NS/ A completely locked-in patient can communicate, thanks to a brain implant
Neuroscience biweekly vol. 55, 22nd March — 5th April
TL;DR
- A man left in a completely locked-in state by amyotrophic lateral sclerosis (ALS) has been able to communicate with his family and carers thanks to an implant. The device helped the patient, who was unable to move any muscles or even open his eyes, contact the outside world using only his brain activity.
- A brain imaging study of young people at high risk of developing bipolar disorder has for the first time found evidence of weakening connections between key areas of the brain in late adolescence.
- A new study led by UCLA Health scientists shows highly creative people’s brains appear to work differently from others’, with an atypical approach that makes distant connections more quickly by bypassing the “hubs” seen in non-creative brains.
- Minuscule involuntary eye movements, known as microsaccades, can occur even while one is carefully staring at a fixed point in space. When paying attention to something in the peripheral vision (called covert attention), these microsaccades sometimes align towards the object of interest. New research by National Eye Institute (NEI) investigators shows that while these microsaccades seem to boost or diminish the strength of the brain signals underlying attention, the eye movements are not drivers of those brain signals. The findings will help researchers interpret studies about covert attention and may open new areas for research into attention disorders and behavior.
- Cichlids and stingrays can perform simple addition and subtraction in the number range of one to five. This has been shown in a recent study by the University of Bonn, which has now been published in the journal Scientific Reports. It is not known what the animals need their mathematical abilities for.
- Researchers have developed a miniature microscope that is designed for high-resolution 3D images inside the brains of living mice. The new, lightweight design could help scientists understand how brain cells operate by imaging deeper into the brain than previously possible with miniature widefield microscopes.
- Recent discoveries may prove vital in improving the treatment of dystonia, a neurological movement disorder. Their findings show that very specific networks in the brain must be stimulated in order to relieve the symptoms seen in different types of dystonia.
- Researchers have shown in detail how COVID-19 affects the central nervous system, according to a new study. The findings are the first comprehensive assessment of neuropathology associated with SARS-CoV-2 infection in a nonhuman primate model.
- A new study by Johns Hopkins Medicine researchers addresses the question of whether psychedelics might change the attribution of consciousness to a range of living and nonliving things.
- A new study sheds light on the little-known phenomenon of binaural beats, where sounds purportedly evoke psychoactive effects.
- And more!
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Latest news and research
Spelling interface using intracortical signals in a completely locked-in patient enabled via auditory neurofeedback training
by Chaudhary, U, Vlachos, I, Zimmermann, JB, et al. in Nature Communications
In the last decade, combinations of brain implants and brain-computer interfaces (BCI) have enabled people with severe brain injuries or neurodegeneration to regain communicative ability. The new study, published in Nature Communications by an international research team, is the first to be used successfully in a patient with such severe neurodegeneration.
The patient, an unnamed man in his late 30s, was first diagnosed with progressive muscle atrophy, a variant of ALS, in August 2015. The disease’s advance was rapid. Unable to walk or speak by the end of 2015, he used an eye-tracking system to communicate. Such systems allow users to interact with a keyboard or software environment, but their limited utility is dependent on the neurons controlling eye movement remaining functional. From August 2017, the patient lost the ability to fixate his gaze. Anticipating that he would eventually lose the ability to even open his eyes, the patient’s family reached out to Dr. Ujwal Chaudhary and Niels Birbaumer, researchers at the University of Tübingen.
What is ALS?
Amyotrophic lateral sclerosis (ALS) is a progressive disease of the nervous system. Affecting the nerve cells that produce movement, the progressive disease robs patients of voluntary control over muscles used for actions like walking and talking. There is currently no cure for the disease and just ten percent of patients live for ten years after diagnosis.
Chaudhary and Birbaumer are co-authors on the resulting paper, the result of more than two years of work that enabled the patient to communicate. Fellow author Dr. Jonas Zimmermann of the Wyss Center in Geneva explained in a news release that the study concludes an enduring debate surrounding the abilities of individuals in the most severe stages of neurodegenerative disease.
“This study answers a long-standing question about whether people with complete locked-in syndrome (CLIS) — who have lost all voluntary muscle control, including movement of the eyes or mouth — also lose the ability of their brain to generate commands for communication.”
In June 2018, as the patient’s last remaining muscle control deteriorated, the team moved him to a hospital near his home, where his motor cortex was implanted with two microelectrode arrays. For the patient, the brain surgery represented only the first ordeal in a grueling journey towards recovering his communication.
At this stage, it was unclear whether he would ever be able to complete that journey. Several previous studies have tracked the ability of patients with locked-in syndrome (LIS) to communicate with BCI interfaces. However, no patient had previously achieved communication once they progressed to a CLIS stage with loss of control over eye movements. Researchers had hypothesized that once all physical movement was lost, the neural signals that enable movement would also be lost, making brain-based communication impossible.
One day after his implant, the patient began his efforts to prove that theory wrong.
The research team asked the patient to mentally adopt his previously employed eye-based movement strategy, hoping that even with no movement, they would be able to decode the brain signals that his motor cortex would have sent to his eyes. However, the team couldn’t detect any consistent signals. Similarly, when the researchers asked the patient to imagine hand or foot movement, the BCI couldn’t detect a reliable signal.
They refused to give up. On day 86 post-implantation, the researchers decided to change tack, adopting a new approach based on neurofeedback. “I decided to play his cell firing back to him, so he could hear it,” Birbaumer tells Technology Networks. This approach has been used previously in BCI research, where subjects, upon being shown their cell firing rate on a screen, gain the ability to modulate it.
Although he couldn’t view the firing rate, the audio-based approach worked for the patient.
“That strategy broke the ice,” says Birbaumer. “Now, he was able to control the BCI.”
To operate his BCI, the patient was played a tone that corresponded to the rate of fire of his neural activity. When the cells increased their firing rate, the tone raised in pitch, while lower activity produced a lower tone. After 12 further days, the patient was able to reliably increase or decrease his neural activity to hit one of two “target” tones. The higher tone was set to represent a “yes” response, while the lower tone meant “no”. This gave the patient the ability to painstakingly select letters read out by the BCI, allowing him to spell words.
Over the next 360 days, the researchers repeatedly visited the patient’s home, conducting multi-hour recording sessions. The study was interrupted by the COVID-19 pandemic, forcing some sessions to be conducted remotely, with the patient’s wife controlling the BCI’s hardware. In total, 135 experimental sessions were recorded.
After months of silence, the patient began to communicate once again. The process was slow — the audio-based system meant that it took one minute on average for the patient to communicate a single character — but the patient persisted with his messages. On the second day, the patient wrote thank you messages to Birbaumer and his team. Writing in his native language German, he split his messages between instructions for his care — “everybody must use gel on my eye more often” and “when visitors are here, head position always very high” — and personal messages for his family, asking his young son whether he wanted to watch Disney’s Robin Hood with him.
The system didn’t work flawlessly and there are limitations to the study to consider. Each day began with training sessions, where the patient had to show the ability to match his brain activity to target tones before proceeding to a speller session where he was allowed to freely select letters using the BCI. On 28 study days, the patient was unable to hit the target tones reliably enough to proceed to the speller sessions. Additionally, the researchers were only able to use a small number of the electrode channels to record signals. The team write in their paper that while they considered altering the approach to record from more channels, they felt that changes to the protocol may have risked breaking down the fragile communication line they had established with their patient.
Finally, the output from the system wasn’t always intelligible, producing intact and understandable phrases on 44 out of 107 days. But, overall, the patient managed to produce 5747 characters that the authors could decode, restoring communication that would have otherwise been impossible for the patient.
“Successful communication has previously been demonstrated with BCIs in individuals with paralysis. But, to our knowledge, ours is the first study to achieve communication by someone who has no remaining voluntary movement and hence for whom the BCI is now the sole means of communication,” said Zimmerman.
While the system used is not currently available outside of clinical research, the investigators have been modifying it to allow its use by the family without the researchers’ technical input. The technology, says Birbaumer, is life-changing.
“With communication possible, quality of life is good in ALS paralyzed patients,” he says. “Patients tell us retrospectively that no communication is torture. [The] standard of care should improve dramatically if you can ask patients about pain, symptoms etc.”
The most important verdict from the trial, however, is that of the patient, who communicated his thoughts on the system.
“Jungs es funktioniert gerade so muehelos,” he wrote in his native German, translating to: “Boys, it works so effortlessly.”
Longitudinal Changes in Structural Connectivity in Young People at High Genetic Risk for Bipolar Disorder
by Gloria Roberts, Alistair Perry, Kate Ridgway, Vivian Leung, Megan Campbell, Rhoshel Lenroot, Philip B. Mitchell, Michael Breakspear in American Journal of Psychiatry
A brain imaging study of young people at high risk of developing bipolar disorder has for the first time found evidence of weakening connections between key areas of the brain in late adolescence.
Up until now, medical researchers knew that bipolar disorder was associated with reduced communication between brain networks that are involved with emotional processing and thinking, but how these networks developed prior to the condition was a mystery.
Today in a study published in The American Journal of Psychiatry, researchers from UNSW Sydney, the Hunter Medical Research Institute (HMRI), the University of Newcastle and international institutions showed evidence of these networks diminishing over time in young adults at high genetic risk of developing bipolar disorder — which has important implications for future intervention strategies.
The researchers used diffusion-weighted magnetic imaging (dMRI) technology to scan the brains of 183 individuals over a two-year period. They examined the progressive changes in the brain scans of people with high genetic risk of developing the condition over a two year period, before comparing them with a control group of people with no risk.
People with a parent or sibling who has bipolar disorder are considered high genetic risk, and are 10 times more likely to develop the condition than people without the close family link. In the brain image scans of 97 people with high genetic risk of bipolar disorder, the researchers noted a decrease in connectivity between regions of the brain devoted to emotion processing and cognition during the two years between scans.
But in the control group of 86 people with no family history of mental illness, they observed the opposite: strengthening in the neural connections between these same regions, when the adolescent brain matures to become more adept at the cognitive and emotional reasoning required in adulthood.
Scientia Professor Philip Mitchell AM, a practising academic psychiatrist with UNSW Medicine & Health, says the findings raise new ideas about treatment and intervention in bipolar disorder developing in young people with a higher risk.
“Our study really helps us understand the pathway for people at risk of bipolar,” he says. “We now have a much clearer idea of what’s happening in the brains of young people as they grow up.”
Prof. Mitchell says that being a clinician as well as a researcher, he sees first-hand how young people can have their lives suddenly turned upside down when they experience their first manic episode.
“We see a lot of bright, capable kids really enjoying life and then bipolar disorder can be a huge impediment to what they want to achieve. With our new knowledge about what actually happens in the brain as at-risk teenagers approach adulthood, we have the opportunity to develop new intervention strategies to either stop the condition in its tracks, or reduce the impact of the illness.”
Professor Michael Breakspear, who led the team at HMRI and the University of Newcastle that carried out the analysis of the dMRI scans, says the study illustrates how advances in technology can potentially bring about life-changing improvements to the way that mental illnesses can be treated.
“The relatives of people with bipolar disorder — especially the siblings and children — often ask about their own future risk, and this is a question of high personal concern,” he says. “It’s also an issue for their doctors, as the presence of bipolar disorder has important medication implications.
“This study is an important step in having imaging and genetic tests we can perform to help identify those likely to develop bipolar disorder, before they develop disabling and stressing symptoms of the disorder. This would bring psychiatry closer to other branches of medicine where screening tests are part of standard care.”
The researchers stress that more research is needed before changes are made to current modes of treatment. It also would not be practical, nor cheap, for all people with a genetic risk of developing bipolar disorder to have brain scans to see if the brain is showing signs of weakened connections.
“The significant finding of our study is that there is progressive change in the brains of young people with risk of bipolar which suggests how important intervention strategies might be,” says Prof. Mitchell. “If we can get in early, whether that’s training in psychological resilience, or maybe medications, then we may be able to prevent this progression towards major changes in the brain.”
Dr. Gloria Roberts, a postdoctoral researcher working primarily on the project since 2008 with UNSW Medicine & Health, has seen how new onsets of mental illness in youth at risk of developing bipolar disorder can significantly impact psychosocial functioning and quality of life.
“By advancing our understanding of the neurobiology of risk as well as resilience in these high-risk individuals we have the opportunity to intervene and improve the quality of life in individuals who are most at-risk.”
As a result of the new findings, the researchers are planning to do a third follow-up scan of participants in the study. They are also in the early stages of developing online programs that assist in the development of resilience while providing young people with skills in managing anxiety and depression, which they hope will reduce their chances of developing bipolar disorder.
Big-C creativity in artists and scientists is associated with more random global but less random local fMRI functional connectivity
by Ariana Anderson, Kevin Japardi, Kendra S. Knudsen, Susan Y. Bookheimer, Dara G. Ghahremani, Robert M. Bilder in Psychology of Aesthetics, Creativity, and the Arts
A new study led by UCLA Health scientists shows highly creative people’s brains appear to work differently from others’, with an atypical approach that makes distant connections more quickly by bypassing the “hubs” seen in non-creative brains.
Exceptionally creative visual artists and scientists — called “Big C” creative types — volunteered to undergo functional MRI brain imaging, giving researchers in psychiatry, behavioral sciences and psychology a look at how regions of the brain connected and interacted when called upon to perform tasks that put creative thinking to the test.
“Our results showed that highly creative people had unique brain connectivity that tended to stay off the beaten path,” said Ariana Anderson, a professor and statistician at the Semel Institute for Neuroscience and Human Behavior at UCLA, the lead author of a new article in the journal Psychology of Aesthetics, Creativity, and the Arts. While non-creatives tended to follow the same routes across the brain, the highly creative people made their own roads.
Although the concept of creativity has been studied for decades, little is known about its biological bases, and even less is understood about the brain mechanisms of exceptionally creative people, said senior author Robert Bilder, director of the Tennenbaum Center for the Biology of Creativity at the Semel Institute. This uniquely designed study included highly creative people representing two different domains of creativity — visual arts and the sciences — and used an IQ-matched comparison group to identify markers of creativity, not just intelligence. The researchers analyzed how connections were made between brain regions globally and locally.
“Exceptional creativity was associated with more random connectivity at the global scale — a pattern that is less ‘efficient’ but would appear helpful in linking distant brain nodes to each other,” Bilder said. “The patterns in more local brain regions varied, depending on whether people were performing tasks. Surprisingly, Big C creatives had more efficient local processing at rest, but less efficient local connectivity when performing a task demanding ‘thinking outside the box.’”
Using airline route maps for comparison, the researchers said the Big C creatives’ brain activity is akin to skipping flights to connecting hubs to get to a small city.
“In terms of brain connectivity, while everyone else is stuck in a three-hour layover at a major airport, the highly creatives take private planes directly to a distant destination,” Anderson said. “This more random connectivity may be less efficient much of the time, but the architecture enables brain activity to ‘take a road less traveled’ and make novel connections.”
Bilder, who has more than 30 years’ experience researching brain-behavior relations, said:
“The fact that Big C people had more efficient local brain connectivity, but only under certain conditions, may relate to their expertise. Consistent with some of our prior findings, they may not need to work as hard as other smart people to perform certain creative tasks.”
The artists and scientists in the study were nominated by panels of experts before being validated as exceptional based on objective metrics. The “smart” comparison group was recruited from participants in a previous UCLA study who had agreed to be contacted for possible participation in future studies, and from advertisements in the community for individuals with graduate degrees. The researchers made efforts to ensure that age, sex, race and ethnicity were comparable to those of participants in the Big C groups.
Microsaccades as a marker not a cause for attention-related modulation
by Gongchen Yu, James P Herman, Leor N Katz, Richard J Krauzlis in eLife
Minuscule involuntary eye movements, known as microsaccades, can occur even while one is carefully staring at a fixed point in space. When paying attention to something in the peripheral vision (called covert attention), these microsaccades sometimes align towards the object of interest. New research by National Eye Institute (NEI) investigators shows that while these microsaccades seem to boost or diminish the strength of the brain signals underlying attention, the eye movements are not drivers of those brain signals. The findings will help researchers interpret studies about covert attention and may open new areas for research into attention disorders and behavior.
Scientists working on the neuroscience of attention have recently become concerned that because both attention and eye movements, like microsaccades, involve the same groups of neurons in the brain, that microsaccades might be required for shifting attention.
“If microsaccades were driving attention, that would bring into question a lot of previous research in the field.” said Richard Krauzlis, Ph.D., chief of the NEI Section on Eye Movements and Visual Selection, and senior author of a study report on the research. “This work shows that while microsaccades and attention do share some mechanisms, covert attention is not driven by eye movements.”
Krauzlis’ previous research has shown that covert attention causes a modulation of certain neuronal signals in an evolutionarily ancient area of the brain called the superior colliculus, which is involved in the detection of events. When attention is being paid to a particular area — for example, the right-hand side of one’s peripheral vision — signals in the superior colliculus relating to events that occur in that area will receive an extra boost, while signals relating to events occurring somewhere else, like on the left-hand side, will be depressed.
When something shows up in our peripheral vision, we quickly shift our eyes — make a large saccade toward the event to take a better look. This movement brings the event into our high-resolution central vision. These eye movements are accompanied by a general decrease in visual signals, as the brain ignores the quickly shifting visual information received by the eye. In laboratory studies of covert attention, primates or people are directed to avoid those types of large saccades, keeping the attended event in the peripheral vision. However, involuntary microsaccades, which are accompanied by similar decreases in visual signals, often occur anyway.
In this study, led by first author Gongchen Yu, Ph.D., the researchers asked whether attention-based signal changes in the superior colliculus are driven by microsaccades, or if the two processes can be separated.
The researchers trained monkeys to hold their eyes straight ahead, while attending to their peripheral vision. The researchers would cue either the left or right side by flashing a ring on the “cued” side. After the cue, the monkeys would release a joystick if they detected a color change on the cued side, while ignoring any color changes on the uncued side. The researchers could measure changes in neuronal activity on both sides of the superior colliculus, detecting a boost to the cued side, and lower signals on the uncued side.
At the same time, the researchers used high-resolution eye-tracking cameras to measure microsaccades during the trials. Sometimes, there would be no microsaccades. In other trials, the monkeys would make a microsaccade toward the cued side, or away from the cued side. By lining up the signals based on the time any microsaccade began, the researchers found that the neuronal signals for attention in the superior colliculus were present before the microsaccade, and then would re-establish after the microsaccade.
In essence, although the eye movement would also trigger changes to neuronal signals in the superior colliculus, attention-related signals occurred independently of the eye movement signals.
“While the neuronal circuits activated by these two systems do overlap, the link between microsaccades and attention is not a causal one,” Krauzlis said.
“The majority of vision neuroscientists have been using this type of experimental system to study visual attention for decades. It’s a big relief to reconfirm that microsaccades are not the driver of the neuronal changes seen with visual attention,” said Yu. “This result means we don’t need to reevaluate decades of work!”
Cichlids and stingrays can add and subtract ‘one’ in the number space from one to five
by V. Schluessel, N. Kreuter, I. M. Gosemann, E. Schmidt in Scientific Reports
Cichlids and stingrays can perform simple addition and subtraction in the number range of one to five. This has been shown in a recent study by the University of Bonn, which has now been published in the journal Scientific Reports. It is not known what the animals need their mathematical abilities for.
Suppose there are some coins on the table in front of you. If the number is small, you can tell right away exactly how many there are. You don’t even have to count them — a single glance is enough. Cichlids and stingrays are astonishingly similar to us in this respect: they can detect small quantities precisely — and presumably without counting. For example, they can be trained to reliably distinguish quantities of three from quantities of four.
This fact has been known for some time. However, the research group led by Prof. Dr. Vera Schluessel from the Institute of Zoology at the University of Bonn has now shown that both species can even calculate.
“We trained the animals to perform simple additions and subtractions,” Schluessel explains. “In doing so, they had to increase or decrease an initial value by one.”
But how do you ask a cichlid for the result of “2+1” or “5–1”? The researchers used a method that other research groups had already successfully used to test the mathematical abilities of bees: They showed the fish a collection of geometric shapes — for example, four squares. If these objects were colored blue, this meant “add one” for the following discrimination. Yellow, on the other hand, meant “subtract one.”
After showing the original stimulus (e.g. four squares), the animals were shown two new pictures — one with five and one with three squares. If they swam to the correct picture (i.e. to the five squares in the “blue” arithmetic task), they were rewarded with food. If they gave the wrong answer, they went away empty-handed. Over time, they learned to associate the blue color with an increase of one in the amount shown at the beginning, and the yellow number with a decrease.
But can the fish apply this knowledge to new tasks? Had they actually internalized the mathematical rule behind the colors?
“To check this, we deliberately omitted some calculations during training,” Schluessel explains. “Namely, 3+1 and 3–1. After the learning phase, the animals got to see these two tasks for the first time. But even in those tests, they significantly often chose the correct answer.”
This was true even when they had to decide between choosing four or five objects after being shown a blue 3 — that is, two outcomes that were both greater than the initial value. In this case, the fish chose four over five, indicating they had not learned the rule ‘chose the largest (or smallest) amount presented’ but the rule ‘always add or subtract
This achievement surprised the researchers themselves — especially since the tasks were even more difficult in reality than just described. The fish were not shown objects of the same shape (e.g. four squares), but a combination of different shapes. A “four,” for example, could be represented by a small and a larger circle, a square and a triangle, whereas in another calculation it could be represented by three triangles of different sizes and a square.
“So the animals had to recognize the number of objects depicted and at the same time infer the calculation rule from their color,” Schluessel says. “They had to keep both in working memory when the original picture was exchanged for the two result pictures. And they had to decide on the correct result afterwards. Overall, it’s a feat that requires complex thinking skills.”
To some it may be surprising because fish don’t have a neocortex — the part of the brain also known as the “cerebral cortex” that’s responsible for complex cognitive tasks in mammals. Moreover, neither species of fish is known to require particularly good numerical abilities in the wild. Other species might pay attention to the strip count of their sexual partners or the amount of eggs in their clutches. “However, this is not known from stingrays and cichlids,” emphasizes the zoology professor at the University of Bonn.
She also sees the result of the experiments as confirmation that humans tend to underestimate other species — especially those that do not belong to our immediate family or mammals in general. Moreover, fish are not particularly cute and do not have cuddly fur or plumage.
“Accordingly, they are quite far down in our favor — and of little concern when dying in the brutal practices of the commercial fishing industry,” says Vera Schluessel.
A Single Belief-Changing Psychedelic Experience Is Associated With Increased Attribution of Consciousness to Living and Non-living Entities
by Nayak SM, Griffiths RR in Frontiers in Psychology
Psychedelic drugs, like psilocybin, an ingredient found in so-called magic mushrooms, have shown promise in treating a range of addictions and mental health disorders. Yet, there’s something mysterious and almost mystical about their effects, and they are commonly believed to provide unique insights into the nature of consciousness. Now, a new study by Johns Hopkins Medicine researchers addresses the question of whether psychedelics might change the attribution of consciousness to a range of living and nonliving things.
The findings, published March 28 in Frontiers in Psychology, reveal that higher ratings of mystical type experiences, which often include a sense that everything is alive, were associated with greater increases in the attribution of consciousness.
“This study demonstrates that when beliefs change following a psychedelic experience, attributions of consciousness to various entities tend to increase,” says Sandeep Nayak, M.D., postdoctoral research fellow at the Johns Hopkins Center for Psychedelic and Consciousness Research and one of the researchers involved in the study. “It’s not clear why, whether that might be an innate drug effect, cultural factors or whether psychedelics might somehow expose innate cognitive biases that attribute features of the mind to the world.”
For the study, the researchers analyzed data gathered between August 2020 and January 2021 on 1,606 people who have had a belief-changing psychedelic experience. Participants averaged 35 years of age and were predominately white (89%), male (67%) and from the United States (69%).
Study participants completed an internet-based survey that included questions focused on belief changes attributed to a single psychedelic experience with a classic psychedelic substance (e.g., psilocybin mushrooms, LSD, ayahuasca). The survey also included questions about demographics, psychedelic use, personality, and scientific knowledge and attitudes.
The study found that among people who have had a single psychedelic experience that altered their beliefs in some way, there were large increases in attribution of consciousness to a range of animate and inanimate things. For example, from before to after the experience, attribution of consciousness to insects grew from 33% to 57%, to fungi from 21% to 56%, to plants from 26% to 61%, to inanimate natural objects from 8% to 26% and to inanimate manmade objects from 3% to 15%.
“On average, participants indicated the belief-changing experience in question occurred eight years prior to taking the survey, so these belief changes may be long-lasting,” says Nayak.
Classic psychedelics — the pharmacological class of compounds that includes psilocybin and LSD — produce visual and auditory illusions and profound changes in consciousness, altering a person’s awareness of their surroundings and of their thoughts and feelings. These substances produce unusual and compelling changes in conscious experience, which have prompted some to propose that psychedelics may provide unique insights into the nature of consciousness itself.
“The results suggesting that a single psychedelic experience can produce a broad increase in attribution of consciousness to other things, raises intriguing questions about possible innate or experiential mechanisms underlying such belief changes,” says Roland Griffiths, Ph.D., the Oliver Lee McCabe III, Ph.D., Professor in the Neuropsychopharmacology of Consciousness at the Johns Hopkins University School of Medicine, and founding director of the Johns Hopkins Center for Psychedelic and Consciousness Research. “The topic of consciousness is a notoriously difficult scientific problem that has led many to conclude it is not solvable.”
Miniature structured illumination microscope for in vivo 3D imaging of brain structures with optical sectioning
by Omkar D. Supekar, Andrew Sias, Sean R. Hansen, Gabriel Martinez, Graham C. Peet, Xiaoyu Peng, Victor M. Bright, Ethan G. Hughes, Diego Restrepo, Douglas P. Shepherd, Cristin G. Welle, Juliet T. Gopinath, Emily A. Gibson in Biomedical Optics Express
Researchers have developed a miniature microscope that is designed for high-resolution 3D images inside the brains of living mice. By imaging deeper into the brain than previously possible with miniature widefield microscopes, the new lightweight microscope could help scientists better understand how brain cells and circuits operate.
“With further development, our microscope will be able to image neural activity over time while an animal is in a naturalistic environment or performing different tasks,” said lead author Omkar Supekar from the University of Colorado Boulder. “We show that it can be used to study cells that play an important role in neurological disorders such as multiple sclerosis.”
In the Optica Publishing Group journal Biomedical Optics Express, the researchers describe their new SIMscope3D, which images fluorescence emitted from tissue or fluorescent tags after the sample is exposed to certain wavelengths of light. The new device is the first miniature microscope to use structured illumination to remove out-of-focus and scattered light, which allowed imaging as deep as 260 microns on fixed brain tissue with an LED light source.
“Developing new treatments for neurological disorders requires understanding the brain at the cellular and circuit-level,” said research team lead Emily Gibson from the University of Colorado Anschutz Medical Campus. “New optical imaging tools — particularly those that can image deep into brain tissue like the microscope our team developed — are important for achieving this goal.”
Head mounted microscopes are used to image the brains of small rodents through transparent windows implanted into their skulls. Researchers have previously developed head-mounted widefield fluorescence microscopes, but light scattered by tissue prevents imaging deep into the brain. Miniature two-photon microscopes can overcome this drawback by eliminating out-of-focus light in each focal plane — a process known as optical sectioning — but typically require expensive pulsed lasers and complex mechanical scanning components.
To design the new microscope, Andrew Sias, Sean Hansen, Gabriel Martinez and Emily Gibson from the Department of Bioengineering at the University of Colorado Anschutz Medical Campus; Douglas Shepherd from the Department of Physics at Arizona State University; Omkar Supekar and Juliet Gopinath from the Department of Electrical, Computer and Energy Engineering, and Victor Bright from the Department of Mechanical Engineering at the University of Colorado Boulder collaborated closely with neuroscientists Graham Peet, Diego Restrepo and Ethan Hughes from the Department of Cell and Developmental Biology and Xiaoyu Peng and Cristin Welle from the Department of Physiology and Biophysics at the University of Colorado Anschutz Medical Campus to optimize it for studying the brain.
Volumetric imaging is accomplished by using an imaging fiber to deliver spatially patterned light to the miniature microscope objective. This process also removes out-of-focus light, enabling optical sectioning similar to that accomplished with two-photon approaches but without the complex components or expensive laser.
The microscope includes a compact tunable electrowetting lens that allows 3D visualization of brain structures by changing the microscope’s focal depth without requiring any moving parts. The researchers also integrated a CMOS camera directly into the microscope. This enables imaging with high lateral resolution while avoiding artifacts that might be induced if the images traveled through the fiber bundle. Using an LED light source, the new microscope can produce sharp contrast even when imaging deeply into highly scattering tissue.
The researchers demonstrated their new system by imaging oligodendrocytes and microglia labeled with a fluorescent protein in mice that were awake but placed in a device that kept their head stationary. In people with multiple sclerosis, oligodendrocytes — which form an insulating layer around axons — are destroyed. This causes the connections in the brain to slow down, leading to impairment of vision, motor skills and other problems.
“We used our miniature microscope to record a time series of glial cell dynamics in awake mice at depths up to 120 microns in the brain,” said Supekar. “Scientists don’t fully understand exactly how these cells work or their repair processes. Our microscope opens the possibility of long-term studies examining how these cells migrate and are repaired.”
The researchers are now working to improve the microscope’s acquisition speed and weight. With minor upgrades, the microscope will be able to image faster dynamics, such as neuronal electrical activity, while the mouse performs different tasks. The researchers say that because the microscope does not require expensive components it could be easily developed into a commercial system for use in neuroscience labs.
Optimal deep brain stimulation sites and networks for cervical vs. generalized dystonia
by Andreas Horn, Martin M. Reich, Siobhan Ewert, Ningfei Li, Bassam Al-Fatly, Florian Lange, Jonas Roothans, Simon Oxenford, Isabel Horn, Steffen Paschen, Joachim Runge, Fritz Wodarg, Karsten Witt, Robert C. Nickl, Matthias Wittstock, Gerd-Helge Schneider, Philipp Mahlknecht, Werner Poewe, Wilhelm Eisner, Ann-Kristin Helmers, Cordula Matthies, Joachim K. Krauss, Günther Deuschl, Jens Volkmann, Andrea A. Kühn in Proceedings of the National Academy of Sciences
Recent discoveries made by researchers from Charité — Universitätsmedizin Berlin may prove vital in improving the treatment of dystonia, a neurological movement disorder. Published in PNAS, their findings show that very specific networks in the brain must be stimulated in order to relieve the symptoms seen in different types of dystonia.
Dystonia is a rare neurological disorder, which is characterized by involuntary, twisting and distorting movements and postures. People with dystonia may be limited in their ability to perform activities of daily living, such as drinking, walking and speaking. In Germany, approximately 160,000 people have dystonia. The condition is subdivided into generalized dystonia, which affects the entire body, and focal dystonia, which is limited to specific parts of the body. The latter category includes cervical dystonia, which affects the neck. The condition’s underlying causes are not fully understood, but experts assume that symptoms are the result of faulty interactions between specific areas of the brain which lead to abnormal signal transmission. Depending on the form of dystonia involved, genetic defects may also play a role.
One treatment option available to patients with dystonia is a neurosurgical procedure involving the implantation of electrodes into specific areas of the brain. Once implanted, the electrodes emit weak electrical signals which help to restore normal brain function. Known as deep brain stimulation, the procedure involves the implantation of a pacemaker-like device and is often the only treatment capable of providing relief of symptoms.
“The precision with which this stimulation has to be adapted to the symptoms seen in different types of dystonia was not clear until now,” explains study lead Prof. Dr. Andrea Kühn, who is Head of the Department of Neurology and Experimental Neurology’s Movement Disorders and Neuromodulation Section and Spokesperson of the ‘ReTune’ Transregional Collaborative Research Center (SFB/Transregio TRR 295), which helped to support the current study.
Prof. Kühn’s team examined a total of 80 patients who had received treatment for either generalized or cervical dystonia at one of five different hospitals in Germany and Austria. After analyzing the electrodes’ precise positions, the researchers were able to generate computer models showing which brain networks were being activated in each of the patients investigated. By mapping data on symptom improvements to their network models, the researchers were then able to determine which of the identified networks were crucial to treatment success.
One key finding was that the optimal target for stimulation depends on the type of dystonia being treated. This means that optimal treatment outcomes were associated with specific connections between the thalamus (the largest structure in the diencephalon, or ‘interbrain’) and the pallidum (a pale-colored structure at the core of the basal ganglia). The basal ganglia are deep-seated brain structures which play a part in movement control. In patients with cervical dystonia, the determining factor was electrical stimulation of a specific neural network which also activated the head and neck region of the primary motor cortex. As the brain’s motor command center, this area is responsible for planning and initiating movements as well as storing movement memory. In contrast, for patients with generalized dystonia, beneficial effects were elicited through the stimulation of a different network which projected to the entire primary motor cortex.
“Our study shows clear differences in optimal stimulation sites, which correspond to the somatotopic structure of the inner pallidum. This means that neural areas in the brain map to the areas of the body they represent,” says the study’s first author, Dr. Andreas Horn of the Department of Neurology and Experimental Neurology. He adds: “Due to the paucity of alternative treatment options beyond deep brain stimulation, our findings make an important contribution to improving treatment for dystonia. In the future, we will be able to more deliberately treat specific types of the disorder.”
Neuropathology and virus in brain of SARS-CoV-2 infected non-human primates
by Ibolya Rutkai, Meredith G. Mayer, Linh M. Hellmers, Bo Ning, Zhen Huang, Christopher J. Monjure, Carol Coyne, Rachel Silvestri, Nadia Golden, Krystle Hensley, Kristin Chandler, Gabrielle Lehmicke, Gregory J. Bix, Nicholas J. Maness, Kasi Russell-Lodrigue, Tony Y. Hu, Chad J. Roy, Robert V. Blair, Rudolf Bohm, Lara A. Doyle-Meyers, Jay Rappaport, Tracy Fischer in Nature Communications
COVID-19 patients commonly report having headaches, confusion and other neurological symptoms, but doctors don’t fully understand how the disease targets the brain during infection.
Now, researchers at Tulane University have shown in detail how COVID-19 affects the central nervous system, according to a new study published in Nature Communications.
The findings are the first comprehensive assessment of neuropathology associated with SARS-CoV-2 infection in a nonhuman primate model.
The team of researchers found severe brain inflammation and injury consistent with reduced blood flow or oxygen to the brain, including neuron damage and death. They also found small bleeds in the brain.
Surprisingly, these findings were present in subjects that did not experience severe respiratory disease from the virus.
Tracy Fischer, PhD, lead investigator and associate professor of microbiology and immunology at the Tulane National Primate Research Center, has been studying brains for decades. Soon after the primate center launched its COVID-19 pilot program in the spring of 2020, she began studying the brain tissue of several subjects that had been infected.
Fischer’s initial findings documenting the extent of damage seen in the brain due to SARS-CoV-2 infection were so striking that she spent the next year further refining the study controls to ensure that the results were clearly attributable to the infection.
“Because the subjects didn’t experience significant respiratory symptoms, no one expected them to have the severity of disease that we found in the brain,” Fischer said. “But the findings were distinct and profound, and undeniably a result of the infection.”
The findings are also consistent with autopsy studies of people who have died of COVID-19, suggesting that nonhuman primates may serve as an appropriate model, or proxy, for how humans experience the disease.
Neurological complications are often among the first symptoms of SARS-CoV-2 infection and can be the most severe and persistent. They also affect people indiscriminately — all ages, with and without comorbidities, and with varying degrees of disease severity.
Fischer hopes that this and future studies that investigate how SARS-CoV-2 affects the brain will contribute to the understanding and treatment of patients suffering from the neurological consequences of COVID-19 and long COVID.
Who uses digital drugs? An international survey of ‘binaural beat’ consumers
by Monica J. Barratt, Alexia Maddox, Naomi Smith, Jenny L. Davis, Lachlan Goold, Adam R. Winstock, Jason A. Ferris in Drug and Alcohol Review
A binaural beat is an illusionary tone created by the brain when presenting two tones separately to each ear that slightly differ in their frequency.
It’s claimed binaural beats can have a psychoactive effect on the brain, although there’s limited research on their efficacy and safety.
Now a new study published in Drug and Alcohol Review has captured how and why people use the tones. Data comes from the Global Drug Survey 2021, which drew on responses from more than 30,000 people in 22 countries.
Respondents mainly used binaural beats to relax or fall asleep (72%) and to change their mood (35%), while 12% reported trying to get a similar effect to that of psychedelic drugs.
The study’s lead author, Dr Monica Barratt of RMIT University in Melbourne, Australia, said the latter motivation was more commonly reported among those who used classic psychedelics.
“Much like ingestible substances, some binaural beats users were chasing a high,” she said. “But that’s far from their only use. Many people saw them as a source of help, such as for sleep therapy or pain relief.”
The audio tracks are often named for their intended use — everything from mindfulness and meditation to tracks named after ingestible drugs like MDMA and cannabis.
The survey revealed binaural beat users were more likely to be younger and to report recent use of all prohibited drugs, compared to rest of the sample.
Most respondents sought to connect with themselves or something bigger than themselves through the experience.
The use of binaural beats to experience altered states was reported by 5% of the total sample.
In the United States 16% of respondents said they’d tried it, while in Mexico and Brazil countries reported use was also above average at 14% and 11.5% respectively.
Video streaming sites like YouTube and Vimeo were the most popular way to listen, followed by Spotify and other streaming apps.
Barratt said the illusionary tones had been accessible for more than a decade, but their popularity had only recently begun to grow.
“It’s very new, we just don’t know much about the use of binaural beats as digital drugs,” she said. “This survey shows this is going on in multiple countries. We had anecdotal information, but this was the first time we formally asked people how, why and when they’re using them.”
Barratt said the binaural beats phenomenon challenges the overall definition of a drug.
“We’re starting to see digital experiences defined as drugs, but they could also be seen as complementary practices alongside drug use,” she said. “Maybe a drug doesn’t have to be a substance you consume, it could be to do with how an activity affects your brain.”
Despite binaural beat listeners being younger, Barratt said they’re not necessarily a gateway to the use of ingestible drugs.
“In the survey, we found most people who listen were already using ingestible substances,” she said. “But that doesn’t discount the need for more research, particularly to document and negate possible harms.”
On the flipside, Barratt said perhaps binaural beats could be used as a therapy method, alongside traditional treatment.
“Evidence is mounting but it’s still unclear, which is why more research is needed into any possible side effects,” she said.
Although the Global Drug Survey is a non-representative sample, the self-reported use of binaural beats as digital drugs by respondents sets the course for more targeted research.
‘Who uses digital drugs? An international survey of ‘binaural beat’ consumers’, with co-authors Monica Barratt, Alexia Maddox, Naomi Smith, Jenny Davis, Lachlan Goold, Adam Winstock and Jason Ferris is published in Drug and Alcohol Review.
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