A new algorithm for automatically detecting epileptiform spikes and its application in epilepsy models_Journal of Biomedical Engineering

Authors：

CHEN Xiaoqian ,  FENG Zhouyan , GUO Zheshan , ZHOU Wenjie , WANG Zhaoxiang

Key Laboratory of Biomedical Engineering of Ministry of Education, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou 310027, P.R.China;

Corresponding author：

FENG Zhouyan, Email: fengzhouyan@139.com

Keywords：

epilepsy model; population spike; automatic detection; 4-aminopyridine; picrotoxin

DOI：

10.7507/1001-5515.201611037

Video：

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Abstract Full text Figures/Tables Video References Cited by

Epilepsy is characterized by abnormally synchronized firing of neuronal populations, which is presented as epileptiform spikes in neural electrical signal recordings. In order to investigate the epileptiform spikes quantitatively, we designed a new window-based algorithm to automatically detect population spikes (PS) in acute epilepsy models in rat hippocampus CA1 region, and to calculate characteristic parameters of PS. Results show that the algorithm could recognize PS waveforms directly in wideband recording signals in epilepsy models induced by 4-aminopyridine (4-AP), a potassium channel blocker, or by picrotoxin (PTX), an antagonist of γ-aminobutyric acid A-type receptor. The PS detection ratios of the two epilepsy models were 94.2%±1.6% (n=11) and 95.9%±1.9% (n=12), respectively. The false positive ratios were 3.5%±2.3% (n=11) and 4.8%±2.3% (n=12), which were significantly lower than those of the conventional threshold method. Comparisons of the PS patterns between the 4-AP model and the PTX model showed that the PS of the 4-AP model had wider waveforms and fired more dispersedly with intervals mainly in the range of 100–700 ms. The PS of the PTX model fired as Burst with a higher firing rate and with intervals mainly in the range of 2–20 ms, resulting in a larger sum of spike amplitudes per second than the 4-AP model. Thus, the synchronous firing of neuronal populations in the PTX model was more intense than that in the 4-AP model. In conclusion, the new algorithm of PS detection can correctly detect and analyze epileptiform population spikes. It provides a useful tool of data analysis for investigating the underlying mechanism of seizure generation and for evaluating new therapeutics of epilepsy.

Citation： CHEN Xiaoqian, FENG Zhouyan, GUO Zheshan, ZHOU Wenjie, WANG Zhaoxiang. A new algorithm for automatically detecting epileptiform spikes and its application in epilepsy models. Journal of Biomedical Engineering, 2017, 34(4): 485-492. doi: 10.7507/1001-5515.201611037 Copy

1.	Kwan P, Arzimanoglou A, Berg A T, et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia, 2010, 51(6): 1069-1077.
2.	Bragin A, Engel J, Staba R J. High-frequency oscillations in epileptic brain. Curr Opin Neurol, 2010, 23(2): 151-156.
3.	Hablitz J J. Picrotoxin-induced epileptiform activity in hippocampus: role of endogenous versus synaptic factors. J Neurophysiol, 1984, 51(5): 1011-1027.
4.	White A M, Williams P A, Ferraro D J, et al. Efficient unsupervised algorithms for the detection of seizures in continuous EEG recordings from rats after brain injury. J Neurosci Methods, 2006, 152(1/2): 255-266.
5.	Kanak D J, Jones R T, Tokhi A, et al. Electrical and pharmacological stimuli reveal a greater susceptibility for CA3 network excitability in hippocampal slices from aged vs. adult Fischer 344 rats. Aging Dis, 2011, 2(4): 318-331.
6.	Avoli M, Louvel J, Pumain R, et al. Cellular and molecular mechanisms of epilepsy in the human brain. Prog Neurobiol, 2005, 77(3): 166-200.
7.	Salazar P, Tapia R, Rogawski M A. Effects of neurosteroids on epileptiform activity induced by picrotoxin and 4-aminopyridine in the rat hippocampal slice. Epilepsy Res, 2003, 55(1/2): 71-82.
8.	Rummens F, Ygorra S, Boussamba H C, et al. Theoretical study and optimisation of a standard deviation estimator circuit for adaptive threshold spike detection. International Journal of Circuit Theory and Applications, 2016, 44(9): 1742-1757.
9.	周基阳, 徐声伟, 林楠森, 等. 一种提取动作电位的自适应阈值算法. 自动化与仪表, 2014, 29(3): 1-5.
10.	丁伟东, 袁景淇, 梁培基. 多电极锋电位信号检测与分类方法研究. 仪器仪表学报, 2006, 27(12): 1626-1640.
11.	牛意坚, 刘涛. 基于窗口法的改进锋电位检测算法. 计算机与数字工程, 2012, 40(2): 19-21.
12.	Chiang C C, Lin C C K, Ju M S, et al. High frequency stimulation can suppress globally seizures induced by 4-AP in the rat hippocampus: an acute in vivo study. Brain Stimul, 2013, 6(2): 180-189.
13.	Yoon K W, Covey D F, Rothman S M. Multiple mechanisms of picrotoxin block of GABA-induced currents in rat hippocampal neurons. J Physiol, 1993, 464: 423-439.
14.	封洲燕, 光磊, 郑晓静, 等. 应用线性电极阵列检测海马场电位和单细胞动作电位. 生物化学与生物物理进展, 2007, 34(4): 401-407.
15.	Theoret Y, Brown A, Fleming S P, et al. Hippocampal field potential: a microcomputer aided comparison of amplitude and integral. Brain Res Bull, 1984, 12(5): 589-595.
16.	Sarje A, Abshire P. Spike detection for integrated circuits: comparative study//26th Southern Biomedical Engineering Conference (SBEC). Maryland, USA: 2010: 282-285.
17.	曹嘉悦, 封洲燕, 郭哲杉, 等. 闭环式电刺激抑制痫样棘波发放的机制研究. 中国生物医学工程学报, 2016, 35(1): 79-87.
18.	Kussener E, Aguilar J, Mainard O, et al. Implantable electrostimulation system in freely moving rodent for DBS treatment//2014 IEEE International Conference on Faible Tension Faible Consommation (FTFC). Monaco: 2014: 1-4.
19.	王兆祥, 封洲燕, 余颖, 等. 适用于宽频带记录信号的锋电位检测法. 仪器仪表学报, 2016, 37(3): 481-489.
20.	Peña F, Tapia R. Seizures and neurodegeneration induced by 4-aminopyridine in rat hippocampus in vivo: role of glutamate- and GABA-mediated neurotransmission and of ion channels. Neuroscience, 2000, 101(3): 547-561.

1. Kwan P, Arzimanoglou A, Berg A T, et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia, 2010, 51(6): 1069-1077.
2. Bragin A, Engel J, Staba R J. High-frequency oscillations in epileptic brain. Curr Opin Neurol, 2010, 23(2): 151-156.
3. Hablitz J J. Picrotoxin-induced epileptiform activity in hippocampus: role of endogenous versus synaptic factors. J Neurophysiol, 1984, 51(5): 1011-1027.
4. White A M, Williams P A, Ferraro D J, et al. Efficient unsupervised algorithms for the detection of seizures in continuous EEG recordings from rats after brain injury. J Neurosci Methods, 2006, 152(1/2): 255-266.
5. Kanak D J, Jones R T, Tokhi A, et al. Electrical and pharmacological stimuli reveal a greater susceptibility for CA3 network excitability in hippocampal slices from aged vs. adult Fischer 344 rats. Aging Dis, 2011, 2(4): 318-331.
6. Avoli M, Louvel J, Pumain R, et al. Cellular and molecular mechanisms of epilepsy in the human brain. Prog Neurobiol, 2005, 77(3): 166-200.
7. Salazar P, Tapia R, Rogawski M A. Effects of neurosteroids on epileptiform activity induced by picrotoxin and 4-aminopyridine in the rat hippocampal slice. Epilepsy Res, 2003, 55(1/2): 71-82.
8. Rummens F, Ygorra S, Boussamba H C, et al. Theoretical study and optimisation of a standard deviation estimator circuit for adaptive threshold spike detection. International Journal of Circuit Theory and Applications, 2016, 44(9): 1742-1757.
9. 周基阳, 徐声伟, 林楠森, 等. 一种提取动作电位的自适应阈值算法. 自动化与仪表, 2014, 29(3): 1-5.
10. 丁伟东, 袁景淇, 梁培基. 多电极锋电位信号检测与分类方法研究. 仪器仪表学报, 2006, 27(12): 1626-1640.
11. 牛意坚, 刘涛. 基于窗口法的改进锋电位检测算法. 计算机与数字工程, 2012, 40(2): 19-21.
12. Chiang C C, Lin C C K, Ju M S, et al. High frequency stimulation can suppress globally seizures induced by 4-AP in the rat hippocampus: an acute in vivo study. Brain Stimul, 2013, 6(2): 180-189.
13. Yoon K W, Covey D F, Rothman S M. Multiple mechanisms of picrotoxin block of GABA-induced currents in rat hippocampal neurons. J Physiol, 1993, 464: 423-439.
14. 封洲燕, 光磊, 郑晓静, 等. 应用线性电极阵列检测海马场电位和单细胞动作电位. 生物化学与生物物理进展, 2007, 34(4): 401-407.
15. Theoret Y, Brown A, Fleming S P, et al. Hippocampal field potential: a microcomputer aided comparison of amplitude and integral. Brain Res Bull, 1984, 12(5): 589-595.
16. Sarje A, Abshire P. Spike detection for integrated circuits: comparative study//26th Southern Biomedical Engineering Conference (SBEC). Maryland, USA: 2010: 282-285.
17. 曹嘉悦, 封洲燕, 郭哲杉, 等. 闭环式电刺激抑制痫样棘波发放的机制研究. 中国生物医学工程学报, 2016, 35(1): 79-87.
18. Kussener E, Aguilar J, Mainard O, et al. Implantable electrostimulation system in freely moving rodent for DBS treatment//2014 IEEE International Conference on Faible Tension Faible Consommation (FTFC). Monaco: 2014: 1-4.
19. 王兆祥, 封洲燕, 余颖, 等. 适用于宽频带记录信号的锋电位检测法. 仪器仪表学报, 2016, 37(3): 481-489.
20. Peña F, Tapia R. Seizures and neurodegeneration induced by 4-aminopyridine in rat hippocampus in vivo: role of glutamate- and GABA-mediated neurotransmission and of ion channels. Neuroscience, 2000, 101(3): 547-561.

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