Altered task-modulated functional connectivity during emotional face processing in euthymic bipolar patients: A whole-brain psychophysiological interaction study.

BACKGROUND: Patients with bipolar disorder (BD) show deficits of facial emotion processing even in the euthymic phase. However, the large-scale functional brain network mechanism underlying the emotional deficit of BD remains unclear. Specifically, it is of importance to understand how the task-modulated functional connectivity (FC) was alternated over distributed brain networks in BD. METHODS: In this study, we analyzed functional MRI data of a face-matching task from 29 euthymic BD patients and 29 healthy controls (HC), and performed whole-brain psychophysiological interaction (PPI) analysis to obtain task-modulated FC. Abnormal FC patterns were identified through support vector machine-based classification. The topological organization of task-modulated FC networks was estimated by the graph theoretical analysis and compared between BD and HC. RESULTS: BD exhibited widely distributed aberrant task-modulated FC patterns not only in core neurocognitive intrinsic brain networks (the fronto-parietal, cingulo-opercular, and default mode networks), but also in the cerebellum and primary processing networks (sensorimotor and visual). Furthermore, the local efficiency of the frontal-parietal network was significantly increased in BD. LIMITATIONS: The modest sample size. Only face pictures with negative emotion were used. Only unidirectional task-modulated FC was investigated. CONCLUSIONS: BD patients showed a widely distributed aberrant task-modulated FC pattern. Particularly, the fronto-parietal network, as one of the core neurocognitive intrinsic brain networks, was the primary network that demonstrated changes of both FC strength and local efficiency in BD. These findings on the task-modulated FC between these intrinsic brain networks might be considered an endophenotype of the BD condition persistent in the euthymic state.

Abnormal transitions of dynamic functional connectivity states in bipolar disorder: A whole-brain resting-state fMRI study.

BACKGROUND: Dynamic functional connectivity (dFC) based on resting-state fMRI has attracted interest in the field of bipolar disorder (BD), because dFC can better capture the evolving processes of emotion and cognition, which are typically impaired in BD. However, previous dFC studies of BD have typically focused on specific seed brain regions or specific functional brain networks, and they have ignored global dynamic information interaction in the whole brain. This study is aimed to reveal aberrant and interpretable whole-brain dFC patterns of BD. METHODS: The resting-state fMRI data collected from 35 euthymic BD patients and 30 healthy people. We developed a new dFC inference pipeline, including the sliding-window method, k-means clustering, a new permutation with zero-inflated Poisson regression method, and a similarity analysis for interpretable states, to examine the different patterns of dFC states between BD patients and healthy participants. RESULTS: BD patients had significantly more frequent transitions between two specific dFC states, which were respectively close to high-level cognitive networks and low-level sensory networks, than healthy controls (p < 0.05, FDR). LIMITATIONS: The size of samples and other BD types need to be expanded to validate the results of this study. Possible confounding effect of medication. CONCLUSIONS: This study detected aberrant dFC pattern of BD, which indicated the increased lability of the processes of cognition and emotion in BD, and this finding could improve our understanding of the neuropathological mechanism of BD.

Fusion analysis of gray matter and white matter in bipolar disorder by multimodal CCA-joint ICA.

BACKGROUND: Bipolar disorder (BD) patients show morphological abnormalities in gray matter (GM) and white matter (WM), which can be revealed by structure MRI (sMRI) and diffusion tensor imaging (DTI) respectively. However, previous studies on BD mainly relied on separated analysis of single neuroimaging modality, and it remains unclear how GM and WM covary to the abnormal brain structures of BD patients. METHODS: We recorded multimodal sMRI-DTI data of 35 BD patients and 30 healthy controls (HC) and used multimodal canonical component analysis and joint independent component analysis (mCCA-jICA) to identify altered covariant structures in GM and WM of BD. Group-discriminative and joint group-discriminative independent components (ICs) were identified between BD and HC. Correlation analysis was performed between the mixing coefficients and behavioral index. RESULTS: For BD patients, experiments results revealed that the GM atrophy in inferior frontal gyrus, right anterior cingulate gyrus and left superior frontal gyrus are associated with the WM integrity reduction in corticospinal tract and superior longitudinal fasciculus. Further, compared with HC, different correlation between mixing coefficients of ICs and age was observed for BD patients. LIMITATIONS: The number of participants needs to be increased to more rigorously validate the results of this study, ideally from multiple sites. Functional imaging data could be utilized to explore structural-functional covariant pattern in BD. Possible confounding effect of medication. CONCLUSIONS: We performed fusion analysis of sMRI and DTI and revealed covariant (GM-WM) structural patterns of BD patients. This study could be useful for developing more reliable neural biomarkers of BD.

Cortical thickness and subcortical volumes alterations in euthymic bipolar I patients treated with different mood stabilizers.

Reported structural abnormalities of patients with bipolar disorder (BD) are inconsistent and the use of psychotropic medication is one of the sources of heterogeneity. A fairly small number of morphometric studies have involved comparison of BD on different mood stabilizers. Here in this study, we aimed to investigate the cortical thickness and subcortical volumes in euthymic BD patients on lithium and valproate and healthy controls (HC), and to elucidate the relationship between the use of medication and brain structure variations. We acquired structural magnetic resonance imaging data from 35 BD patients (19/valproate;16/lithium) and 30 HC subjects. Cortical thickness was compared in multiple locations across the continuous cortical surface, and subcortical volumes were compared on a structure-by-structure basis. Group analyses revealed widespread thinning of the prefrontal cortex in BD. Compared with BD on valproate, BD on lithium showed significant increased cortical thickness of the left rostral middle frontal cortex and right superior frontal cortex, while cortical thickness was not significantly different between BD on lithium and HC in the bilateral rostral middle frontal cortex. Moreover, no significant difference was observed in subcortical volume. Limitations of this study comprise the possible effect of other psychotropic drugs, small sample size and the cross-sectional design. Therefore, the results suggest medication-related neurobiological difference between BD patients on different mood stabilizers, but no casual role can be proposed. Our findings provided new evidence about the effects of psychotropic medication upon neuroanatomy in BD, and could help to explain the inconsistency of existing studies as well as contribute to the extraction of reliable neuroimaging biomarkers in BD.

Abnormal brain activation during emotion processing of euthymic bipolar patients taking different mood stabilizers.

Numerous functional magnetic resonance imaging studies have been conducted to elucidate emotion processing of patients with bipolar disorder (BD), but due to different inclusion criteria used, especially for the history of medication use, the results for euthymic BD patients are inconsistent. For this reason, brain functional effects of psychopharmacological treatments on BD patients have been investigated by numerous fMRI studies, but there is no existing report for brain functional effects of different mood stabilizers. In this study, we compared the emotion processing in BD patients treated by two popularly used mood stabilizer, lithium (N = 13; 30 ± 9 years) and valproate (N = 16; 33 ± 8 years), as well as healthy controls (HC; N = 16; 29 ± 7 years). Two emotional tasks were applied in this study: one used emotional pictures of everyday objects and scenes, and another used emotional facial expression pictures. The main findings were that BD on lithium showed increased fMRI activation in the right dorsal anterior cingulate cortex and bilateral lingual gyrus in response to the positive pictures relative to neutral pictures compared with BD on valproate and HC. Besides, no abnormal activation was observed in the amygdala. Limitations of this study comprise the small sample size and the cross-sectional design. Therefore, the results were suggestive of a different effect of lithium and valproate on brain activities during emotion processing but no causal role can be proposed. The enduring impairments in euthymic state could provide clues to the brain regions involved in the primary pathology of BD.

Alterations in regional homogeneity of resting-state brain activity in patients with major depressive disorder screening positive on the 32-item hypomania checklist (HCL-32).

BACKGROUND: Bipolar disorder (BD) is difficult to diagnose in the early stages of the illness, with the most frequent misdiagnosis being major depressive disorder (MDD). We aimed to use a regional homogeneity (ReHo) approach with resting-state functional magnetic resonance imaging (rs-fMRI) to investigate the features of spontaneous brain activity in MDD patients screening positive on the 32-item Hypomania Checklist (HCL-32). METHODS: Nineteen MDD patients screening positive (HCL-32(+); 9 males; 24.9±5.7 years) and 18 patients screening negative (HCL-32(-); 9 males; 27.1±6.7 years), together with 24 healthy controls (HC; 11 males; 26.4±3.9 years) were studied. ReHo maps were compared and an receiver operating characteristic (ROC) analysis was conducted to confirm the utility of the identified ReHo differences in classifying the patients. RESULTS: The MDD versus HC showed different ReHo in many brain areas, especially in the frontal and parietal cortex. The HCL-32(+) versus HCL-32(-) showed significant increase of ReHo in the right medial superior frontal cortex, left inferior parietal cortex and middle/inferior temporal cortex, and decrease of ReHo in the left postcentral cortex and cerebellum. ROC analysis showed good sensitivity and specificity for distinguishing these two subgroups of MDD. LIMITATIONS: Recruited patients were all on antidepressants and standard mania rating scales were not performed to assess their hypomanic symptoms. CONCLUSIONS: The rs-fMRI measurement of ReHo in distributed brain regions may be putative biomarkers which could differentiate subthreshold BD from MDD.

Evaluation of Mood Disorder Questionnaire (MDQ) in patients with mood disorders: a multicenter trial across China.

BACKGROUND: The aim of this study was to test the ability of the Chinese version of the Mood Disorder Questionnaire (MDQ) to identify Bipolar Disorders (BD) in patients diagnosed with Major Depressive Disorder (MDD) or Unipolar Disorder (UD) in the clinical setting. METHODS: 1,487 being treated for MDD or UD at 12 mental health centers across China, completed the MDQ and subsequently examined by the Mini International Neuropsychiatric Interview (MINI). Receiver Operating Characteristic(ROC) curves were used to determine the ability of the MDQ to differentiate between BD (BD, BD-I and BD-II) and MDD or UD and patients with BD-I from patients with BD-II. RESULTS: Of the 1,487 patients, 309 (20.8%) satisfied the DSM-IV criteria for BD: 118 (7.9%) for BD-I and 191 (12.8%) for BD-II. When only part one of the MDQ was used, the best cutoff was 7 between BD and UD (sensitivity 0.66, specificity 0.88, positive predictive value 0.59, negative predictive value 0.91), 6 between BD-II and UD, and 10 between BD-I and BD-II. If all three parts of the MDQ were used, the MDQ could not distinguish between BD and UD at a cutoff of 7 (or 6), and the sensitivity was only 0.22 (or 0.24). CONCLUSION: The Chinese version of the MDQ had good psychometric features in screening bipolar disorders from depressive patients with mood disorders when part two and part three of the MDQ were ignored.

Kallikrein gene transfer induces angiogenesis and further improves regional cerebral blood flow in the early period after cerebral ischemia/reperfusion in rats.

AIMS: The aims of this study were to find out whether kallikrein could induce angiogenesis and affect the cerebral blood flow (rCBF) in the early period after cerebral ischemia/reperfusion (CI/R). METHODS: The adenovirus carried human tissue kallikrein (HTK) gene was administrated into the periinfarction region after CI/R. At 12, 24, and 72 h after treatments, neurological deficits were evaluated; expression of HTK and vascular endothelial growth factor (VEGF) were detected by immunohistochemistry staining; the infarction volume was measured; and rCBF was examined by( 14) C-iodoantipyrine microtracing technique. RESULTS: The expression of VEGF was enhanced significantly in pAdCMV-HTK group than controls over all time points (P < 0.05). Furthermore, the rCBF in pAdCMV-HTK group increased markedly than controls at 24 and 72 h after treatment (P < 0.05), and the improved neurological deficit was accompanied by reduced infarction volume in pAdCMV-HTK group 24 and 72 h posttreatment. CONCLUSION: In the early period after CI/R, kallikrein could induce the angiogenesis and improve rCBF in periinfarction region, and further reduce the infarction volume and improve the neurological deficits.