fMRI correlates of white matter hyperintensities in late-life depression

Abstract

Objective: This study tests whether or not the structural white matter lesions that are characteristic of late-life depression are associated with alterations in the functional affective circuits of late-life depression. This study used an emotional faces paradigm that has been shown to engage the affective limbic brain regions.

Method: Thirty-three elderly depressed patients and 27 nondepressed comparison subjects participated in this study. The patients were recruited through the NIMH-sponsored Advanced Center for Interventions and Services Research for the Study of Late-Life Mood Disorders at the University of Pittsburgh Center for Bioethics and Health Law. Structural and functional MRI was used to assess white matter hyperintensity (WMH) burden and functional magnetic resonance imaging (fMRI) blood-oxygen-level-dependent (BOLD) response on a facial expression affective-reactivity task in both elderly participants with nonpsychotic and nonbipolar major depression (unmedicated) and nondepressed elderly comparison subjects.

Results: As expected, greater subgenual cingulate activity was observed in the depressed patients relative to the nondepressed comparison subjects. This same region showed greater task-related activity associated with a greater burden of cerebrovascular white matter change in the depressed group. Moreover, the depressed group showed a significantly greater interaction of WMH by fMRI activity effect than the nondepressed group.

Conclusions: The observation that high WMH burden in late-life depression is associated with greater BOLD response on the affective-reactivity task supports the model that white matter ischemia in elderly depressed patients disrupts brain mechanisms of affective regulation and leads to limbic hyperactivation.

FIGURE 1

Faces and Shapes fMRI Task Used to Examine Neural Circuitry in a Study of White Matter Hyperintensities in Late-Life Depressiona ^a The faces and shapes block design task involves six trials per block and nine blocks: five blocks of shapes and four blocks of faces.

FIGURE 2

Histograms of White Matter Hyperintensity (WMH) Burden in Late-Life Depression Patients and in Nondepressed Elderly Comparison Subjectsa ^a T₂-weighted FLAIR (fluid attenuated inversion recovery) images from late-life depression patients (top panel) and nondepressed elderly comparison subjects (bottom panel) in the low- and high-burden groups are shown to illustrate the degree of WMH burden.

FIGURE 3

Main Effect of the Faces and Shapes Task in a Study of White Matter Hyperintensitites in Late-Life Depressiona ^a A brain activation map for full group contrast of faces > shapes is shown. The crosshairs point out the robust amygdala BOLD response with this task.

FIGURE 4

Brain Activation Map Showing Areas With Greater BOLD Response in Late-Life Depression Patients Relative to Nondepressed Elderly Comparison Subjects in a Study of White Matter Hyperintensitiesa ^a Crosshairs point out the rostral (subgenual) cingulate region.

FIGURE 5

High Compared With Low White Matter Hyperintensity (WMH) Burden in Late-Life Depression Patients and Nondepressed Elderly Comparison Subjectsa ^a Brain activation map shows areas with greater BOLD response in high WMH burden compared with low WMH burden in late-life depression patients (top) and nondepressed elderly comparison subjects (middle), as well as the interaction between the two (bottom). The crosshairs point out the rostral (subgenual) cingulate region.