Altered cerebellar-cerebral functional connectivity in geriatric depression

Abstract

Although volumetric and activation changes in the cerebellum have frequently been reported in studies on major depression, its role in the neural mechanism of depression remains unclear. To understand how the cerebellum may relate to affective and cognitive dysfunction in depression, we investigated the resting-state functional connectivity between cerebellar regions and the cerebral cortex in samples of patients with geriatric depression (n = 11) and healthy controls (n = 18). Seed-based connectivity analyses were conducted using seeds from cerebellum regions previously identified as being involved in the executive, default-mode, affective-limbic, and motor networks. The results revealed that, compared with controls, individuals with depression show reduced functional connectivity between several cerebellum seed regions, specifically those in the executive and affective-limbic networks with the ventromedial prefrontal cortex (vmPFC) and increased functional connectivity between the motor-related cerebellum seed regions with the putamen and motor cortex. We further investigated whether the altered functional connectivity in depressed patients was associated with cognitive function and severity of depression. A positive correlation was found between the Crus II-vmPFC connectivity and performance on the Hopkins Verbal Learning Test-Revised delayed memory recall. Additionally, the vermis-posterior cinglate cortex (PCC) connectivity was positively correlated with depression severity. Our results suggest that cerebellum-vmPFC coupling may be related to cognitive function whereas cerebellum-PCC coupling may be related to emotion processing in geriatric depression.

Figure 1. Resting-state functional connectivity of cerebellum seed regions (row five) with cerebral regions from the healthy control group (rows one and two) and depression group (rows three and four).

The significant functional connectivity maps shown in each column were computed from the cerebellar seed region shown in the bottom row. The seed regions shown here include: Crus II_Exec2, the Crus II region found to be functionally connected with a cerebral executive region (the posterior dlPFC) in previous studies; Lobule VI_antExec, the Lobule VI region found to be functionally connected with a cerebral executive region (the anterior dlPFC) in previous studies; Crus I_DMN, the Crus I region found to be functionally connected with the default-mode network (mPFC) in previous studies; Vermis_Limbic, the vermis region found to be functionally connected with a limbic region (ACC); Lobule V_Motor, the Lobule V region found to be functionally connected with the motor cortex.

Figure 2. Significantly reduced functional connectivity in depressed patients between cerebellar executive and affective-limbic seed regions (shown in the lower row) with the ventromedial prefrontal cortex (vmPFC).

Figure 3. Significantly reduced functional connectivity in depressed patients between cerebellar executive and default-mode seed regions (shown in the lower row) with cerebral areas.

Figure 4. Significantly increased functional connectivity in depressed patients between cerebellar executive and motor seed regions (shown in the lower row) with cerebral areas.

Figure 5. Significant correlation of decreased right Crus II _Exec2-vmPFC connectivity with poorer performance on the HVLT-R delay across both depressed (purple squares) and control subjects (blue dots).

Data from all participants were included in this regression analysis.

Figure 6. Significant correlation of increased Vermis_Limbic- PCC connectivity with severity of depression symptoms in the depressed group (purple squares).

Data from the depressed patients only were included in this regression analysis.