Visual-somatosensory integration (VSI) as a novel marker of Alzheimer’s disease: A comprehensive overview of the VSI study

Identification of novel, non-invasive, non-cognitive based markers of Alzheimer’s disease (AD) and related dementias are a global priority. Growing evidence suggests that Alzheimer’s pathology manifests in sensory association areas well before appearing in neural regions involved in higher-order cognitive functions, such as memory. Previous investigations have not comprehensively examined the interplay of sensory, cognitive, and motor dysfunction with relation to AD progression. The ability to successfully integrate multisensory information across multiple sensory modalities is a vital aspect of everyday functioning and mobility. Our research suggests that multisensory integration, specifically visual-somatosensory integration (VSI), could be used as a novel marker for preclinical AD given previously reported associations with important motor (balance, gait, and falls) and cognitive (attention) outcomes in aging. While the adverse effect of dementia and cognitive impairment on the relationship between multisensory functioning and motor outcomes has been highlighted, the underlying functional and neuroanatomical networks are still unknown. In what follows we detail the protocol for our study, named The VSI Study, which is strategically designed to determine whether preclinical AD is associated with neural disruptions in subcortical and cortical areas that concurrently modulate multisensory, cognitive, and motor functions resulting in mobility decline. In this longitudinal observational study, a total of 208 community-dwelling older adults with and without preclinical AD will be recruited and monitored yearly. Our experimental design affords assessment of multisensory integration as a new behavioral marker for preclinical AD; identification of functional neural networks involved in the intersection of sensory, motor, and cognitive functioning; and determination of the impact of early AD on future mobility declines, including incident falls. Results of The VSI Study will guide future development of innovative multisensory-based interventions aimed at preventing disability and optimizing independence in pathological aging

Subject Based Registration for Individualized Analysis of Diffusion Tensor MRI

<div><p>Registration of subject and control brains to a common anatomical space or <i>template</i> is the basis for quantitatively delineating regions of abnormality in an individual brain. Normally, a brain atlas is chosen as the template. Limitations in the registration process result in persistent differences between individual subject brains and template, which can be a source of error in an analysis. We propose a new approach to the registration process where the <i>subject of interest</i> is the registration template. Through this change, we eliminate errors due to differences between a brain template and a subject’s brain. We applied this method to the analysis of FA values derived from DTI data of 20 individual mTBI patients as compared to 48 healthy controls. Subject-centered analysis resulted in identification of significantly fewer regions of abnormally low FA compared to two separate atlas-centered analyses, with subject-centered abnormalities essentially representing the common subset of abnormal low FA regions detected by the two atlas-centered methods. Whereas each atlas-centered approach demonstrated abnormalities in nearly every subject (19/20 and 20/20), the subject-centered approach demonstrated abnormalities in fewer than half the subjects (9/20). This reduction of diffusion abnormalities observed using the subject-centered approach is due to elimination of misregistration errors that occur when registering the subject of interest to a template. Evaluation of atlas-centered analyses demonstrated that 9.8% to 13.3% of subject GM and CSF was misregistered onto the WM of the brain atlas, resulting in the observation of additional low FA clusters compared to the subject-centered approach. Without careful evaluation, these misregistrations could be misinterpreted as pathology. An additional benefit of the subject-centered approach is that diffusion abnormalities can now be visualized directly in the subject’s anatomical space, rather than interpolating results from the brain atlas space, and can thereby enhance correlation with other components of an imaging protocol.</p></div

Brain Metabolite Proton T2 Mapping at 3.0 T in Relapsing-Remitting Multiple Sclerosis1

For 3.0-T T2-weighted MR imaging in relapsing-remitting multiple sclerosis, one T2 signal per metabolite suffices in any brain region, irrespective of disease duration, thus validating the hypothesis that the spectroscopic signal intensity changes predominantly represent metabolite levels and not T2 weighting

Diffusion tensor tractography in an mTBI patient based on sBR derived clusters.

<p>Overlying the 3D rendered T1WI a tractogram generated from the patient’s diffusion tensor imaging is shown in color. Tractography was performed using the Medinria software package (v1.8.0) and a single seed ROI within the right middle cerebellar peduncle (red). The seed ROI is a cluster of abnormally low FA generated from voxelwise analysis using the sBR approach. An additional ROI in the right cerebral peduncle was used as a waypoint.</p

Tracking individual voxels through the registration process.

<p>Figure demonstrates a single labeled voxel within the <i>hand-knob</i> region of the left precentral gyrus in each of fifteen control subjects prior to transformation to the template.</p

Number of Abnormally Low FA Voxels within Clusters.

<p>⁺ Volume adjusted to Patient Volume</p><p>^* Number of Additional Low FA Voxels Compared to sBR</p><p>Number of Abnormally Low FA Voxels within Clusters.</p

Abnormally low FA clusters detected in a single mTBI patient using three different registration approaches.

<p>Abnormally low FA clusters are shown in red overlaid on axial T1-weighted images: the patient’s anatomy (sBR), the MNI atlas (aBR-MNI) and the JHU atlas (aBR-JHU), respectively (left to right). Most abnormally low FA clusters observed using sBR were also present using the aBR methods, as demonstrated by the 3 clusters seen in the right frontal lobe. However, additional clusters (e.g., yellow arrow) detected using a particular aBR template generally will not overlap with the alternate aBR template or sBR.</p

Demonstration of the registration result of aBR and sBR approaches.

<p>(A) Registration using the aBR-JHU method: all voxels are located within the hand-knob region, one voxel (blue), from control 6 (C6), has been displaced into GM. (B) Registration using the sBR approach, using C6 as the template, demonstrates the resultant location of these same 15 voxels. Using the sBR approach, the labeled voxel of C6 remains centered in the <i>hand-knob</i> gyrus with the labeled voxels of the other subjects, while still present in the gyrus, are distributed around the C6 voxel.</p