Category: Neurology

Study Uncovers Mechanism Behind Visual Impairment in Traumatic Brain Injury

A healthy neuron.
A healthy neuron. Credit: NIH

Traumatic brain injury can lead to long-term visual impairment, which researchers have found is caused by a dramatic drop in the number of neurons in the visual cortex. Their findings were published in Communications Biology.

Traumatic brain injury (TBI) is associated with mechanical brain damage and a wide range of neuronal abnormalities.  Injuries to the posterior occipital cortex are common in humans, and can result in visual impairment. Up to 75% of current or former soldiers live with permanent visual dysfunction or cortical blindness. 

The human brain possesses surprising neuroplasticity, which allows other areas of the brain to take over the functions of a damaged area.

Such neuroplasticity is also characteristic of the sensory areas of the visual cortex, which is final component of the visual pathway, responsible for receiving and processing visual impressions. The primary visual cortex (V1) is reached by the nerve fibres of the optic radiation, which carry nerve impulses from the retinas of both eyes.

Until now, scientists knew little about the effects of TBI on long-term visual circuit function. Using mice, a team of researchers examined how neurons respond to visual stimuli two weeks and three months after mild injury to the primary visual cortex (V1). V1 neurons normally show sensitivity to different features of a visual stimulus, such as colour or direction of movement. The preprocessed data is transmitted to subsequent areas of the visual cortex. This study showed that although the primary visual cortex remained largely intact after the brain injury, there was a 35% reduction in the number of neurons. This loss largely affected inhibitory neurons rather than excitatory neurons, which inhibit or stimulate action in the target cells, respectively.

After TBI, fewer than half of the isolated neurons were sensitive to visual stimuli (32% at two weeks after injury; 49% at three months after the event), compared with 90% of V1 cells in the control group. Up to a threefold decrease in neuronal activity was seen after the brain injury, and the cells themselves had worse spatial orientation. The overall results mean that even minor, superficial brain injuries cause long-term impairment in the way visual stimuli are perceived, persisting several months after the event.

Such a deeper understanding of the functional impairments in damaged visual cortex could provide a basis for developing circuit-level therapies for visual cortex damage.

Source: Institute of Physical Chemistry of the Polish Academy of Sciences

Prompts During Sleep Boosts Recall of Names and Faces

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Hearing names repeated during deep sleep may help bolster recall of names and faces, according to new research from Northwestern University.

The researchers found that people’s name recall improved significantly when memories of newly learned face-name associations were reactivated while they were napping. Uninterrupted deep sleep was key in this improvement.

“It’s a new and exciting finding about sleep, because it tells us that the way information is reactivated during sleep to improve memory storage is linked with high-quality sleep,” said lead author Nathan Whitmore, a PhD candidate in the Interdepartmental Neuroscience Program at Northwestern University.

The research is reported in the Nature partner journal npj Science of Learning.

The three main stages of the experiment of Whitmore et al. (2022). First, participants learned 80 face-name associations. Next, they slept while EEG was monitored to determine sleep stage, and 20 of the spoken names were presented softly over background music during slow-wave sleep. Finally, memory testing showed superior memory due to memory reactivation during sleep, but only when sleep was undisturbed by sound presentations. Credit: Nathan Whitmore, a Ph.D. candidate in the Interdepartmental Neuroscience Program at Northwestern University.

The results also highlighted the importance of adequate sleep: for study participants with EEG measurements that indicated disrupted sleep, the memory reactivation had no effect and may even be detrimental. But in those with uninterrupted sleep during the specific times of sound presentations, the reactivation helped participants recall just over 1.5 more names.

The study recruited 24 participants, aged 18-31 years old, who were asked to memorise the faces and names of 40 pupils from a hypothetical Latin American history class and another 40 from a Japanese history class. When each face was presented again, they were asked to recall the associated name. After the learning exercise, participants took a nap while the researchers carefully monitored brain activity using EEG measurements. When participants reached the N3 “deep sleep” state, some of the names were softly played on a speaker with music that was associated with one of the classes.

When participants awoke, they were again tested on recognising faces and recalling their names.

According to the researchers, the finding on the relationship between sleep disruption and memory accuracy is noteworthy for several reasons.

“We already know that some sleep disorders like apnoea can impair memory,” said Whitmore. “Our research suggests a potential explanation for this—frequent sleep interruptions at night might be degrading memory.”

The lab is currently exploring the reactivation of memories and deliberately disrupting sleep in order to learn more about the relevant brain mechanisms.

Source: EurekAlert!

A Brain ‘Breathalyser’ for THC Intoxication

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Scientists have developed a noninvasive brain imaging procedure to identify individuals whose performance has been impaired by THC, the psychoactive ingredient of cannabis. As reported in Neuropsychopharmacology, the technique uses functional near-infrared spectroscopy (fNIRS) to measure brain activation patterns linked to THC intoxication. The technology could have a great impact on road and workplace safety. 

The increasing legalisation of cannabis has driven the need for a portable brain imaging procedure that can distinguish between THC-caused impairment and mild intoxication. “Our research represents a novel direction for impairment testing in the field,” explained lead author Jodi Gilman, PhD. “Our goal was to determine if cannabis impairment could be detected from activity of the brain on an individual level. This is a critical issue because a ‘breathalyser’ type of approach will not work for detecting cannabis impairment, which makes it very difficult to objectively assess impairment from THC during a traffic stop.”

In previous studies, THC has been shown to impair cognitive and psychomotor performance essential to safe driving, a factor thought to at least double the risk of fatal motor vehicle accidents. However, concentration of THC in the body does not correspond well to functional impairment. Regular cannabis users often can have high levels of THC in the body and not be impaired. Metabolites of THC can remain in the bloodstream for weeks after the last cannabis use, well beyond the period of intoxication. Thus, there is a need for a different method to determine impairment from cannabis intoxication.

In the study, 169 cannabis users underwent fNIRS brain imaging before and after receiving either oral THC or a placebo. Participants who reported intoxication after being given oral THC showed an increased oxygenated haemoglobin concentration (HbO) – a type of neural activity signature from the prefrontal cortex region of the brain – compared to those who reported low or no intoxication.

“Identification of acute impairment from THC intoxication through portable brain imaging could be a vital tool in the hands of police officers in the field,” said senior author and principal investigator A. Eden Evins, MD, MPH, founding director of the Center for Addiction Medicine. “The accuracy of this method was confirmed by the fact impairment determined by machine learning models using only information from fNIRS matched self-report and clinical assessment of impairment 76% of the time.”

The study suggested the feasibility of inexpensive, lightweight, battery-powered fNIRS devices that could be incorporated into a headband or cap, and thus require minimal set-up time.

“Companies are developing breathalyser devices that only measure exposure to cannabis but not impairment from cannabis,” said Dr Gilman. “We need a method that won’t penalise medical marijuana users or others with insufficient amounts of cannabis in their system to impair their performance. While it requires further study, we believe brain-based testing could provide an objective, practical and much needed solution.”

Source: Massachusetts General Hospital

New Genetic Insights into Basal Ganglia Diseases

Source: Pixabay

A new study published in Developmental Medicine & Child Neurology uncovered a number of genetic causes of basal ganglia diseases.

Basal ganglia are deep grey matter structures in the brain involved in the control of posture and voluntary movements, cognition, behaviour, and motivational states. Several conditions are known to affect basal ganglia during childhood, but many questions remain.

In a study that included 62 children with basal ganglia diseases who were followed for two years, investigators identified multiple genetic aetiologies including mitochondrial diseases (57%), Aicardi–Goutières syndrome (20%), and single-gene causes of dystonia and/or epilepsy (17%) mimicking Leigh syndrome. Radiological abnormalities included T2-hyperintense lesions (n=26) and lesions caused by calcium or manganese mineralisation (n=9).

The researchers identified three clusters: the pallidal, neostriatal, and striatal, plus the last including mtDNA defects in the oxidative phosphorylation system with prominent brain atrophy. Mitochondrial biomarkers showed poor sensitivity and specificity in children with mitochondrial disease, whereas an interferon signature was observed in all patients with Aicardi–Goutières syndrome.

Radiological imaging tests also revealed several characteristics in patients that could help lead to an earlier diagnosis of basal ganglia diseases.

Source: Wiley

Scientists Find Epilepsy Biomarker in Autistic Children

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Scientists have discovered that an important brain protein that quiets overactive brain cells and is abnormally low in children with autism, which may explain why so many children with autism also have epilepsy. The findings were published in Neuron.

This protein can be detected in the cerebrospinal fluid, making it a promising marker to diagnose autism and potentially treat the epilepsy that accompanies the disorder.

Mutated versions of this gene were known to cause autism combined with epilepsy, and epilepsy appears in 30% to 50% of children with autism. Autism, which is 90% genetic, affects 1/58 children in the US.

Appropriately nicknamed ‘catnap2’, the protein, CNTNAP2, is produced by the brain cells when they become overactive. Because the brains of children with autism and epilepsy lack sufficient CNTNAP2, scientists found, their brains become overactive, leading to seizures.

For the study, the researchers analysed the cerebrospinal fluid in individuals with autism and epilepsy, and in mouse models. Though, cerebrospinal fluid has been used in researching disorders such as Parkinson’s, this is the first study showing it is an important biomarker in autism.

The new finding about CNTNAP2’s role in calming the brain in autism and epilepsy may lead to new treatments.

“We can replace CNTNAP2,” said lead study author Peter Penzes, the director of the Center for Autism and Neurodevelopment at Northwestern University Feinberg School of Medicine. “We can make it in a test tube and should be able to inject it into children’s spinal fluid, which will go back into their brain.”

Penzes’ lab is currently working on this technique in preclinical research.

The level in the spinal cord is proxy for the level in the brain, explained Penzes. When brain cells are too active because of overstimulation, they produce more CNTNAP2, which floats away and binds to other brain cells to calm them. The protein also leaks into the cerebrospinal fluid, where scientists were able to measure it, giving them a clue for how much is produced in the brain.

Source: EurekAlert!

Why Antidepressants Take Weeks to Provide Relief

A healthy neuron.
A healthy neuron. Credit: NIH

The findings of a study published in Science Translational Medicine paint a new picture of how current antidepressant drugs work and suggest a new drug target in depression. As with most drugs, antidepressants were developed through trial and observation. Some 40% of patients with the disorder don’t respond adequately to the drugs, and when they do work, antidepressants take weeks to provide relief. Why this is has remained largely a mystery.

To figure out why these drugs have a delayed onset, the team examined a mouse model of chronic stress that leads to changes in behaviours controlled by the hippocampus. The hippocampus is vulnerable to stress and atrophies in people with major depression or schizophrenia. Mice exposed to chronic stress show cognitive deficits, a hallmark of impaired hippocampal function.

“Cognitive impairment is a key feature of major depressive disorder, and patients often report that difficulties at school and work are some of the most challenging parts of living with depression. Our ability to model cognitive impairment in lab mice gives us the chance to try and understand how to treat these kinds of symptoms,” said Professor Dane Chetkovich, MD, PhD, who led the study.

The study focussed on an ion transporter channel in nerve cell membranes known as the HCN channelPrevious work has shown HCN channels have a role in depression and separately to have a role in regulation of cognition. According to the authors, this was the first study to explicitly link the two observations.

Examination of postmortem hippocampal samples led the team to establish that HCN channels are more highly expressed in people with depression. HCN channel activity is modulated by a small signaling molecule called cAMP, which is increased by antidepressants. The team used protein receptor engineering to increase cAMP signaling in mice and establish in detail the effects this has on hippocampal HCN channel activity and, through that connection, on cognition.

Turning up cAMP was found to initially increase HCN channel activity, limit the intended effects of antidepressants and negatively impact cognition (as measured in standard lab tests).

However, a total reversal took place over a period of some weeks. Previous work by the researchers had established that an auxiliary subunit of the HCN channel, TRIP8b, is essential for the channel’s role in regulating animal behaviour. The new study shows that, over weeks, a sustained increase in cAMP starts to interfere with TRIP8b’s ability to bind to the HCN channel, thereby quieting the channel and restoring cognitive abilities.

“This leaves us with acute and chronic changes in cAMP, of the sort seen in antidepressant drug therapy, seen here for the first time to be regulating the HCN channel in the hippocampus in two distinct ways, with opposing effects on behaviour,” Prof Chetkovich said. “This appears to carry promising implications for new drug development, and targeting TRIP8b’s role in the hippocampus more directly could help to more quickly address cognitive deficits related to chronic stress and depression.”

Source: Vanderbilt University

What Causes Stuttering?

A healthy neuron. Credit: NIH

During childhood, about one in 20 people go through a period of stuttering. Until the latter half of the 20th century, stuttering was believed to be a psychological problem stemming from lack of effort or from trauma.

Nowadays, neuroimaging techniques are leading to a much better understanding of brain function during speech and how stuttering arises. Frank Guenther, from Boston University, reported findings from a new study at the 181st Meeting of the Acoustical Society of America

Guenther gives the example of speech being a jukebox that plays CDs. The jukebox has two circuits: one that chooses a CD and one that plays the CD.

In the brain, this corresponds to one circuit initiating the desired speech in the basal ganglia, while another circuit coordinates the muscles needed to generate the speech. Stuttering stems from the initiation of speech, so only the first of the two circuits is impaired.

“In stuttering, the CDs themselves are fine, but the mechanism for choosing them is impaired,” said Guenther.

This theory is in agreement with behavioural observations of stuttering: people will often speak words fluently later in a sentence, even if those same words cause stuttering at the start of a sentence.

Guenther and his team created computational models of how the speech initiation circuit performs in a non-stuttering individual. Since Parkinson’s disease also affects the initiation circuit, they can compare these models directly to data taken from the basal ganglia during deep brain stimulation surgery in patients with the disease.

“This gives us a fighting chance of finding the specific problems underlying stuttering and addressing them with highly targeted drugs or technological treatments that have minimal unwanted side effects,” said Guenther.

Source: EurekAlert!

About 1% of Hospitalised COVID Patients Develop Neurological Complications

49-year-old female with past medical history of mitral valve disease and tricuspid valve regurgitation who developed headache followed by cough and fever presented to the ER with right upper eyelid ptosis (drooping). Credit: Radiological Society of North America and Scott H. Faro, M.D.

Approximately one in 100 patients hospitalised with COVID will likely develop complications of the central nervous system, according to a large international study. These can include stroke, haemorrhage, and other potentially fatal complications. The study was presented at the annual meeting of the Radiological Society of North America (RSNA).

“Much has been written about the overall pulmonary problems related to COVID, but we do not often talk about the other organs that can be affected,” said study lead author Scott H. Faro, MD, FASFNR, professor of radiology and neurology at Thomas Jefferson University. “Our study shows that central nervous system complications represent a significant cause of morbidity and mortality in this devastating pandemic.”

Dr Faro initiated the study after finding that only a small number of cases informed existing literature on central nervous system complications in hospitalised COVID patients.

To build a more complete picture, he and his colleagues analysed nearly 40 000 cases of hospitalised COVID patients, admitted between September 2019 and June 2020. Their average age was 66 years old, and two thirds were men.

Confusion and altered mental status were the most common causes of admission followed by fever. Comorbidities such as hypertension, cardiac disease and diabetes were common.

There were 442 acute neuroimaging findings most likely associated with the viral infection, with central nervous system complications in 1.2% of this large patient group.

“Of all the inpatients who had imaging such as MRI or a CT scan of the brain, the exam was positive approximately 10% of the time,” Dr Faro said. “The incidence of 1.2% means that a little more than one in 100 patients admitted to the hospital with COVID are going to have a brain problem of some sort.”

Ischaemic stroke, with an incidence of 6.2%, was the most common complication, followed by intracranial haemorrhage (3.72%) and encephalitis (0.47%).

A small percentage of unusual findings was uncovered, such as acute disseminating encephalomyelitis, an inflammation of the brain and spinal cord, and posterior reversible encephalopathy syndrome, a syndrome that mimics many of the symptoms of a stroke.

“It is important to know an accurate incidence of all the major central nervous system complications,” Dr Faro said. “There should probably be a low threshold to order brain imaging for patients with COVID.”

Source: EurekAlert!

Significant White Matter Changes in Autism Revealed by MRI

Significant alterations in the brain’s white matter in adolescents with autism spectrum disorder (ASD). Credit: RSNA and researcher, Clara Weber

Using specialised MRI, researchers found significant changes in the microstructure of the brain’s white matter, especially in the corpus callosum in adolescents and young adults with autism spectrum disorder (ASD) compared to controls. This research will be presented next week at the annual meeting of the Radiological Society of North America (RSNA).

“One in 68 children in the U.S. is affected by ASD, but high variety in symptom manifestation and severity make it hard to recognise the condition early and monitor treatment response,” explained Clara Weber, postgraduate research fellow at Yale University School of Medicine. “We aim to find neuroimaging biomarkers that can potentially facilitate diagnosis and therapy planning.”

Researchers reviewed diffusion tensor imaging (DTI) brain scans from a large dataset of patients between the age of six months and 50 years. DTI is an MRI technique that measures connectivity in the brain by detecting how water moves along its white matter tracts. Water molecules diffuse differently through the brain, depending on the integrity, architecture and presence of barriers in tissue.

“If you think of gray matter as the computer, white matter is like the cables,” Weber said. “DTI helps us assess how connected and intact those cables are.”

For the study, clinical and DTI data from 583 patients from four existing studies of distinct patient populations were analysed: infants (median age 7 months), toddlers (median age 32 months), adolescents, and young adults.

“One of the strengths of our study is that we looked at a wide range of age groups, not just school-aged children,” Weber said.

To assess the influences of age and ASD diagnosis on white matter microstructure, the research team created fractional anisotropy, mean diffusivity and radial diffusivity maps using data from the four studies.

Fractional anisotropy is the extent water diffusion is restricted to just one direction. A value of zero means that diffusion is unrestricted in all directions, while one means that diffusion is unidirectional. Mean diffusivity is the overall mobility of water molecules, indicating how densely cells are packed together. Radial diffusivity is the extent water diffuses perpendicular to a white matter tract.

“When white matter integrity is disrupted, we see more water diffusing perpendicularly, which translates to a higher radial diffusivity,” Weber said.

The key finding of the analysis was reduced fractional anisotropy within the anterior/middle tracts of the corpus callosum in adolescent and young adult ASD patients compared to individuals in the control group. The corpus callosum is a thick bundle of nerve fibers that connects and allows the two sides of the brain to communicate. Corresponding increases in ASD-related mean diffusivity and radial diffusivity were found in young adults.

“In adolescents, we saw a significant influence of autism,” Weber said. “In adults, the effect was even more pronounced. Our results support the idea of impaired brain connectivity in autism, especially in tracts that connect both hemispheres.”

Compared to controls, no reduction in fractional anisotropy was seen in the same tracts in toddlers and infants with ASD.

The researchers hope the findings can help improve early diagnosis of ASD and provide potential objective biomarkers to monitor treatment response.

“We need to find more objective biomarkers for the disorder that can be applied in clinical practice,” Weber said.

Source: EurekAlert!

Hypertension Doubles Epilepsy Risk

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A new study has found that hypertension may double an adult’s risk of developing epilepsy, according to a new study published in Epilepsia.

The study recruited 2986 US participants with an average age of 58 years, 55 new cases of epilepsy were identified during an average follow-up of 19 years. Hypertension, defined as presence of elevated blood pressure or use of antihypertensive medications, was linked to a nearly 2-fold higher risk of epilepsy. After excluding participants with normal blood pressure who were taking antihypertensive medications, hypertension was linked to a 2.44-times higher risk of epilepsy.

“Our study shows that hypertension, a common, modifiable, vascular risk factor, is an independent predictor of epilepsy in older age,” said co–lead author Maria Stefanidou, MD, MSc, of Boston University School of Medicine. “Even though epidemiological studies can only show association and not causation, this observation may help identify subgroups of patients who will benefit from targeted, aggressive hypertension management and encourage performance of dedicated clinical studies that will focus on early interventions to reduce the burden of epilepsy in older age.”

Source: Wiley