humanOS Radio

Insomnia is a uniquely vexing medical problem. It is the most common sleep-related issue, thought to affect around 10-40% of the population in the US. So it is a challenge that affects a whole lot of us. Yet despite its prevalence, treatments for the condition are lackluster at best. Why is this the case? Perhaps because it remains poorly understood. Insomnia has been known and documented for thousands of years, but it has proven to be difficult to study for a number of reasons. It’s hard to develop good animal models for the condition, it’s difficult to objectively define, and symptoms manifest quite differently in individuals. In order to address a complex disorder like insomnia, we need to get to the root cause. Generally speaking, it seems clear that the origin lies within the brain. This has compelled some very clever researchers to take snapshots inside the heads of patients with insomnia (via positron emission tomography, or PET), and compare them to normal controls. The results of such studies have been enlightening. And that brings me to our guest for this episode. In this episode of humanOS Radio, Dan speaks with Eric Nofzinger. Dr. Nofzinger has spent more than 35 years practicing sleep medicine and studying the neurobiology of insomnia at the University of Pittsburgh School of Medicine. As a researcher at Pittsburgh, Dr. Nofzinger frequently interacted with patients with insomnia. They would often attribute their inability to sleep to a “racing mind.” If you’ve ever had trouble falling asleep due to incessant rumination, that characterization probably sounds pretty relatable. Furthermore, they would often claim to have hardly slept at all, even when polysomnography showed that they had experienced normal sleep. He, along with other scientists in the field, suspected that there was a biological basis for these commonly reported complaints. To gain meaningful insight into what was going on, he couldn’t just look at sleep patterns - he needed to look inside the brain. To that end, he started conducting functional imaging studies on patients with insomnia to examine patterns of brain activity and metabolism during sleep. In one such trial, subjects completed regional cerebral glucose metabolic assessments while awake and while asleep using the FDG PET method. These scans were telling. During normal healthy sleep, there are typically substantial reductions in brain activity, particularly in the frontal cortex. But imaging for individuals with insomnia painted a very different picture. Their brains remained comparatively active during sleep, particularly in the frontal cortex, and they exhibited greater cerebral glucose metabolism during sleep and while awake. So, when these people claimed that their minds were racing throughout the night - when their brains should have been resting - that was actually a remarkably accurate assessment. These kinds of studies demonstrate that insomnia is, in essence, a disorder of hyperarousal of the brain. With this revelation, what can be done to slow down the racing mind? Cooling it down. It has been known for some time that application of a cooling stimulus to the head can lower the brain temperature in the underlying cortex, and in turn reduce brain metabolism. This insight led to the development of Ebb, a sleep therapy unlike any other that has yet been invented. Here’s how it works: the device is comprised of a headband attached to a bedside unit. Cold fluid circulates through the forehead pad from the bedside unit, keeping your forehead at a cool temperature throughout the night. In this way, Nofzinger and his colleagues hope to target the root cause of insomnia, calming the mind and body. To learn more about Ebb and Dr. Nofzinger’s research, check out the interview!

On this episode of humanOS Radio, Dan welcomes Nicola Bondonno to the show. Her research has been examining the effects of bioactive compounds occurring naturally in plant-based foods and beverages, and how they are linked to the cardiovascular health benefits associated with a plant-rich diet. It has become axiomatic that fruits and vegetables are protective against disease. Humans have intuitively recognized the link between edible plants and health for thousands of years. However, it is only very recently in our history as a species that we have been able to identify these benefits through empirical methods. Over the past decades, countless scientific studies have investigated the relationship between consumption of fruits and vegetables and human health and disease, and compelling evidence has emerged. But why specifically are plant foods so good for you? What exactly makes them special? We now believe that biologically active constituents within plants are in large part responsible for their disease-fighting power. Nicola’s own work has zeroed in on the health-promoting effects of flavonoids, a large class of polyphenolic compounds found in fruits and vegetables. They carry out a variety of important functions in plants, and they affect our bodies as well when we eat them. Just as one example, flavonoids have been shown to enhance bioavailability of nitric oxide, a molecule that regulates vascular tone. Specifically, nitric oxide relaxes the walls of blood vessels, which in turn reduces blood pressure and improves blood flow. With respect to cardiovascular health, you can imagine that this would be a very good thing. In a recent study, Nicky and her team analyzed data from the Danish Diet, Cancer and Health cohort. This study assessed the diets of 53048 middle-aged Danish residents over the course of up to 23 years. The researchers estimated the flavonoid content of the foods and beverages that these subjects reported consuming, and compared this dietary intake to the medical outcomes and cause of death (if applicable) of the participants. From this data, a number of important questions could be addressed: Did flavonoid intake affect mortality, when adjusting for other potential confounders? What dose of flavonoids is required for benefits to be achieved? Are certain subclasses of flavonoids responsible for observed benefits? And do flavonoids have different effects in individuals who drink or smoke? To hear what they found, and to learn more about dietary flavonoids and their role in health and disease, please check out the interview!

On this episode of humanOS Radio, Dan welcomes Daniel Gartenberg to the show. Dan has dedicated his life to helping people sleep better (a calling that we here at humanOS can certainly relate to). Daniel has a Ph.D in Human Factors and Applied Cognition from George Mason University, and is an adjunct assistant professor at Penn State University. He has conducted grant-funded research from the National Science Foundation and the National Institute of Aging to develop sound environments that can diagnose and treat sleep disorders, improve sleep quality, and optimize daytime alertness. He has also developed several mobile sleep apps, such as the Sonic Sleep Coach, which provides personalized sleep feedback and sounds that are designed to modulate sleep quality. His current research is focused upon accurately tracking sleep quality through wearable technology. But he doesn’t just want to measure it, he wants to make it better. Dan is particularly interested in using technology to enhance slow wave sleep (also known as deep sleep), which we have addressed previously on this show, through temperature, light, and sound. He delivered an excellent TED talk that explains how stimulating deep sleep can help us learn and consolidate memories, regenerate our tissues, and generally make us healthier and more productive. In this interview, the two Dans discuss how sleep is studied in a clinical study, how sleep monitoring devices have advanced over the past ten years, potential pitfalls in how these devices are used, ways to augment deep sleep and REM sleep, and much more. To learn about the future of consumer technology and sleep enhancement, check out the podcast!

In this episode of humanOS Radio, Dan speaks with Sander Kooijman. Sander is a post-doctoral researcher at Leiden University Medical Center, where he is investigating brown adipose tissue activation as a therapeutic target to attenuate obesity, type 2 diabetes, and atherosclerosis in humans. He and his colleagues recently published a paper examining how light exposure and environmental temperature affect measures of glucose and lipid metabolism in two large population-based European cohorts. It is well established that exposure to bright light at night is linked to metabolic perturbations. A number of studies have found positive associations between artificial light exposure in the evening and risk of type 2 diabetes. In particular, one experiment from Phyllis Zee’s lab at Northwestern showed that just a single night of blue light exposure during sleep increased insulin resistance in healthy adults. But what about bright light during the day? Now that’s a different story altogether. Observational evidence suggests that light exposure - particularly sun exposure - may in fact be beneficial for glucose metabolism. For example, a cohort study found that participants who received a lot of sunlight exposure during the day had a 30% lower risk of developing type 2 diabetes, compared to those who didn’t get much sun. In the study discussed on this show, the researchers collected data from a combined cohort of more than 10,000 healthy middle-aged subjects enrolled in the Oxford Biobank study (OBB) and the Netherlands Epidemiology of Obesity study (NEO). Participants in these studies have provided body composition measurements (weight, body mass index, body fat percentage) as well as bloodwork (fasting glucose, insulin, fasting lipid concentrations, insulin resistance, etc). However, these studies do not assess temperature or light exposure. To capture the impact of these variables, Sander and his team very cleverly collected data on mean outdoor temperature and hours of bright sunlight (defined as global radiation >120 W/m2) from local weather stations. From this information, they were able to calculate mean outdoor temperature and bright sunlight duration during a 7-day and 30-day period before the date of blood sampling. Sure enough, increased bright sunlight exposure was found to be associated with lower fasting insulin (−1.27% per extra hour of bright sunlight), lower triglyceride levels (−1.28%), and reduced insulin resistance (HOMA-IR; −1.36%). After adjustment for bright sunlight, there was no association between outdoor temperature and measures of glucose and lipid metabolism, suggesting that it was indeed the light that was responsible here. But why? What mechanisms mediate this relationship? To find out why Sander thinks bright sunlight might enhance cardiometabolic health, and more about his fascinating work, check out the podcast!

Pamela Maher, a research scientist at the Salk Institute, delves into the neuroprotective powers of flavonoids like fisetin and facetin. She explains how these compounds can enhance nerve cell function and potentially combat neurodegenerative diseases by crossing the blood-brain barrier. The conversation also touches on the cognitive benefits of flavonoids for older populations, the challenges of achieving effective doses through diet, and the promising future of natural compounds in healthcare.

In this episode of humanOS Radio, Dan speaks with Javier Gonzalez. Dr. Gonzalez is a professor at the Department for Health at the University of Bath in the UK. He and his colleagues recently published a hypothesis suggesting that carbohydrate availability plays a key role in the regulation of energy balance, and explains both why exercise increases hunger and (paradoxically) why people who are highly active exhibit better appetite regulation. What do I mean by carbohydrate availability? Well, our storage capacity for carbohydrates is relatively minuscule, compared to fat stores - even on a very lean individual. These stored carbs can be depleted much faster, and several studies suggest that alterations in carbohydrate availability may be carefully monitored by the body. Importantly, physical activity alters carbohydrate availability by expending muscle glycogen. This may be why exercise has been shown to acutely lower fasting leptin concentrations. Reductions in carbohydrate availability resulting in a drop in leptin levels may explain, for instance, why individuals who utilize carbs faster during exercise seem to be more prone to increased appetite after exercise. But high physical activity levels - and accompanying high physical fitness - produces relevant changes in carbohydrate and fat metabolism, that might actually make them better able to rein in their appetite after a bout of exercise or after a larger-than-normal meal. To learn about these changes, and more about his fascinating hypothesis, check out the podcast!

We live in an era of unprecedented access to information. Technology has endowed us with the ability to immediately retrieve whatever we want to see or whatever we want to read, just by tapping on a screen a few times. Perhaps even more importantly, we have never had so much immediate access to one another, even when we are very far away. In turn, other people - as well as our devices - have the ability to reach out to us and seize our attention, literally 24 hours per day, seven days per week. But how does this relationship with technology affect our brains? Researchers are examining the impact of digital tools on how we think and perform, and the results are not entirely rosy. Much of this research has investigated what we commonly refer to as “multi-tasking.” You already know this implicitly: when you are rapidly switching between two different activities, typically your performance on both suffers. This area of research has also examined the impact of interrupted work, often in the form of digital notifications, like from email, text, or phone apps. You know how common this is, but you probably don’t realize the full impact. Studies that track employees have revealed that office workers who are interrupted take about 25 minutes to return to whatever task they were working on. And these interruptions take a significant toll on our well-being - research shows that these kinds of disruptions increase stress levels as well as impair productivity. In this show, Dan speaks with Professor Gloria Mark, who is in the department of informatics at UC Irvine, where she studies multi-tasking behavior in information workers, and technology use in disrupted environments. Her work examines how interaction with information technology affects attention, mood, and stress.

In this episode of humanOS Radio, Dan speaks with Scott Byrne. Scott is a professor at the University of Sydney School of Medicine. He is a cellular immunologist who is studying how the ultraviolet part of the solar spectrum activates regulatory pathways that result in immune suppression and tolerance. When Scott and his team were investigating skin cancer development in mice, they happened to notice that mice receiving ultraviolet radiation gained less weight than counterparts. These observations inspired Scott and his team to perform a series of experiments examining how regular exposure to physiologically relevant doses of solar ultraviolet radiation (like an amount that you could realistically get on a sunny day) influences weight gain and cardiovascular disease. And the findings were pretty eye-opening. To learn what they discovered, and more in general about the far-reaching effects of sun exposure on human health, check out this interview!

On this episode of humanOS Radio, Dan welcomes Pankaj Kapahi to the show. Pankaj is a professor at the Buck Institute, an independent biomedical research institute that is devoted solely to research on aging. He and his team have begun to investigate the role of advanced glycation end products (also known as AGEs) in the aging process. Advanced glycation end products are compounds that are formed when proteins or lipids become glycated, as a result of being exposed to sugars. This has been carefully studied and exploited by the food industry for decades, because of its appealing effects on sensory qualities of food. However, it was only recognized comparatively recently that AGEs may impair our health and function over time. Aptly enough, the formation and accumulation of AGEs is a hallmark of age. AGEs wreak havoc by binding with cell surface receptors and cross-linking with body proteins, altering their structure and function. This produces a range of deleterious effects throughout the body. So, how can we reduce our exposure to advanced glycation end products in the food that we eat? And how can we control the formation of AGEs inside the body? To learn more, check out the interview below!

On this episode of humanOS Radio, Dan speaks with Dan Siegel. Dr. Siegel is a clinical professor of psychiatry at the UCLA School of Medicine, and is the founding co-director of the Mindful Awareness Research Center at UCLA. He is a pioneer in a field known as interpersonal neurobiology (sometimes referred to as relational neuroscience). Interpersonal neurobiology characterizes human development and function as a product of interactions between the body, the mind, and relationships with one another. Dan is also the executive director of the Mindsight Institute, a unique educational organization that provides online learning and in-person lectures that examines the interface of human relationships and basic biological processes, with the goal of cultivating mindsight in individuals, families, and communities. So what exactly is mindsight? Mindsight is a theoretical construct that is related to theory of mind. However, mindsight goes beyond merely being able to conceive of one’s own mind and that of others. Mindsight refers to the capacity to sense patterns of shared communication of energy and information change within relationships. It also captures the ability to look inside ourselves, recognizing our own emotions, without being consumed by them. An illustration of this concept, commonly cited by Dr. Siegel, is the subtle difference between “I am sad,” as opposed to “I feel sad.” The latter implies recognition of a feeling you are experiencing in the moment - a state that isn’t permanent, and to which you can control your response. As you might imagine, mindsight and the intricacies of interpersonal neurobiology are very challenging concepts to understand and research, at least using the tools currently available to biologists and scientists, which is why Dr. Siegel’s work in this area is so valuable. To learn more, check out the interview!