ORIGINAL RESEARCH

Neuroplasticity Intervention, Amygdala and Insula

Retraining (AIR), Significantly Improves Overall Health
and Functioning Across Various Chronic Conditions
Alexandra J. Bratty, PhD

Abstract
Chronic conditions, sometimes referred to as cell activation syndrome [MCAS]) and others. This
functional somatic disorders, such as myalgic novel and exploratory research examined self-reported
encephalomyelitis/chronic fatigue syndrome (ME/ health and functioning levels before and after using
CFS), fibromyalgia (FM), and more recently, long AIR. A series of paired-sample t tests with Bonferroni
COVID (LC), affect millions of people worldwide. Yet, correction demonstrated that after 3+ months of using
after decades of research and testing, the etiology and AIR (the minimum recommended time for the
treatment for many of these diseases is still unclear. intervention), participants experienced a significant
Recently, a consortium of clinicians and researchers increase in overall health and functioning for 14 of 16
have proposed that while many different chronic conditions tested (P < .001 for all but one, which was
conditions exist, the root cause of each may be a similar P = .001) and approached significance for the remaining
brain-body connection, as the brain responds to two conditions (P = .039 and P = .005). Of the 14
perceived biological threats and transmits danger signficant findings, 11 had a large effect size and three
signals to the body that manifest as somatic symptoms. had a medium effect size. Naturally, this study has
This hypothesis suggests that treating chronic conditions limitations. It was a cross-sectional design with a small
requires an approach that addresses the neural networks convenience sample and self-reported data. Future
involved. One such method, known as Amygdala and research with larger samples and randomized controlled
Insula Retraining (AIR), otherwise known as The trials is needed to provide further evidence of AIR’s
Gupta Program, has shown promise in recent years for effectiveness. Nonetheless, these preliminary findings
treating such conditions, including ME/CFS, FM, and suggest that AIR is a viable method for improving the
LC. The present study aimed to demonstrate that AIR health of people suffering from chronic conditions, and
could be an effective approach for numerous other clinicians and researchers might consider incorporating
chronic illnesses (e.g., Lyme disease, mold illness, mast AIR into their protocols for these patients.

Alexandra J. Bratty, PhD, AB Research Consulting, Shelter Therefore, chronic conditions are debilitating and
Island Heights, NY, USA. negatively impact millions of people worldwide,2,5,6 costing
the global economy trillions of dollars.7
Corresponding author: Alexandra J. Bratty, PhD Consequently, effective treatment is necessary. Yet it
E-mail address: [email protected] remains elusive for these conditions. Decades of research
exploring numerous causes and remedies have yet to
identify a “gold standard” method of treatment.8,9
INTRODUCTION Additionally, clinicians and researchers have only recently
Chronic conditions, sometimes referred to as concluded that the root cause of these various conditions
functional somatic disorders,1 are complex diseases often might be found in neural networks, implying that while
with unknown etiology. There are numerous such numerous different chronic conditions exist, treatment for
conditions, though myalgic encephalomyelitis/chronic them could largely be the same.10 This suggestion does not
fatigue syndrome (ME/CFS), fibromyalgia (FM), pain mean the bodily symptoms experienced by patients are not
syndromes, and more recently, long COVID (LC) are real or “all in their head” as some providers often suggest.
arguably the most commonly recognized. While each Rather, these clinicians and researchers propose that when
condition has its own set of wide-ranging symptoms, these a threat to well-being is perceived, it triggers alarm systems
chronic diseases are often characterized by similar in our neural networks that manifest as bodily symptoms,
symptoms, such as extreme fatigue, myalgia, sleep such as fatigue or pain. The symptoms act as warning
problems, digestive issues, and cognitive impairment.2-4 signals that we are not safe and that the body must adapt to

20 Integrative Medicine • Vol. 22, No. 6 • January 2024 Bratty—Neuroplasticity AIR Significantly Improves Overall Health
the perceived danger. While such a brain-body response and nervous systems via the amygdala and insula.14,15 The
may be evolutionarily helpful in the moment, in some cases, amygdala is part of the limbic system and its primary role
it can persist because the neural networks interpret the is detecting threats and activating responses to them.25-27
bodily symptoms as another threat, thus reactivating the The insula or insular cortex (IC) is located between the
neural networks and sending more danger signals back to temporal lobe and inferor parietal cortex, and is important
the body. Consequently, the brain and body get locked in a in regulating the nervous and immune systems.28-29 Prior
never-ending loop of misinterpreted signals that ultimately research suggests that the amygdala and insula are
develop into chronic illness.10 implicated in nervous and immune responses to signals
Currently, few treatments are available for chronic coming from the viscera.30-31 The insula is involved in
conditions that are grounded in the idea that many of these acquiring and evoking conditioned immune responses,
illnesses are caused by misdirected or misfiring neural while the amygdala appears to mediate the visceral inputs
networks. Still, one such approach has shown promise in that are needed at acquisition.31-32 Further, the signature of
recent years. A neuroplasticity program, known as the a previous immune response can be re-triggered in the
Amygdala and Insula Retraining (AIR) or The Gupta insula. Indeed, the IC has recently been shown to store
Program, is a method that allows patients to self-manage and receive immune responses, indicating that internal
their symptoms via a low-cost and easily accessible online and external stressors can cause IC neurons to misfire,
intervention. Neuroplasticity refers to the brain’s ability to which initiates an inappropriate immune response from
“re-wire” its neural connections. Thus, AIR is effectively a the stored memory.33 These inaccurate signals are sent to
brain-retraining program whereby individuals learn how to the immune and nervous systems, which manifest as
disrupt adverse neural pathways and create new, positive functional somatic symptoms. In turn, these symptoms
connections that lead to better overall health and functioning. are interpreted as danger signals that reactivate the
AIR has demonstrated effectiveness in treating symptoms inappropriate immunological response, thereby creating a
of ME/CFS, FM, and LC in pilot randomized controlled trials. self-perpetuating cycle that keeps the brain and body in a
In one study, AIR significantly improved energy and reduced hyper-vigilant state (i.e., on high alert, constantly scanning
pain and fatigue in patients with ME/CFS.11 Additionally, AIR, for threats) with chronically over-triggered immune and
in combination with treatment-as-usual, has effectively nervous systems.14-15
reduced pain, fatigue, anxiety, and depressive symptoms (3) Gupta also theorizes that there are a range of
among people with FM.11,12 In a more recent investigation, AIR primary and secondary symptoms that can occur and feed
significantly reduced fatigue and increased energy among into the cycle.14,15 Primary symptoms include but are not
people suffering from LC.13 Therefore, the evidence suggests limited to pain, fatigue, cognitive dysfunction, muscle
AIR has the potential to address various chronic conditions, atrophy, and post-exertional malaise, etc. Secondary
though to date, it has only been tested for ME/CFS, FM, and symptoms might include exhaustion of the adrenal glands
LC. Accordingly, the purpose of the present study was to and compromised mitochondrial function, as well as
evaluate the effectiveness of AIR in addressing the overall allergies and sensitivies to food and chemicals, etc. Both
health and functioning of people across various chronic sets of symptoms contribute to the signals sent back to the
conditions beyond just ME/CFS, FM, and LC. brain, where the amygdala and insula interpret them as
AIR is based on the hypothesis that the root cause of threats and respond accordingly. Thus, the amygdala and
numerous chronic conditions may be a disorder in the insula are effectively creating the symptoms they are
brain (specifically in the amygdala and insula) that trying to mitigate in the self-perpetuating loop.
continually triggers the immune and nervous systems Thus, per the hypothesis outlined above, if the brain
unnecessarily, causing various bodily symptoms.14,15 and body are constantly in a hyper-vigilant and overactive
More specifically, the AIR hypothesis proposes the state, it is reasonable to propose that one possible method
following sequence of events that triggers and perpetuates of addressing the condition is to calm the nervous and
a vicious chronic illness cycle, as proposed by Ashok immune systems, and re-wire the signals that are being
Gupta,14,15 the founder of the AIR intervention. sent between the brain and body. The AIR intervention
(1) Factors such as genetic predisposition (i.e., an was developed from this logic.
individual’s genetic makeup), lifestyle (e.g., smoking, AIR is hypothesized to strengthen neurological
alcohol, lack of sleep and exercise, etc.), environmental inhibitory mechanisms in areas of the prefrontal cortex,
(e.g., exposure to toxins, chemicals, and pollution, etc.), insula, and anterior and posterior cingulate. This
and psychosocial (e.g., loneliness, stress, trauma, etc.) bolstering helps reduce the magnification of incoming
inputs can increase inflammation in the body and somatic signals and down-regulate the hyper-stimulation
adversely impact immune responses,16-24 making it of the autonomic nervous system and aspects of the
vulnerable to acute traumatic assaults, such as infection, immune system by the amygdala and the insula so that
virus, or even a damaging psychological event. the immune system and the autonomic nervous system
(2) Gupta proposes that any combination of these can return to normal function, and the body can achieve
factors can lead to maladaptive responses by the immune homeostasis.14-15

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 The AIR intervention includes specialized Table 1. Demographic Information for Study
neuroplasticity techniques, supported by secondary Participants
techniques such as breathing, meditation, and other
lifestyle therapies. A key component of AIR is consistent Used AIR 3+ Months (n = 222)
repetition of neuroplasticity techniques to enable the Count Percentage
development of new neural pathways that signal safety to Gender
Male 25 11%
the brain and body. Indeed, prior research indicates that Female 196 88%
users of AIR experience greater benefits after they have Another Identity 1 0%
been actively engaged with the program for at least 3 Mean Age (SD) 51.1 (12.30) NA
months.13 Therefore, as the present study aimed to Country
determine the effect of AIR across numerous conditions, United States 75 34%
United Kingdom 49 22%
the hypothesis was that self-reported health and
Rest of Europe 71 32%
functioning among chronic condition patients would Other Countries 27 12%
significantly improve after using AIR for 3+ months. This Length of time using AIR
investigation was important because of the practical 3-5 months 69 31%
implications. Namely, that numerous chronic conditions 6-11 months 67 30%
negatively impact millions of people who often suffer from 12 months or more 86 39%
them for years without effective therapy or treatment,8-9
and it is possible that AIR could be a helpful approach for Note: AIR, Amygdala and Insula Retraining (also
reducing or eliminating their symptoms. known as The Gupta Program). Other countries
included Australia, Canada, Columbia, India, New
Methods Zealand, and South Africa.
Research design and participants
The current research was an international cross-
sectional study. Participants were recruited from The The AIR Intervention
Gupta Program database of people who had purchased the The AIR intervention is comprised of specialized
intervention. Emails were sent to the database, inviting neuroplasticity techniques and breathing, meditation, and
respondents to participate in an online survey. This other lifestyle therapies. The foundational hypothesis of
recruitment process may have resulted in self-selection the intervention is that numerous chronic conditions are
bias, which limits the generalizability of findings. However, caused and perpetuated by brain signals that continually
it was the only feasible method available given time and and needlessly activate the immune and nervous systems.
budget constraints. This non-stop triggering of the immune and nervous
Two screening criteria determined eligibility. First, systems manifests as a range of symptoms experienced in
participants had signed up for The Gupta Program at least the body, including but not limited to pain, fatigue,
one month before taking the survey. Second, they had insomnia, cognitive issues, and distress. Therefore, the
been actively using The Gupta Program for at least one primary neuroplasticity technique of AIR is intended to
month. Before completing the survey, participants were disrupt these brain signals that lead to adverse somatic
informed that the purpose of it was to gather feedback on symptoms and replace them with new, positive neural
The Gupta Program and its effectiveness in addressing connections that signal safety to the brain and reduce
various chronic conditions. They were also reassured that hyperactivity in the immune and nervous systems.
their responses would be kept strictly confidential. Creating these new neural pathways requires repetition.
Participation in the study was voluntary, and respondents Consequently, individuals are encouraged to practice the
could choose to disengage at any point during the survey. primary neuroplasticity technique daily over a period of at
A total of N = 315 participants completed the survey, least 3 months, and ideally for 6 months.
among which n = 222 reported actively using the program The AIR program also recommends that participants
for 3 months or more. As noted above, 3+ months of engage in some secondary supporting techniques. These
actively using AIR is optimal for noticeable improvement. include mindfulness-based meditation, where participants
Therefore, for the purpose of this study, only participants listen to soothing guided meditations that help them focus
who self-reported using the program for 3+ months were on the present; specific breathing techniques, including
considered. Table 1 displays the demographic information alternate nostril breathing; and other lifestyle
for this sample. Importantly, the use of self-report data for modifications, such as eating anti-inflammatory foods,
length of time participants engaged in the program and getting enough sleep, and developing a calming morning
the measured outcome variables introduced the possibility routine to ease into the day.
of risk of response bias (i.e., that respondents do not Participants are advised to spend approximately 30-60
provide accurate answers), which may have impacted the minutes daily practicing the various AIR components,
data collected and subsequent analyses. preferably in the morning. The division of time is typically

22 Integrative Medicine • Vol. 22, No. 6 • January 2024 Bratty—Neuroplasticity AIR Significantly Improves Overall Health
2-5 minutes of alternate nostril breathing, 20 minutes in with an initial alpha level set at .05 for significance.
meditation, and 15-30 minutes engaging in the main However, conducting multiple tests across the same
neuroplasticity process. Additionally, short versions (i.e., dataset can increase the chance of a Type I error (i.e., a
30-60 seconds) of the neuroplasticity techniques are false positive). Therefore, the Bonferroni correction was
recommended at various points during the day to interrupt applied for the 16 tests, reducing the required alpha level
any in-the-moment somatic signals and provide further for significance from .05 to .003.
repetition in training the new neural pathways.
The intervention is provided digitally via a website Results
member area and consists of a video course with audio Paired-sample t tests demonstrated that at the
exercises and meditations. There are 15 modules that Bonferroni-adjusted significance level of .003, AIR
teach and demonstrate meditation, breathing techniques, participants experienced a significant increase in overall
the primary neuroplasticity techniques and abbreviated health and functioning across 14 of the 16 different chronic
versions of them, attitudes for success, how to pace conditions. Two conditions approached significance. These
oneself, and reintegrate back into daily life once symptoms were chronic inflammatory response syndrome (CIRS; P =
have diminished. A printed manual of the whole program .039) and small intestinal bacterial overgrowth (SIBO; P =
is also mailed to participants. Additionally, weekly live and .005). The remaining 14 conditions were significant at P <
recorded webinars are led by Ashok Gupta. Optional one- .001 for all but electromagnetic hypersensitivity (EHS; P =
on-one and group coaching is also available upon demand .001), and each with a medium or large Cohen’s d effect size
with AIR-trained coaches. Since this study was conducted, (Cohen’s d small effect size is 0.2; medium effect size is 0.5;
the program is now also delivered via a mobile app, and large effect size is 0.8). Among the 14 conditions that
offers live daily experiential sessions led by an AIR-trained yielded significant findings, the increase in mean scores
coach providing a supportive community environment, from before to after using AIR ranged from 15.64 points for
which may make the program easier to use for patients. mast cell activation syndrome (MCAS), a 52% improvement
rate, to 28.26 points for Lyme disease, a 116% improvement
Measures rate. Specifically, among those suffering from ME/CFS and
Health and Functioning. Overall health and FM, post-AIR health mean scores were 70% and 62%
functioning were measured using a variation of the higher, respectively, than before-AIR mean scores. Among
EQ-5D Visual Analogue Scale.34 The EQ-5D Visual those with LC, the health mean score was 84% higher after
Analogue Scale asks respondents to rate their present using AIR. Table 2 displays the mean scores for each
health state from 0 (worst) to 100 (best). The modified condition before and after using AIR for 3+ months, the
version used in this study asked participants to rate their change in those scores, and the results from the t tests. Still,
overall health and functioning before and after using The it is worth noting the small sample sizes for each condition
Gupta Program: How would you rate your overall health and the variability in the data, with standard deviation
and functioning (before starting/at present, after using) The scores ranging from 17.88 (Panic pre-AIR) to 29.22 (EHS
Gupta Program? Please rate this using a scale of 0 to 100, post-AIR), suggesting that larger sample sizes are needed to
where 100 represents full health and functioning. For provide more robust analysis. Indeed, conditions with
example, 10 would be poor health and low functioning, and higher p values had some of the smallest sample sizes, which
80-90 would be great health and high functioning. The could have impacted statistical power.
length of time noted between the two measures was Subgroup analysis within the various conditions was
dependent on how long participants self-reported using not possible due to the small sample sizes for each of them.
The Gupta Program. For example, if a respondent reported However, the full sample was examined at a subgroup level
using the program for 4 months, the time between the to highlight additional findings. The Bonferroni-adjusted
before and after measures was allocated as such. alpha level for these tests was .004 taking into account the
12 subgroups analyzed. As displayed in Table 3, regardless
Analyses of gender, age group, country of residence, or length of
A series of paired-sample t tests along with effect sizes time using the AIR intervention, paired sample t test
were used to analyze the data in IBM SPSS v26.0. The data results were significant; P < .001 for all subgroups except
were normal, with skewness and kurtosis scores within the men, which showed P = .001. Additionally, the Cohen’s d
±2 acceptable range. Additionally, no outliers were effect sizes were all medium or large and the percentage
detected. Five respondents did not answer the measures change improvement from pre- to post-AIR was 50% or
and were removed from the dataset to allow for an higher. Notably, participants who reported using AIR for
accurate and complete investigation of the remaining n = 12 months or more experienced an improvement of 102%,
217 respondents. While removing cases from a dataset can as compared to 50% and 52% for those using it for 3-5
sometimes impact findings, that was not expected with so months or 6-11 months, respectively. This finding suggests
few removed in this instance (i.e., 2.25% of cases). that prolonged consistency with the AIR intervention can
Therefore, the final analyses were performed for n = 217, yield enhanced health and functioning outcomes.

Bratty—Neuroplasticity AIR Significantly Improves Overall Health Integrative Medicine • Vol. 22, No. 6 • January 2024 23
 Table 2. Health and Functioning Before and After 3+ Months of Using AIR by Condition

Condition (sample size) Pre-AIR M(SD) Post-AIR M(SD) Diff. Percent Change df t Sig. (2-tailed) Cohen’s d
ME/CFS (n = 139) 28.20 (20.24) 47.80 (27.49) 19.60 70% 138 9.49 <.001 0.81
Fibromyalgia (n = 52) 27.04 (20.21) 43.79 (25.69) 16.75 62% 51 5.64 <.001 0.78
Long COVID (n = 30) 24.57 (21.03) 45.30 (25.65) 20.73 84% 29 4.05 <.001 0.74
MCAS (n = 56) 30.36 (20.56) 46.00 (24.31) 15.64 52% 55 4.93 <.001 0.66
MCS (n = 53) 29.62 (22.43) 54.89 (27.62) 25.27 85% 52 6.02 <.001 0.83
Mold (n = 40) 30.78 (21.06) 51.45 (27.06) 20.67 67% 39 4.42 <001 0.70
CIRS (n = 19) 24.58 (23.19) 39.37 (25.72) 14.79 60% 18 2.22 .039 0.51
EHS (n = 18) 27.50 (23.67) 50.11 (29.22) 22.61 82% 17 3.94 .001 0.93
Anxiety (n = 121) 29.21 (21.12) 49.17 (26.59) 19.96 68% 120 8.65 <.001 0.79
Panic (n = 34) 24.47 (17.88) 48.94 (25.50) 24.47 100% 33 6.12 <.001 1.05
Burnout (n = 33) 28.00 (19.53) 49.30 (25.73) 21.30 76% 32 4.55 <.001 0.79
IBS (n = 66) 28.44 (21.45) 46.74 (27.37) 18.30 64% 65 6.78 <.001 0.83
Food sensitivities (n = 97) 32.08 (21.70) 50.08 (24.65) 18.00 56% 96 7.71 <.001 0.78
SIBO (n = 30) 25.17 (19.33) 36.83 (23.75) 11.66 46% 29 3.07 .005 0.56
Pain (n = 26) 29.23 (19.44) 45.50 (25.88) 16.27 56% 25 3.87 <.001 0.76
Lyme (n = 27) 24.37 (20.03) 52.63 (27.27) 28.26 116% 26 5.30 <.001 1.02

Abbreviations: AIR, Amygdala and Insula Retraining; Diff, difference in mean scores from pre-AIR to post-AIR;
Percent Change, the percentage change in mean score from pre-AIR to post-AIR; MCS, Multiple Chemical
Sensitivities; CIRS, Chronic Inflammatory Response Syndrome; EHS, Electromagnetic Hypersensitivity; IBS,
Irritable Bowel Syndrome; SIBO, Small Intestinal Bacterial Overgrowth; MCAS, Mast Cell Activation Syndrome.

Table 3. Health and Functioning Before and After 3+ Months of Using AIR by Subgroup

Condition (sample size) Pre-AIR M(SD) Post-AIR M(SD) Diff. Percent Change df t Sig.(2-tailed) Cohen’s d
Overall (N = 217) 29.52 (20.83) 49.71 (27.16) 20.19 68% 216 12.12 <.001 0.82
Gender
Male (n = 25) 34.40 (23.99) 57.44 (22.20) 23.04 67% 24 3.60 .001 0.72
Female (n = 191) 28.69 (20.24) 48.72 (27.70) 20.03 70% 190 11.85 <.001 0.86
Age
18-44 (n = 67) 29.76 (20.93) 47.45 (26.79) 17.69 59% 66 6.18 <.001 0.76
45-54 (n = 62) 31.55 (21.82) 52.11 (26.28) 20.57 65% 61 6.52 <.001 0.83
55+ (n = 88) 27.91 (20.14) 49.75 (28.19) 21.84 78% 87 8.11 <.001 0.86
Country
United States (n = 75) 31.11 (23.19) 49.08 (28.63) 17.97 58% 74 5.91 <.001 0.68
United Kingdom (n = 48) 31.85 (19.54) 49.38 (26.17) 17.52 55% 47 5.96 <.001 0.86
Rest of Europe (n = 69) 26.61 (19.39) 49.04 (26.70) 22.43 84% 68 7.21 <.001 0.87
Other Countries (n = 25) 28.32 (19.74) 54.12 (26.98) 25.80 91% 24 5.77 <.001 1.15
Length of time using AIR
3-5 months (n = 68) 30.34 (19.43) 45.49 (24.92) 15.15 50% 67 7.60 <.001 0.92
6-11 months (n = 66) 33.27 (23.86) 50.73 (27.16) 17.46 52% 65 5.45 <.001 0.67
12+ months (n = 83) 25.87 (18.92) 52.73 (28.78) 26.50 102% 82 8.75 <.001 0.96

Abbreviations: AIR, Amygdala and Insula Retraining; Diff, difference in mean scores from pre-AIR to post-AIR;
Percent Change, the percentage change in mean score from pre-AIR to post-AIR.

Though these findings are derived from cross- rates for placebo intervention groups are 20% or less,35
sectional data, they are relevant for clinical application. which is substantially lower than the rates observed in the
Considered in aggregate, the results indicated that the AIR present study.
intervention can yield statistically significant improvements
in health and functioning across numerous conditions and Discussion
regardless of subgroup. Of the 14 conditions that This novel and exploratory study aimed to evaluate
demonstrated significant results, the percentage the impact of AIR across a range of different chronic
improvement in self-reported health and functioning conditions. Results from a series of paired-sample t tests
ranged from 52% to 116%. Similarly, across subgroups, the supported the hypothesis that self-reported overall health
percentage improvement ranged from 50% to 102%. Of and functioning would improve after using AIR for 3+
course, there was no control group in this study. However, months. Indeed, the increase in participants’ wellness
other research has suggested that standard improvement scores was significant for 14 of the 16 chronic conditions

24 Integrative Medicine • Vol. 22, No. 6 • January 2024 Bratty—Neuroplasticity AIR Significantly Improves Overall Health
tested and approached significance for two of the 16 randomized controlled trials, with studies reporting
conditions after participants actively engaged with the AIR medium to large effect sizes.11-13 Moreover, in some of
intervention for at least 3 months. these studies, AIR demonstrated significantly better
Of course, no control group was used in this study. results than structurally-equivalent non-pharmacological
However, standard improvement rates among placebo interventions provided to the control groups.12-13 A possible
intervention groups have been observed at 20% or less35 reason for AIR’s superior performance could be that it is
and generally show small effect sizes,36-38 both of which strategically designed to target the root cause of chronic
are notably less than the 52% to 116% improvement rate conditions (discussed in further detail below), rather
and medium to large effect sizes detected in this cross- than just symptom management as is often the primary
sectional study. objective of other non-pharmacological interventions.42
Moreover, the study findings are consistent with The cross-condition and comparative effectiveness of
randomized controlled studies. In research conducted AIR may be explained by its underlying hypothesis and the
among patients with FM and/or ME/CFS, statistically mechanisms by which neurobiological research suggests
significant improvements in physical health, energy, pain, the amygdala and insula are involved in the chronic illness
symptom distress, motivation, activity, and fatigue were cycle. The AIR hypothesis proposes that the root cause
observed among those who received the AIR intervention of several chronic conditions is found in the brain,10,14-15
in combination with standard care compared to a control specifically the amygdala and insula. For example,
group who received only standard care.11 Another study LeDoux’s theory43 implies that adverse environmental
among FM patients also demonstrated AIR’s effectiveness. events can trigger the amygdala, which is the primary
Compared to an active control group who engaged in defense mechanism in the brain. Additionally, other
a relaxation therapy program structurally equivalent research has suggested that the brain’s defensive responses
to AIR, patients who received the AIR intervention are controlled by a higher-order cortical network that
posted significantly lower scores in functional involves the amygdala, insula, interior cingulate, medial
impairment, anxiety, pain catastrophizing, psychological prefrontal cortex, and other areas. When this higher-
inflexibility, clinical severity, depression, and brain- order cortical network does not appropriately control
derived neurotrophic factor (BDNF). Additionally, they defensive responses, it may contribute to disorders such as
showed significantly higher scores in mindfulness, self- posttraumatic stress disorder.44
compassion, and health-related quality of life.12 Moreover, As applied to chronic conditions, the foundational
a study conducted among people suffering from LC tested hypothesis of AIR is that dysregulated amygdala and insula
the impact of AIR compared to a structurally equivalent responses lead to a continual over-triggering of defense
health and wellness intervention. Results showed that the responses that results in a vicious cycle of persistent illness.
AIR intervention was four times more effective at reducing The mechanism for this cycle is activated when certain
fatigue and twice as effective at increasing levels of energy precipitating factors or threats are present (e.g., physical
compared to a structurally equivalent wellness program. illness or an acute traumatic event) that spur the nervous
Furthermore, the AIR group approached the US adult’s and immune systems into action. In normal circumstances,
normal level of fatigue after 3 months.13 Consequently, this is an adaptive response and once the threat is mitigated,
there is growing evidence that AIR is an effective method the body returns to homeostasis. However, the defense
for addressing various symptoms across different chronic response can dysfunction when threats are re-experienced
conditions. and/or previously neutral stimuli become conditioned
AIR also seems to be a more valuable approach than stimuli that trigger a defense reaction.14-15,45
other similar non-pharmacological interventions. Several The amygdala is widely considered to play a primary
therapies encompassing psychological, biofeedback, role in detecting threats and activating defensive responses,
mindfulness, movement, and relaxation have shown as well as assigning meaning to various neutral stimuli.30
promise in alleviating symptoms associated with specific Thus, even when a stimulus is benign, the amygdala
chronic conditions, including ME/CFS and FM. However, can perceive it as a threat and trigger an unnecessary
the evidence supporting these interventions is characterized defense response.46-49 Indeed, much research points to
as low quality with inconsistent results.39-40 Additionally, the amygdala’s role in classical fear conditioning whereby
the lack of standardization in interventions and outcome a previously neutral stimulus becomes associated with
measures further complicates the interpretation of a threat stimulus to the point where just the presence of
findings.39 Robust evidence is conspicuously absent the neutral stimulus triggers the defense response.26,43,49-50
regarding non-pharmacological treatments for the Studies have demonstrated that such fear conditioning is
management of other chronic conditions, including LC mainly controlled by the amygdala along with other areas
and various post-viral fatigue syndromes.41-42 of the brain, including the insula, anterior cingulate, and
By contrast, AIR as a standardized intervention, medial prefrontal cortex.43,50-51 Consequently, the AIR
has consistently demonstrated efficacy across several hypothesis posits that the amygdala can assign threat status
conditions and outcomes when tested in high-quality to a previously neutral stimulus and that information is

Bratty—Neuroplasticity AIR Significantly Improves Overall Health Integrative Medicine • Vol. 22, No. 6 • January 2024 25
 stored in the insula. Thus, maladaptive conditioning and which prohibits the ability to draw any causal inferences
defense responses can be triggered when the amygdala from the results. Second, the research design used a
and insula erroneously assume that bodily symptoms are convenience sample that elevated the possibility of self-
threats.14-15 Recent neurobiological animal research has selection and risk of response biases that might impact the
supported this theory. reliability and generalizability of findings. Still, it is worth
In one study, the brain processes of underlying noting the consistently significant findings across gender,
conditioned immune responses in rats were examined, age, country, and chronic conditions, suggesting that AIR
revealing that the amygdala mediates the visceral input may be helpful for various populations. Third, the sample
required for the acquisition of an immune response while size for several conditions and subgroups was small, which
the insular cortex plays a central role in acquisition and may have reduced statistical power. Fourth, the study used
induction of the response.32 In another study, the neural self-reported measures, and participants’ memory of their
activity of mice was recorded while two gastrointestinal baseline health status before using AIR could be inaccurate
inflammatory conditions were stimulated. After removing when recalling it 3+ months later. Finally, conducting
the inflammatory stimuli and complete recovery in the multiple tests on the same data increases the chance of
mice, reactivation of the same neural activity in the insular Type I error (i.e., a false positive). However, this issue was
cortex triggered the inflammatory condition. Additionally, mitigated by applying the Bonferroni correction and
inflammation diminished when activation in the insular adjusting the alpha level accordingly.
cortex was inhibited.33 Considered together, these studies Limitations notwithstanding, the findings from this
suggest that the amygdala and insular cortex are crucial study are intriguing and promising. Together with various
components in immunological conditioning. randomized-controlled trial outcomes, these results
Therefore, even absent a real threat, the amygdala provide further evidence that AIR could be a viable and
and insula can trigger danger signals to the immune and accessible treatment for multiple chronic illnesses. Future
nervous systems. These danger signals are experienced as research should engage in more rigorous testing of AIR.
bodily symptoms which, in turn, are misinterpreted as This could include randomized controlled trials for various
threats. In essence, the amygdala and insula seem to get chronic illnesses, including but not limited to the 16
trapped in a continuous cycle of receiving and sending conditions explored in this study. It would also be helpful
adverse signals to the body, as they try to fight off the very to conduct Phase II and Phase III clinical trials for
symptoms they are creating. This cycle keeps the immune conditions that have already demonstrated AIR’s
and nervous systems in a constant state of flux and effectiveness in pilot studies for ME/CFS, FM, and LC.
perpetuating the symptoms of various chronic diseases.14-15 Moreover, evidence of AIR’s cross-condition effectiveness
Given the underlying hypothesis and mechanisms, could be expanded by conducting initial clinical trials for
it follows that the AIR intervention would be effective in emerging conditions, such as Lyme disease, mold illness,
alleviating the various symptoms of chronic illness. As mast cell activation syndrome (MCAS), and many others.
noted above, the intervention is designed to interrupt the Study robustness could also be bolstered by incorporating
danger signals going back-and-forth between the brain objective biomarkers and health professionals’ observations
and body, and create new, neural pathways that signal in addition to self-reported measures. Finally, in addition
safety. Such brain-retraining helps the amygdala and to exploring the effectiveness of AIR in improving patient
insula to reduce the hyper-vigilant activity and return the health and functioning, other studies could examine the
body to homeostasis. impact of AIR on quality of life, economic productivity,
and social functioning.
Strengths and Limitations
This study’s primary strength is its novelty in analyzing Practical Implications
the impact of AIR across multiple chronic conditions. Despite its various limitations, this novel study has
While other studies have used more rigorous research numerous practical implications. From a clinical and
methods in evaluating the effectiveness of AIR, they have patient-centered care perspective, AIR is a promising
focused on only a few conditions (i.e., ME/CFS, FM, and approach for addressing numerous conditions that are
LC). By contrast, the sample used in this study included often difficult to treat. The intervention is readily accessible
people suffering from a range of chronic illnesses. Thus, via a member website and app, and provides patients with
the effectiveness of AIR was assessed across 16 different a comprehensive selection of care options, including 15
conditions, providing more evidence and insight into the video and audio modules, weekly live and recorded
potential reach and influence of the intervention. webinars, live daily group coaching, and customized one-
Additionally, these findings support the recently proposed on-one coaching. Anecdotal reports indicate that clinicians
theory that different chronic conditions can potentially be have been integrating AIR at various stages of the patient
treated using an in-common neuroplasticity method.10 journey. Some patients respond well to engaging with AIR
Still, the present investigation has obvious limitations. before other treatment if they are sensitive to medications
First, this study was cross-sectional and not experimental, and supplements; others are able to successfully incorporate

26 Integrative Medicine • Vol. 22, No. 6 • January 2024 Bratty—Neuroplasticity AIR Significantly Improves Overall Health
AIR alongside other treatments; and some might need Informed Consent Statement
Explicit informed consent was not obtained from subjects involved in the study.
other urgent primary care before working with AIR. However, participants were informed about the purpose of the study before
From a societal and health care systems perspective, participating, and the study design was a self-report survey in which respondents
AIR is also a promising avenue for addressing chronic could voluntarily participate or drop out at any time.

conditions, many of which are incapacitating and adversely Data Availability Statement
The data are not publicly available because the sample consists of vulnerable adults
affect millions of people worldwide,2,5,6 costing the global with chronic medical conditions. Individuals were reassured that their data would
economy trillions of dollars.7 In the United States alone, be kept strictly confidential.
the cost of ME/CFS is estimated at $17 to $24 billion,52 the
minimum cost of FM is estimated at $7 billion,53-54 and LC Conflicts of Interest
Alexandra J. Bratty is the CEO of AB Research Consulting, which provides
is pegged at at least $140 billion.55 Most of these costs are consulting services to The Gupta Program, the commercial version of the
due to reduced quality of life and earnings for patients, Amygdala and Insula Retraining (AIR) intervention. Her company was
and increased medical spending because current compensated for this work by independent donors.

treatments have such varied success in alleviating References

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