Functional and structural alterations in the pain-related circuit in major depressive disorder induced by electroconvulsive therapy.

Approximately two-thirds of major depressive disorder (MDD) patients have pain, which exacerbates the severity of depression. Electroconvulsive therapy (ECT) is an efficacious treatment that can alleviate depressive symptoms; however, treatment for pain and the underlying neural substrate is elusive. We enrolled 34 patients with MDD and 33 matched healthy controls to complete clinical assessments and neuroimaging scans. MDD patients underwent second assessments and scans after ECT. We defined a pain-related network with a published meta-analysis and calculated topological patterns to reveal topologic alterations induced by ECT. Using the amplitude of low-frequency fluctuations (ALFFs), we probed local function aberrations of pain-related circuits in MDD patients. Subsequently, we applied gray matter volume (GMV) to reveal structural alterations of ECT relieving pain. The relationships between functional and structural aberrations and pain were determined. ECT significantly alleviated pain. The neural mechanism based on pain-related circuits indicated that ECT weakened the circuit function (ALFF: left amygdala and right supplementary motor area), while augmenting the structure (GMV: bilateral amygdala/insula/hippocampus and anterior cingulate cortex). The topologic patterns became less efficient after ECT. Correlation analysis between the change in pain and GMV had negative results in bilateral amygdala/insula/hippocampus. Similarity, there was a positive correlation between a change in ALFF in the left amygdala and improved clinical symptoms. ECT improved pain by decreasing brain local function and global network patterns, while increasing structure in pain-related circuits. Functional and structural alterations were associated with improvement in pain.

Electroconvulsive therapy changes temporal dynamics of intrinsic brain activity in depressed patients.

Electroconvulsive therapy (ECT) has been demonstrated to be effective in treating depressed patients. Previous neuroimaging studies have focused mainly on alterations in static brain activity and connectivity to study the effects of ECT in depressed patients. However, it remains unclear whether the temporal dynamics of brain activity are associated with mechanisms of ECT in depressed patients. We measured the dynamics of spontaneous brain activity using dynamic amplitude of low-frequency fluctuation (dALFF) in healthy controls (n = 40) and patients diagnosed with unipolar depression (UD, n = 36) or bipolar disorder (BD, n = 9) before and after ECT. Furthermore, the temporal variability of intrinsic brain activity (iBA) was quantified as the variance of dALFF across sliding window. In addition, correlation analysis was performed to investigate the relationships among dALFF, depressive symptoms, and cognitive function in depressed patients. We lack second resting-state functional magnetic resonance imaging (rs-fMRI) data for healthy controls. After ECT, patients showed decreased brain dynamics (less temporal variability) in the right dorsal anterior cingulate cortex (dACC) and the right precuneus, whereas they showed increased brain dynamics in the bilateral superior medial frontal cortex (mSFC). No significant correlation was found between the dALFF and clinical variables in depressed patients. Our findings suggest that right dACC, right precuneus, and bilateral mSFC play an important role in response to ECT depressed patients from the perspective of dynamic local brain activity, indicating that the dALFF variability may be useful in further understanding the mechanisms of ECT's antidepressant effects.

Nodal degree changes induced by electroconvulsive therapy in major depressive disorder: Evidence in two independent cohorts.

OBJECTIVE: Electroconvulsive therapy (ECT), a rapidly acting treatment for major depressive disorder (MDD), has been reported to regulate brain networks. Nodes and their connections are the main components of the brain network and are essential for establishing and maintaining effective information transmission. This study aimed to evaluate the role of nodes in mediating antidepressant effects of ECT. METHODS: Voxel-based nodal degree analysis was performed in 42 patients with MDD receiving ECT and 42 matched healthy controls at two time points to identify the nodal changes induced by ECT. Verification analysis was evaluated in a second, independent cohort of 23 MDD patients. RESULTS: MDD patients showed improved nodal degree of the bilateral angular cortex (AG), precuneus, inferior frontal gyrus (IFG) and the right superior frontal gyrus (SFG) after ECT, and the increased nodal degree index (IND) rate of the AG and precuneus were negatively correlated to the depressive changes following ECT. Furthermore, validation analysis revealed a similar pattern of IND abnormalities in the first and second cohort of MDD patients. CONCLUSION: ECT regulates the disrupted nodal degree of the AG and precuneus to achieve an antidepressant effect. This study may provide further insights into the pathogenesis of depression and provide potential targets for antidepressant pharmacotherapies.

Impaired neurovascular coupling and cognitive deficits in anti-N-methyl-D-aspartate receptor encephalitis.

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a recently identified autoimmune disorder with heterogeneous neurological, psychiatric, and cognitive manifestations. The NMDAR is a key signaling node for neurovascular coupling, the mechanism by which cerebral blood perfusion is enhanced to meet local metabolic requirements from increased neuronal activity. Therefore, anti-NMDAR encephalitis may disrupt neurovascular coupling and induce cognitive deficits. This study examined neurovascular coupling and cognitive function in anti-NMDAR encephalitis patients to identify prognostic biomarkers, reveal potential pathogenic mechanisms, and provide clues to possible therapeutic strategies. In this study, twenty-three anti-NMDAR encephalitis patients and thirty healthy controls received neuropsychological testing and multimodal magnetic resonance imaging (MRI). Cerebral blood flow (CBF) was calculated from arterial spin labeling, and regional homogeneity (ReHo) was computed from functional MRI. Pearson's correlation coefficients between CBF and ReHo were calculated to obtain neurovascular coupling. At the whole gray matter level, CBF‒ReHo coupling was reduced in patients compared to healthy controls. At the regional level, CBF‒ReHo was significantly lower among patients in the precentral gyrus, frontal gyrus, insula, cuneus, inferior parietal lobe, supramarginal gyrus, angular gyrus, precuneus, temporal gyrus, and temporal pole. Reduced CBF‒ReHo in the left superior medial frontal gyrus of patients was significantly correlated with a deficit in verbal inhibition control, and the reduced CBF‒ReHo in the left insula was significantly correlated with impaired executive function. In conclusion, anti-NMDAR encephalitis is associated with both global and regional disruptions in neurovascular coupling that may in turn lead to deficits in specific cognitive domains.

Abnormal connectivity of anterior-insular subdivisions and relationship with somatic symptom in depressive patients.

Depressive patients frequently present with somatic complaints such as pain and fatigue. The anterior insula (AI) is a crucial region for somatic processing, but reported contributions of AI dysfunction to somatic symptoms have varied across studies. We speculated that functional heterogeneity among AI subdivisions may contribute to this inconsistency. To reveal the correlation between each subdivision and somatic symptoms, we investigated resting-state functional connectivity (RSFC) based on seeds within distinct AI subdivisions in 45 depressive patients and 35 matched healthy controls (HCs). Depressive and somatic symptoms were assessed using the Hamilton Depression Rating Scale (HDRS) and the 15-item somatic symptom severity scale of the Patient Health Questionnaire (PHQ-15), respectively. The contributions of AI subregion-specific pathways to depression were further validated by examining changes in symptom severity and RSFC following electroconvulsive therapy (ECT). At baseline, depressive patients exhibited weaker RSFC between ventral AI (vAI) and right orbitofrontal cortex (rOFC) than HCs. Moreover, vAI-rOFC RSFC strength was negatively correlated with PHQ-15 and HDRS scores, indicating that weaker RSFC predicted greater symptom severity. ECT reduced depressive and somatic symptoms, and symptom mitigation was correlated with enhanced vAI-rOFC RSFC. The findings suggest that reduced vAI-rOFC RSFC underlies the somatic symptoms of depression and that enhancing vAI-rOFC RSFC can contribute to amelioration of somatic symptoms.

Altered neural activity in the reward-related circuit and executive control network associated with amelioration of anhedonia in major depressive disorder by electroconvulsive therapy.

Anhedonia is a core characteristic of depression, the amelioration of which accounts for depressive symptom improvement. Electroconvulsive therapy (ECT) has been shown remarkable antidepressive effect, however, less is known about the effect of ECT on anhedonia and its underlying neural mechanism. Herein, we investigated local and global intrinsic brain functional alterations during the resting state in 46 patients with pre- and post-ECT major depressive disorder using the amplitude of low-frequency fluctuations (ALFF) and degree centrality (DC) approach. Functional connectivity (FC) was also calculated between nodes with significant local and global intrinsic brain functional alterations. The severity of anhedonia and depression was assessed with the Temporal Experience of Pleasure Scale and Hamilton Depression Rating Scale, respectively. The relationship between the change in anhedonia and depressive symptoms and brain functional alterations was determined. Increased ALFF and DC were observed in the bilateral dorsal medial prefrontal cortex (dmPFC), right dorsal lateral prefrontal cortex (dlPFC), left orbitofrontal cortex, and right orbitofrontal cortex (ROFC) after ECT. Correlational analysis between the change in anhedonia and ALFF had positive results in the dmPFC. Similarly, there was a positive correlation between the change in anhedonia and change in DC in the dmPFC, right dlPFC, ROFC, and middle frontal gyrus. Furthermore, there was a significant relationship between the change in anhedonia and altered dmPFC-dlPFC FC. These results revealed that amelioration of anhedonia may be associated with intrinsic neural activity alteration in the reward-related circuit and executive control network following ECT.

Bifrontal electroconvulsive therapy changed regional homogeneity and functional connectivity of left angular gyrus in major depressive disorder.

Electroconvulsive therapy (ECT) is a rapid and effective treatment for MDD. However, the mechanism of ECT for MDD has not been clarified. In this study, we used resting-state functional magnetic resonance imaging (rs-fMRI) to explore the mechanism of ECT. Two groups of subjects were recruited: healthy controls (HCs) and MDD patients who received bifrontal ECT. MDD patients and HCs underwent rs-fMRI scans and clinical assessments (Hamilton Depression Rating Scale, Rey-Auditory Verbal Learning Test (RAVLT), and the verbal fluency test). Regional homogeneity (ReHo) and functional connectivity were evaluated for the analysis of rs-fMRI data. The results showed that ReHo values in the left angular gyrus (LAG) significantly increased in MDD patients after ECT, and the functional connectivity of the LAG with bilateral inferior temporal gyrus, bilateral middle frontal gyrus, left superior frontal gyrus, left middle temporal gyrus, left precuneus, left posterior cingulate gyrus, and right angular gyrus was found to be strengthened after ECT. The scores of delayed recall trial in the RAVLT of MDD patients were related to the functional connectivity of the LAG with the left inferior temporal gyrus and the left posterior cingulate gyrus. It indicated LAG palyed an important role in the mechanism of ECT in MDD.