Approximately 30%-40% of epilepsy patients do not respond well to adequate anti-seizure medications(ASMs),a condition known as pharmacoresistant epilepsy.The management of pharmacoresistant epilepsy remains an intract...Approximately 30%-40% of epilepsy patients do not respond well to adequate anti-seizure medications(ASMs),a condition known as pharmacoresistant epilepsy.The management of pharmacoresistant epilepsy remains an intractable issue in the clinic.Its early prediction is important for prevention and diagnosis.However,it still lacks effective predictors and approaches.Here,a classical model of pharmacoresistant temporal lobe epilepsy(TLE)was established to screen pharmacoresistant and pharmaco-responsive individuals by applying phenytoin to amygdaloid-kindled rats.Ictal electroencephalograms(EEGs)recorded before phenytoin treatment were analyzed.Based on ictal EEGs from pharmacoresistant and pharmaco-responsive rats,a convolutional neural network predictive model was constructed to predict pharmacoresistance,and achieved 78% prediction accuracy.We further found the ictal EEGs from pharmacoresistant rats have a lower gamma-band power,which was verified in seizure EEGs from pharmacoresistant TLE patients.Prospectively,therapies targeting the subiculum in those predicted as“pharmacoresistant”individual rats significantly reduced the subsequent occurrence of pharmacoresistance.These results demonstrate a new methodology to predict whether TLE individuals become resistant to ASMs in a classic pharmacoresistant TLE model.This may be of translational importance for the precise management of pharmacoresistant TLE.展开更多
Epilepsy is a common neurological disorder characterized by hyperexcitability in the brain.Its pathogenesis is classically associated with an imbalance of excitatory and inhibitory neurons.Calretinin(CR)is one of the ...Epilepsy is a common neurological disorder characterized by hyperexcitability in the brain.Its pathogenesis is classically associated with an imbalance of excitatory and inhibitory neurons.Calretinin(CR)is one of the three major types of calcium-binding proteins present in inhibitory GABAergic neurons.The functions of CR and its role in neural excitability are still unknown.Recent data suggest that CR neurons have diverse neurotransmitters,morphologies,distributions,and functions in different brain regions across various species.Notably,CR neurons in the hippocampus,amygdala,neocortex,and thalamus are extremely susceptible to excitotoxicity in the epileptic brain,but the causal relationship is unknown.In this review,we focus on the heterogeneous functions of CR neurons in different brain regions and their relationship with neural excitability and epilepsy.Importantly,we provide perspectives on future investigations of the role of CR neurons in epilepsy.展开更多
Previous studies show that infrared radiation temperature(IRT)abnormalities are always accompanied by the crack development in rocks under external loads.In this context,experiments were conducted on preflawed sandsto...Previous studies show that infrared radiation temperature(IRT)abnormalities are always accompanied by the crack development in rocks under external loads.In this context,experiments were conducted on preflawed sandstone to investigate the infrared radiation characteristics during failure process.Two indicators were defined herein,i.e.coefficient of variation of IRT(CVIRT)and skewness of IRT(SIRT).The regression analysis shows that the IRT probability distributions during loading process fit the Gaussian model.The variations in the CVIRT are characterized by four stages:primary stage,steady stage,accelerating stage and post-peak stage.Besides,the variations in the SIRT are divided into three stages:primary stage,steady stage and failure and post-peak stage.The precursor point for preflawed rock failure is identified based on the CVIRTetime curve,with average precursor point of 83%of the peak stress.Compared with other IRT indicators,the proposed two IRT indicators have higher sensitivity to IRT abnormalities during failure process.Furthermore,the connection between the IRT indicators and the rock fracturing was investigated to interpret the IRT indicator abnormalities.Based on the Verhulst inverse function,a new quantitative model was presented to describe the primary stage,steady stage and accelerating stage of the CVIRTetime curve.The results obtained in this study can provide early-warning information for rock failure prediction.展开更多
Schizophrenia is a common and severe mental disorder with a lifetime prevalence of~1%[1]Apart from the typical positive symptoms,such as hallucinations and delusions,which mainly make patients seek medication,60%-70%o...Schizophrenia is a common and severe mental disorder with a lifetime prevalence of~1%[1]Apart from the typical positive symptoms,such as hallucinations and delusions,which mainly make patients seek medication,60%-70%of patients are tortured by negative symptoms(e.g.apathy and alogia)and cognitive deficits that impose a long-term burden on patients[2].展开更多
Temporal lobe epilepsy(TLE),one of the most common drug-resistant epilepsies,is characterized by abnormal recurrent excitatory activity originating from the temporal lobe.In the dentate gyrus(DG)of the hippocampus.
A recent study published in Neuron by Tiwari et al.identified the critical role of 5-HT2A receptor in ventral hippocampal parvalbumin(PV)interneurons(INs)in mediating the acute anxiolytic effects of the serotonergic p...A recent study published in Neuron by Tiwari et al.identified the critical role of 5-HT2A receptor in ventral hippocampal parvalbumin(PV)interneurons(INs)in mediating the acute anxiolytic effects of the serotonergic psychedelic 2,5-dimethoxy-4-iodoamphetamine(DOI).This study not only advances psychedelic neuropharmacology but also provides a robust framework for developing novel rapid-acting therapeutics for anxiety disorders[1].展开更多
Temporal lobe epilepsy(TLE),one common type of medically refractory epilepsy,is accompanied with altered adult-born dentate granule cells(abDGCs).However,the causal role of abDGCs in recurrent seizures of TLE is not f...Temporal lobe epilepsy(TLE),one common type of medically refractory epilepsy,is accompanied with altered adult-born dentate granule cells(abDGCs).However,the causal role of abDGCs in recurrent seizures of TLE is not fully understood.Here,taking advantage of optogenetic and chemogenetic tools to selectively manipulate abDGCs in a reversible manner.展开更多
基金supported by grants from the National Key R&D Program of China(2020YFA0803900)the National Natural Science Foundation of China(82173796 and U21A20418)+1 种基金the Natural Science Foundation of Zhejiang Province(LD22H310003)the Key R&D Plan of Zhejiang Province(2021C03116).
文摘Approximately 30%-40% of epilepsy patients do not respond well to adequate anti-seizure medications(ASMs),a condition known as pharmacoresistant epilepsy.The management of pharmacoresistant epilepsy remains an intractable issue in the clinic.Its early prediction is important for prevention and diagnosis.However,it still lacks effective predictors and approaches.Here,a classical model of pharmacoresistant temporal lobe epilepsy(TLE)was established to screen pharmacoresistant and pharmaco-responsive individuals by applying phenytoin to amygdaloid-kindled rats.Ictal electroencephalograms(EEGs)recorded before phenytoin treatment were analyzed.Based on ictal EEGs from pharmacoresistant and pharmaco-responsive rats,a convolutional neural network predictive model was constructed to predict pharmacoresistance,and achieved 78% prediction accuracy.We further found the ictal EEGs from pharmacoresistant rats have a lower gamma-band power,which was verified in seizure EEGs from pharmacoresistant TLE patients.Prospectively,therapies targeting the subiculum in those predicted as“pharmacoresistant”individual rats significantly reduced the subsequent occurrence of pharmacoresistance.These results demonstrate a new methodology to predict whether TLE individuals become resistant to ASMs in a classic pharmacoresistant TLE model.This may be of translational importance for the precise management of pharmacoresistant TLE.
基金supported by grants from the National Natural Science Foundation of China(8163009&81973298,and 81821091).
文摘Epilepsy is a common neurological disorder characterized by hyperexcitability in the brain.Its pathogenesis is classically associated with an imbalance of excitatory and inhibitory neurons.Calretinin(CR)is one of the three major types of calcium-binding proteins present in inhibitory GABAergic neurons.The functions of CR and its role in neural excitability are still unknown.Recent data suggest that CR neurons have diverse neurotransmitters,morphologies,distributions,and functions in different brain regions across various species.Notably,CR neurons in the hippocampus,amygdala,neocortex,and thalamus are extremely susceptible to excitotoxicity in the epileptic brain,but the causal relationship is unknown.In this review,we focus on the heterogeneous functions of CR neurons in different brain regions and their relationship with neural excitability and epilepsy.Importantly,we provide perspectives on future investigations of the role of CR neurons in epilepsy.
基金The research was funded by the National Natural Science Foundation of China(Grant No.11902128)the Applied Basic Research Foundation of Yunnan Province(Grant Nos.2019FI012 and 2018FB093)。
文摘Previous studies show that infrared radiation temperature(IRT)abnormalities are always accompanied by the crack development in rocks under external loads.In this context,experiments were conducted on preflawed sandstone to investigate the infrared radiation characteristics during failure process.Two indicators were defined herein,i.e.coefficient of variation of IRT(CVIRT)and skewness of IRT(SIRT).The regression analysis shows that the IRT probability distributions during loading process fit the Gaussian model.The variations in the CVIRT are characterized by four stages:primary stage,steady stage,accelerating stage and post-peak stage.Besides,the variations in the SIRT are divided into three stages:primary stage,steady stage and failure and post-peak stage.The precursor point for preflawed rock failure is identified based on the CVIRTetime curve,with average precursor point of 83%of the peak stress.Compared with other IRT indicators,the proposed two IRT indicators have higher sensitivity to IRT abnormalities during failure process.Furthermore,the connection between the IRT indicators and the rock fracturing was investigated to interpret the IRT indicator abnormalities.Based on the Verhulst inverse function,a new quantitative model was presented to describe the primary stage,steady stage and accelerating stage of the CVIRTetime curve.The results obtained in this study can provide early-warning information for rock failure prediction.
文摘Schizophrenia is a common and severe mental disorder with a lifetime prevalence of~1%[1]Apart from the typical positive symptoms,such as hallucinations and delusions,which mainly make patients seek medication,60%-70%of patients are tortured by negative symptoms(e.g.apathy and alogia)and cognitive deficits that impose a long-term burden on patients[2].
文摘Temporal lobe epilepsy(TLE),one of the most common drug-resistant epilepsies,is characterized by abnormal recurrent excitatory activity originating from the temporal lobe.In the dentate gyrus(DG)of the hippocampus.
基金supported by the National Natural Science Foundation of China(82204353).
文摘A recent study published in Neuron by Tiwari et al.identified the critical role of 5-HT2A receptor in ventral hippocampal parvalbumin(PV)interneurons(INs)in mediating the acute anxiolytic effects of the serotonergic psychedelic 2,5-dimethoxy-4-iodoamphetamine(DOI).This study not only advances psychedelic neuropharmacology but also provides a robust framework for developing novel rapid-acting therapeutics for anxiety disorders[1].
基金This project was supported by grants from the National Natural Science Foundation of China(82022071,81973298 and 82204350)the National Key Research and Development Program of China(2020YFA0803902)the Natural Science Foundation of Zhejiang Province(LD22H310003).
文摘Temporal lobe epilepsy(TLE),one common type of medically refractory epilepsy,is accompanied with altered adult-born dentate granule cells(abDGCs).However,the causal role of abDGCs in recurrent seizures of TLE is not fully understood.Here,taking advantage of optogenetic and chemogenetic tools to selectively manipulate abDGCs in a reversible manner.
