Optimal propagation of neuronal electrical impulses depends on the insulation of axons by myelin,produced in the central nervous system by oligodendrocytes.Myelin is an extension of the oligodendrocyte plasma membrane...Optimal propagation of neuronal electrical impulses depends on the insulation of axons by myelin,produced in the central nervous system by oligodendrocytes.Myelin is an extension of the oligodendrocyte plasma membrane,which wraps around an axon to form a compact multi-layered sheath.Myelin is composed of a substantially higher proportion of lipids compared to other biological membranes and enriched in a small number of specialized proteins.展开更多
The goal of developing treatments for central nervous system（CNS）injuries is becoming more attainable with the recent identification of various drugs that can repair damaged axons.These discoveries have stemmed from...The goal of developing treatments for central nervous system（CNS）injuries is becoming more attainable with the recent identification of various drugs that can repair damaged axons.These discoveries have stemmed from screening efforts,large expression datasets and an improved understanding of the cellular and molecular biology underlying axon growth.It will be important to continue searching for new compounds that can induce axon repair.Here we describe how a family of adaptor proteins called 14-3-3s can be targeted using small molecule drugs to enhance axon outgrowth and regeneration.14-3-3s bind to many functionally diverse client proteins to regulate their functions.We highlight the recent discovery of the axon-growth promoting activity of fusicoccin-A,a fungus-derived small molecule that stabilizes 14-3-3 interactions with their client proteins.Here we discuss how fusicoccin-A could serve as a starting point for the development of drugs to induce CNS repair.展开更多
BACKGROUND： The interpretation of non-verbal social signals relies heavily on the ability to perceive biological motion. The posterior superior temporal sulcus is an important part of a network involved in biological...BACKGROUND： The interpretation of non-verbal social signals relies heavily on the ability to perceive biological motion. The posterior superior temporal sulcus is an important part of a network involved in biological motion processing. However, the underlying functional organization remains poorly understood. Several studies have suggested topographical representation of motion from different body parts within this region. However, other studies have shown that the posterior superior temporal sulcus responds equally to any body part. OBJECTIVE： Through the use of functional magnetic resonance imaging, the effects of socially relevant biological motion stimuli to activate a specific cortical area within posterior superior temporal sulcus, even if different body parts are involved in motion, will be analyzed. DESIGN, TIME AND SETTING： A functional magnetic resonance imaging, block-design was performed at the Magnetic Resonance Imaging, Surgical Medical Investigation Center, Havana, Cuba between 2004 and 2005. PARTICIPANTS： Thirteen healthy volunteers, from 19 to 55 years of age and compris!ng eight males and five females, were included in the study. METHODS： A conjunction analysis of responses to natural, dynamic, fearful, facial expressions and point-light, body-motion animations. MAIN OUTCOME MEASURES： The corresponding functionally specialized areas, as well as neural areas significant for both types of stimuli, were identified. RESULTS： One region within the posterior superior temporal sulcus of the right hemisphere was equally activated by facial and body complex motion. CONCLUSION： A site of common neural activity existed within the posterior superior temporal sulcus, which was not specific to a biological motion type. In addition, the activity was not related to a topographically organized body-part map, which suggested high-level visual representation of biological motion in this region.展开更多
Multiple sclerosis (MS) currently affects ~2.5 million people worldwide. MS is typically diagnosed in young adults and is usually not fatal, meaning people live long lives with MS. Affected individuals usually suffer ...Multiple sclerosis (MS) currently affects ~2.5 million people worldwide. MS is typically diagnosed in young adults and is usually not fatal, meaning people live long lives with MS. Affected individuals usually suffer from progressive physical and/or cognitive disability, often including fatigue (89.6%), depression (53.9%), memory loss (49.0%), motor or sensory dysfunction (76.4%, 70.4%) and urinary incontinence (50.8%).展开更多
Oligodendrocytes are the myelinating cells of the central nervous system(CNS)that ensheath nearby axons to support action potential propagation and axon metabolism.Myelination involves the rapid production of lipid-ri...Oligodendrocytes are the myelinating cells of the central nervous system(CNS)that ensheath nearby axons to support action potential propagation and axon metabolism.Myelination involves the rapid production of lipid-rich membrane,compaction of the multilamellar myelin sheath,and the resultant restriction of cytoplasm to non-compact compartments.During myelination,septate-like junctions form between the axon and lateral cytoplasmic endings of the myelin sheath at a specialized domain called the paranode(Figure 1A).展开更多
In this paper,the effects of an electron beam on X-pinch-produced spectra of L-shellMoplasma are investigated for the first time by principal component analysis(PCA);this analysis is compared with that of line ratio d...In this paper,the effects of an electron beam on X-pinch-produced spectra of L-shellMoplasma are investigated for the first time by principal component analysis(PCA);this analysis is compared with that of line ratio diagnostics.A spectral database for PCA extraction is arranged using a non-Local Thermodynamic Equilibrium(non-LTE)collisional radiative L-shell Mo model.PC vector spectra of L-shell Mo,including F,Ne,Na and Mg-like transitions are studied to investigate the polarization types of these transitions.PC1 vector spectra of F,Ne,Na and Mg-like transitions result in linear polarization of Stokes Q profiles.Besides,PC2 vector spectra show linear polarization of Stokes U profiles of 2p^(5)3s of Ne-like transitions which are known as responsive to a magnetic field[Trabert,Beiersdorfer,and Crespo Lo´pez-Urrutia,Nucl.InstrumMethods Phys.Res.,Sect.B 408,107–109(2017)].A 3D representation of PCA coefficients demonstrates that addition of an electron beam to the non-LTE model generates quantized,collective clusters which are translations of each other that follow V-shaped cascade trajectories,except for the case f=0.0.The extracted principal coefficients are used as a database for an Artificial Neural Network(ANN)to estimate the plasma electron temperature,density and beam fractions of the time-integrated,spatially resolved L-shellMoX-pinch plasma spectrum.PCA-based ANNs provide an advantage in reducing the network topology,with a more efficient backpropagation supervised learning algorithm.The modeled plasma electron temperature is about Te;660 eV and density n_(e)=1×10^(20) cm^(-3),in the presence of the fraction of the beams with f-0.1 and centered energy of 5 keV.展开更多
The letter by Bouton et al.（2016）“Restoring cortical control of functional movement in a human with quadriplegia”presents a case report of a 24 year old male with tetraplegia（C5–6）.The goal of the work was to b...The letter by Bouton et al.（2016）“Restoring cortical control of functional movement in a human with quadriplegia”presents a case report of a 24 year old male with tetraplegia（C5–6）.The goal of the work was to bypass the spinal cord injury（SCI）lesion to stimulate the right forearm muscles to perform six movements and daily functional tasks.展开更多
Ventromedial frontal lobe (VMF) damage is associated with impaired decision making. Recent efforts to understand the functions of this brain region have focused on its role in tracking reward, punishment and risk. How...Ventromedial frontal lobe (VMF) damage is associated with impaired decision making. Recent efforts to understand the functions of this brain region have focused on its role in tracking reward, punishment and risk. However, decision making is complex, and frontal lobe damage might be expected to affect it at other levels. This study used process-tracing techniques to explore the effect of VMF damage on multi-attribute decision making under certainty. Thirteen subjects with focal VMF damage were compared with 11 subjects with frontal damage that spared the VMF and 21 demographically matched healthy control subjects. Participants chose rental apartments in a standard information board task drawn from the literature on normal decision making. VMF subjects performed the decision making task in a way that differed markedly from all other groups, favouring an‘alternative-based’information acquisition strategy (i.e. they organized their information search around individual apartments). In contrast, both healthy control subjects and subjects with damage predominantly involving dorsal and/or lateral prefrontal cortex pursued primarily ‘attribute-based’search strategies (in which information was acquired about categories such as rent and noise level across several apartments). This difference in the pattern of information acquisition argues for systematic differences in the underlying decision heuristics and strategies employed by subjects with VMF damage, which in turn may affect the quality of their choices. These findings suggest that the processes supported by ventral and medial prefrontal cortex need to be conceptualized more broadly, to account for changes in decision making under conditions of certainty, as well as uncertainty, following damage to these areas.展开更多
As biomarkers are important in the early diagnosis ofAlzheimer’s disease （AD）, the frst collab-orative work of recruiting early-onset familial AD （EO-FAD） families in Canada and China was initiated in 2012. The r...As biomarkers are important in the early diagnosis ofAlzheimer’s disease （AD）, the frst collab-orative work of recruiting early-onset familial AD （EO-FAD） families in Canada and China was initiated in 2012. The registration networks have collected hundreds of pedigrees, for which genetic screening, neuropsycholog-ical tests and amyloid and tau imaging was used to study diagnostic biomarkers for preclinical and mild cognitive impairment （MCI） stages of AD. Besides identifying ped-igrees with novel mutations in presenilins （PSENs）/amy-loid precursor protein （APP）, the program has benefted training of Chinese research fellows, AD clinical trials forprevention,the ethical concernsfor clinical fndings, and other collaborative projects with Chinese investiga-tors. Further research of the collaborative program may facilitate the testing and clinical use of novel treatments for EOFAD and late onset AD and contribute to dementia prevention strategies in Canada and China.展开更多
Understanding the neural substrates of human cognition is a central goal of neuroscience research.Modern imaging techniques,such as functional magnetic resonance imaging(fMRI),provide an opportunity to map cognitive f...Understanding the neural substrates of human cognition is a central goal of neuroscience research.Modern imaging techniques,such as functional magnetic resonance imaging(fMRI),provide an opportunity to map cognitive function in vivo.To date,modeling shared information in task-evoked neural dynamics across individuals remains challenging,largely due to pronounced inter-subject variability in brain anatomy,function,and behaviors[1],[2].An emerging topic,known as hyperalignment or functional alignment,has been proposed recently[3],to map subject-specific neural responses onto a common representational space using either linear transformations of task-evoked neural activity[4]or resting-state connectivity profiles[5].However,these approaches often assume uniform neural responses across individuals,struggling to capture group heterogeneity and model functional interactions between brain areas[6].展开更多
The human brain, a marvel of intricate connections, functions as a complex network comprising structurally and functionally integrated regions. This network orchestrates a multitude of complex patterns through high-le...The human brain, a marvel of intricate connections, functions as a complex network comprising structurally and functionally integrated regions. This network orchestrates a multitude of complex patterns through high-level integration and continuous cooperation, essential for overall brain functionality [1].展开更多
Human cognition is usually underpinned by intrinsic structure and functional neural co-activation in spatially distributed brain regions.Owing to lacking an effective approach to quantifying the covarying of structure...Human cognition is usually underpinned by intrinsic structure and functional neural co-activation in spatially distributed brain regions.Owing to lacking an effective approach to quantifying the covarying of structure and functional responses,how the structural–functional circuits interact and how genes encode the relationships,to deepen our knowledge of human cognition and disease,are still unclear.Here,we propose a multimodal covariance network(MCN)construction approach to capture interregional covarying of the structural skeleton and transient functional activities for a single individual.We further explored the potential association between brain-wide gene expression patterns and structural–functional covarying in individuals involved in a gambling task and individuals with major depression disorder(MDD),adopting multimodal data from a publicly available human brain transcriptomic atlas and 2 independent cohorts.MCN analysis showed a replicable cortical structural–functional fine map in healthy individuals,and the expression of cognition-and disease phenotype-related genes was found to be spatially correlated with the corresponding MCN differences.Further analysis of cell type-specific signature genes suggests that the excitatory and inhibitory neuron transcriptomic changes could account for most of the observed correlation with task-evoked MCN differences.展开更多
Functional magnetic resonance imaging(fMRI)is a prevalent technology in brain research of cognition,emotion,development,and brain disorders.The traditional fMRI analysis is based on volume-based preprocessing pipeline...Functional magnetic resonance imaging(fMRI)is a prevalent technology in brain research of cognition,emotion,development,and brain disorders.The traditional fMRI analysis is based on volume-based preprocessing pipelines and algorithms,which means that the brain MRI data is to be registered to a 3-dimensional(3D)coordinate[1].However,the relatively low spatial resolution of fMRI may lead to partial-volume-effect(e.g.,a 3D region may contain signals from grey matter,white matter and even cerebrospinal fluid).Given the human brain function is organized in a brain surface mesh manner,therefore,a growing number of studies conducted surface-based preprocessing pipelines and algorithms.Surface-based methods reconstructed the brain grey matter into 2-dimensional cortical surface which better represent the curving structure of the brain.Surface-based method is superior to volume-based method on brain registration,signal–noise ratio and reproducibility of algorithms[2].Specifically,the traditional volume-based approach was reported with a spatial localization that is only 35%of the best surface-based method[2].展开更多
Parkinson's disease(PD)is characterized by motor deficits and a wide variety of non-motor symptoms.The age of onset,rate of disease progression and the precise profile of motor and non-motor symptoms display consi...Parkinson's disease(PD)is characterized by motor deficits and a wide variety of non-motor symptoms.The age of onset,rate of disease progression and the precise profile of motor and non-motor symptoms display considerable individual variation.Neuropathologically,the loss of substantia nigra dopaminergic neurons is a key feature of PD.The vast majority of PD patients exhibit alpha-synuclein aggregates in several brain regions,but there is also great variability in the neuropathology between individuals.While the dopamine replacement therapies can reduce motor symptoms,current therapies do not modify the disease progression.Numerous clinical trials using a wide variety of approaches have failed to achieve disease modification.It has been suggested that the heterogeneity of PD is a major contributing factor to the failure of disease modification trials,and that it is unlikely that a single treatment will be effective in all patients.Precision medicine,using drugs designed to target the pathophysiology in a manner that is specific to each individual with PD,has been suggested as a way forward.PD patients can be stratified according to whether they carry one of the risk variants associated with elevated PD risk.In this review we assess current clinical trials targeting two enzymes,leucine-rich repeat kinase 2(LRRK2)and glucocerebrosidase(GBA),which are encoded by two most common PD risk genes.Because the details of the pathogenic processes coupled to the different LRRK2 and GBA risk variants are not fully understood,we ask if these precision medicinebased intervention strategies will prove"precise"or"personalized"enough to modify the disease process in PD patients.We also consider at what phases of the disease that such strategies might be effective,in light of the genes being primarily associated with the risk of developing disease in the first place,and less clearly linked to the rate of disease progression.Finally,we critically evaluate the notion that therapies targeting LRRK2 and GBA might be relevant to a wider segment of PD patients,beyond those that actually carry risk variants of these genes.展开更多
Developmental exposure to bisphenol A(BPA),an endocrine-disrupting contaminant,impairs cognitive function in both animals and humans.However,whether BPA affects the development of primary sensory systems,which are the...Developmental exposure to bisphenol A(BPA),an endocrine-disrupting contaminant,impairs cognitive function in both animals and humans.However,whether BPA affects the development of primary sensory systems,which are the first to mature in the cortex,remains largely unclear.Using the rat as a model,we aimed to record the physiological and structural changes in the primary auditory cortex(A1)following lactational BPA exposure and their possible effects on behavioral outcomes.We found that BPA-exposed rats showed significant behavioral impairments when performing a sound temporal rate discrimination test.A significant alteration in spectral and temporal processing was also recorded in their A1,manifested as degraded frequency selectivity and diminished stimulus rate-following by neurons.These post-exposure effects were accompanied by changes in the density and maturity of dendritic spines in A1.Our findings demonstrated developmental impacts of BPA on auditory cortical processing and auditory-related discrimination,particularly in the temporal domain.Thus,the health implications for humans associated with early exposure to endocrine disruptors such as BPA merit more careful examination.展开更多
基金supported by on operating grant(#1038154) from the Multiple Sclerosis Society of Canada (to TEK)a Multiple Sclerosis Society of Canada Post-Doctoral Fellowship (to JDMG)。
文摘Optimal propagation of neuronal electrical impulses depends on the insulation of axons by myelin,produced in the central nervous system by oligodendrocytes.Myelin is an extension of the oligodendrocyte plasma membrane,which wraps around an axon to form a compact multi-layered sheath.Myelin is composed of a substantially higher proportion of lipids compared to other biological membranes and enriched in a small number of specialized proteins.
基金funded by the Canadian Institutes for Health Research and the Multiple Sclerosis Society of Canada
文摘The goal of developing treatments for central nervous system（CNS）injuries is becoming more attainable with the recent identification of various drugs that can repair damaged axons.These discoveries have stemmed from screening efforts,large expression datasets and an improved understanding of the cellular and molecular biology underlying axon growth.It will be important to continue searching for new compounds that can induce axon repair.Here we describe how a family of adaptor proteins called 14-3-3s can be targeted using small molecule drugs to enhance axon outgrowth and regeneration.14-3-3s bind to many functionally diverse client proteins to regulate their functions.We highlight the recent discovery of the axon-growth promoting activity of fusicoccin-A,a fungus-derived small molecule that stabilizes 14-3-3 interactions with their client proteins.Here we discuss how fusicoccin-A could serve as a starting point for the development of drugs to induce CNS repair.
文摘BACKGROUND： The interpretation of non-verbal social signals relies heavily on the ability to perceive biological motion. The posterior superior temporal sulcus is an important part of a network involved in biological motion processing. However, the underlying functional organization remains poorly understood. Several studies have suggested topographical representation of motion from different body parts within this region. However, other studies have shown that the posterior superior temporal sulcus responds equally to any body part. OBJECTIVE： Through the use of functional magnetic resonance imaging, the effects of socially relevant biological motion stimuli to activate a specific cortical area within posterior superior temporal sulcus, even if different body parts are involved in motion, will be analyzed. DESIGN, TIME AND SETTING： A functional magnetic resonance imaging, block-design was performed at the Magnetic Resonance Imaging, Surgical Medical Investigation Center, Havana, Cuba between 2004 and 2005. PARTICIPANTS： Thirteen healthy volunteers, from 19 to 55 years of age and compris!ng eight males and five females, were included in the study. METHODS： A conjunction analysis of responses to natural, dynamic, fearful, facial expressions and point-light, body-motion animations. MAIN OUTCOME MEASURES： The corresponding functionally specialized areas, as well as neural areas significant for both types of stimuli, were identified. RESULTS： One region within the posterior superior temporal sulcus of the right hemisphere was equally activated by facial and body complex motion. CONCLUSION： A site of common neural activity existed within the posterior superior temporal sulcus, which was not specific to a biological motion type. In addition, the activity was not related to a topographically organized body-part map, which suggested high-level visual representation of biological motion in this region.
文摘Multiple sclerosis (MS) currently affects ~2.5 million people worldwide. MS is typically diagnosed in young adults and is usually not fatal, meaning people live long lives with MS. Affected individuals usually suffer from progressive physical and/or cognitive disability, often including fatigue (89.6%), depression (53.9%), memory loss (49.0%), motor or sensory dysfunction (76.4%, 70.4%) and urinary incontinence (50.8%).
基金This work was supported by grants from the Multiple Sclerosis Society of Canada(No.3009 to TEK and No.2407 to DSN).
文摘Oligodendrocytes are the myelinating cells of the central nervous system(CNS)that ensheath nearby axons to support action potential propagation and axon metabolism.Myelination involves the rapid production of lipid-rich membrane,compaction of the multilamellar myelin sheath,and the resultant restriction of cytoplasm to non-compact compartments.During myelination,septate-like junctions form between the axon and lateral cytoplasmic endings of the myelin sheath at a specialized domain called the paranode(Figure 1A).
文摘In this paper,the effects of an electron beam on X-pinch-produced spectra of L-shellMoplasma are investigated for the first time by principal component analysis(PCA);this analysis is compared with that of line ratio diagnostics.A spectral database for PCA extraction is arranged using a non-Local Thermodynamic Equilibrium(non-LTE)collisional radiative L-shell Mo model.PC vector spectra of L-shell Mo,including F,Ne,Na and Mg-like transitions are studied to investigate the polarization types of these transitions.PC1 vector spectra of F,Ne,Na and Mg-like transitions result in linear polarization of Stokes Q profiles.Besides,PC2 vector spectra show linear polarization of Stokes U profiles of 2p^(5)3s of Ne-like transitions which are known as responsive to a magnetic field[Trabert,Beiersdorfer,and Crespo Lo´pez-Urrutia,Nucl.InstrumMethods Phys.Res.,Sect.B 408,107–109(2017)].A 3D representation of PCA coefficients demonstrates that addition of an electron beam to the non-LTE model generates quantized,collective clusters which are translations of each other that follow V-shaped cascade trajectories,except for the case f=0.0.The extracted principal coefficients are used as a database for an Artificial Neural Network(ANN)to estimate the plasma electron temperature,density and beam fractions of the time-integrated,spatially resolved L-shellMoX-pinch plasma spectrum.PCA-based ANNs provide an advantage in reducing the network topology,with a more efficient backpropagation supervised learning algorithm.The modeled plasma electron temperature is about Te;660 eV and density n_(e)=1×10^(20) cm^(-3),in the presence of the fraction of the beams with f-0.1 and centered energy of 5 keV.
文摘The letter by Bouton et al.（2016）“Restoring cortical control of functional movement in a human with quadriplegia”presents a case report of a 24 year old male with tetraplegia（C5–6）.The goal of the work was to bypass the spinal cord injury（SCI）lesion to stimulate the right forearm muscles to perform six movements and daily functional tasks.
文摘Ventromedial frontal lobe (VMF) damage is associated with impaired decision making. Recent efforts to understand the functions of this brain region have focused on its role in tracking reward, punishment and risk. However, decision making is complex, and frontal lobe damage might be expected to affect it at other levels. This study used process-tracing techniques to explore the effect of VMF damage on multi-attribute decision making under certainty. Thirteen subjects with focal VMF damage were compared with 11 subjects with frontal damage that spared the VMF and 21 demographically matched healthy control subjects. Participants chose rental apartments in a standard information board task drawn from the literature on normal decision making. VMF subjects performed the decision making task in a way that differed markedly from all other groups, favouring an‘alternative-based’information acquisition strategy (i.e. they organized their information search around individual apartments). In contrast, both healthy control subjects and subjects with damage predominantly involving dorsal and/or lateral prefrontal cortex pursued primarily ‘attribute-based’search strategies (in which information was acquired about categories such as rent and noise level across several apartments). This difference in the pattern of information acquisition argues for systematic differences in the underlying decision heuristics and strategies employed by subjects with VMF damage, which in turn may affect the quality of their choices. These findings suggest that the processes supported by ventral and medial prefrontal cortex need to be conceptualized more broadly, to account for changes in decision making under conditions of certainty, as well as uncertainty, following damage to these areas.
文摘As biomarkers are important in the early diagnosis ofAlzheimer’s disease （AD）, the frst collab-orative work of recruiting early-onset familial AD （EO-FAD） families in Canada and China was initiated in 2012. The registration networks have collected hundreds of pedigrees, for which genetic screening, neuropsycholog-ical tests and amyloid and tau imaging was used to study diagnostic biomarkers for preclinical and mild cognitive impairment （MCI） stages of AD. Besides identifying ped-igrees with novel mutations in presenilins （PSENs）/amy-loid precursor protein （APP）, the program has benefted training of Chinese research fellows, AD clinical trials forprevention,the ethical concernsfor clinical fndings, and other collaborative projects with Chinese investiga-tors. Further research of the collaborative program may facilitate the testing and clinical use of novel treatments for EOFAD and late onset AD and contribute to dementia prevention strategies in Canada and China.
基金supported by the STI2030-Major Projects(2021ZD0200201,2022ZD0211500)the National Natural Science Foundation of China(62201519,52307259,62327805,and 82151307).
文摘Understanding the neural substrates of human cognition is a central goal of neuroscience research.Modern imaging techniques,such as functional magnetic resonance imaging(fMRI),provide an opportunity to map cognitive function in vivo.To date,modeling shared information in task-evoked neural dynamics across individuals remains challenging,largely due to pronounced inter-subject variability in brain anatomy,function,and behaviors[1],[2].An emerging topic,known as hyperalignment or functional alignment,has been proposed recently[3],to map subject-specific neural responses onto a common representational space using either linear transformations of task-evoked neural activity[4]or resting-state connectivity profiles[5].However,these approaches often assume uniform neural responses across individuals,struggling to capture group heterogeneity and model functional interactions between brain areas[6].
基金supported by the Sci-Tech Innovation 2030-Major Project of Brain Science and Brain-inspired Intelligence Technology (2021ZD0200600)the National Natural Science Foundation of China (82122035,81671774,81630031)+3 种基金the Key Research Program of the Chinese Academy of Sciences (ZDBSSSW-JSC006)Beijing Nova Program of Science and Technology (Z191100001119104 and 20230484465)Beijing Natural Science Foundation (J230040)the Scientific Foundation of Institute of Psychology,Chinese Academy of Sciences (E2CX4425YZ)。
文摘The human brain, a marvel of intricate connections, functions as a complex network comprising structurally and functionally integrated regions. This network orchestrates a multitude of complex patterns through high-level integration and continuous cooperation, essential for overall brain functionality [1].
基金the STI 2030-Major Projects(#2022ZD0208500,#2022ZD02114000,and#2022ZD0208900)the National Natural Science Foundation of China(#62103085,#61961160705,#U19A2082,and#62006197)+2 种基金the Science and Technology Development Fund,Macao SAR(file no.0045/2019/AFJ)the Key R&D Projects of Science&Technology Department of Sichuan Province(#23ZDYF0961)the Scientific Research Foundation of Sichuan Provincial People's Hospital(#2021LY21).
文摘Human cognition is usually underpinned by intrinsic structure and functional neural co-activation in spatially distributed brain regions.Owing to lacking an effective approach to quantifying the covarying of structure and functional responses,how the structural–functional circuits interact and how genes encode the relationships,to deepen our knowledge of human cognition and disease,are still unclear.Here,we propose a multimodal covariance network(MCN)construction approach to capture interregional covarying of the structural skeleton and transient functional activities for a single individual.We further explored the potential association between brain-wide gene expression patterns and structural–functional covarying in individuals involved in a gambling task and individuals with major depression disorder(MDD),adopting multimodal data from a publicly available human brain transcriptomic atlas and 2 independent cohorts.MCN analysis showed a replicable cortical structural–functional fine map in healthy individuals,and the expression of cognition-and disease phenotype-related genes was found to be spatially correlated with the corresponding MCN differences.Further analysis of cell type-specific signature genes suggests that the excitatory and inhibitory neuron transcriptomic changes could account for most of the observed correlation with task-evoked MCN differences.
基金supported by the National Natural Science Foundation of China(82122035,81671774,and 81630031)the 13th Five-year Informatization Plan of Chinese Academy of Sciences(XXH13505)+1 种基金the Key Research Program of the Chinese Academy of Sciences(ZDBS-SSW-JSC006)the Beijing Nova Program of Science and Technology(Z191100001119104)。
文摘Functional magnetic resonance imaging(fMRI)is a prevalent technology in brain research of cognition,emotion,development,and brain disorders.The traditional fMRI analysis is based on volume-based preprocessing pipelines and algorithms,which means that the brain MRI data is to be registered to a 3-dimensional(3D)coordinate[1].However,the relatively low spatial resolution of fMRI may lead to partial-volume-effect(e.g.,a 3D region may contain signals from grey matter,white matter and even cerebrospinal fluid).Given the human brain function is organized in a brain surface mesh manner,therefore,a growing number of studies conducted surface-based preprocessing pipelines and algorithms.Surface-based methods reconstructed the brain grey matter into 2-dimensional cortical surface which better represent the curving structure of the brain.Surface-based method is superior to volume-based method on brain registration,signal–noise ratio and reproducibility of algorithms[2].Specifically,the traditional volume-based approach was reported with a spatial localization that is only 35%of the best surface-based method[2].
基金P.B.was supported by grants from the National Institutes of Health(1R01DC016519-01,5R21NS 093993-02,1R21 NS 106078-01A1)P.B.received additional awards from Office of the Assistant Secretary of Defense for Health Affairs(Parkinson's Research Program,Award No.W81XWH-17-1-0534)+1 种基金the Peter C.and Emajean Cook Foundation,which are outside but relevant to the submitted workZ.G.O.was supported by grants from the Michael J.Fox Foundation,the Canadian Consortium on Neurodegeneration in Aging(CCNA),the Canada First Research Excellence Fund(CFREF)from Parkinson Canada,awarded to McGill University for the Healthy Brains for Healthy Lives(HBHL)program.
文摘Parkinson's disease(PD)is characterized by motor deficits and a wide variety of non-motor symptoms.The age of onset,rate of disease progression and the precise profile of motor and non-motor symptoms display considerable individual variation.Neuropathologically,the loss of substantia nigra dopaminergic neurons is a key feature of PD.The vast majority of PD patients exhibit alpha-synuclein aggregates in several brain regions,but there is also great variability in the neuropathology between individuals.While the dopamine replacement therapies can reduce motor symptoms,current therapies do not modify the disease progression.Numerous clinical trials using a wide variety of approaches have failed to achieve disease modification.It has been suggested that the heterogeneity of PD is a major contributing factor to the failure of disease modification trials,and that it is unlikely that a single treatment will be effective in all patients.Precision medicine,using drugs designed to target the pathophysiology in a manner that is specific to each individual with PD,has been suggested as a way forward.PD patients can be stratified according to whether they carry one of the risk variants associated with elevated PD risk.In this review we assess current clinical trials targeting two enzymes,leucine-rich repeat kinase 2(LRRK2)and glucocerebrosidase(GBA),which are encoded by two most common PD risk genes.Because the details of the pathogenic processes coupled to the different LRRK2 and GBA risk variants are not fully understood,we ask if these precision medicinebased intervention strategies will prove"precise"or"personalized"enough to modify the disease process in PD patients.We also consider at what phases of the disease that such strategies might be effective,in light of the genes being primarily associated with the risk of developing disease in the first place,and less clearly linked to the rate of disease progression.Finally,we critically evaluate the notion that therapies targeting LRRK2 and GBA might be relevant to a wider segment of PD patients,beyond those that actually carry risk variants of these genes.
基金the National NaturalScienceFoundationofChina(32171134and 32161160325)the National Science and Technology Innovation 2030 Major Program(2022ZD0204804)+2 种基金a Project of Shanghai Science and Technology Commission(21490713200)the Program of Introducing Talents of Discipline to Universities(B16018)a matching fund from the NYU-ECNU Institute of Brain and Cognitive Science at NYU Shanghai.
文摘Developmental exposure to bisphenol A(BPA),an endocrine-disrupting contaminant,impairs cognitive function in both animals and humans.However,whether BPA affects the development of primary sensory systems,which are the first to mature in the cortex,remains largely unclear.Using the rat as a model,we aimed to record the physiological and structural changes in the primary auditory cortex(A1)following lactational BPA exposure and their possible effects on behavioral outcomes.We found that BPA-exposed rats showed significant behavioral impairments when performing a sound temporal rate discrimination test.A significant alteration in spectral and temporal processing was also recorded in their A1,manifested as degraded frequency selectivity and diminished stimulus rate-following by neurons.These post-exposure effects were accompanied by changes in the density and maturity of dendritic spines in A1.Our findings demonstrated developmental impacts of BPA on auditory cortical processing and auditory-related discrimination,particularly in the temporal domain.Thus,the health implications for humans associated with early exposure to endocrine disruptors such as BPA merit more careful examination.
