White Matter Hyperintensities Relate to Basal Ganglia Functional Connectivity and Memory Performance in aMCI and SVMCI

Abstract

Cerebral small vessel diseases play a crucial role in both vascular and non-vascular dementias. The location of white matter hyperintensities (WMHs), a neuroimaging marker of cerebral small vessel disease, has been found to vary between different types of dementias, and those in the basal ganglia (BG) have been particularly associated with vascular cognitive impairment (VCI). However, anatomical variation of WMHs across BG nuclei and its effect on brain network dysconnectivity has not been clearly elucidated. The study sample consisted of 40 patients with amnestic mild cognitive impairment (aMCI), 40 with subcortical vascular MCI (SVMCI), and 40 healthy control subjects. We examined the volume of WMH using T2-weighted magnetic resonance imaging. We also assessed the disturbances in BG-cortical communication by measuring resting-state functional connectivity (rsFC) from the functional magnetic resonance imaging signal. WMHs were more pronounced in the SVMCI group particularly in the caudate regions. In SVMCI patients, while higher WMHs in the dorsal caudate correlated with weaker FC with executive control regions and worse immediate recall performance, WMHs in the ventral caudate were associated with weaker FC with anterior default mode regions and worse delayed recall performance. In contrast, in aMCI patients, BG WMHs were not correlated with their changes in functional connectivity changes, which showed weaker connectivity with almost all BG structures, rather than restricting to specific BG subdivisions as observed in the SVMCI group. Our findings demonstrate that heterogeneously distributed BG WMHs are associated with changes in functional network interactions and verbal episodic memory performance only in SVMCI patients, which establishes a link between cerebrovascular-related structural abnormality, functional integrity of BG circuits, and episodic memory impairments in SVMCI, and may reflect a differential role of the cerebrovascular pathology in disrupting network-level communications and cognition between Alzheimer's and subcortical vascular dementia.

Keywords: amnestic mild cognitive impairment; basal ganglia; functional connectivity; subcortical vascular cognitive impairment; white matter hyperintensity.

FIGURE 1

(A) White matter hyperintensity (WMH) differences across different groups and regions of interest (ROI). ▲ indicates a significant difference between caudate and the other basal ganglia (BG) regions. ^∗ indicates significant group by ROI effect in certain regions. (B) Relationship between Auditory Verbal Learning Test (AVLT) scores and WMH in left dorsal and ventral caudate in subcortical vascular mild cognitive impairment (SVMCI) patients.

FIGURE 2

(A) Group-regions of interest (ROI) interaction effects in basal ganglia (BG) functional connectivity between subcortical vascular mild cognitive impairment (SVMCI) and normal control (NC) groups. (B) Brain regions with significant group (SVMCI vs. NC) by ROI interaction effects are distributed in five major brain systems. (C) Brain regions showing significant differences between SVMCI and NC groups in functional connectivity with dorsal and ventral caudate nucleus. The brain surface maps were rendered by using the BrainNet Viewer (http://www.nitrc.org/projects/bnv/) (Xia et al., 2013).

FIGURE 3

(A) Group effects in basal ganglia functional connectivity between amnestic mild cognitive impairment (aMCI) and normal control (NC) groups. (B) Brain regions with significant group (aMCI vs. NC) effects are distributed in three major brain modules. (C) Functional connectivity differences between aMCI and NC groups with each basal ganglia seed region.

FIGURE 4

(A) Relationship between Auditory Verbal Learning Test (AVLT) immediate recall scores and resting-state functional connectivity (rsFC) of left ventral caudate with subcortical vascular mild cognitive impairment (SVMCI)-affected regions belonging to the executive control network (ECN; left panel) and between AVLT delayed recall scores and rsFC of left ventral caudate with SVMCI-affected regions belonging to the default mode network (DMN; right panel) in SVMCI patients. (B) Relationship between Mini-Mental State Examination (MMSE) and rsFC of left nucleus accumbens (NAcc) with amnestic MCI (aMCI)-affected regions belonging to the DMN in aMCI patients.

FIGURE 5

Relationship between white matter hyperintensity (WMH) in dorsal/ventral caudate and their resting-state functional connectivity (rsFC) in subcortical vascular mild cognitive impairment (SVMCI) patients.