Evaluating Sensory Dysfunction in Aging Using Combined fMRI and MRS Image Analyses

Hypothesis

Hypothesis

Hypothesis:
1. Aging results in a loss of inhibitory neurons that are responsible for reducing distractions from background information when an individual is attending to a specific stimulus. Due to this loss of inhibitory control, elderly subjects will exhibit a decrease in cross-modal deactivations in primary sensory cortex during unimodal stimulation.
2. Aging results in an increase in the magnitude of activation in cross-modal brain regions when presented with nonmatching stimulus pairs.
3. Brain metabolites measured using MRS will reveal neuronal loss/dysfunction in cross-modal portions of the cingulate gyrus and in unimodal auditory and visual cortex of elderly subjects.

Goals:
1. Compare neural activation patterns between groups of young and aged subjects during unimodal and cross-modal sensory stimulation using fMRI.
2. Compare brain metabolite levels between groups of young and aged subjects in unimodal (visual and auditory) and cross-modal brain areas using MRS.
3. Perform an integrated, voxel-by-voxel fMRI/MRS data analysis to identify brain regions where neuronal metabolites effectively predict brain activity associated with cross-modal sensory processing.

Methods:
Functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS) measures will be compared between young and elderly subjects to identify changes in unimodal and cross-modal sensory processing. Whole-brain fMRI will performed using a standard echo-planar sequence. Cortical activation and deactivation patterns will be evaluated in visual and auditory cortex in response to nonmatching unimodal stimulation. Brain regions responsive to contextual congruence between cross-modal stimuli will be identified using paired visual and auditory stimuli that either match (congruent) or do not match (incongruent). MR spectroscopic imaging will use a Carr-Purcell double spin echoes (PRESS) sequence. Phase encoding in the PRESS spectroscopic imaging sequence will be used to obtain 3D spectral arrays with a nominal spatial resolution of 1 x 1 x 1 mm. The 3D MR spectroscopic imaging data will be acquired within a 20 minute acquisition time with aTR of 1 s and a TE of 144ms.

Statistical parametric maps (SPMs) will be generated from the fMRI data to identify regional brain activation. MRS images will be reconstructed, and whole-brain maps for n-acetyl aspartate (NAA), choline (Cho), and creatine (Cr) will be generated. Following reconstruction, each of the metabolite maps will be normalized to Montreal Neurological Institute (MNI) space using image header information to determine the 16-parameter affine transform between the metabolite maps and the T1-weighted images. An fMRI/MRS combined analysis will be performed to identify brain regions that exhibit age-related changes in both functional activity and brain metabolite concentrations.

Findings:
We completed a functional and structural brain imaging study of 60 subjects that range in age from 18 – 80 years old. These studies were directed at understanding how changes in brain function are related to changes in brain structure in older adults. We utilized a combination of advanced magnetic resonance imaging (MRI) techniques to image the brain. Our results demonstrated that decreases in brain activity in older adults are related to loss of brain volume. We also demonstrated that changes in deep portions of the brain (white matter) are best observed using a technique called diffusion tensor imaging (DTI).

The results from these studies served as preliminary data for two successfully funded NIH grants (a K08 and an R21) to study aging.