Mind’s sensory switchboard has advanced connections to autism | Spectrum
Since sensory differences became part of the diagnostic criteria for autism in 2013, more and more autism researchers have been drawn to the thalamus, the egg-shaped sensory relay station deep in the brain. The surge of interest has created an argument for the thalamus as an important sensory filter that may function differently in autism, and helps explain why some autistic people are unusually sensitive to (or sometimes attracted to) sensory stimuli.
But it has also suggested that the role of the thalamus in autism goes beyond the sensory world. New research shows that the thalamus affects functions as diverse as sleep, social cognition, attention, and learning.
“The thalamus plays a role in many of the cognitive functions involved in autism, so studying it is a breeze,” said Antonio Hardan, professor of psychiatry and behavioral science at Stanford University in California.
Studies of the role of the thalamus in autism have also expanded our knowledge of the structure of the region by assigning different functions to subregions and shedding light on how they work with the rest of the brain. Links between the thalamus and autism genes and traits “lead us to think much more carefully about what the thalamus is doing,” says Guoping Feng, professor of brain and cognitive science at the Massachusetts Institute of Technology, Cambridge.
Leaking filters:
It has long been believed that the thalamus’s job is to carry signals from the eyes, ears, and other sensory organs to the cerebral cortex, the outer layer of the brain, where the information is processed. In the mid-2000s, researchers found that signals from the thalamus help determine how parts of the cortex in developing mice are attuned to specific sensory stimuli, underscoring the role of structure in brain maturation.
“This really suggested that the thalamus might play a role in atypical development, the atypical functional specialization of the cerebral cortex in autism,” said Ralph-Axel Müller, professor of psychology at San Diego State University in California.
Scientists soon documented atypical communication between the thalamus and cortex in people with autism. In 2006, Müller and his team reported that autistic people have unusually strong functional connectivity – a measure of how synchronized two brain regions are in their activity – between the thalamus and parts of the cortex. Other studies since then have shown changes in the connectivity between the thalamus and cortex in autism.
Researchers have accumulated ample evidence that the thalamus contributes to unusual sensory responses in people with autism. For example, the stronger the connections between the thalamus and the auditory cortex, the more sensitive an autistic person reacts to sounds, reported Müller’s team in 2018. And a study with 38 children, half of whom were autistic, showed unusual communication between the thalamus and the cerebral cortex in autistic children, if they were exposed to loud traffic noise and a scratchy piece of cloth was rubbed on their arm.
Changes in brain chemistry offer more support for a central role of the thalamus in autism. The thalamus of people with autism contains low levels of N-acetyl aspartate, a marker of neural integrity, and has other chemical differences from controls, Hardan and colleagues reported in 2018. Two years later, the researchers reported on a potential deficit in levels of gamma-aminobutyric acid (GABA), a signaling molecule that dampens brain activity, in both the thalamus and the prefrontal cortex in adults with autism. Low levels of GABA in neural circuits connecting the thalamus and cerebral cortex have also been linked to sensory sensitivity in people with autism, where typical sensory stimuli become bothersome or overwhelming.
A deficiency in GABA can make the thalamus not only more receptive to stimuli, but also less selective in the information it passes on, says Michael Halassa, professor of brain and cognitive science at the Massachusetts Institute of Technology. This means that the thalamus is not only a relay station, but also a filter that is responsible for amplifying important sensory information and blocking out unimportant information. And a “leaky” thalamic filter can help explain the difficulty some autistic people have, such as focusing on a particular conversation at a party or turning off the sound of a ticking clock, says Halassa.
This filtering function also helps regulate sleep, in part by suppressing sensory input when people are sleeping. A thalamus that does not filter out stimuli during slumber can cause insomnia or other sleep problems that are common in autistic people. To support this assumption, young autistic children with atypically strong connections between the thalamus and cerebral cortex also tend to have more sleep problems than those with weaker connections, as Müller’s team showed in July.
Social piece:
The psychologist Aarti Nair has been investigating the functional connectivity between the thalamus and the cerebral cortex in people with autism since her doctoral student in Müller’s laboratory in the early 2010s. Their studies suggest a pattern of over-connectivity between the thalamus and sensory areas of the cortex and under-connectivity to areas involved in social cognition, memory, and planning, such as the prefrontal cortex. The work is part of a growing body of evidence that the role of the thalamus in autism extends to emotions, cognition, and behavioral regulation.
“Baby siblings” – children who have an older autistic sibling – show this pattern of altered connectivity between the thalamus and cortex at 6 weeks of age, Nair and her colleagues reported in September. Nair and Müller’s earlier studies in older children (ages 7-17) link this altered connectivity to social difficulties in autistic people, as well as to some of their problems with executive function, including impulse control and cognitive flexibility, which are essential for smooth functioning social interactions are required. “That social aspect really stands out,” says Nair, now an assistant professor of psychology at Loma Linda University in California.
Studies in mouse models of autism also support a role for the thalamus in social behavior. Researchers reported in 2017 that activity in a circuit connecting the prefrontal cortex and part of the thalamus called the mediodorsal thalamus is weaker than normal in three mouse models of autism and is associated with behavioral changes in one of the mouse models (social Behavior was not tested in the other two). But surprisingly, inhibiting the circulation – rather than increasing its activity – alleviates these social problems.
“I was like, ‘Geez, maybe these changes I’m seeing at the cortex level are really compensatory changes,'” said Audrey Brumback, assistant professor of neurology and pediatrics at the University of Texas at Austin. In other words, changes in cortical function can compensate for atypical activities deeper in the brain. This idea also suggests a new strategy for therapy: Perhaps in some cases we “don’t want us to want to reverse the things the brain is doing. Actually, we might want to improve these things, ”she says.
Brumback has since identified some of the specific neurons involved in these effects. She and her colleagues found in one of the autism mouse models decreased activity in a number of neurons that send signals from the thalamus to the prefrontal cortex. In other experiments with wild-type mice, the researchers showed that activation of the same neurons that connect the mediodorsal thalamus and medial prefrontal cortex made the animals less social; they spend less time examining other mice. Taken together, these results suggest that the prefrontal cortex requires input from the thalamus to regulate behavior.
The talks of the thalamus with the prefrontal cortex may also underlie restricted interests and repetitive behaviors in autism, other researchers speculate. A disturbed thalamus may not help suppress the impulse to repeat a behavior or fixate on something when it’s time to move on, Hardan says. He examines this hypothesis by looking for links between repetitive behaviors and changes in brain chemistry in the thalamus and other areas of the brain.
Share and conquer:
Brumback and others are also working to understand the anatomy of the thalamus, which is made up of many subunits, or nuclei. Each core has connections to specific parts of the brain and likely different functions that can affect certain autism characteristics. “It’s a relatively small structure that is incredibly complex in terms of its functional organization,” says Müller.
Brumback’s work suggests a role for the mediodorsal thalamus in social behavior, while other nuclei appear to control aspects of learning, attention, and other cognitive functions. In a 2016 study, Feng, Halassa, and their colleagues showed that mice lacking the autism-related gene PTCHD1 in the thalamic reticular nucleus are hyperactive and inattentive, suggesting that this sub-region may play a role in attention . The breakdown of PTCHD1 in another nucleus, the anterodorsal thalamus, causes learning and memory problems in the mice, Feng and his colleagues reported in August. The disruption of several other autism genes in the anterodorsal thalamus leads to similar results, further suggesting a cognitive function for this part of the structure.
In both experiments, the team identified drugs that could reverse the attention or memory problems in the mice. Ultimately, a deeper understanding of the functions of thalamic nuclei could help researchers manage specific difficulties in people with autism, researchers say. For example, a drug targeting neurons in the thalamic reticular core could solve problems with focus, or deep brain stimulation could modulate activity in the mediodorsal thalamus to improve social skills.
The list of possible strategies is long as the thalamus has many functions and connections to almost every part of the brain. “I was wondering, is there something the thalamus doesn’t do that it isn’t involved in?” Brumback says. “And I couldn’t think of anything.”
Quote the article: https://doi.org/10.53053/HNKB4296
