Tag: neuroscience

LGBTQ Concerns Put Brain Imaging Study on Hold

Person holding rainbow-themed cake slice. Photo by Sharon McCutcheon on Unsplash.

A study investigating brain functions of gender dysphoria at UCLA’s Semel Institute for Neuroscience & Human Behavior, has been put on hold after concerns from LGBTQ groups.

According to the Diagnostic and Statistical Manual of Mental disorders, gender dysphoria is a “marked incongruence between their experienced or expressed gender and the one they were assigned at birth.” Gender Justice LA and the California LGBTQ Health and Human Services Network released a joint statement, citing major ethical concerns.

Study leader Jamie Feusner, MD, a psychiatrist, told MedPage Today that he has asked UCLA’s Institutional Review Board to “re-review our entire protocol to ensure that it meets all ethics and safety standards.”

He added that his team is “actively engaged with members of the LGBTQ community” to help inform potential adjustments to study protocols. It wasn’t clear whether the entire study is on hold or just enrollment of new participants.

Ezak Perez, executive director of Gender Justice LA, wrote that the “research design unapologetically aims to cause mental health distress to trigger ‘dysphoria’ to an already marginalised and vulnerable community.”

The advocacy groups said that researchers from the Semel Institute reached out to the transgender, gender non-conforming, and intersex community in the region to take part in a meeting to help the study design. When they expressed concerns during this meeting and realised the study was already underway with approval from the IRB, leaders from Gender Justice LA and the California LGBTQ Health and Human Services Network wrote a letter to UCLA’s Office of the Human Research Protection Program.

“The researchers are falsely advertising this study without clarity about the expectations of participants and without consideration of the need for direct access to mental health after care,” wrote Perez and Dannie Cesena, program manager of LGBTQ Health and Human Services Network.

The call for participants was for looking for transgender, nonbinary, and cisgender adults to complete an assessment and one or more MRI scans. Participants would also be “photographed from the neck down while wearing a unitard,” a point of contention cited by Perez in his statement. The enrollment announcement also noted that participants who experience discomfort during this process could withdraw from the study at any point. Requirements included not being psychiatric medications, and that trans and nonbinary participants could not already be on hormone therapy or have had gender-affirming surgery. Participants would be paid a small amount and have expenses reimbursed.

The study in question would use the ‘body morph’ test, designed in 2015 by Feusner and colleagues. During the test, participants are photographed from various angles in a nude-colored, full-body unitard, with faces, hand and feet cropped out.. Participant images are then morphed with pictures of different bodies.

Writing to MedPage Today, Feusner and co-researcher Ivanka Savic-Berglund, MD, PhD, wrote that at the time that Feusner created the ‘body morph’ test, “experiences of body-self incongruence were not easily understood. The test uses images to estimate the degree of alignment between individuals’ body perception and their gender-specific self-identity.”

Perez and Cesena strongly objected to the idea that capturing the neurological response of gender dysphoria through brian imaging could provide any scientific data that could ‘help’ trans people.

“It is suggestive of a search for medical ‘cure,’ which can open the door for more gatekeeping and restrictive policies and practices in relation to access to gender-affirming care,” the letter stated.

Feusner and Savic-Berglund, however, explained that “by demonstrating that body-self incongruence was linked to brain structure and function, we aimed to help provide a biological basis and increase empathy for the life stories of transgender individuals. From the beginning, the aim was to help increase acceptance of transgender individuals.”

Source: MedPage Today

Brain ‘Rewired’ by Sound Early in the Womb

Playing music to foetuses in the womb to enhance their brain development is a popular practice even if thus far not grounded in science, but new research has shown that there may be some effect even at very early stages.

New research from John Hopkins University indicates that ‘wiring changes’ made in response to sounds occur even earlier than thought before. The ear canals of newborn mice only open after 11 days, while in humans, the ear canals open at 20 weeks’ gestation. The researchers used the mice as a model for human foetuses, and examined their neural connections at one week old.

“As scientists, we are looking for answers to basic questions about how we become who we are,” said Patrick Kanold, PhD, professor of biomedical engineering at The Johns Hopkins University and School of Medicine. “Specifically, I am looking at how our sensory environment shapes us and how early in foetal development this starts happening.”

Prof Kanold started out in electrical engineering before switching to neuroscience. His field of research is on the cortex, the outer layer of neurons underneath which lies the white matter which consists of connective neurons.

In developing foetuses, in the white matter, subplate neurons can be found at 12 weeks in human gestation and the second embryonic week in mice. This subplate neurons are the precursors to neurons and die off over a period lasting from before birth to several months old. Before they disappear, they make a connection between the thalamus, which is an important sensory gateway, and the middle layers of the cortex.

“The thalamus is the intermediary of information from the eyes, ears and skin into the cortex,” explained Prof Kanold. “When things go wrong in the thalamus or its connections with the cortex, neurodevelopmental problems occur.”

The subplate neurons respond to sound before the cortical neurons, prompting two questions for Prof Kanold: When sound signals reach the subplate neurons, does anything happen, and can a change in sound signals reflect changes in the brain circuits at these young ages?

To answer these questions, the researchers used mice genetically engineered to be deaf, unable to convert sound into nerve signals. In deaf, week-old mice, there were 25-30% more connections between subplate and cortical neurons.

“When neurons are deprived of input, such as sound, the neurons reach out to find other neurons, possibly to compensate for the lack of sound,” said Prof Kanold. “This is happening a week earlier than we thought it would, and tells us that the lack of sound likely reorganises connections in the immature cortex.”

To compare the difference extra auditory stimuli made, the researchers put 2-day old pups in a quiet enclosure or an enclosure with a constant beeping sound. There were differences between the subplate neuron connections for beeping and quiet enclosure mice, but not as great as between the deaf and hearing mice. The quiet enclosure mice had stronger connections between the subplate and cortical neurons, similar to the deaf mice. The mice in the beeping enclosure also had a greater diversity in neural circuitry.

“In these mice we see that the difference in early sound experience leaves a trace in the brain, and this exposure to sound may be important for neurodevelopment,” explained Prof Kanold.

The researchers are planning to examine how sound in early development impacts the brain in later life, as well as how sounds in the womb influences neural wiring. This has application for cochlear implants for children born deaf. They also plan to study premature infants neural wiring problems and develop biomarkers for abnormal subplate neuron development. 

Source: Medical Xpress

Journal information: Early peripheral activity alters nascent subplate circuits in the auditory cortex, Science Advances (2021). DOI: 10.1126/sciadv.abc9155

Women are Better ‘Mind Readers’ Than Men, Study Finds

Women are better at ‘reading minds’ than men, finds a new study aimed at better understanding social interaction and the challenges faced by people with autism. 

Sometimes known in the field of psychology as ‘mentalising‘, the process is when people try to ascertain what others are really thinking, for example when they are sarcastic or even lying. Mind-reading has some basis in neuroscience: for example, some research indicates that sensitivity to social interactions is associated with the posterior superior temporal sulcus, an area of the brain which is also known to process biological motion. Everybody has some proficiency with mind reading, and some are inherently better than others. However, some lack the ability to a point where it becomes difficult to function in society, for example in autism.

The study made use of a self-report questionnaire asking participants to rate how well, for example, they could relate to others. It used four questions, each with ratings from one to four, giving a maximum total score of 16. The researchers determined that women scored higher than men on the questionnaire, and also confirmed the challenges reported by those with autism. 

Senior author Dr Punit Shah, at the University of Bath’s Department of Psychology explained: “We will all undoubtedly have had experiences where we have felt we have not connected with other people we are talking to, where we’ve perceived that they have failed to understand us, or where things we’ve said have been taken the wrong way. Much of how we communicate relies on our understanding of what others are thinking, yet this is a surprisingly complex process that not everyone can do.”

Dr Shah emphasised that there is a different between mind-reading and empathy, saying: “Mind-reading refers to understanding what other people are thinking, whereas empathy is all about understanding what others are feeling. The difference might seem subtle but is critically important and involves very different brain networks. By focussing carefully on measuring mind-reading, without confusing it with empathy, we are confident that we have just measured mind-reading. And, when doing this, we consistently find that females reported greater mind-reading abilities than their male counterparts.”

Lead researcher, Rachel Clutterbuck, emphasised the clinical importance of the questionnaire. She said: “This new test, which takes under a minute to complete, has important utility in clinical settings. It is not always obvious if someone is experiencing difficulties understanding and responding to others—and many people have learnt techniques which can reduce the appearance of social difficulties, even though these remain.

“This work has great potential to better understand the lived experience of people with mind-reading difficulties, such as those with autism, whilst producing a precise quantitative score that may be used by clinicians to identify individuals who may benefit from interventions.”

Dr Shah added that this study was about helping to understand mind-reading capabilities, and had created a freely available questionnaire for other efforts in this regard.

Source: Medical Xpress

Journal information: Rachel A. Clutterbuck et al, Development and validation of the Four-Item Mentalising Index., Psychological Assessment (2021). DOI: 10.1037/pas0001004

Geometric Model of Sherlock Episode Reveals How We Recall Events

Using a TV episode and a geometrical model, researchers at Dartmouth have come up with a new way to understand how the brain evaluates which experiences to store as memories and which to discard.

The researchers based their study around participants’ recall of a BBC episode of Sherlock against a geometric model of the events that happened in it. Their results allowed new insights into how memories are stored and then related to others.

Senior author Jeremy R Manning, an assistant professor of psychological and brain sciences, and director of the Contextual Dynamics Lab at Dartmouth, explained: “When we represent experiences and memories as shapes, we can use the tools provided by the field of geometry to explore how we remember our experiences, and to test theories of how we think, learn, remember, and communicate.

“When you experience something, its shape is like a fingerprint that reflects its unique meaning, and how you remember or conceptualise that experience can be turned into another shape. We can think of our memories like distorted versions of our original experiences. Through our research, we wanted to find out when and where those distortions happen (i.e. what do people get right and what do people get wrong), and examine how accurate our memories of experiences are.”

Using a public dataset of brain recordings from 17 participants who had viewed the same Sherlock episode and described what had happened. This dataset also contained detailed notes on what took place in that episode. They took these notes to create a list of 32 topics, which were then represented as a 32-dimensional model. Visualised in 2 dimensions, a dot-to-dot shape emerges, to which the shapes made by the participants’ recall of events can be compared.

Using the episode’s shape as a structure, they were able to see at what points the participants’ memories matched the episode, and what points they forgot or had distorted recollections. The shape also featured extraneous elements of fine detail, like architectural embellishments such as carvings, which reflected low-conceptual details. Some participants accurately recounted these low-conceptual details while others could only recall high-level plot points.

“One of our most intriguing findings was that, as people were watching the episode, we could use their brain activity patterns to predict the distorted shapes that their memories would take on when they recounted it later,” explained Manning. “This suggests that some of the details about our ongoing experiences get distorted in our brains from the moment they are stored as new memories. Even when two people experience the same physical event, their subjective experiences of that event start to diverge from the moment their brains start to make sense of what happened and distill that event into memories.”

These findings could be used as the basis for research into improving educational delivery, as well as patients’ understanding of matters explained to them by their doctors.

Source: Medical Xpress

Journal information: Geometric models reveal behavioural and neural signatures of transforming experiences into memories, Nature Human Behavior (2021). DOI: 10.1038/s41562-021-01051-6

Caffeine Shown to Alter Brain Pathways in Utero

Caffeine consumption during pregnancy could change key brain pathways, resulting in children having significant behavioural problems in later life. 

“These are sort of small effects and it’s not causing horrendous psychiatric conditions, but it is causing minimal but noticeable behavioural issues that should make us consider long term effects of caffeine intake during pregnancy,” said John Foxe, PhD, director of the Del Monte Institute for Neuroscience. “I suppose the outcome of this study will be a recommendation that any caffeine during pregnancy is probably not such a good idea.” Foxe also pointed out that this was a retrospective study, reliant on mothers’ recall of caffeine consumption.

Studies had already linked caffeine to other outcomes, such as a meta-review which found a nearly linear link between caffeine consumption and low birth weight. It is known that foetuses do not possess the enzyme necessary to break down caffeine, which crosses the placenta into the foetal bloodstream.

Researchers at the Del Monte Institute for Neuroscience at the University of Rochester Medical Center (URMC) analysed brain scans of thousands of children. The researchers observed increased behavioural and attention problems along with hyperactivity in these children. They observed distinct changes in how the white matter tracks (which connect brain regions) were organised in children of mothers who reported caffeine consumption during pregnancy.

“What makes this unique is that we have a biological pathway that looks different when you consume caffeine through pregnancy,” said first author Zachary Christensen, an MD/PhD candidate in the Medical Science Training Program. “Previous studies have shown that children perform differently on IQ tests, or they have different psychopathology, but that could also be related to demographics, so it’s hard to parse that out until you have something like a biomarker. This gives us a place to start future research to try to learn exactly when the change is occurring in the brain.”

At this stage it is not known what the relationship between amounts of caffeine are, or what effects arise in each trimester.

“Current clinical guidelines already suggest limiting caffeine intake during pregnancy—no more than two normal cups of coffee a day,” added Christensen. “In the long term, we hope to develop better guidance for mothers, but in the meantime, they should ask their doctor as concerns arise.”

Source: Medical Xpress

Journal information: Zachary P. Christensen et al, Caffeine exposure in utero is associated with structural brain alterations and deleterious neurocognitive outcomes in 9–10 year old children, Neuropharmacology (2021). DOI: 10.1016/j.neuropharm.2021.108479

LSD Shown to Heighten Sociability in Mice

Scientists at McGill University have discovered that mice micro-dosed with LSD have an increased level of sociability, pointing to a mechanism by which the drug can influence behaviour at these low concentrations.

Lysergic acid diethylamide (LSD) was discovered by accident while developing stimulants, and was first used to study psychotic states. There was initially great interest in and use of LSD for psychiatric treatment, but the harmful and lasting side-effects resulted in it steadily being outlawed. However, recent anecdotal evidence of individuals self-administering micro-doses of LSD to improve cognitive functioning have helped spur renewed interest in the famous drug.To investigate the ways LSD might be working on the brain, the McGill University researchers dosed mice with low levels of LSD over seven days, and observed a measurable increase in sociability.

This is useful as a main outcome of the study is a mechanism that describes the increased feelings of empathy and awareness that users of LSD describe.

Co-lead author Prof Nahum Sonenberg at McGill University, world renowned expert in the molecular biology of diseases, explained: “The fact that LSD binds the 5-HT2A receptor was previously known. The novelty of this research is to have identified that the prosocial effects of LSD activate the 5-HT2 receptors, which in-turn activate the excitatory synapses of the AMPA receptor as well as the protein complex mTORC1, which has been demonstrated to be dysregulated in diseases with social deficits such as autism spectrum disorder.

“Their next research goal is treating mutant mice with behavioural deficits mimicking human psychological pathologies, and to find out if micro-dosed LSD or some derivative could be a safe and effective therapeutic option.

“Social interaction is a fundamental characteristic of human behaviour,” noted co-lead author Dr Gabriella Gobbi, Professor in the Department of Psychiatry at McGill and psychiatrist at the McGill University Health Centre. “These hallucinogenic compounds, which, at low doses, are able to increase sociability may help to better understand the pharmacology and neurobiology of social behavior and, ultimately, to develop and discover novel and safer drugs for mental disorders.”

Source: Medical Xpress

Journal information: Danilo De Gregorio et al, Lysergic acid diethylamide (LSD) promotes social behavior through mTORC1 in the excitatory neurotransmission, Proceedings of the National Academy of Sciences (2021). DOI: 10.1073/pnas.2020705118

Paralysed Mice Walk Again with ‘Designer’ Cytokines

Scientists have sought a means to regenerate spinal cord injuries which leaves patients paraplegic or quadriplegic – and now a breakthrough by researchers at Ruhr-University Bochum, Germany, may see that dream realised.

By the time humans reach adulthood, after an injury they can no longer regenerate the axons which transfer nerve impulses from brain to muscles. In 2013, the researchers discovered that a cytokine called interleukin-6 (IL-6) promoted the regeneration of optic axon fibres in vitro. IL-6 was known to be involved in nerve regeneration as well as in neuropathic pain from peripheral nerve injuries. As promising as this experiment was, delivery of the cytokine to the injury location deep in the body was an obstacles, as was the fact that it had a fairly weak effect on stimulating nerve tissue regrowth.

The team subsequently developed hyper-IL-6, an artificial variant of IL-6 that was far more potent than its natural counterpart. However, the “designer” cytokine still could not be delivered to the injured tissue where it was needed. To get around this, the researchers turned to a somewhat novel delivery method: gene therapy. A few motor neurons in the brain’s sensorimotor cortex are altered via engineered viruses to produce hyper-IL-6, which is then distributed along the axon’s length to the injury site.

“Thus, gene therapy treatment of only a few nerve cells stimulated the axonal regeneration of various nerve cells in the brain and several motor tracts in the spinal cord simultaneously,” explained senior author Dr Dietmar Fischer.

After a single injection of the engineered virus and its hyper-IL-6 payload, mice with severed spinal cords were able to walk again after two to three weeks.

“This came as a great surprise to us at the beginning, as it had never been shown to be possible before after full paraplegia,” said Dr. Fischer.
Following the success of these experiments, Dr. Fischer’s team is looking at combining the engineered cytokine treatment to other promising applications, such as tissue grafts. Additionally, they are investigating whether the hyper-IL-6 treatment can regenerate spinal cord damage that occurred weeks beforehand.

“This aspect would be particularly relevant for application in humans. We are now breaking new scientific ground. These further experiments will show, among other things, whether it will be possible to transfer these new approaches to humans in the future.”

However, adapting this designer cytokine treatment to be one that is safe for humans will take several years.

Source: Medical News Today

Mid-life Exercise Positively Shapes Late-life Brain Structure

That exercise in one’s middle years benefits health in later life is perhaps no surprise given our current understanding of its benefits, but and MRI study has shown to influence the brain’s structure in later years.

Using MRI scans, high levels (150 minutes per week or more) of self-reported moderate-to-high physical activity were associated with reduced risk of lacunar infarct in late life (OR 0.68, 95% CI 0.46-0.99) and more intact white matter integrity.

“Our study suggests that getting at least an hour and 15 minutes of moderate-to-vigorous intensity physical activity a week or more during midlife may be important throughout your lifetime for promoting brain health and preserving the actual structure of your brain,” said Priya Palta, PhD, of Columbia University Irving Medical Center. “In particular, engaging in more than 2 and a half hours of physical activity per week in middle age was associated with fewer signs of brain disease.”

There has been mixed evidence linking physical activity to brain measures or improvements in cognitive function. PhDs Nicole Spartano, of Boston University School of Medicine, and Leonardo Pantoni, MD, of University of Milan, noted in an accompanying editorial that the “most consistent evidence for the protective effect of physical activity against dementia risk has been reported to be leisure time physical activity, and it is unclear whether there is benefit to other types of physical activity that may be less ‘enriching.'”

“It is possible that future work will uncover the requirement that physical activity interventions to reduce dementia risk actually have an enriching element, such as in leisure-time activities, rather than be strictly rote, mechanical movement,” Spartano and Pantoni added.

Recruiting 1 604 individuals with a mean baseline age of 54, the participants had five examinations over 25 years and MRI at a mean age of 72. At baseline (1987-1989) and 25 years later, participants had their moderate-to-vigorous physical activity assessed in a questionnaire. 

At midlife, 11% had low levels of moderate-to-high intensity activity (1 to 74 minutes a week), 16% middle levels (75 to 149 minutes a week), and 39% high levels (150 minutes a week or more), with the remainder reporting none.

High moderate-to-vigorous midlife activity was associated with better white matter integrity in late life, compared with no moderate-to-vigorous midlife activity, but there was no association with grey matter volume.

While the risk of lacunar infarcts were lower with more intense midlife activity, risk of cortical infarcts or subcortical microhemorrhage were not. “The associations of greater levels of mid-life physical activity with fewer lacunar (but not cortical) infarcts and greater white matter microstructural integrity suggest cerebrovascular mechanisms are primarily at play,” Palta and colleagues wrote.

When adjusted for vascular risk factors, the association of midlife physical activity to lacunar infarcts was weakened, but the association with white matter microstructure. The editorialists said that it implies that “evidence from this study supports a hypothesis that the mechanisms linking physical activity and the brain are likely multi-dimensional, including mechanisms other than simply improving cerebrovascular health.” 

Late-life moderate-to-vigorous physical activity also was associated with most brain measures compared with no moderate-to-vigorous activity, but as this was a prospective study that spanned decades, the “association between midlife physical activity levels and later-life brain imaging features makes a much stronger case for causality than does the same relationship when measured only in late life,” the researchers noted.

The study had several limitations, which included using self-reported data, did not include non leisure-related activity, and participant attrition.

Source: MedPage Today

Journal information: Source Reference: Palta P, et al. A prospective analysis of leisure-time physical activity in midlife and beyond and brain damage on MRI in older adults, Neurology 2020; DOI: 10.1212/WNL.0000000000011375.

Tinnitus Severity Measured with Non-invasive Brain Imaging

Tinnitus, experienced by about 20% of people, has long been a complaint without any overt signs to measure. Recent bran imaging techniques showed that tinnitus was related to increased neural firing and changes in connectivity in certain brain regions.

Using functional near-infrared spectroscopy (fNIRS), researchers in 2014 were able to map anomalous activity in the right auditory cortex of tinnitus sufferers, and in 2018, researchers showed that signals there were related to both the presence and intensity of the tinnitus.

fNIRS measures the absorption of near-infrared light shining into the head to measure oxy- and deoxyhaemoglobin levels, which are associated with cerebral activity.

Using machine learning which compared 25 patients with tinnitus to 21 healthy patients, the researchers were able to isolate two distinct areas of 

The algorithms were able to diagnose tinnitus with 78% accuracy and gauge intensity with 87% accuracy.

The imaging showed higher connectivity in the temporal-frontal lobe, linked to tinnitus duration and stress, and higher connectivity in the temporal-occipital lobe, which is linked to sound intensity. It opens the possibility of measuring both loudness and annoyance with fNIRS, and also supports preliminary research showing that by making the brain process other information, the tinnitus intensity can be reduced.

Source: Science Alert

‘Flight or Flight’ Brain Region Linked to Heart Disease

Research on marmosets as reported in The Conversation has revealed the role that a region of the brain called sgACC plays in emotional arousal. Over-activity of sgACC was already associated with the dampening of pleasure and reward stimulus, seen in depression. 

A threat was presented to the marmosets in the form of a rubber snake and the marmosets were conditioned with a tone to create an association. The tone was later made without the snake to de-associate it from threat. The experimental group had over-activity induced in sgACC, the control group did not.

They found that marmosets who had not had sgACC over-stimulated responding normally to the de-association, calming down more quickly, but the over-activity group displayed fear and elevated blood pressure for much longer.

The over-activity of sgACC was also linked to abnormal heart function – increased heart rate and reduced variability in heart rate even at rest, without the presence of a threat.

Such changes reflect the presence of anxiety. The abnormal heart rates suggests that sgACC promotes the “flight or fight” response.
Brain imaging showed, with over-activity in sgACC, concurrent increased activity in the amygdala and hypothalamus, and reduced activity in the lateral prefrontal cortex, which is also seen in depression. Ketamine, a drug being investigated to treat depression, was shown to treat the depression aspects of sgACC over-activity, but in this case not anxiety – the marmosets remained fearful to stimulus.