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

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

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.

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.

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])

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

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.

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.

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.

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)

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

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.

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