Journal of Computational Neuroscience最新文献

{"title":"Noise induced quiescence of epileptic spike generation in patients with epilepsy.","authors":"Charith N Cooray,&nbsp;Ana Carvalho,&nbsp;Gerald K Cooray","doi":"10.1007/s10827-020-00772-3","DOIUrl":"https://doi.org/10.1007/s10827-020-00772-3","url":null,"abstract":"<p><p>Clinical scalp electroencephalographic recordings from patients with epilepsy are distinguished by the presence of epileptic discharges i.e. spikes or sharp waves. These often occur randomly on a background of fluctuating potentials. The spike rate varies between different brain states (sleep and awake) and patients. Epileptogenic tissue and regions near these often show increased spike rates in comparison to other cortical regions. Several studies have shown a relation between spike rate and background activity although the underlying reason for this is still poorly understood. Both these processes, spike occurrence and background activity show evidence of being at least partly stochastic processes. In this study we show that epileptic discharges seen on scalp electroencephalographic recordings and background activity are driven at least partly by a common biological noise. Furthermore, our results indicate noise induced quiescence of spike generation which, in analogy with computational models of spiking, indicate spikes to be generated by transitions between semi-stable states of the brain, similar to the generation of epileptic seizure activity. The deepened physiological understanding of spike generation in epilepsy that this study provides could be useful in the electrophysiological assessment of different therapies for epilepsy including the effect of different drugs or electrical stimulation.</p>","PeriodicalId":54857,"journal":{"name":"Journal of Computational Neuroscience","volume":"49 1","pages":"57-67"},"PeriodicalIF":1.2,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10827-020-00772-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39147355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modeling suggests combined-drug treatments for disorders impairing synaptic plasticity via shared signaling pathways.","authors":"Paul Smolen,&nbsp;Marcelo A Wood,&nbsp;Douglas A Baxter,&nbsp;John H Byrne","doi":"10.1007/s10827-020-00771-4","DOIUrl":"https://doi.org/10.1007/s10827-020-00771-4","url":null,"abstract":"<p><p>Genetic disorders such as Rubinstein-Taybi syndrome (RTS) and Coffin-Lowry syndrome (CLS) cause lifelong cognitive disability, including deficits in learning and memory. Can pharmacological therapies be suggested that improve learning and memory in these disorders? To address this question, we simulated drug effects within a computational model describing induction of late long-term potentiation (L-LTP). Biochemical pathways impaired in these and other disorders converge on a common target, histone acetylation by acetyltransferases such as CREB binding protein (CBP), which facilitates gene induction necessary for L-LTP. We focused on four drug classes: tropomyosin receptor kinase B (TrkB) agonists, cAMP phosphodiesterase inhibitors, histone deacetylase inhibitors, and ampakines. Simulations suggested each drug type alone may rescue deficits in L-LTP. A potential disadvantage, however, was the necessity of simulating strong drug effects (high doses), which could produce adverse side effects. Thus, we investigated the effects of six drug pairs among the four classes described above. These combination treatments normalized impaired L-LTP with substantially smaller individual drug 'doses'. In addition three of these combinations, a TrkB agonist paired with an ampakine and a cAMP phosphodiesterase inhibitor paired with a TrkB agonist or an ampakine, exhibited strong synergism in L-LTP rescue. Therefore, we suggest these drug combinations are promising candidates for further empirical studies in animal models of genetic disorders that impair histone acetylation, L-LTP, and learning.</p>","PeriodicalId":54857,"journal":{"name":"Journal of Computational Neuroscience","volume":"49 1","pages":"37-56"},"PeriodicalIF":1.2,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10827-020-00771-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38589095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimal templates for signal extraction by noisy ideal detectors and human observers.","authors":"Peter Neri","doi":"10.1007/s10827-020-00768-z","DOIUrl":"https://doi.org/10.1007/s10827-020-00768-z","url":null,"abstract":"<p><p>The optimal template for signal detection in white additive noise is the signal itself: the ideal observer matches each stimulus against this template and selects the stimulus associated with largest match. In the noisy ideal observer, internal noise is added to the decision variable returned by the template. While the ideal observer represents an unrealistic approximation to the human visual process, the noisy ideal observer may be applicable under certain experimental conditions. For template values constrained to lie within a specified range, theory predicts that the template associated with a noisy ideal observer should be a clipped image of the signal, a result which we demonstrate analytically using variational calculus. It is currently unknown whether the human process conforms to theory. We report a targeted analysis of the theoretical prediction for an experimental protocol that maximizes template-matching on the part of human participants. We find indicative evidence to support the theoretical expectation when internal noise is compared across participants, but not within each participant. Our results indicate that implicit knowledge about internal variability in different individuals is reflected by their detection templates; no implicit knowledge is retained for internal-noise fluctuations experienced by a given participant during data collection. The results also indicate that template encoding is constrained by the dynamic range of weight specification, rather than the range of output values transduced by the template-matching process.</p>","PeriodicalId":54857,"journal":{"name":"Journal of Computational Neuroscience","volume":"49 1","pages":"1-20"},"PeriodicalIF":1.2,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10827-020-00768-z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38552030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modeling nucleus accumbens : A Computational Model from Single Cell to Circuit Level.","authors":"Rahmi Elibol,&nbsp;Neslihan Serap Şengör","doi":"10.1007/s10827-020-00769-y","DOIUrl":"https://doi.org/10.1007/s10827-020-00769-y","url":null,"abstract":"<p><p>Nucleus accumbens is part of the neural structures required for reward based learning and cognitive processing of motivation. Understanding its cellular dynamics and its role in basal ganglia circuits is important not only in diagnosing behavioral disorders and psychiatric problems as addiction and depression but also for developing therapeutic treatments for them. Building a computational model would expand our comprehension of nucleus accumbens. In this work, we are focusing on establishing a model of nucleus accumbens which has not been considered as much as dorsal striatum in computational neuroscience. We will begin by modeling the behavior of single cells and then build a holistic model of nucleus accumbens considering the effect of synaptic currents. We will verify the validity of the model by showing the consistency of simulation results with the empirical data. Furthermore, the simulation results reveal the joint effect of cortical stimulation and dopaminergic modulation on the activity of medium spiny neurons. This effect differentiates with the type of dopamine receptors.</p>","PeriodicalId":54857,"journal":{"name":"Journal of Computational Neuroscience","volume":"49 1","pages":"21-35"},"PeriodicalIF":1.2,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10827-020-00769-y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38581221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational modeling of seizure spread on a cortical surface","authors":"Viktor Sip, M. Guye, F. Bartolomei, Viktor Jirsa","doi":"10.1101/2020.12.22.423957","DOIUrl":"https://doi.org/10.1101/2020.12.22.423957","url":null,"abstract":"In the field of computational epilepsy, neural field models helped to understand some large-scale features of seizure dynamics. These insights however remain on general levels, without translation to the clinical settings via personalization of the model with the patient-specific structure. In particular, a link was suggested between epileptic seizures spreading across the cortical surface and the so-called theta-alpha activity (TAA) pattern seen on intracranial electrographic signals, yet this link was not demonstrated on a patient-specific level. Here we present a single patient computational study linking the seizure spreading across the patient-specific cortical surface with a specific instance of the TAA pattern recorded in the patient. Using the realistic geometry of the cortical surface we perform the simulations of seizure dynamics in The Virtual Brain platform, and we show that the simulated electrographic signals qualitatively agree with the recorded signals. Furthermore, the comparison with the simulations performed on surrogate surfaces reveals that the best quantitative fit is obtained for the real surface. The work illustrates how the patient-specific cortical geometry can be utilized in The Virtual Brain for personalized model building, and the importance of such approach.","PeriodicalId":54857,"journal":{"name":"Journal of Computational Neuroscience","volume":"50 1","pages":"17 - 31"},"PeriodicalIF":1.2,"publicationDate":"2020-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42861709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered neuronal excitability in a Hodgkin-Huxley model incorporating channelopathies of the delayed rectifier potassium channel.","authors":"Omar A Hafez,&nbsp;Allan Gottschalk","doi":"10.1007/s10827-020-00766-1","DOIUrl":"https://doi.org/10.1007/s10827-020-00766-1","url":null,"abstract":"<p><p>Channelopathies involving acquired or genetic modifications of the delayed rectifier K⁺ channel Kv1.1 include phenotypes characterized by enhanced neuronal excitability. Affected Kv1.1 channels exhibit combinations of altered expression, voltage sensitivity, and rates of activation and deactivation. Computational modeling and analysis can reveal the potential of particular channelopathies to alter neuronal excitability. A dynamical systems approach was taken to study the excitability and underlying dynamical structure of the Hodgkin-Huxley (HH) model of neural excitation as properties of the delayed rectifier K⁺ channel were altered. Bifurcation patterns of the HH model were determined as the amplitude of steady injection current was varied simultaneously with single parameters describing the delayed rectifier rates of activation and deactivation, maximal conductance, and voltage sensitivity. Relatively modest changes in the properties of the delayed rectifier K⁺ channel analogous to what is described for its channelopathies alter the bifurcation structure of the HH model and profoundly modify excitability of the HH model. Channelopathies associated with Kv1.1 can reduce the threshold for onset of neural activity. These studies also demonstrate how pathological delayed rectifier K⁺ channels could lead to the observation of the generalized Hopf bifurcation and, perhaps, other variants of the Hopf bifurcation. The observed bifurcation patterns collectively demonstrate that properties of the nominal delayed rectifier in the HH model appear optimized to permit activation of the HH model over the broadest possible range of input currents.</p>","PeriodicalId":54857,"journal":{"name":"Journal of Computational Neuroscience","volume":"48 4","pages":"377-386"},"PeriodicalIF":1.2,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10827-020-00766-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38590144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A computational investigation of electrotonic coupling between pyramidal cells in the cortex.","authors":"Jennifer Crodelle,&nbsp;Douglas Zhou,&nbsp;Gregor Kovačič,&nbsp;David Cai","doi":"10.1007/s10827-020-00762-5","DOIUrl":"https://doi.org/10.1007/s10827-020-00762-5","url":null,"abstract":"<p><p>The existence of electrical communication among pyramidal cells (PCs) in the adult cortex has been debated by neuroscientists for several decades. Gap junctions (GJs) among cortical interneurons have been well documented experimentally and their functional roles have been proposed by both computational neuroscientists and experimentalists alike. Experimental evidence for similar junctions among pyramidal cells in the cortex, however, has remained elusive due to the apparent rarity of these couplings among neurons. In this work, we develop a neuronal network model that includes observed probabilities and strengths of electrotonic coupling between PCs and gap-junction coupling among interneurons, in addition to realistic synaptic connectivity among both populations. We use this network model to investigate the effect of electrotonic coupling between PCs on network behavior with the goal of theoretically addressing this controversy of existence and purpose of electrotonically coupled PCs in the cortex.</p>","PeriodicalId":54857,"journal":{"name":"Journal of Computational Neuroscience","volume":"48 4","pages":"387-407"},"PeriodicalIF":1.2,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10827-020-00762-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38446336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational analysis of a 9D model for a small DRG neuron.","authors":"Parul Verma,&nbsp;Achim Kienle,&nbsp;Dietrich Flockerzi,&nbsp;Doraiswami Ramkrishna","doi":"10.1007/s10827-020-00761-6","DOIUrl":"https://doi.org/10.1007/s10827-020-00761-6","url":null,"abstract":"<p><p>Small dorsal root ganglion (DRG) neurons are primary nociceptors which are responsible for sensing pain. Elucidation of their dynamics is essential for understanding and controlling pain. To this end, we present a numerical bifurcation analysis of a small DRG neuron model in this paper. The model is of Hodgkin-Huxley type and has 9 state variables. It consists of a Na_v1.7 and a Na_v1.8 sodium channel, a leak channel, a delayed rectifier potassium, and an A-type transient potassium channel. The dynamics of this model strongly depend on the maximal conductances of the voltage-gated ion channels and the external current, which can be adjusted experimentally. We show that the neuron dynamics are most sensitive to the Na_v1.8 channel maximal conductance ([Formula: see text]). Numerical bifurcation analysis shows that depending on [Formula: see text] and the external current, different parameter regions can be identified with stable steady states, periodic firing of action potentials, mixed-mode oscillations (MMOs), and bistability between stable steady states and stable periodic firing of action potentials. We illustrate and discuss the transitions between these different regimes. We further analyze the behavior of MMOs. As the external current is decreased, we find that MMOs appear after a cyclic limit point. Within this region, bifurcation analysis shows a sequence of isolated periodic solution branches with one large action potential and a number of small amplitude peaks per period. For decreasing external current, the number of small amplitude peaks is increasing and the distance between the large amplitude action potentials is growing, finally tending to infinity and thereby leading to a stable steady state. A closer inspection reveals more complex concatenated MMOs in between these periodic MMO branches, forming Farey sequences. Lastly, we also find small solution windows with aperiodic oscillations which seem to be chaotic. The dynamical patterns found here-as consequences of bifurcation points regulated by different parameters-have potential translational significance as repetitive firing of action potentials imply pain of some form and intensity; manipulating these patterns by regulating the different parameters could aid in investigating pain dynamics.</p>","PeriodicalId":54857,"journal":{"name":"Journal of Computational Neuroscience","volume":"48 4","pages":"429-444"},"PeriodicalIF":1.2,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10827-020-00761-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38324222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A modeling study of spinal motoneuron recruitment regulated by ionic channels during fictive locomotion.","authors":"Qiang Zhang,&nbsp;Yue Dai","doi":"10.1007/s10827-020-00763-4","DOIUrl":"https://doi.org/10.1007/s10827-020-00763-4","url":null,"abstract":"<p><p>During fictive locomotion cat lumbar motoneurons exhibit changes in membrane proprieties including a decrease in voltage threshold (V_th), afterhyperpolarization (AHP) and input resistance (R_in) and an increase in non-linear membrane property. The impact of these changes on the motoneuron recruitment remains unknown. Using modeling approach we investigated the channel mechanism regulating the motoneuron recruitment. Three types of motoneuron pools including slow (S), fatigue-resistant (FR) and fast-fatigable (FF) motoneurons were constructed based on the membrane proprieties of cat lumbar motoneurons. The transient sodium (NaT), persistent sodium (NaP), delayed-rectifier potassium [K(DR)], Ca²⁺-dependent K⁺ [K(AHP)] and L-type calcium (Ca_L) channels were included in the models. Simulation results showed that (1) Strengthening synaptic inputs increased the number of recruitments in all three types of motoneurons following the size principle. (2) Increasing NaT or NaP or decreasing K(DR) or K(AHP) lowered rheobase of spike generation thus increased recruitment of motoneuron pools. (3) Decreasing R_in reduced recruitment in all three types of motoneurons. (4) The FF-type motoneuron pool, followed by FR- and S-type, were the most sensitive to increase of synaptic inputs, reduction of R_in, upregulation of NaT and NaP, and downregulation of K(DR) and K(AHP). (5) Increasing Ca_L enhanced overall discharge rate of motoneuron pools with little effect on the recruitment. Simulation results suggested that modulation of ionic channels altered the output of motoneuron pools with either modulating the number of recruited motoneurons or regulating the overall discharge rate of motoneuron pools. Multiple channels contributed to the recruitment of motoneurons with interaction of excitatory and inhibitory synaptic inputs during walking.</p>","PeriodicalId":54857,"journal":{"name":"Journal of Computational Neuroscience","volume":"48 4","pages":"409-428"},"PeriodicalIF":1.2,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10827-020-00763-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38353385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A model for the transfer of control from the brain to the spinal cord through synaptic learning.","authors":"Preeti Sar,&nbsp;Hartmut Geyer","doi":"10.1007/s10827-020-00767-0","DOIUrl":"https://doi.org/10.1007/s10827-020-00767-0","url":null,"abstract":"<p><p>The spinal cord is essential to the control of locomotion in legged animals and humans. However, the actual circuitry of the spinal controller remains only vaguely understood. Here we approach this problem from the viewpoint of learning. More precisely, we assume the circuitry evolves through the transfer of control from the brain to the spinal cord, propose a specific learning mechanism for this transfer based on the error between the cord and brain contributions to muscle control, and study the resulting structure of the spinal controller in a simplified neuromuscular model of human locomotion. The model focuses on the leg rebound behavior in stance and represents the spinal circuitry with 150 muscle reflexes. We find that after learning a spinal controller has evolved that produces leg rebound motions in the absence of a central brain input with only three structural reflex groups. These groups contain individual reflexes well known from physiological experiments but thought to serve separate purposes in the control of human locomotion. Our results suggest a more holistic interpretation of the role of individual sensory projections in spinal networks than is common. In addition, we discuss potential neural correlates for the proposed learning mechanism that may be probed in experiments. Together with such experiments, neuromuscular models of spinal learning likely will become effective tools for uncovering the structure and development of the spinal control circuitry.</p>","PeriodicalId":54857,"journal":{"name":"Journal of Computational Neuroscience","volume":"48 4","pages":"365-375"},"PeriodicalIF":1.2,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10827-020-00767-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38451023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}