Although most knowledge regarding antidepressant effects is at the receptor level, the neurophysiological correlates of these neurochemical changes remain poorly understood. Such an understanding could benefit from elucidation of antidepressant effects at the level of neural circuits, which would be crucial in identifying biomarkers for monitoring treatment efficacy of antidepressants. In this study, we recruited 20 first‐episode drug‐naive major depressive disorder (MDD) patients and performed resting‐state functional magnetic resonance imaging (MRI) scans before and after 8 weeks of treatment with a selective serotonin reuptake inhibitor—escitalopram. Twenty healthy controls (HCs) were also scanned twice with an 8‐week interval. Whole‐brain connectivity was analyzed using a graph‐theory approach—functional connectivity strength (FCS). The analysis of covariance of FCS was used to determine treatment‐related changes. We observed significant group‐by‐time interaction on FCS in the bilateral dorsomedial prefrontal cortex and bilateral hippocampi. Post hoc analyses revealed that the FCS values in the bilateral dorsomedial prefrontal cortex were significantly higher in the MDD patients compared to HCs at baseline and were significantly reduced after treatment; conversely, the FCS values in the bilateral hippocampi were significantly lower in the patients at baseline and were significantly increased after treatment. Importantly, FCS reduction in the dorsomedial prefrontal cortex was significantly correlated with symptomatic improvement. Together, these findings provided evidence that this commonly used antidepressant can selectively modulate the intrinsic network connectivity associated with the medial prefrontal‐limbic system, thus significantly adding to our understanding of antidepressant effects at a circuit level and suggesting potential imaging‐based biomarkers for treatment evaluation in MDD. Hum Brain Mapp 36:768–778, 2015. © 2014 Wiley Periodicals, Inc.

The Effects of Antidepressant Treatment onResting-State Functional Brain Networks inPatients With Major Depressive Disorder

What is dry eye syndrome? Dry eye syndrome (also called keratoconjunctivitis sicca) is a condition in which the amount of aqueous (the watery component of tears) produced by the lacrimal gland is insufficient. You may also experience symptoms of dry eye syndrome if other components of the tears (mucus and lipid) are insufficient. This may occur if you have an eyelid or conjunctival disease, such as blepharitis (inflammation of the eyelids), or when normal blinking is disrupted by neurological or eyelid abnormalities.

Dry eye syndrome.

Background: The pathophysiology of patients with dry eye disease (DED) is associated with abnormal functional connectivity (FC). The present study aims to probe alterations of voxel-wise brain-wide FC in patient with DED at rest in an unbiased way. Method: A total of 20 patients with DED and 23 controls matched by age, sex, and years of education underwent resting-state functional magnetic resonance imaging scans. Global-brain FC (GFC) was adopted to analyze the images. Support vector machine (SVM) was utilized to differentiate the patients from the controls. Results: Compared with the controls, patients with DED exhibited decreased GFC in the right cerebellum lobule VIII/inferior semi-lunar lobule and left thalamus that belonged to the cerebello-thalamo-cortical network. The GFC values in the left thalamus were positively correlated to the illness duration (r = 0.589, p = 0.006) in the patients. Decreased GFC values in the left thalamus could be used to discriminate the patients from the controls with optimal accuracy, sensitivity and specificity (88.37, 85.00, and 91.30%). Conclusions: Our findings indicate that decreased GFC in the brain regions associated with cerebello-thalamo-cortical network may provide a new insight for understanding the pathological changes of FC in DED. GFC values in the left thalamus may be utilized as a potential biomarker to identify the patients from the controls.

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Reduced Global-Brain Functional Connectivity of the Cerebello-Thalamo-Cortical Network in Patients With Dry Eye Disease.

Pathophysiology of dry eye disease and novel therapeutic targets.

Role of ocular surface neurobiology in neuronal-mediated inflammation in dry eye disease

Background: Altered functional connectivity (FC) is related to pathophysiology of patients with cervical dystonia (CD). However, inconsistent results may be obtained due to different selected regions of interest. We explored voxel-wise brain-wide FC changes in patients with CD at rest in an unbiased manner and analyzed their correlations with symptomatic severity using the Tsui scale. Method: A total of 19 patients with CD and 21 sex- and age-matched healthy controls underwent resting-state functional magnetic resonance imaging scans. Global-brain FC (GFC) was applied to analyze the images. Support vector machine was used to distinguish the patients from the controls. Results: Patients with CD exhibited decreased GFC in the right precentral gyrus and right supplementary motor area (SMA) that belonged to the M1-SMA motor network. Significantly negative correlation was observed between GFC values in the right precentral gyrus and symptomatic severity in the patients (r = -0.476, p = 0.039, uncorrected). Decreased GFC values in these two brain regions could be utilized to differentiate the patients from the controls with good accuracies, sensitivities and specificities (83.33, 85.71, and 80.95% in the right precentral gyrus; and 87.59, 89.49, and 85.71% in the right SMA). Conclusions: Our investigation suggests that patients with CD show reduced GFC in brain regions of the M1-SMA motor network and provides further insights into the pathophysiology of CD. GFC values in the right precentral gyrus and right SMA may be used as potential biomarkers to recognize the patients from the controls.

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Reduced Global-Brain Functional Connectivity and Its Relationship With Symptomatic Severity in Cervical Dystonia.

Background Primary blepharospasm (BSP) is one of the most common focal dystonia and its pathophysiological mechanism remains unclear. An unbiased method was used in patients with BSP at rest to observe voxel-wise brain-wide functional connectivity (FC) changes. Method A total of 48 subjects, including 24 untreated patients with BSP and 24 healthy controls, were recruited to undergo functional magnetic resonance imaging (fMRI). The method of global-brain FC (GFC) was adopted to analyze the resting-state fMRI data. We designed the support vector machine (SVM) method to determine whether GFC abnormalities could be utilized to distinguish the patients from the controls. Results Relative to healthy controls, patients with BSP showed significantly decreased GFC in the bilateral superior medial prefrontal cortex/anterior cingulate cortex (MPFC/ACC) and increased GFC in the right postcentral gyrus/precentral gyrus/paracentral lobule, right superior frontal gyrus (SFG), and left paracentral lobule/supplement motor area (SMA), which were included in the default mode network (DMN) and sensorimotor network. SVM analysis showed that increased GFC values in the right postcentral gyrus/precentral gyrus/paracentral lobule could discriminate patients from controls with optimal accuracy, specificity, and sensitivity of 83.33%, 83.33%, and 83.33%, respectively. Conclusion This study suggested that abnormal GFC in the brain areas associated with sensorimotor network and DMN might underlie the pathophysiology of BSP, which provided a new perspective to understand BSP. GFC in the right postcentral gyrus/precentral gyrus/paracentral lobule might be utilized as a latent biomarker to differentiate patients with BSP from controls.

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Voxel-Wise Brain-Wide Functional Connectivity Abnormalities in Patients with Primary Blepharospasm at Rest.

Whether brain function is altered in patients with dry eye disease (DED) remains unclear. Twenty patients with DED and 23 healthy controls (HCs) were scanned using resting-state functional magnetic resonance imaging. Regional homogeneity (ReHo) and support vector machine (SVM) were used to analyze the imaging data. Relative to the HCs, the patients with DED showed significantly increased ReHo values in the left inferior occipital gyrus (IOG), left superior temporal gyrus, and right superior medial prefrontal cortex, and significantly decreased ReHo values in the right superior frontal gyrus/middle frontal gyrus and bilateral middle cingulum (MC). SVM results indicated that the combination of ReHo values in the left MC and the left IOG in distinguishing patients with DED from HCs had a sensitivity of 95.00%, a specificity of 91.30%, and an accuracy of 93.02%. The present study found that the patients with DED had abnormal ReHo values in the limbic-cortical circuits. A combination of ReHo values in the left MC and the left IOG could be applied as a potential imaging biomarker to distinguish patients with DED from HCs. The dysfunction of limbic-cortical circuits may play an important role in the pathophysiology of DED.

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Abnormal Spontaneous Brain Activities of Limbic-Cortical Circuits in Patients With Dry Eye Disease

Objective The purpose of this study was to investigate the characteristics of different frequency bands in the spontaneous brain activity among patients with acute basal ganglia ischemic stroke (BGIS). Methods In the present study, thirty-four patients with acute BGIS and forty-four healthy controls were examined by resting-state functional magnetic resonance imaging (rs-fMRI) from May 2019 to December 2020. Two amplitude methods including amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF) calculated in three frequency bands (conventional frequency band: 0.01-0.08 Hz; slow-5 frequency band: 0.01-0.027 Hz; and slow-4 frequency band: 0.027-0.073 Hz) were conducted to evaluate the spontaneous brain activity in patients with acute BGIS and healthy controls (HCs). Gaussian Random Field Theory (GRF, voxel p < 0.01 and cluster p < 0.05) correction was applied. The correlation analyses were performed between clinical scores and altered metrics values. Results Compared to HCs, patients with acute BGIS showed decreased ALFF in the right supramarginal gyrus (SMG) in the conventional and slow-4 bands, increased fALFF in the right middle frontal gyrus (MFG) in the conventional and slow-4 bands, and increased fALFF in the bilateral caudate in the slow-5 frequency band. The fALFF value of the right caudate in the slow-5 frequency band was negatively correlated with the clinical scores. Conclusion In conclusion, this study showed the alterations in ALFF and fALFF in three frequency bands between patients with acute BGIS and HCs. The results reflected that the abnormal LFO amplitude might be related with different frequency bands and promoted our understanding of pathophysiological mechanism in acute BGIS.

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Wenmei Li

Papers

Reduced Global-Brain Functional Connectivity and Its Relationship With Symptomatic Severity in Cervical Dystonia.

Voxel-Wise Brain-Wide Functional Connectivity Abnormalities in Patients with Primary Blepharospasm at Rest.

Reduced Global-Brain Functional Connectivity of the Cerebello-Thalamo-Cortical Network in Patients With Dry Eye Disease.

Abnormal Spontaneous Brain Activities of Limbic-Cortical Circuits in Patients With Dry Eye Disease

Frequency-Specific Changes of Amplitude of Low-Frequency Fluctuations in Patients with Acute Basal Ganglia Ischemic Stroke