Ultra-High Field MRI Reveals Subtle Brain Differences in Individuals with Down Syndrome

Individuals with Down syndrome (DS) have subtle differences in the structure and function of their hippocampus, according to images captured with ultra-high field MRI.

For the first time, researchers have been able to make this in vivo comparison with healthy participants, helping them better understand how each subregion of the hippocampus – the brain region tied to memory and learning – functionally connects to other parts of the brain in patients with DS.

“The ultimate goal of this approach is to have an objective technique to complement neuropsychological assessments to measure the functional skills of those with DS,” said senior author Alberto Costa, M.D., Ph.D., professor of pediatrics and psychiatry at Case Western Reserve University School of Medicine.

This study, published in Brain Communications, marks the first demonstration of how high-field MRI can pick up subtle differences in individuals with DS, offering gains in sensitivity and image resolution, said Costa’s colleague and first author Katherine Koenig, Ph.D., assistant professor of radiology at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University.

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The findings, they said, can potentially be used to develop MRI-driven measures as surrogate markers to study the efficacy of medications that could improve cognitive function in this group. Being able to do so could be significant, they added, because individuals with DS can also display neuropathology similar to Alzheimer’s disease (AD).

For their study, Costa’s team enrolled 37 teen-agers and young adults with DS with an average age of 24, as well as 27 healthy controls of equivalent age. All participants underwent three protocols run on the same MRI scanner (Siemens 7T Magnetom) during a single session. The team captured whole-brain T1-weighted images to create a whole-brain functional connectivity map for the left and right hippocampus, revealing the strength of these regions to the whole brain.

Gathering this data is particularly important with this patient group because their cognitive function is heavily dependent on how this hippocampus is impacted.

“That’s why we focused on this structure deep inside the brain that is responsible for functions, such as forming memories of episodes in one’s life and spatial memory,” Costa said.

Based on this analysis, the team determined that individuals with DS have increased mean cortical thickness, larger mean lateral ventricle volume, and decreased cerebral white matter volume. They also demonstrated weaker connectivity between the left and right hippocampus, as well as a weaker connection between the right hippocampus and right middle temporal gyrus.

In addition, patients with DS exhibited lower connectivity between multiple frontal lobe regions (bilateral medial frontal gyri, right middle/superior frontal gyrus, left superior frontal gyrus, left anterior cingulate gyrus, and right precentral gyrus) and the bilateral hippocampi.

Ultimately, the team said, their results add to the body of knowledge surrounding the neurological health of individuals with DS.

“The finding that neither hippocampal volume nor functional connectivity changes were associated with age in this sample of teen-agers and young adults with DS is important from the perspective of studying neurodegenerative processes and their potential prevention in those with DS,” the team said. “As even young individuals with DS can display AD-like neuropathology, this finding points toward a window of time during which, although pathology may be present, it may exist in the context of well-preserved neural structure and function, i.e., in a state in which potential therapeutic interventions would have their best chance of being effective.”

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