accident that left him disabled. The Benigno family’s passion and dedication in finding a cure for their son and millions of others was my inspiration to act in Congress. Through the Task Force, I work on a bipartisan basis to raise public awareness of brain injuries among Americans of all stripes. We try to bring both federal support and public support to bear here. Public awareness is everything.

BrainWise: You co-chair the task force with Rep. Don Bacon, a Republican from Nebraska. At this time of such division in Congress it appears that you have been able to work across the aisle for this important cause. How?

Rep. Pascrell: On commonsense issues, compromise is not just possible but essential. When I speak with my Democratic and Republican colleagues on the need to raise awareness for brain injuries, they understand, and they are eager to get involved. Both parties working together has helped secure hundreds of millions of dollars to advance awareness and support those with traumatic brain injuries. We have passed legislation that recognizes the life-altering impact and supports researching into brain injuries that has affected millions of Americans.

BrainWise:  You have also been instrumental in bringing awareness to those who have experienced blast injuries; this resulted in The National Defense Authorization Act for Fiscal Year 2020. Why was that act so important, and why is it so important to help those who have suffered from these traumatic brain injuries?

Rep. Pascrell: This federal support has been critical to aid Traumatic Brain Injury victims. It is one thing to talk the talk and another to walk the walk. Politicians can speak a big game, but enacting actual federal aid is the key, and we have done that with these pieces of legislation we have gotten signed into law. That bill included language that I pushed for on blast exposure. Specifically, my language ensures blast exposure history will be recorded in medical records of servicemembers, requiring the enclosure of critical details including the date and duration of the incident. The National Academy of Medicine has concluded that servicemembers with blast exposure history are at increased risk of long-term health issues, including depression, Alzheimer’s-like symptoms, seizures, and problems with social functioning. Optimizing the readiness of servicemembers and recording blast exposure data is essential so that soldiers receive proper care for any service-connected medical issues that may arise later.

BrainWise: Finally, the issue of Chronic Traumatic Encephalopathy (CTE) is one we see grabbing a lot of headlines these days. Research into what causes this is ongoing, and early studies indicate CTE is not as connected to repeated head injuries as the mainstream media has portrayed. To what extent do you think our government should get involved in regulating activities that could potentially lead to CTE?

Rep. Pascrell: I think it starts with focusing a bright light on these problems. Congress can do that very well with hearings, public events, and public statements.  I have demanded answers from leading sporting organizations about how they are protecting athletes and students. Our kids and future generations are learning more and more about these harms, and we cannot treat them lightly.

What happens when you treat depression with ketamine

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It was a Wednesday afternoon. March 27, 2019. The out-of-office notification popped up on the team calendar at my corporate job. I told everyone I had a “doctor’s appointment” – technically accurate, yet spiritually a lie. I wasn’t going to the doctor’s; I was going to space.

Okay, not actual space–a ketamine clinic just a block or so away from the University of Texas at Austin. I answered a few clipboards full of questions. They sat me in a chair, read my blood pressure, and asked me “What is your intention for today’s infusion?” I do not recall my answer.

Then the infusionist hooked me up to an EKG and poked a vein. The machine beeped and the bag began to drip. The next hour was the weirdest of my entire life–I was about to go into a K-hole to treat a depression I’d been battling for years.

Why I chose ketamine

I received my first official diagnosis of major depressive disorder in the spring of 2001. I was a freshman at Syracuse University, struggling with being a working-class kid from the Rust Belt at a prestigious private school that was a popular magnet for the types of kids we’d call “nepo-babies” in today’s parlance. I was not taking great care of myself. I exercised but forgot to eat. I made friends but not as quickly as I lost them. Occasionally, I even went to class. I got good grades but felt like a misfit.

For treatment, I tried Zoloft. I saw a social worker for counseling. I can’t say either worked. This began a years-long journey on therapists’ couches and doctors’ pills, trying to understand why I felt so sad, anxious, and broken – and, hopefully, feel better. My mental health waxed and waned, but in late 2018 I was low enough (and well-off enough) to try new alternatives.

When my counselor first suggested ketamine infusion therapy after my latest 90-day course of Lexapro yielded unremarkable results, I recoiled. I was never a fan of “drugs.” Too scary. Too much can go wrong. I saw kids put powdered ketamine up their noses in college, sink back in their chairs, and fall out of touch with reality. I thought to myself, “That looks like no fun at all and I’m never going to do that.”

Never say never, I guess. My counselor assured me I would be safe. “I can refer you. I’m good friends with the woman who runs the clinic and her husband’s the doctor there. They’ll take good care of you.” Eventually, I acquiesced. Weeks later, there I was in the chair: determined and pot-committed. I paid $500 to be there (and $3,000 for the initial course of treatment) and put my faith in this Y2K-era club drug. I had some good research on my side.

How ketamine works

Developed in 1962 as a dissociative anesthetic, chemists created the novel compound to be a safer and less hallucinogenic alternative to phencyclidine (PCP). At anesthetic doses, ketamine provides pain relief, sedation, and amnesia. Breathing function is preserved, your blood pressure rises, and your pulse ticks upward. It’s short-acting and quickly metabolized, providing relief within seconds and acute effects that last for an hour or less. It’s antidepressant potential was first noted in 1975.

Unlike conventional antidepressants, which target monoamines, ketamine acts upon the glutamate system of the brain as an N-methyl-d-aspartate (NMDA) receptor antagonist, mediating activity of GABA and glutamate neurotransmitters. Glutamate plays an important role in modulating responsive synaptic changes related to experiences associated with learning and memory.

If how ketamine works is unusual, how fast ketamine works is genuinely unprecedented. Recipients notice an improvement in mood within hours–improvements that can last over a week on their own and, when coupled with integrative therapies and proper care pre- and post-infusion, can last for months if not years.

Researchers at the University of British Columbia conclude, “[Ketamine’s] effects may ‘reset the system’ by counteracting the synaptic deficits, neuronal atrophy, and loss of connectivity in depression.” If you think of the brain as a computer–ketamine appears to perform a soft reboot, a quick start, a system restore, a hard-drive cleanup, and defragmentation all in one.

Ketamine’s ace in the hole is the way it appears to actually “rewire the brain” by increasing neuroplasticity. The brain can heal itself more easily by allowing new neural pathways to develop. Theodora Blanchfield, AMFT, a Los Angeles-based ketamine therapist posits that “the new neural pathways—think of them as new roads in your brain—allow you to create more positive thoughts and, therefore, behaviors. This is compared to traditional antidepressants, which only work as long as they are in your system.”

We can even observe this rewiring visually. In 2022, University of Pennsylvania researchers reported that ketamine switches off specific neurons involved in normal awake brain function and switches on an entirely different and previously inactive set of cells – believed to be a network of cells that enable “dreams, hypnosis, or some type of unconscious state”.

In an interview with Harvard Gazette, anesthesia researcher Fangyun Tian, Ph.D., summarized her own research by drilling down even further, reporting “high-frequency gamma oscillations in the prefrontal cortex and the hippocampus known to be involved in ketamine’s antidepressant effects from other studies.” Additionally, the researchers “found a three-hertz oscillation in the posteromedial cortex that another study showed might be related to ketamine’s dissociative effects.”

These gamma oscillations appear to promote the profound changes in cognition and perception that permeate the psychedelic experience–and also appear to aid in shaking the brain out of the “default mode network,” allowing people to more easily experience mental health breakthroughs and behavioral shifts.

Research into the potential applications yields buzzy headlines and buzzier results, suggesting ketamine-powered neuroplasticity improvements can aid in everything from OCD to PTSD to smoking cessation to alcohol use disorder to learning to tolerate tropical house music.

If this all sounds a bit bullish, it doesn’t come without risks or unknowns. While generally (and often exceptionally) safe, especially in short-term clinical settings, adverse side-effects among long-term clinical ketamine recipients include impairments in memory, executive functioning, self-awareness, and increases in emotional blunting and reward processing. Additionally, a 2022 review published in Frontiers in Neuroanatomy proposes that long-term recreational ketamine use was “associated with lower gray matter volume and less white matter integrity, lower functional thalamocortical and corticocortical connectivity.”

How a therapeutic K-Hole actually feels

My ketamine infusion treatment course consisted of six doses over three weeks. I received progressively increasing amounts, starting at 50mg and ending at 200mg. While no two infusions were alike, they were similar enough to be able to speak about them in broad strokes. Each infusion took about an hour. They started slowly, gradually warmed up, peaked, then waxed and waned in their cognitive distortions until the last drop. The emotional whiplash was sudden, frequent, random, and severe. I laughed, cried, and screamed – sometimes all at once. All the while, I felt a warm glow, a genuine sense of awe-struck wonder, and a slight tinge of dread that this could all go very wrong at any given moment.

Immediately after each dose, I journaled my thoughts in an attempt to remember as much of what I had just experienced as I could. I described the infusions as a “solo space flight,” the Antoine de Saint-Exupéry novella “La Petit Prince,” a journey into “the operating system” of reality to modify the UI and UX, “a wafer-thin atmosphere buffering a sort of meta-reality, enveloped by a dark abyss of nothingness, monitored by scientists in lab coats,” the “minus world” video game glitch in the original Super Mario Bros., and “the flume ride in the Mexico installation at Disney’s EPCOT theme park.” By the final infusion, I started coining terms like “soul meridian” and comparing myself to Simba from The Lion King and the Manchurian Candidate.

Other common ketamine experiences for me included: speaking in perfect French with my dead Papa as a young man at a Parisian cafe, faceless people performing heavy industrial work, feeling as though I’m hanging from the ceiling, feeling watched by MK Ultra-era government medical observers, staring in the direction of a precipice that never quite arrives, and a procession of formless deep blues and greens that wash into each other.

One frequent recurring experience was what I call the “coffin moment.” Approximately two-thirds of the way through most of the infusions, the chair in which I was sitting in folded into a coffin that rose from below the floor and onto a stage where people passed and pay respects. Then I levitated and floated toward a bright light on a well-lit path (think: Rainbow Road from Super Mario Kart). My life fast-forwarded like the climax of a montage that ended in silence and white stillness. I walked to a white door. That was when I heard a voice whisper “not yet,” and I dropped back into my body. I didn’t always make it all the way through that progression–sometimes I ended at the rising coffin–but the moment always played out the same: I was dead and I shouldn’t have been. Then the ketamine subsided.

For as insane as “pretend death” sounds, it’s not uncommon in a psychedelic context. In fact, ketamine is so adept at simulating near-death experiences that there’s peer-reviewed literature detailing the phenomenon. People taking clinical doses of ketamine report experiencing these sensations with uncanny levels of accuracy and consistency.

Not all of my ketamine infusions were pleasant; on two occasions out of the roughly 40 (including boosters) I’ve received, my hallucinations were so painful and intense that I had to cut the infusion short. On a handful of other occasions, my blood pressure spiked to levels that caused clinicians to draw the same dosage out over 75 or even 90 minutes instead of 60.

Still, at doses that cause full dissociation–approaching anesthesia–I progressed through states of curiosity, childlike immersion, omniscient appraisal of life and reality, existential dread, death, rebirth, and newfound confidence. Just about always in that order.

How it feels when it works (and when it doesn’t)

In my experience, there’s been no correlation between how an infusion feels and how successful it is. I’ve had profoundly meaningful and pleasant infusions that did next to nothing; I’ve had frightening and elegiac infusions that changed me in lasting ways.

Post-infusion care and integration are every bit as vital to neural rewiring as the ketamine itself.

My gameplan for what I call the “afterburn” (the 24 hours post-infusion) is to drink plenty of water, eat plenty of food, get plenty of sleep, and avoid all of the following: calls, work, driving, decision-making, the news, deep thought, stress, alcohol, and tobacco.

While most infusions register some improvement, a handful have not–usually due to something sabotaging the post-infusion window. Booze. Bad sleep. Dehydration. Stress. The Buffalo Bills losing to the Kansas City Chiefs in the playoffs.

When ketamine works–and I was usually able to tell by day No. 2, if not sooner–it was obvious. I started incorporating healthier habits. I felt myself become kinder and more empathetic, clearer in thought and morality, more courageous and self-assured, more compassionate toward myself, and less reactive to slights or mistakes. I laughed often and more easily.

Most noticeably, I became more curious. Ketamine may not be a wonder drug, per se, but my elementary understanding of neuronal function and limited experience with other psychotropic medication has convinced me to believe that there may be no other substance that sparks wonder so subtly or effectively.

It’s the curiosity and wonder that have led me to believe that this is the “rewiring” in action. I was often reminded of the Overview Effect–a cognitive shift experienced by astronauts upon seeing the Earth in full from space for the first time. When they return from orbit, they report increased feelings of cooperation and collectivism and a kind of self-transcendence. They become more appreciative, empathetic, and kind. They change the way they show up.

So … does it work?

It’s been four years since I first explored ketamine treatment for my depression. Since then, we’ve endured a deadly global pandemic and a distressing decline in our social and political climates. There’s not enough ketamine in the world to cure what ails us collectively. There’s so much of that noise in the data – plus unrelated work, home, and life stressors – that I can’t tell you whether I’m “still depressed” or if the infusions were worth it.

In short, I think it was worth trying, but it also was no magic bullet.

What I can tell you is this: Ketamine made me a marginally better person. Clearer, kinder, more curious, and occasionally happier. At the same time, I recognized that ketamine is just one part of a bigger picture. Improving your mood requires diligent self-care and self-inquiry, the absence of significant personal and systemic challenges, robust relationships with people close to you, and the curiosity and enthusiasm required to keep learning and growing. Ketamine helps facilitate that final piece and only that final piece.

If that feels like an underwhelming appraisal of something that repeatedly simulates near-death experiences for $500 per hour, let me close with this anecdote. In 2019, I collected my ketamine notes into a 10,000-word essay I published on Medium. It became my most popular and critically lauded written work and earned me enough money and professional and public service opportunities – including writing this very article – to radically change my life. It wasn’t the chemical that changed me; it was what I did with the opportunity it granted me that did. I’ve learned, grown, changed, and evolved – maybe that’s all we can do. Maybe that’s the best we can do. I’ll take it.