Researchers Offer New Insights into Cognitive Deficits in Multiple Sclerosis Patients

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A new study led by researchers at the Center for BrainHealth at the University of Texas at Dallas and The University of Texas Southwestern Medical Center recently revealed that multiple sclerosis (MS) patients experience cognitive deficits due to a decreased connectivity between functional networks in the brain. The study was published in the journal Neuropsychology and is entitled “Asynchrony in Executive Networks Predicts Cognitive Slowing in Multiple Sclerosis.

MS is a chronic, progressive neurodegenerative disorder that results from an attack to the central nervous system (brain, spinal cord and optical nerves) by the body’s own immune system, causing inflammation and damage to the myelin layer that covers and protects neurons resulting in motor function impairment (coordination, balance, speech and vision), irreversible neurological disability and paralysis. It is estimated that half of MS patients experience cognitive deficits including impaired memory, attention, concentration and judgment. Most patients experience their first symptom between 20 and 40 years of age and it is estimated that more than 2.3 million people in the world suffer from the disease. There is currently no cure for MS.

The biological mechanisms that lead to these cognitive deficits are poorly understood. In the study, researchers compared for the first time MS patients and healthy individuals in terms of cognitive abilities by analyzing changes in the dorsolateral prefrontal networks in the brain.

In total, 29 patients with relapsing-remitting MS (RRMS; the most frequent form of the disease) and 23 age and sex matched healthy controls were assessed. All participants were submitted to functional magnetic resonance imaging (fMRI) while performing a test to assess cognitive processing speed and task-based connectivity. Briefly, participants were given for four seconds a nine-item key of number and symbol pairs (for instance, “3” “+”) and one number-symbol pair probe. Participants were then asked to indicate whether or not the probe appeared in the key through the use of right and left buttons.

Researchers found that although both groups had a similar accuracy in their responses, RRMS patients were slower than the healthy controls on the processing speed tasks. The team found that MS patients have a weaker connectivity between right and left dorsolateral prefrontal cortex and the task-relevant brain regions. Interestingly, MS patients with stronger functional connections with the dorsolateral prefrontal cortex performed the tasks faster than patients with weaker connections, suggesting that the patient’s connectivity in this brain region accounts for the processing speed.

“These findings reveal a diffuse pattern of disconnectivity with executive areas of the brain,” explained the study’s lead author Nicholas Hubbard in a news release. “Importantly, these decreases in connectivity predicted MS-related cognitive slowing both in and out of the fMRI environment suggesting that these results were not specific to our task, but rather were able to generalize to other situations where cognitive speed is required.”

The research team believes that this decreased connectivity between functional network-specific brain regions is the cause of the cognitive deficits observed in MS patients, and that it likely reflects the decrease in white matter surrounding neurons in the brain.

“Our study is the first to really zero in on the physiology of cognitive speed, the central cognitive deficit in MS,” said the study’s senior author Dr. Bart Rypma. “While white matter is essential to efficient network communication, white matter degradation is symptomatic of MS. This study really highlights how tightly coupled connectivity is to performance and illuminates the larger, emerging picture of white matter’s importance in human cognitive performance.”

The authors suggest that emphasis should be given to therapies focused on white matter structures and proliferation. The team is currently investigating the physiology of white matter in order to obtain more insight into the decrease in cognitive speed not only in MS patients, but also in healthy aging individuals.

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Patrícia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.
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