Tag: white matter

Categories : NeurologyTags :

White Matter may Aid Recovery from Spinal Cord Injuries

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View of the spinal cord. Credit: Scientific Animations CC4.0

Injuries, infection and inflammatory diseases that damage the spinal cord can lead to intractable pain and disability but some degree of recovery may be possible. The question is, how best to stimulate the regrowth and healing of damaged nerves.

At the Vanderbilt University Institute of Imaging Science (VUIIS), scientists are focusing on a previously understudied part of the brain and spinal cord – white matter, which is made up of axons that relay signals. Their discoveries could lead to treatments that restore nerve activity through the targeted delivery of electromagnetic stimuli or drugs.

In a recent paper published in the Proceedings of the National Academy of Sciences, Anirban Sengupta, PhD, John Gore, PhD, and their colleagues report the detection of signals from white matter in the spinal cord in response to a stimulus that are as robust as grey matter signals.

“In the spinal cord, the white matter signal is quite large and detectable, unlike in the brain, where it has less amplitude than the grey matter (signal),” said Sengupta, research instructor in Radiology and Radiological Sciences at Vanderbilt University Medical Center.

“This may be due to the larger volume of white matter in the spinal cord compared to the brain,” he added. Alternatively, the signal could represent “an intrinsic demand” in metabolism within the white matter, reflecting its critical role in supporting grey matter.

For several years, Gore, who directs the VUIIS, and his colleagues have used functional magnetic resonance imaging (fMRI) to detect blood oxygenation-level dependent (BOLD) signals, a key marker of nervous system activity, in white matter.

Last year, they reported that when participants undergoing fMRI perform a task, like wiggling their fingers, BOLD signals increase in white matter throughout the brain.

The current study monitored changes in BOLD signals in the white matter of the spinal cord at rest and in response to a vibrotactile stimulus applied to the fingers in an animal model. In response to stimulation, white matter activity was higher in “tracts” of ascending fibres that carry the signal from the spine to the brain.

This result is consistent with white matter’s known neurobiological function, the researchers noted. White matter contains non-neuronal glial cells that do not produce electrical impulses, but which regulate blood flow and neurotransmitters, the signaling molecules that transmit signals between nerve cells.

Much remains to be learned about the function of white matter in the spinal cord. But the findings from this research may help in improved understanding of diseases that affect white matter in the spinal cord, including multiple sclerosis, Sengupta said.

“We will be able to see how activity in the white matter changes in different stages of the disease,” he said. Researchers also may be able to monitor the effectiveness of therapeutic interventions, including neuromodulation, in promoting recovery following spinal cord injury.

Source: Vanderbilt University Medical Center

Categories : NeurologyTags :

Significant White Matter Changes in Autism Revealed by MRI

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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!

Categories : Injury & Trauma NeurologyTags :

White Matter Changes Uncovered in Repeated Brain Injury

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Photo by MART PRODUCTION from Pexels

A new study has uncovered insights into white matter changes that occur during chronic traumatic encephalopathy (CTE), a progressive brain disease associated with repetitive head impacts. This discovery may help in identifying new targets for therapies.

CTE been diagnosed after death in the brains of American football players and other contact sport athletes as well as members of the armed services. The disease has been identified as causing impulsivity, explosivity, depression, memory impairment and executive dysfunction.

Though much prior research focused on repetitive head trauma leading to the development of abnormal tau, this study focused on white matter changes, particularly the oligodendrocytes which myelinate nerve sheaths. The results have been published online [PDF] in the journal Acta Neuropathologica.

“Research to date has focused on the deposition of abnormal tau in the gray matter in CTE. This study shows that the white matter undergoes important alterations as well.  There is loss of oligodendrocytes and alteration of oligodendrocyte subtypes in CTE that might provide new targets for prevention and therapies,” explained corresponding author Ann McKee, MD, chief of neuropathology at VA Boston Healthcare, director of the BU CTE Center.

Dr McKee and her team isolated cellular nuclei from the postmortem dorsolateral frontal white matter in eight cases of CTE and eight matched controls. They conducted single-nucleus RNA-seq (snRNA-seq) with these nuclei, revealing transcriptomic, cell-type-specific differences between the CTE and control cases. In doing so, they discovered that the white matter in CTE had fewer oligodendrocytes and the oligodendroglial subtypes were altered compared to control tissue.

Since previous studies have largely focused on the CTE-specific tau lesion located in the cortex in the brain, these findings are particularly informative as they explain a number of features of the disease. “In comparison, the cellular death process occurring in white matter oligodendrocytes in CTE appears to be separate from the accumulation of hyperphosphorylated tau,” she said. “We know that the behavioural and mood changes that occur in CTE are not explained by tau deposition. This study suggests that white matter alterations are also important features of the disease, and future studies will determine whether these white matter changes play a role in the production of behavioral or mood symptoms in CTE, such as explosivity, violence, impulsivity, and depression.”

Source: Boston University School of Medicine

Journal information: Chancellor, K. B., et al. (2021) Altered oligodendroglia and astroglia in chronic traumatic Encephalopathy. Acta Neuropathologica. doi.org/10.1007/s00401-021-02322-2.