The Neuroscience of NuCalm

36 years of patented neuroscience. NuCalm began in 1990. In 2009, NuCalm formed a 52-member medical advisory board of leading doctors, research scientists and academicians.

In the invention process we focused on 4 critical areas of the brain: the reticular activating system, the corpus callosum, the HPA axis, and the autonomic nervous system. To create effective neurobiofeedback within the complexities of the brain, we leveraged the auditory motor cortex, not just as a gateway for collecting auditory signals, but for its function in stimulating the prefrontal and frontal motor cortex. The brain is nonlinear, thus using proprietary, complex methods to present patterns that the brain won’t easily get bored with represents a significant challenge. The binaural signal processing, frequency-following-response neurobiofeedback is foundational to the software but cannot be the only effective elements. We also used specific techniques to evoke potential on a cellular level and increase electrical output focused on certain brain regions.

NuCalm 1.0 launched in 2009, NuCalm 2.0 in 2016, and NuCalm 3.0 in November 2021. The method of action has always been the neuroacoustic software. The clinical system also supported biochemistry using supplements and a stimulation device. After 12 years of constant innovation, we strengthened the neuroacoustic software to a place where we no longer needed biochemistry support. Now, it’s just the software.

A typical song file is about 5 MB. One NuCalm neuroacoustic program is over 1,536 MB, about 307 times the size of a song. U.S. Patent No. 9,079,030, issued July 14, 2015: “Systems and methods for balancing and maintaining the health of the human autonomic nervous system.” U.S. Patent No. 11,090,459, issued August 17, 2021: “Methods and devices for applying dynamic, non-linear oscillations and vibrations [to elicit a physiological state change in humans].”

Starting takes seconds: set your device to Do Not Disturb and press play. Rescue, PowerNap andFlowState are used lying down, with an eye mask and headphones. During a session, people often describe their breathing slowing and their body feeling heavy. There are no pills and no side effects.

“Developing a beneficial meditation practice can take countless hours over a period of years. By using NuCalm I can effectively and quickly access a state of mind where I have the ability to respond instead of react. I use NuCalm because I have post-traumatic stress. With as little as 20 minutes a day I get to respond to my feelings and thoughts instead of react to them. When I have the ability to respond I can be humble, thoughtful, patient and kind. When I react instead of respond I can be aggressive, irritable and fearful. NuCalm aids me into being the version of myself that is genuine and real. It is who I am without PTS.”

“I use NuCalm every day and I have been for over 5 years. In fact, I feel like I’m at a disadvantage if I don’t use it. I call it my secret weapon and I’ve noticed with NuCalm in my life – I sleep better. I have less stress. I certainly have greater focus. And my focus has always been strong, but it’s definitely stronger. I have more mental alertness, greater levels of mental energy, and less brain fog. I have a deep sense of calm and peace. For me, peace of mind is high currency.”

“The ability of NuCalm to reduce sympathetic discharge, and its impact on the autonomic nervous system, is clearly a freestanding and noteworthy contribution to society and our high-paced, stress-filled lives. We know that every organ system in the human body is disturbed when sympathetic tone predominates excessively and chronically. The sympathetic discharge associated with sleep deprivation and long working hours under stress allows opportunistic viruses and bacteria to colonize and challenge our system. When confronted with chronic inflammatory conditions, cancer, bacterial/viral infections, and other assaults to homeostasis, it becomes critical to optimize the immune system. NuCalm demonstrates the immune-boosting role of shifting to a parasympathetic-dominated tone.”

Numerous physiological markers are available which provide data to analyze the efficacy of the NuCalm clinical system in decreasing the sympathetic nervous system response and anxiety. These markers include galvanic skin response, temperature, blood volume pulse, heart rate, heart rate variability (including HRV amp, SDNN, RMSSD, %LF, %HF, and LF/HF) and brain waves (including beta, alpha, theta, and delta amplitudes, alpha/theta crossover and slow cortical potentials). Each of these physiologic markers demonstrates a particular response (increase or decrease) under sympathetic and parasympathetic stimulation.

Galvanic skin response (GSR) is a method of measuring the electrical conductivity of the skin, which varies with its moisture level. This is notable because the eccrine glands are controlled by the sympathetic nervous system, so skin conductance is used as an indication of psychological or physiological arousal. There is a relationship between sympathetic activity and emotional arousal such as fear and anger. The GSR is highly sensitive to emotions in some people. Human eccrine glands receive primary signals from sympathetic cholinergic fibers that are controlled by the neurotransmitter acetylcholine. In measuring GSR, a very slight electrical current is run through the skin and changes in the salt and water in the sweat gland ducts are measured. The more emotionally aroused the subject is, the more active the sweat glands are and the greater the electrical conductivity of the skin. An increase in GSR occurs with sympathetic stimulation and decreases with parasympathetic stimulation.

Dermal temperature is another measure of sympathetic arousal. Dermal temperature decreases with sympathetic stimulation and increases with parasympathetic stimulation.

Blood volume pulse (BVP) is measured by photoplethysmography, which is a non-invasive transducer to measure the relative changes of blood volume in a subject’s finger or temple. An infrared light source is transmitted through or reflected off the tissue, detected by a phototransistor, and quantified in arbitrary units. Less light is absorbed when blood flow is greater, increasing the intensity of the light reaching the sensor. The wave form obtained from such a transducer represents the BVP of the subject, which is the phasic change in blood volume with each heartbeat. Heart rate is simply the number of beats of the heart per time interval. Heart rate increases with sympathetic stimulation and decreases with parasympathetic stimulation. The BVP likewise increases with sympathetic stimulation and decreases with parasympathetic stimulation.

Heart rate variability (HRV) consists of beat-to-beat differences in intervals between successive heartbeats. In general, emotional stress gives rise to heart rhythm patterns that appear irregular and erratic. The heart rate variability waveform under stress appears as a series of uneven, jagged peaks (i.e., an incoherent heart rhythm pattern). Physiologically, this pattern indicates that the signals produced by the two branches of the autonomic nervous system are out of sync with each other. This incoherent pattern of physiological activity associated with stressful emotions can cause the body to operate inefficiently, deplete energy, and produce extra wear-and-tear on the body. This is especially true if emotional stress is prolonged or frequent. During positive emotions, the heart rhythm pattern becomes highly ordered, appearing like a smooth, harmonious wave. This is called a coherent heart rhythm pattern. With coherent heart rhythm, the activity in the two branches of the autonomic nervous system is synchronized and the body’s systems operate with increased efficiency and harmony.

HRV data can identify anxiety and stressful influences on the cardiovascular system. The interbeat interval is a portal through which parasympathetic and sympathetic influences may be observed. HRV is a measure of the variation of the beat-to-beat interval. Increased HRV has been shown to have positive clinical significance, whereas reduced HRV has been associated with negative clinical outcomes and conditions. Variation in the beat-to-beat interval is a physiological phenomenon resulting from several different inputs to the sinoatrial node, which is the impulse-generating, pacemaker tissue located in the right atrium of the heart, and thus the generator of normal sinus rhythm. The main inputs are the sympathetic and the parasympathetic nervous systems. The two primary fluctuations are respiratory arrhythmia and low-frequency oscillations. Respiratory arrhythmia is associated with the respiratory rate and low-frequency oscillations are associated with Mayer waves of blood pressure (waves in arterial blood pressure brought about by oscillations in baroreceptor and chemoreceptor reflex control systems).

The most widely used methods for measuring HRV are time-domain methods and frequency-domain methods. The time-domain methods are based on the beat-to-beat or NN intervals, which are analyzed in a variety of ways. Included among these are the SDNN (the standard deviation of NN intervals) and the RMSSD (the square root of the mean squared difference of successive NNs). These are measures representing sympathetic or parasympathetic influence. Increased scores of these measures represent greater parasympathetic influence. Norms for these measures are: RMSSD 27.2 +/- 12.3 and SDNN 136.5 +/- 33.4.

Measurements assessed with frequency-domain methods include LF, LF norm, HF, HF norm, and LF/HF ratio. HRV rhythms in the low frequency (LF) range (between 0.04 to 0.15Hz) reflect mixed sympathetic and parasympathetic activity. Mental stress increases LF activity and is usually considered a marker of sympathetic modulation. The high frequency (HF) range (between 0.15 to 0.4Hz) contains rhythms regulated by parasympathetic activity and corresponds to N-N variations caused by respiration. Deep, even breathing activates the parasympathetic nervous system and raises the amplitude of HF. Mental stress decreases HF activity. Vagal activity is the major contributor to the HF component. With the LF/HF ratio, high numbers mean dominance of sympathetic activity while low numbers mean dominance of the parasympathetic activity. After deep and even breathing, an increase reflects changes in the parasympathetic regulation. HRV decreases with sympathetic stimulation and increases with parasympathetic stimulation. Consistent with this result, the HRV LF% and the LF/HF ratio increase with sympathetic stimulation and decrease with parasympathetic stimulation.

Various brain waves are associated with states of wakefulness and sleep, mental activity related to cognitive, sensory, and motor activities, and emotions such as fear and anxiety. Beta brain waves are fast brain waves that reflect normal waking consciousness. Beta amplitudes increase with sympathetic stimulation. There is a range of beta waves: low beta, relaxed but alert (~13Hz - 15Hz), the middle of the range, often linked with active learning (~15Hz - 19Hz), and high beta, which is the anxious brain (associated with fear and anxiety) exhibiting brain wave frequencies ~23Hz - 38Hz. Alpha waves indicate a comfortable, relaxed state, 8Hz - 12Hz, and are associated with relaxation, daydreaming, and idleness. Theta waves reflect a deeply relaxed state, 4Hz - 7Hz. Delta waves are indicative of the sleep state wherein signals are moving through clusters of neurons very slowly, around 4Hz. Delta amplitude progressively decreases during sleep. Delta waves are related to V waves, which occur during sleep, and to slow cortical potentials.

The production of alpha and theta patterns in the brain is correlated to the relaxation response. The relaxation response reduces heart rate and blood pressure, relaxes muscles, and increases oxygen to the brain. The relaxation response is extremely beneficial to learning and problem solving and is accompanied by alpha (higher amplitude, lower frequency brain waves) and theta rhythms (even greater amplitude, lower frequency brain waves). The brain wave frequencies increase with sympathetic stimulation and decrease with parasympathetic stimulation.

Alpha to theta crossover occurs just at pre-sleep, providing a dissociative hypnagogic experience of profound relaxation. Alpha to theta crossover is where people experience restorative sleep and the loss of a sense of time and place. It is sometimes called the hypnagogic state. The alpha-theta crossover state is a deeply relaxed state in the alpha (8-12Hz) and the theta (4-7Hz) range, right on the edge of sleep. The name comes from the behavior of the brain waves. Alpha waves are usually higher in amplitude, or more powerful, than theta. Alpha-theta crossover is when the amplitude of the alpha waves drops and the theta amplitude rises to the point where it crosses over the alpha waves, indicating it has become more powerful. Alpha-theta crossovers decrease with sympathetic stimulation and increase with parasympathetic stimulation.

Slow cortical potentials (SCPs) are gradual changes in the membrane potentials of cortical dendrites which are in the frequency range below 1Hz - 2Hz that last from 300ms to several seconds. Negative potential shifts indicate mobilization or higher excitability, positive SCP shifts represent reduced excitability or inhibition of neuronal activity. Slow cortical potential shifts in the electrical negative direction reflect the depolarization of large cortical cell assemblies, reducing their excitation threshold. SCPs increase with sympathetic stimulation and decrease with parasympathetic stimulation.

Stress is a biological response to the stimulus of a threat, either real or perceived. During an acute stress response, two parallel pathways are activated to prepare the body for fight-or-flight, the sympathetic adreno-medullary (SAM) arm of the autonomic nervous system and the HPA axis. Both systems can be triggered in a bottom-up manner from the brainstem by critical homeostatic perturbations, like respiratory distress, pain, or inflammation – which pose real threats. They can also be triggered in a top-down fashion from the limbic system, particularly from the amygdala, by psychogenic stressors, either innate or experiential – perceived threats. Your thoughts can trigger this response, and often do. The SAM triggers the release of epinephrine (adrenaline) and norepinephrine (noradrenaline) from the adrenal medulla into the bloodstream.

As these hormones circulate through the body, respiratory rate and heart rate accelerate and blood pressure increases to maximize the delivery of oxygenated blood to vital organs. This alerts the body to speed up, tense up, become hypervigilant, and take action for survival. In parallel, the HPA axis (The Hypothalamus-Pituitary-Adrenal axis) triggers a series of hormonal signals to maintain this state of hyper-alertness. The hypothalamus releases corticotropin-releasing factor (CRF), which signals the anterior pituitary gland, to release adrenocorticotropic hormone (ACTH). This hormone travels to the adrenal glands, prompting them to release cortisol, the well-known stress hormone. The release of cortisol can increase the production of epinephrine, as well as trigger the glucose release from protein to supply the body with energy.

Once this happens, blood vessels that supply oxygen and nutrients to our body’s cells and organs are constricted so that more blood can be made available to nourish the tissues of our body’s major muscle groups, especially in our arms and legs, since it is primarily these extremities that the body uses to fend off external attacks and get out of harm’s way. Prior to this response, the blood in the body is concentrated in what are known as the abdominal visceral organs. These include our adrenal glands, kidneys, liver, gallbladder, stomach, intestines, colon, and appendix – the organs responsible for digestion and absorption of foods and nutrients, excretion, and various other functions that provide for proper cell growth and production of cellular energy. As blood is rushed to the tissues of the arms and legs, the visceral organs cannot function at 100%, causing all growth-related activities in the body to become limited. If this process continues for sustained periods of time, our body’s overall functioning is compromised, and we begin to break down. Once the fight-or-flight adrenaline response is activated, the mind cannot rationalize itself or self-regulate until the threat is removed and time passes, because the amygdala has taken oxygen rich red blood cells from the frontal cortex, negating access to executive function, logic, and decision making.

When there aren’t any threats, the HPA axis is in what might be described as “idle mode.” This state of idleness allows the rest of our body to flourish the way that nature intended. And the way nature intended for all humans is to be in autonomic nervous system balance, where we exhibit sympathetic nervous system responses throughout the day, but also activate the rest and digest restoration of the parasympathetic nervous system.

Chronically elevated stress hormones are linked with suppressed immune function, impaired digestion and increased muscle tension.

Sleep disorders are another area where stress is involved. To achieve healthy sleep our body’s normal cycle of hormone production must operate efficiently, especially regarding cortisol. When we are healthy, cortisol levels are highest in the morning (6-8 AM) and lowest in the evening, where they continue at a low level as we fall asleep. This allows our body to release sleep enhancing hormones, such as melatonin and serotonin, leading to deep, restful sleep. Stress interferes with this process. When we are stressed, cortisol levels remain high, even into the night, preventing restful sleep. Over time, the cycle of cortisol production becomes unbalanced, and even reversed, with levels spiking in the evening and falling in the morning, resulting in feelings of exhaustion. Trouble falling asleep and restless sleep (awakening throughout the night) are both common examples of sleep disorders that are associated with nighttime spikes in cortisol and other stress hormones, including, in some cases, adrenaline. Stress compromises the amount and quality of restorative sleep.

Stress, more than anything else, has the greatest potential to sabotage every aspect of our life. Our health, our relationships, our work, our productivity, our brain function, and cognitive abilities, and even our ability to simply enjoy our day can all be negatively impacted by stress. Yet, despite all that we know about the importance of managing stress, as a society we seem more stressed than ever before, especially with COVID-19.

So, what can we do about stress? Well, the first thing we can do is to accept it, appreciate it, and understand that stress is real, stress impacts every human on Earth every day, and the human physiological response as described above is the same in each of us. No one is impregnable to stress, so we must address it. Many people seek yoga, Tai Chi, mindfulness, or deep breathing exercises as healthy pathways to managing stress and activating the parasympathetic nervous system. Many others manage stress through the consumption of drugs and/or alcohol. All these approaches have an impact on slowing down the human stress response, but as most of us know, the path of drugs and alcohol has negative consequences that lead to more stress and depreciation of the mind and body.

But there is also another path to managing stress, and this one is founded in applied neuropsychobiology, has no drugs, no side effects, and is easy to use. NuCalm was invented out of necessity by Dr. Blake Holloway. Dr. Holloway served the military veteran community in San Antonio, Texas for more than 40 years. His invention path began over 35 years ago, which illustrates the challenges inherent in trying to solve complex problems such as down regulating the sympathetic tone (stress response) with predictability, reliability, safety, and ease for people suffering from Post-Traumatic Stress, often comorbid with addiction.

Rescue, PowerNap and FlowState are designed to guide brain wave activity toward alpha & theta, a deeply relaxed state. When the fight-or-flight response is active, resources shift toward survival and away from the prefrontal and frontal cortex, where patience, presence and decision making live. That’s why, under stress, people tend to react instead of respond.

Practices like yoga, breathing exercises and mindfulness help many people, and they take time and practice. Drugs and alcohol carry the risks of addiction and physical harm. NuCalm asks for neither practice nor pills: pick your state of mind and press play.

Starting takes seconds: set your device to Do Not Disturb and press play. Rescue, PowerNap andFlowState are used lying down, with an eye mask and headphones. During a session, people often describe their breathing slowing and their body feeling heavy. There are no pills and no side effects.

“We are measuring the impact of NuCalm on human physiology and concussion healing using heart rate measurement and heart rate variability (HRV). We look for enhancing the vagal tone, which reflects the parasympathetic system (rest and relaxation) response. Heart rate variability is the easiest way to evaluate the vagal response. Although other expressions of stress response are certainly present such as pupillary dilation, increased heart rate, increased respiratory rate and increased concentrations of cortisol and catecholamines, the measure of HRV has become our Gold Standard in evaluating concussion healing. The PNS plays a major role in immunity and response to inflammation. It is therefore important in recovery from brain injury healing since the inflammatory response following concussion is responsible for the post-concussive symptoms. We have been researching the impact of NuCalm on concussion patients – measuring the response versus a sham. Thus far, the results have been significant. NuCalm enhances the parasympathetic state, which is clearly beneficial in post-concussive recovery.”