Lower Activation in Frontal Cortex and Posterior Cingulate Cortex Observed during Sex Determination Test in Early-Stage Dementia of the Alzheimer Type

Abstract

Face-labeling refers to the ability to classify faces into social categories. This plays a critical role in human interaction as it serves to define concepts of socially acceptable interpersonal behavior. The purpose of the current study was to characterize, what, if any, impairments in face-labeling are detectable in participants with early-stage clinically diagnosed dementia of the Alzheimer type (CDDAT) through the use of the sex determination test (SDT). In the current study, four (1 female, 3 males) CDDAT and nine (4 females, 5 males) age-matched neurotypicals (NT) completed the SDT using chimeric faces while undergoing BOLD fMRI. It was expected that CDDAT participants would have poor verbal fluency, which would correspond to poor performance on the SDT. This could be explained by decreased activation and connectivity patterns within the fusiform face area (FFA) and anterior cingulate cortex (ACC). DTI was also performed to test the association of pathological deterioration of connectivity in the uncinate fasciculus (UF) and verbally-mediated performance. CDDAT showed lower verbal fluency test (VFT) performance, but VFT was not significantly correlated to SDT and no significant difference was seen between CDDAT and NT for SDT performance as half of the CDDAT performed substantially worse than NT while the other half performed similarly. BOLD fMRI of SDT displayed differences in the left superior frontal gyrus and posterior cingulate cortex (PCC), but not the FFA or ACC. Furthermore, although DTI showed deterioration of the right inferior and superior longitudinal fasciculi, as well as the PCC, it did not demonstrate significant deterioration of UF tracts. Taken together, early-stage CDDAT may represent a common emerging point for the loss of face labeling ability.

Keywords: Alzheimer; brain networks; chimeric faces; face-processing; neurodegeneration; neuroimaging.

Figure 1

Examples of the sex determination test (SDT). SDT examples in response to the question: “ARE THE TWO PEOPLE OF THE SAME SEX?” (left) “yes”; two males (center) “yes”; two females (right) “no”; male (top) and female (bottom).

Figure 2

Behavioral results. (A) Results of Verbal Fluency Test (VFT) and SDT performance. (B) Correlation of VFT and SDT performance. NT, Neurotypicals; CDDAT, Clinically diagnosed dementia of the Alzheimer type. Thickened line is VFT classifier score at 31–35; p = 0.014.

Figure 3

(A) Significant fMRI activations for SDT when participants responded “yes” in left-Superior Frontal Gyrus and left-Posterior cingulate cortex (PCC; threshold free cluster enhancement, threshold free cluster enhancement, TFCE of z > 1.5 and a cluster-corrected significance threshold of p < 0.05). (B) Pertinent DTI results for the SDT. Significant differences were observed for the superior longitudinal fasciculi (number 1) and inferior longitudinal fasciculi (number 2) for the left (top left) and right (top right) hemispheres and for the PCC (blue crescent outline), but not the anterior cingulate cortex (ACC; red crescent outline) for the left (bottom left) and right (bottom right) hemispheres. For Figures: areas where NT brain activity > CDDAT brain activity are shown in red and CDDAT brain activity > NT brain activity are shown in blue. For fMRI figures: areas where NT brain activity > CDDAT brain activity are shown in red. For DTI figures: areas where NT > CDDAT for fractional anisotropy (FA) measures are shown in red. Green lines represent the FA skeleton. NT, Neurotypicals; CDDAT, Clinically Diagnosed Dementia of the Alzheimer Type. (C) Significant fMRI activations for SDT when participants responded “yes” are listed for the NT > CDDAT contrast (TFCE of z > 1.5 and a cluster-corrected significance threshold of p < 0.05). No significant fMRI activations for SDT were seen for the CDDAT > NT contrast.