Dynamic effective connectivity in the cerebellar dorsal dentate nucleus and the cerebrum, cognitive impairment, and clinical correlates in patients with schizophrenia.

BACKGROUND: Schizophrenia (SZ) is characterized by disconnected cerebral networks. Recent studies have shown that functional connectivity between the cerebellar dorsal dentate nucleus (dDN) and cerebrum is correlated with psychotic symptoms, and processing speed in SZ patients. Dynamic effective connectivity (dEC) is a reliable indicator of brain functional status. However, the dEC between the dDN and cerebrum in patients with SZ remains largely unknown. METHODS: Resting-state functional MRI data, symptom severity, and cognitive performance were collected from 74 SZ patients and 53 healthy controls (HC). Granger causality analysis and sliding time window methods were used to calculate dDN-based dEC maps for all subjects, and k-means clustering was performed to obtain several dEC states. Finally, between-group differences in dynamic effective connectivity variability (dECV) and clinical correlations were obtained using two-sample t-tests and correlation analysis. RESULTS: We detected four dEC states from the cerebrum to the right dDN (IN states) and three dEC states from the right dDN to the cerebrum (OUT states), with SZ group having fewer transitions in the OUT states. SZ group had increased dECV from the right dDN to the right middle frontal gyrus (MFG) and left lingual gyrus (LG). Correlations were found between the dECV from the right dDN to the right MFG and symptom severity and between the dECV from the right dDN to the left LG and working memory performance. CONCLUSIONS: This study reveals a dynamic causal relationship between cerebellar dDN and the cerebrum in SZ and provides new evidence for the involvement of cerebellar neural circuits in neurocognitive functions in SZ.

Alterations in resting-state global brain connectivity in bipolar I disorder patients with prior suicide attempt.

BACKGROUND: Bipolar I disorder (BD-I) is associated with a high risk of suicide attempt; however, the neural circuit dysfunction that confers suicidal vulnerability in individuals with this disorder remains largely unknown. Resting-state functional magnetic resonance imaging (rs-fMRI) allows non-invasive mapping of brain functional connectivity. The current study used an unbiased voxel-based graph theory analysis of rs-fMRI to investigate the intrinsic brain networks of BD-I patients with and without suicide attempt. METHODS: A total of 30 BD-I patients with suicide attempt (attempter group), 82 patients without suicide attempt (non-attempter group), and 67 healthy controls underwent rs-fMRI scan, and then global brain connectivity (GBC) was computed as the sum of connections of each voxel with all other gray matter voxels in the brain. RESULTS: Compared with the non-attempter group, we found regional differences in GBC values in emotion-encoding circuits, including the left superior temporal gyrus, bilateral insula/rolandic operculum, and right precuneus (PCu)/cuneus in the bipolar disorder (BD) attempter group, and these disrupted hub-like regions displayed fair to good power in distinguishing attempters from non-attempters among BD-I patients. GBC values of the right PCu/cuneus were positively correlated with illness duration and education in the attempter group. CONCLUSIONS: Our results indicate that abnormal connectivity patterns in emotion-encoding circuits are associated with the increasing risk of vulnerability to suicide attempt in BD patients, and global dysconnectivity across these emotion-encoding circuits might serve as potential biomarkers for classification of suicide attempt in BD patients.