The "Fixed" Brain

Back in the time of Aristotle, people thought the heart was the seat of intelligence. They figured that the brain was there to function as a cooling mechanism for the heart, and that this cooling ability was what separated us from cold-blooded animals; humans were more rational than animals because we had larger brains to cool our hot-bloodedness. In ancient Egypt, when they prepared a body for mummification, the brain was regularly removed, extracted with an iron hook and discarded, because since the heart was assumed to be the seat of intelligence, the vital organ of humanity, discarding the brain was no different than discarding the stomach or the liver.

For centuries, no one questioned the heart theory, until the 5th century BC, when a Greek physician named Alcmaeon of Croton was dissecting an animal, and noticed that the animal’s eyes were connected to the brain, not the heart. He started looking at the other senses, hearing, smell, and taste, and realized they too were all located on the head, with passages that seemed to lead inward toward the brain. Even with this discovery, nearly two centuries passed before physicians Herophilus and Erasistratus in Alexandria actually dissected human bodies and were able to provide the clear evidence for what Alcmaeon of Croton was asserting: that the brain, not the heart, was the center of intelligence. They were even able to map some of the brain out, distinguishing between the cerebrum and cerebellum, identifying the ventricles, and documenting the dura mater.

Around 170 AD, a Roman physician named Galen was observing what happened to people with brain injuries, and he noticed how damage to specific parts of the brain affected mental activity, movement, and sensation. He too concluded definitively that mental activity occurred in the brain rather than the heart. But even then people weren't convinced. They were too anchored to their previous beliefs, unable to let go of what they’d been taught for generations. It wasn't until the 1600s, another 1,400 years later, that this truth was finally accepted by medicine.

Once medicine finally accepted that mental activity occurred in the brain, researchers could start asking how it actually worked. By the 1900s, scientists were studying how signals traveled through the body, how injuries affected function, and whether damaged nerves could heal. In 1913, Santiago Ramón y Cajal was studying nerves' ability to regenerate. He found that some nerves were able to regenerate, and some were not. Your peripheral nervous system, which is the network of nerves that go from your brain out to the rest of your body like your arms, legs, and heart, can regenerate. When you sever a nerve in your arm, for example, it can grow back and restore its function, at least somewhat. But he found that in your central nervous system, which is your brain and your spinal cord, if those neurons, which are the cells that make up those systems, get damaged, they aren't able to physically regenerate. The connections that were severed stayed severed. Cajal could see this clearly under his microscope: axons physically regrowing in specimen after specimen in peripheral nerves, but never in the brain or spinal cord. However he also understood, and even publicly stated, that the brain must be able to reorganize somehow. Otherwise we wouldn't be able to change our minds about anything. That reorganization just wasn't happening through physical neuronal growth like it does in our arms or lungs.

Cajal didn’t actually like what he’d proven. He didn’t like the idea that our brains couldn’t regenerate into adulthood the way the rest of our nervous system could, so he issued a challenge of sorts: he said "In adult centers the nerve paths are something fixed, ended, immutable. Everything may die, nothing may be regenerated. It is for the science of the future to change, if possible, this harsh decree." Meaning basically he had found that in adult brains, the nerves are fixed, and can die but not be regenerated, and that it was the challenge of future scientists to try to prove him wrong if they could. He was literally challenging the future of medicine to figure out how to overturn his observations, hoping humanity's fate wasn’t that of a fixed brain.

He’d done other research in his career as well, that spoke to the parts of the brain that are changeable. In the 1890s Cajal had introduced a concept he called "neuronal plasticity." He'd documented cases where damaged brains formed new circuits to work around injury. As an example, he'd seen how long axon cells could convert into short axon cells with new collateral branches after trauma, creating alternate pathways that could restore function even when the original connections were destroyed. And in addition to these observable changes he saw happening in the brain, a completely fixed, rigid brain made no logical sense to him. How could learning happen? How could we adapt to new situations? How could therapy or practice improve anything? The brain, he argued, had to have the capacity to reorganize its existing connections even if it couldn't grow entirely new neurons. He'd seen it happen, and he’d documented it. The structure might be fixed, but the function was dynamic.

But medicine didn't hear that part. Or maybe it heard it and chose to ignore it. Because what stuck, what got taught in medical schools for the next three generations, was the first part: the brain is fixed, ended, immutable. Everything may die, nothing may be regenerated. That became the operating assumption of neurology, the foundational principle that shaped how doctors thought about brain injury, stroke, developmental disorders, mental illness, and aging. If the brain couldn't change, then damage was permanent. If someone had a stroke, whatever function they lost in the first few months was gone forever. If a child's brain developed abnormally, there was a narrow window for intervention and after that, nothing could be done. If someone's mental faculties declined with age, that was simply the inevitable march toward death. The textbooks said so. Cajal had said so. And Cajal was the father of modern neuroscience, the man who'd won the Nobel Prize for describing the structure of neurons. His authority was absolute.

The irony is that Cajal was right about both things. We now know that you can't grow new neurons in most of the adult brain. Adult neurogenesis does happen, but only in specific regions like the hippocampus and the olfactory bulb. For the vast majority of your brain, the neurons you have are the neurons you'll die with. Cajal was also right that damaged neurons in the central nervous system don't regenerate their axons the way peripheral nerves do. Cut the connection and it stays cut. But he was equally right about the other part, the part that got discarded. The brain reorganizes its existing connections constantly, throughout our entire lives. Every time you learn something new, every time you practice a skill, every time you change your mind about something, your brain is physically rewiring itself. Not by growing new neurons, but by strengthening some synaptic connections, weakening others, and forming new pathways. The structure Cajal described so beautifully was always in motion, always adapting, and capable of significant change, throughout our entire lives.

Mapping the brain

It took until the 1980s for someone to actually prove what Cajal had observed about plasticity. Michael Merzenich, a neuroscientist at UC San Francisco, started doing experiments that would finally prove the brain could reorganize itself, though that wasn’t what he set out to do when he started his work. The prevailing assumption at that time was that these brain maps were fixed. You were born with them, they developed in childhood, and then they stayed put for the rest of your life. That's what localizationism said—specific areas of the brain handle specific functions, these areas were the same in everybody, and they were unchanging. So Merzenich and his colleagues actually only set out to create more detailed maps, essentially documenting with greater precision which exact parts of the brain corresponded to which parts of the body to establish the standard brain organization that everyone assumed was fixed and universal. But as he did this work, he started noticing that when he mapped the same monkey twice, weeks or months apart, the maps were changing. The boundaries had shifted. The territory devoted to one finger might be slightly larger or smaller. It was subtle, but it was there. And the maps varied from one monkey to the next too - they weren't identical copies of a universal template.

Based on what he was seeing, Merzenich hypothesized that the brain might actually be changeable, and that these maps weren't fixed blueprints but living, dynamic territories that shifted based on use. To test this, he designed a series of experiments.

First, he mapped the hand area in the brain of an adult monkey, identifying exactly which neurons responded when each finger was touched. Then he amputated the monkey's middle finger. According to everything medicine believed at the time, the part of the brain that had processed sensation from that finger should go dark, essentially unused for the rest of the animal's life. But when Merzenich remapped the same area months later, he found that the brain map for the middle finger was gone, but the areas representing the two adjacent fingers had expanded, taking over the territory that had been abandoned. Touch the index finger or ring finger, and the neurons that used to respond only to the middle finger now fired for these adjacent fingers. The brain had reorganized itself.

This wasn't supposed to be possible. And since the reorganization was only a millimeter or two, skeptics argued this could be explained by existing but dormant connections between adjacent areas. Maybe there were always some overlapping nerve fibers at the borders, and when one area lost its input, the neighboring areas just activated those pre-existing connections. It was interesting, sure, but it didn't prove the brain could really change in any meaningful way.

So Merzenich went further. In another experiment, he mapped a normal monkey's hand, then he sewed two of the monkey's fingers together so that both fingers moved as one. After several months of the monkey using its sewn fingers, Merzenich remapped the brain. The two separate brain maps for those originally independent fingers had merged into a single map. Touch any point on either finger, and the entire combined map would light up. Because all the movements and sensations in those fingers now occurred simultaneously, the brain had wired them together as a single unit. Neurons that fired together in time wired together to make one map.

He kept pushing. When he stimulated all five fingers simultaneously, 500 times a day for a month, the brain eventually mapped them as one "finger"—a single unified territory instead of five separate ones. When he surgically moved a patch of skin with nerve endings from one finger to another, stimulation at the new location eventually caused the corresponding brain area to reorganize and respond to the transplanted tissue.

Then Bill Jenkins joined Merzenich's team at UCSF to study how the brain changed when an animal actually acquired a new skill rather than just losing function. They taught a monkey to touch a spinning disk with one finger, training it over and over until it became proficient at the task. Before training, they mapped the sensory cortex for that finger. After training, they mapped it again, and found that the brain territory devoted to that specific fingertip had expanded significantly. Learning the skill had caused the brain to devote more processing power to the finger doing the work. And it wasn't just that the map got bigger—the individual neurons within that expanded territory became more efficient, more finely tuned to the specific task the monkey was practicing.

This represented a complete reversal of everything medicine had believed for eighty years. The adult brain wasn't fixed. It reorganized based on what you did with it, what you practiced, what you paid attention to. Use a finger more, and its brain territory grows. Stop using a finger, and its territory gets invaded by neighbors. Make two fingers move together, and their brain maps merge. Practice a skill, and the neurons processing that skill become more numerous and more efficient.

Then in 1991, a researcher named Timothy Pons worked with a group of macaque monkeys that had been used in an earlier, unrelated experiment about a decade prior, in which the sensory nerves from one arm had been cut where they entered the spinal cord. These monkeys had lived for over a decade with no sensory input from that arm. Pons planted electrodes in their brains to see what had happened to the portion of the brain map that should have been processing signals from the now-disconnected limb. He expected to find maybe a couple millimeters of encroachment from the adjacent areas, consistent with what Merzenich had seen. Instead, he found that the face region had completely invaded the neighboring cortex—about half an inch of brain tissue had switched functions. The entire hand and arm zone now responded when the monkey's face was touched. This was neural reorganization on a massive scale, impossible to explain by dormant connections or pre-existing pathways. The brains of these monkeys had fundamentally rewired themselves.

Seeing the changes in humans

Around the same time, the technology finally caught up to allow us to see this happening in living human brains. Functional MRI made it possible to watch which areas of the brain lit up during different tasks, to track how those patterns changed over time, to observe the physical reorganization that Cajal had predicted but couldn't directly measure. Studies on stroke patients showed that the brain could reorganize within weeks of intensive therapy. Research on London taxi drivers revealed that the part of their brain devoted to spatial navigation, the hippocampus, was enlarged compared to bus drivers, and the longer someone had been a taxi driver, the bigger the change. When people learned to juggle, their visual-motor areas reorganized. When musicians practiced, the finger areas of their motor cortex expanded.

By the 1990s, the evidence was overwhelming. The brain wasn't fixed. It had never been fixed. Cajal had been right in the 1890s when he wrote about neuronal plasticity. But it had taken a hundred years, multiple generations of scientists, and the development of entirely new technologies to prove what he'd already observed: the brain reorganizes its existing connections constantly, throughout our entire lives, based on what we do with it.

Medicine now knew that intensive practice causes physical changes in brain structure, that recovery from injury was possible through targeted behavioral interventions. The National Institutes of Health (NIH) sponsored workshops, leading scientists gathered to discuss clinical applications, papers flooded the journals documenting the therapeutic potential.

And then... not much happened.

It's not that nothing at all changed. Some things did. Stroke rehabilitation shifted toward more intensive task-specific training. Constraint-induced movement therapy emerged, forcing stroke patients to use their affected limbs by restraining the good one, capitalizing on the brain's ability to rewire. Some physical therapy protocols incorporated principles of neuroplasticity. Research programs investigated how to enhance plasticity with various interventions: brain stimulation techniques like transcranial magnetic stimulation, vagus nerve stimulation, peripheral nerve stimulation. Virtual reality systems were developed to create immersive rehabilitation environments. Robotic therapy and exoskeletons were designed to facilitate movement and guide practice. Neurofeedback and brain-computer interfaces offered new ways to work with the brain directly.

The field of neurorehabilitation experienced what researchers called a "paradigm shift," moving from a focus on compensation, which is teaching people to work around deficits, to a focus on recovery through neuroplasticity. On paper, this looked revolutionary, but in practice, most of these advanced technological interventions remained largely confined to specialized research centers and expensive private clinics.

And the basic interventions that DID reach mainstream medicine? They showed up almost exclusively in rehabilitation for acute neurological injury: stroke, traumatic brain injury, spinal cord injury, Parkinson's disease. Even there, the interventions are often diluted versions of what the research suggests would actually work. Insurance typically covers a limited number of physical therapy sessions per year after a stroke, when the research suggests daily practice for months or years would produce far better outcomes. The therapies are delivered in clinical settings for an hour a few times a week, when the principles of neuroplastic change suggest they should be practiced every day in real-world contexts.

So why hasn't neuroplasticity-based treatment expanded beyond this narrow window? There's no money in it. Pharmaceutical companies fund research on things they can patent. Drugs and devices. Things that lead to recurring revenue for them. Neuroplasticity-based interventions can't be patented - you're just teaching people to use their own brains differently. So the research doesn't get funded, which means the large-scale studies don't get done.

Physical therapy would seem to be an exception to the idea that medicine only funds and thus integrates drug or device or procedure innovation, but it turns out that it’s the exception that proves the rule - it actually emerged from wartime necessity before the current pharmaceutical-dominated research model took hold, and even now, most 'rehabilitation research' funding goes to prosthetics and assistive technology, things that can actually be sold. The behavioral interventions get almost nothing, and have remained largely unchanged because of it.

The implications of neuroplasticity are far broader than the narrow window medicine is using it for. If the brain reorganizes based on what you do with it, based on what you practice and pay attention to, then neuroplasticity is relevant to virtually every condition involving brain function. Which is…well, everything. Parkinson’s, depression, anxiety, chronic pain, diabetes, PTSD…literally any condition involving patterns of brain activity that have been wired in through repeated activation.

But medicine hasn't gone there. Or more precisely, it hasn't acknowledged that's what it's doing even when it is. Allergy desensitization? That's neuroplasticity: retraining the immune response through repeated exposure. But that’s just one thing, and it’s not the first line treatment for allergies either. The first line treatment is to just avoid the thing causing the reaction.

So here's where we are: the science of neuroplasticity is robust and well-established. The principles are clear. The potential applications are vast. And the actual clinical use is limited to a narrow band of rehabilitation for acute neurological injury, implemented in diluted forms, inaccessible to most people. And it's completely disconnected from the broader implications of what the research actually shows—that the brain reorganizes constantly based on what you do with it, and that deliberately harnessing this could transform how we approach virtually any condition involving brain function.

Disease and the changeable brain

So what about chronic diseases? There has been some research. Scientists have documented extensively that the immune system and nervous system learn patterns of disease just as readily as the brain learns to play piano. And once learned, these patterns can spread and entrench themselves in ways that look exactly like what we saw with Merzenich's monkeys.

In 1962, a researcher named Turnbull proposed that maybe asthma was actually a learned response. The idea came from observing that asthma patients would sometimes have attacks in the complete absence of any allergen. The most famous case was reported back in 1886, when a woman had a full asthmatic attack after seeing an artificial rose. Not a real rose that could trigger an immune response, but a fake one made of paper and cloth. Her body had learned the pattern so well that the visual cue alone was enough to trigger the entire physiological cascade.

Medicine dismissed this as psychological, something separate from "real" asthma with its documented immune responses and airway inflammation. But researchers kept finding the same pattern. They could condition guinea pigs to have asthma attacks in response to completely neutral stimuli, pairing the stimulus with an allergen until eventually the neutral stimulus alone would trigger the whole cascade: bronchoconstriction, inflammation etc. The body was learning associations between arbitrary cues and immune responses, and wiring them together through repetition until they became automatic. And once wired, these learned responses proved remarkably persistent, showing up even when the animals were stressed or in new contexts.

Medicine has documented that when someone has repeated asthma attacks, the sensory nerves in their airways become more sensitive, firing at lower thresholds. The brainstem neurons controlling breathing become more reactive. The parasympathetic nerves that trigger airway constriction become hyperresponsive. Chronic inflammation increases the density of nerves in the airways. The more attacks someone has, the more efficiently their nervous system learns to produce them. It's Merzenich's principle playing out in the respiratory system: use it and it grows stronger. Practice makes you better at what you practice, even when what you're practicing is having asthma attacks. This has been documented across body systems. The first seizure someone gets lowers the threshold for the next one. Each seizure makes future seizures easier to trigger. This is so well documented neurologists have a name for it: kindling. After a first heart attack, the risk of a second is dramatically higher. After a first stroke, subsequent strokes become more likely. Once you’ve had one kidney stone your chances of another go up dramatically. Once the body learns a pattern, it gets easier and easier to repeat it the more it gets practiced.

These practiced patterns can and do also generalize out to other related things with similar pathways. In asthma for example kids who start out reactive to one allergen, say cat dander, often become reactive over time to more and more triggers. First cats, then dogs. Then dust mites. Then pollen. Then cold air. Then exercise. Medicine tracks this with molecular precision, measuring exactly which proteins a child reacts to, the list growing longer year by year. They can see that children sensitized to four or more allergens by age two have more than four times the risk of having asthma by age ten compared to kids sensitized to one allergen or none. The pattern spreads through repeated activation of the same underlying inflammatory cascade, each new trigger strengthens and expands the pathway and gives the system more opportunities to practice.

And like we discussed in the last chapter, once you get diagnosed, you're given a list of triggers to watch out for, which helps this process along. You start to pay more attention to those triggers, and your brain sees that attention and vigilance and adds those things to the list. Just like we saw in the placebo and nocebo chapters. We tell our brains what to expect, and they oblige. And in the case of a preexisting condition, our bodies already have a practiced body reaction to use to enact these expected reactions. Every time you're around cats and you expect a reaction, you're more likely to have one. Every time you exercise and worry about your breathing, you're practicing the association between exertion and bronchospasm. The diagnosis that was meant to help you manage the condition actually gives your nervous system a comprehensive training program on how to be more efficiently asthmatic.

And this spreading isn’t confined to just airway triggers. Over half of children with severe eczema go on to develop asthma, because both conditions involve barrier dysfunction in epithelial tissues, both involve immune hyperreactivity, both show the same pattern of sensitization spreading over time. Medicine calls this the "atopic march," the progression from eczema in infancy to food allergies in toddlerhood to asthma in childhood. And while they frame it as a genetic predisposition playing out developmentally, what they're actually documenting is the nervous system learning a pattern of immune overreaction and then applying that learned pattern to different barrier tissues. The broken skin barrier in eczema teaches the immune system to freak out about allergens, and then when those same immune responses show up in the lungs or the gut, the pattern is already established, already practiced, ready to be triggered by an expanding list of stimuli.

The same sensitization pattern shows up in IBS, where an initial infection or inflammatory event can sensitize the gut's nervous system, creating visceral hypersensitivity that persists long after the original trigger has resolved. The nerves fire at lower thresholds, foods that were previously fine become triggers, and patients end up hypervigilant about eating, scanning for symptoms, reinforcing the very patterns that keep them stuck.

What all of these conditions share is the mechanism we've been tracking through this chapter: the nervous system learning through repetition, associations forming between triggers and responses, patterns becoming automatic and then spreading to similar contexts, neuroplastic changes that start as temporary sensitivity and become permanent architecture. Medicine has documented every piece of this in isolation, the immune responses in asthma, the central sensitization in IBS, the atopic march from eczema to other allergic conditions, kindling in seizure patients, but they didn't connect them as examples of the same underlying process. They didn't recognize that what they were seeing was maladaptive neuroplasticity, the brain and nervous system learning patterns that made people sicker, using the exact same mechanisms that allow us to learn piano or a new language or any other skill.

Now, there are some people using this knowledge to try to make changes in disease, but they get very little attention. Behavioral neuroplasticity-based programs, which use interventions that work to change these patterns we’ve been documenting. Stopping the body from firing off responses to non threatening stimuli. These programs don't use fancy equipment. They use awareness, attention, recontextualization, and repeated practice. Exactly the principles Merzenich's monkey experiments demonstrated; repeated, attention-driven engagement with the pattern you're trying to change. The same processes that conditioned these responses in the first place, just reversed.

In 2025, a randomized controlled trial tested one of these programs on fibromyalgia patients. The results showed close to 50% reduction in pain in the active group compared to 9% in the control group. Depression was nearly halved. Perceived health increased by 47% in the active group versus 16% in controls. This was, according to the researchers, the first randomized controlled trial ever published on a neuroplasticity-based program for chronic illness. The findings were described as groundbreaking. The researchers noted they'd want to do longer studies, six months to a year, to see the full effects, since they recommend patients continue the program for at least six months to achieve complete recovery. For comparison, this study showed effect sizes 4-9 times larger than the gold standard pharmaceutical treatment of antidepressants, and maybe most importantly, the range given is because it’s helping multiple ‘different’ conditions at once. Something almost no mainstream medical intervention does. This study hints at the possibilities that open up when you use interventions that are actually addressing the upstream cause of disease.

But these interventions can't be patented. There's no device to sell, no pharmaceutical to market. The research is difficult to fund because no company has a financial interest in the outcome. One researcher noted explicitly that it's difficult to get funding for formal studies wherever pharmaceuticals are not involved. The studies that do get done are small, underfunded, and published in lower-tier journals. Which means the larger medical establishment can dismiss them as having insufficient evidence, not being rigorous enough, and needing far more research before widespread adoption. So the neuroplasticity research remains siloed, known to very select specialists, occasionally mentioned in academic papers, and rarely making it into standard clinical practice.

How thoughts alone maintain pathostasis

But the evidence keeps piling up anyway. In the 1980s Susan Nolen-Hoeksema, who would later become chair of psychology at Yale, began studying what she called "ruminative thinking.” She defined rumination as repetitive, passive thinking about one's problems, their causes, and their consequences. So basically when your thoughts circle the same worries over and over without resolving anything. Through decades of longitudinal studies following thousands of participants, she and other researchers documented that people who ruminated more developed a whole range of physical health problems at higher rates than those who didn't. Rumination reliably predicted future illness even after controlling for current health status. Something about the thinking pattern itself seemed to be driving disease.

In 2006 Brosschot and his colleagues explained how and why rumination is causing these outcomes. They realized that while a stressful event might last minutes or hours, rumination can keep the stress response activated for days, weeks, or years. Your body can't tell the difference between a threat that's currently happening and a threat you're just vividly imagining.

In 2014, Peggy Zoccola's team at Ohio University brought healthy young women into the lab and had them give a stressful speech. Then they randomly assigned half the women to ruminate about how the speech went, while the other half were distracted with neutral thoughts about sailing ships and grocery stores. The researchers drew blood samples and tracked inflammatory markers, and the women who ruminated showed sustained elevation in C-reactive protein, an inflammatory marker, that continued rising for at least an hour after the speech. While the markers of the women who were distracted returned to baseline.

A major meta-analysis published in Psychological Bulletin in 2016 synthesized the research across dozens of studies. The findings consistently showed that rumination and worry were associated with elevated blood pressure, elevated heart rate, elevated cortisol, and reduced heart rate variability. The same physiological patterns that show up in chronic disease. Thinking about stress was, physiologically speaking, producing the same effects as experiencing it.

And these weren't just temporary blips that resolved when people stopped worrying. In 1997, Kubzansky and her colleagues published a landmark prospective study where they followed 1,759 men without heart disease for twenty years. They measured their worry levels at the start, and after controlling for cholesterol, blood pressure, smoking, and diabetes—all the standard cardiac risk factors—worry independently predicted who would have heart attacks. Men in the highest worry category had more than double the risk compared to those in the lowest category, and there was a clear dose-response relationship. Meaning the more they worried, the more heart attacks they had over a two decade period.

Structural brain changes

In 2002, researchers at the National Centre for Biological Sciences published a foundational study in the Journal of Neuroscience demonstrating how chronic stress reshapes neural architecture. Vyas and colleagues subjected rats to chronic immobilization stress and then examined their brains at the cellular level. They found that in the hippocampus—the region that helps regulate memory, emotion, and the stress response itself—chronic stress caused dendritic atrophy. Meaning the neurons shrank and their branches retracted, and the structures they use to communicate with other neurons withered. These changes were visible under a microscope, and they correlated with impaired function. One of the functions of the hippocampus is to help stop the stress response, putting on the brakes and providing negative feedback to calm things down after a threat has passed. If you shrink the hippocampus, you weaken those brakes.

In the amygdala—the brain's threat detection center—the opposite happened. Neurons sprouted new dendrites, grew new branches, and formed more connections. The amygdala got stronger, more elaborate, and more connected to everything else. So the region responsible for triggering the alarm expanded its capacity while the region responsible for calming things down contracted.

The prefrontal cortex, which is the part of the brain responsible for executive control, and for consciously overriding automatic responses, shows similar changes. This is the part of the brain that can say "I know this feels dangerous but it's actually fine." Chronic stress causes dendritic retraction here too, weakening the very circuits that allow us to regulate our emotional responses. More recent research has revealed how this happens: microglia, the brain's immune cells, become overactive under chronic stress and start pruning synapses in the prefrontal cortex. A 2023 study showed that stress elevates complement C3, which tags synapses for elimination, and microglia then engulf them. The brain is literally dismantling its own regulatory capacity.

These changes persist even after the stressor is gone. The brain has been architecturally reorganized to maintain a state of vigilance: stronger threat detection, weaker threat regulation, reduced capacity to override the alarm once it's triggered. And this reorganized brain is now more likely to ruminate, which creates a feedback loop. In 2011, J. Paul Hamilton's team at Stanford used functional MRI to examine the brains of people who ruminated frequently, and they could actually see the neuroplastic maps that were being built through these thought patterns. Just as Merzenich saw in the monkeys. The pathways for self-focused worry had been practiced and strengthened, making rumination the path of least resistance.

So let's bring it all together. Rumination maintains pathostatic chemistry even in the absence of actual stressors—your thoughts alone keep the threat response firing. Those chemicals physically remodel the brain: the hippocampus shrinks, the prefrontal cortex loses synapses, the amygdala grows and becomes hyperconnected. And this remodeled brain is now wired to ruminate more easily and regulate less effectively, which maintains pathostasis, which drives more remodeling. Each piece making this feedback loop harder and harder to interrupt. Researchers have mapped each of these connections across thousands of papers.

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So what we’re seeing is that our brains can be remodelled into illness. Which doesn’t make a lot of evolutionary sense. Animals in the wild don’t get sick the way humans do; why would humans evolve this perfect set up for disease? Let’s look at that next.