“People with bigger waists and higher BMI were more likely to have thinning in the cortex area of the brain, which implies that obesity is associated with reduced gray matter of the brain,” said study author Tatjana Rundek, M.D., Ph.D., a UHealth neurologist, professor of neurology, epidemiology, and public health and scientific director of the Evelyn F. McKnight Brain Research Institute.

“These associations were especially strong in those who were younger than 65, which adds weight to the theory that having poor health indicators in mid-life may increase the risk for brain aging and problems with memory and thinking skills in later life,” said Dr. Rundek,

The study involved 1,289 people with an average age of 64. Two-thirds of the participants were Latino. Participants’ BMI and waist circumference were measured at the beginning of the study. An average of six years later, participants had MRI brain scans to measure the thickness of the cortex area of the brain, overall brain volume and other factors.

A total of 346 of the participants had a BMI of less than 25, which is considered normal weight; 571 people had a BMI of 25 to 30, which is considered overweight; and 372 people had a BMI of 30 or higher, which is considered obese.

For waist circumference, which can be different for men and women, the normal weight group, which was 54 percent women, had an average of 33 inches, the overweight group, which was 56 percent women, had an average of 36 inches, and the obese group, which was 73 percent women, had an average of 41 inches.

Having a higher BMI was associated with having a thinner cortex, even after researchers adjusted for other factors that could affect the cortex, such as high blood pressure, alcohol use and smoking. In overweight people, every unit increase in BMI was associated with a 0.098 millimeter (mm) thinner cortex and in obese people with a 0.207 mm thinner cortex. Having a thinner cortex has been tied to an increased risk of Alzheimer’s disease.

Having a bigger waist was also associated with a thinner cortex after adjusting for other factors.

Rundek said, “In normal aging adults, the overall thinning rate of the cortical mantle is between 0.01 and 0.10 mm per decade, and our results would indicate that being overweight or obese may accelerate aging in the brain by at least a decade.”

“These results are exciting because they raise the possibility that by losing weight, people may be able to stave off aging of their brains and potentially the memory and thinking problems that can come along with brain aging,” Rundek said. “However, with the rising number of people globally who are overweight or obese and the difficulty many experience with losing weight, obviously this is a concern for public health in the future as these people age.”

Rundek noted that the study does not prove that extra weight causes the cortex to get thinner; it only shows an association.

A limitation of the study was that, like many studies of older people, it is possible that the healthiest people are more likely to live longer and take part in studies, so that may affect the results.

The study was supported by the National Institute of Neurological Disorders and Stroke and the Evelyn F. McKnight Brain Institute.

Scientists at Princeton University, led by electrical engineering Professor Andrew Houck, built an electronic array on a microchip that simulates particle interactions in a hyperbolic plane, a geometric surface in which space curves away from itself at every point.

“This research may advance quantum simulation in a way that enables us to not only develop a better understanding of materials relevant to Army goals, but also help us explore questions at the forefront of other fields of Army relevance,” said Dr. Sara Gamble, a program manager with the Army Research Office, an element of the U.S. Army Combat Capabilities Development Command’s Army Research Laboratory. “In addition to the potential materials applications, the fantastic results obtained by the research team can provide insight into communication networks and ultimately enable the DOD to develop more efficient networking capabilities.”

The research, published in Nature, used superconducting circuits to create a lattice that functions as a hyperbolic space. When the researchers introduce photons into the lattice, they can answer a wide range of difficult questions by observing the photons’ interactions in simulated hyperbolic space.

“The problem is that if you want to study a very complicated quantum mechanical material, then computer modeling is very difficult,” said Dr. Alicia Kollár, a postdoctoral research associate at the Princeton Center for Complex Materials. “We’re trying to implement a model at the hardware level so that nature does the hard part of the computation for you.”

The centimeter-sized chip is etched with a circuit of superconducting resonators that provide paths for microwave photons to move and interact. The resonators on the chip are arranged in a lattice pattern of heptagons, or seven-sided polygons. The structure exists on a flat plane, but simulates the unusual geometry of a hyperbolic plane.

“In normal 3-D space, a hyperbolic surface doesn’t exist,” said Princeton electrical engineering Prof. Andrew Houck. “This material allows us to start to think about mixing quantum mechanics and curved space in a lab setting.”

Trying to force a three-dimensional sphere onto a two-dimensional plane reveals that space on a spherical plane is smaller than on a flat plane. This is why the shapes of countries appear stretched out when drawn on a flat map of the spherical Earth. In contrast, a hyperbolic plane would need to be compressed in order to fit onto a flat plane.

To simulate the effect of compressing hyperbolic space onto a flat surface, the researchers used a special type of resonator called a coplanar waveguide resonator. When microwave photons pass through this resonator, they behave in the same way whether their path is straight or meandering. The meandering structure of the resonators offers flexibility to “squish and scrunch” the sides of the heptagons to create a flat tiling pattern, said Kollár, who is starting a faculty position at the University of Maryland and Joint Quantum Institute.

Looking at the chip’s central heptagon is akin to looking through a fisheye camera lens, in which objects at the edge of the field of view appear smaller than in the center — the heptagons look smaller the farther they are from the center. This arrangement allows microwave photons that move through the resonator circuit to behave like particles in a hyperbolic space.

The chip’s ability to simulate curved space could enable new investigations in quantum mechanics, including properties of energy and matter in the warped space-time around black holes. The material could also be useful for understanding complex webs of relationships in mathematical graph theory and communication networks. Kollár noted that this research could eventually aid the design of new materials.

But first, she and her colleagues will need to further develop the photonic material, both by continuing to examine its mathematical basis and by introducing elements that enable photons in the circuit to interact.

“By themselves, microwave photons don’t interact with each other — they pass right through,” Kollár said. Most applications of the material would require “doing something to make it so that they can tell there’s another photon there.”

“The research team is forming connections with researchers in other disciplines because of these results, and the addition of photon interactions into the systems will increase the application space for advancing Army capabilities even further,” Gamble said.

This study is the most in-depth analysis to date of medulloblastoma using single-cell RNAseq technology. The findings shed light on the relationship between the four known subtypes of medulloblastoma. Additionally, the researchers suggest a previously unknown cell of origin for the understudied Group 4 subgroup.

“The ability to look at individual cells has propelled us 10 steps forward in our understanding of how the subtypes of medulloblastoma arise, what drives them and how we can make treatments more effective for patients,” said co-senior author Paul Northcott, Ph.D., of the St. Jude Department of Developmental Neurobiology.

Previous research by the Northcott laboratory and others has classified medulloblastoma into four distinct subtypes: WNT and SHH (which are driven by their namesake genetic mutations), Group 3 and Group 4. Group 3 and Group 4 constitute 60% of all medulloblastoma but are the least understood. This is in part because there are currently no genetically accurate laboratory models that mimic Group 4.

Using tumor samples from patients with each of the four subtypes, the researchers conducted single-cell RNA sequencing. This technique evaluates each cell, providing the investigators with a more detailed portrait of how the subtypes arise and relate to each other. Going beyond traditional genetic sequencing, RNAseq drills down into how genes are controlled, highlighting important mechanisms that can dictate a cell’s behavior.

These results provide for the first time an indication that Group 4 medulloblastoma tumors may arise from cells in the cerebellum called glutamatergic cerebellar nuclei and unipolar brush cells. This is a critical finding for future research into Group 4 medulloblastoma, because understanding the cell of origin may make it possible to develop accurate laboratory models.

The study did not confirm a cell of origin for Group 3 medulloblastoma. However, the results did suggest several possible explanations. For example, Group 3 may arise from tissues outside the cerebellum which were not studied. It is also possible that the oncogene MYC, which characterizes Group 3, alters the cells to make them unrecognizable when compared to their origins. Future studies will focus on understanding more about the origins of Group 3.

“Group 3 and Group 4 medulloblastomas have confounded the field, with some very clearly belonging to one subtype or the other but another group exhibiting the hallmarks of both subtypes,” said co-senior author Mario Suva, M.D., Ph.D., of Massachusetts General Hospital and the Broad Institute of MIT and Harvard. “Now, we can more clearly see that there is an intermediate group, straddling Group 3 and Group 4 classification.”

By digging into the biology of intermediate Group3/4 medulloblastoma, the investigators showed these tumors consist of a mixture of immature and mature tumor cells, explaining current challenges associated with their classification. This unique biology may prompt investigators to think differently about how these tumors are stratified and may have implications for the design of future clinical trials.

The study also confirmed that SHH tumors likely arise from cerebellar granule neuron progenitors. The findings advanced understanding of the ways that SHH tumors can differ based on the patient’s age. The investigators found that in infants, SHH tumors are largely differentiated, meaning the cells have already matured into their final cell type; whereas in adults, SHH tumors are more primitive and less differentiated. This difference may be tied to the increased number of genetic mutations present in adult tumors. The research also provided insights into WNT tumors, showing that WNT tumors can be subdivided into four distinct tumor cell populations based on gene expression profiles.

Autism spectrum disorder is characterised by social communication impairments and by repetitive and restricted behaviours. There is limited understanding of why some autistic people appear neurotypical in their behaviours, despite having autism-related cognitive difficulties or differences.

Compensation is an adaptive process whereby new behaviours are generated in order to avoid negative outcomes. It is different from masking, where presumed undesirable behaviours are hidden or stopped. In the case of people with autism, people may use past experience or logic to respond to social situations to increase opportunities and “fit in” with society. However, they continue to be autistic at a neurocognitive level and this can lead to challenges in diagnosing and supporting individuals.

Lucy Livingston, lead author of the study from King’s College London, UK, says: “This study highlights that compensation is an adaptive response to external societal pressures. This finding is in line with research that autistic people are, despite the negative impact on their wellbeing, driven to meet society’s expectations of behaviour. Neurotypical society could do more to accommodate people with autism, which we speculate might reduce the need for them to compensate.”

The authors advertised to recruit participants for their study via social media and with the National Autistic Society. 136 adults were asked to complete an online study. Of the participants, 58 had a clinical diagnosis, 19 self-identified without a formal diagnosis and 59 were not diagnosed or self-identified, but reported social difficulties. The study looked into what compensatory strategies participants used, whether the strategies used were similar in diagnosed and undiagnosed people, and how compensatory strategies affected diagnosis.

The participants were asked to self-report autistic traits by completing a ten-item autism spectrum questionnaire and then a series of open questions about their social compensatory strategies. They also reported how successful and tiring their strategies were, and the likelihood of their recommending them to others with social difficulties.

The team identify several strategies used by people with and without an autism diagnosis (including behavioural masking such as holding back true thoughts or suppressing atypical behaviours, shallow and deep compensation such as planning and rehearsing conversations or learning rules about verbal and non-verbal behaviours, and accommodation strategies such as going out of your way to be helpful), which were used equally by people who were formally diagnosed with autism and those who were not.

Shallow strategies such as laughing after joke cues were common in participants who reported more autistic traits and were linked to negative consequences of compensation. Crucially these shallow strategies are more difficult in stressful situations or when tired.

Participants used their intellectual and planning abilities to regulate social behaviour and follow social norms — making eye contact — preplanning social niceties — asking others questions about themselves — and switching between social rules. These strategies were more difficult when distracted or stressed, but crucially, they did not reduce participants’ internal social cognitive difficulties.

There were wide-ranging motivations for using these strategies, most notably social motivation and a desire to develop meaningful relationships. One participant says: “With compensation, I have a job in which people respect my work and ask for my help and opinions…I am liked by my colleagues and friends…I haven’t lived on the edge, lost and lonely, as I could have. I have been super super lucky.”

There was also a perception that neurotypical individuals could “see through” these strategies. One participant reported: “There are obvious flaws, if you are observant — I repeat myself or use tv/film phrases and sometimes say things that are out of place.” And another noted: “I feel like I am acting most of the time and when people say that I have a characteristic, I feel like a fraud because I’ve made that characteristic appear.”

The use of these strategies was linked with poor mental health, and autism diagnosis and support appeared to be affected too. 47 out of 58 of the diagnosed participants were diagnosed late in adulthood. The other 11 were diagnosed before the age of 18 years.

External environments were found to affect compensation and it may be the case that people with autism present as neurotypical in certain situations but not in others. Clinicians should be aware of this when measuring compensation and diagnosing autism. Recent evidence suggests that only 40% of UK general practitioners — the first point of contact for individuals seeking diagnosis — are confident in identifying autism spectrum disorder.

Lucy Livingston says: “Until now, no study has directly investigated compensatory strategies used by autistic people in social situations and we provide evidence for their existence and modulation by various factors. Because they present a barrier to diagnosis of autism, increasing awareness of compensatory strategies among clinicians will help detection and the provision of support for autistic people who use them. We hope this study will lead to the refinement of diagnostic manuals which currently contain little guidance on compensatory strategies in autism and co-occurring mental health conditions.”

The authors note some limitations, including that their sample included a high proportion of female, late diagnosed and well educated participants. Because of self-reporting it may not have captured subconscious behaviours. Future research should take both of these limitations into account, using more representative population samples and quantitative measures. Additionally, the role of other factors that affect social pressure, such as multiple intersecting identities and their role in compensation, could be investigated in future.

In a linked Comment article, Dr Julia Parish Morris of the Centre for Autism Research at the Children’s Hospital of Philadelphia, USA, says: “Although many people compensate during social interaction, it can be an especially exhausting and distressing exercise for people with autism spectrum disorder. This finding begs the question: should subjective distress be listed in the diagnostic criteria for autism spectrum disorder? For example, DSM-5 could be revised to read: “Symptoms cause clinically significant impairment in social, occupational, or other important areas of current functioning [-including subjective distress].”

This study was funded by the Medical Research Council and National Institute for Health Research. It was conducted by researchers from King’s College London and the University of Bath.