Talking Sleep

In this episode of Talking Sleep, host Dr. Seema Khosla welcomes Dr. Carrie Mahoney, a neuroscientist and faculty member in the Department of Neurology at Harvard Medical School and Beth Israel Deaconess Medical Center, to discuss her groundbreaking research on how oxytocin may regulate social cataplexy in narcolepsy.

With FDA approval of new narcolepsy medications, understanding the neural mechanisms underlying cataplexy has never been more clinically relevant. Dr. Mahoney's research began with a simple but profound clinical observation: cataplexy attacks occurred reliably when patients laughed with close friends and family members, but rarely when joking with coworkers or strangers. This pattern of emotion-triggered muscle weakness in social contexts prompted investigation into whether oxytocin—the hormone associated with bonding and social connection—might play a role.

Dr. Mahoney explains social cataplexy and discusses whether most cataplexy episodes occur in social contexts. She traces how she came to hypothesize oxytocin's involvement, moving from clinical observation to basic science investigation. The research explores how the amygdala—typically associated with fear—also processes other emotional responses including the joy and bonding feelings that characterize close relationships.

The episode walks through her research methodology. Using orexin knock-out mice (which model narcolepsy), Dr. Mahoney observed increased cataplexy during social interactions. She then systematically investigated oxytocin signaling in the amygdala to understand the mechanism. She employed advanced neuroscience techniques including chemogenetics and optogenetics—tools that allow precise manipulation and observation of specific neural circuits. The conversation clarifies what these approaches reveal about oxytocin's role in triggering muscle atonia during emotional social situations.

A crucial ethical question emerges: If oxytocin facilitates social bonding but also triggers cataplexy, would blocking oxytocin eliminate this important neurochemical? Dr. Mahoney addresses whether targeted intervention might be possible without sacrificing the neurochemical foundation of human connection and social behavior.

The research faced significant setbacks during COVID-19, affecting experimental timelines and animal studies. Dr. Mahoney discusses how she navigated these disruptions and the collaborative nature of validating complex neuroscience findings. She co-published this work with John Peever, highlighting how competitive yet collaborative the field must be to advance understanding.

An intriguing comparison emerges: Just as AI models solving previously unsolved math problems require human validation, complex neuroscience discoveries need replication and independent confirmation. Dr. Mahoney explains how her research will be validated and what the competitive landscape looks like in basic sleep neuroscience.

The ultimate goal is translation to clinical benefit. Would oxytocin-targeted therapy be preventive medication taken before social events, or a daily medication to modulate cataplexy susceptibility? Dr. Mahoney discusses how she communicates detailed scientific findings to patients and clinicians in understandable language, acknowledging the collaboration with science communicators like Kara Weaver.

Her research extends beyond cataplexy—orexin knock-out mice are also being used to investigate menopause-related sleep changes, suggesting broader applications of her findings.

Whether you're interested in narcolepsy pathophysiology, basic neuroscience approaches to understanding sleep disorders, or how fundamental research translates to clinical treatments, this episode illuminates the meticulous work underlying next-generation narcolepsy therapies.

Join us for this fascinating discussion about how curiosity-driven neuroscience research may transform how we treat cataplexy and understand the biology of narcolepsy.

In this episode of Talking Sleep, host Dr. Seema Khosla welcomes three patient advocates who are reshaping how sleep medicine is practiced and funded. Matt Horsnell, living with two sleep disorders and active as an author and panelist; Emma Cooksey, a patient-advocate and host of the Sleep Apnea Stories podcast; and Julie Flygare, a lawyer, author, and founder of Project Sleep, share their transformative advocacy work.

While clinicians often think of advocacy as writing letters or making donations, these three demonstrate that patient advocacy encompasses far more complexity and impact. They explain the multiple dimensions of advocacy work: legislative advocacy that influences policy and funding, educational advocacy that raises awareness and understanding, and research advocacy that shapes the scientific agenda.

The conversation begins with personal stories—what brought each advocate to this work and how living with sleep disorders motivated their commitment to systemic change. Matt shares insights as someone navigating two sleep conditions, while Emma and Julie discuss how legal training informed their approaches to advocacy and systems change.

Legislative advocacy receives detailed exploration. The guests explain how patient voices influence congressional action, regulatory decisions, and funding priorities. They discuss educational advocacy—raising public awareness, changing misconceptions, and helping people recognize sleep disorders they might otherwise dismiss or normalize.

Project Sleep, Julie's organization, serves as a centerpiece for discussion. While Project Sleep doesn't fund research directly, the conversation addresses which organizations do fund sleep medicine research and how clinicians and patients can access federal funding mechanisms. The guests provide insights into how disease-specific organizations like Wake-up Narcolepsy secure funding and the lessons applicable to sleep medicine more broadly.

Project Sleep's helpline receives attention—what it offers, who it serves, and the critical challenge of sustainability when grant funding ends. The guests discuss Rising Voices, an initiative amplifying patient narratives and lived experience in policy and clinical discussions.

A particularly valuable discussion addresses how clinicians can meaningfully engage with patient advocacy. Is this space exclusively for people living with sleep disorders, or can healthcare providers contribute? The conversation explores collaboration opportunities without appropriating patient voices or experiences.

The guests address practical questions: How do you sustain advocacy work without becoming discouraged? What does advocacy look like at local versus federal levels? What's on the wish list for sleep medicine advocacy? A recurring theme emerges: sustained funding remains elusive despite growing recognition of sleep disorders' impact on public health.

The episode acknowledges that patients bring irreplaceable perspectives to clinical practice, research prioritization, and policy development. Their lived experience of navigating diagnoses, treatments, and healthcare systems provides insights clinicians cannot access through clinical practice alone.

Whether you're interested in supporting patient-led advocacy, seeking to collaborate with patient organizations, curious about how to engage in legislative efforts, or simply wanting to understand the power of patient voices in healthcare transformation, this episode provides essential perspectives and practical guidance.

Join us for this important conversation with patient advocates who are leading meaningful change in sleep medicine.

Episode Correction: During the audio recording, federal funding for circadian research was misspoken as $60 Million. The correct amount is $600 Million.

Project Sleep Links

https://project-sleep.com/

https://www.instagram.com/project_sleep/

https://www.facebook.com/ProjectSleepAwareness/

https://www.linkedin.com/company/project-sleep/

https://www.youtube.com/user/projectsleepvideos

 

Get Project Sleep’s Print Resources Sent to Your Door!

https://project-sleep.com/sleep-info/sleep-resources/#request

 

In this episode of Talking Sleep, host Dr. Seema Khosla welcomes Dr. Sahil Chopra to discuss research challenging a fundamental assumption: that residual AHI measurements from PAP device downloads accurately reflect whether patients' sleep apnea is adequately treated.

Sleep medicine clinicians routinely rely on residual AHI from PAP downloads to determine treatment success, typically targeting an AHI under 5. But what if this metric significantly underestimates untreated sleep apnea? Dr. Chopra's study comparing PAP-determined residual AHIs to cardiopulmonary coupling (CPC)-derived AHIs reveals striking discrepancies: mean residual AHI was 2.4 via PAP download versus 12.1 via objective testing. Even more concerning, 85% of nights showing residual AHI under 5 on PAP downloads had elevated AHI based on objective CPC measurement.

Dr. Chopra explains why he chose cardiopulmonary coupling as the comparator metric, using a PPG-based wearable ring worn for 7-10 nights. He clarifies why PAP devices may systematically underestimate residual disease through mask leak, unstable breathing, and periodic breathing patterns.

A particularly concerning finding involves residual hypoxia. Dr. Chopra discovered significant hypoxic burden in many patients considered "well-treated" by PAP standards—important since hypoxic burden, not just AHI, drives cardiovascular risk.

Dr. Chopra's conclusion isn't that PAP-derived AHI is "bad"—rather, that it shouldn't be the sole metric for assessing treatment efficacy. Even patients with good symptoms may have significant residual respiratory events and hypoxia that PAP downloads fail to detect.

Clinical applications are discussed, including when to pursue objective testing and what interventions to consider when objective testing reveals inadequate control despite acceptable AHI.

Whether you rely on PAP downloads to assess treatment efficacy, manage patients with residual symptoms, or seek emerging objective metrics, this episode provides essential perspectives on optimizing PAP therapy.

Join us for this important discussion that challenges current assumptions about measuring treatment success in sleep apnea.

In this episode of Talking Sleep, host Dr. Seema Khosla welcomes Dr. Andrea Matsumura, a sleep physician with specialized certification in menopause medicine and national advisor for Monarch MD, to discuss how sleep clinicians can better support patients struggling with perimenopausal sleep disturbances.

Since the FDA removed the black box warning on hormone replacement therapy, more patients are inquiring about medications to treat perimenopausal sleep symptoms. Dr. Matsumura, who left traditional practice to pursue menopause certification and now works at the intersection of sleep medicine, mental health, and women's midlife health, provides practical guidance on this increasingly important clinical area.

The conversation begins with Dr. Matsumura's career evolution. After training as an internist with a leadership role at Kaiser Permanente and practicing sleep medicine in a group setting, she pursued specialized menopause certification—a credentialing process explained in detail. Dr. Matsumura discusses what menopause certification encompasses, who can pursue it, and her own path into this specialty. She also discusses her work developing specialized supplements for perimenopausal sleep support.

The episode systematically addresses how perimenopause disrupts sleep. Rather than focusing solely on hot flashes, Dr. Matsumura explains the full spectrum of sleep-related changes. She clarifies the timeline of perimenopause—when it starts and ends—and discusses less commonly recognized phenomena like menstrual hypersomnia that clinicians may not immediately associate with menopause.

A critical discussion addresses patient expectations around hormone replacement therapy. Many patients expect sleep clinicians to prescribe HRT, which raises legitimate concerns for providers unfamiliar with menopause management. Dr. Matsumura provides practical guidance on these conversations and clarifies the role of hormone level testing—addressing the debate between treating symptoms versus checking levels before initiating therapy.

The conversation explores the complex relationship between sleep apnea and menopause. Dr. Matsumura explains why and how obstructive sleep apnea may worsen during perimenopause, how to have these conversations with patients, and when referral to OBGYN colleagues is appropriate for collaborative care.

Additional topics include the role of hypnotics in perimenopausal sleep disorders, absolute contraindications to hormone replacement therapy, how to initiate HRT when appropriate, and whether restless leg syndrome worsens with perimenopause.

Dr. Matsumura addresses common misconceptions about menopause and sleep, helping clinicians understand what practitioners and patients frequently get wrong about this life stage. The episode emphasizes that sleep medicine clinicians don't need to become menopause specialists, but understanding these connections enables better patient care and appropriate referrals.

Join us for this important conversation about supporting women's sleep health through midlife transitions.