Anomalous neurovascular coupling in patients with generalized anxiety disorder evaluated by combining cerebral blood flow and functional connectivity strength.

Coupling between neuronal activity and blood perfusion is termed neurovascular coupling, and it provides a new mechanistic perspective into understanding numerous brain diseases. Although abnormal brain activity and blood supply have been separately reported in generalized anxiety disorder (GAD), whether anomalous neurovascular coupling would still be presented in such disease is hitherto unknown. In this study, the neuronal activity and blood supply were measured using the functional connectivity strength (FCS) and cerebral blood flow (CBF). The voxel-wise CBF-FCS correlations and CBF/FCS ratio were separately used to assess global and local neurovascular coupling in participants. Patients with GAD showed decreased voxel-wise CBF-FCS correlation, implicating global neurovascular decoupling. They also exhibited increased CBF/FCS ratio in the right superior parietal gyrus (SPG), and the enhanced CBF/FCS ratio in this region was negatively correlated with the self-esteem scores of GAD. The abnormal neurovascular coupling of GAD may indicate the disrupted balance between the intrinsic functional organization of the brain and corresponding blood perfusion of patients, and the abnormally increased local neurovascular coupling of the right SPG may be correlated with the abnormal self in GAD. These findings provide new information in understanding the brain dysfunction and abnormal cognition of GAD from the perspective of neurovascular coupling.

Disrupted dynamic local brain functional connectivity patterns in generalized anxiety disorder.

Previous studies have reported abnormalities in static brain activity and connectivity in patients with generalized anxiety disorder (GAD). However, the dynamic patterns of brain connectivity in patients with GAD have not been fully explored. In this study, we aimed to investigate the dynamic local brain functional connectivity in patients with GAD using dynamic regional phase synchrony (DRePS), a newly developed method for assessing intrinsic dynamic local functional connectivity. Seventy-four patients with GAD and 74 healthy controls (HCs) were enrolled and underwent resting-state functional magnetic resonance imaging. Compared to the HCs, patients with GAD exhibited decreased DRePS values in the bilateral caudate, left hippocampus, left anterior insula, left inferior frontal gyrus, and right fusiform gyrus extending to inferior temporal gyrus. The DRePS value of the left hippocampus was negatively correlated with the Hamilton Anxiety Rating Scale scores. Moreover, these abnormal DRePS patterns could be used to distinguish patients with GAD from HCs in an independent sample (18 patients with GAD and 21 HCs). Our findings provide further evidence on brain dysfunction in GAD from the perspective of the dynamic behaviour of local connections, suggesting that patients with GAD may have an insufficient brain adaptation. This study provides new insights into the neurocognitive mechanism of GAD and could potentially inform the diagnosis and treatment of this disease. Future studies on GAD could benefit from combining the DRePS method with task-related functional magnetic resonance imaging and non-invasive brain stimulation.

Functional dysconnectivity within the emotion-regulating system is associated with affective symptoms in major depressive disorder: A resting-state fMRI study.

OBJECTIVE: Major depressive disorder (MDD) can be characterized as a multidimensional and system-level disorder. The neuropathophysiological abnormalities have been reported to be distributed in emotion regulation system, involving the prefrontal cortex (PFC), limbic and striatum in convergent studies. Decrease of positive affect and increase of negative affect are recognized as a hallmark of MDD. However, the dysfunctions in affective processing in MDD within the emotion regulation system remains largely unclear. In this study, our goals are to characterize the dysconnectivity pattern within this system and explore the relationships between this kind of dysconnectivity pattern and affective symptoms, which might help us better look into the neuropathophysiological mechanisms underlying MDD. METHODS: A total of 34 MDD and 34 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (rsfMRI). The alterations in functional connectivity (FC) within the emotion regulation system and their relationships with affective symptoms were explored. RESULTS: Compared with HCs, MDD patients showed aberrant FC within this system. Importantly, deceased FC was mainly involved in the prefrontal-limbic system, while elevated FC was observed in the prefrontal-striatum system. In the MDD group, decreased FC of right posterior hippocampus-left dorsolateral prefrontal cortex (dlPFC) was negatively associated with the negative affect scores and Hamilton Depression Rating Scale scores and the FC of left ventral striatum-left dlPFC was significantly negatively related with the positive affect scores. CONCLUSIONS: These findings demonstrated that MDD showed characteristic pathological alterations of the emotion regulation system. Dysconnectivity within prefrontal-limbic system might be more related to the dysregulation of negative affect, whereas dysconnectivity within prefrontal-striatum system might influence more on positive affect processing. The decrease in positive affect and increase in negative affect in MDD might have different pathological basis. These results could help better understand the dysconnectivity pattern in the emotion-regulating system underlying depression.

Hippocampal functional connectivity-based discrimination between bipolar and major depressive disorders.

Despite the impressive advancements in the neuropathology of mood disorders, patients with bipolar disorder (BD) are often misdiagnosed on the initial presentation with major depressive disorder (MDD). With supporting evidence from neuroimaging studies, the abnormal functional connectivity (FC) of the hippocampus has been associated with various mood disorders, including BD and MDD. However, the features of the hippocampal FC underlying MDD and BD have not been directly compared. This study aims to investigate the hippocampal resting-state FC (rsFC) analyses to distinguish these two clinical conditions. Resting-state functional magnetic resonance imaging (fMRI) data was collected from a sample group of 30 patients with BD, 29 patients with MDD and 30 healthy controls (HCs). One-way ANOVA was employed to assess the potential differences of the hippocampus FC across all subjects. BD patients exhibited increased FC of the bilateral anterior/posterior hippocampus with lingual gyrus and inferior frontal gyrus (IFG) relative to patients MDD patients. In comparison with HCs, patients with BD and MDD had an increased FC between the right anterior hippocampus and lingual gyrus and a decreased FC between the right posterior hippocampus and right IFG. The results revealed a distinct hippocampal FC in MDD patients compared with that observed in BD patients. These findings may assist investigators in attempting to distinguish mood disorders by using fMRI data.

Dysfunctional connectivity between raphe nucleus and subcortical regions presented opposite differences in bipolar disorder and major depressive disorder.

As the source of most serotonergic neurons projecting throughout the brain, the raphe nucleus has been repeatedly implicated in bipolar disorder (BD) and major depressive disorder (MDD). However, whether the functional connectivity (FC) of the raphe nucleus is altered differently in BD and MDD patients is not well understood. In the current study, we aimed to find the difference in altered FC of the raphe nucleus in BD and MDD patients. Resting-state functional magnetic resonance imaging data from 40 BD patients, 54 MDD patients and 44 matched healthy controls (HCs) were collected. Seed-based FC of the raphe nucleus was calculated in three groups and compared using statistical tests. Results showed that BD patients mainly presented increased FC in cortical regions and decreased FC in subcortical regions. MDD patients presented overall decreased FC. The overlapping abnormalities found in BD and MDD patients were very low. Functional connections of subcortical regions such as the thalamus, putamen and hippocampus connected to the raphe nucleus presented opposite differences in BD and MDD patients compared with HCs. In MDD patients, these differences were correlated with the total scores of the Beck Hopelessness Scale. Thus, BD and MDD patients presented opposite differences in altered FC of the raphe nucleus mainly in subcortical regions. Altered functional connectivity of subcortical regions connected to the raphe nucleus played different roles in the physiological mechanisms between BD and MDD and could help us understand specific pathogenesis between BD and MDD patients.

Altered resting-state cerebral blood flow and functional connectivity of striatum in bipolar disorder and major depressive disorder.

BACKGROUND: Clinically distinguishing bipolar disorder (BD) from major depressive disorder (MDD) during depressive states is difficult. Neuroimaging findings suggested that patients with BD and those with MDD differed with respect to the gray matter volumes of their subcortical structures, especially in their striatum. However, whether these disorders have different effects on functionally striatal neuronal activity and connectivity is unclear. METHODS: Arterial spin labeling and resting-state functional MRI was performed on 25 currently depressive patients with BD, 25 depressive patients with MDD, and 34 healthy controls (HCs). The functional properties of striatal neuronal activity (cerebral blood flow, CBF) and its functional connectivity (FC) were analyzed, and the results from the three groups were compared. The result of the multiple comparisons was corrected on the basis of the Gaussian Random Field theory. RESULTS: The patients with BD and those with MDD both had higher CBF values than the HCs in the right caudate and right putamen. The hyper-metabolism of right striatum in BD patients was associated with increased average duration per depressive episode. The two disorders showed commonly increased FC between the striatum and dorsolateral prefrontal cortex, whereas the altered FC of the striatum with precuneus/cuneus was observed only in patients with BD. CONCLUSIONS: Patients with BD and those with MDD had a common deficit in their prefrontal-limbic-striatal circuits. The altered striato-precuneus FC can be considered as a marker for the differentiation of patients with BD from those with MDD.