Epilepsy is believed to be caused by a lack of balance between excitation and inhibitation in the brain. A promising strategy for the control of the disease is closed-loop brain stimulation. How to determine the stimu...Epilepsy is believed to be caused by a lack of balance between excitation and inhibitation in the brain. A promising strategy for the control of the disease is closed-loop brain stimulation. How to determine the stimulation control parameters for effective and safe treatment protocols remains, however, an unsolved question. To constrain the complex dynamics of the biological brain, we use a neural population model（NPM）. We propose that a proportional-derivative（PD） type closed-loop control can successfully suppress epileptiform activities. First, we determine the stability of root loci, which reveals that the dynamical mechanism underlying epilepsy in the NPM is the loss of homeostatic control caused by the lack of balance between excitation and inhibition. Then, we design a PD type closed-loop controller to stabilize the unstable NPM such that the homeostatic equilibriums are maintained; we show that epileptiform activities are successfully suppressed. A graphical approach is employed to determine the stabilizing region of the PD controller in the parameter space, providing a theoretical guideline for the selection of the PD control parameters. Furthermore, we establish the relationship between the control parameters and the model parameters in the form of stabilizing regions to help understand the mechanism of suppressing epileptiform activities in the NPM. Simulations show that the PD-type closed-loop control strategy can effectively suppress epileptiform activities in the NPM.展开更多
A new control strategy based on nonlinear unscented Kalman filter （UKF） is proposed for a neural mass model that serves as a model for simulating real epileptiform stereo-electroeneephalographic （SEEG） signals. Th...A new control strategy based on nonlinear unscented Kalman filter （UKF） is proposed for a neural mass model that serves as a model for simulating real epileptiform stereo-electroeneephalographic （SEEG） signals. The UKF is used as an observer to estimate the state from the noisy measurement because it has been proved to be effective for state estimation of nonlinear systems. A UKF controller is constructed via the estimated state and is illustrated to be effective for epileptiform spikes suppression of aforementioned model by numerical simulations.展开更多
A hierarchical multi-method integrated approach is proposed in this paper to detect and classify the epileptic waves in EEG automatically. The initial clinical results are encouraging.
Coexistence of fast and slow traveling waves without synaptic transmission has been found in hhhippocampal tissues,which is closely related to both normal brain activity and abnormal neural activity such as epileptic ...Coexistence of fast and slow traveling waves without synaptic transmission has been found in hhhippocampal tissues,which is closely related to both normal brain activity and abnormal neural activity such as epileptic discharge. However, the propagation mechanism behind this coexistence phenomenon remains unclear. In this paper, a three-dimensional electric field coupled hippocampal neural network is established to investigate generation of coexisting spontaneous fast and slow traveling waves. This model captures two types of dendritic traveling waves propagating in both transverse and longitude directions: the N-methyl-D-aspartate(NMDA)-dependent wave with a speed of about 0.1 m/s and the Ca-dependent wave with a speed of about 0.009 m/s. These traveling waves are synaptic-independent and could be conducted only by the electric fields generated by neighboring neurons, which are basically consistent with the in vitro data measured experiments. It is also found that the slow Ca wave could trigger generation of fast NMDA waves in the propagation path of slow waves whereas fast NMDA waves cannot affect the propagation of slow Ca waves. These results suggest that dendritic Ca waves could acted as the source of the coexistence fast and slow waves. Furthermore, we also confirm the impact of cellular spacing heterogeneity on the onset of coexisting fast and slow waves. The local region with decreasing distances among neighbor neurons is more liable to promote the onset of spontaneous slow waves which, as sources, excite propagation of fast waves. These modeling studies provide possible biophysical mechanisms underlying the neural dynamics of spontaneous traveling waves in brain tissues.展开更多
Exploring the transition from inter-ictal to ictal epileptiform discharges(IDs) and how GABAAreceptormediated action affects the onset of IDs will enrich our understanding of epileptogenesis and epilepsy treatment.We ...Exploring the transition from inter-ictal to ictal epileptiform discharges(IDs) and how GABAAreceptormediated action affects the onset of IDs will enrich our understanding of epileptogenesis and epilepsy treatment.We used Mg2+-free artificial cerebrospinal fluid(ACSF) to induce epileptiform discharges in juvenile mouse hippocampal slices and used a micro-electrode array to record the discharges. After the slices were exposed to Mg2+-free ACSF for 10 min–20 min, synchronous recurrent seizurelike events were recorded across the slices, and each event evolved from inter-ictal epileptiform discharges(IIDs) to pre-ictal epileptiform discharges(PIDs), and then to IDs.During the transition from IIDs to PIDs, the duration of discharges increased and the inter-discharge interval decreased. After adding 3 lmol/L of the GABAAreceptor agonist muscimol, PIDs and IDs disappeared, and IIDs remained. Further, the application of 10 lmol/L muscimol abolished all the epileptiform discharges. When the GABAAreceptor antagonist bicuculline was applied at 10 lmol/L, IIDs and PIDs disappeared, and IDs remained at decreased intervals. These results indicated that there are dynamic changes in the hippocampal network preceding the onset of IDs, and GABAAreceptor activity suppresses the transition from IIDs to IDs in juvenile mouse hippocampus.展开更多
The epileptic seizure is a dynamic process involving a rapid transition from normal activity to a state of hypersynchronous neuronal discharges. Here we investigated the network properties of epileptiform discharges i...The epileptic seizure is a dynamic process involving a rapid transition from normal activity to a state of hypersynchronous neuronal discharges. Here we investigated the network properties of epileptiform discharges in hippocampal slices in the presence of high K ＋ concentration （8.5 mmol/L） in the bath, and the effects of the anti-epileptic drug valproate （VPA） on epileptiform discharges, using a microelectrode array. We demonstrated that epileptiform discharges were predominantly initiated from the stratum pyramidale layer of CA3a-b and propagated bi-directionally to CA1 and CA3c. Disconnection of CA3 from CA1 abolished the discharges in CA1 without disrupting the initiation of discharges in CA3. Further pharmacological experiments showed that VPA at a clinically relevant concentration （100 μmol/L） suppressed the propagation speed but not the rate or duration of high-K＋-induced discharges. Our findings suggest that pacemakers exist in the CA3a-b region for the generation of epileptiform discharges in the hippocampus. VPA reduces the conduction of such discharges in the network by reducing the propagation speed.展开更多
Background Lennox-gastaut syndrome(LGS)is an epileptic encephalopathy often associated with behavioral and psychiatric disorders.Vagus nerve stimulation(VNS)has been approved effective for LGS treatment.Surgical resec...Background Lennox-gastaut syndrome(LGS)is an epileptic encephalopathy often associated with behavioral and psychiatric disorders.Vagus nerve stimulation(VNS)has been approved effective for LGS treatment.Surgical resection is also an option for LGS patients with focal pathology,offering a high probability of seizure control.However,it is challenging to accurately localize the seizure focus.Case presentation The case presented here is a 19-year-old male with a 16-year history of epilepsy with comorbid severe cognitive and psychiatric disorders.He was diagnosed with LGS due to generalized slow spike-wave discharges and multiple seizure types.He was treated with VNS in 2017 at the age of 15.After that,the frequency of the short tonic seizures decreased from 4–5 times per day to 2–5 times per year,and the generalized tonic–clonic seizure pattern did not recur,which had a frequency of 2–4 times per month before the surgery.In 2019,the generalized abnormal interictal epileptiform discharges changed to be localized in the right frontal–temporal lobe at the age of 17 years(2019).Conclusions This case report suggested that the generalized epileptiform discharges evolve into localized discharges after VNS treatment,which may help reveal the primary seizure focus for resection surgery in patients with LGS.展开更多
目的通过多导睡眠图(PSG)探讨抗癫痫发作药物(ASM)及偏侧化发作间期癫痫样放电(IED)对癫痫患者睡眠结构及睡眠期相关事件的影响。方法选取2018年3月至2022年12月在福建省级机关医院神经内科、睡眠医学中心门诊或病房治疗的癫痫患者75例...目的通过多导睡眠图(PSG)探讨抗癫痫发作药物(ASM)及偏侧化发作间期癫痫样放电(IED)对癫痫患者睡眠结构及睡眠期相关事件的影响。方法选取2018年3月至2022年12月在福建省级机关医院神经内科、睡眠医学中心门诊或病房治疗的癫痫患者75例,其中32例服用ASM、43例未服用ASM,对两组患者进行PSG(含视频及16个导联的脑电图)+动态脑电图监测,比较两组患者的睡眠结构及睡眠期相关事件。并对两组患者单、双侧IED的睡眠结构及睡眠期相关事件的不同结果进行分析。结果两组患者的睡眠结构比较差异无统计学意义(P>0.05);而服药癫痫组的血氧饱和度高于未服药癫痫组[95(94,96)%vs 94(93,95)%],在未服药癫痫组中,单、双侧IED组的睡眠结构及睡眠期相关事件比较差异均无统计学意义(P>0.05);在服药癫痫组中,单侧IED组的非快速眼动睡眠1期比例(N1%)[(21.48±15.61)%vs(12.06±6.55%)]、觉醒指数[12.9(7.75,18.3)次/h vs 8.8(6.5,10.9)次/h]均高于双侧IED组,差异有统计学意义(P<0.05)。结论ASM对IED患者的睡眠结构影响不大,服药癫痫组的血氧饱和度高于未服药癫痫组。服用ASM的患者单侧IED对睡眠期各结构的影响更大,主要表现为N1%及觉醒指数增高。展开更多
目的:研究"无镁细胞外液"诱导海马神经元产生癫痫样放电形式,建立离体癫痫模型。方法:采用24h新生Wistar大鼠,取海马神经元原代培养,神经元特异性烯醇化酶(Neuron specific enolase,NSE)免疫荧光鉴定神经元。体外培养至第9d时...目的:研究"无镁细胞外液"诱导海马神经元产生癫痫样放电形式,建立离体癫痫模型。方法:采用24h新生Wistar大鼠,取海马神经元原代培养,神经元特异性烯醇化酶(Neuron specific enolase,NSE)免疫荧光鉴定神经元。体外培养至第9d时,用"无镁细胞外液"处理3h,使用全细胞膜片钳技术记录神经元在相应时间点的放电情况。结果:通过鉴定可见,所培养的海马神经元纯度接近100%。在"无镁细胞外液"处理3h后致恢复正常细胞培养液培养24h,神经元仍存在自发的"癫痫样放电"。结论:采用本方法体外培养的海马神经元在"无镁细胞外液"的作用下可形成稳定的癫痫样放电,为今后进行癫痫发病机制的研究提供了一种的理想模型。展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.61473208,61025019,and 91132722)ONR MURI N000141010278NIH grant R01EY016281
文摘Epilepsy is believed to be caused by a lack of balance between excitation and inhibitation in the brain. A promising strategy for the control of the disease is closed-loop brain stimulation. How to determine the stimulation control parameters for effective and safe treatment protocols remains, however, an unsolved question. To constrain the complex dynamics of the biological brain, we use a neural population model（NPM）. We propose that a proportional-derivative（PD） type closed-loop control can successfully suppress epileptiform activities. First, we determine the stability of root loci, which reveals that the dynamical mechanism underlying epilepsy in the NPM is the loss of homeostatic control caused by the lack of balance between excitation and inhibition. Then, we design a PD type closed-loop controller to stabilize the unstable NPM such that the homeostatic equilibriums are maintained; we show that epileptiform activities are successfully suppressed. A graphical approach is employed to determine the stabilizing region of the PD controller in the parameter space, providing a theoretical guideline for the selection of the PD control parameters. Furthermore, we establish the relationship between the control parameters and the model parameters in the form of stabilizing regions to help understand the mechanism of suppressing epileptiform activities in the NPM. Simulations show that the PD-type closed-loop control strategy can effectively suppress epileptiform activities in the NPM.
基金Project supported by the National Natural Science Foundation of China （Grant Nos. 61004050 and 60125019） and the Natural Science Foundation of Scientific Research of Hebei Education Department, China （Grant No. 2009482）.
文摘A new control strategy based on nonlinear unscented Kalman filter （UKF） is proposed for a neural mass model that serves as a model for simulating real epileptiform stereo-electroeneephalographic （SEEG） signals. The UKF is used as an observer to estimate the state from the noisy measurement because it has been proved to be effective for state estimation of nonlinear systems. A UKF controller is constructed via the estimated state and is illustrated to be effective for epileptiform spikes suppression of aforementioned model by numerical simulations.
文摘A hierarchical multi-method integrated approach is proposed in this paper to detect and classify the epileptic waves in EEG automatically. The initial clinical results are encouraging.
基金supported in part by the National Natural Science Foundation of China (Grant Nos. 62171312 and 61771330)the Tianjin Municipal Education Commission Scientific Research Project (Grant No. 2020KJ114)。
文摘Coexistence of fast and slow traveling waves without synaptic transmission has been found in hhhippocampal tissues,which is closely related to both normal brain activity and abnormal neural activity such as epileptic discharge. However, the propagation mechanism behind this coexistence phenomenon remains unclear. In this paper, a three-dimensional electric field coupled hippocampal neural network is established to investigate generation of coexisting spontaneous fast and slow traveling waves. This model captures two types of dendritic traveling waves propagating in both transverse and longitude directions: the N-methyl-D-aspartate(NMDA)-dependent wave with a speed of about 0.1 m/s and the Ca-dependent wave with a speed of about 0.009 m/s. These traveling waves are synaptic-independent and could be conducted only by the electric fields generated by neighboring neurons, which are basically consistent with the in vitro data measured experiments. It is also found that the slow Ca wave could trigger generation of fast NMDA waves in the propagation path of slow waves whereas fast NMDA waves cannot affect the propagation of slow Ca waves. These results suggest that dendritic Ca waves could acted as the source of the coexistence fast and slow waves. Furthermore, we also confirm the impact of cellular spacing heterogeneity on the onset of coexisting fast and slow waves. The local region with decreasing distances among neighbor neurons is more liable to promote the onset of spontaneous slow waves which, as sources, excite propagation of fast waves. These modeling studies provide possible biophysical mechanisms underlying the neural dynamics of spontaneous traveling waves in brain tissues.
基金supported by the Key Basic Research Project of Science and Technology Commission of Shanghai (13DJ1400303)the Shanghai Jiao Tong University Fund for Interdisciplinary Research for Medical Applications (YG2012ZD08)the Seed Fund of Ren Ji Hospital (RJ ZZ13-005)
文摘Exploring the transition from inter-ictal to ictal epileptiform discharges(IDs) and how GABAAreceptormediated action affects the onset of IDs will enrich our understanding of epileptogenesis and epilepsy treatment.We used Mg2+-free artificial cerebrospinal fluid(ACSF) to induce epileptiform discharges in juvenile mouse hippocampal slices and used a micro-electrode array to record the discharges. After the slices were exposed to Mg2+-free ACSF for 10 min–20 min, synchronous recurrent seizurelike events were recorded across the slices, and each event evolved from inter-ictal epileptiform discharges(IIDs) to pre-ictal epileptiform discharges(PIDs), and then to IDs.During the transition from IIDs to PIDs, the duration of discharges increased and the inter-discharge interval decreased. After adding 3 lmol/L of the GABAAreceptor agonist muscimol, PIDs and IDs disappeared, and IIDs remained. Further, the application of 10 lmol/L muscimol abolished all the epileptiform discharges. When the GABAAreceptor antagonist bicuculline was applied at 10 lmol/L, IIDs and PIDs disappeared, and IDs remained at decreased intervals. These results indicated that there are dynamic changes in the hippocampal network preceding the onset of IDs, and GABAAreceptor activity suppresses the transition from IIDs to IDs in juvenile mouse hippocampus.
基金supported by the Natural Science Foundation of Shanghai(11ZR1421800,12ZR1413800)the Shanghai Jiao Tong University Fund for Interdisciplinary Research for Medical Applications(G08PETZD05)
文摘The epileptic seizure is a dynamic process involving a rapid transition from normal activity to a state of hypersynchronous neuronal discharges. Here we investigated the network properties of epileptiform discharges in hippocampal slices in the presence of high K ＋ concentration （8.5 mmol/L） in the bath, and the effects of the anti-epileptic drug valproate （VPA） on epileptiform discharges, using a microelectrode array. We demonstrated that epileptiform discharges were predominantly initiated from the stratum pyramidale layer of CA3a-b and propagated bi-directionally to CA1 and CA3c. Disconnection of CA3 from CA1 abolished the discharges in CA1 without disrupting the initiation of discharges in CA3. Further pharmacological experiments showed that VPA at a clinically relevant concentration （100 μmol/L） suppressed the propagation speed but not the rate or duration of high-K＋-induced discharges. Our findings suggest that pacemakers exist in the CA3a-b region for the generation of epileptiform discharges in the hippocampus. VPA reduces the conduction of such discharges in the network by reducing the propagation speed.
基金Natural Science Foundation of Yunnan Province(202105AC160029,KYRLMY20200026 and YNGXCXTD2018012)Major Science and Technology Special Project of Yunnan Province(202002AA100204).
文摘Background Lennox-gastaut syndrome(LGS)is an epileptic encephalopathy often associated with behavioral and psychiatric disorders.Vagus nerve stimulation(VNS)has been approved effective for LGS treatment.Surgical resection is also an option for LGS patients with focal pathology,offering a high probability of seizure control.However,it is challenging to accurately localize the seizure focus.Case presentation The case presented here is a 19-year-old male with a 16-year history of epilepsy with comorbid severe cognitive and psychiatric disorders.He was diagnosed with LGS due to generalized slow spike-wave discharges and multiple seizure types.He was treated with VNS in 2017 at the age of 15.After that,the frequency of the short tonic seizures decreased from 4–5 times per day to 2–5 times per year,and the generalized tonic–clonic seizure pattern did not recur,which had a frequency of 2–4 times per month before the surgery.In 2019,the generalized abnormal interictal epileptiform discharges changed to be localized in the right frontal–temporal lobe at the age of 17 years(2019).Conclusions This case report suggested that the generalized epileptiform discharges evolve into localized discharges after VNS treatment,which may help reveal the primary seizure focus for resection surgery in patients with LGS.
文摘目的通过多导睡眠图(PSG)探讨抗癫痫发作药物(ASM)及偏侧化发作间期癫痫样放电(IED)对癫痫患者睡眠结构及睡眠期相关事件的影响。方法选取2018年3月至2022年12月在福建省级机关医院神经内科、睡眠医学中心门诊或病房治疗的癫痫患者75例,其中32例服用ASM、43例未服用ASM,对两组患者进行PSG(含视频及16个导联的脑电图)+动态脑电图监测,比较两组患者的睡眠结构及睡眠期相关事件。并对两组患者单、双侧IED的睡眠结构及睡眠期相关事件的不同结果进行分析。结果两组患者的睡眠结构比较差异无统计学意义(P>0.05);而服药癫痫组的血氧饱和度高于未服药癫痫组[95(94,96)%vs 94(93,95)%],在未服药癫痫组中,单、双侧IED组的睡眠结构及睡眠期相关事件比较差异均无统计学意义(P>0.05);在服药癫痫组中,单侧IED组的非快速眼动睡眠1期比例(N1%)[(21.48±15.61)%vs(12.06±6.55%)]、觉醒指数[12.9(7.75,18.3)次/h vs 8.8(6.5,10.9)次/h]均高于双侧IED组,差异有统计学意义(P<0.05)。结论ASM对IED患者的睡眠结构影响不大,服药癫痫组的血氧饱和度高于未服药癫痫组。服用ASM的患者单侧IED对睡眠期各结构的影响更大,主要表现为N1%及觉醒指数增高。
文摘目的:研究"无镁细胞外液"诱导海马神经元产生癫痫样放电形式,建立离体癫痫模型。方法:采用24h新生Wistar大鼠,取海马神经元原代培养,神经元特异性烯醇化酶(Neuron specific enolase,NSE)免疫荧光鉴定神经元。体外培养至第9d时,用"无镁细胞外液"处理3h,使用全细胞膜片钳技术记录神经元在相应时间点的放电情况。结果:通过鉴定可见,所培养的海马神经元纯度接近100%。在"无镁细胞外液"处理3h后致恢复正常细胞培养液培养24h,神经元仍存在自发的"癫痫样放电"。结论:采用本方法体外培养的海马神经元在"无镁细胞外液"的作用下可形成稳定的癫痫样放电,为今后进行癫痫发病机制的研究提供了一种的理想模型。
