Curiosity-driven exploration study Credit Francesco Poli & Maran Koolen (created using Pixabay and DALL-E, CC-BY 4.0, https://creativecommons.org/licenses/by/4.0/)
A new study published this week in PLOS Computational Biology, led by Francesco Poli from Radboud University in the Netherlands, found that individuals with more vital autistic traits demonstrated unique exploration patterns and increased persistence while playing a computer game. As a result, they performed better than those with lower levels of autistic traits.
Scientists understand that individuals exhibit curiosity and explore their surroundings to gain knowledge. The choices a person makes regarding what to explore significantly impact their learning. Research has demonstrated that the levels of exploration vary greatly among individuals.
In a recent study, researchers tested 77 university students using a curiosity-driven exploration task. In this task, participants needed to learn the hiding patterns of multiple characters to predict their locations. The participants’ levels of autistic traits were assessed through both self-reported questionnaires and those reported by their parents regarding social behaviour.
People with lower scores of general autistic traits were less persistent and sought learning opportunities by engaging with characters more in the early stages of exploration. People with higher scores of autistic traits were more persistent and explored for longer times, even when learning was not easy. This meant that they performed better on this task.
Dr Mary Doherty, Clinical Associate Professor at UCD School of Medicine
Recent groundbreaking research examining the experiences of autistic psychiatrists has found that those who are unaware of their autism may struggle to recognize the condition in their patients. This study, conducted by researchers from University College Dublin, London South Bank University, and Brighton and Sussex Medical School, is the first of its kind to explore the lives of neurodivergent psychiatrists. It was published today in BJPsych Open.
Dr. Mary Doherty, a Clinical Associate Professor at UCD School of Medicine, stated, “Understanding that you are autistic can be a transformative experience.” She also noted that over 187,000 people in England are currently waiting for an autism assessment. The situation becomes even more challenging when psychiatrists, who may be unaware of their autism, misdiagnose patients. Greater recognition of autism could provide benefits for both psychiatrists and their patients.
The research team, consisting of medical professionals and academics identifying as neurodivergent, conducted in-depth interviews with eight senior psychiatrists based in the UK. Six of these psychiatrists are consultants working within the NHS. Their specialities include various areas, including Child and Adolescent Mental Health and adult services, including intellectual disabilities.
The study examined how psychiatrists came to realize they were autistic, often through personal experiences like their child’s diagnosis or by noticing similarities between themselves and their autistic patients. Notably, some were even identified as autistic by their patients.
Once self-recognition took place, psychiatrists began to notice that many of their colleagues—particularly those specializing in autism or ADHD—might also be autistic without realizing it. This lack of awareness can lead to significant consequences, as these psychiatrists may unintentionally overlook the diagnosis in their autistic patients. However, after becoming aware of their neurodivergence, the psychiatrists found it easier to recognize autism in others and to establish therapeutic solid relationships.
The study also revealed that understanding their autism had a positive impact on the psychiatrists’ self-esteem and mental health. However, the researchers pointed out that many patients miss out on this benefit when assessed by psychiatrists who, while sharing their experiences, do not recognise they are also autistic.
Your brain processes what you see and makes continuous predictions based on your experiences. This predictive process may be less refined in autistic people.
When someone throws a ball at you, you instinctively know to catch it—even before you consciously think about it. In the past, people believed that the brain worked like a camera: an image of the flying ball enters through your eyes and is then processed by your brain. After that, the brain programs a suitable action in response. However, doesn’t that process take too long? Would you still be able to catch the ball in time?
Researchers Christian Keysers, Giorgia Silani, and Valeria Gazzola reveal that the brain processes information differently than expected. Christian explains, “Your brain doesn’t simply react to what your eyes see; instead, it predicts what will happen based on your expectations and past experiences. Doing this keeps our actions in sync with the ball, even though it takes the brain several hundred milliseconds to process visual input and coordinate movement. It plans to ensure enough time to execute the action and catch the ball. The image that enters through your eyes is primarily used to verify whether your expectations align with reality. It is only when there’s a discrepancy between your expectations and what you see that your brain relies on visual input to adjust its predictions more accurately.”
Predicting others
Ms Gazzola shared, “What’s interesting is that we use our motor programs and somatosensory cortices to predict the actions of others. For instance, when you perform a physical action, like lifting a carton of milk to pour some into your coffee, you have certain expectations about the carton’s weight and how it should feel in your hand as you lift it. Typically, you don’t consciously notice the weight of the carton because your brain has already predicted it. However, if someone else has finished the milk and the carton is much lighter than you anticipated, the sudden discrepancy between your expectations and the sensory feedback will catch your attention.”
“When you see someone else do so, you don’t directly feel the weight of the carton. Still, you can make predictions using your motor programs and test them against what you see. So, you still feel surprised if the carton flies skywards much faster than you expected. We think this has to do with so-called mirror neurons, cells within your motor cortex that become active when you see someone else act. This acts as a sort of ‘shortcut,’ allowing you to use your motor programs and the predictive machinery necessary for your actions to predict the behaviour of others.”
But what about emotions? Gazzola explains: “We know that regions in our brain that are involved in our own emotions become active while we witness the emotions of others. However, how we predict the emotions of others is not fully understood. Reviewing the literature revealed that the regions in our brain that are active when we receive a reward or punishment also become active when someone else receives a reward or punishment. Reward and punishment are therefore valuable predictors for the emotions of others.”
Complex system
Christian Keysers: “Imagine I have a button, and every time I press it, an actor starts screaming in pain. If I do this five times, your expectations change: the first time, it’s unexpected, but by the fifth time, you can predict what will happen.”
“According to the traditional theory of perception, where the brain only processes the image you see, you should see the same reaction in the brain each time. But if the outside world primarily serves to test your predictions, you’d expect a strong brain response the first time and a much smaller response the last time because you already know what will happen.”
“So what happens in the brain? Over many studies, we have seen that it’s quite complex. Some brain areas respond relatively consistently across all five times. At the same time, there are also brain regions where activity changes across the five times. In this review paper, we look at the many studies that have emerged on the topic to propose how these different brain systems organize into a coherent predictive brain. For example, if some actions become predictable, your premotor cortex knows how to act as your body. This region will then inhibit visual regions in your brain, leading to less visual input. What you perceive is no longer what you see but expect to see. Only if something unexpected happens will this inhibition become ineffective. The visual areas now show a strong response sent forwards to the premotor cortex to revise the predictions”.
Predictions and autism
It’s believed that the predictive system in people with autism is less well-tuned. This makes the world around them more unpredictable, leading to less suppressed stimuli. Christian Keysers: “Imagine standing in a crowded room with many people. Because our brain makes a lot of predictions, we can ignore most stimuli and focus only on what’s important. But when this predictive system doesn’t work well, such a busy environment can suddenly feel overwhelming.”
“The brain is complex and has the unique ability to adapt. It’s interesting to realize that your brain isn’t just a camera simply processing what comes in. Instead, your brain constantly operates based on predictions. Your brain is always ahead and continuously constructs what the world should be.”
Researchers at Flinders University tested the belief that autistic adults are more likely than non-autistic adults to be criminally exploited due to difficulties in recognizing criminal intent.
“It is not uncommon for defence lawyers, often with the backing of testimony from ‘expert’ witnesses, to claim that autistic adults struggle to interpret the intentions of others or understand their thoughts. This difficulty can make them more susceptible to being lured into criminal activity,” says Professor Neil Brewer, Matthew Flinders Distinguished Emeritus Professor of Psychology in the College of Education, Psychology, and Social Work.
“Such arguments reflect the widely-held perspective that difficulties reading others’ intentions, emotions, and motivations are fundamental features of autism.
However, this perspective may not withstand scrutiny, and we found that, in general, autistic adults are no more vulnerable to being involved in criminal acts than non-autistic adults.
“Furthermore, the difficulties in mindreading often associated with autism are not universally present among autistic adults.”
In a study published in the American Psychological Society’s journal, Law and Human Behavior, former PhD student Zoe Michael and her supervisor, Professor Neil Brewer, developed a new and realistic approach called the Suspicious Activity Paradigm (SAP). This paradigm was designed to evaluate how effectively adults can recognize and respond to cues that indicate social interactions may lead to criminal behaviour.
The study included 197 participants: 102 autistic adults and 95 non-autistic adults, who role-played in scenarios that progressively indicated criminal intent from their interactions.
They were asked about their reactions at different stages as the scenarios developed to evaluate their ability to recognize and respond to suspicious actions from others, thus gauging their susceptibility to being unknowingly drawn into criminal activities.
“We found that, overall, both autistic and non-autistic adults responded in similar ways to suspicious behaviour across various scenarios,” says Professor Brewer.
“Importantly, autistic adults did not show lower rates of suspicion or adaptive responses when compared to their non-autistic counterparts as the scenarios unfolded. Nor did they take longer to recognise the potentially problematic nature of the interaction.”
Building on previous research, the study found that verbal intelligence and Theory of Mind (ToM) – a term used to describe the ability to take the perspective or read the mind of others – predicted someone’s ability to recognise and respond to suspicious activity.
“Our findings indicate that the ability to understand others’ perspectives and intentions – and not the presence of an autism diagnosis – was a critical factor influencing their vulnerability to crime,” he says.
In other words, while autistic individuals who had difficulty discerning others’ intentions were vulnerable, the same was true of their non-autistic peers.
It is important to note, however, that a relatively small proportion of autistic individuals’ performance on the mindreading measure was below that of any of the non-autistic sample, a finding consistently replicated by the Flinders research team that developed the measure.
This indicates that there will be some autistic individuals who will likely be particularly vulnerable because of mindreading difficulties – but such challenges cannot be assumed.
“Thus, rather than defence lawyers and clinicians assuming, and arguing, that a diagnosis of autism automatically signals a particular vulnerability to being lured into crime, it is important to formally assess and demonstrate that a criminal suspect or defendant has significant mindreading difficulties that likely have rendered them vulnerable,” he adds.
A cerebral organoid showing rosettes (or whirls) of newly developing and migrating new neurons (shown in purplish-red). Credit Scripps Research
Researchers at Scripps Research have created personalized “mini-brains” (or organoids) from stem cells derived from patients with a rare and severe form of autism spectrum disorder and intellectual disability. These lab-grown organoids have enabled the team to gain deeper insights into how a specific genetic mutation contributes to autism spectrum disorder. Additionally, they found that an experimental drug called NitroSynapsin can reverse some brain dysfunction associated with autism in these models.
“Our research demonstrates how a genetic mutation linked to autism disrupts the normal balance of brain cells during development,” says Stuart A. Lipton, MD, PhD, Step Family Foundation Endowed Professor and co-director of the Neurodegeneration New Medicines Center at Scripps Research. However, we have also found potential ways to address this imbalance later in life.”
Learning from patients
Autism is a neurological and developmental disorder that impacts social interactions and communication and leads to repetitive interests and behaviours. The exact causes of autism are still not fully understood; various genetic variants have been linked to the disorder, but each accounts for only a small percentage of cases. For many years, research on autism has focused on creating models of the disorder in mice or examining isolated human brain cells. However, neither of these methods accurately captures the complexity of an interconnected human brain.
Lipton and his colleagues studied MEF2C haploinsufficiency syndrome (MHS), a rare and severe form of autism and intellectual disability caused by a genetic variation in the MEF2C gene. They isolated skin cells from patients with MHS and applied modern stem cell biology techniques to transform these cells into human stem cells. Subsequently, they grew them into small, millimetre-sized “mini-brain” organoids, allowing the researchers to investigate how the various types of brain cells interact with one another.
“We were able to replicate key features of patients’ brains to study their electrical activity and other properties,” says Lipton. “We even invited children into the lab to see their own mini-brains, which was an emotional experience for both the kids and their families.”
In healthy human brains and brain organoids, neural stem cells develop into nerve cells, or neurons, which communicate messages throughout the brain. They also differentiate into various types of glial cells, which support neurons and play important roles in signalling and immune function. A healthy brain maintains a balance between excitatory neurons, which enhance electrical signalling, and inhibitory neurons, which suppress it. Autism is associated with an imbalance between these types of neurons, often resulting in excessive excitation.
In the organoids created from cells of children with MHS, researchers found that neural stem cells more frequently developed into glial cells, resulting in a higher proportion of glial cells compared to neurons. Notably, the MHS organoids had fewer inhibitory neurons than normal, leading to excessive electrical signaling in these mini-brains, similar to what is observed in many human brains affected by autism.
A role for microRNA
When Lipton’s group probed exactly how MEF2C mutations could lead to this imbalance between cell types, they found nearly 200 genes directly controlled by the MEF2C gene. Three of these genes stood out—rather than encoding DNA that led to messenger (m)RNA and then protein expression, they encoded genes for microRNA molecules.
MicroRNAs (miRNAs) are small RNA molecules that bind to DNA to control gene expression rather than producing proteins themselves. This month, two scientists won the 2024 Nobel Prize in Physiology or Medicine for their work describing the discovery of miRNA molecules and how they can impact cell development and behaviour.
“In our study, a few specific miRNAs appear to be important in telling developing brain cells whether to become glial cells, excitatory neurons, or inhibitory neurons,” says Lipton. “Mutations in MEFC2 alter the expression of these miRNAs which, in turn, prevent the developing brain from making proper nerve cells and proper connections or synapses between nerve cells.”
Lipton’s group found that early-developing brain cells from patients with MHS have lower levels of three specific miRNAs. When the researchers added extra copies of these miRNA molecules to the patient-derived brain organoids, the mini-brains developed more normally, with a standard balance of neurons and glial cells.
A potential treatment
Since autism is generally not diagnosed during fetal brain development, treatments that aim to alter initial development—such as correcting a mutated gene or adding miRNA molecules to stop the imbalance of cell types—are not currently feasible. However, even after development, Lipton was already developing another drug that could help promote the balance between excitatory and inhibitory neurons.
Lipton’s group recently tested a drug they invented and patented called NitroSynapsin (also known as EM-036) for its ability to restore brain connections in “mini-brains” derived from cells affected by Alzheimer’s disease.
In the new paper, they tested whether the drug could also help treat the MHS form of autism. Using the patient-derived brain organoids, Lipton and his colleagues showed that in fully developed brain organoids that had an imbalance between cell types, NitroSynapsin could partially correct the imbalance, preventing the hyperexcitability of the neurons and restoring excitatory/inhibitory balance in the mini-brain. This also protects nerve cell connections or synapses.
More work is needed to show whether the drug improves the symptoms of patients with MHS or influences other types of autism spectrum disorder that are not caused by mutations in the MEF2C gene. Lipton hypothesizes this could be the case since MEF2C is known to influence many other genes associated with autism.
“We are continuing to test this drug in animal models to get it into people soon,” says Lipton. “This is an exciting step in that direction.”
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