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Objective: In order to examine whether individualized peak functional connectivity could potentially serve as a target for repetitive transcranial magnetic stimulation (rTMS) therapy, we investigated the location of peak functional connectivity (FC) between the cortical motor area and the key brain region, the globus pallidus internus (GPi), in Tourette syndrome, and explored the relationship between the severity of the disease and these aberrant functional connections., Methods: The study involved a cohort of 103 children diagnosed with Tourette syndrome and 66 age-matched typically developing children. The GPi was served as the seed, and the study compared individualized peak FC strength in the supplementary motor area (SMA) and premotor area between the two groups. Spatial distribution of peak FC in the motor area and GPi-based voxel-wise FC were also analyzed., Results: Children with Tourette syndrome exhibited lower peak FC in the left SMA when using left GPi as the seed. This reduction in peak FC demonstrated a significant and negative correlation with the Yale Global Tic Severity Scale scores., Conclusions: SMA-GPi FC is one of the key pathological circuit in Tourette syndrome., Significance: The individual peak FC location in the left SMA potentially serve as stimulation targets for rTMS treatment of TS., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Autism spectrum disorder (ASD) is a behaviorally defined complex neurodevelopmental syndrome characterized by persistent social communication and interaction deficit. Transcranial magnetic stimulation (TMS) is a promising and emerging tool for the intervention of ASD by reducing both core and associate symptoms. Several reviews have been published regarding TMS-based ASD treatment, however, a systematic review on study characteristics, specific stimulating parameters, localization techniques, stimulated targets, behavioral outcomes, and neuroimage biomarker changes is lagged behind since 2018. Here, we performed a systematic search on literatures published after 2018 in PubMed, Web of Science, and Science Direct. After screening, the final systematic review included 17 articles, composing seven randomized controlled trial studies and ten open-label studies. Two studies are double-blind, while the other studies have a moderate to high risk of bias attributing to inadequate subject- and evaluator-blinding to treatment allocation. Five studies utilize theta-burst stimulation mode, and the others apply repetitive TMS with low frequency (five studies), high frequency (six studies), and combined low and high frequency stimulation (one study). Most researchers prioritize the bilateral dorsolateral prefrontal lobe as stimulation target, while parietal lobule, inferior parietal lobule, and posterior superior temporal sulci have also emerged as new targets of attention. One third of the studies use neuronavigation based on anatomical magnetic resonance imaging to locate the stimulation target. After TMS intervention, discernible enhancements across a spectrum of scales are evident in stereotyped behavior, repetitive behavior, and verbal social domains. A comprehensive review of literature spanning the last five years demonstrates the potential of TMS treatment for ASD in ameliorating the clinical core symptoms., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Li-xia Yuan reports article publishing charges was provided by Special Project for Research and Development in Key Areas of Guangdong Province. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Recent advances in open neuroimaging data are enhancing our comprehension of neuropsychiatric disorders. By pooling images from various cohorts, statistical power has increased, enabling the detection of subtle abnormalities and robust associations, and fostering new research methods. Global collaborations in imaging have furthered our knowledge of the neurobiological foundations of brain disorders and aided in imaging-based prediction for more targeted treatment. Large-scale magnetic resonance imaging initiatives are driving innovation in analytics and supporting generalizable psychiatric studies. We also emphasize the significant role of big data in understanding neural mechanisms and in the early identification and precise treatment of neuropsychiatric disorders. However, challenges such as data harmonization across different sites, privacy protection, and effective data sharing must be addressed. With proper governance and open science practices, we conclude with a projection of how large-scale imaging resources and collaborations could revolutionize diagnosis, treatment selection, and outcome prediction, contributing to optimal brain health., (Copyright © 2024 Science China Press. Published by Elsevier B.V. All rights reserved.)

US Food and Drug Administration (FDA) cleared a Transcranial Magnetic Stimulation (TMS) system with functional Magnetic Resonance Imaging-guided (fMRI) individualized treatment protocol for major depressive disorder, which employs resting state-fMRI (RS-fMRI) functional connectivity (FC) to pinpoint the target individually to increase the accuracy and effeteness of the stimulation. Furthermore, task activation-guided TMS, as well as the use of RS-fMRI local metrics for targeted the specific abnormal brain regions, are considered a precise scheme for TMS targeting. Since 1.5 T MRI is more available in hospitals, systematic evaluation of the test-retest reliability and sensitivity of fMRI metrics on 1.5 T and 3 T MRI may provide reference for the application of fMRI-guided individualized-precise TMS stimulation. Twenty participants underwent three RS-fMRI scans and one scan of finger-tapping task fMRI with self-initiated (SI) and visual-guided (VG) conditions at both 3 T and 1.5 T. Then the location reliability derived by FC (with three seed regions) and peak activation were assessed by intra-individual distance. The test-retest reliability and sensitivity of five RS-fMRI local metrics were evaluated using intra-class correlation and effect size, separately. The intra-individual distance of peak activation location between 1.5 T and 3 T was 15.8 mm and 19 mm for two conditions, respectively. The intra-individual distance for the FC derived targets at 1.5 T was 9.6-31.2 mm, compared to that of 3 T (7.6-31.1 mm). The test-retest reliability and sensitivity of RS-fMRI local metrics showed similar trends on 1.5 T and 3 T. These findings hasten the application of fMRI-guided individualized TMS treatment in clinical practice., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Impaired basic academic skills (e.g., word recognition) are common in children with Attention Deficit Hyperactivity Disorder (ADHD). The underlying neuropsychological and neural correlates of impaired Chinese reading skills in children with ADHD have not been substantially explored. Three hundred and two children with ADHD (all medication-naïve) and 105 healthy controls underwent the Chinese language skill assessment, and 175 also underwent fMRI scans (84 ADHD and 91 controls). Between-group and mediation analyses were applied to explore the interrelationships of the diagnosis of ADHD, cognitive dysfunction, and impaired reading skills. Five ADHD-related brain functional networks, including the default mode network (DMN) and the dorsal attention network (DAN), were built using predefined regions of interest. Voxel-based group-wise comparisons were performed. The ADHD group performed worse than the control group in word-level reading ability tests, with lower scores in Chinese character recognition (CR) and word chains (WS) (all P < 0.05). With full-scale IQ and sustained attention in the mediation model, the direct effect of ADHD status on the CR score became insignificant (P = 0.066). The underlying neural correlates for the orthographic knowledge (OT) and CR differed between the ADHD and the control group. The ADHD group tended to recruit more DMN regions to maintain their reading performance, while the control group seemed to utilize more DAN regions. Children with ADHD generally presented impaired word-level reading skills, which might be caused by impaired sustained attention and lower IQ. According to the brain functional results, we infer that ADHD children might utilize a different strategy to maintain their orthographic knowledge and character recognition performance., (© 2024. The Author(s).)

Parietal alpha activity shows a specific pattern of phasic changes during working memory. It decreases during the encoding and recall phases but increases during the maintenance phase. This study tested whether online rTMS delivered to the parietal cortex during the maintenance phase of a working memory task would increase alpha activity and hence improve working memory. Then, 46 healthy volunteers were randomly assigned to two groups to receive 3-day parietal 10 Hz online rTMS (either real or sham, 3600 pulses in total) that were time-locked to the maintenance phase of a spatial span task (180 trials in total). Behavioral performance on another spatial span task and EEG signals during a change detection task were recorded on the day before the first rTMS (pretest) and the day after the last rTMS (posttest). We found that rTMS improved performance on both online and offline spatial span tasks. For the offline change detection task, rTMS enhanced alpha activity within the maintenance phase and improved interference control of working memory at both behavioral (K score) and neural (contralateral delay activity) levels. These results suggested that rTMS with alpha frequency time-locked to the maintenance phase is a promising way to boost working memory., (© 2024 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Background: The social motivation hypothesis proposes that the social deficits of autism spectrum disorder (ASD) are related to reward system dysfunction. However, functional connectivity (FC) patterns of the reward network in ASD have not been systematically explored yet., Methods: The reward network was defined as eight regions of interest (ROIs) per hemisphere, including the nucleus accumbens (NAc), caudate, putamen, anterior cingulate cortex (ACC), ventromedial prefrontal cortex (vmPFC), orbitofrontal cortex (OFC), amygdala, and insula. We computed both the ROI-wise resting-state FC and seed-based whole-brain FC in 298 ASD participants and 348 typically developing (TD) controls from the Autism Brain Imaging Data Exchange I dataset. Two-sample t-tests were applied to obtain the aberrant FCs. Then, the association between aberrant FCs and clinical symptoms was assessed with Pearson's correlation or Spearman's correlation. In addition, Neurosynth Image Decoder was used to generate word clouds verifying the cognitive functions of the aberrant pathways. Furthermore, a three-way multivariate analysis of variance (MANOVA) was conducted to examine the effects of gender, subtype and age on the atypical FCs., Results: For the within network analysis, the left ACC showed weaker FCs with both the right amygdala and left NAc in ASD compared with TD, which were negatively correlated with the Autism Diagnostic Observation Schedule (ADOS) total scores and Social Responsiveness Scale (SRS) total scores respectively. For the whole-brain analysis, weaker FC (i.e., FC between the left vmPFC and left calcarine gyrus, and between the right vmPFC and left precuneus) accompanied by stronger FC (i.e., FC between the left caudate and right insula) were exhibited in ASD relative to TD, which were positively associated with the SRS motivation scores. Additionally, we detected the main effect of age on FC between the left vmPFC and left calcarine gyrus, of subtype on FC between the right vmPFC and left precuneus, of age and age-by-gender interaction on FC between the left caudate and right insula., Conclusions: Our findings highlight the crucial role of abnormal FC patterns of the reward network in the core social deficits of ASD, which have the potential to reveal new biomarkers for ASD., Competing Interests: Declaration of competing interest The authors report that they have no financial conflicts of interest with respect to the content of this manuscript., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Inattention is a key characteristic of attention deficit hyperactivity disorder (ADHD). Specific brain abnormalities associated with this symptom form a discernible pattern related with ADHD in children (i.e., ADHD related pattern) in our earlier research. The developmental processes of segregation and integration may be crucial to ADHD. However, how brains reconfigure these processes of the ADHD related pattern in different subtypes of ADHD and across sexes remain unclear., Methods: Nested-spectral partition method was applied to identify effects of subtype and sex on segregation and integration of the ADHD related pattern, using 145 ADHD patients and 135 typically developing controls (TDC) aged 7-14. Relationships between the measures and inattention symptoms were also investigated., Results: Children with ADHD exhibited lower segregation of the ADHD related pattern (p = 1.17 × 10 -8 ) than TDCs. Only the main effect of subtype was significant (p = 1.14 × 10 -5 ). Both ADHD-C (p = 2.16 × 10 -6 ) and ADHD-I (p = 2.87 × 10 -6 ) patients had lower segregation components relative to the TDC. Moreover, segregation components were negatively correlated with inattention scores., Conclusions: This study identified impaired segregation in the ADHD related pattern of children with ADHD and found shared neural bases among different subtypes and sexes., Competing Interests: Declaration of competing interest The authors declare no biomedical financial interests or potential conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: A range of imaging modalities have reported Alzheimer's disease-related abnormalities in individuals experiencing subjective cognitive decline (SCD). However, there has been no consistent local abnormality identified across multiple neuroimaging modalities for SCD., Objective: We aimed to investigate the convergent local alterations in amyloid-β (Aβ) deposition, glucose metabolism, and resting-state functional MRI (RS-fMRI) metrics in SCD., Methods: Fifty SCD patients (66.4±5.7 years old, 19 men [38%]) and 15 normal controls (NC) (66.3±4.4 years old, 5 men [33.3%]) were scanned with both [18F]-florbetapir PET and [18F]-fluorodeoxyglucose PET, as well as simultaneous RS-fMRI from February 2018 to November 2018. Voxel-wise metrics were retrospectively analyzed, including Aβ deposition, glucose metabolism, amplitude of low frequency fluctuation (ALFF), regional homogeneity (ReHo), and degree centrality(DC)., Results: The SCD group showed increased Aβ deposition and glucose metabolism (p < 0.05, corrected), as well as decreased ALFF, ReHo, and DC (p < 0.05, uncorrected) in the left dorsal precuneus (dPCu). Furthermore, the dPCu illustrated negative resting-state functional connectivity with the default mode network. Regarding global Aβ deposition positivity, the Aβ deposition in the left dPCu showed a gradient change, i.e., Aβ positive SCD > Aβ negative SCD > Aβ negative NC. Additionally, both Aβ positive SCD and Aβ negative SCD showed increased glucose metabolism and decreased RS-fMRI metrics in the dPCu., Conclusions: The dorsal precuneus, an area implicated in early AD, shows convergent neuroimaging alterations in SCD, and might be more related to other cognitive functions (e.g., unfocused attention) than episodic memory.

Functional connectivity (FC) derived from resting-state functional magnetic resonance imaging has been widely applied to guide precise repetitive transcranial magnetic stimulation (rTMS). The left, right, and bilateral dorsolateral prefrontal cortices (DLPFC) have been used as rTMS treatment target regions for autism spectrum disorder (ASD), albeit with moderate efficacy. Thus, we aimed to develop an individualized localization method for rTMS treatment of ASD. We included 266 male ASDs and 297 male typically-developed controls (TDCs) from the Autism Brain Imaging Data Exchange Dataset. The nucleus accumbens (NAc) was regarded as a promising effective region, which was used as a seed and individualized peak FC strength in the DLPFC was compared between ASD and TDC. Correlation analysis was conducted between individualized peak FC strength and symptoms in ASD. We also investigated the spatial distribution of individualized peak FC locations in the DLPFC and conducted voxel-wise analysis to compare NAc-based FC between the two groups. ASD showed stronger peak FC in the right DLPFC related to TDC (Cohen's d = -.19, 95% CI: -0.36 to -0.03, t = -2.30, p = .02). Moreover, negative correlation was found between the peak FC strength in the right DLPFC and Autism Diagnostic Observation Schedule (ADOS) scores, which assessed both the social communication and interaction (r = -.147, p = .04, uncorrected significant), and stereotyped behaviors and restricted interests (r = -.198, p = .02, corrected significant). Peak FC locations varied substantially across participants. No significant differences in NAc-based FC in the DLPFC were found in the voxel-wise comparison. Our study supports the use of individualized peak FC-guided precise rTMS treatment of male ASD. Moreover, stimulating the right DLPFC might alleviate core symptoms of ASD., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Study Objectives: Insomnia and depression are common mental health problems reported by mental health professionals during the COVID-19 pandemic. Network analysis is a fine-grained approach used to examine associations between psychiatric syndromes at a symptom level. This study was designed to elucidate central symptoms and bridge symptoms of a depression-insomnia network among psychiatric practitioners in China. The identification of particularly important symptoms via network analysis provides an empirical foundation for targeting specific symptoms when developing treatments for comorbid insomnia and depression within this population., Methods: A total of 10,516 psychiatric practitioners were included in this study. The Insomnia Severity Index (ISI) and 9-item Patient Health Questionnaire (PHQ-9) were used to estimate prevalence rates of insomnia and depressive symptoms, respectively. Analyses also generated a network model of insomnia and depression symptoms in the sample., Results: Prevalence rates of insomnia (ISI total score ≥8), depression (PHQ-9 total score ≥5) and comorbid insomnia and depression were 22.2% (95% confidence interval: 21.4-22.9%), 28.5% (95% confidence interval: 27.6-29.4%), and 16.0% (95% confidence interval: 15.3-16.7%), respectively. Network analysis revealed that "Distress caused by sleep difficulties" (ISI7) and "Sleep maintenance" (ISI2) had the highest strength centrality, followed by "Motor dysfunction" (PHQ8) and "Sad mood" (PHQ2). Furthermore, the nodes "Sleep dissatisfaction" (ISI4), "Fatigue" (PHQ4), and "Motor dysfunction" (PHQ8) had the highest bridge strengths in linking depression and insomnia communities., Conclusions: Both central and bridge symptoms (ie, Distress caused by sleep difficulties, Sleep maintenance, Motor dysfunction, Sad mood, Sleep dissatisfaction, and Fatigue) should be prioritized when testing preventive measures and specific treatments to address comorbid insomnia and depression among psychiatric practitioners during the COVID-19 pandemic., Citation: Zhao N, Zhao Y-J, An F, et al. Network analysis of comorbid insomnia and depressive symptoms among psychiatric practitioners during the COVID-19 pandemic. J Clin Sleep Med . 2023;19(7):1271-1279., (© 2023 American Academy of Sleep Medicine.)

Amplitude of low-frequency fluctuation (ALFF) has been widely used for localization of abnormal activity at the single-voxel level in resting-state fMRI (RS-fMRI) studies. However, previous ALFF studies were based on fast Fourier transform (FFT-ALFF). Our recent study found that ALFF based on wavelet transform (Wavelet-ALFF) showed better sensitivity and reproducibility than FFT-ALFF. The current study aimed to test the reliability and validity of Wavelet-ALFF, and apply Wavelet-ALFF to investigate the modulation effect of repetitive transcranial magnetic stimulation (rTMS). The reliability and validity were assessed on multicenter RS-fMRI datasets under eyes closed (EC) and eyes open (EO) conditions (248 healthy participants in total). We then detected the sensitivity of Wavelet-ALFF using a rTMS modulation dataset (24 healthy participants). For each dataset, Wavelet-ALFF based on five mother wavelets (i.e., db2, bior4.4, morl, meyr and sym3) and FFT-ALFF were calculated in the conventional band and five frequency sub-bands. The results showed that the reliability of both inter-scanner and intra-scanner was higher with Wavelet-ALFF than with FFT-ALFF across multiple frequency bands, especially db2-ALFF in the higher frequency band slow-2 (0.1992-0.25 Hz). In terms of validity, the multicenter ECEO datasets showed that the effect sizes of Wavelet-ALFF with all mother wavelets (especially for db2-ALFF) were larger than those of FFT-ALFF across multiple frequency bands. Furthermore, Wavelet-ALFF detected a larger modulation effect than FFT-ALFF. Collectively, Wavelet db2-ALFF showed the best reliability and validity, suggesting that db2-ALFF may offer a powerful metric for inspecting regional spontaneous brain activities in future studies., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

The amplitude of low-frequency fluctuation (ALFF) describes the regional intensity of spontaneous blood-oxygen-level-dependent signal in resting-state functional magnetic resonance imaging (fMRI). How the fMRI-ALFF relates to the amplitude in electrophysiological signals remains unclear. We here aimed to investigate the neural correlates of fMRI-ALFF by comparing the spatial difference of amplitude between the eyes-closed (EC) and eyes-open (EO) states from fMRI and magnetoencephalography (MEG), respectively. By synthesizing MEG signal into amplitude-based envelope time course, we first investigated 2 types of amplitude in MEG, meaning the amplitude of neural activities from delta to gamma (i.e. MEG-amplitude) and the amplitude of their low-frequency modulation at the fMRI range (i.e. MEG-ALFF). We observed that the MEG-ALFF in EC was increased at parietal sensors, ranging from alpha to beta; whereas the MEG-amplitude in EC was increased at the occipital sensors in alpha. Source-level analysis revealed that the increased MEG-ALFF in the sensorimotor cortex overlapped with the most reliable EC-EO differences observed in fMRI at slow-3 (0.073-0.198 Hz), and these differences were more significant after global mean standardization. Taken together, our results support that (i) the amplitude at 2 timescales in MEG reflect distinct physiological information and that (ii) the fMRI-ALFF may relate to the ALFF in neural activity., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The low-frequency (<0.1 Hz) fluctuation in sustained attention attracts enormous interest in cognitive neuroscience and clinical research since it always leads to cognitive and behavioral lapses. What is the source of the spontaneous fluctuation in sustained attention in neural activity, and how does the neural fluctuation relate to behavioral fluctuation? Here, we address these questions by collecting and analyzing two independent fMRI and behavior datasets. We show that the neural (fMRI) fluctuation in a key brain network, the default-mode network (DMN), mediate behavioral (reaction time) fluctuation during sustained attention. DMN shows the increased amplitude of fluctuation, which correlates with the behavioral fluctuation in a similar frequency range (0.01-0.1 Hz) but not in the lower (<0.01 Hz) or higher (>0.1 Hz) frequency range. This was observed during both auditory and visual sustained attention and was replicable across independent datasets. These results provide a novel insight into the neural source of attention-fluctuation and extend the former concept that DMN was deactivated in cognitive tasks. More generally, our findings highlight the temporal dynamic of the brain-behavior relationship., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Most stroke repetitive transcranial magnetic stimulation (rTMS) studies have used hand motor hotspots as rTMS stimulation targets; in addition, recent studies demonstrated that functional magnetic resonance imaging (fMRI) task activation could be used to determine suitable targets due to its ability to reveal individualized precise and stronger functional connectivity with motor-related brain regions. However, rTMS is unlikely to elicit motor evoked potentials in the affected hemisphere, nor would activity be detected when stroke patients with severe hemiplegia perform an fMRI motor task using the affected limbs. The current study proposed that the peak voxel in the resting-state fMRI (RS-fMRI) motor network determined by independent component analysis (ICA) could be a potential stimulation target. Twenty-one healthy young subjects underwent RS-fMRI at three visits (V1 and V2 on a GE MR750 scanner and V3 on a Siemens Prisma) under eyes-open (EO) and eyes-closed (EC) conditions. Single-subject ICA with different total number of components (20, 30, and 40) were evaluated, and then the locations of peak voxels on the left and right sides of the sensorimotor network (SMN) were identified. While most ICA RS-fMRI studies have been carried out on the group level, that is, Group-ICA, the current study performed individual ICA because only the individual analysis could guide the individual target of rTMS. The intra- (test-retest) and inter-scanner reliabilities of the peak location were calculated. The use of 40 components resulted in the highest test-retest reliability of the peak location in both the left and right SMN compared with that determined when 20 and 30 components were used for both EC and EO conditions. ICA with 40 components might be another way to define a potential target in the SMN for poststroke rTMS treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hu, Yue, Ge, Feng, Wang and Zang.)

Resting-state magnetic resonance imaging (RS-fMRI) studies indicated that the repetitive transcranial magnetic stimulation (rTMS) exerts antidepression effect through the functional connectivity (FC) of the DLPFC with the subgenual anterior cingulate cortex (sgACC), pregneual ACC (pgACC), or nucleus accumbens (NAc). It is proposed that the FC-guided individualized precise stimulation on the DLPFC would be more effective. The current study systematically investigated the reliability of the RS-fMRI FC location as well as the FC strength with multiple potential factors. We aimed to provide a stable stimulation target for future FC-guided TMS therapy for affective related disorders. Twenty-one subjects under RS-fMRI conditions with the first two times (V1, V2) scanned on a GE 3 T scanner and the third visit (V3) on a Siemens 3 T scanner. Then the FC strength and location reliability were assessed by using intra-class correlation (ICC) and intra-individual distance, respectively. The factors included deep seed ROIs (midline (mid-) sgACC, left pgACC, mid-pgACC, and left NAc), eyes closed (EC) vs eyes open (EO), frequency bands, FC algorithm (Pearson vs Spearman), scanning length (half a session vs whole session), and location method (FC peak vs center of gravity (COG)). The reliability of the voxel-wise FC strength was low to moderate. The intra-individual distances of the COG were 3.8-7.3 mm across all factors, much smaller than that of FC peak (approximately 30 mm). The COG of seed-based FC might be a potential rTMS stimulation target. Anyway, all potential stimulation targets should be tested in future rTMS treatment studies., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: In familial cortical myoclonic tremor with epilepsy, photic stimulation can trigger visual symptoms and induce a photoparoxysmal response, or photosensitivity, on electroencephalography. However, the mechanism is poorly understood. In this study, we aimed to explore the neuroimaging changes related to visual symptoms and photosensitivity in genetically confirmed familial cortical myoclonic tremor with epilepsy type 1., Methods: Resting-state functional magnetic resonance imaging and electroencephalography data were collected from 31 patients carrying the heterozygous pathogenic intronic pentanucleotide (TTTCA)n insertion in the sterile alpha motif domain-containing 12 gene and from 52 age- and sex-matched healthy controls., Results: (1) Both regional homogeneity and degree centrality values in the bilateral calcarine sulcus were significantly increased in patients compared with healthy controls. (2) When the calcarine sulcus area with increased regional homogeneity was taken as a seed, increased functional connectivity values were observed in the right precentral gyrus, while decreased functional connectivity values were observed in the right superior frontal gyrus and right inferior parietal lobule. (3) Independent component analysis showed increased connectivity in the left calcarine sulcus inside the medial visual network. (4) Correlation analysis revealed a significant positive correlation between regional homogeneity values and frequency of seizure, and photoparoxysmal response grades were positively correlated with the severity of cortical tremor and duration of epilepsy., Conclusion: These findings provide strong evidence for the interpretation of visual symptoms and photosensitivity in familial cortical myoclonic tremor with epilepsy. We speculate that functional changes in the primary visual cortex may be an imaging biomarker for the disease., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Attention-deficit/hyperactivity disorder (ADHD) is increasingly being diagnosed in both children and adults, but the neural mechanisms that underlie its distinct symptoms and whether children and adults share the same mechanism remain poorly understood. Here, we used a nested-spectral partition approach to study resting-state brain networks of ADHD patients (n = 97) and healthy controls (HCs, n = 97) across the lifespan (7-50 years). Compared to the linear lifespan associations of brain segregation and integration with age in HCs, ADHD patients have a quadratic association in the whole-brain and in most functional systems, whereas the limbic system dominantly affected by ADHD has a linear association. Furthermore, the limbic system better predicts hyperactivity, and the salient attention system better predicts inattention. These predictions are shared in children and adults with ADHD. Our findings reveal a lifespan association of brain networks with ADHD and provide potential shared neural bases of distinct ADHD symptoms in children and adults., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)

Previous resting state functional magnetic resonance imaging (RS-fMRI) studies suggested that repetitive transcranial magnetic stimulation (rTMS) can modulate local activity in distant areas via functional connectivity (FC). A brain region has more than one connection with the superficial cortical areas. The current study proposed a multi-target focused rTMS protocol for indirectly stimulating a deep region, and to investigate 1) whether FC strength between stimulation targets (right middle frontal gyrus [rMFG] and right inferior parietal lobule [rIPL]) and effective region (dorsal anterior cingulate cortex [dACC]) can predict local activity changes of dACC and 2) whether multiple stimulation targets can focus on the dACC via FC. A total of 24 healthy participants received rTMS with two stimulation targets, both showing strong FC with the dACC. There were four rTMS conditions (>1 week apart, 10 Hz, 1800 pulses for each): rMFG-target, rIPL-target, Double-targets (900 pulses for each target), and Sham. The results failed to validate the multi-target focused rTMS hypothesis. But rMFG-target significantly decreased the local activity in the dACC. In addition, stronger dACC-rMFG FC was associated with a greater local activity change in the dACC. Future studies should use stronger FC to focus stimulation effects on the deep region., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Characterizing the functional involvement of specific brain regions has long been a central challenge in cognitive neuroscience. Functional magnetic resonance imaging (fMRI) techniques have offered solutions for mapping functional neural networks. The complex nature of structure-function correspondence makes an elaborate task design difficult to fully capture higher-order cognitive function. Other research practices, such as brain-behavior association or between-group comparisons, are thus widely used to explore cognitive correlations with specific brain regions. However, interpreting the results derived from a specific brain region with their underlying cognitive functions has been too general in publications. Here, we use two examples, i.e., a brain-intelligence correlation study and a depression-control comparison meta-study, to demonstrate use of two neuroimaging online databases, BrainMap and Neurosynth. One key utility of the two databases is collecting results from massive cognitive task-based fMRI (tb-fMRI) studies, i.e., coordinates in standard brain space. Just like looking up a "coordinate-based cognition dictionary", researchers can receive a plethora of related tb-fMRI activation information characterized by cognitive domains, specific cognitive functions, cognitive task paradigms, and related publications. Surprisingly, we found that only less than 1% of brain-behavior association or between-group comparison studies have utilized this dictionary approach. We encourage the community to further engage with the existing databases for specific and comprehensive interpretation of neuroimaging as well as guidance of future experimental tb-fMRI design., (Copyright © 2022 IBRO. All rights reserved.)

Despite a growing neuroimaging literature on the pathophysiology of major depressive disorder (MDD), reproducible findings are lacking, probably reflecting mostly small sample sizes and heterogeneity in analytic approaches. To address these issues, the Depression Imaging REsearch ConsorTium (DIRECT) was launched. The REST-meta-MDD project, pooling 2428 functional brain images processed with a standardized pipeline across all participating sites, has been the first effort from DIRECT. In this review, we present an overview of the motivations, rationale, and principal findings of the studies so far from the REST-meta-MDD project. Findings from the first round of analyses of the pooled repository have included alterations in functional connectivity within the default mode network, in whole-brain topological properties, in dynamic features, and in functional lateralization. These well-powered exploratory observations have also provided the basis for future longitudinal hypothesis-driven research. Following these fruitful explorations, DIRECT has proceeded to its second stage of data sharing that seeks to examine ethnicity in brain alterations in MDD by extending the exclusive Chinese original sample to other ethnic groups through international collaborations. A state-of-the-art, surface-based preprocessing pipeline has also been introduced to improve sensitivity. Functional images from patients with bipolar disorder and schizophrenia will be included to identify shared and unique abnormalities across diagnosis boundaries. In addition, large-scale longitudinal studies targeting brain network alterations following antidepressant treatment, aggregation of diffusion tensor images, and the development of functional magnetic resonance imaging-guided neuromodulation approaches are underway. Through these endeavours, we hope to accelerate the translation of functional neuroimaging findings to clinical use, such as evaluating longitudinal effects of antidepressant medications and developing individualized neuromodulation targets, while building an open repository for the scientific community., Competing Interests: One of the authors, Dr Qi-Yong Gong, is also the editor-in-chief of Psychoradiology. He was blinded from reviewing or making decisions on the manuscript., (© The Author(s) 2022. Published by Oxford University Press on behalf of West China School of Medicine/West China Hospital (WCSM/WCH) of Sichuan University.)

The nucleus accumbens (NAc) is considered a hub of reward processing and a growing body of evidence has suggested its crucial role in the pathophysiology of major depressive disorder (MDD). However, inconsistent results have been reported by studies on reward network-focused resting-state functional MRI (rs-fMRI). In this study, we examined functional alterations of the NAc-based reward circuits in patients with MDD via meta- and mega-analysis. First, we performed a coordinated-based meta-analysis with a new SDM-PSI method for all up-to-date rs-fMRI studies that focused on the reward circuits of patients with MDD. Then, we tested the meta-analysis results in the REST-meta-MDD database which provided anonymous rs-fMRI data from 186 recurrent MDDs and 465 healthy controls. Decreased functional connectivity (FC) within the reward system in patients with recurrent MDD was the most robust finding in this study. We also found disrupted NAc FCs in the DMN in patients with recurrent MDD compared with healthy controls. Specifically, the combination of disrupted NAc FCs within the reward network could discriminate patients with recurrent MDD from healthy controls with an optimal accuracy of 74.7%. This study confirmed the critical role of decreased FC in the reward network in the neuropathology of MDD. Disrupted inter-network connectivity between the reward network and DMN may also have contributed to the neural mechanisms of MDD. These abnormalities have potential to serve as brain-based biomarkers for individual diagnosis to differentiate patients with recurrent MDD from healthy controls., (© 2022. The Author(s).)

Objective: Although previous imaging studies have reported cerebellar gray matter loss in patients with familial cortical myoclonic tremor with epilepsy (FCMTE), the corresponding white matter alterations remain unknown. We investigated white matter structural changes in FCMTE1 and compared them with clinical and electrophysiological features., Methods: We enrolled 36 patients carrying heterozygous pathogenic intronic pentanucleotide insertions in the SAMD12 gene and 52 age- and sex-matched healthy controls. Diffusion tensor imaging-derived metrics, including fractional anisotropy, mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), were calculated along with white matter voxel-based morphometry (VBM) analysis. We also examined correlations between magnetic resonance metrics and clinical and electrophysiological features., Results: We detected widespread white matter reductions in MD, RD, and AD values in FCMTE1 patients, including in the commissural, projection, and association fibers. VBM analysis revealed that increases in white matter volume predominantly occurred in the right cerebellum and sagittal stratum. MD, RD, AD, and VBM analysis clearly indicated changes in the sagittal stratum. We found a positive correlation between VBM values in the right cerebellum and somatosensory-evoked potential P25-N33 amplitude. Decreased MD and AD values in the right sagittal stratum were detected in patients with versus without photophobia., Significance: FCMTE is a network disorder involving a wide range of cortical and subcortical structures, including the cerebellum, thalamus, thalamocortical connections, and corticocortical connections. The right sagittal stratum is closely related with visual symptoms, especially photophobia. Our findings indicate that cerebellum and cortical hyperexcitability are closely linked, and emphasize the important role of the cerebellum in the pathophysiological mechanisms of cortical tremor., (© 2022 International League Against Epilepsy.)

Functional magnetic resonance imaging (fMRI) is one of the best techniques for precise localization of abnormal brain activity non-invasively. Machine-learning approaches have been widely used in neuroimaging studies; however, few studies have investigated the single-voxel modeling of fMRI data under cognitive tasks. We proposed a hybrid one-dimensional (1D) convolutional neural network (1D-CNN) based on the temporal dynamics of single-voxel fMRI time-series and successfully differentiated two continuous task states, namely, self-initiated (SI) and visually guided (VG) motor tasks. First, 25 activation peaks were identified from the contrast maps of SI and VG tasks in a blocked design. Then, the fMRI time-series of each peak voxel was transformed into a temporal-frequency domain by using continuous wavelet transform across a broader frequency range (0.003-0.313 Hz, with a step of 0.01 Hz). The transformed time-series was inputted into a 1D-CNN model for the binary classification of SI and VG continuous tasks. Compared with the univariate analysis, e.g., amplitude of low-frequency fluctuation (ALFF) at each frequency band, including, wavelet-ALFF, the 1D-CNN model highly outperformed wavelet-ALFF, with more efficient decoding models [46% of 800 models showing area under the curve (AUC) > 0.61] and higher decoding accuracies (94% of the efficient models), especially on the high-frequency bands (>0.1 Hz). Moreover, our results also demonstrated the advantages of wavelet decompositions over the original fMRI series by showing higher decoding performance on all peak voxels. Overall, this study suggests a great potential of single-voxel analysis using 1D-CNN and wavelet transformation of fMRI series with continuous, naturalistic, steady-state task design or resting-state design. It opens new avenues to precise localization of abnormal brain activity and fMRI-guided precision brain stimulation therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wu, Hu, Wang, Zang and Zhang.)

Hyperactivity is one of the three core symptoms of attention deficit hyperactivity disorder (ADHD) that is a common childhood mental disorder. Objective assessments of hyperactivity are seldom utilized compared with measures of inattention and impulsivity during clinical diagnosis and evaluation. Acceleration-sensitive devices (e.g., Actigraph) and motion tracking systems (e.g., QbTest) are two main groups of devices that can be used to objectively measure hyperactivity. The Actigraph and QbTest have good discriminant validity, convergent validity, and sensitivity to the effects of stimulants. Furthermore, the assessment setting (i.e., research laboratory, school, or home) can greatly influence the presence and severity of hyperactivity. Nevertheless, objective assessments for hyperactivity have poor ability to distinguish ADHD from other disorders, or among the three types of ADHD. Thus, further studies are needed to assess objective measurements of hyperactivity in terms of discriminant and convergent validity, test-retest reliability in different settings, and correlations with brain activity., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Aberrant topological organization of whole-brain networks has been inconsistently reported in studies of patients with major depressive disorder (MDD), reflecting limited sample sizes. To address this issue, we utilized a big data sample of MDD patients from the REST-meta-MDD Project, including 821 MDD patients and 765 normal controls (NCs) from 16 sites. Using the Dosenbach 160 node atlas, we examined whole-brain functional networks and extracted topological features (e.g., global and local efficiency, nodal efficiency, and degree) using graph theory-based methods. Linear mixed-effect models were used for group comparisons to control for site variability; robustness of results was confirmed (e.g., multiple topological parameters, different node definitions, and several head motion control strategies were applied). We found decreased global and local efficiency in patients with MDD compared to NCs. At the nodal level, patients with MDD were characterized by decreased nodal degrees in the somatomotor network (SMN), dorsal attention network (DAN) and visual network (VN) and decreased nodal efficiency in the default mode network (DMN), SMN, DAN, and VN. These topological differences were mostly driven by recurrent MDD patients, rather than first-episode drug naive (FEDN) patients with MDD. In this highly powered multisite study, we observed disrupted topological architecture of functional brain networks in MDD, suggesting both locally and globally decreased efficiency in brain networks., (© 2021. The Author(s).)

Background: Depression has been a common mental health problem during the COVID-19 epidemic. From a network perspective, depression can be conceptualized as the result of mutual interactions among individual symptoms, an approach that may elucidate the structure and mechanisms underlying this disorder. This study aimed to examine the structure of depression among residents in Wuhan, the epicenter of the COVID-19 outbreak in China, in the later stage of the COVID-19 pandemic. Methods: A total of 2,515 participants were recruited from the community via snowball sampling. The Patient Health Questionnaire was used to assess self-reported depressive symptoms with the QuestionnaireStar program. The network structure and relevant centrality indices of depression were examined in this sample. Results: Network analysis revealed Fatigue, Sad mood, Guilt and Motor disturbances as the most central symptoms, while Suicide and Sleep problems had the lowest centrality. No significant differences were found between women and men regarding network structure (maximum difference = 0.11, p = 0.44) and global strength (global strength difference = 0.04; female vs. male: 3.78 vs. 3.83, p = 0.51), a finding that suggests there are no gender differences in the structure or centrality of depressive symptoms. Limitations: Due to the cross-sectional study design, causal relationships between these depressive symptoms or dynamic changes in networks over time could not be established. Conclusions: Fatigue, Sad mood, Guilt, and Motor disturbances should be prioritized as targets in interventions and prevention efforts to reduce depression among residents in Wuhan, in the later stage of the COVID-19 pandemic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer JL declared a shared affiliation, with no collaboration, with the author TC at the time of the review., (Copyright © 2021 Zhao, Li, Zhang, Yang, Sha, Cheung, Jackson, Zang and Xiang.)

Background: High-frequency rTMS over the dorsolateral prefrontal cortex (DLPFC) has demonstrated mixed effects on chronic and provoked pain., Objectives/methods: In this study, a meta-analysis was conducted to characterise the potential analgesic effects of high-frequency rTMS over the DLPFC on both chronic and provoked pain., Results: A total of 626 studies were identified in a systematic search. Twenty-six eligible studies were included for the quantitative review, among which 17 modulated chronic pain and the remaining investigated the influence on provoked pain. The left side DLPFC was uniformly targeted in the chronic pain studies. While our data identified no overall effect of TMS across chronic pain conditions, there was a significant short-term analgesia in neuropathic pain conditions only (SMD = -0.87). In terms of long-lasting analgesia, there was an overall pain reduction in the midterm (SMD = -0.53, 24.6 days average) and long term (SMD = -0.63, 3 months average) post DLPFC stimulation, although these effects were not observed within specific chronic pain conditions. Surprisingly, the number of sessions was demonstrated to have no impact on rTMS analgesia. In the analysis of provoked pain, our data also indicated a significant analgesic effect following HF-rTMS over the DLPFC (SMD = -0.73). Importantly, we identified a publication bias in the studies of provoked pain but not for chronic pain conditions., Conclusions: Overall, our findings support that HF-DLPFC stimulation is able to induce an analgesic effect in chronic pain and in response to provoked pain. These results highlight the potential of DLPFC-rTMS in the management of certain chronic pain conditions and future directions are discussed to enhance the potential long-term analgesic effects., Competing Interests: Declaration of competing interest XC is supported by the National Natural Science Foundation of China (4045F41120040), and Provincial Advantage Discipline Project (20JYXK034). PF is supported by an NHMRC Practitioner Fellowship (606907), and RFHC is supported by the Australian Research Council (DE200101708). YZ is supported by Key Project of the Department of Science and Technology of Zhejiang Province (2015C03037). The authors declare no competing financial interests., (Copyright © 2021. Published by Elsevier Inc.)

Asymmetries in gray matter alterations raise important issues regarding the pathological co-alteration between hemispheres. Since homotopic areas are the most functionally connected sites between hemispheres and gray matter co-alterations depend on connectivity patterns, it is likely that this relationship might be mirrored in homologous interhemispheric co-altered areas. To explore this issue, we analyzed data of patients with Alzheimer's disease, schizophrenia, bipolar disorder and depressive disorder from the BrainMap voxel-based morphometry database. We calculated a map showing the pathological homotopic anatomical co-alteration between homologous brain areas. This map was compared with the meta-analytic homotopic connectivity map obtained from the BrainMap functional database, so as to have a meta-analytic connectivity modeling map between homologous areas. We applied an empirical Bayesian technique so as to determine a directional pathological co-alteration on the basis of the possible tendencies in the conditional probability of being co-altered of homologous brain areas. Our analysis provides evidence that: the hemispheric homologous areas appear to be anatomically co-altered; this pathological co-alteration is similar to the pattern of connectivity exhibited by the couples of homologues; the probability to find alterations in the areas of the left hemisphere seems to be greater when their right homologues are also altered than vice versa, an intriguing asymmetry that deserves to be further investigated and explained., (© 2021. The Author(s).)

Volitional eye closure is observed only in conscious and awake humans, and is rare in animals. It is believed that eye closure can focus one's attention inward and facilitate activities such as meditation and mental imagery. Congenital blind individuals are also required to close their eyes for these activities. Resting-state functional magnetic resonance imaging (RS-fMRI) studies have found robust differences between the eyes-closed (EC) and eyes-open (EO) conditions in some brain regions in the sighted. This study analyzed data from 21 congenital blind individuals and 21 sighted controls by using amplitude of low-frequency fluctuation (ALFF) of RS-fMRI. The blind group and the sighted group shared similar pattern of differences between the EC and EO condition: ALFF was higher in the EC condition than the EO condition in the bilateral primary sensorimotor cortex, bilateral supplementary motor area, and inferior occipital cortex, while ALFF was lower in the EC condition than the EO condition in the medial prefrontal cortex, highlighting the "nature" effect on the difference between the EC and EO conditions. The results of other matrices such as fractional ALFF (fALFF) and regional homogeneity (ReHo) showed similar patterns to that of ALFF. Moreover, no significant difference was observed between the EC-EO pattern of the two subgroups of congenital blind (i.e., with and without light perception), suggesting that the EC-EO difference is irrespective of residual light perception which reinforced the "nature" effect. We also found between-group differences, i.e., more probably "nurture effect", in the posterior insula and fusiform. Our results suggest that the acts of closing and opening the eyes are of importance for the congenital blind, and that these actions and their differences might be inherent in the nature of humans., Competing Interests: Declaration of Competing Interest The authors report no biomedical financial interests or potential conflicts of interest related to the present work, (Copyright © 2021. Published by Elsevier Inc.)

The article "MiRNA-146b-5p inhibits the malignant progression of gastric cancer by targeting TRAF6, by J.-N. Ding, Y.-F. Zang, Y.-L. Ding, published in Eur Rev Med Pharmacol Sci 2020; 24 (17): 8837-8844-DOI: 10.26355/eurrev&#95;202009&#95;22823-PMID: 32964972" has been withdrawn from the authors due to some technical reasons (some data are not reproducible). The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/22823#:~:text=TRAF6%20was%20the%20target%20of,of%20GC%20by%20targeting%20TRAF6.

Background: Functional specialization is a feature of human brain for understanding the pathophysiology of major depressive disorder (MDD). The degree of human specialization refers to within and cross hemispheric interactions. However, most previous studies only focused on interhemispheric connectivity in MDD, and the results varied across studies. Hence, brain functional connectivity asymmetry in MDD should be further studied., Methods: Resting-state fMRI data of 753 patients with MDD and 451 healthy controls were provided by REST-meta-MDD Project. Twenty-five project contributors preprocessed their data locally with the Data Processing Assistant State fMRI software and shared final indices. The parameter of asymmetry (PAS), a novel voxel-based whole-brain quantitative measure that reflects inter- and intrahemispheric asymmetry, was reported. We also examined the effects of age, sex and clinical variables (including symptom severity, illness duration and three depressive phenotypes)., Results: Compared with healthy controls, patients with MDD showed increased PAS scores (decreased hemispheric specialization) in most of the areas of default mode network, control network, attention network and some regions in the cerebellum and visual cortex. Demographic characteristics and clinical variables have significant effects on these abnormalities., Limitations: Although a large sample size could improve statistical power, future independent efforts are needed to confirm our results., Conclusions: Our results highlight the idea that many brain networks contribute to broad clinical pathophysiology of MDD, and indicate that a lateralized, efficient and economical brain information processing system is disrupted in MDD. These findings may help comprehensively clarify the pathophysiology of MDD in a new hemispheric specialization perspective., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Studies regarding the impact of Parkinson's disease (PD) on quality of life (QOL) have reported conflicting results, and the underlying QOL domains require further study. In order to understand the association between PD and QOL, we conducted this meta-analysis to systematically compare QOL between PD patients and healthy controls., Method: The PubMed, PsycINFO, EMBASE, and Web of Science databases were systematically searched. Data were analyzed using the random-effects model., Results: Twenty studies covering 2707 PD patients and 150,661 healthy controls were included in the study. Compared with healthy controls, PD patients had significantly poorer QOL overall and in most domains with moderate to large effects sizes. Different QOL measures varied in their association with quality of life, with the Parkinson's Disease Questionnaire-39 (PDQ-39) having the largest effect size (standard mean difference, SMD = -1.384, 95% CI: -1.607, -1.162, Z = 12.189, P < 0.001), followed by the Europe Quality of Life Questionnaire-visual analogue scale (EQ-VAS) (SMD = -1.081, 95% CI: -1.578, -0.584, Z = -4.265, P < 0.001), Europe Quality of Life Questionnaire-5D (EQ-5D) (SMD = -0.889, 95% CI: -1.181, -0.596, Z = -5.962, P < 0.001), and the Short-form Health Survey (SF) scales (physical dimension: SMD = -0.826, 95% CI: -1.529, -0.123, Z = -2.303, P = 0.021; mental dimension: SMD = -0.376, 95% CI: -0.732, -0.019, Z = -2.064, P = 0.039)., Conclusion: PD patients had lower QOL compared with healthy controls in most domains, especially in physical function and mental health. Considering the negative impact of poor QOL on daily life and functional outcomes, effective measures should be developed to improve QOL in this population., (© 2020 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)

Anxious major depressive disorder is a common subtype of major depressive disorder; however, its unique neural mechanism is not well-understood currently. Using multimodal MRI data, this study examined common and specific alterations of amygdala subregions between patients with and without anxiety. No alterations were observed in the gray matter volume or intra-region functional integration in either patient group. Compared with the controls, both patient groups showed decreased functional connectivity between the left superficial amygdala and the left putamen, and between the right superficial amygdala and the bilateral anterior cingulate cortex and medial orbitofrontal cortex, while only patients with anxiety exhibited decreased activity in the bilateral laterobasal and superficial amygdala. Moreover, the decreased activity correlated negatively with the Hamilton depression scale scores in the patients with anxiety. These findings provided insights into the pathophysiologic processes of anxious major depressive disorder and may help to develop new and effective treatment programs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Ni, You, Qing, Wang, Yao, Ren, Zhang, Liu, Song, Wang, Zang, Shen and Chen.)

Tourette syndrome (TS) is a developmental neuropsychiatric disorder with onset during childhood. Because of its complex spectrum of phenotypes, the underlying pathophysiology of TS is still unclear. Resting-state functional magnetic resonance imaging demonstrated aberrant spontaneous neural synchronization in conventional frequency band (0.01-0.08 Hz) in TS. No published studies have reported abnormalities of local synchronization across different frequency bands. We estimated the alterations of local synchronization across five bands ranging from 0 to 0.25 Hz. Seventy-nine children with TS and 63 age-, sex-, and handedness-matched healthy children were recruited. Frequency-specific regional homogeneity (ReHo) and independent component analysis were used to identify functional alterations between TS and healthy children. TS patients showed significantly increased ReHo in the left precentral gyrus and decreased ReHo in the right operculum. Abnormal ReHo alterations of the superior frontal gyrus, superior parietal gyrus, anterior cingulate gyrus, putamen, superior temporal gyrus, and operculum were observed in different frequency bands. TS patients showed increased connectivity of the right superior frontal gyrus within the left executive control network. In addition, a significantly negative correlation was found between Yale Global Tic Severity Scale (YGTSS) vocal score and ReHo values of the right operculum in the highest frequency bands (0.198-0.25 Hz), while a significant positive correlation was found between YGTSS motor score and altered connectivity of the right superior frontal gyrus. The present study revealed frequency-specific abnormal alterations of ReHo in the whole brain and altered connectivity within the executive control network of TS children. Its neural importance and clinical practicability require further investigation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Lou, Li, Wang, Ji, Zang, Wang and Feng.)

Objective: MicroRNAs (miRNAs) are 22 nucleotides long that are extensively expressed in eukaryotes. They are vital regulators in pathological processes. This study aims to illustrate the role of miRNA-146b-5p in the development of gastric cancer (GC)., Patients and Methods: MiRNA-146b-5p levels in 62 GC species and matched paracancerous ones were detected. Influences of miRNA-146b-5p level on clinical parameters of GC patients were assessed. Phenotype changes of AGS and SGC-7901 cells overexpressing miRNA-146b-5p were evaluated by Cell Counting Kit-8 (CCK-8) and transwell assay, respectively. Luciferase assay and rescue experiments were conducted to uncover the mechanism of miRNA-146b-5p in regulating the development of GC., Results: MiRNA-146b-5p was downregulated in GC species than paracancerous ones. Lower level of miRNA-146b-5p was observed in GC patients combined lymphatic metastasis and distant metastasis than those without metastases. In vitro overexpression of miRNA-146b-5p attenuated proliferative and migratory potentials of GC cells. TRAF6 was the target of miRNA-146b-5p, which was responsible for the development of GC regulated by miRNA-146b-5p., Conclusions: MiRNA-146b-5p level is negatively correlated to lymphatic metastasis and distant metastasis rates of GC. It suppresses the malignant development of GC by targeting TRAF6.

Background: Single incision plus one port left-side approach (SILS+1/L) totally laparoscopic distal gastrectomy (TLDG) is an emerging technique for the treatment of gastric cancer. Reduced port laparoscopic gastrectomy has a number of potential advantages for patients compared with conventional laparoscopic gastrectomy: relieving postoperative pain, shortening hospital stay and offering a better cosmetic outcome. Nevertheless, there are no previous reports on the use of SILS+1/L TLDG with uncut Roux-en-Y (uncut R-Y) reconstruction., Aim: To investigate the initial feasibility of SILS+1/L TLDG with uncut Roux-en-Y digestive tract reconstruction (uncut R-Y reconstruction) to treat distal gastric cancer., Methods: A total of 21 patients who underwent SILS+1/L TLDG with uncut R-Y reconstruction for gastric cancer were enrolled. All patients were treated at The Second Hospital of Shandong University. Reconstructions were performed intracorporeally with 60 mm endoscopic linear stapler and 45 mm no-knife stapler. The clinicopathological characteristics, surgical details, postoperative short-term outcomes, postoperative follow-up upper gastrointestinal radiography findings and endoscopy results were analyzed retrospectively., Results: All SILS+1/L operations were performed by SILS+1/L TLDG successfully. The patient population included 13 men and 8 women with a mean age of 48.2 years (ranged from 40 years to 70 years) and median body mass index of 22.8 kg/m 2 . There were no conversions to open laparotomy, and no other port was placed. The mean operation time was 146 min (ranged 130-180 min), and the estimated mean blood loss was 54 mL (ranged 20-110 mL). The mean duration to flatus and discharge was 2.3 (ranged 1-3.5) and 7.3 (ranged 6-9) d, respectively. The mean number of retrieved lymph nodes was 42 (ranged 30-47). Two patients experienced mild postoperative complications, including surgical site infection (wound at the navel incision) and mild postoperative pancreatic fistula (grade A). Follow-up upper gastrointestinal radiography and endoscopy were carried out at 3 mo postoperatively. No patients experienced moderate or severe food stasis, alkaline gastritis or bile reflux during the follow-up period. No recanalization of the biliopancreatic limb was found., Conclusion: SILS+1/L TLDG with uncut R-Y reconstruction could be safely performed as a reduced port surgery., Competing Interests: Conflict-of-interest statement: We declare that there are no conflicts of interest to disclose., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Reaction-time variability is a critical index of sustained attention. However, researchers still lack effective measures to establish the association between neurophysiological activity and this behavioral variability. Here, the present study recorded reaction time (RT) and cortical electroencephalogram (EEG) in healthy subjects when they continuously performed an alternative responding task. The frontal theta activity and reaction-time variability were examined trial by trial using the measures of standard deviation (SD) in the time domain and amplitude of low-frequency fluctuation (ALFF) in the frequency domain. Our results showed that the SD of reaction-time variability did not have any correlation with the SD of trial-by-trial frontal theta activity, and the ALFF of reaction-time variability has a significant correlation with the ALFF of trial-by-trial frontal theta activity in 0.01-0.027 Hz. These results suggested the methodological significance of ALFF in establishing the association between neurophysiological activity and reaction-time variability. Furthermore, these findings also support the low-frequency fluctuation as a potential feature of sustained attention., (Copyright © 2020 Wang, Sun, Liu, Pan, Zheng, Wang, Zang and Zhang.)

Objective: The aim of the study was to observe the effect of F-box/WD repeat-containing protein 7 (FBW7) on hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) pathway in chondrocytes (CHs) under IL-1β induced degeneration., Patients and Methods: We explored the levels of FBW7, HIF-1α, and VEGF in degenerated cartilage from osteoarthritis (OA) and chondrocytes (CHs) treated by IL-1β. Meanwhile, we regulated HIF-1α and FBW7 expression in IL-1β treated CHs and observed the effects FBW7 of the HIF-1α/VEGF pathway., Results: FBW7 expression was significantly decreased along with the increased HIF-1α and VEGF expression both in OA cartilage and IL-1β induced degenerated CHs. Additionally, suppression of HIF-1α decreased VEGF level, which contributed to the production of collagen II, aggrecan and SOX-9, and inhibited collagen I and Runx-2 expression. Furthermore, FBW7 suppressed HIF-1α/VEGF pathway and promoted the integration of collagen II, aggrecan, and SOX-9, but inhibited the collagen I and Runx-2 expression., Conclusions: FBW7 negatively regulates HIF-1α/VEGF pathway and plays a protective role in the IL-1β induced CHs degeneration.

Background: Intronic pentanucleotide insertion in the sterile alpha motif domain-containing 12 gene was recently identified as the genetic cause of familial cortical myoclonic tremor with epilepsy type 1., Objectives: We thereafter conducted a multimodal MRI research to further understand familial cortical myoclonic tremor with epilepsy type 1., Methods: We enrolled 31 patients carrying heterozygous pathogenic intronic pentanucleotide insertion in the sterile alpha motif domain-containing 12 gene and 31 age- and sex-matched healthy controls. We compared multimodal MRI metrics, including voxel-based morphometry, fractional anisotropy of diffuse tensor imaging, frequency-dependent percent amplitude fluctuation, and seed-based functional connectivity of resting-state functional MRI., Results: Significant decreased gray matter volume was found in the cerebellum. Percent amplitude fluctuation analysis showed significant interaction effect of "Frequency by Group" in three regions, including the vermis VIII, left cerebellar lobule VIII, and left precentral gyrus. Specifically, the lowest-frequency band exhibited significant increased percent amplitude fluctuation in patients in the two cerebellar subregions, whereas the highest-frequency band exhibited decreased percent amplitude fluctuation in the precentral gyrus in patients. Discriminative analysis by support vector machine showed a mean accuracy of 82% (P = 1.0 -5 ). An increased functional connectivity between vermis VIII and the left precentral gyrus was found in patients with familial cortical myoclonic tremor with epilepsy type 1. A positive correlation between the percent amplitude fluctuation in the left cerebellar lobule VIII and duration of cortical tremor was also found., Conclusion: The cerebellum showed both structural and functional damages. The distinct change of spontaneous brain activity, that is, increased ultra-low-frequency amplitude in the cerebellum and the decreased higher-frequency amplitude in the motor cortex, might be a pathophysiological feature of familial cortical myoclonic tremor with epilepsy type 1. © 2020 International Parkinson and Movement Disorder Society., (© 2020 International Parkinson and Movement Disorder Society.)

Background: The dorsolateral prefrontal cortex (DLPFC) is the standard stimulation target for the repetitive transcranial magnetic stimulation (rTMS) treatment of major depression disorder (MDD). A retrospective study by Fox and colleagues found that a more negative resting-state functional magnetic resonance imaging (RS-fMRI) functional connectivity (FC) between left DLPFC and the subgenual anterior cingulate cortex (sgACC) in a large group of healthy participants is associated with a better curative effects of rTMS in MDD, suggesting that the sgACC may be an effective region. However, a recent meta-analysis on RS-fMRI studies found that the pregenual ACC (pgACC), rather than the sgACC, of MDD patients showed increased local activity., Methods: We used the stimulation coordinates in the left DLPFC analyzed by Fox et al. to perform RS-fMRI FC between the stimulation targets obtained from previous rTMS MDD studies and the potential effective regions (sgACC and pgACC, respectively) on the RS-fMRI data from 88 heathy participants., Results: (a) Both the pgACC and the sgACC were negatively connected to the left DLPFC; (b) both FCs of sgACC-DLPFC and pgACC-DLPFC were more negative in responders than in nonresponders; and (c) the associations between DLPFC-sgACC functional connectivity and clinical efficacy were clustered around the midline sgACC., Conclusions: Both the pgACC and the sgACC may be potential effective regions for rTMS on the left DLPFC for treatment of MDD. However, individualized ACC-DLPFC FC-based rTMS on depression should be performed in the future to test the pgACC or the sgACC as effective regions., (© 2020 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)

The fast Fourier transform (FFT) is a widely used algorithm used to depict the amplitude of low-frequency fluctuation (ALFF) of resting-state functional magnetic resonance imaging (RS-fMRI). Wavelet transform (WT) is more effective in representing the complex waveform due to its adaptivity to non-stationary or local features of data and many varieties of wavelet functions with different shapes being available. However, there is a paucity of RS-fMRI studies that systematically compare between the results of FFT versus WT. The present study employed five cohorts of datasets and compared the sensitivity and reproducibility of FFT-ALFF with those of Wavelet-ALFF based on five mother wavelets (namely, db2, bior4.4, morl, meyr, and sym3). In addition to the conventional frequency band of 0.0117-0.0781 Hz, a comparison was performed in sub-bands, namely, Slow-6 (0-0.0117 Hz), Slow-5 (0.0117-0.0273 Hz), Slow-4 (0.0273-0.0742 Hz), Slow-3 (0.0742-0.1992 Hz), and Slow-2 (0.1992-0.25 Hz). The results indicated that the Wavelet-ALFF of all five mother wavelets was generally more sensitive and reproducible than FFT-ALFF in all frequency bands. Specifically, in the higher frequency band Slow-2 (0.1992-0.25 Hz), the mean sensitivity of db2-ALFF results was 1.54 times that of FFT-ALFF, and the reproducibility of db2-ALFF results was 2.95 times that of FFT-ALFF. The findings suggest that wavelet-ALFF can replace FFT-ALFF, especially in the higher frequency band. Future studies should test more mother wavelets on other RS-fMRI metrics and multiple datasets., (Copyright © 2020 Luo, Wang, Yuan, Zhou, Xu, Ma, Zang and Zhang.)