Research Recap with Skye: The Atomoxetine Trial

Summary

Hacking Your ADHD – Research Recap with Skye: The Atomoxetine Trial

Host: William Curb
Guest: Skye Waterson
Date: February 13, 2026

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Episode Overview

In this episode of Hacking Your ADHD, host William Curb and guest Skye Waterson (of Unconventional Organization) dive into a pivotal 2015 research paper on Atomoxetine, a non-stimulant ADHD medication. They explore how Atomoxetine impacts the relationship between two key brain networks—the Default Mode Network (DMN) and the Task Positive Network (TPN)—in adults with ADHD who have never taken medication before (medication naïve). The discussion goes beyond medication, touching on brain differences in ADHD, practical implications, and the value of acknowledging neurodiversity.

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Key Discussion Points and Insights

1. Introducing the Paper and Key Terms

[01:18–02:42]

• The paper discussed is titled: "Atomoxetine Treatment Strengthens an Anticorrelation Relationship Between Functional Brain Networks in Medication-Naïve Adults with Attention Deficit Hyperactivity Disorder: A Randomized Double-Blind Placebo-Controlled Clinical Trial".
• William jokes about the “full, lengthy name” but underscores the importance of the study’s design.
• The study focuses on the Default Mode Network (DMN) and Task Positive Network (TPN) and their interrelation in ADHD.
• Default Mode Network (DMN): Active during rest, mind-wandering, and self-referential thoughts. ("It's kind of that part of your brain...I'm chilling out and I'm daydreaming." – William Curb, 02:42)
• Task Positive Network (TPN): Active during focused tasks and external problem-solving; essentially executive function. These two networks typically work in a push-pull manner.
• In ADHD, this “see-saw” relationship is disrupted, and the study aims to evaluate if Atomoxetine can help rebalance it.

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2. The Study Design and What Makes it Important

[04:04–06:41]

• Skye highlights the rigor: randomized, double-blind, placebo-controlled trial—an “expensive” and rare setup especially with medication-naïve adults.
  • “It’s particularly hard to work with medication-naïve adults.” – Skye Waterson, 04:41
• Two groups: 24 medication-naïve adults with ADHD and 24 matched control participants.
• ADHD participants were carefully diagnosed using DSM criteria—this wasn’t based on self-report alone.
  • “This was not a ‘Do you think you have ADHD? Pop your hand up’...” – Skye, 06:41
• The study used fMRI scans to track brain activity before and after administering Atomoxetine or a placebo.
• Memorable moment: William jokes about the study noting no participants fell asleep in the fMRI scanner.
  • “Who's falling asleep in an MRI machine?” – William, 06:24
  • Skye laughs: “It was six minutes... they said they didn't nap and we don't think anyone lied.” ([06:24–06:41])

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3. What Did the Study Find?

[07:10–08:57]

• The primary question: Does Atomoxetine restore the typical anticorrelation between DMN and TPN observed in neurotypical brains?
• The findings: Atomoxetine did show effectiveness in “reducing” the disordered interaction between these networks.
• Practical translation: This is relevant to everyday symptoms like daydreaming when supposed to be working—or vice versa, struggling to relax because the “task” network won’t shut off.
• William expresses personal interest in the “other way” (trying to relax but remaining task-focused), though the study mostly focused on active task engagement.
  • “There’s not a lot... on how, when you’re trying to relax, the Task Positive Network is still going on. I find that to be awful.” – William, 07:10

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4. Implications Beyond Medication

[08:57–11:47]

• Skye relates that while medication is helpful, more significant is the evidence showing a real (biologically observable) difference between ADHD and neurotypical brains.
  • “If it was just about the medication, I don’t know if I would have pulled a paper from 2015. But the fact that they were able to show... a very specific difference in the way your brain works when you have ADHD is so interesting...” – Skye, 08:57
• The finding helps shift the narrative away from blaming oneself for ADHD struggles.
  • “People are like, ‘Surely my brain is working like everyone else’s and I’m just a bad person.’ These papers really help to change that narrative.” – Skye, 09:43
• William shares a personal anecdote about ineffective study strategies in college, underscoring the importance of tailoring strategies to ADHD brains.
  • “That was such a bad strategy... you needed to do something different with your brain to get it to activate in the ways that you wanted it to.” – William, 10:11
• The DMN-TPN relationship isn’t a simple switch—it’s more like “a clunky old dial” or “hand crank” that takes effort to shift.
  • “It’s not an automatic switch. It’s more like a clunky old dial that we have to turn.” – Skye, 10:42
• This supports the need for individualized accommodations—some may need more or less stimulation to get into a task-focus or to relax.

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5. Practical Takeaways and Strategies

[11:47–13:37]

• William and Skye discuss real-world adaptations:
  • Fidgets and sensory input can help activate the right network when needed.
  • For people with ADHD, relaxing often still requires some stimulation (e.g., watching TV with a fidget or knitting).
  • “I gotta have something to do with my hands... I need that little bit of extra stimulation.” – William, 11:47
• Skye notes similar patterns in her clients—finding that background activity or multitasking can make leisure or family time more accessible.
  • “I've worked with a lot of clients where... they take up knitting or something like that because they need something to do.” – Skye, 12:22
  • She gently addresses family guilt and encourages small adjustments, like background music, to make presence more achievable.
  • “You want to be present for your family, but actually do need a little bit higher stimulation than just staring at your child who's playing a game...” – Skye, 12:22
• When supporting ADHD children, fidgets during activities like board games may help them remain present.

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6. The Value of Research in Self-Understanding

[13:12–13:37]

• Powerful message: Having evidence of brain-based differences can legitimize experiences and practices that work for people with ADHD.
  • “There’s another thing to be like, here is how it works differently. And because of that, there are specific things we can do.” – William, 13:37
• Both William and Skye stress that scientific validation supports both medication and non-medication approaches to living well with ADHD.

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Notable Quotes & Memorable Moments (with Timestamps)

• “It’s this like, active part of your brain...that’s active during your rest, mind-wandering, and like, self-referential thoughts. You’re kind of like, ‘I’m chilling out and I’m daydreaming.’”
  – William Curb (02:42)
• “You have this push-pull, seesaw relationship...in a neurotypical brain. With ADHD brains, that relationship does not work.”
  – William Curb (03:34)
• “They had 48 adults...and they were popped into an fMRI...what are the funniest things I saw in there was, ‘we didn’t have anything to make sure they didn’t fall asleep in the MRI machine.’”
  – William Curb (05:36)
• “Who’s falling asleep in an MRI machine?”
  – William (06:24)
• “It’s hard to get the funding to do such a deep dive into this particular topic...to work with medication-naïve adults.”
  – Skye Waterson (04:41)
• “One of the biggest problems I have is getting people to start it because they think they should just be white-knuckling...they think, ‘Surely my brain is working like everyone else’s and I’m just a bad person.’”
  – Skye (09:43)
• “It’s not an automatic switch. It’s more like a clunky old dial...a hand crank, if you will.”
  – Skye (10:42)
• “I gotta have something to do with my hands because they need that little bit of extra stimulation.”
  – William (11:47)
• “You want to be present for your family...but actually do need a little bit higher stimulation than just staring at your child who's playing a game...”
  – Skye (12:22)
• “Here is how it works differently. And because of that, there are specific things we can do.”
  – William (13:37)

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Important Segment Timestamps

• [01:18] – Episode/guests and subject introduction
• [02:42] – Explanation of Default Mode Network (DMN) and Task Positive Network (TPN)
• [04:04] – Study design and significance; what is unique about this research
• [05:36] – Describing the study protocol and memorable MRI anecdote
• [07:10] – The main findings: Atomoxetine's effect on DMN/TPN anticorrelation in ADHD
• [09:43] – Changing the narrative: ADHD as a brain difference, not a character flaw
• [10:42] – Analogy: Network shifting isn’t automatic—ADHD brains are “clunky old dials”
• [11:47] – Everyday adaptations: fidgets, multitasking, relaxation strategies
• [13:37] – The importance of validating research in ADHD self-understanding

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Summary & Main Takeaways

• The episode unpacks a significant study showing that Atomoxetine can restore a more typical pattern of brain network activity in medication-naïve adults with ADHD.
• The findings highlight a meaningful, measurable brain difference in ADHD, supporting both pharmacological and behavioral intervention.
• Validation from rigorous studies helps shift self-blame and encourages more effective, personalized coping strategies—it's not about “white-knuckling” through tasks.
• Everyday strategies like using fidgets, multitasking, or adjusting stimulation levels are legitimate needs for ADHD brains.
• The science gives people with ADHD (and those who support them) “permission” to work differently rather than feeling broken or lazy.

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For more resources and strategies on ADHD, check out unconventionalorganization.com (Skye’s site mentioned at [14:01]).

Transcript

[A]

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[B]

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[C]

Welcome to Hacking youg ADHD I'm your host William Curb and I have adhd. On this podcast I dig into tools, tactics and best practices to help you work with your ADHD brain. Today I'm joined by Sky Waterson for our Research Recap series. In this series, we take a look at a single research paper and dive into what the paper says, how it was conducted, and try and find any practical takeaways. In this episode we're going to be discussing a paper called Automoxine Treatment Strengths An Anticorrelation Relationship Between Functional Brain Networks and Medication Naive Adults with Attention Deficit Hyperactivity Disorder. A randomized double blind placebo controlled clinical trial. Yes, that's the full study name. It's quite a lot. And this study is about this push pull relationship between the Default Mode network and the Task Positive Network and then how Atomoxicine treats Mint can be effective in dealing with it. So let's get into it by kind of maybe jumping into some of these terms that we're going to be talking about.

[D]

Yeah, I think we should start with some terms. So I will say as well, this paper is from 2015, so it's a bit of an older paper, but it was also the Paper that really nailed this topic in terms of what? You know, a randomized double blind, placebo controlled study, which basically means that they did this. Well, let's talk about what it is first, then we'll talk about how they did it. So take us through what the task mode is, the default mode and all that stuff.

[C]

Okay, so the default mode network. We've, you know, I've done episodes about this and we've talked about it on the podcast before and it's something I think is really interesting to discuss because it's this like active part of your brain. So it's the regions of your brain that light up and when we're, when light up in the terms of. That's what you see. What's active during an mri, which is, we're going to be talking about the study. But so it's this active during your rest, mind watering and like self referential thoughts. It's, you know, you're kind of like, I'm chilling out and I'm daydreaming. It's kind of that part of your brain. And then your task positive network is active when you're focused on the external world to solve problems, to pay attention. This is, you know, the executive function part of your brain that goes, we're doing stuff. And typically in a neurotypical brain, you have this push pull, seesaw relationship where you have the default node network turn on and the test positive goes down. And with the, when you start doing work, the default mode network turns off and the test positive network is going on. I know. And this paper talks a lot about how that relationship does not work with ADHD brains and then also how they try and treat this with atomoxifene.

[D]

Yeah, exactly, exactly. And for those of you who are like what this is a system people have thing that switch that turns off and on 100%. And that's one of the reasons why we talk about this stuff so much and why we struggle with this. So the interesting thing here was by treating it in this particular way. And again, this is an example of what we've talked about before, which is papers don't always come to us fully formed in a way that is made to support people with adhd, it's often how to support medication. And so in this context what they did is they did a very solid study which shows us that yes, atomoxetine is helpful, but also that there's definitely a difference between the ADHD brain and the non ADHD brain, which to me is almost more interesting because it's hard to get the funding to do such a deep dive into this particular topic. It's particularly hard to work with medication naive adults. So people who haven't taken the medication who have adhd, compare them to normal controls and then give half of those adults with ADHD a placebo that they don't know is a placebo, and half of those adults with ADHD at amoxetine and test the results in an fmri, which is expensive. And that's exactly what they were able to do.

[C]

Yeah. So they were, you know, they grabbed. They had 48 adults. Great. You know, so they had 24 that were, you know, these medication naive adults, and then 24 that were controlled and then matched so that they, you know, you kind of had this. Group that, you know, you had similar populations that were studying and, you know, some were given atomoxine and some weren't, and then they were popped into a FMRI and, you know, looking at their brain, what are the funniest things I saw in there was they're like, we didn't have anything to make sure that they didn't fall asleep in the MRI machine. But everyone reported. But I'm like, who's falling asleep in an MRI machine?

[D]

And it was six minutes. I was like, I had the exact same thought. I was like, they were like, nobody said they, they said they didn't nap. And we don't think anyone lied.

[C]

I was like, I, I, I, I, I, I believe you rise are intense.

[D]

Yeah. Yeah. Feels like a strange place to take a nap. And I want to also say that the patients who were part of this. Yeah, they called them patients. Sorry, just interesting use of terminology there. Fulfilled the DSM criteria for childhood and current ADHD diagnoses. So this was not a. Do you think you have adhd? Pop your hand up and we'll pop you in an if MRI study, which some of them are. So I just wanted to make that clear.

[C]

Mm. And yeah, so they were looking like, hey, does the. Does this medication actually produce this anti correlation that is supported in adhd? So, meaning that does. And they're specifically here looking at. Does the. When we're doing a task, do we see a reduction in our default mode network when we're taking this medication and they're specifically looking at this one because those are our external ADHD symptoms of daydreaming while someone's. While we're trying to do something else? I'm very interested in the other way the correlation goes, but there is not a lot on whether the. On how when you're trying to relax, how the Task Positive network is still going on, I find that to be awful.

[D]

Yeah, they're not that interested.

[C]

Take a nap.

[D]

This feels like the, the medication holiday conversation that we've had in previous things all over again. Like, we're not that interested in what you're doing with your spare time and your fun time and how that's affecting your brain, but we mostly want to know how you're getting tasks done.

[C]

Yeah, but, yeah, so they were looking at this effect and whether the medication worked and they. Well, not as interesting for us. It was effective in having some reduction there. And I mean that. I think the more important result here is that it is showing that, hey, not only does this correlation exist, this is a function of ADHD symptoms and it can be reduced.

[D]

I think that was the thing that really, like, if it was just about the medication, I don't know if I would have pulled a paper from 2015. But the fact that they were able to show, especially back then, I think, you know, we've developed, we've got more stuff now. If MRIs are different, for starters, the fact that they were able to showcase that there is a very specific difference in the way your brain works when you're ADHD is so interesting because for a lot of people it just feels like a personal thing, like one of the, one of the systems that I teach. And actually if you Message Me Task 2025, we'll give you this paper, we'll give you the GBT that takes you through the Step into Focus routine to help you with this is specifically designed for this network. And one of the biggest problems I have is getting people to start it because they think they should just be white knuckling. Like number one problem people are like, it's just adherence to a process that's different from what you were taught because it feels like surely my brain is working like everyone else's and I'm just a bad person. And these papers really help to, to change that narrative.

[C]

Yeah. I mean, I remember in college I would go to the library to try and force myself to get through whatever I was working on and be like, I'm going to go there for eight hours and it doesn't matter how long it takes, I'll just get through writing this, I'll get through reading this. And that was such a bad strategy. Especially with like this kind of paper. It's like, yeah, you, you needed to do something different. You needed to do something different with your brain to get it to activate in the ways that you wanted it to.

[D]

Exactly, exactly. And there's a few things we need to do. I think the way to describe it is like, it's not an automatic switch. It's more like a clunky old dial that we have to turn. Hand crank, if you will, you know, to try and actually get into the zone of doing work. And yeah, the fact that they found that, you know, they were displaying this relationship, you know, and they can use the word causal, they have a lot more ability to make those kinds of. Those kinds of statements because of how much they did. The placebo, the randomized control, the fact that people didn't know what they were taking, all of that kind of stuff just gives us more ability to. To, I guess, feel confident when we're going into a situation where we have ADHD to say, hey, I work differently and I need different things. I might need more stimulation while I'm working or less stimulation or whatever it is to try and get to the levels that help me. Because my, my networks aren't just going to turn off and on.

[C]

I mean, this has got my, my fidget here, which is for whatever I'm on. I gotta have something to do with my hands because they're gonna be. They. They need that little bit of extra stimulation. And I do think this is also the, the opposite is true, is we need. When we're trying to relax, we also need a little bit of stimulation to deal with the task. Positive network part of things, I think, like watching tv, you know, having a fidget, sitting there, doing something so that I'm not, you know, going on my phone constantly and I'm not watching. I'm not paying attention to the tv, I'm not really paying attention to my phone and I'm not having a good time.

[D]

Yeah. Yeah, that's so true. I've worked with a lot of clients where we've ended up, you know, like they take up knitting or something like that because they need something to do. And, and this actually comes up a lot with family because people are talking about. I feel really bad because I want to spend time with my family, especially, you know, going into holidays. I want to be present for my family. But I actually do need a little bit higher stimulation than just staring at my child who's playing a game that is so interesting for five minutes. And then it's. Maybe we should put some music in the background, you know, just like little shifts that you can do. Yeah.

[C]

Or if you're dealing with that ADHD child and you're trying to play a board game and they're getting up and going to the other room and stuff like, oh, maybe they just need a fidget with them to kind of help focus them on what is present.

[D]

Yeah. And it's nice that when we have these conversations, we can say, oh, and also, by the way, the reason we're having these conversations is because of these papers that are showing this stuff, even if they're doing it for medication, which is obviously, you know, great if you, if you need it. But more than that, for everybody having the, having the papers showing the brain differences, I cannot get enough of those papers personally.

[C]

Yeah, absolutely. It's one thing to understand that your ADHD brain works differently. Just be like, oh yeah, I do things differently. And there's another thing to be like, here is how it works differently. And because of that, there are specific things we can do.

[D]

Hello. So you were just listening to a research recap. I'm Skye Waterson of Unconventional Organization. If you like that, there's lots more information about ADHD and support for you at unconventionalorganization.com you can go ahead and check that out. Lots of free resources, lots of strategies. And if you want to join our programs, you can do that as well. And we'll see you there. Unconventional Organization.

[B]

WSECU isn't just one of Washington's best credit unions. We're a Forbes Best in State five years running. Why? Because we put you first. Lower fees, early paydays, financial guidance and service second to none. As a member owned cooperative, we love Washington as much as you do. From the Olympic mountains to the rolling Palouse. Join us and discover how much we care about your financial wellbeing. Because what we really do best is invest in you. Visit wsecu. Org today to learn more. Washington let's credit union.