A small percentage of people who consume psychedelics experience strange lingering effects, sometimes years after they took the drug.
- LSD flashbacks have been studied for decades, though scientists still aren't quite sure why some people experience them.
- A subset of people who take psychedelics and then experience flashbacks develop hallucinogen persisting perception disorder (HPPD), a rare condition in which people experience regular or near-constant psychedelic symptoms.
- There's currently no cure for the disorder, though some studies suggest medications may alleviate symptoms.
In February 2021, Josh was in his room and looking at his phone when he was struck by a strange feeling.
"The room looked normal, nothing was moving, but I felt as though I was under the influence of a psychedelic," he told Big Think.
As a teenager, Josh had experimented with LSD, mushrooms, and other psychedelics a couple dozen times. Now 25, he had been sober for about a year. He brushed off the incident.
But soon, Josh, which is not his real name, was struck again by the same strange feeling.
"I had no idea what was going on in my brain at that time and the anxiety and paranoia grew so intense that I became fearful I had developed everything from brain cancer to schizophrenia," he said.
The physical and psychological symptoms he began suffering were "devastating."
"The world [looked] crooked and out of focus, pictures had an eerie quality to them, things would go in and out of focus, at night while falling asleep I would experience vivid and terrifying hypnagogic hallucinations that made rest impossible."
After three weeks, Josh said his visual symptoms amplified with "unbelievable intensity."
"The floors would [breathe], paint on the walls looked wet, visual snow was so intense [that] pure black looked like it was glowing, at night I would see tracers everywhere, halos appeared around text. [...] I did not sleep, my thoughts were anxious and at times deranged, I had unbelievably intense dereliction that made the world seem fake."
What Josh experienced is commonly called an LSD flashback. It's a mysterious phenomenon in which someone who's previously taken a hallucinogenic drug suddenly and temporarily experiences the effects of that drug days, weeks, or even years after consuming it.
Flashbacks can occur after taking a wide range of psychedelic drugs. But compared to other hallucinogens, flashbacks seem to be most common among people who have consumed LSD, according to studies.
Credit Newwup via Adobe Stock
People have reported acid flashbacks for decades. The earliest recorded case may be
Havelock Ellis' 1898 report of taking mescaline and then experiencing sustained heightened sensitization to "the more delicate phenomena of light and shade and color."
But it wasn't until the 1950s, little more than a decade after Albert Hoffman first synthesized LSD, that scientists started researching LSD and its potential long-term effects. While studies have illuminated some aspects of how psychedelics affect the brain, scientists still have much to learn about the nature of LSD flashbacks, what causes them, and how to treat them.
What's certain, however, is that a small percentage of people who consume psychedelics report bizarre and sometimes debilitating effects that emerge long after taking hallucinogens.
Symptoms of LSD flashbacks
Among the most common symptoms of LSD flashbacks are visual distortions. In a 1983 study titled " Visual Phenomenology of the LSD Flashback," the psychiatrist and LSD researcher Dr. Henry David Abraham described 16 common visual disturbances reported by people with LSD flashbacks. To name a few:
- Acquired color confusion: The color of objects changed or presented a newly discovered problem of color confusion.
- Difficulty reading: Text may appear jumbled or leave afterimages of the type against the background of the page.
- Geometric phosphenes: Phosphenes, or eigengrau, are non-specific luminous perceptions that occur when the eyes are closed and may originate from entopic (i.e., arising from within the eye itself) stimuli in normal persons. They also may be induced by gentle pressure on the closed eyelid.
- Pareidolias: This is literally an image within an image. These were described when a subject gazed into a finely reticulated design in linoleum, veneer, or a cloud formation. Besides the abstract pattern of the linoleum, subjects often would be able to see a series of concrete images as well, such as "a fish," "a face," and "a little boy."
- Macropsia: Macropsia is the perception of an object larger than it really is. A characteristic description of this phenomenon came from a subject who noticed that his hand was enormous and then of normal size a few seconds later.
- Micropsia: Micropsia is the perception of an object smaller than reality. One subject said, "My feet looked so tiny, like they were a million miles away."
The effects of LSD flashbacks aren't limited to visual distortions. In a 1970 study called "Analysis of the LSD Flashback," researchers sorted LSD flashbacks into three broad categories: perceptual, somatic (meaning of the body), and emotional.
The emotional flashback is "far more distressing" than the other two, the researchers wrote, providing a case study of a 21-year-old woman who was suffering from LSD flashbacks:
"The patient had these frightening flashbacks during the day, while walking down the street, after smoking marijuana or drinking wine, during the night, and occasionally even while asleep. In one situation she awoke during the middle of the night with a feeling of panic and began running around her house fleeing an imagined threat she could not identify or comprehend. She had taken LSD a number of times, but her last few trips were bad ones with panic and fright followed by loneliness to the point of suicidal despair when she 'came down.' The combination of bad trips and emotional flashbacks made her seek professional help because of her fear that she would harm herself."
To be sure, LSD flashbacks aren't always emotionally distressing. A 2010 survey of 600 hallucinogen users found that, of the minority of users who reported experiencing at least one flashback, only 3 percent described it as a negative experience. In fact, some people enjoyed their flashbacks. On the website Erowid, which promotes research of psychedelic drugs, one user wrote:
"After 2 years of my last acid trip, while on vacation in a very nice wilderness place I was sitting on a rock and then I experienced a clear acid high. I was looking at a very steep hill and suddenly it started moving in nice patterns, exactly as one sees patterns while on acid. It wasn't something uncomfortable. In fact it was really pleasant and there was absolutely no trace of the nasty anxiousness after effects common to LSD. It lasted approximately 2 minutes and I enjoyed it very much."
But some LSD flashbacks are neither brief nor pleasant. A subset of people who use psychedelics develop hallucinogen persisting perception disorder (HPPD), a rare and poorly understood condition in which people experience omnipresent or recurring flashbacks. While the symptoms of HPPD vary, the condition can cause intense pain, irreversible perceptual distortions, emotional and psychological distress, and even suicidal thoughts.
HPPD: The never-ending trip
HPPD is estimated to affect between one to five percent of LSD users, though the actual figure is impossible to determine without better data. The disorder was first described formally in 1986 by the American Psychiatric Association's Diagnostic & Statistical Manual of Mental Disorders, 3rd edition, revised (DSM-III-R). The current edition of the manual (DSM-5) says patients need to meet several criteria to be diagnosed with HPPD:
- Patients must reexperience perceptual symptoms they experienced while intoxicated with the hallucinogen.
- These symptoms must cause "significant distress or impairment in social, occupational, or other important areas of functioning."
- These symptoms aren't due to a separate medical condition or mental disorder.
So, what's the difference between a flashback and HPPD? Mainly frequency and duration. A 2017 review published in Frontiers in Psychiatry noted that while "a flashback is usually reported to be infrequent and episodic, HPPD is usually persisting and long-lasting."
A 2014 review published in the Israel Journal of Psychiatry and Related Sciences outlined two types of HPPD. The first, HPPD I, is the "flashback type," which is a generally short-term, non-distressing, benign and reversible state accompanied by a pleasant affect. The severity of HPPD I varies, with some people describing their mild flashbacks as annoying, while others say it's like getting "free trips."
But HPPD II is a different beast. The condition can be permanent, with perceptual distortions and other symptoms manifesting irregularly or almost constantly.
"The symptoms usually include palinopsia (afterimages effects), the occurrence of haloes, trails, akinetopsia, visual snows, etc.," according to the aforementioned 2017 review. "Sounds and other perceptions are usually not affected. Visual phenomena have been reported to be uncontrollable and disturbing. Symptomatology may be accompanied by depersonalization, derealization, anxiety, and depression."
What causes flashbacks and HPPD?
When asked what causes flashbacks and HPPD, Dr. Abraham told Popular Science, "I've spent my life studying this problem and I don't know, is the short answer."
But researchers have proposed explanations. One centers on memory. Because psychedelics can cause extremely powerful and emotional experiences, it's theoretically possible that certain environmental stimuli can remind people of those experiences, and then memory "transports" them back into that subjective mindset — similar to how a soldier with post-traumatic stress disorder might suffer an episode after hearing a loud, sudden noise.
Another hypothesis involves how LSD interacts with the brain's visual processing center. Dr. Abraham proposed that HPPD may arise due to "disinhibition of visual processing related to a loss of serotonin receptors on inhibitory interneurons," which may be caused by consuming LSD.
The basic idea is that LSD somehow changes the way the brain interprets visual stimuli. That might explain why people with HPPD have difficulty properly "disengaging" from the things they see around them. For example, a red stoplight might appear not as a discrete red circle but as a streak of red light painted across their field of vision; or a strobe light might not appear as a flickering light but a light that's constantly on.
Credit Yurok Aleksandrovich via Adobe Stock
"Such a locking of visual circuitry into an 'on' position following perception of a visual stimulus would explain such diverse complaints as trailing, color intensification, positive afterimages, phosphenes, and color confusions, each of which may represent a failure of the respective visual function to turn off the brain's response to the stimulus once the stimulus is gone," Dr. Abraham
It's also possible that people are genetically predisposed to HPPD and that ingesting LSD is the key that unlocks the disorder. This hypothesis would help explain why people have reportedly developed HPPD after taking a single, moderate dose of LSD.
Ultimately, the exact causes of HPPD are unclear. Partially as a result, there's currently no cure for the disorder, though studies show that people with HPPD have reported improvements in symptomatology after taking benzodiazepines. There's also anecdotal evidence that fasting can alleviate the disorder.
Despite uncertainty over the causes of HPPD, researchers do have a good idea of what can trigger "flare-ups" of HPPD. Dr. Abraham's 1983 study listed the most common triggers, some of which include:
- Emergence into a dark environment
- Intention (intentionally inducing visual aberrations by, say, staring at a blank wall)
People with HPPD describe the condition
To get a better understanding of HPPD, Big Think posted a questionnaire to the HPPD community on Reddit. Here are some of the responses:
How did HPPD first manifest for you?
"First I noticed highly enhanced creativity and intense visuals when [high on] weed and I really enjoyed that part. The realization that this is not going to go away soured the whole experience tho."
"My enhanced creativity left me after about a week and what I was left with was mild visual snow. I hardly knew anything about HPPD at the time and just didn't really care about my symptoms and still thought they were just going to vanish at some point, which they didn't. I kept taking drugs simply because I was addicted and felt like life is no fun without them. My HPPD got gradually worse over time and more symptoms appeared. First, I noticed mild tracers, which got worse over time (again due to continued drug use) and then tinnitus and brain fog. But primarily my symptoms are visual."
Are your symptoms episodic or constant?
"Both constant and episodic," wrote user LotsOfShungite. "A stressful event can trigger my symptoms off into the deep end."
"Except the brain fog and head pressure that varies, my visual disturbances are constant. The most debilitating ones are the visual snow, especially when I'm inside except if I watch the TV since it filters some of it out. It's also VERY frustrating that I no longer can focus on objects/details (can't stare) and the astigmatism-like symptoms that I got, like blurriness, especially in the distance and ghosting (double vision) plus starbursts from strong light sources. When I'm outside, the pattern glare is really annoying, same with the excessive amount of floaters that came with this. I also see halos from light sources."
"My symptoms are mostly constant and only change through rather obvious outside influences, such as certain drugs (almost all drugs), stress, lack of sleep, etc. Although my HPPD is quite pronounced, I have learned to accept it and almost only notice it when I pay attention to it. I always [know] it's there and it somewhat bugs me but I get along."
What are some common misconceptions about HPPD?
"One of if not the biggest 'misconception' is that many people believe that HPPD does not exist. But I guess there is no way to prove to another person that it does, so this is gonna stay the case until HPPD enters the public consciousness of the psychedelic community."
"They usually don't understand anything about it since most haven't heard about it, which really is crazy considering how debilitating this disorder is for many. And as Dr. Abraham said: in the medical field it's highly under- and misdiagnosed. Often as psychosis."
Lopyriev via Adobe Stock
Hope for HPPD
Since experiencing his first acid flashback in February, Josh has found a few helpful strategies to minimize symptoms, including seeing a psychologist, staying sober, getting enough sleep, staying productive, and talking regularly with friends. He seemed optimistic about the future:
"The symptoms will lessen with time and sobriety, and HPPD provides an opportunity to improve yourself. That being said, because thoughts of suicide are apparently common with people that have HPPD, the medical community should take the condition seriously. Especially given how many people use psychedelics today."
While the future of HPPD research remains unclear, general psychedelic research is going through something of a renaissance. In recent years, researchers have published a growing body of studies showing how psychedelics like psilocybin, LSD, and MDMA can help treat conditions like depression, anxiety, post-traumatic stress disorder, and existential distress.
But, among people with HPPD, opinions on the utility of psychedelics vary. Josh advised caution:
"I would not recommend [hallucinogenic] drugs be taken for recreational purposes. They are tools to help us treat illnesses and should be treated as such. If someone has depression or other mental health issue, maybe psychedelics administered in a clinical setting by a doctor is appropriate, but otherwise, playing with your brain like it's a chemistry playset is asking for trouble down the road."
New research suggests that there is no "typical" form of Alzheimer's disease, as the condition can manifest in at least four different ways.
- A new study suggests that not all cases of Alzheimer's are the same.
- The disease progresses differently depending on where the tau protein is accumulating in the brain.
- This finding may provide a new route for research and treatment options.
A new study by an international team of researchers suggests that there are at least four distinct forms of Alzheimer's disease, each of which attacks a different part of the brain. The findings, published in Nature Medicine, may be the foundation for a new understanding of a disease which is expected to affect millions of people in the coming decades.
The leading hypothesis on the mechanism of Alzheimer's is that the disease is caused by unusual aggregation and spread of the tau protein in the brain. While there is still debate over if the strange behavior of these proteins is the cause of Alzheimer's or merely a symptom of the disease, the spread of such proteins can be used to identify the condition.
The authors reviewed the positron emission tomography (PET) data of 1,143 people. The PET images allowed the scientists to view where in the brain tau proteins were building up. An algorithm was applied to this data which was able to categorize the patterns in the images. In those brains with tau protein abnormalities, there were four distinct variations in how they manifested in the brain as seen below:
The four different Alzheimer's subtypes identified by the study. Areas in warmer colors had higher concentrations of tau proteins. The progression of the disease was related to the region of the brain that was most impacted. Image: Jacob Vogel
Four types of Alzheimer's disease
This could mean that there are four subtypes of Alzheimer's, each with different affected areas of the brain, symptoms, and prognoses. The authors described them as follows:
Type one is characterized by the tau protein spreading within the temporal lobe, impacting memory. This type was observed in 33% of Alzheimer's cases.
Type two is the inverse of type one in many ways. The tau protein spreads primarily in the cerebral cortex rather than in the temporal lobe. Patients with this variation have fewer memory problems than those with type one but more difficulties with planning and performing actions. This type appeared in 18% of cases.
Type three targets the visual cortex, the part of the brain that processes visual information. Those with this variant had particular difficulty with orientation, movement, and processing sensory information. This type occurred in 30% of cases.
Type four features the protein spreading in the left hemisphere of the brain and seems to principally affect language ability. This manifested in the remaining 19% of cases.
Beyond the differences in symptoms and pathology, the prognosis of each subtype appears to differ. After reviewing the long-term data of the patients, it appears that people with the third subtype have the slowest rate of mental decline, while those with the fourth endured a much steeper rate of facility loss.
Study co-author Oskar Hansson of Lund University in Sweden, commented on the findings in a press release:
"We identified four clear patterns of tau pathology that became distinct over time. The prevalence of the subgroups varied between 18 and 30 percent, which means that all these variants of Alzheimer's are actually quite common and no single one dominates as we previously thought. The varied and large databases of tau-PET that exist today, along with newly developed methods for machine learning that can be applied to large amounts of data, made it possible for us to discover and characterize these four subtypes of Alzheimer's. However, we need a longer follow-up study over five to ten years to be able to confirm the four patterns with even greater accuracy."
If the authors are correct, a more accurate Alzheimer's diagnosis may help provide specialized treatment to future patients.
A lab identifies which genes are linked to abnormal repetitive behaviors found in addiction and schizophrenia.
These behaviors, termed stereotypies, are also apparent in animal models of drug addiction and autism.
In a new study published in the European Journal of Neuroscience, researchers at the McGovern Institute for Brain Research have identified genes that are activated in the brain prior to the initiation of these severe repetitive behaviors.
"Our lab has found a small set of genes that are regulated in relation to the development of stereotypic behaviors in an animal model of drug addiction," says MIT Institute Professor Ann Graybiel, who is the senior author of the paper. "We were surprised and interested to see that one of these genes is a susceptibility gene for schizophrenia. This finding might help to understand the biological basis of repetitive, stereotypic behaviors as seen in a range of neurologic and neuropsychiatric disorders, and in otherwise 'typical' people under stress."
A shared molecular pathway
In work led by Research Scientist Jill Crittenden, scientists in the Graybiel lab exposed mice to amphetamine, a psychomotor stimulant that drives hyperactivity and confined stereotypies in humans and in laboratory animals and that is used to model symptoms of schizophrenia.
They found that stimulant exposure that drives the most prolonged repetitive behaviors led to activation of genes regulated by Neuregulin 1, a signaling molecule that is important for a variety of cellular functions including neuronal development and plasticity. Neuregulin 1 gene mutations are risk factors for schizophrenia.
The new findings highlight a shared molecular and circuit pathway for stereotypies that are caused by drugs of abuse and in brain disorders, and have implications for why stimulant intoxication is a risk factor for the onset of schizophrenia.
"Experimental treatment with amphetamine has long been used in studies on rodents and other animals in tests to find better treatments for schizophrenia in humans, because there are some behavioral similarities across the two otherwise very different contexts," explains Graybiel, who is also an investigator at the McGovern Institute and a professor of brain and cognitive sciences at MIT. "It was striking to find Neuregulin 1 — potentially one hint to shared mechanisms underlying some of these similarities."
Drug exposure linked to repetitive behaviors
Although many studies have measured gene expression changes in animal models of drug addiction, this study is the first to evaluate genome-wide changes specifically associated with restricted repetitive behaviors.
Stereotypies are difficult to measure without labor-intensive direct observation, because they consist of fine movements and idiosyncratic behaviors. In this study, the authors administered amphetamine (or saline control) to mice and then measured with photobeam-breaks how much they ran around. The researchers identified prolonged periods when the mice were not running around (i.e., were potentially engaged in confined stereotypies), and then they videotaped the mice during these periods to observationally score the severity of restricted repetitive behaviors (e.g., sniffing or licking stereotypies).
They gave amphetamine to each mouse once a day for 21 days and found that, on average, mice showed very little stereotypy on the first day of drug exposure but that, by the seventh day of exposure, all of the mice showed a prolonged period of stereotypy that gradually became shorter and shorter over the subsequent two weeks.
"We were surprised to see the stereotypy diminishing after one week of treatment. We had actually planned a study based on our expectation that the repetitive behaviors would become more intense, but then we realized that this was an opportunity to look at what gene changes were unique to that day of high stereotypy," says first author Jill Crittenden.
The authors compared gene expression changes in the brains of mice treated with amphetamine for one day, seven days, or 21 days. They hypothesized that the gene changes associated specifically with high-stereotypy-associated seven days of drug treatment were the most likely to underlie extreme repetitive behaviors and could identify risk-factor genes for such symptoms in disease.
A shared anatomical pathway
Previous work from the Graybiel lab has shown that stereotypy is directly correlated to circumscribed gene activation in the striatum, a forebrain region that is key for habit formation. In animals with the most intense stereotypy, most of the striatum does not show gene activation, but immediate early gene induction remains high in clusters of cells called striosomes. Striosomes have recently been shown to have powerful control over cells that release dopamine, a neuromodulator that is severely disrupted in drug addiction and in schizophrenia. Strikingly, striosomes contain high levels of Neuregulin 1.
"Our new data suggest that the upregulation of Neuregulin-responsive genes in animals with severely repetitive behaviors reflects gene changes in the striosomal neurons that control the release of dopamine," Crittenden explains. "Dopamine can directly impact whether an animal repeats an action or explores new actions, so our study highlights a potential role for a striosomal circuit in controlling action-selection in health and in neuropsychiatric disease."
Patterns of behavior and gene expression
Striatal gene expression levels were measured by sequencing messenger RNAs (mRNAs) in dissected brain tissue. mRNAs are read out from "active" genes to instruct protein-synthesis machinery in how to make the protein that corresponds to the gene's sequence. Proteins are the main constituents of a cell, thereby controlling each cell's function. The number of times a particular mRNA sequence is found reflects the frequency at which the gene was being read out at the time that the cellular material was collected.
To identify genes that were read out into mRNA before the period of prolonged stereotypy, the researchers collected brain tissue 20 minutes after amphetamine injection, which is about 30 minutes before peak stereotypy. They then identified which genes had significantly different levels of corresponding mRNAs in drug-treated mice than in mice treated with saline.
A wide variety of genes showed modest mRNA increases after the first amphetamine exposure, which induced mild hyperactivity and a range of behaviors such as walking, sniffing, and rearing in the mice.
By the seventh day of treatment, all of the mice were engaged for prolonged periods in one specific repetitive behavior, such as sniffing the wall. Likewise, there were fewer genes that were activated by the seventh day relative to the first treatment day, but they were strongly activated in all mice that received the stereotypy-inducing amphetamine treatment.
By the 21st day of treatment, the stereotypy behaviors were less intense, as was the gene upregulation — fewer genes were strongly activated, and more were repressed, relative to the other treatments. "It seemed that the mice had developed tolerance to the drug, both in terms of their behavioral response and in terms of their gene activation response," says Crittenden.
"Trying to seek patterns of gene regulation starting with behavior is correlative work, and we did not prove 'causality' in this first small study," explains Graybiel. "But we hope that the striking parallels between the scope and selectivity of the mRNA and behavioral changes that we detected will help in further work on the tremendously challenging goal of treating addiction."
This work was funded by the National Institute of Child Health and Human Development, the Saks-Kavanaugh Foundation, the Broderick Fund for Phytocannabinoid Research at MIT, the James and Pat Poitras Research Fund, The Simons Foundation, and The Stanley Center for Psychiatric Research at the Broad Institute.
A recent study used fMRI to compare the brains of psychopathic criminals with a group of 100 well-functioning individuals, finding striking similarities.
- The study used psychological inventories to assess a group of violent criminals and healthy volunteers for psychopathy, and then examined how their brains responded to watching violent movie scenes.
- The fMRI results showed that the brains of healthy subjects who scored high in psychopathic traits reacted similarly as the psychopathic criminal group. Both of these groups also showed atrophy in brain regions involved in regulating emotion.
- The study adds complexity to common conceptions of what differentiates a psychopath from a "healthy" individual.
When considering what precisely makes someone a psychopath, the lines can be blurry.
Psychological research has shown that many people in society have some degree of malevolent personality traits, such as those described by the "dark triad": narcissism (entitled self-importance), Machiavellianism (strategic exploitation and deceit), and psychopathy (callousness and cynicism). But while people who score high in these traits are more likely to end up in prison, most of them are well functioning and don't engage in extreme antisocial behaviors.
Now, a new study published in Cerebral Cortex found that the brains of psychopathic criminals are structurally and functionally similar to many well-functioning, non-criminal individuals with psychopathic traits. The results suggest that psychopathy isn't a binary classification, but rather a "constellation" of personality traits that "vary in the non-incarcerated population with normal range of social functioning."
Assessing your inner psychopath
The researchers used functional magnetic resonance imaging (fMRI) to compare the brains of violent psychopathic criminals to those of healthy volunteers. All participants were assessed for psychopathy through commonly used inventories: the Hare Psychopathy Checklist-Revised and the Levenson Self-Report Psychopathy Scale.
Experimental design and sample stimuli. The subjects viewed a compilation of 137 movie clips with variable violent and nonviolent content.Nummenmaa et al.
Both groups watched a 26-minute-long medley of movie scenes that were selected to portray a "large variability of social and emotional content." Some scenes depicted intense violence. As participants watched the medley, fMRI recorded how various regions of their brains responded to the content.
The goal was to see whether the brains of psychopathic criminals looked and reacted similarly to the brains of healthy subjects who scored high in psychopathic traits. The results showed similar reactions: When both groups viewed violent scenes, the fMRI revealed strong reactions in the orbitofrontal cortex and anterior insula, brain regions associated with regulating emotion.
These similarities manifested as a positive association: The more psychopathic traits a healthy subject displayed, the more their brains responded like the criminal group. What's more, the fMRI revealed a similar association between psychopathic traits and brain structure, with those scoring high in psychopathy showing lower gray matter density in the orbitofrontal cortex and anterior insula.
There were some key differences between the groups, however. The researchers noted that the structural abnormalities in the healthy sample were mainly associated with primary psychopathic traits, which are: inclination to lie, lack of remorse, and callousness. Meanwhile, the functional responses of the healthy subjects were associated with secondary psychopathic traits: impulsivity, short temper, and low tolerance for frustration.
Overall, the study further illuminates some of the biological drivers of psychopathy, and it adds nuance to common conceptions of the differences between psychopathy and being "healthy."
Why do some psychopaths become criminals?
The million-dollar question remains unanswered: Why do some psychopaths end up in prison, while others (or, people who score high in psychopathic traits) lead well-functioning lives? The researchers couldn't give a definitive answer, but they did note that psychopathic criminals had lower connectivity within "key nodes of the social and emotional brain networks, including amygdala, insula, thalamus, and frontal pole."
"Thus, even though there are parallels in the regional responsiveness of the brain's affective circuit in the convicted psychopaths and well-functioning subjects with psychopathic traits, it is likely that the disrupted functional connectivity of this network is specific to criminal psychopathy."
Neuroplasticity is a major driver of learning and memory in humans.
Neuroplasticity – the ability of neurons to change their structure and function in response to experiences – can be turned off and on by the cells that surround neurons in the brain, according to a new study on fruit flies that I co-authored.
The big idea
As fruit fly larvae age, their neurons shift from a highly adaptable state to a stable state and lose their ability to change. During this process, support cells in the brain – called astrocytes – envelop the parts of the neurons that send and receive electrical information. When my team removed the astrocytes, the neurons in the fruit fly larvae remained plastic longer, hinting that somehow astrocytes suppress a neuron's ability to change. We then discovered two specific proteins that regulate neuroplasticity.
Sarah DeGenova Ackerman, CC BY-ND
Why it matters
The human brain is made up of billions of neurons that form complex connections with one another. Flexibility at these connections is a major driver of learning and memory, but things can go wrong if it isn't tightly regulated. For example, in people, too much plasticity at the wrong time is linked to brain disorders such as epilepsy and Alzheimer's disease. Additionally, reduced levels of the two neuroplasticity-controlling proteins we identified are linked to increased susceptibility to autism and schizophrenia.
Similarly, in our fruit flies, removing the cellular brakes on plasticity permanently impaired their crawling behavior. While fruit flies are of course different from humans, their brains work in very similar ways to the human brain and can offer valuable insight.
One obvious benefit of discovering the effect of these proteins is the potential to treat some neurological diseases. But since a neuron's flexibility is closely tied to learning and memory, in theory, researchers might be able to boost plasticity in a controlled way to enhance cognition in adults. This could, for example, allow people to more easily learn a new language or musical instrument.
In this image showing a developing fruit fly brain on the right and the attached nerve cord on the left, the astrocytes are labeled in different colors showing their wide distribution among neurons.Sarah DeGenova Ackerman, CC BY-ND
How we did the work
My colleagues and I focused our experiments on a specific type of neurons called motor neurons. These control movements like crawling and flying in fruit flies. To figure out how astrocytes controlled neuroplasticity, we used genetic tools to turn off specific proteins in the astrocytes one by one and then measured the effect on motor neuron structure. We found that astrocytes and motor neurons communicate with one another using a specific pair of proteins called neuroligins and neurexins. These proteins essentially function as an off button for motor neuron plasticity.
What still isn't known
My team discovered that two proteins can control neuroplasticity, but we don't know how these cues from astrocytes cause neurons to lose their ability to change.
Additionally, researchers still know very little about why neuroplasticity is so strong in younger animals and relatively weak in adulthood. In our study, we showed that prolonging plasticity beyond development can sometimes be harmful to behavior, but we don't yet know why that is, either.
I want to explore why longer periods of neuroplasticity can be harmful. Fruit flies are great study organisms for this research because it is very easy to modify the neural connections in their brains. In my team's next project, we hope to determine how changes in neuroplasticity during development can lead to long–term changes in behavior.
There is so much more work to be done, but our research is a first step toward treatments that use astrocytes to influence how neurons change in the mature brain. If researchers can understand the basic mechanisms that control neuroplasticity, they will be one step closer to developing therapies to treat a variety of neurological disorders.