This study examines the atrophy rates of subjects with mild cognitive impairment (MCI) compared to controls in four regions within the medial temporal lobe: the transentorhinal cortex (TEC), entorhinal cortex (ERC), hippocampus, and amygdala. These regions were manually segmented and then corrected for undesirable longitudinal variability via Large Deformation Diffeomorphic Metric Mapping (LDDMM) based longitudinal diffeomorphometry. Diffeomorphometry techniques were used to compare thickness measurements in the TEC with the ERC. There were more significant changes in thickness atrophy rate in the TEC than medial regions of the entorhinal cortex. Volume measures were also calculated for all four regions. Classifiers were constructed using linear discriminant analysis to demonstrate that average thickness and atrophy rate of TEC together was the most discriminating measure compared to the thickness and volume measures in the areas examined, in differentiating MCI from controls. These findings are consistent with autopsy findings demonstrating that initial neuronal changes are found in TEC before spreading more medially in the ERC and to other regions in the medial temporal lobe. These findings suggest that the TEC thickness could serve as a biomarker for Alzheimer's disease in the prodromal phase of the disease.

This study examines the atrophy patterns in the entorhinal and transentorhinal cortices of subjects that converted from normal cognition to mild cognitive impairment. The regions were manually segmented from 3T MRI, then corrected for variability in boundary definition over time using an automated approach called longitudinal diffeomorphometry. Cortical thickness was calculated by deforming the gray matter-white matter boundary surface to the pial surface using an approach called normal geodesic flow. The surface was parcellated based on four atlases using large deformation diffeomorphic metric mapping. Average cortical thickness was calculated for (1) manually-defined entorhinal cortex, and (2) manually-defined transentorhinal cortex. Group-wise difference analysis was applied to determine where atrophy occurred, and change point analysis was applied to determine when atrophy started to occur. The results showed that by the time a diagnosis of mild cognitive impairment is made, the transentorhinal cortex and entorhinal cortex was up to 0.6 mm thinner than a control with normal cognition. A change point in atrophy rate was detected in the transentorhinal cortex 9–14 years prior to a diagnosis of mild cognitive impairment, and in the entorhinal cortex 8–11 years prior. The findings are consistent with autopsy findings that demonstrate neuronal changes in the transentorhinal cortex before the entorhinal cortex.

In hair cells, mechanotransduction channels are located in the membrane of stereocilia tips, where the base of the tip link is attached. The tip-link force determines the system of other forces in the immediate channel environment, which change the channel open probability. This system of forces includes components that are out of plane and in plane relative to the membrane; the magnitude and direction of these components depend on the channel environment and arrangement. Using a computational model, we obtained the major forces involved as functions of the force applied via the tip link at the center of the membrane. We simulated factors related to channels and the membrane, including finite-sized channels located centrally or acentrally, stiffness of the hypothesized channel-cytoskeleton tether, and bending modulus of the membrane. Membrane forces are perpendicular to the directions of the principal curvatures of the deformed membrane. Our approach allows for a fine vectorial picture of the local forces gating the channel; membrane forces change with the membrane curvature and are themselves sufficient to affect the open probability of the channel.

Further studies will be needed to identify potential markers of future transition to psychosis though cortical thinning of the ACG might be one of the candidates.

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