Memory problems in MS tied to lesions in brain’s ‘memory circuit’

The presence of lesions, or regions of damage, in a brain circuit tied to memory in stroke patients also associate with memory problems in multiple sclerosis (MS), a study shows.

Findings may help to determine which lesions are likely to cause memory issues in people with the neurodegenerative condition, which has been difficult to establish in previous research.

The study, “Multiple sclerosis lesions that impair memory map to a connected memory circuit,” was published in the Journal of Neurology.

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MS lesions can be evident in multiple brain regions at the same time

MS is caused by inflammatory damage to nerve fibers in the brain and spinal cord, affecting nerve signaling and ultimately giving rise to disease symptoms. In MRI scans, spots where nerve tissue has been injured and scarred as a result of inflammation are visible as MS lesions.

The location of disease lesions is thought to have a direct relationship with the symptoms that a patient experiences. For example, lesions in the nerves that connect the eyes to the brain can give rise to vision problems.

Problems with memory are a common symptom of MS, affecting up to half of patients. Theoretically, memory problems would be expected to develop in people with lesions in memory-related parts of the brain. However, identifying brain regions where lesions give rise to memory issues has proven challenging, in large part because MS usually affects many different brain areas at the same time.

Scientists at the Brigham and Women’s Hospital, in Massachusetts, aimed to explore these connections by applying lessons learned when studying stroke, a neurological disorder that occurs when blood supply to a part of the brain is cut off, killing brain tissue in a specific area.

Memory problems sometimes develop after stroke, and in previous studies, scientists have been able to identify an associated memory circuit — interconnected parts of the brain — where damage tends to cause memory problems. The researchers now wanted to see whether MS lesions in these same areas also might link with memory problems.

“In a recent study, stroke lesions causing memory dysfunction occurred in many different brain locations, but they were all part of a functionally connected brain circuit centered on the hippocampus,” the researchers wrote. “As such, this stroke-based memory circuit provides an a priori template that may be useful for investigating MS memory dysfunction.”

The hippocampus, a deep-brain structure within the medial temporal lobe, is known to associate with memory and learning. The circuit, however, extended beyond the hippocampus and involved other brain regions also associated with memory, the researchers noted.

“By applying a circuit-based approach, we show that lesions associated with MS memory dysfunction connect to a memory circuit,” Isaiah Kletenik, MD, a study co-author and neurologist at Brigham and Women’s Hospital, said in a press release.

Data collected covered 431 people with MS who were enrolled from 2015 to 2019 in SysteMS, a large study following MS patients for several years to assess their disease course. These patients underwent brain scans to assess lesion location as well as standardized tests of memory.

MS and ischemic stroke lesions seen to ‘map to a common brain circuit’

In statistical models, the scientists showed that, similar to people with stroke, MS patients with more damage to the memory circuit also tended to report poorer scores on memory tests.

This indicates that “MS and ischemic stroke lesions causing a common symptom (memory dysfunction) map to a common brain circuit,” the team wrote. Scientists also noted some slight differences in the specific circuit affected in MS as compared with stroke.

Patients with higher overall lesion volume also tended to have more memory problems, but the statistical tests suggested that the connection between total lesion volume and memory was almost entirely mediated by damage to the memory circuit.

In other words, data suggested that people with more lesions are more likely to have memory problems simply because the memory circuit is more likely to be among damaged areas.

This finding “lends potential insight into why increasing MS lesion burden is associated with memory dysfunction, suggesting that this may occur because more lesions are more likely to hit the memory circuit,” the researchers wrote.

They speculated that a similar approach may help to identify brain locations involved in other common but poorly understood MS symptoms, like fatigue and depression.

The researchers noted that this study was limited because it only focused on overall lesion load — rather than looking individually at actively inflamed lesions — and they relied on one score to measure memory.