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Artificial intelligence meets body sense: task-driven neural networks reveal computational principles of the proprioceptive pathway

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3147-3149页

作者： Leonard E.van Dyck Frank Bremmer Katharina Dobs department of Psychology Justus Liebig University GiessenGiessenGermany Max Planck Institute for Human Cognitive and brain Sciences LeipzigGermany Center for Mind Brain and BehaviorUniversities of MarburgGiessenand DarmstadtMarburgGermany department of Neurophysics Philipps-Universitat MarburgMarburgGermany

In a recent study published in Cell,Marin Vargas and Bisi et al.1 present an innovative approach to unravel the computational principles underlying proprioceptive processing in non-human *** findings showcase the utility of task-driven modeling in advancing neuroscience and offer translational potential by providing seminal insights into the goals and mechanisms by which the brain encodes body position and movements.

关键词： networks neural principles

SH2B1 Tunes Hippocampal ERK Signaling to Influence Fluid Intelligence in Humans and Mice

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Research 2024年第3期2023卷 369-389页

作者： Xiujuan Du Yuhua Yan Juehua Yu Tailin Zhu Chu-Chung Huang Lingli Zhang Xingyue Shan Ren Li Yuan Dai Hui LV Xiao-Yong Zhang Jianfeng Feng Wei-Guang Li Qiang Luo Fei Li Developmental and Behavioral Pediatric department Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research and Ministry of Education-Shanghai Key Laboratory for Children's Environmental HealthXinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China Developmental and Behavioral Pediatric department Shanghai Xinhua Children's HospitalShanghai 200092China National Clinical Research Center for Aging and Medicine at Huashan Hospital Institute of Science and Technology for Brain-lnspired IntelligenceMinistry of Education-Key Laboratory of Computational Neuroscience and Brain-lnspired IntelligenceFudan UniversityShanghai 200433China State Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for brain Science Institutes of Brain Science and Human Phenom InstituteFudan UniversityShanghai 200032China Shanghai Key Laboratory of brain Functional Genomics(Ministry of Education) School of Life SciencesEast China Normal UniversityShanghai 200062China department of Rehabilitation Medicine Huashan HospitalInstitute for Translational Brain ResearchState Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain ScienceFudan UniversityShanghai 200032China Center for Experimental Studies and Research The First Affliated Hospital of Kunming Medical UniversityKunming 650032China Shanghai Research Center for brain Science and brain-lnspired Intelligence Shanghai201210China Institute of Cognitive Neuroscience School of Psychology and Cognitive ScienceEast China Normal UniversityShanghai 200062China.

Fluid intelligence is a cognitive domain that encompasses general reasoning, pattern recognition, and problem-solving abilities independent of task-specific experience. Understanding its genetic and neural underpinnings is critical yet challenging for predicting human development, lifelong health, and well-being. One approach to address this challenge is to map the network of correlations between intelligence and other constructs. In the current study, we performed a genome-wide association study using fluid intelligence quotient scores from the UK Biobank to explore the genetic architecture of the associations between obesity risk and fluid intelligence. Our results revealed novel common genetic loci (SH2B1, TUFM, ATP2A1, and FOXO3) underlying the association between fluid intelligence and body metabolism. Surprisingly, we demonstrated that SH2B1 variation influenced fluid intelligence independently of its effects on metabolism but partially mediated its association with bilateral hippocampal volume. Consistently, selective genetic ablation of Sh2b1 in the mouse hippocampus, particularly in inhibitory neurons, but not in excitatory neurons, significantly impaired working memory, short-term novel object recognition memory, and behavioral flexibility, but not spatial learning and memory, mirroring the human intellectual performance. Single-cell genetic profiling of Sh2B1-regulated molecular pathways revealed that Sh2b1 deletion resulted in aberrantly enhanced extracellular signal-regulated kinase (ERK) signaling, whereas pharmacological inhibition of ERK signaling reversed the associated behavioral impairment. Our cross-species study thus provides unprecedented insight into the role of SH2B1 in fluid intelligence and has implications for understanding the genetic and neural underpinnings of lifelong mental health and well-being.

关键词： metabolism impaired reversed

Vitamin D-binding protein in plasma microglia-derived extracellular vesicles as a potential biomarker for major depressive disorder

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Genes & Diseases 2024年第2期11卷 1009-1021页

作者： Gaojia Zhang Ling Li Yan Kong Dandan Xu Yu Bao Zhiting Zhang Zhixiang Liao Jiao Jiao Dandan Fan Xiaojing Long Ji Dai Chunming Xie Zhiqiang Meng Zhijun Zhang department of Neurology Affiliated Zhongda HospitalResearch Institution of NeuropsychiatrySchool of MedicineSoutheast UniversityNanjingJiangsu 210009China department of Biochemistry and Molecular Biology School of MedicineSoutheast UniversityNanjingJiangsu 210009China Shenzhen Key Laboratory of Drug Addiction Brain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of Sciences (CAS)ShenzhenGuangdong 518000China CAS Key Laboratory of brain Connectome and Manipulation The Brain Cognition and Brain Disease Institute (BCBDI)Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518055China Lauterbur Research Center for Biomedical Imaging Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518055China Shenzhen-Hong Kong Institute of brain Sciences-Shenzhen Fundamental Research Institutions ShenzhenGuangdong 518000China brain Cognition and brain Disease Institute Department of Mental Health and Public HealthFaculty of Life and Health SciencesShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518055China

No well-established biomarkers are available for the clinical diagnosis of major depressive disorder(MDD).Vitamin D-binding protein(VDBP)is altered in plasma and postmortem dorsolateral prefrontal cortex(DLPFC)tissues of MDD ***,the role of VDBP as a potential biomarker of MDD diagnosis was further *** extracellular vesicles(EVs)and brain cell-derived EVs(BCDEVs)were isolated from the plasma of first-episode drug-naïve or drug-free MDD patients and well-matched healthy controls(HCs)in discovery(20 MDD patients and 20 HCs)and validation cohorts(88 MDD patients and 38 HCs).VDBP level in the cerebrospinal fluid(CSF)from chronic glucocorticoid-induced depressed rhesus macaques or prelimbic cortex from lipopolysaccharide(LPS)-induced depressed mice and wild control groups was measured to evaluate its relationship with VDBP in plasma microglia-derived extracellular vesicles(MDEVs).VDBP was significantly decreased in MDD plasma MDEVs compared to HCs,and negatively correlated with HAMD-24 score with the highest diagnostic accuracy among *** in plasma MDEVs was decreased both in depressed rhesus macaques and mice.A positive correlation of VDBP in MDEVs with that in CSF was detected in depressed rhesus *** levels in prelimbic cortex microglia were negatively correlated with those in plasma MDEVs in depressed *** main results suggested that VDBP in plasma MDEVs might serve as a prospective candidate biomarker for MDD diagnosis.

关键词： Biomarker Cerebrospinal fluid Major depressive disorder Microglia derived extracellular vesicles Vitamin-D binding protein

Rapid Unconscious Acquisition of Conditioned Fear with Low-Spatial-Frequency but Emotionally Neutral Stimuli

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Research 2024年第1期2023卷 753-762页

作者： Yujie Chen Si Chen Zhongju Sun Xilei Zhang Xiangyong Yuan Liang Wang Yi Jiang State Key Laboratory of brain and Cognitive Sciences CAS Center for Excellence in Brain Science and Intelligence TechnologyInstitute of PsychologyChinese Academy of SciencesBeijing 100101China department of Psychology University of Chinese Academy of SciencesBeijing 100049China Chinese Institute for brain Research Beijing 102206China CAS Key Laboratory of Mental Health Institute of PsychologyChinese Academy of SciencesBeijing 100101China

It has long been proposed that emotionally“prepared”(i.e.,fear-related)stimuli are privileged in the unconscious acquisition of conditioned ***,as fear processing is suggested to highly depend on the coarse,low-spatial-frequency(LSF)components of the fear-related stimuli,it is plausible that LSF may play a unique role in the unconscious fear conditioning even with emotionally neutral ***,we provided empirical evidence that,following classical fear conditioning,an invisible,emotionally neutral conditioned stimulus(CS+)with LSF,but not with high spatial frequency(HSF),can rapidly elicit stronger skin conductance responses(SCRs)and larger pupil diameters than its CS−*** comparison,consciously perceived emotionally neutral CS+with LSF and HSF elicited comparable *** together,these results support that the unconscious fear conditioning does not necessarily entail emotionally prepared stimuli but prioritizes LSF information processing and highlight the crucial distinctions between the unconscious and the conscious fear *** findings not only coincide with the postulation that a rapid,spatial-frequency-dependent subcortical route is engaged in unconscious fear processing but also suggest the existence of multiple routes for conscious fear processing.

关键词： neutral necessarily diameters

Progress and Implications from Genetic Studies of Bipolar Disorder

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Neuroscience Bulletin 2024年第8期40卷 1160-1172页

作者： Lingzhuo Kong Yiqing Chen Yuting Shen Danhua Zhang Chen Wei Jianbo Lai Shaohua Hu department of Psychiatry the First Affiliated HospitalZhejiang University School of MedicineHangzhou310003China The Key Laboratory of Mental Disorder Management in Zhejiang Province Hangzhou310003China brain Research Institute of Zhejiang University Hangzhou310003China Zhejiang Engineering Center for Mathematical Mental Health Hangzhou310003China department of Neurobiology NHC and CAMS Key Laboratory of Medical NeurobiologySchool of Brain Science and Brian Medicineand MOE Frontier Science Center for Brain Science and Brain-machine IntegrationZhejiang University School of MedicineHangzhou310003China

With the advancements in gene sequencing technologies,including genome-wide association studies,polygenetic risk scores,and high-throughput sequencing,there has been a tremendous advantage in mapping a detailed blueprint for the genetic model of bipolar disorder(BD).To date,intriguing genetic clues have been identified to explain the development of BD,as well as the genetic association that might be applied for the development of susceptibility prediction and pharmacogenetic *** genes of BD,such as CACNA1C,ANK3,TRANK1,and CLOCK,have been found to be involved in various pathophysiological processes correlated with *** the specific roles of these genes have yet to be determined,genetic research on BD will help improve the prevention,therapeutics,and prognosis in clinical *** latest preclinical and clinical studies,and reviews of the genetics of BD,are analyzed in this review,aiming to summarize the progress in this intriguing field and to provide perspectives for individualized,precise,and effective clinical practice.

关键词： Bipolar disorder Genetics Risk gene Genome-wide association study Sequencing technology

Neuroprotective effects of chaperone-mediated autophagy in neurodegenerative diseases

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Neural Regeneration Research 2024年第6期19卷 1291-1298页

作者： Qi Jia Jin Li Xiaofeng Guo Yi Li You Wu Yuliang Peng Zongping Fang Xijing Zhang department of Anesthesiology and Perioperative Medicine and department of Intensive Care Unit Xijing HospitalThe Fourth Military Medical UniversityXi’anShaanxi ProvinceChina department of Critical Care Medicine Air Force Medical CenterBeijingChina Translational Research Institute of brain and brain-Like Intelligence Shanghai Fourth People’s HospitalSchool of MedicineTongji UniversityShanghaiChina

Chaperone-mediated autophagy is one of three types of autophagy and is characterized by the selective degradation of ***-mediated autophagy contributes to energy balance and helps maintain cellular homeostasis,while providing nutrients and support for cell ***-mediated autophagy activity can be detected in almost all cells,including *** to the extreme sensitivity of neurons to their environmental changes,maintaining neuronal homeostasis is critical for neuronal growth and ***-mediated autophagy dysfunction is closely related to central nervous system *** has been shown that neuronal damage and cell death are accompanied by chaperone-mediated autophagy *** certain conditions,regulation of chaperone-mediated autophagy activity attenuates *** this paper,we review the changes in chaperone-mediated autophagy in neurodegenerative diseases,brain injury,glioma,and autoimmune *** also summarize the most recent research progress on chaperone-mediated autophagy regulation and discuss the potential of chaperone-mediated autophagy as a therapeutic target for central nervous system diseases.

关键词： chaperone-mediated autophagy neurodegenerative disease neuronal homeostasis neuroprotection

Chinese patients with adult onset leukodystrophy caused by CST3 variants

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Journal of Genetics and Genomics 2024年第7期51卷 778-780页

作者： Yi Zhang Zhi-Ying Wu department of Medical Genetics and Center for Rare Diseases Zhejiang Key Laboratory of Rare Diseases for Precision Medicine and Clinical TranslationSecond Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China Nanhu brain-computer Interface Institute HangzhouZhejiang 314050China department of Neurology Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China MOE Frontier Science Center for brain Science and brain-machine Integration School of Brain Science and Brain MedicineZhejiang UniversityHangzhouZhejiang 310012China

Leukodystrophies represent a group of cerebral white matter disorders that mainly affect axon-glia *** disorders are clinically diverse and display significant genetic *** is challenging to differentiate hereditary leukodystrophies,particularly those that present in adulthood,from acquired leukodystrophies and other genetic disorders,such as multiple sclerosis(MS)or hereditary spastic paraplegia(HSP)(Wei et al.,2021).Over the past few decades,a series of causative genes associated with leukodystrophies have been identified(Kohler et al.,2018).Nevertheless,a significant proportion of patients still lack a precise molecular diagnosis.

关键词： al. patients Kohler

Glioma-derived ANXA1 suppresses the immune response to TLR3 ligands by promoting an anti-inflammatory tumor microenvironment

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Cellular & Molecular Immunology 2024年第1期21卷 47-59页

作者： Yu Zheng Haihui Jiang Naixue Yang Shaoping Shen Daosheng Huang Lemei Jia Jing Ling Longchen Xu Mingxiao Li Kefu Yu Xiaohui Ren Yong Cui Xun Lan Song Lin Xin Lin Institute for Immunology and School of Medicine Tsinghua UniversityBeijing100084China department of Neurosurgery Beijing Tiantan HospitalCapital Medical UniversityChina.National Clinical Research Center for Neurological DiseasesCenter of Brain TumorBeijing Institute for Brain Disorders and Beijing Key Laboratory of Brain TumorBeijing100070China department of Neurosurgery Peking University Third HospitalPeking UniversityBeijing100191China Tsinghua-Peking Center for Life Sciences Beijing100084China

A highly immunosuppressive tumor microenvironment(TME)and the presence of the blood‒brain barrier are the two major obstacles to eliciting an effective immune response in patients with high-grade glioma(HGG).Here,we tried to enhance the local innate immune response in relapsed HGG by intracranially injecting poly(I:C)to establish a robust antitumor immune response in this registered clinical trial(NCT03392545).During the follow-up,12/27(44.4%)patients who achieved tumor control concomitant with survival benefit were regarded as responders in our *** found that the T-cell receptor(TCR)repertoire in the TME was reshaped after poly(I:C)*** on the RNA-seq analysis of tumor samples,the expression of annexin A1(ANXA1)was significantly upregulated in the tumor cells of nonresponders,which was further validated at the protein *** vitro and in vivo experiments showed that ANXA1 could induce the production of M2-like macrophages and microglia via its surface receptor formyl peptide receptor 1(FPR1)to establish a Treg cell-driven immunosuppressive TME and suppress the antitumor immune response facilitated by poly(I:C).The ANXA1/FPR1 signaling axis can inhibit the innate immune response of glioma patients by promoting an anti-inflammatory and Treg-driven ***,ANXA1 could serve as a reliable predictor of response to poly(I:C),with a notable predictive accuracy rate of 92.3%.In light of these notable findings,this study unveils a new perspective of immunotherapy for gliomas.

关键词： glioma ANXA1 TLR3 poly(I:C) immunotherapy

Treatment with intravenous alteplase in ischaemic stroke patients with onset time between 4.5 and 24 hours(HOPE):protocol for a randomised,controlled,multicentre study

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Stroke & Vascular Neurology 2024年第3期9卷 318-323,I0274-I0282页

作者： Zhongyu Luo Ying Zhou Yaode He Shenqiang Yan Zhicai Chen Xuting Zhang Yi Chen Lu-Sha Tong Wansi Zhong Haitao Hu Kemeng Zhang Jiansheng Yang Bruce C V Campbell Min Lou department of Neurology Zhejiang University School of Medicine Second Affiliated HospitalHangzhouZhejiangChina department of Medicine and Neurology Melbourne Brain Centre at Royal Melbourne HospitalParkvilleVictoriaAustralia

Background While intravenous thrombolysis is recommended for patients who had an acute ischaemic stroke(AIS)within 4.5hours of symptom onset,there are few randomised trials investigating the benefits of thrombolysis beyond this therapeutic *** To determine whether patients who had an AIS selected with the presence of potentially salvageable tissue on CT perfusion at 4.5–24hours after stroke onset(for stroke with unknown onset time,the midpoint of the time last known to be well and symptom recognition time;for wake-up stroke,the midpoint of the time last known to be well or sleep onset and wake up time)will benefit from intravenous *** HOPE is a prospective,multicentre,randomised,open-label blinded endpoint trial with the stage of phase *** treatment allocation employs 1:1 *** treatment arm under investigation is alteplase with standard therapy,the control arm is standard *** imaging criteria include ischaemic core volume≤70mL,penumbra≥10mL and mismatch≥20%.Study outcomes The primary outcome is non-disabled functional outcome(assessed as modified Rankin Scale score of 0–1 at 90 days).Discussion HOPE is the first trial to investigate whether intravenous thrombolysis with alteplase offers benefits in patients who had an AIS presenting within 4.5–24hours,which has the potential to extend time window and expand eligible population for thrombolysis therapy.

关键词： patients intravenous centre