Category: Neurology

Optical Illusions Originate in the Retina, not the Brain

The bar in the middle is all one grey level, but it appears lighter on the left and darker on the right due to the background. Credit Jolyon Troscianko

Numerous visual illusions are caused by limits in the way our eyes and visual neurones work – rather than more complex psychological processes, as demonstrated by new research published in PLOS Computational Biology.

Researchers examined illusions in which an object’s surroundings affect the way we see its colour or pattern. Scientists and philosophers have long debated whether these illusions are caused by neural processing in the eye and low-level visual centres in the brain, or involve higher-level mental processes such as context and prior knowledge.

In the new study Dr Jolyon Troscianko, from the University of Exeter, co-developed a model that suggests simple limits to neural responses – not deeper psychological processes – explain these illusions.

“Our eyes send messages to the brain by making neurones fire faster or slower,” said Dr Troscianko. “However, there’s a limit to how quickly they can fire, and previous research hasn’t considered how the limit might affect the ways we see colour.”

The model combines this “limited bandwidth” with information on how humans perceive patterns at different scales, together with an assumption that our vision performs best when we are looking at natural scenes.

The model was developed by researchers from the Universities of Exeter and Sussex to predict how animals see colour, but it was also found to correctly predict many visual illusions seen by humans.

“This throws into the air a lot of long-held assumptions about how visual illusions work,” Dr Troscianko said.

He said the findings also shed light on the popularity of high-definition televisions.

“Modern high dynamic range televisions create bright white regions that are over 10 000 times brighter than their darkest black, approaching the contrast levels of natural scenes,” Dr Troscianko added.

“How our eyes and brains can handle this contrast is a puzzle because tests show that the highest contrasts we humans can see at a single spatial scale is around 200:1.

“Even more confusingly, the neurones connecting our eyes to our brains can only handle contrasts of about 10:1.

“Our model shows how neurones with such limited contrast bandwidth can combine their signals to allow us to see these enormous contrasts, but the information is ‘compressed’ – resulting in visual illusions.

“The model shows how our neurones are precisely evolved to use of every bit of capacity.

“For example, some neurones are sensitive to very tiny differences in grey levels at medium-sized scales, but are easily overwhelmed by high contrasts.

“Meanwhile, neurones coding for contrasts at larger or smaller scales are much less sensitive, but can work over a much wider range of contrasts, giving deep black-and-white differences.

“Ultimately this shows how a system with a severely limited neural bandwidth and sensitivity can perceive contrasts larger than 10 000:1.”

Source: University of Exeter

Endocrine-disrupting Chemicals may Raise Risk of Cognitive Disorders in Future Generations

Adverse cognitive effects linked to polychlorinated biphenyls (PCBs) exposure, a type of endocrine-disrupting chemical (EDC), have the potential to be passed down through generations, according to an animal study being presented Thursday at ENDO 2023, the Endocrine Society’s annual meeting in Chicago, USA.

PCBs can mimic the effect of oestrogen on the body, contributing to a variety of neuroendocrine, metabolic and reproductive problems.

“Endocrine-disrupting chemicals present in our food, air, water and personal products may cause cognitive-behavioural disorders like attention-deficit/hyperactivity disorder or overeating in future generations,” said Emily N. Hilz, PhD, a postdoctoral fellow at the University of Texas at Austin.

To explore this further, Hilz and colleagues administered a common PCB mixture called Aroclor 1221 to pregnant female rats. The adults (n=40), their offspring (n=80), and their future grandchildren (n=80) were all tested on behavioural tasks to assess pleasure-seeking, ability to pay attention, and cognitive flexibility.

“The grandchildren of rats exposed to EDCs while pregnant performed significantly worse on these tasks, showing impaired cognitive function and increased pleasure-seeking,” Hilz said. “This suggests EDCs program potential cognitive disorders or behavioural problems that only emerge in later generations.”

Grandchildren of rats that were exposed to the PCB mixture were more interested in eating for pleasure, according to the results of the sucrose preference test. While all of the tested animals preferred the sucrose solution to water, the grandchildren of mothers exposed to the PCB mixture consumed more of the sucrose solution.

The same rats had an impaired ability to switch between tasks or learn new rules. However, only the male grandchildren were more likely to become fixated with a visual cue, which is common in disorders such as ADHD.

The PCB mixture impaired different aspects of cognitive behavior between male and female rats, depending on the life stage when they were exposed. It’s not yet clear which biological systems might be driving this.

“Our findings suggest regulating EDCs in industrial and consumer products could reduce the prevalence of certain cognitive or behavioural disorders in the future,” Hilz said.

Source: The Endocrine Society

‘Digital Bridging’ Enables Paraplegic Man to Walk Again

Study participant Gert-Jan Oskam walking with the brain-spine interface. Credit: Swiss Federal Institute of Technology in Lausanne

A 40 year-old man, Gert-Jan Oskam, has regained the ability to walk independently after being paralysed from a spinal cord injury with the use of a new brain-spine interface. The ‘digital bridging’ technology, developed at the Swiss Federal Institute of Technology in Lausanne and described in Nature, consists of implants and a computer to translate brain signals of the intention to move into stimulations that move the legs accordingly..

This BSI system could be calibrated in minutes, and remained stable for one year, including use at home. The BSI enabled the participant to exert natural control over the movements of his legs to stand, walk, climb stairs and even traverse complex terrains.

In addition to the digital bridging, neurorehabilitation supported by the BSI improved neurological recovery. The participant regained the ability to walk with crutches overground even when the BSI was switched off. This digital bridge establishes a framework to restore natural control of movement after paralysis.

The system consists of a pair cortical of sensors, each an array with 64 electrodes housed in 5cm-diameter titanium discs. These discs are implanted snugly in the skull to pick up brain activity. They transmit the data wirelessly to a personalised headset, which also provides power for the sensors. The headset then sends the data to a portable processing unit (which may be carried in a backpack). Using specialised software, it uses this brain signal data to generates real-time predictions of motor intentions. These decoded intentions are translated into stimulation commands and sent on to another implant, a paddle array of 16 electrodes implanted next to the spinal cord, delivering current to the targeted dorsal root entry zones.

Neurosurgical implantation procedure

Oskam had sustained an incomplete cervical (C5/C6) spinal cord injury during a biking accident 10 years previously. He had already participated in a neurological recovery programme, the STIMO trial, which had used neurostimulation to get him to the stage where he could walk with the aid of a front-wheel walker. The neurorehabilitation from the trial also enabled him to use his hip flexors and lift his legs against gravity, but recovery had plateaued for the three years prior to his participation in the present study.

For the BSI to function, the researchers needed to locate neural features related to the intention to move the legs. To pinpoint the cortical regions associated with the intention to move, they used CT scans and magnetoencephalography. Taking into account anatomical restraints, they then decided on the positions of the implants.

Under general anaesthesia, surgeons performed a bicoronal incision of the scalp to allow two circular-shaped craniotomies over the planned locations of the left and right hemispheres. They then replaced the bone flaps with the two implantable recording devices, before closing the scalp.

The paddle lead had already been emplaced over the dorsal root entry zones of the lumbar spinal cord during the STIMO clinical trial. Its optimal positioning was identified using high-resolution structural imaging of the spine, and its final position was decided during the surgery based on electrophysiological recordings. The implantable pulse generator was inserted subcutaneously in the abdomen. Oskam was able to return home 24 hours after each procedure.

Study Tests a Simple, Personalised Approach to Tinnitus Treatment

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A recent study published in JAMA Network Open suggests that relief might be possible for debilitating cases of tinnitus by using a bi-sensory approach, combining mild but bothersome electrical stimulation with sound.

The study, by researchers at the University of Michigan’s Kresge Hearing Research Institute, was based on research into the processing of bi-sensory information, which could be used for personalised stimulation to treat tinnitus.

In a double-blind, randomised clinical trial, researchers recruited 99 individuals with somatic tinnitus, which 70% of tinnitus sufferers have. In this form, movements such as clenching the jaw, or applying pressure to the forehead, cause a noticeable change in pitch or loudness of experienced sounds.

Susan Shore, PhD, Professor Emerita in Michigan Medicine’s Department of Otolaryngology and U-M’s Departments of Physiology and Biomedical Engineering, led the research, in which candidates with bothersome, somatic tinnitus, as well as normal-to-moderate hearing loss, were eligible to participate.

“After enrolment, participants received a portable device developed and manufactured by in2being, LLC, for in-home use,” she said. “The devices were programmed to present each participant’s personal tinnitus spectrum, which was combined with electrical stimulation to form a bi-sensory stimulus, while maintaining participant and study team blinding.”

Study participants were randomly assigned to one of two groups. The active group received bi-sensory treatment first, while the control group received sound-only treatment first.

For the first six weeks, participants were instructed to use their devices for 30 minutes each day. The next six weeks gave participants a break from daily use, followed by six more weeks of the treatment not received in the beginning of the study.

Participants completed the Tinnitus Functional Index (TFI), and Tinnitus Handicap Inventory (THI) to measure the daily impact of tinnitus. Participants also had their tinnitus loudness assessed during this time.

The team found that when participants received the bi-sensory treatment, they consistently reported improved quality of life, lower handicap scores and significant reductions in tinnitus loudness. These effects were not seen in the control group.

Additionally, more than 60% of participants reported significantly reduced tinnitus symptoms after the six weeks of active – treatment, but not for the control. This matches earlier work from Shore’s team, which showed that the longer participants received active treatment, the greater the reduction in their tinnitus symptoms.

“This study paves the way for the use of personalised, bi-sensory stimulation as an effective treatment for tinnitus, providing hope for millions of tinnitus sufferers,” said Shore.

Source: Michigan Medicine – University of Michigan

The Geometry of the Brain May Influence Brain Functions

Photo by Robina Weermeijer on Unsplash

For over 100 years, scientists have thought that the brain activity patterns that define human consciousness arose from how different brain regions communicate with each other through trillions of cellular connections.

Now, by examining more than 10 000 different maps of human brain activity, Monash University-led researchers found that the overall shape of a person’s brain has a much greater influence on thought and behaviour than its neuronal connectivity. This may sound like the old pseudoscience of phrenology, which based theories of personality and cognition on the shape of the head and its bumps.

Not so for this study, which combines approaches from physics, neuroscience and psychology to overturn the century-old model revolving around complex brain connectivity, instead revealing a relationship between brain shape and activity. The researchers published their ground-breaking findings in the journal Nature.

Lead author Dr James Pang said the findings were significant because they greatly simplified the way that we can study how the brain functions, develops and ages.

“The work opens opportunities to understand the effects of diseases like dementia and stroke by considering models of brain shape, which are far easier to deal with than models of the brain’s full array of connections,” Dr Pang said.

“We have long thought that specific thoughts or sensations elicit activity in specific parts of the brain, but this study reveals that structured patterns of activity are excited across nearly the entire brain, just like the way in which a musical note arises from vibrations occurring along the entire length of a violin string, and not just an isolated segment,” he said.

Using magnetic resonance imaging (MRI), the researchers studied eigenmodes, which are the natural patterns of vibration or excitation in a system, where different parts of the system are all excited at the same frequency. Eigenmodes are normally used in areas such as physics to study physical systems only recently have they been applied to studying brain.

Their study focused on developing the optimal way to construct the eigenmodes of the brain.

“Just as the resonant frequencies of a violin string are determined by its length, density and tension, the eigenmodes of the brain are determined by its structural – physical, geometric and anatomical – properties, but which specific properties are most important has remained a mystery,” said co-lead author, Dr Kevin Aquino, of BrainKey and The University of Sydney.

‘Like the shape of a drum influences the sounds that it can make’

The team, led by Professor Alex Fornito, compared how well eigenmodes derived from models of brain shape could account for different patterns of activity as opposed to eigenmodes from models of brain connectivity.

“We found that eigenmodes defined by brain geometry – its contours and curvature – represented the strongest anatomical constraint on brain function, much like the shape of a drum influences the sounds that it can make,” said Fornito.

“Using mathematical models, we confirmed theoretical predictions that the close link between geometry and function is driven by wave-like activity propagating throughout the brain, just as the shape of a pond influences the wave ripples that are formed by a falling pebble,” he said.

“These findings raise the possibility of predicting the function of the brain directly from its shape, opening new avenues for exploring how the brain contributes to individual differences in behavior and risk for psychiatric and neurological diseases.”

The research team found that, across over 10 000 MRI activity maps, obtained as people performed different tasks developed by neuroscientists to probe the human brain, activity was dominated by eigenmodes with spatial patterns that have very long wavelengths, extending over distances exceeding 40 mm.

“This result counters conventional wisdom, in which activity during different tasks is often assumed to occur in focal, isolated areas of elevated activity, and tells us that traditional approaches to brain mapping may only show the tip of the iceberg when it comes to understanding how the brain works,” Dr Pang said.

Source: MedicalXpress

Elon Musk’s Neuralink Brain-computer Interface Receives Human Testing Approval

Elon Musk’s company Neuralink had finally received approval for human testing of its brain-computer interface (BCI). After initially rejecting the application, the US Food and Drug Administration finally gave the company the go-ahead on Thursday.

Neuralink, which aims to develop an implant that would allow humans to interface directly with computers as well as enabling medical applications such as controlling prostheses. Last year, the company showed off a monkey that was able to play the simple video game Pong on a monitor using its mind.

Neuralink is by no means the first company to try to achieve these goals. Many other institutions have made advances over the past decades, but the field is a difficult one and progress is slow. In its previous rejection, the FDA cited concerns such as the devices using lithium for their batteries, migration of the wires inside the brain and the difficulty of extracting the devices without harming brain tissue.

The company’s use of animals to develop the technology has infuriated activists, but this is a standard practice in development of BCI technology. Last year, whistleblowers accused the company of killing 1500 animals since its inception.

In a guidance document, the FDA says that, “The field of implanted BCI devices is progressing rapidly from fundamental neuroscience discoveries to translational applications and market access. Implanted BCI devices have the potential to bring benefit to people with severe disabilities by increasing their ability to interact with their environment, and consequently, providing new independence in daily life.”

China is also aggressively pursuing the development of BCIs as part of their ‘China Brain Project’, as discussed in the journal Neuron. It has a significant advantage as it has a large population of macaques to draw on, along with fewer ethical concerns and policies expediting biotech research.

Low Maternal Vitamin D Levels may Increase Schizophrenia Risk of Offspring

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Neuroscientists published in the Journal of Neurochemistry, shows that maternal levels of vitamin D are key in the development of dopaminergic neurons, which are thought to be involved in schizophrenia.

Professor Darryl Eyles has built on past research out of his laboratory at the Queensland Brain Institute linking maternal vitamin D deficiency and brain development disorders, such as schizophrenia, to understand the functional changes taking place in the brain.

Schizophrenia is associated with many developmental risk factors, both genetic and environmental. While the precise neurological causes of the disorder are unknown, what is known is that schizophrenia is associated with a pronounced change in the way the brain uses dopamine, the neurotransmitter often referred to as the brain’s ‘reward molecule’.

Professor Eyles has followed the mechanisms that might relate to abnormal dopamine release and discovered that maternal vitamin D deficiency affects the early development and later differentiation of dopaminergic neurons.

The team at the Queensland Brain Institute developed dopamine-like cells to replicate the process of differentiation into early dopaminergic neurons that usually takes place during embryonic development.

They cultured the neurons both in the presence and absence of the active vitamin D hormone. In three different model systems they showed dopamine neurite outgrowth was markedly increased. They then showed alterations in the distribution of presynaptic proteins responsible for dopamine release within these neurites.

“What we found was the altered differentiation process in the presence of vitamin D not only makes the cells grow differently, but recruits machinery to release dopamine differently,” Professor Eyles said.

Using a new visualisation tool known as false fluorescent neurotransmitters, the team could then analyse the functional changes in presynaptic dopamine uptake and release in the presence and absence of vitamin D.

They showed that dopamine release was enhanced in cells grown in the presence of the hormone compared to a control.

“This is conclusive evidence that vitamin D affects the structural differentiation of dopaminergic neurons.”

Leveraging advances in targeting and visualising single molecules within presynaptic nerve terminals has enabled Professor Eyles and his team to further explore their long-standing belief that maternal vitamin D deficiency changes how early dopaminergic circuits are formed.

The team is now exploring whether other environmental risk factors for schizophrenia such as maternal hypoxia or infection similarly alter the trajectory of dopamine neuron differentiation.

Eyles and his team believe such early alterations to dopamine neuron differentiation and function may be the neurodevelopmental origin of dopamine dysfunction later in adults who develop schizophrenia.

Source: University of Queensland

Instead of Dying, Motor Neurons Just Lose Connectivity with Age

Source: CC0

A new study published in the Journal of Clinical Investigation Insight offers a blueprint to help scientists prevent and reverse motor deficits that occur in old age. Their findings showed that loss of connectivity of motor neurons in the spinal cord – not the death of those neurons, as was previously thought – is what impairs voluntary movements during aging.

As humans age, tasks that require coordinated motor skills, such as navigating stairs or writing a letter, become increasingly difficult to perform. Reduced mobility caused by aging is strongly associated with adverse health outcomes and a diminished quality of life.

Researchers at Brown University led by Gregorio Valdez, an associate professor of molecular biology, cell biology and biochemistry, discovered that motor neurons start to have fewer synapses.

“This is an important fundamental discovery because it tells us that treatments are possible to prevent and reverse motor deficits that occur as we age,” said Valdez, who is affiliated with both the Center for Translational Neuroscience and the Center for Alzheimer’s Disease Research at the Carney Institute and Brown’s Center on the Biology of Aging. “The primary hardware, motor neurons, are spared by aging. If we can figure out how to keep synapses from degenerating, or mimic their actions using pharmacological interventions, we may be able to treat motor issues in the elderly that often lead to injuries due to falls.”

For the study, researchers examined spinal motor neurons in three species, including humans, rhesus monkeys and mice.

“These findings revealed that, as individuals age, motor neurons lose many of the connections that direct their function,” said Ryan Castro, first author of the study, who earned a PhD in neuroscience from Brown in 2022.    

Because of their critical function, Valdez said, the loss of either motor neurons or their synapses would impair voluntary movements. 

The number and size of motor neurons do not significantly change during aging, the researchers discovered. However, they undergo other processes that contribute to aging.

“Aging causes motor neurons to engage in self-destructive behaviour,” Valdez said. “While motor neurons do not die in old age, they progressively increase expression of molecules that cause degeneration of their own synapses and cause glial cells to attack neurons, and that increases inflammation.” 

Some of these aging-related genes and pathways are also found altered in motor neurons affected with amyotrophic lateral sclerosis (ALS).

The researchers now plan to pursue studies to target molecular mechanisms they found altered in motor neurons that could be responsible for the loss of their own synapses with advancing age.  

Source: Brown University

Study Measures the True Facial Processing Ability of ‘Super-recognisers’

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So-called ‘super-recognisers’ are people with a much greater ability to recognise faces in a variety of contexts, but their ability has not been empirically tested. A new study in PNAS shows that super-recognisers do in fact possess greatly superior facial recognition compared to normal peers.

While police departments have known of their abilities for quite some time, it was just over a decade ago, when super-recognisers were described in the literature as having exceptional facial processing abilities. With the increasing use of CCTV in police investigations and the potential for human error, there have been questions raised as to whether super-recognisers could do a better job – or indeed, whether they have empirically superior abilities. A means for actually identifying and defining a super-recogniser as opposed to someone who merely seems to better at recalling faces is therefore needed.

The performance of people with normal facial recognition abilities is not very impressive. While performance is good when people are familiar with the person pictured, studies report an error as high as 35% with unfamiliar faces. Even when people are asked to compare a live person standing in front of them with a photo, a recent study found they still got more than 20% of their answers wrong.

For this study, researchers enrolled 73 super-recogniser and 45 control participants. They compared the two groups on performance on three challenging tests of face identity processing recommended for super-recogniser identification; as well as performance for perpetrator identification using four CCTV sequences depicting five perpetrators and police line-ups created for criminal investigation purposes. They found that the face identity processing tests used here are valid in measuring such abilities and identifying super-recognisers. In addition, they determined that super-recognisers excel at perpetrator identification relative to control participants, with more correct perpetrator identifications, the better their performance across lab tests.

Navigating the Maze of the Brain’s Glymphatic System

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Like the lymphatic system in the body, the glymphatic system in the brain clears metabolic waste and distributes nutrients and other important compounds. Impairments in this system may contribute to brain diseases, such as neurodegenerative diseases and stroke.

A team of researchers has found a noninvasive and nonpharmaceutical method to influence glymphatic transport using focused ultrasound, opening the opportunity to use the method to further study brain diseases and brain function. Their findings are published in PNAS.

Hong Chen, associate professor of biomedical engineering in McKelvey Engineering and of neurological surgery in the School of Medicine, and her team, including Dezhuang (Summer) Ye, a postdoctoral research associate, and Si (Stacie) Chen, a former postdoctoral research associate, found the first direct evidence that focused ultrasound, combined with circulating microbubbles (FUSMB) could mechanically enhance glymphatic transport in the mouse brain.

Focused ultrasound can penetrate the scalp and skull to reach the brain and precisely target a defined region within the brain. Previously, Chen’s team found that microbubbles injected into the bloodstream amplify the effects of the ultrasound waves on the blood vessels and generate a pumping effect, which helps with the accumulation of intranasally delivered agents in the brain, such as drugs or gene therapy treatments.

“Intranasal delivery provides a novel, noninvasive route to investigate the glymphatic pathway in intact brains,” Chen said. “This route for investigating glymphatic transport has the potential to be utilised in the study of glymphatic function in humans, which is currently limited by the absence of noninvasive approaches to access the glymphatic system.”

In the new research, the team administered a fluorescently labelled tracer intranasally. Then they administered focused ultrasound waves aimed deep in the brain at the thalamus after intravenous injection of microbubbles. When they conducted 3D imaging of the brain tissue on the treated side, they found that FUSMB boosted the transport of the tracer in the perivascular space.

They compared this with three control groups with various combinations of focused ultrasound, microbubbles and the tracer. All of the mice in the three control groups showed lower tracer accumulation, which verified to the team that the enhanced tracer transport was the result of the focused ultrasound with microbubbles.

To further validate their results, they used the FUSMB treatment after injecting the tracer directly to the cerebral spinal fluid, an invasive yet commonly used method. They found that FUSMB also enhanced the transport of tracers along the vessels at the focused-ultrasound targeted brain site by about two- to threefold compared with the non-targeted side.

“Regardless of whether tracers were delivered via the intranasal or injected route, FUSMB consistently improved glymphatic transport,” Ye said. “Our study using confocal microscopy imaging combined with brain-tissue clearing obtained direct evidence that unequivocally proved that FUSMB enhanced the glymphatic transport of a labeled protein agent in mice.”

The team also investigated various types of vessels, including arterioles, capillaries and venules, that facilitate FUSMB-enhanced transport of the tracer using both intranasal and injected delivery of the tracer. They saw improved glymphatic transport of the tracer in both arterioles and capillaries with both types of delivery. They found that the fluorescence intensity was higher along arterioles than capillaries and venules.

“This study opens new opportunities to use ultrasound combined with microbubbles as a noninvasive and nonpharmacological approach to manipulate glymphatic transport,” Ye said. “Focused ultrasound-activated microbubbles have the promise to enhance waste clearance in the brain and potentially mitigate brain diseases caused by impairments in glymphatic system function.”

Chen said the team will now focus on applying this noninvasive and nonpharmacological method for brain waste clearance to potentially combat neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases.

Source: University of Washington in St. Louis