A supervised machine learning approach to characterize spinal network function.

Spontaneous activity is a common feature of immature neuronal networks throughout the central nervous system and plays an important role in network development and consolidation. In postnatal rodents, spontaneous activity in the spinal cord exhibits complex, stochastic patterns that have historically proven challenging to characterize. We developed a software tool for quickly and automatically characterizing and classifying episodes of spontaneous activity generated from developing spinal networks. We recorded spontaneous activity from in vitro lumbar ventral roots of 16 neonatal [postnatal day (P)0-P3] mice. Recordings were DC coupled and detrended, and episodes were separated for analysis. Amplitude-, duration-, and frequency-related features were extracted from each episode and organized into five classes. Paired classes and features were used to train and test supervised machine learning algorithms. Multilayer perceptrons were used to classify episodes as rhythmic or multiburst. We increased network excitability with potassium chloride and tested the utility of the tool to detect changes in features and episode class. We also demonstrate usability by having a novel experimenter use the program to classify episodes collected at a later time point (P5). Supervised machine learning-based classification of episodes accounted for changes that traditional approaches cannot detect. Our tool, named SpontaneousClassification, advances the detail in which we can study not only developing spinal networks, but also spontaneous networks in other areas of the nervous system. NEW & NOTEWORTHY Spontaneous activity is important for nervous system network development and consolidation. Our software uses machine learning to automatically and quickly characterize and classify episodes of spontaneous activity in the spinal cord of newborn mice. It detected changes in network activity following KCl-enhanced excitation. Using our software to classify spontaneous activity throughout development, in pathological models, or with neuromodulation, may offer insight into the development and organization of spinal circuits.

[1]  Interaction between developing spinal locomotor networks in the neonatal mouse. , 2008, Journal of neurophysiology.

[2]  L. Landmesser,et al.  The development of hindlimb motor activity studied in the isolated spinal cord of the chick embryo , 1987, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[3]  Ulises Cortés,et al.  A machine learning methodology for the selection and classification of spontaneous spinal cord dorsum potentials allows disclosure of structured (non-random) changes in neuronal connectivity induced by nociceptive stimulation , 2015, Front. Neuroinform..

[4]  Ataollah Ebrahimzadeh,et al.  Classification of electrocardiogram signals with support vector machines and genetic algorithms using power spectral features , 2010, Biomed. Signal Process. Control..

[5]  Abdulhamit Subasi,et al.  EEG signal classification using PCA, ICA, LDA and support vector machines , 2010, Expert Syst. Appl..

[6]  J. Huguenard,et al.  Early postnatal switch in GABAA receptor α-subunits in the reticular thalamic nucleus. , 2016, Journal of neurophysiology.

[7]  S. Hochman,et al.  Conversion of the Modulatory Actions of Dopamine on Spinal Reflexes from Depression to Facilitation in D3 Receptor Knock-Out Mice , 2004, The Journal of Neuroscience.

[8]  Modulation of Rhythmic Activity in Mammalian Spinal Networks Is Dependent on Excitability State , 2017, eNeuro.

[9]  O. Garaschuk,et al.  Developmental profile and synaptic origin of early network oscillations in the CA1 region of rat neonatal hippocampus , 1998, The Journal of physiology.

[10]  Bekir Karlik Machine Learning Algorithms for Characterization of EMG Signals , 2014 .

[11]  C. Goodrich Measurement of body temperature in neonatal mice. , 1977, Journal of applied physiology: respiratory, environmental and exercise physiology.

[12]  Collin M. Stultz,et al.  Machine Learning Improves Risk Stratification After Acute Coronary Syndrome , 2017, Scientific Reports.

[13]  F. Clarac,et al.  Spontaneous and locomotor‐related GABAergic input onto primary afferents in the neonatal rat , 2000, The European journal of neuroscience.

[14]  Marla B. Feller,et al.  Spontaneous patterned retinal activity and the refinement of retinal projections , 2005, Progress in Neurobiology.

[15]  P. Rudomín,et al.  Changes in correlation between spontaneous activity of dorsal horn neurones lead to differential recruitment of inhibitory pathways in the cat spinal cord , 2012, The Journal of physiology.

[16]  Andrew Zisserman,et al.  Deep Face Recognition , 2015, BMVC.

[17]  N. Kudo,et al.  Morphological and physiological studies of development of the monosynaptic reflex pathway in the rat lumbar spinal cord. , 1987, The Journal of physiology.

[18]  M.H. Sadreddini,et al.  EEG Signal Classification using an Association Rule-Based Classifier , 2007, 2007 IEEE International Conference on Signal Processing and Communications.

[19]  Qiao Li,et al.  Ventricular Fibrillation and Tachycardia Classification Using a Machine Learning Approach , 2014, IEEE Transactions on Biomedical Engineering.

[20]  P. Whelan,et al.  Monoaminergic control of cauda-equina-evoked locomotion in the neonatal mouse spinal cord. , 2006, Journal of neurophysiology.

[21]  Luis Diambra,et al.  Neural networks that learn how to detect epileptic spikes , 1998 .

[22]  R.N. Scott,et al.  The application of neural networks to myoelectric signal analysis: a preliminary study , 1990, IEEE Transactions on Biomedical Engineering.

[23]  Jimeng Sun,et al.  Using recurrent neural network models for early detection of heart failure onset , 2016, J. Am. Medical Informatics Assoc..

[24]  F. Clarac,et al.  Early olfactory-induced rhythmic limb activity in the newborn rat. , 1998, Brain research. Developmental brain research.

[25]  Michael J. O'Donovan,et al.  Properties of rhythmic activity generated by the isolated spinal cord of the neonatal mouse. , 2000, Journal of neurophysiology.

[26]  Michael J. O'Donovan,et al.  Early Functional Impairment of Sensory-Motor Connectivity in a Mouse Model of Spinal Muscular Atrophy , 2011, Neuron.

[27]  C. Shatz,et al.  Early functional neural networks in the developing retina , 1995, Nature.

[28]  Anastasios Bezerianos,et al.  Ischemia detection with a self-organizing map supplemented by supervised learning , 2001, IEEE Trans. Neural Networks.

[29]  R. L. Kennedy,et al.  Artificial neural network models for prediction of acute coronary syndromes using clinical data from the time of presentation. , 2005, Annals of emergency medicine.

[30]  M. Hanson,et al.  Normal Patterns of Spontaneous Activity Are Required for Correct Motor Axon Guidance and the Expression of Specific Guidance Molecules , 2004, Neuron.

[31]  Tara N. Sainath,et al.  FUNDAMENTAL TECHNOLOGIES IN MODERN SPEECH RECOGNITION Digital Object Identifier 10.1109/MSP.2012.2205597 , 2012 .

[32]  Liset Menendez de la Prida,et al.  Analytical characterization of spontaneous activity evolution during hippocampal development in the rabbit , 1996, Neuroscience Letters.

[33]  D. Copenhagen,et al.  Development of Precise Maps in Visual Cortex Requires Patterned Spontaneous Activity in the Retina , 2005, Neuron.

[34]  O. Kiehn Decoding the organization of spinal circuits that control locomotion , 2016, Nature Reviews Neuroscience.

[35]  O. Kiehn,et al.  Activation of groups of excitatory neurons in the mammalian spinal cord or hindbrain evokes locomotion , 2010, Nature Neuroscience.

[36]  M. Hanson,et al.  Characterization of the Circuits That Generate Spontaneous Episodes of Activity in the Early Embryonic Mouse Spinal Cord , 2003, The Journal of Neuroscience.

[37]  Richard Axel,et al.  Spontaneous Neural Activity Is Required for the Establishment and Maintenance of the Olfactory Sensory Map , 2004, Neuron.

[38]  Ulas Bagci,et al.  Deep learning beyond cats and dogs: recent advances in diagnosing breast cancer with deep neural networks. , 2018, The British journal of radiology.

[39]  Juha Voipio,et al.  The cation‐chloride cotransporter NKCC1 promotes sharp waves in the neonatal rat hippocampus , 2006, The Journal of physiology.

[40]  Alanna J. Watt,et al.  Traveling waves in developing cerebellar cortex mediated by asymmetrical Purkinje cell connectivity , 2009, Nature Neuroscience.

[41]  Jack L. Feldman,et al.  In vitro brainstem-spinal cord preparations for study of motor systems for mammalian respiration and locomotion , 1987, Journal of Neuroscience Methods.

[42]  Katsunori Shimohara,et al.  EMG pattern recognition by neural networks for prosthetic fingers control , 1992 .

[43]  F. Clarac,et al.  Early walking in the neonatal rat: a kinematic study. , 1998, Behavioral neuroscience.

[44]  Anna A Penn,et al.  Thalamic Relay of Spontaneous Retinal Activity Prior to Vision , 1996, Neuron.

[45]  Luis Diambra,et al.  Nonlinear models for detecting epileptic spikes , 1999 .

[46]  M S Lewicki,et al.  A review of methods for spike sorting: the detection and classification of neural action potentials. , 1998, Network.

[47]  Yang Song,et al.  Computer‐aided diagnosis of prostate cancer using a deep convolutional neural network from multiparametric MRI , 2018, Journal of magnetic resonance imaging : JMRI.

[48]  Levi J. Hargrove,et al.  A Comparison of Surface and Intramuscular Myoelectric Signal Classification , 2007, IEEE Transactions on Biomedical Engineering.

[49]  L. Maffei,et al.  Spontaneous impulse activity of rat retinal ganglion cells in prenatal life. , 1988, Science.

[50]  B. Schmidt,et al.  Regional distribution of the locomotor pattern-generating network in the neonatal rat spinal cord. , 1997, Journal of neurophysiology.

[51]  Sterling C. Johnson,et al.  Multimodal and Multiscale Deep Neural Networks for the Early Diagnosis of Alzheimer's Disease using structural MR and FDG-PET images , 2017, ArXiv.

[52]  N. Grzywacz,et al.  Emergence of complex receptive field properties of ganglion cells in the developing turtle retina. , 1995, Journal of neurophysiology.