About four years ago, I started experiencing full-body muscle twitching.
It would happen at rest, at night, sometimes while I was sitting completely still. Fasciculations — the clinical term for involuntary muscle twitches — moving through my legs, my arms, my torso.
For most people, this would be unsettling. For me, it was terrifying in a very specific way.
About a year earlier, my mother had been diagnosed with ALS — Lou Gehrig’s Disease. I had watched her lose function rapidly. I also knew that she and I share a genetic predisposition to both ALS and frontotemporal dementia. So when my body started twitching postpartum, my nervous system did not respond with mild concern. It responded with the full weight of everything I had witnessed and everything I feared.
I knew, clinically, that postpartum muscle twitching has many benign causes. Magnesium depletion. Sleep deprivation. Elevated cortisol. A nervous system that had been through a lot.
I also knew that knowing something intellectually does not stop your amygdala from sounding the alarm.
The twitching eventually resolved. But it changed how I think about healing.
Healing isn’t only about identifying the right diagnosis or finding the right supplement. Sometimes the brain has become convinced the body isn’t safe. And until you address that, it can be incredibly difficult to move forward — even when you’re doing everything else right.
That’s part of why we built our programs the way we did. And it’s why limbic system retraining is integrated into most of what we do at Rise.
What the Limbic System Actually Does
The limbic system is a network of structures deep in the brain — including the amygdala, hippocampus, hypothalamus, and cingulate cortex. Its primary job is to scan your internal and external environment for threats and keep you alive.
When it detects danger, it activates the HPA axis — the hypothalamic-pituitary-adrenal axis — which floods the body with cortisol and adrenaline. Heart rate increases. Digestion slows. Immune function shifts. The body mobilizes for a threat.
In a healthy system, once the threat passes, the limbic system stands down. Cortisol normalizes. The body returns to a state where it can heal, repair, and regulate.
That’s how it’s supposed to work.
When the Limbic System Gets Stuck
Chronic stress, prolonged illness, trauma, mold exposure, and chronic inflammation can impair the limbic system — lowering its threat-detection threshold until it begins treating ordinary, non-threatening stimuli as emergencies.
The amygdala becomes hyper-reactive. The loop looks like this:
A minor trigger fires — eating a certain food, reading a stressful email, feeling a body sensation — and the limbic system misreads it as a massive threat. The brain triggers the stress response: cortisol, inflammatory cytokines, a cascade of physical symptoms. And then the brain logs those symptoms as proof that the trigger was dangerous, strengthening the pathway for next time.
This is not psychological weakness. It is a learned neural pattern — one that forms as a protective response to real, sustained threat. And it drives measurable physiological changes.
Chronic limbic activation leads to:
- Sustained HPA axis dysregulation and elevated cortisol
- Increased intestinal permeability — what’s often called “leaky gut” [1]
- Immune sensitization and heightened food reactivity
- Systemic inflammation
- Hormonal disruption
Research published in The Journal of Physiology confirms that HPA axis activation and the cortisol it releases directly increase intestinal permeability — which helps explain why gut symptoms often persist even when diet is optimized. [1] A 2025 review in Molecular and Cellular Biochemistry further documents how chronic stress disrupts the gut microbiota and immune function through this same HPA-driven mechanism. [2]
This is why a patient can follow a careful elimination diet, take the right supplements, and still feel terrible. If the limbic system is continuously signaling danger, the gut lining will struggle to heal and the immune system will remain reactive — regardless of what’s on the plate.
Who This Is Most Relevant For
Limbic system impairment is not rare. It is a common thread running through many of the conditions we see at Rise.
You may recognize yourself in this if:
- You’ve been doing everything “right” — the diet, the supplements, the sleep hygiene — and you’re still not moving forward
- You react strongly to many foods, chemicals, or environmental triggers
- Your symptoms feel disproportionate to the trigger
- You have a history of chronic illness, mold exposure, Lyme disease, long COVID, POTS, MCAS, fibromyalgia, chronic fatigue, or autoimmune disease
- Your nervous system feels perpetually “on” — reactive, vigilant, hard to settle
- You’ve been told your labs are normal, but your body tells a different story
This is also particularly relevant for perimenopausal women. Estrogen plays a direct role in regulating the amygdala — it modulates the brain networks responsible for threat appraisal, stress response, and emotional regulation. [3] As estrogen levels fluctuate and decline during the perimenopause transition, the brain’s threat-detection system can become more reactive. A 2026 review in Life specifically identifies limbic hyperreactivity in the amygdala as a feature of the perimenopausal brain. [4]
This means that anxiety, mood instability, and heightened sensitivity to stress during perimenopause are not simply “hormonal.” They often reflect a limbic system that has lost one of its key regulatory inputs — and that responds well to targeted support.
The Difference Between Nervous System Regulation and Limbic Retraining
These two approaches are related but distinct — and understanding the difference matters.
Nervous system regulation uses bottom-up, somatic tools — breathwork, EFT tapping, vagus nerve stimulation, gut-directed hypnotherapy — to send a signal of safety up to the brain. These tools are excellent for managing acute stress and improving vagal tone. They work in the moment.
Limbic system retraining is a top-down, neuroplasticity-based approach. Rather than calming the stress response after it fires, the goal is to rewire the neural pathways that generate the false alarm in the first place.
The fundamental principle is neuroplasticity: the brain’s ability to reorganize itself by forming new neural connections throughout life. “Neurons that fire together, wire together.” Every time you fall into an old limbic loop, you strengthen that pathway. But the opposite is equally true — by consciously interrupting the loop and replacing it with a new, grounded narrative, you can prune the old pathways and build new ones.
Over time, this raises the brain’s threat threshold back toward normal. The chronic stress response quiets. Cortisol normalizes. The body can finally direct its energy toward healing.
Both approaches have a place. We use both at Rise. They work at different levels — and together, they amplify each other.
What the Research Shows
The evidence base for neuroplasticity-based limbic retraining has grown meaningfully in recent years. Most of the clinical research has focused on amygdala and insula retraining (AIR) — a structured brain-retraining protocol — across chronic illness populations.
A 2020 pilot randomized controlled trial in women with fibromyalgia found that a combined mindfulness and amygdala retraining program (MAIR) produced significantly greater reductions in functional impairment, anxiety, and depression compared to control. [5]
A 2023 randomized controlled trial tested AIR specifically for long COVID fatigue and found it significantly reduced fatigue and increased energy compared to a structurally equivalent wellness intervention. [6] A second 2023 RCT combining AIR with mindfulness in long COVID patients showed meaningful improvements in quality of life. [7]
A 2023 cross-condition study published in Integrative Medicine: A Clinician’s Journal examined AIR across 16 chronic conditions — including ME/CFS, fibromyalgia, MCAS, Lyme disease, mold illness, IBS, and food sensitivities. Significant improvements were found in 14 of 16 conditions, with health and functioning scores improving by 52–116% after 3 or more months of practice. [8]
On the neuroimaging side, a 2020 study using real-time fMRI neurofeedback demonstrated that cognitive retraining directly reduced measurable amygdala activation in patients with PTSD — providing direct evidence that brain-based retraining changes amygdala activity, not just subjective symptoms. [9]
A note on the evidence: most of the RCT data is in fibromyalgia, ME/CFS, and long COVID specifically. The research is promising and growing, but limbic retraining as a category is still an emerging field. We integrate it because the mechanistic rationale is strong, the clinical evidence is encouraging, and we consistently see patients move forward when this layer is added.
What Limbic Retraining Actually Involves
The practice is structured and daily. It is not meditation in the traditional sense, and it is not positive thinking. It is a specific, evidence-based protocol that includes:
Mapping your loop. Before you can interrupt a pattern, you have to see it clearly. Most patients are surprised by how predictable their loop is once it’s written out — the specific trigger, the story the brain tells, the early body signal, the symptoms, and the belief that gets reinforced.
Identifying the belief underneath. Loops are held in place by beliefs that formed under threat: My body is broken. I can’t trust my body. If I relax, something bad will happen. These aren’t character flaws — they’re protective adaptations. Naming them is not blame. It’s information.
Writing a new narrative. Not a positive affirmation — the brain rejects what it knows to be untrue. A working narrative is truthful, forward-moving, and grounded in real evidence of progress. Something the nervous system can actually register as safe.
Daily structured practice. A morning framing sequence, in-the-moment loop interrupts, and an evening anchoring practice. Together, about 10–15 minutes a day. The brain learns through repetition, not intensity.
Why We Integrate This Into Our Programs
Functional medicine without addressing the brain pattern has a ceiling.
We can optimize gut health, replace with hormone therapy, improve mitochondrial function, and reduce inflammation — and all of that matters. But if the limbic system is continuously generating a threat response, the body stays in a state that works against healing.
Limbic retraining is not a replacement for the clinical work. It’s the layer that makes the clinical work stick.
For patients who have been sick for a long time, who have been dismissed by conventional medicine, who have normalized feeling terrible — the nervous system has often learned patterns that need to be actively unlearned. That’s not a character flaw. It’s biology. And it’s addressable.
A Note on My Own Experience
I want to be clear about something: I did not figure this out from a textbook.
I figured it out because I lived through a period where my own limbic system was running a very convincing false alarm — one that had a rational basis, a genetic backstory, and a mother I was watching lose her life to the disease I feared I had.
The twitching eventually resolved. But what stayed with me was the understanding of how completely a stuck threat response can take over — and how little intellectual knowledge can do to reach it. You can know something is probably fine and still feel like you’re dying.
That experience is part of why I take this seriously as a clinical tool. Not because it’s trendy. Because I’ve been on the other side of it.
Dr. Ashley Shrader, DNP, IFMCP is the founder of Rise Functional Medicine, a telehealth functional medicine practice serving patients in DC, Maryland, Virginia, Oregon, Florida, Massachusetts, Colorado, Idaho, and Washington. She specializes in perimenopause, hormone health, gut health, and brain health optimization.
References
- Leigh SJ, Uhlig F, Wilmes L, et al. The impact of acute and chronic stress on gastrointestinal physiology and function: a microbiota–gut–brain axis perspective. J Physiol. 2023;601(20):4491–4538. https://doi.org/10.1113/JP281951
- Jia H, Guo X, Wei Y, et al. Chronic stress, gut microbiota, and immunity: interconnections and implications for health. Mol Cell Biochem. 2025. https://doi.org/10.1007/s11010-025-05376-y
- Albert KM, Newhouse PA. Estrogen, stress, and depression: cognitive and biological interactions. Annu Rev Clin Psychol. 2019;15:399–423. https://doi.org/10.1146/annurev-clinpsy-050718-095557
- Marano G, d’Abate C, Traversi G, et al. Neuroinflammation and the female brain: sex-specific mechanisms underlying mood disorders and stress vulnerability. Life. 2026;16(1 ):139. https://doi.org/10.3390/life16010139
- Sanabria-Mazo JP, Montero-Marin J, Feliu-Soler A, et al. Mindfulness-based program plus amygdala and insula retraining (MAIR ) for the treatment of women with fibromyalgia: a pilot randomized controlled trial. J Clin Med. 2020;9(10):3246. https://doi.org/10.3390/jcm9103246
- Toussaint LL, Bratty AJ. Amygdala and insula retraining (AIR ) significantly reduces fatigue and increases energy in people with long COVID. Evid Based Complement Alternat Med. 2023;2023:7068326. https://doi.org/10.1155/2023/7068326
- Gasión V, Barceló-Soler A, Beltrán-Ruiz M, et al. Effectiveness of an amygdala and insula retraining program combined with mindfulness training to improve the quality of life in patients with long COVID: a randomized controlled trial. BMC Complement Med Ther. 2023;23:404. https://doi.org/10.1186/s12906-023-04240-0
- Bratty AJ. Neuroplasticity intervention, amygdala and insula retraining (AIR ), significantly improves overall health and functioning across various chronic conditions. Integr Med (Encinitas). 2023;22(6):20–28. PMCID: PMC10886399.
- Zweerings J, Sarkheil P, Keller M, et al. Rt-fMRI neurofeedback-guided cognitive reappraisal training modulates amygdala responsivity in posttraumatic stress disorder. NeuroImage Clin. 2020;28:102483. https://doi.org/10.1016/j.nicl.2020.102483
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