Phenomena of hypo- and hyperconnectivity in basal ganglia-thalamo-cortical circuits linked to major depression: a 7T fMRI study

Abstract

Major depressive disorder (MDD) typically manifests itself in depressed affect, anhedonia, low energy, and additional symptoms. Despite its high global prevalence, its pathophysiology still gives rise to questions. Current research places alterations in functional connectivity among MDD's most promising biomarkers. However, given the heterogeneity of previous findings, the use of higher-resolution imaging techniques, like ultra-high field (UHF) fMRI (≥7 Tesla, 7T), may offer greater specificity in delineating fundamental impairments. In this study, 7T UHF fMRI scans were conducted on 31 MDD patients and 27 age-gender matched healthy controls to exploratorily contrast cerebral resting-state functional connectivity patterns between both groups. The CONN toolbox was used to generate functional network connectivity (FNC) analysis based on the region of interest (ROI)-to-ROI correlations in order to enable the identification of clusters of significantly different connections. Correction for multiple comparisons was implemented at the cluster level using a false discovery rate (FDR). The analysis revealed three significant clusters differentiating MDD patients and healthy controls. In Clusters 1 and 2, MDD patients exhibited between-network hypoconnectivity in basal ganglia-cortical pathways as well as hyperconnectivity in thalamo-cortical pathways, including several individual ROI-to-ROI connections. In Cluster 3, they showed increased occipital interhemispheric within-network connectivity. These findings suggest that alterations in basal ganglia-thalamo-cortical circuits play a substantial role in the pathophysiology of MDD. Furthermore, they indicate potential MDD-related deficits relating to a combination of perception (vision, audition, and somatosensation) as well as more complex functions, especially social-emotional processing, modulation, and regulation. It is anticipated that these findings might further inform more accurate clinical procedures for addressing MDD.

Fig. 1. Resting-state functional connectivity clusters of significant differences between MDD patients and healthy controls.

Depicted collectively (A) and separately (B–D). Contrast [1 -1]: MDD patients > healthy controls. Blue: decreased connectivity, red: increased connectivity. aSTG: anterior superior temporal gyrus, pSTG: posterior superior temporal gyrus, PreCG: precentral gyrus, PostCG: postcentral gyrus, iLOC: inferior lateral occipital cortex, TOFusC: temporal-occipital fusiform cortex, AC: anterior cingulate gyrus, sLOC: superior lateral occipital cortex; l: left, r: right.

Fig. 2. Cluster 1: Mean connectivity values and 90% confidence intervals (Fisher’s z-transformed correlation coefficients) within each group.

Averaged (A) and ROI-to-ROI specific (B). Blue: MDD patients, red: healthy controls. TOFusC: temporal-occipital fusiform cortex, iLOC: inferior lateral occipital cortex, AC: anterior cingulate gyrus; l: left, r: right.

Fig. 3. Cluster 2: Mean connectivity values and 90% confidence intervals (Fisher’s z-transformed correlation coefficients) within each group.

Averaged (A) and ROI-to-ROI specific (B). Blue: MDD patients, red: healthy controls. aSTG: anterior superior temporal gyrus, pSTG: posterior superior temporal gyrus, PostCG: postcentral gyrus, PreCG: precentral gyrus; l: left, r: right.

Fig. 4. Cluster 3: Mean connectivity values and 90% confidence intervals (Fisher’s z-transformed correlation coefficients) within each group.

Blue: MDD patients, red: healthy controls. sLOC: superior lateral occipital cortex; l: left, r: right.