Functional response in ventral temporal cortex differentiates mild cognitive impairment from normal aging

Abstract

This study sought to identify altered brain activation patterns in amnestic mild cognitive impairment (MCI) that could precede frank task impairment and neocortical atrophy. A high-accuracy lexical decision (LD) task was therefore employed. Both MCI and normal seniors (NS) groups completed the LD task while functional magnetic resonance imaging (fMRI) was performed. Accuracy on the LD task was high (> or =89% correct for both groups), and both groups activated a network of occipitotemporal regions and inferior frontal cortex. However, compared with the NS group, the MCI group showed reduced fMRI activation in these regions and increased activation in bilateral portions of anterior cingluate cortex. The results from a voxel-based morphometry analysis indicated that altered activations in the MCI group were not within regions of atrophy. Receiver operating characteristic curves demonstrated that reduced fMRI response in the left and right midfusiform gyri accurately discriminated MCI from NS. When activation magnitude in both fusiform gyri were included in a single logistic regression model, group classification accuracy was very high (area under the curve = 0.93). These results showed that a disrupted functional response in the ventral temporal lobe accurately distinguishes individuals with MCI from NS, a finding which may have implications for identifying seniors at risk for cognitive decline.

Figure 1

Brain activation patterns associated with lexical decision. Both the NS group (top) and the MCI group (bottom) activated a network of predominantly occipitotemporal regions, with additional activation in the frontal cortex. The level of significance is indicated by the color bar at the right side. A significance threshold of P < 0.001, corrected to P < 0.05 via cluster thresholding, was employed.

Figure 2

Between‐group differences in lexical decision activation. Warm colors (red–yellow) indicate regions showing increased activation in the NS group and cold colors (blue) indicate regions showing increased activation in the MCI group. The level of significance is indicated by the color bar at the right side. A significance threshold of P < 0.001 was employed, masked by activations in the lexical decision fixation comparison presented in Figure 1.

Figure 3

Regions of significantly smaller volume in the MCI group compared with the NS group. Maps depict volumetric differences on the canonical MNI T1 template after global intracranial differences have been removed. The intersection position of the cross lines is centered on the largest volumetric cluster, within the left hippocampus. The color bar presents t‐values of the clusters. A significance threshold of P < 0.001 (uncorrected) was employed.

Figure 4

Receiver operator characteristic curve. The area under the curve (AUC) for a model combining the left and right mid‐FFG fMRI magnitudes during lexical decision. This bilateral mid‐FFG model was highly accurate in discriminating individuals with MCI from NS, with an AUC of 0.93.