3D Tibia Reconstruction Using 2D Computed Tomography Images.

Objective: Skeletal stress fracture of the lower limbs remains a significant problem for the military. The objective of this study was to develop a subject-specific 3D reconstruction of the tibia using only a few CT images for the prediction of peak stresses and locations.

Methods: Full bilateral tibial CT scans were recorded for 63 healthy college male participants.

A Fast-Running, End-to-End Concussion Risk Model for Assessment of Complex Human Head Kinematics.

An end-to-end, mechanism-based concussion risk model, linking head motion to axonal injury, has been demonstrated to predict concussion outcomes with greater sensitivity and specificity than external correlates such as peak head acceleration. The development of this model was driven by the need to more accurately translate head-worn sensor measurements into injury assessment in near-real time. The full end-to-end model is a detailed multi-scale model, composed of complex components (e.

Callosal injury-induced working memory impairment: a computational network modeling study.

Mild traumatic brain injury (mTBI) often results in working memory (WM) impairment, but the mechanistic relationship between the two remains elusive. We used a computational model of two cortical neuronal networks linked by myelinated callosal axons with distance-dependent conduction delays to simulate callosal dysfunction in mTBI and quantify its impact on WM. WM maintenance and termination in the model network depended on short-term synaptic plasticity.

A Mechanistic End-to-End Concussion Model That Translates Head Kinematics to Neurologic Injury.

Past concussion studies have focused on understanding the injury processes occurring on discrete length scales (e.g., tissue-level stresses and strains, cell-level stresses and strains, or injury-induced cellular pathology).

Callosal dysfunction explains injury sequelae in a computational network model of axonal injury.

Mild traumatic brain injury (mTBI) often results in neurobehavioral aberrations such as impaired attention and increased reaction time. Diffusion imaging and postmortem analysis studies suggest that mTBI primarily affects myelinated axons in white matter tracts. In particular, corpus callosum, mediating interhemispheric information exchange, has been shown to be affected in mTBI.

Perinodal glial swelling mitigates axonal degradation in a model of axonal injury.

Mild traumatic brain injury (mTBI) has been associated with the damage to myelinated axons in white matter tracts. Animal models and in vitro studies suggest that axonal degradation develops during a latent period following a traumatic event. This delay has been attributed to slowly developing axonal membrane depolarization that is initiated by injury-induced ionic imbalance and in turn, leads to the activation of Ca(2+) proteases via pathological accumulation of Ca(2+).

Primary paranode demyelination modulates slowly developing axonal depolarization in a model of axonal injury.

Neurological sequelae of mild traumatic brain injury are associated with the damage to white matter myelinated axons. In vitro models of axonal injury suggest that the progression to pathological ruin is initiated by the mechanical damage to tetrodotoxin-sensitive voltage-gated sodium channels that breaches the ion balance through alteration in kinetic properties of these channels. In myelinated axons, sodium channels are concentrated at nodes of Ranvier, making these sites vulnerable to mechanical injury.

Computer modeling of mild axonal injury: implications for axonal signal transmission.

Diffusion imaging and postmortem studies of patients with mild traumatic brain injury (mTBI) of the concussive type are consistent with the observations of diffuse axonal injury to the white matter axons. Mechanical trauma to axons affects the properties of tetrodotoxin-sensitive sodium channels at the nodes of Ranvier, leading to axonal degeneration through intra-axonal accumulation of calcium ions and activation of calcium proteases; however, the immediate implications of axonal trauma regarding axonal functionality and their relevance to transient impairment of function as observed in concussion remain elusive. A biophysically realistic computational model of a myelinated axon was developed to investigate how mTBI could immediately affect axonal function.

Divide and conquer: functional segregation of synaptic inputs by astrocytic microdomains could alleviate paroxysmal activity following brain trauma.

Traumatic brain injury often leads to epileptic seizures. Among other factors, homeostatic synaptic plasticity (HSP) mediates posttraumatic epileptogenesis through unbalanced synaptic scaling, partially compensating for the trauma-incurred loss of neural excitability. HSP is mediated in part by tumor necrosis factor alpha (TNFα), which is released locally from reactive astrocytes early after trauma in response to chronic neuronal inactivity.

Computational quest for understanding the role of astrocyte signaling in synaptic transmission and plasticity.

The complexity of the signaling network that underlies astrocyte-synapse interactions may seem discouraging when tackled from a theoretical perspective. Computational modeling is challenged by the fact that many details remain hitherto unknown and conventional approaches to describe synaptic function are unsuitable to explain experimental observations when astrocytic signaling is taken into account. Supported by experimental evidence is the possibility that astrocytes perform genuine information processing by means of their calcium signaling and are players in the physiological setting of the basal tone of synaptic transmission.

Computational models of neuron-astrocyte interaction in epilepsy.

Astrocytes actively shape the dynamics of neurons and neuronal ensembles by affecting several aspects critical to neuronal function, such as regulating synaptic plasticity, modulating neuronal excitability, and maintaining extracellular ion balance. These pathways for astrocyte-neuron interaction can also enhance the information-processing capabilities of brains, but in other circumstances may lead the brain on the road to pathological ruin. In this article, we review the existing computational models of astrocytic involvement in epileptogenesis, focusing on their relevance to existing physiological data.

A tale of two stories: astrocyte regulation of synaptic depression and facilitation.

Short-term presynaptic plasticity designates variations of the amplitude of synaptic information transfer whereby the amount of neurotransmitter released upon presynaptic stimulation changes over seconds as a function of the neuronal firing activity. While a consensus has emerged that the resulting decrease (depression) and/or increase (facilitation) of the synapse strength are crucial to neuronal computations, their modes of expression in vivo remain unclear. Recent experimental studies have reported that glial cells, particularly astrocytes in the hippocampus, are able to modulate short-term plasticity but the mechanism of such a modulation is poorly understood.

Downregulation of parvalbumin at cortical GABA synapses reduces network gamma oscillatory activity.

Postmortem and functional imaging studies of patients with psychiatric disorders, including schizophrenia, are consistent with a dysfunction of interneurons leading to compromised inhibitory control of network activity. Parvalbumin (PV)-expressing, fast-spiking interneurons interacting with pyramidal neurons generate cortical gamma oscillations (30-80 Hz) that synchronize cortical activity during cognitive processing. In postmortem studies of schizophrenia patients, these interneurons show reduced PV and glutamic acid decarboxylase 67 (GAD67), an enzyme that synthesizes GABA, but the consequences of this downregulation are unclear.

Pattern of trauma determines the threshold for epileptic activity in a model of cortical deafferentation.

Epileptic activity often occurs in the cortex after a latent period after head trauma; this delay has been attributed to the destabilizing influence of homeostatic synaptic scaling and changes in intrinsic properties. However, the impact of the spatial organization of cortical trauma on epileptogenesis is poorly understood. We addressed this question by analyzing the dynamics of a large-scale biophysically realistic cortical network model subjected to different patterns of trauma.

Topological basis of epileptogenesis in a model of severe cortical trauma.

Epileptic activity often arises after a latent period following traumatic brain injury. Several factors contribute to the emergence of post-traumatic epilepsy, including disturbances to ionic homeostasis, pathological action of intrinsic and synaptic homeostatic plasticity, and remodeling of anatomical network synaptic connectivity. We simulated a large-scale, biophysically realistic computational model of cortical tissue to study the mechanisms underlying the genesis of post-traumatic paroxysmal epileptic-like activity in the deafferentation model of a severely traumatized cortical network.

Gap junctions and epileptic seizures--two sides of the same coin?

Electrical synapses (gap junctions) play a pivotal role in the synchronization of neuronal ensembles which also makes them likely agonists of pathological brain activity. Although large body of experimental data and theoretical considerations indicate that coupling neurons by electrical synapses promotes synchronous activity (and thus is potentially epileptogenic), some recent evidence questions the hypothesis of gap junctions being among purely epileptogenic factors. In particular, an expression of inter-neuronal gap junctions is often found to be higher after the experimentally induced seizures than before.

Synaptic scaling stabilizes persistent activity driven by asynchronous neurotransmitter release.

Small networks of cultured hippocampal neurons respond to transient stimulation with rhythmic network activity (reverberation) that persists for several seconds, constituting an in vitro model of synchrony, working memory, and seizure. This mode of activity has been shown theoretically and experimentally to depend on asynchronous neurotransmitter release (an essential feature of the developing hippocampus) and is supported by a variety of developing neuronal networks despite variability in the size of populations (10-200 neurons) and in patterns of synaptic connectivity. It has previously been reported in computational models that "small-world" connection topology is ideal for the propagation of similar modes of network activity, although this has been shown only for neurons utilizing synchronous (phasic) synaptic transmission.

Shunting inhibition controls the gain modulation mediated by asynchronous neurotransmitter release in early development.

The sensitivity of a neuron to its input can be modulated in several ways. Changes in the slope of the neuronal input-output curve depend on factors such as shunting inhibition, background noise, frequency-dependent synaptic excitation, and balanced excitation and inhibition. However, in early development GABAergic interneurons are excitatory and other mechanisms such as asynchronous transmitter release might contribute to regulating neuronal sensitivity.

Nonlinear gap junctions enable long-distance propagation of pulsating calcium waves in astrocyte networks.

A new paradigm has recently emerged in brain science whereby communications between glial cells and neuron-glia interactions should be considered together with neurons and their networks to understand higher brain functions. In particular, astrocytes, the main type of glial cells in the cortex, have been shown to communicate with neurons and with each other. They are thought to form a gap-junction-coupled syncytium supporting cell-cell communication via propagating Ca(2+) waves.

Erratum to: Glutamate regulation of calcium and IP(3) oscillating and pulsating dynamics in astrocytes.

[This corrects the article DOI: 10.1007/s10867-009-9155-y.].

Signal processing in local neuronal circuits based on activity-dependent noise and competition.

We study the characteristics of weak signal detection by a recurrent neuronal network with plastic synaptic coupling. It is shown that in the presence of an asynchronous component in synaptic transmission, the network acquires selectivity with respect to the frequency of weak periodic stimuli. For nonperiodic frequency-modulated stimuli, the response is quantified by the mutual information between input (signal) and output (network's activity) and is optimized by synaptic depression.

Locally balanced dendritic integration by short-term synaptic plasticity and active dendritic conductances.

The high degree of variability observed in spike trains and membrane potentials of pyramidal neurons in vivo is thought to be a consequence of a balance between excitatory and inhibitory inputs, which depends on the dynamics of the network. We simulated synaptic currents and ion channels in a reconstructed hippocampal CA1 pyramidal cell and show here that a local balance can be achieved on a dendritic branch with a different mechanism, based on presynaptic depression of quantal release interacting with active dendritic conductances. This mechanism, which does not require synaptic inhibition, allows each dendritic branch to remain sensitive to correlated synaptic inputs, induces a high degree of variability in the output spike train, and can be combined with other balance mechanisms based on network dynamics.

Glutamate regulation of calcium and IP3 oscillating and pulsating dynamics in astrocytes.

Recent years have witnessed an increasing interest in neuron-glia communication. This interest stems from the realization that glia participate in cognitive functions and information processing and are involved in many brain disorders and neurodegenerative diseases. An important process in neuron-glia communications is astrocyte encoding of synaptic information transfer-the modulation of intracellular calcium (Ca(2+)) dynamics in astrocytes in response to synaptic activity.

Multimodal encoding in a simplified model of intracellular calcium signaling.

Many cells use calcium signaling to carry information from the extracellular side of the plasma membrane to targets in their interior. Since virtually all cells employ a network of biochemical reactions for Ca(2+) signaling, much effort has been devoted to understand the functional role of Ca(2+) responses and to decipher how their complex dynamics is regulated by the biochemical network of Ca(2+)-related signal transduction pathways. Experimental observations show that Ca(2+) signals in response to external stimuli encode information via frequency modulation (FM) or alternatively via amplitude modulation (AM).

The emergence and properties of mutual synchronization in in vitro coupled cortical networks.

We have studied the emergence of mutual synchronization and activity propagation in coupled neural networks from rat cortical cells grown on a micro-electrode array for parallel activity recording of dozens of neurons. The activity of each sub-network by itself is marked by the formation of synchronized bursting events (SBE) - short time windows of rapid neuronal firing. The joint activity of two coupled networks is characterized by the formation of mutual synchronization, i.