The gene that could change how we treat ADHD

What if your brain had a volume knob? Researcher Dr. Zachary Gershon joins Rae to explain Homer1a, a gene variant that may hold the key to how we focus. When levels are lower during development, the brain gets better at filtering out distractions, or what scientists call “neural noise.” This discovery could one day lead to non-stimulant treatment options for ADHD. And it started with one scientist’s very personal question.

• Watch: Is ADHD genetic? We asked a Harvard scientist | Hyperfocus

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Rae Jacobson: What if there were a way to turn the volume down on all the extraneous noise in your brain? A distractions down knob is something that, as an ADHD person, I have always wished for. But in an age of endless, relentless distraction, who isn't looking for a way to quiet the noise and focus on what's actually important?

We are bombarded by all of the sensory information all the time. Well, recently, a team of scientists may have discovered a way to do just that: a gene that has the potential to calm the mind, improve focus, and potentially, one day, change the way we treat ADHD forever. Essentially, we're turning down the volume on all of that background noise that we're getting on the day—to—day.

I'm Rae Jacobson, and today on "Hyperfocus," Homer1, the gene that's changing how we think about attention. I want to welcome Dr. Zachary Gershon. You go by Zach?

Dr. Zachary Gershon: Yep, Zach is fine.

Rae: To the show, and you are here to tell me about something that I am very, very interested in understanding and currently understand basically not at all. So I'm so glad that you're here to explain because you just led a team of researchers — is that fair to say, led?

Zach: Yep.

Rae: In this really exciting, novel research on how we understand attention in the brain, and it could potentially change how we treat ADHD.

Zach: Hopefully, yes. Thanks for having me.

Rae: Thank you for coming. I'm sorry to be like, "Here's this giant pronouncement," but that was how I felt when I saw this article for the first time. I was like, "Wait, wait, what is this?" So Zach, what is this?

Zach: So we found this version of a gene called Homer1 and this specific version called Homer1A. And we found that mice that had less of this gene version when they were growing up actually had better attention as adults. And the way that this seems to work is by quieting the background noise in this part of the brain called the prefrontal cortex. The prefrontal cortex is sort of the executive control center of the brain. So all the things that we think about when we think about like cognitive ability, basically, there's prefrontal cortex involvement and control.

Rae: All of that makes sense to me so far.

Zach: Great, that means I'm doing my job.

Rae: Zach did this research as part of his PhD with his advisor, Dr. Priya Rajasethupathy, at the Rockefeller University. The gene version that Zach's talking about, Homer1A, plays a role in how much information your brain processes at any given moment. When you have a lot of it, your brain zings around, letting in too many signals, like a bunch of weaving cars zooming down a busy street, which isn't safe for anybody.

But when you have less of it, the traffic is less overwhelming, as if there were suddenly traffic guards giving directions — "You can go, no, you stop." AKA, less Homer1A equals less distractibility, so it's easier to focus on one or two things at a time instead of, you know, like five or six or a thousand.

(03:36) How the research shifts the focus from simply increasing attention to actively filtering out competing signals.

Rae: So this sounds like it has huge implications for how we see attention in the brain. Can you help me understand that a little bit?

Zach: So a lot of the work that's been done on attention previously focuses on ways to increase activity in the prefrontal cortex and increase, you know, that signal that can direct where the attention is going and how much of it is allocated. But what our work does is sort of an addendum to that paradigm and saying that it's not just that relevance signal that's important; it could also be that we're boosting the signal by reducing all the competing signals that we get.

Rae: All right, not to be pedantic, but I feel like distractible as we are, I really want to put the finest of points on the big discovery here. Zach and his team's work shows that attention isn't just about helping your brain focus on one important thing; it's about helping your brain not focus on the nine million other things that are happening at the same time.

Zach: We are bombarded by all of the sensory information all the time. There's even in the studio, right — like we're talking and, you know, it's quiet, but there's all of these lights and, you know, there's the texture of this chair. And so our brains right now are forced to take all of that in because, you know, our bodies are designed to constantly take in sensory information. But we then filter it so that, hopefully, most of the time when we're having a conversation, we're just paying attention to each other.

Rae: Wouldn't that be amazing if that were how our brains really worked, because you and I both have ADHD.

Zach: Absolutely, yes.

Rae: And that is not how my brain works.

Zach: No, no. Like the texture of this chair, I'm listening to you but I am also very aware of it.

Rae: So could you turn down, potentially, that noise in the paper? There was a phrase that I really loved; it said "neural noise." Can you tell me how that — well, what that is in scientific terms?

Zach: So essentially, that neural noise is all of these extraneous signals. And so I like to talk about this filtering process through an analogy where imagine, right, a parent and a child are crossing the street. And the child is, you know, talking to their parent, carefree — and the parent is mostly listening, right, you know. Then all of a sudden, a car comes speeding down the street. The parent is going to recognize the danger, even though the kid might not and the kid could still be talking and going on and on.

The parent is not going to process what the kid is saying, despite the fact that they're still receiving that information. And they're going to just focus on rushing.

Rae: Their brain goes to the important thing, which is the car.

Zach: Exactly, exactly. And so if we stop in that split second, right, when the parent notices the car, there are a bunch of calculations, you know, that the brain is making of, "All right, what is all of this information that I'm getting — and what is the most important?" And so there's first the prioritization and then what we only have enough mental resources to allocate to the most important parts. And that's filtering because all of the unimportant stuff or, hopefully, most of the unimportant stuff gets filtered out.

Rae: Yeah, but for the ADHD brain, that's not how it works.

Zach: No. So I mean, sometimes, because we — yes, we know we do have the squirrel or shiny effect. But some of us sometimes can, you know, sit down and do things and even the hyperfocus, right — sometimes we engage, you know, that filtering mechanism to what might be sometimes a detrimental effect, right? So it's, you know, there's a lack of control of that filtering and prioritization.

Rae: Yes. I've heard many people say that ADHD isn't a disorder of a lack of attention; it's an attention regulation disorder.

Zach: Yes. Yes.

Rae: So up to now, this is all in mice, who have tiny, tiny pea brains, I assume.

Zach: Yes.

Rae: What would this look like in the brain of a human?

Zach: Essentially, we're turning down the volume on all of that background noise that we're getting on the day-to-day, so that it makes it easier for us to hone in on what is the most important information that we're getting.

Rae: That makes sense. So if I was a mouse, "cheese, cheese, cheese, cheese," but more importantly, "cat!" That would be better than having all of the distraction. And in a human, like you said, it could be "noise, noise, noise, noise, car!" Or "noise, noise, noise, noise, term paper," which is the important thing that you're supposed to be focusing on. It turns the volume down on the things that are pulling you in all the different directions.

Zach: Exactly.

(08:46) How manipulating the Homer1 gene during early development could lead to more refined attention in adulthood.

Rae: So the thing that's really exciting about this gene is that it can be manipulated. Zach and his colleagues found that if they took a baby mouse — like a little baby mouse — with lots of Homer1A and they suppressed the gene, the mouse became more attentive as an adult. Turning down the gene made the mouse better at focusing. Extremely cool. But there's a big caveat.

Zach: One of the important things for what we found is that the difference in Homer1A level really only made a difference if the mice had that difference from the time they were babies or adolescents.

Rae: Oh.

Zach: Because attention is a developmental process. And we tried changing it in adult mice and we found nothing happened.

Rae: Is that because of neuroplasticity or, like, what is the reason for that?

Zach: That is a great question, and I don't have the answer to tell you specifically. What I can tell you is that, if we're going to stay in the realm of neuroplasticity, this inhibition, those stop signals, do a lot of sculpting of neural pathways during development. And so, based on our results from what we found in our brain recording experiments, it seems like when we lower the Homer1 levels in baby mice and let them grow up, that as adults, they feel those stop signals more acutely.

Rae: So if you lowered the levels of Homer1 ostensibly, you know, right now baby mice, but in the future potentially in baby humans — you know, a kid gets diagnosed with ADHD, you know that this is something that you can target in whatever way that's possible — you lower those levels. Then as they grow up, developmentally, they will simply be better at tuning out the things that don't matter? Their attention will be finer tuned?

Zach: Hopefully. That would be where that thought would go to.

Rae: Wow. That's wild.

Zach: Yeah. Now not to be a killjoy, but though this is all fascinating and potentially really exciting, it's all in the very, very early stages. We don't know if this information will help us create new ADHD treatments for humans, not baby mice. And if we can, it would still be a very, very long way off. But Zach is hopeful, and not just as a scientist, because for him, this is personal.

Zach: A phrase I picked up along the way is that sometimes, you know, your research is really "me-search."

Rae: I like that. That's a good one.

Zach: And I, you know, I don't know if this is vanity, but I, you know, am very interested in things that affect me.

Rae: I mean, there is a reason that I do this show, let me tell you.

(11:42) Zach’s personal journey with ADHD, dyslexia, and auditory processing disorder, highlighting the motivation behind his "me-search."

Zach: So I was diagnosed with ADHD at the end of college. And growing up, I don't know if you use the term "twice exceptional" on the show — so I, you know, had been identified as twice exceptional. I was very fortunate that I had a parent, or have a parent, who special education degrees, general education degrees, clinical social work degree. She, while I was doing my PhD, did her doctorate in cognitive diversity.

Rae: Wow.

Zach: And so growing up, like she was very attuned that I was bright, but there was something like I was reading slower, not that I couldn't read, just like the pace at which I read was slower. And so I got a dyslexia diagnosis, which is there. And then I was having trouble, you know, I didn't always catch what my teachers were saying, and I got an auditory processing disorder diagnosis. And that is still there; I wear hearing aids.

All of this improved in, you know — if you think about school accommodations, a lot of what I got was extra time on tests and, you know, testing in a separate quiet location which, huh, also works for a kid with ADHD.

Rae: Weird how that happens.

Zach: And so it, you know, it wasn't necessarily caught because I was a classic hyperfocuser. And I would just lock in to the detriment of everything. I would forget to eat; I would, for, you know, stay up — oh, it's 2:00 in the morning, I'm finishing homework kind of thing. I didn't realize that what I had thought was just like some executive dysfunction was diagnosable ADHD.

And that was about six months before I started my PhD. And I had wanted to go to grad school and study neuroscience because I had always been interested in like, "Wow, why does my brain work differently than everybody around me?" And I really just wanted to figure that out. So I was wondering whether it could be genetic because I also have, you know, a sibling that has some learning differences and is also diagnosed with ADHD. And so that led me to, "Okay, what is this genetic underpinning of attention?" — and that brought me to this project, really.

Rae: Such a sensible way to come to something too, to be like, "This is genuinely going to change the way that I understand my own experience of being alive." I mean, why wouldn't you want to understand more about your own brain, about how the brain works in general? Like this is clearly like something you were interested in anyway. I don't know that many people who are like, "I want to be a neuroscientist." You know, that's a pretty specific thing.

All of this comes together in this study, though, this really interesting thing. And now you have something that you can kind of hold in your hands and say, like, "I have learned this. This is something new that I've brought to the field." Like what does that feel like?

Zach: It feels incredible, I will tell you. I don't think about it often, I think just because you don't want to get caught in past victories; you always want to — I don't know, I always want to move forward and see, "Okay, cool, what's the next thing I can learn?" But it's also the, you know, the sense of accomplishment of like, "I set out to do this thing and I did this thing."

Rae: I finished a task.

Zach: Yes, I finished a task. Exactly. That's like kind of a big deal. And it took a long time, but I finished a task.

Rae: So but I have to ask, like, task finished acknowledged, but like 10, 20, 30 years from now, like where do you hope this goes and what are you excited about?

Zach: So I mean, I hope that this can be, you know, turned into an effective treatment method. Partnered maybe with stimulants or on its own —  I want to say I'm not a physician. There's a clinical side of this that like scientifically I can talk about, but I want to be very clear about that. But I think it would be really, really awesome if, you know, this made its way into a treatment mechanism that was part of a prescriber's, you know, modality.

And I know people that, you know, have ADHD and struggle in their lives and they don't want to take stimulant medication because, you know, they're afraid of it. And and hey, I respect everybody's preference, you know. I'm not pro- or anti-medication one way or the other. But, you know, maybe something that's not a stimulant might be a viable option for somebody who has those concerns.

Rae: Yeah, or for somebody who has any type of health thing that prevents them from taking stimulants. I think about that a lot. Also, I wonder sometimes, like, you know, I think you live in this world too, stimulants — the conversation about stimulants controls a lot of how people talk about ADHD in general. The idea that there would be another treatment modality that sort of circumvents some of the stigma that can come along with a currently existing treatment methods is kind of exciting in a completely other direction, you know?

Zach: Yeah. Absolutely. I mean, I think that — I mean look, that's the hope of a study like this, of we found this mechanism and maybe it does provide an alternative.

Rae: That's all for today. Thank you so much to Zach for coming and for explaining all of this very complicated stuff to me. If you're interested in ADHD and genetics, and come on, who isn't? Check out our episode with Dr. Anne Arnett, a Harvard researcher studying the genetics of disorders like ADHD and autism. We'll leave a link in the show notes. See you next time.

"Hyperfocus" is made by me, Rae Jacobson, and Cody Nelson. Calvin Knie is our video producer, and video is edited by Alissa Shea. Our research correspondent is Dr. KJ Wynne. Briana Berry is our production director, and Neil Drumming is our editorial director. If you have any questions for us or ideas for future episodes, write me an email or send a voice memo to hyperfocus@understood.org.

This show is brought to you by Understood.org. Our executive directors are Laura Key, Scott Cocchiere, and Jordan Davidson. Understood is a nonprofit dedicated to empowering people with learning and thinking differences like ADHD and dyslexia. If you want to help us continue this work, you can donate at understood.org/give.