May 26, 2021 | Vanessa B. Sanchez, PennNeuroKnow

Have you ever put on music to help you study? Or to calm you down after a stressful day? Maybe you’re scrolling on Youtube right now trying to figure out what to listen to next…Well, have you ever considered listening to binaural beats? 

What are binaural beats?

Binaural beats are a perceptual phenomenon (or illusion) that occurs when two different tones are presented separately to each ear¹. When these two tones are presented, you, the listener, perceive the difference between the sound waves entering the left and right ear^2-3. 

For example, if the left ear registers a tone at 400 Hz and the right ear registers one at 410 Hz, what you actually hear is halfway between the two tones: 405 Hz – the binaural beat (Figure 1) ^3,6.  Because your brain is trying to interpret these two frequencies, this binaural beat of 405 Hz is considered an illusory tone^3,6. Scientists from around the world have shown that in order for a binaural beat to occur, the difference between the two frequencies (e.g., 400 Hz – 410 Hz = 10 Hz) must be small (≤ 30 Hz)⁷. If the difference is not small ( 30 Hz), your ears will be able to capture the two tones separately and no binaural beat will be perceived⁶. Will you perceive a binaural beat if you listen to 10 Hz from both ears? No, because a binaural beat is the difference between the two frequencies, which is why it is considered an auditory phenomenon or illusory tone^3,4,6! 

 

 

 

How are binaural beats processed in the brain?

How your brain is processing these binaural beats is still not exactly clear. Some scientists believe the phenomenon of binaural beats is thought to occur through a process called interhemispheric coherence^3,9. Your brain can be divided up into two major parts: the left and the right hemisphere. In each hemisphere lies a region called the auditory cortex, which is where and how auditory information (in this case binaural beats) gets processed. Normally, the sounds that your right and left auditory cortices are processing are very similar. When you listen to binaural beats, your auditory cortices become confused because they are trying to process the two different tones⁹. To solve this binaural puzzle, scientists believe that your auditory cortices communicate with each other more, and therefore become more synchronized⁹. 

Some scientists believe that this synchrony is associated with your brainwaves^1-10. Brain waves are electrical impulses that reflect how the neurons in your brain are communicating with each other¹⁰. These brain waves can occur at certain frequencies and can be either slow or fast. Your brain has five different types of brain waves that each fall within a certain range of frequencies. These types of brain waves represent what is called a brain state. For example, if your brain waves occur at high frequency (or what’s called the “gamma” or “beta” states), you are likely to be learning and deeply concentrated^4,10. Other brain waves at a slower frequency like “delta” and/or “theta” states are associated with sleep and relaxation^4,10. In between, are “alpha” states which are associated with reducing stress and positive thinking^4,10. Interestingly, some scientists believe that the frequency of sounds that the auditory cortex is processing can affect the frequency of your brain waves^4,6,8,10. So, if binaural beats are also in these lower frequencies like 4 – 8 Hz (theta state), it is thought that your brain waves will synchronize with these frequencies, which would then make you feel relaxed. 

Is this true?

Dentists think so…

Many of us have experienced the anxiety that comes with getting our wisdom teeth removed. In one study, some patients were lucky enough to be offered a chance to listen to binaural beats before surgery. If they agreed, they listened to binaural beats (9.3 Hz ~ theta waves) through stereo headsets for 10 minutes and during this time they were given a local anesthetic⁷. Those who chose not to listen were just given the local anesthetic and sat alone, in silence, for 10 minutes. To measure anxiety levels scientists used a visual analog scale (VAS) before and after the 10 minutes (where patients either sat in silence or listened to binaural beats).  You’ve probably seen a VAS at your local dentist’s office; it is just a line that represents a continuum of “no anxiety at all” to “worst anxiety imaginable” and can also be represented as 6 faces that go from a happy face (no anxiety) to a face with tears (worst anxiety)⁷. What scientists found was that those who chose not to listen to binaural beats leaned towards the right side of the spectrum: worst anxiety. Meanwhile, patients who originally reported high levels of anxiety and then listened to binaural beats (for 10 min) reported that their anxiety levels significantly decreased⁷. Remember, theta waves are associated with relaxation, so it is not surprisingly if these patients might have felt more relaxed after listening to binaural beats and reported lower anxiety levels. Overall, this interesting study suggests that listening to binaural beats can reduce anxiety levels in a variety of situations.  

Other interesting studies that have been conducted on binaural beats show that they help to improve cognition, focus, motivation, memory, and even confidence!⁹ With all this in mind, I would encourage you to check them out – you never know unless you try. Curious? My favorite binaural beat to help me focus is here.

References:

1. Oster, G. (1973). Auditory beats in the brain. Scientific American, 229(4), 94-103.
2. Lane, J. D., Kasian, S. J., Owens, J. E., & Marsh, G. R. (1998). Binaural auditory beats affect vigilance performance and mood. Physiology & behavior, 63(2), 249-252.
3. Garcia-Argibay, M., Santed, M. A., & Reales, J. M. (2019). Efficacy of binaural auditory beats in cognition, anxiety, and pain perception: a meta-analysis. Psychological Research, 83(2), 357-372.
4. Booth, S. (2019, May 14). This Is Your Brain on Binaural Beats. Retrieved March 25, 2021, from https://www.healthline.com/health-news/your-brain-on-binaural-beats
5. Lentz, J. J., He, Y., & Townsend, J. T. (2014). A new perspective on binaural integration using response time methodology: super capacity revealed in conditions of binaural masking release. Frontiers in Human Neuroscience, 8, 641.
6. Gao, X., Cao, H., Ming, D., Qi, H., Wang, X., Wang, X., … & Zhou, P. (2014). Analysis of EEG activity in response to binaural beats with different frequencies. International Journal of Psychophysiology, 94(3), 399-406.
7. Isik, B. K., Esen, A., Büyükerkmen, B., Kilinc, A., & Menziletoglu, D. (2017). Effectiveness of binaural beats in reducing preoperative dental anxiety. British Journal of Oral and Maxillofacial Surgery, 55(6), 571-574.
8. Solca, M., Mottaz, A., & Guggisberg, A. G. (2016). Binaural beats increase interhemispheric alpha-band coherence between auditory cortices. Hearing research, 332, 233-237.
9. Garcia-Argibay, M., Santed, M. A., & Reales, J. M. (2019). Binaural auditory beats affect long-term memory. Psychological research, 83(6), 1124-1136
10. Buskila, Y., Bellot-Saez, A., & Morley, J. W. (2019). Generating brain waves, the power of astrocytes. Frontiers in neuroscience, 13, 1125.

Cover image: Photo by Andrea Piacquadio from Pexels

Your generous Donations allow IAES to continue our important work and save lives!

Become an Advocate by sharing your story. It may result in accurate diagnosis for someone suffering right now who is yet to be correctly identified. Submit your story with two photos to IAES@autoimmune-encephalitis.org  

International Autoimmune Encephalitis Society (IAES), home of the AEWarrior®, is the only Family/Patient-centered organization that assists members from getting a diagnosis through to recovery and the many challenges experienced in their journey. Your donations are greatly appreciated and are the direct result of IAES’ ability to develop the first product in the world to address the needs of patients, Autoimmune Encephalitis Trivia Playing Cards. Every dollar raised allows us to raise awareness and personally help Patients, Families, and Caregivers through their Journey with AE to ensure that the best outcomes can be reached. Your contribution to our mission will help save lives and improve the quality of life for those impacted by AE.   For this interested in face masks, clothing, mugs, and other merchandise, check out our AE Warrior Store!  This online shop was born out of the desire for the AE patient to express their personal pride in fighting such a traumatic disease and the natural desire to spread awareness. Join our AE family and help us continue our mission to support patients, families and caregivers while they walk this difficult journey.  

Be a part of the solution by supporting IAES with a donation today.

April 14, 2021 | Sarah Reitz, PennNeuroKnow

Major depressive disorder, commonly called depression, is a disorder that affects more than 168 million people worldwide^1,2. Symptoms include depressed mood, lack of energy, loss of interest/pleasure, sleep disturbances, significant weight changes, and thoughts of suicide³. While depression can occur on its own, which is known as primary depression, it can also be caused by other diseases or medical conditions. This form of depression, called secondary depression, is relatively common in patients diagnosed with chronic illnesses, and is one of the key factors resulting in an impaired quality of life experienced by patients with chronic diseases⁴.

Research has shown that patients with autoimmune diseases involving the brain and spinal cord, such as multiple sclerosis (MS), Hashimoto encephalopathy, and autoimmune encephalitis (AE), are at increased risk for depression and other mood disorders^5,6. One study found that depressive symptoms occur in up to half of all patients with MS⁷, and another showed that prior hospitalization for an autoimmune disease increases the risk of developing a major mood disorder by 45%⁸. Some of this increase is likely a reaction to the diagnosis itself and the impairments caused by the disease. However, increased rates of depression are seen in MS patients up to 2 years before they are diagnosed with MS. These findings suggest that there is a biological link between autoimmune disease and depression that increases the risk of developing depression, independent of any reaction to the diagnosis or resulting lifestyle changes. ^9,10. Research over the last 2 decades supports this idea, with increasing evidence linking the immune system and inflammation to a number of psychiatric disorders, including depression.

A link between the immune system and depression?

One indicator that the immune system can affect mood and behavior is the phenomenon of cytokine-induced sickness behavior. During an illness, cells in the immune system release small proteins called cytokines to help regulate and synchronize the immune system’s response to an invading bacteria or virus. Some examples of cytokines include interleukins (IL), tumor necrosis factors (TNF), and interferons (IFN). This increase in cytokines leads to specific behaviors many of us have experienced before while sick, including decreased activity, loss of energy, and even depressed mood¹¹.

Based on the observation that increased cytokines during sickness can lead to depression-like symptoms, researchers began to examine cytokine levels in patients diagnosed with depression and other psychiatric disorders. Many studies have found that patients with depression, who were otherwise medically healthy, showed signs of immune system activation, with increased levels of IL-6 and, in some cases, TNF-alpha¹². Another study examined brain tissue from patients diagnosed with depression and found increased levels of many types of interleukins as well as IFN-gamma¹³. Additionally, mice treated with cytokines or drugs that increase levels of cytokines show depression-like behaviors, further linking the immune system and inflammatory response to depression¹⁴. This effect is also seen in humans, with one study finding that 17% of patients treated with IFN-alpha developed psychiatric side effects, including depression, and that these side effects improve once the cytokine treatment is stopped¹⁵.

Just as increases in cytokine levels are linked to an increased risk of depression, research suggests that decreasing cytokines and inflammation can improve depression symptoms. A number of antidepressant therapies, including selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, and even psychotherapy have anti-inflammatory effects, lowering levels of certain pro-inflammatory cytokines^16-19. Taking this even further, there is evidence that anti-inflammatory drugs can improve depression symptoms²⁰. However, anti-inflammatory treatments can sometimes interfere with the anti-depressant effects of SSRIs, so adding an anti-inflammatory drug (including drugs such as aspirin or ibuprofen) to a depression treatment plan should only be done after careful discussion with your doctor²¹.

Depression in autoimmune encephalitis

Given this link between immune system activation and depression, it is not altogether surprising that depression and other psychiatric symptoms are common in AE and other autoimmune disorders. For reasons that are still not understood, patients with autoimmune encephalitis with antibodies directed against cell surface antigens (especially anti-NMDA receptor encephalitis) are more likely to experience psychiatric symptoms compared to patients with antibodies directed against intracellular antigens (such as anti-Hu or anti-Ma encephalitis)²². In fact, between 65-80% of patients with anti-NMDA receptor encephalitis experience psychiatric symptoms, with depression being among the most common^23,24. This has also been demonstrated in a mouse model of AE, where mice received infusions of cerebrospinal fluid into their brains containing antibodies from patients with NMDA receptor encephalitis. As the anti-NMDA receptor antibodies attacked their NMDA receptors, the mice developed depressive-like behaviors and lost interest in things they had previously found pleasurable (in this case, a sugary drink). Once the infusions stopped and the NMDA receptor levels returned to normal, these depressive-like behaviors improved²⁵.

In NMDA receptor encephalitis, psychiatric symptoms often appear before any neurologic symptoms²⁶. As a result, it can be difficult to distinguish the initial phases of the disease from psychiatric disorders such as depression or schizophrenia. This leads many patients to assume they have a purely psychiatric disorder and to seek help from a psychiatrist first. One study found that this occurred in 76% of patients ultimately diagnosed with NMDA receptor encephalitis²⁷!

This becomes problematic when psychiatrists are not aware that early stages of autoimmune encephalitis can mimic psychiatric disorders. Rather than ordering antibody tests to examine a potential autoimmune disorder, they may assume the patient has major depressive disorder or another psychiatric disorder. Based on this assumption, they may attempt to treat the patient with anti-depressant therapies rather than treatments aimed at the underlying autoimmune condition. This is unfortunately not a hypothetical scenario. In a study examining a group of 464 people with NMDA receptor encephalitis, nearly 10% were initially diagnosed with a psychiatric disorder, including depression, before the correct diagnosis of NMDA receptor encephalitis was reached⁶.

A timely diagnosis is critical in treating autoimmune encephalitis, since earlier administration of immunotherapies is associated with better patient outcomes²⁸. A delay in a correct diagnosis and treatment plan can be especially harmful given that an estimated 10% of patients with NMDA receptor encephalitis experience suicidal thoughts²⁹. Luckily, as more is learned about AE, psychiatrists are becoming increasingly educated and aware of the psychiatric symptoms of the disease. An improved awareness of AE will allow for faster and more accurate diagnoses, leading to faster treatment and improved outcomes for patients suffering from this disease.

References

1. Kessler RC, Bromet EJ. The epidemiology of depression across cultures. Annu Rev Public Health. (2013) 34:119–38. doi: 10.1146/annurev-publhealth-031912-114409
2. Abajobir AA, et al. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. (2017) 390:1211–59. doi: 10.1016/S0140-6736(17)32154-2
3. American Psychiatric Association. Diagnostic and statistical manual of mental disorders (5^th ed.) (2013). doi: 10.1176/appi.books.9780890425596
4. Moussavi S, Chatterji S, Verdes E, Tandon A, Patel V, Ustun B. Depression, chronic diseases, and decrements in health: results from the World Health Surveys. Lancet. (2007) 370:851–8. doi: 10.1016/S0140-6736(07)61415-9
5. Pape K, Tamouza R, Leboyer M, Zipp F. Immunoneuropsychiatry – novel perspectives on brain disorders. Nat Rev Neurol (2019) 15(6):317–28. doi: 10.1038/s41582-019-0174-4
6. Al-Diwani A et al. The psychopathology of NMDAR-antibody encephalitis in adults: a systematic review and phenotypic analysis of individual patient data. Lancet Psychiatry (2019) 6(3):235–46. doi: 10.1016/S2215-0366(19)30001
7. Patten SB, Marrie RA, Carta MG. Depression in multiple sclerosis. Int Rev Psychiatry (2017) 29(5):463–72. doi: 10.1080/09540261.2017.1322555
8. Benros, M. E. et al. Autoimmune diseases and severe infections as risk factors for schizophrenia: a 30-year population-based register study. Am. J. Psychiatry (2011)168, 1303–1310.
9. Hoang H, Laursen B, Stenager EN, Stenager E. Psychiatric co-morbidity in multiple sclerosis: The risk of depression and anxiety before and after MS diagnosis. Mult Scler J. (2016) 22:347–53. doi: 10.1177/1352458515588973
10. Marrie RA et al. Rising incidence of psychiatric disorders before diagnosis of immune-mediated inflammatory disease. Epidemiol Psychiatr Sci. (2017) 28:333–42. doi: 10.1017/S2045796017000579
11. Kelley, K. W. et al. Cytokine-induced sickness behavior. Brain Behav. Immun. (2003) 17(Suppl. 1):112–118
12. Haapakoski, R., Mathieu, J., Ebmeier, K. P., Alenius, H. & Kivimaki, M. Cumulative meta-analysis of interleukins 6 and 1β, tumour necrosis factor α and C-reactive protein in patients with major depressive disorder. Brain Behav. Immun. (2015) 49, 206–215
13. Shelton RC, Claiborne J, Sidoryk-Wegrzynowicz M, Reddy R, Aschner M, Lewis DA, Mirnics K. Altered expression of genes involved in inflammation and apoptosis in frontal cortex in major depression. Mol Psychiatry (2011) 16:751–762
14. Fu X, Zunich SM, O’Connor JC, Kavelaars A, Dantzer R, Kelley KW. Central administration of lipopolysaccharide induces depressive-like behavior in vivo and activates brain indoleamine 2,3 dioxygenase in murine organotypic hippocampal slice cultures. J Neuroinflammation(2010) 7(43):1–12
15. Renault PF et al. Psychiatric complications of long-term interferon alfa therapy. Arch Intern Med. (1987) 147:1577–80. doi: 10.1001/archinte.1987.00370090055011
16. Mohr DC, Goodkin DE, Islar J, Hauser SL, Genain CP. Treatment of depression is associated with suppression of nonspecific and antigen-specific TH1 responses in multiple sclerosis. Arch Neurol. (2001) 58:1081. doi: 10.1001/archneur.58.7.1081
17. Ohgi Y, Futamura T, Kikuchi T, Hashimoto K. Effects of antidepressants on alternations in serum cytokines and depressive-like behavior in mice after lipopolysaccharide administration. Pharmacol Biochem Behav. (2013) 103:853–9. doi: 10.1016/j.pbb.2012.12.003
18. Hannestad J, Dellagioia N, Bloch M. The effect of antidepressant medication treatment on serum levels of inflammatory cytokines: a meta-analysis. Neuropsychopharmacology. (2011) 36:2452–9. doi: 10.1038/npp.2011.132
19. Ramirez K, Shea DT, Mckim DB, Reader BF, Sheridan JF. Imipramine attenuates neuroinflammatory signaling and reverses stress-induced social avoidance. Brain Behav Immun. (2015) 46:212–20. doi: 10.1016/j.bbi.2015.01.016
20. Kohler, O. et al. Effect of anti-inflammatory treatment on depression, depressive symptoms, and adverse effects: a systematic review and meta-analysis of randomized clinical trials. JAMA Psychiatry (2014) 71:1381–1391
21. Warner-Schmidt JL, Vanover KE, Chen EY, Marshall JJ, Greengard P. Antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) are attenuated by antiinflammatory drugs in mice and humans. Proc Natl Acad Sci USA. (2011) 108:9262–7. doi: 10.1073/pnas.1104836108
22. Hansen N and Timaus C. Autoimmune encephalitis with psychiatric features in adults: historical evolution and prospective challenge. J. Neural Transm. (2021) 128:1-14
23. Kruse JL et al. Psychiatric autoimmunity: N-methyl-D-aspartate receptor IgG and beyond. Psychosomatics. (2015) 56(3)227-241
24. Wang W, Zhang L, Chi XS, He L, Zhou D, Li JM. Psychiatric symptoms of patients with anti-NMDA receptor encephalitis. Front in Neurol.(2020) doi: 10.3389/fneur.2019.01330
25. Planaguma J et al. Human N-methyl-D-aspartate receptor antibodies alter memory and behaviour in mice. Brain 138(1):94-109
26. Dalmau J, Armangué T, Planagumà J, Radosevic M, Mannara F, Leypoldt F, Geis C, Lancaster E, Titulaer MJ, Rosenfeld MR, Graus F (2019) An update on anti-NMDA receptor encephalitis for neurologists and psychiatrists: mechanisms and models. Lancet Neurol 18:1045–1057
27. Dalmau J et al. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol., (2008) 1091-1098.
28. Titulaer MJ, et al. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol (2013)12:157-165.
29. Zhang L et al. Suicidality is a common and serious feature of anti-N-methyl-D-aspartate receptor encephalitis. J Neurol. (2017) 264(12):2378-2386.

Your generous Donations allow IAES to continue our important work and save lives!

Become an Advocate by sharing your story. It may result in accurate diagnosis for someone suffering right now who is yet to be correctly identified. Submit your story with two photos to IAES@autoimmune-encephalitis.org  

International Autoimmune Encephalitis Society (IAES), home of the AEWarrior®, is the only Family/Patient-centered organization that assists members from getting a diagnosis through to recovery and the many challenges experienced in their journey. Your donations are greatly appreciated and are the direct result of IAES’ ability to develop the first product in the world to address the needs of patients, Autoimmune Encephalitis Trivia Playing Cards. Every dollar raised allows us to raise awareness and personally help Patients, Families, and Caregivers through their Journey with AE to ensure that the best outcomes can be reached. Your contribution to our mission will help save lives and improve the quality of life for those impacted by AE.   For this interested in face masks, clothing, mugs, and other merchandise, check out our AE Warrior Store!  This online shop was born out of the desire for the AE patient to express their personal pride in fighting such a traumatic disease and the natural desire to spread awareness. Join our AE family and help us continue our mission to support patients, families and caregivers while they walk this difficult journey.  

Be a part of the solution by supporting IAES with a donation today.