| Part I The fMRI study of asthmatic patients with depressionStudy 1 The spontaneous activity and functional connectivity of insula in asthmatic patients with depressionObjectives: Depression is common in asthmatic patients, and insula is demonstrated associated with depression and asthma. In order to explore the underlying neurobiological mechanism of depression in asthma, the regional homogeneity (ReHo)in insula and functional connectivity (FC) were used to probe the differences between depressed asthma (DA) and non-depressed asthma (NDA) patients.Methods: 18 DA patients, 24 NDA patients and 60 healthy controls (HCs) received the assessments of HDRS-17 and ACT (except HCs), and resting-state functional magnetic resonance imaging (rs-fMRI) scan. Statistical tests of ReHo and FC in insula across groups were performed using a voxel-based ANCOVA. Brain regions which exhibited difference among three groups were further selected as region of interests (ROIs). Mean FC values were extracted within each of these ROIs for further ROC curve analyses.Furthermore, partial correlation coefficients were computed between the extracted insula subregions FC values within these ROIs and the clinical assessments of DA patients.Results: There were no significant differences of ReHo values in insula between three groups. ANCOVA analysis found that the FC between left vAI and left cerebellum posterior lobe, left MTG, bilateral ACC, bilateral parietal lobe increased among three groups. FC between right vAI and left putamen, right caudate also increased among three groups. However, the decreased FC between insula and certain brain regions were not found. DA patients showed increased FC between left vAI and left middle temporal gyrus compared with both NDA and HCs groups, and it could separate DA patients from NDA (AUC = 0.759, P = 0.004) and HCs (AUC = 0.831, P< 0.001). In addition,when compared with HCs, the DA and NDA patients both exhibited increased FC between left vAI with right ACC, decreased FC between left vAI with bilateral parietal lobe, increased FC between right vAI with left putamen and right caudate. Furthermore,the increased FC between left vAI with bilateral ACC could differentiate HCs from both DA patients (AUC = 0.828, P < 0.001) and NDA patients (AUC = 0.709, P =0.003). The increased FC between right vAI with left putamen and right caudate could highlight NDA patients from HCs (AUC = 0.778, P < 0.001). However, significant correlations between altered ReHo or FC values in insula of DA patients were not found in the present study as well as NDA and HCs (all P > 0.05).Conclusions: The current study showed the first evidence of altered vAI FC of depression, which would be involved in the neuropathology of depression in asthma.The increased FC between left vAI with left MTG might be used to distinguish DA from both NDA and HCs groups.Study 2 The cerebral blood flow in asthmatic patients with depressionObjectives: Previous studies suggested that asthma shared certain neural circuits involved in emotion. Abnormal CBF was also reported in patients with dyspnea and depression. In order to understand the neural mechanisms of depression in asthma, we used CBF to probe the difference between DA and NDA patients.Methods: 18 DA patients, 24 NDA patients and 57 HCs received the assessments of HDRS-17 and ACT (except HCs), pASL scan for measuring CBF and rs-fMRI scan.Statistical tests of CBF across groups were performed using a voxel-based ANCOVA.Brain regions which exhibited difference among three groups were further selected as region of interests (ROIs). Mean rCBF values were extracted within each of these ROIs for further ROC curve analyses. Furthermore, partial correlation coefficients were computed between the extracted rCBF values within these ROIs and the clinical assessments of DA patients.Results: ANCOVA analysis found that the rCBF were increased in the right cerebellum posterior lobe among three groups. Compared to NDA, DA patients exhibited increased rCBF in the right cerebellum posterior lobe. Compared to HCs, DA patients showed decreased rCBF in the right cerebellum posterior lobe. NDA also displayed lower rCBF in the right cerebellum posterior lobe than HCs. No significant correlations between rCBF values in right cerebellum posterior lobe and HDRS-17 as well as ACT scores were found both in DA and NDA groups (all P > 0.05). Significant distinguish ability of rCBF values in right cerebellum posterior lobe in ROC analysis was not found between DA and NDA (AUC = 0.591, P = 0.315) or DA and HCs (AUC = 0.369, P =0.096).Conclusions: We uncovered the first evidence of altered rCBF in the right cerebellum posterior lobe of depression in asthma using pASL, which appeared to be involved in the underpinnings of depression in asthma.Part Ⅱ The therapeutic mechanisms study of group cognitive behavior therapy for asthmatic patientsStudy 1 The effectiveness and influence of group cognitive behavior therapy on brain regional homogeneity in asthmatic patientsObjectives: GCBT is an effective treatment in improving self-management behaviors and quality of life for asthmatic patients. However, the effects of GCBT on the underlying neurobiology remain unknown. Therefore, we explored the changes of brain spontaneous activity before and after GCBT in asthma.Methods: 39 asthmatic patients and 60 HCs received assessments of HDRS-17 and ACT (except HCs) and rs-fMRI scan at baseline. In addition, 21 asthamtic patients volunteered to participant an 8 sessions GCBT treatment. There were 17 patients completed the treatment. After GCBT, asthmatic patients received the second assessments of HDRS-17, ACT and rs-fMRI scan at the 8-week period. To explore the ReHo difference between asthmatic patients and HCs, a two-sample t-test was performed on the group zReHo maps in a voxel-by-voxel manner. Then selected the abnormal brain regions at baseline as masks for the further paired-t test. Paired-t test was undertaken between after and before in GBCT group. Pearson’s correlation analyses were then performed to examine correlations between abnormal brain regions’ReHo values and psychological performance of asthmatic patients.Results: Compared to HCs, asthmatic patients shown significantly increased ReHo in the bilateral occipital lobe and sensorimotor cortex. After GCBT, patients exhibited decreased ReHo in above brain regions including bilateral calcarine, bilateral occipital lobe, left paracentral lobule and right sensorimotor cortex. Moreover, significantly higher ACT scores (P < 0.001) and lower HDRS-17 scores (P = 0.001) were found in patients compared with pre-GCBT. Significant correlations between altered ReHo value and HDRS-17 as well as ACT scores were not found in asthmatic patients at baseline (all P > 0.05). After GCBT, the changes of ReHo values in asthmatic patients were not correlated with the changes of HDRS-17 and ACT scores either (all P > 0.05).Conclusions: This study demonstrated that successful GCBT was associated with a reversed effect on the coordination of brain spontaneous activity in occipital lobe and sensorimotor cortex in asthma.Study 2 The effectiveness and influence of group cognitive behavior therapy on insula subregions functional connectivity in asthmatic patientsObjectives: GCBT is an effective treatment in improving self-management behaviors and quality of life for asthmatic patients. However, the mechanisms by which GCBT improves asthma-related clinical symptoms remain unknown. Previous studies have indicated that insula is an important region involved in the neuropathology of asthma.Therefore, we examined the possible alteration of ReHo in insula, FC between its subregions and whole brain respectively before and after GCBT in asthmatic patients.Methods: 42 asthmatic patients and 60 HCs received assessments of HDRS-17, ACT(except HCs) and rs-fMRI scan at baseline. In addition, 21 asthamtic patients volunteered to participant an 8 sessions GCBT treatment, and there were 17 patients completed it. After GCBT, asthmatic patients received the second assessments of HDRS-17, ACT and rs-fMRI scan at the 8-week period. To explore the insula FC difference between asthmatic patients and HCs, a two-sample t-test was performed on the group FC maps. Then selected the abnormal brain regions at baseline as masks for the further paired-t test. Paired-t test was undertaken between after and before GBCT group. Pearson’s correlation analyses were then performed to examine correlations between abnormal brain regions’ FC values and psychological performance of asthmatic patients.Results: Asthmatic patients had greater left vAI FC with the left cerebellum posterior lobe, right MTG and bilateral ACC, but less FC with bilateral postcentral gyrus,bilateral occipital lobe and left precentral gyrus compared with HCs. FC between left PI and left medial frontal gyrus also increased in the patients. In addition, right vAI showed increased FC with right caudate and left putamen. FC between right dAI and left calcarine however decreased. The increase of FC in insula subregions were significantly improved following GCBT. FC between the left vAI connectivity and left postcentral gyrus was positively correlated with the percentage of improvement in HDRS-17 scores (r = 0.481, P = 0.05), and FC between the right dAI and left calcarine was negatively associated with the improvement percentage in ACT scores (r = 0.481,P=0.05).Conclusions: This study in the first time demonstrated that GCBT led to significant improvement of FC between insula subregions and other brain regions. |
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