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Dynamic Altered Amplitude of Low-Frequency Fluctuations in Patients With Major Depressive Disorder.

ABSTRACT: Background: Major depressive disorder (MDD) has demonstrated abnormalities of static intrinsic brain activity measured by amplitude of low-frequency fluctuation (ALFF). Recent studies regarding the resting-state functional magnetic resonance imaging (rs-fMRI) have found the brain activity is inherently dynamic over time. Little is known, however, regarding the temporal dynamics of local neural activity in MDD. Here, we investigated whether temporal dynamic changes in spontaneous neural activity are influenced by MDD. Methods: We recruited 81 first-episode, drug-naive MDD patients and 64 age-, gender-, and education-matched healthy controls who underwent rs-fMRI. A sliding-window approach was then adopted for the estimation of dynamic ALFF (dALFF), which was used to measure time-varying brain activity and then compared between the two groups. The relationship between altered dALFF variability and clinical variables in MDD patients was also analyzed. Results: MDD patients showed increased temporal variability (dALFF) mainly focused on the bilateral thalamus, the bilateral superior frontal gyrus, the right middle frontal gyrus, the bilateral cerebellum posterior lobe, and the vermis. Furthermore, increased dALFF variability values in the right thalamus and right cerebellum posterior lobe were positively correlated with MDD symptom severity. Conclusions: The overall results suggest that altered temporal variability in corticocerebellar-thalamic-cortical circuit (CCTCC), involved in emotional, executive, and cognitive, is associated with drug-naive, first-episode MDD patients. Moreover, our study highlights the vital role of abnormal dynamic brain activity in the cerebellar hemisphere associated with CCTCC in MDD patients. These findings may provide novel insights into the pathophysiological mechanisms of MDD.

SUBMITTER: Zheng R

PROVIDER: S-EPMC8328277 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background Insomnia is considered one of the manifestations of sleep disorders, and its intensity is linked to the treatment effect or suicidal thoughts. Major depressive disorder (MDD) is classified into various subtypes due to heterogeneous symptoms. Melancholic MDD has been considered one of the most common subtypes with special sleep features. However, the brain functional mechanisms in melancholic MDD with insomnia remain unclear. Materials and methods Melancholic MDD and healthy controls (HCs, n = 46) were recruited for the study. Patients were divided into patients with melancholic MDD with low insomnia (mMDD-LI, n = 23) and patients with melancholic MDD with high insomnia (mMDD-HI, n = 30), according to the sleep disturbance subscale of the 17-item Hamilton Depression Rating Scale. The dynamic amplitude of low-frequency fluctuation was employed to investigate the alterations of brain activity among the three groups. Then, the correlations between abnormal dALFF values of brain regions and the severity of symptoms were investigated. Results Lower dALFF values were found in the mMDD-HI group in the right middle temporal gyrus (MTG)/superior temporal gyrus (STG) than in the mMDD-LI (p = 0.014) and HC groups (p < 0.001). Melancholic MDD groups showed decreased dALFF values than HC in the right middle occipital gyri (MOG)/superior occipital gyri (SOG), the right cuneus, the bilateral lingual gyrus, and the bilateral calcarine (p < 0.05). Lower dALFF values than HC in the left MOG/SOG and the left cuneus in melancholic MDD groups were found, but no significant difference was found between the mMDD-LI group and HC group (p = 0.079). Positive correlations between the dALFF values in the right MTG/STG and HAMD-SD scores (the sleep disturbance subscale of the HAMD-17) in the mMDD-HI group (r = 0.41, p = 0.042) were found. In the pooled melancholic MDD, the dALFF values in the right MOG/SOG and the right cuneus (r = 0.338, p = 0.019), the left MOG/SOG and the left cuneus (r = 0.299, p = 0.039), and the bilateral lingual gyrus and the bilateral calcarine (r = 0.288, p = 0.047) were positively correlated with adjusted HAMD scores. Conclusion The occipital cortex may be related to depressive symptoms in melancholic MDD. Importantly, the right MTG/STG may play a critical role in patients with melancholic MDD with more severe insomnia.

Project description:Temporal neural synchrony disruption can be linked to a variety of symptoms of major depressive disorder (MDD), including mood rigidity and the inability to break the cycle of negative emotion or attention biases. This might imply that altered dynamic neural synchrony may play a role in the persistence and exacerbation of MDD symptoms. Our study aimed to investigate the changes in whole-brain dynamic patterns of the brain functional connectivity and activity related to depression using the hidden Markov model (HMM) on resting-state functional magnetic resonance imaging (rs-fMRI) data. We compared the patterns of brain functional dynamics in a large sample of 314 patients with MDD (65.9% female; age (mean ± standard deviation): 35.9 ± 13.4) and 498 healthy controls (59.4% female; age: 34.0 ± 12.8). The HMM model was used to explain variations in rs-fMRI functional connectivity and averaged functional activity across the whole-brain by using a set of six unique recurring states. This study compared the proportion of time spent in each state and the average duration of visits to each state to assess stability between different groups. Compared to healthy controls, patients with MDD showed significantly higher proportional time spent and temporal stability in a state characterized by weak functional connectivity within and between all brain networks and relatively strong averaged functional activity of regions located in the somatosensory motor (SMN), salience (SN), and dorsal attention (DAN) networks. Both proportional time spent and temporal stability of this brain state was significantly associated with depression severity. Healthy controls, in contrast to the MDD group, showed proportional time spent and temporal stability in a state with relatively strong functional connectivity within and between all brain networks but weak averaged functional activity across the whole brain. These findings suggest that disrupted brain functional synchrony across time is present in MDD and associated with current depression severity.

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Dynamic Altered Amplitude of Low-Frequency Fluctuations in Patients With Major Depressive Disorder.

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