Abnormality of anxious behaviors and functional connectivity between the amygdala and the frontal lobe in maternally deprived monkeys.

OBJECTIVE: Anxious behaviors often occur in individuals who have experienced early adversity. Anxious behaviors can bring many hazards, such as social withdrawal, eating disorders, negative self-efficacy, self-injurious thoughts and behaviors, anxiety disorders, and even depression. Abnormal behavior are is closely related to changes in corresponding circuit functions in the brain. This study investigated the relationship between brain circuits and anxious behaviors in maternal-deprived rhesus monkey animal model, which mimic early adversity in human. METHODS: Twenty-five rhesus monkeys (Macaca mulatta) were grouped by two different rearing conditions: 11 normal control and mother-reared (MR) monkeys and 14 maternally deprived and peer-reared (MD) monkeys. After obtaining images of the brain areas with significant differences in maternal separation and normal control macaque function, the relationship between functional junction intensity and stereotypical behaviors was determined by correlation analysis. RESULTS: The correlation analysis revealed that stereotypical behaviors were negatively correlated with the coupling between the left lateral amygdala subregion and the left inferior frontal gyrus in both MD and MR macaques. CONCLUSION: This study suggests that early adversity-induced anxious behaviors are associated with changes in the strength of the amygdala-prefrontal connection. The normalization of the regions involved in the functional connection might reverse the behavioral abnormality. It provides a solid foundation for effective intervention in human early adversity. SIGNIFICANCE STATEMENT: This study suggests that early adversity-induced anxious behaviors are associated with changes in the strength of the amygdala-prefrontal connection. The higher the amygdala-prefrontal connection strength, the less stereotyped behaviors exhibited by monkeys experiencing early adversity. Thus, in the future, changing the strength of the amygdala-prefrontal connection may reverse the behavioral abnormalities of individuals who experience early adversity. This study provides a solid foundation for effective intervention in humans' early adversity.

Prolonged Longitudinal Transcutaneous Auricular Vagus Nerve Stimulation Effect on Striatal Functional Connectivity in Patients with Major Depressive Disorder.

BACKGROUND: Transcutaneous auricular vagus nerve stimulation (taVNS) is effective for treating major depressive disorder (MDD). We aimed to explore the modulating effect of prolonged longitudinal taVNS on the striatal subregions' functional connectivity (FC) in MDD patients. METHODS: Sixteen MDD patients were enrolled and treated with taVNS for 8 weeks. Sixteen healthy control subjects (HCs) were recruited without intervention. The resting-state FC (rsFC) based on striatal subregion seed points and the Hamilton Depression Scale (HAMD) were evaluated in the MDD patients and HCs at baseline and after 8 weeks. A two-way ANCOVA test was performed on each rsFC metric to obtain the (group-by-time) interactions. RESULTS: The rsFC values between the left ventral caudate (vCa) and right ventral prefrontal cortex (vPFC), and between the right nucleus accumbens (NAc) and right dorsal medial prefrontal cortex (dmPFC) and ventrolateral prefrontal cortex (vlPFC) are lower in the MDD patients compared to the HCs at baseline, and increase following taVNS; the rsFC values between the left vCa and right, superior occipital gyrus (SOG), and between the left dorsal caudate (dCa) and right cuneus are higher in MDD patients and decrease following taVNS. CONCLUSIONS: Prolonged longitudinal taVNS can modulate the striatum rsFC with the prefrontal cortex, occipital cortex, temporal cortex, and intra-striatum, and these changes partly underlie any symptomatic improvements. The results indicate that prolonged longitudinal taVNS may produce beneficial treatment effects by modulating the cortical striatum circuitry in patients with MDD.

MonkeyTrail: A scalable video-based method for tracking macaque movement trajectory in daily living cages.

Behavioral analysis of macaques provides important experimental evidence in the field of neuroscience. In recent years, video-based automatic animal behavior analysis has received widespread attention. However, methods capable of extracting and analyzing daily movement trajectories of macaques in their daily living cages remain underdeveloped, with previous approaches usually requiring specific environments to reduce interference from occlusion or environmental change. Here, we introduce a novel method, called MonkeyTrail, which satisfies the above requirements by frequently generating virtual empty backgrounds and using background subtraction to accurately obtain the foreground of moving animals. The empty background is generated by combining the frame difference method (FDM) and deep learning-based model (YOLOv5). The entire setup can be operated with low-cost hardware and can be applied to the daily living environments of individually caged macaques. To test MonkeyTrail performance, we labeled a dataset containing >8 000 video frames with the bounding boxes of macaques under various conditions as ground-truth. Results showed that the tracking accuracy and stability of MonkeyTrail exceeded that of two deep learning-based methods (YOLOv5 and Single-Shot MultiBox Detector), traditional frame difference method, and naïve background subtraction method. Using MonkeyTrail to analyze long-term surveillance video recordings, we successfully assessed changes in animal behavior in terms of movement amount and spatial preference. Thus, these findings demonstrate that MonkeyTrail enables low-cost, large-scale daily behavioral analysis of macaques.

Abnormal Degree Centrality of Bilateral Putamen and Left Superior Frontal Gyrus in Schizophrenia with Auditory Hallucinations: A Resting-state Functional Magnetic Resonance Imaging Study.

BACKGROUND: Dysconnectivity hypothesis of schizophrenia has been increasingly emphasized. Recent researches showed that this dysconnectivity might be related to occurrence of auditory hallucination (AH). However, there is still no consistent conclusion. This study aimed to explore intrinsic dysconnectivity pattern of whole-brain functional networks at voxel level in schizophrenic with AH. METHODS: Auditory hallucinated patients group (n = 42 APG), no hallucinated patients group (n = 42 NPG) and normal controls (n = 84 NCs) were analyzed by resting-state functional magnetic resonance imaging. The functional connectivity metrics index (degree centrality [DC]) across the entire brain networks was calculated and evaluated among three groups. RESULTS: DC decreased in the bilateral putamen and increased in the left superior frontal gyrus in all the patients. However, in APG, the changes of DC were more obvious compared with NPG. Symptomology scores were negatively correlated with the DC of bilateral putamen in all patients. AH score of APG positively correlated with the DC in left superior frontal gyrus but negatively correlated with the DC in bilateral putamen. CONCLUSION: Our findings corroborated that schizophrenia was characterized by functional dysconnectivity, and the abnormal DC in bilateral putamen and left superior frontal gyrus might be crucial in the occurrence of AH.

Discriminating Bipolar Disorder From Major Depression Based on SVM-FoBa: Efficient Feature Selection With Multimodal Brain Imaging Data.

Discriminating between bipolar disorder (BD) and major depressive disorder (MDD) is a major clinical challenge due to the absence of known biomarkers; hence a better understanding of their pathophysiology and brain alterations is urgently needed. Given the complexity, feature selection is especially important in neuroimaging applications, however, feature dimension and model understanding present serious challenges. In this study, a novel feature selection approach based on linear support vector machine with a forward-backward search strategy (SVM-FoBa) was developed and applied to structural and resting-state functional magnetic resonance imaging data collected from 21 BD, 25 MDD and 23 healthy controls. Discriminative features were drawn from both data modalities, with which the classification of BD and MDD achieved an accuracy of 92.1% (1,000 bootstrap resamples). Weight analysis of the selected features further revealed that the inferior frontal gyrus may characterize a central role in BD-MDD differentiation, in addition to the default mode network and the cerebellum. A modality-wise comparison also suggested that functional information outweighs anatomical by a large margin when classifying the two clinical disorders. This work validated the advantages of multimodal joint analysis and the effectiveness of SVM-FoBa, which has potential for use in identifying possible biomarkers for several mental disorders.

Proton magnetic resonance spectroscopy predicts radiotherapy response and time-to-progression in high-grade gliomas after surgery.

BACKGROUND: Reliable early prediction response to therapy and time-to-progression (TTP) remain an important goal of high-grade gliomas (HGGs) research. Proton magnetic resonance spectroscopy ((1)H-MRS) has been applied with variable success in clinical application, and we hypothesize that (1)H-MRS in predictive value should perform well as a marker of TTP in patients treated with radiotherapy (RT) after surgery. METHODS: (1)H-MRS was performed before surgery on 25 patients who had undergone resection of HGGs; then the ratios of lipid/creatine (Lip/Cr) and myo-inositol/creatine (mI/Cr) were determined in the solid tumor. RT response was classified as follows: complete resolution (CR), partial response (PR), stable disease (SD), and progressive disease (PD) by comparison of pre-treatment and post-radiotherapy scans. TTP was defined at the time to radiographic progression by MacDonald criteria. Correlation was evaluated between the ratios of Lip/Cr, mI/Cr and treatment response, TTP. The chi-square test and Pearson correlation test were used for data analyses. RESULTS: Multivariate analysis revealed that the prognostic value of spectroscopic variables was independent of age, sex, WHO histologic grade, extent of surgery, and Karnofsky score (KPS). The correlation between the ratios of lipid/Cr and TTP was significant (r = 0.894, P = 0.000), and between the ratios of mI/Cr and TTP was also significant (r = 0.891, P = 0.000). As predicted, RT response correlated significantly with TTP (r = 0.59, P = 0.002): median TTP was 49.9 days for patients with PD compared with 202.7 days for SD, 208.0 days for PR, and 234.5 days for CR. CONCLUSION: The ratios of Lip/Cr and mI/Cr of the solid tumor region before surgery could provide important information in predicting RT response and TTP in patients with HGGs treated by radiation alone after surgery.

[A diffusion tensor magnetic resonance imaging for studying white matter changes in patients with mild cognitive impairment.].

OBJECTIVES: To measure the microstructural differences in the brains of participants with amnestic mild cognitive impairment (aMCI) and compare with a control group using a magnetic resonance diffusion tensor imaging (DTI) technique with fully automated image analysis tools. METHODS: A standardized clinical and neuropsychological evaluation was conducted on each subject. 31 participants (15 participants with aMCI, 16 healthy elderly adults) underwent magnetic resonance imaging (MRI)-based DTI. To control the effects of anatomical variation, the diffusion images of all participants were registered to standard anatomical space. Voxel-by-voxel comparisons showed significant regional reductions in white matter regions of fractional anisotropy (FA) in the participants with aMCI as compared with the controls. RESULTS: Significantly decreased FA value measurements (P < 0.001) were observed in the right frontal white matter in participants with aMCI. Moreover, there was a statistically significant difference between the patients with aMCI and controls in considering the small regions of bilateral superior frontal gyrus white matter (P < 0.001). CONCLUSIONS: White matter damage of frontal lobe may play an important role in histopathologic changes associated with amnestic mild cognitive impairment.

Default mode network as revealed with multiple methods for resting-state functional MRI analysis.

Recently, human brain activity during a resting-state has attracted increasing attention. Several studies have found that there are two networks: the default mode network and its anti-correlation network. Some studies have subsequently showed that the functions of brain areas within the default mode network are crucial in human mental activity. To further discern the brain default mode network as well as its anti-correlation network during resting-state, we used three methods to analyze resting-state functional magnetic resonance imaging (fMRI) data; regional homogeneity analysis, linear correlation and independent component analysis, on four groups of dataset. Our results showed the existence of these two networks prominently and consistently during a resting- and conscious-state across the three methods. This consistency was exhibited in four independent groups of normal adults. Moreover, the current results provided evidences that the brain areas within the two anti-correlated networks are highly integrated at both the intra- and inter-regional level.

Fisher discriminative analysis of resting-state brain function for attention-deficit/hyperactivity disorder.

In this study, a resting-state fMRI based classifier, for the first time, was proposed and applied to discriminate children with attention-deficit/hyperactivity disorder (ADHD) from normal controls. On the basis of regional homogeneity (ReHo), a mapping of brain function at resting state, PCA-based Fisher discriminative analysis (PC-FDA) was trained to build a linear classifier. Permutation test was then conducted to identify the brain areas with the most significant contribution to the final discrimination. Experimental results showed a correct classification rate of 85% using a leave-one-out cross-validation. Moreover, some highly discriminative brain regions, like the prefrontal cortex and anterior cingulate cortex, well confirmed the previous findings on ADHD. Interestingly, some important but less reported regions such as the thalamus were also identified. We conclude that the classifier, using resting-state brain function as classification feature, has potential ability to improve current diagnosis and treatment evaluation of ADHD.

Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI.

In children with attention deficit hyperactivity disorder (ADHD), functional neuroimaging studies have revealed abnormalities in various brain regions, including prefrontal-striatal circuit, cerebellum, and brainstem. In the current study, we used a new marker of functional magnetic resonance imaging (fMRI), amplitude of low-frequency (0.01-0.08Hz) fluctuation (ALFF) to investigate the baseline brain function of this disorder. Thirteen boys with ADHD (13.0+/-1.4 years) were examined by resting-state fMRI and compared with age-matched controls. As a result, we found that patients with ADHD had decreased ALFF in the right inferior frontal cortex, [corrected] and bilateral cerebellum and the vermis as well as increased ALFF in the right anterior cingulated cortex, left sensorimotor cortex, and bilateral brainstem. This resting-state fMRI study suggests that the changed spontaneous neuronal activity of these regions may be implicated in the underlying pathophysiology in children with ADHD.

[Diffusion tensor imaging of the normal-appearing brain tissue in relapsing-remitting multiple sclerosis].

OBJECTIVE: To investigate whether normal-appearing brain tissue (NABT) on conventional MRI has occult damage in patients with relapsing-remitting multiple sclerosis (RRMS) by using diffusion tensor imaging (DTI) histogram analysis, and to determine the correlations between DTI histogram-derived measures of the NABT and expanded disability status scale (EDSS) scores, disease durations, T2WI lesion volumes and brain tissue volumes in RRMS patients. METHODS: Conventional MRI and DTI scans were performed in 24 patients with RRMS and 24 sex- and age-matched healthy controls. After segmentation of the NABT, the mean diffusivity (MD) and fractional anisotropy (FA) histograms of the NABT were created and analyzed. RESULTS: In patients with RRMS, the average MD (1.014 x 10(-3) mm2 x s(-1)) of the NABT was higher than that (0.910 x 10(-3) mm2 x s(-1)) of control subjects (t = 7.238, P < 0.001); the MD histogram peak height (8.858 per thousand) of the NABT was lower than that (0.767 per thousand) of control subjects (t = 6.161, P < 0.001); the MD histogram peak location (0.809 x 10(-3) mm2 x s(-1)) of the NABT was higher than that (0.767 x 10(-3) mm2 x s(-1)) of control subjects (t = 5.324, P < 0.001); the average FA (0.231) of the NABT was lower than that (0.254) of control subjects (t = 6.217, P < 0.001); the FA histogram peak height (4.502 per thousand) of the NABT was higher than that (4.107 per thousand) of control subjects (t = 4.198, P < 0.001); no significant difference was found in the FA histogram peak location of the NABT between these two groups (t = 1.223, P = 0.227); none of the DTI histogram-derived measures correlated with EDSS scores or disease durations (P > 0.05); the average MD and all the FA histogram-derived measures correlated with T2WI lesion volumes (P < 0.05); and the average MD, the MD histogram peak height and all the FA histogram-derived measures correlated with brain tissue volumes (P < 0.05). In healthy controls, however, only the average FA of the NABT correlated with brain tissue volumes. CONCLUSION: Patients with RRMS had occult damage in the NABT and the extent of NABT damage was related to the lesion load of brain and to the extent of brain tissue atrophy.

Finding potential ligands for PDZ domains by tailfit, a JAVA program.

OBJECTIVE: To deduce all potential ligands undiscovered experimentally by searching all the proteins containing same C-termini, which can bind a certain PDZ domain. METHODS: We developed a JAVA program for searching short exact sequence matches at C-terminus. According to the known C-termini, which PDZ domains recognized experimentally, Swissprot database has been searched by this program for all potential ligands. RESULTS: Some PDZ domains may have more potential ligand proteins, which are undiscovered yet experimentally. These bioinformatic results also provide clues for studying functions of hypothetical proteins and PDZ domains' protein interactions in many different organisms. CONCLUSION: The results may provide useful clues for discovering potential functions of hypothetical proteins and new functions of known proteins.