By Dr. Ryan, Neely, PhD
Elemind worked for 76% of clinical trial participants. Why not for the other 24%?
In Elemind’s clinical trial, 76% of participants saw a reduction in the time it took them to fall asleep. Future studies will increase our sample size to gain better confidence in this value and learn how we might increase it. However, an interesting question is: What happened in the other 24%? Why didn’t Elemind work for everyone? Attempting to answer this question is a great way to improve our understanding behind the mechanisms of acoustic neuromodulation, interpersonal differences in brain function, and the complex spectrum of reasons why people have trouble falling asleep.
Individual responses to drugs: it’s all about molecules
In the case of most drugs, but certainly in the case of sleep aids, the therapeutic and side effect profile will differ greatly across individuals. For example, a recent meta-analysis reported that 24% of users experienced short-term improvement in sleep symptoms when using Zolpidem (Ambien), and 48% experienced adverse events1. Compare this to Melatonin, which improved symptoms in 18% of participants and caused adverse events in 42%, according to the same study. Why might a therapeutic help one person fall asleep, but cause nausea in someone else? In the case of drugs, which are typically molecules that are introduced into the body, a big factor influencing their effectiveness is metabolism. Drugs are broken down or transformed by specialized proteins known as enzymes, many of which are found in the liver. Due to genetic differences that affect the structure and function of these enzymes, different individuals may be better or worse at breaking down certain drugs, meaning they’ll last for different durations in the body. The presence of other medications and even certain foods can also impact drug function - for example by occupying the active sites on enzymes or by interacting with the drug molecule itself. Finally, drugs are usually designed to act on biological targets in the body - for example a drug could bind a particular receptor on the surface of a cell that triggers a change in how the cell functions. Individual differences, which could be genetic or related to health status, can influence the number of available receptors for a drug to bind, which can make its effects more or less potent.
Individual responses to neuromodulation: a moving target
In the case of neuromodulation, including electrical stimulation or acoustic stimulation (such as the type used by Elemind), there are no molecules involved to bind receptors or be metabolized. The ability to directly affect the activity of the nervous system without relying on molecules may contribute to the superior efficacy of treatments like deep brain stimulation relative to pharmaceuticals2, especially because the blood-brain barrier prevents many larger molecules from entering the brain at all. However, individual differences still play a role in how neuromodulation impacts the function of the nervous system. Although most people’s brains are constructed with the same general structure dictated by the genetic code, neural tissue is incredibly plastic and the circuits and synapses that underlie cognition are continually being remodeled by our experiences and interactions with the world. Even the neural responses to the same visual stimuli can change over time3, reflecting the continual dynamic changes that occur in the brain every day. This means that even within the same individual, stimulating the same group of neurons can have different effects depending on the day, external context, and cognitive or emotional state of the individual. When considering how neuromodulation may affect individuals differently, we need consider macrostructural differences such as differences in the size and composition of different brain regions, but also microstructural differences, like how particular brain circuitry may have been wired based on an individual’s life experience and personal development. Finally, it’s also important to consider the internal and external context in which the neuromodulation is being delivered. The presence of different environmental stimuli and especially the state of the individual (are they hungry, stressed, angry, etc) can have significant influences on brain activity, and therefore can also influence the response of the brain to neuromodulation.
Factors that may impact the efficacy of Elemind
To return to our original question, what may have influenced the difference in efficacy for participants in our clinical trial? As stated above, the acoustic neuromodulation used by Elemind will likely have had different effects on participants’ brains depending on the macro- and microstructure of their brain, and also the context in which they were using the device. In the case of our particular study, there are additional specific elements to consider:
- The strength and location of alpha generators: Elemind is designed to target alpha frequency oscillations detected from locations on the front of the scalp. Across our test population, we saw significant differences in the strength of alpha oscillations across individuals. Even among Elemind employees, we’ve noticed that some individuals generate consistently strong alpha oscillations at the electrode locations, while others have alpha that is barely detectable. This is likely a consequence of structural and functional differences across individuals, including the location of alpha generators in different brains. Alpha oscillations are not generated by one single source, but are instead generated by many different brain regions (in fact, alpha is thought to be one frequency that different brain regions use to coordinate their activity). These differences may result in Elemind’s headband tracking alpha oscillations generated by different neural populations in different individuals, which may have contributed to the range of observed effect sizes.
- The unique causes of sleep disturbances in different individuals: Difficulties initiating sleep can be due to a wide variety of reasons. For example, one individual may have difficulty falling asleep due to circadian rhythm dysfunction, a mismatch between the body’s internal clock and the time zone in which they live. Another individual may be experiencing insomnia due to cortical hyper-arousal, while a third individual may have chronic pain that keeps them awake. Elemind targets alpha oscillations which are more commonly associated with the hyper-arousal states that contribute to insomnia4,5, which means that our approach may not be as applicable to other causes of prolonged sleep onset.
- External factors, such as the sleep environment or device use: Finally, because our study was conducted with participants using Elemind in their own homes, there were a number of factors that were not possible to monitor or control. For example, some individuals may have been disturbed by excessive light or sound during the testing week compared to the sham week that impacted their sleep. Or, they may have used Elemind improperly. Testing the device in participants’ own homes allowed us to gain a sense of real-world efficacy, but also meant that certain elements of the study were beyond our control.
How to improve the chances that Elemind will work for you
It’s not possible to change the macrostructure of your brain, but it is possible to control some elements that will improve the chances that Elemind will improve your sleep. Here are a few tips that can improve your experience:
- Practice good sleep hygiene. When you’re ready to sleep, keep noise, light, and distractions to a minimum. Avoid browsing the internet or watching TV while attempting to fall asleep, and keep a consistent bedtime and bedtime routine.
- Help Elemind lock on to your alpha oscillations. Elemind works by measuring and delivering sound pulses intended to interact with the moment-by-moment phase of your alpha oscillations. To do this effectively, the headband needs to get a good reading of your brain activity. To facilitate this, begin wearing the band (without turning it on) several minutes before you intend to start your session. This allows the electrodes to warm up to your skin, which can improve the signal you get at the beginning of the night. Additionally, wait to start your session until you are ready to close your eyes. Alpha oscillations are usually only detectable when your eyes are closed.
- Choose the volume that’s right for you. Elemind’s sound stimulation will work as long as you can hear it, so choose the lowest perceptible volume that you can still hear. Increasing the volume beyond this point won’t make the stimulation any more effective, and if it’s too loud it might keep you awake. Keeping the volume low (but audible) will maximize the performance of your Elemind band.
Although we can’t guarantee that Elemind will work for everyone, these tips will help you get the best performance from your device. As we continue to collect data on all of the different brains we encounter, we’ll continue to update our algorithms to better personalize and fine-tune our stimulation to improve the performance of Elemind for all of our users.
Works Cited
1De Crescenzo, F., D'Alò, G.L., Ostinelli, E.G., Ciabattini, M., Di Franco, V., Watanabe, N., Kurtulmus, A., Tomlinson, A., Mitrova, Z., Foti, F. and Del Giovane, C., 2022. Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and network meta-analysis. The Lancet, 400(10347), pp.170-184.
2Pouratian, N., Thakkar, S., Kim, W. and Bronstein, J.M., 2012. Deep brain stimulation for the treatment of Parkinson’s disease: efficacy and safety. Degenerative neurological and neuromuscular disease, pp.107-117.
3Marks, T.D. and Goard, M.J., 2021. Stimulus-dependent representational drift in primary visual cortex. Nature communications, 12(1), p.5169.
4Zhao, W. et al. EEG spectral analysis in insomnia disorder: A systematic review and meta
analysis. Sleep Med. Rev. 59, 101457 (2021).
5Riedner, B. A. et al. Regional Patterns of Elevated Alpha and High-Frequency
Electroencephalographic Activity during Nonrapid Eye Movement Sleep in Chronic
Insomnia: A Pilot Study. Sleep 39, 801–812 (2016).