Musculoskeletal Issues in Pediatric Burn Patients.

A burn injury affects virtually every organ system. The purpose of this article is to review musculoskeletal issues in children with burn injuries. Both acute and long-term problems will be discussed. A low threshold to consult a pediatric orthopaedist is recommended.

Cellular mechanisms of cooperative context-sensitive predictive inference.

We argue that prediction success maximization is a basic objective of cognition and cortex, that it is compatible with but distinct from prediction error minimization, that neither objective requires subtractive coding, that there is clear neurobiological evidence for the amplification of predicted signals, and that we are unconvinced by evidence proposed in support of subtractive coding. We outline recent discoveries showing that pyramidal cells on which our cognitive capabilities depend usually transmit information about input to their basal dendrites and amplify that transmission when input to their distal apical dendrites provides a context that agrees with the feedforward basal input in that both are depolarizing, i.e., both are excitatory rather than inhibitory. Though these intracellular discoveries require a level of technical expertise that is beyond the current abilities of most neuroscience labs, they are not controversial and acclaimed as groundbreaking. We note that this cellular cooperative context-sensitivity greatly enhances the cognitive capabilities of the mammalian neocortex, and that much remains to be discovered concerning its evolution, development, and pathology.

Dysfunctions of cellular context-sensitivity in neurodevelopmental learning disabilities.

Pyramidal neurons have a pivotal role in the cognitive capabilities of neocortex. Though they have been predominantly modeled as integrate-and-fire point processors, many of them have another point of input integration in their apical dendrites that is central to mechanisms endowing them with the sensitivity to context that underlies basic cognitive capabilities. Here we review evidence implicating impairments of those mechanisms in three major neurodevelopmental disabilities, fragile X, Down syndrome, and fetal alcohol spectrum disorders. Multiple dysfunctions of the mechanisms by which pyramidal cells are sensitive to context are found to be implicated in all three syndromes. Further deciphering of these cellular mechanisms would lead to the understanding of and therapies for learning disabilities beyond any that are currently available.

Sirenomelia: Review of a Rare Syndrome with Case Report, Review of Anatomy, and Thoughts on Management.

BACKGROUND: Sirenomelia is a rare syndrome in which the infant is born with the legs fused from the pelvis to the feet. Sirenomelia is often fatal in the neonatal period because of multiple other anomalies. The feet may be absent; if present, they are often splayed outward or face backward. There are no case reports of any patient with this syndrome who has been able to walk after separation of the legs. METHODS: The authors report on their patient with sirenomelia who was born with the feet facing backward but otherwise normal-appearing hips and thighs and no other anomalies that would lead to fatality in the near future. After preoperative tissue expansion, the authors performed separation of the legs with through-knee amputations, utilizing a vascularized flap from the lower part of the legs based on the sciatic vessels for coverage of the perineum. There was no need for skin grafts or dermal matrices and the patient was referred to physical therapy after recovery from surgery in an attempt to allow her to ambulate. RESULTS: The patient began to ambulate on her stumps early after surgical repair and is now walking with stubby prostheses. Her other medical issues have remained stable and nonproblematic. CONCLUSIONS: Selected patients with sirenomelia may be able to walk after separation of the legs, depending on the status of other congenital differences as well as the status of the legs when separated. Careful workup with multidisciplinary planning of overall care as well as surgical care is essential.

A Comparison of Partial Information Decompositions Using Data from Real and Simulated Layer 5b Pyramidal Cells.

Partial information decomposition allows the joint mutual information between an output and a set of inputs to be divided into components that are synergistic or shared or unique to each input. We consider five different decompositions and compare their results using data from layer 5b pyramidal cells in two different studies. The first study was on the amplification of somatic action potential output by apical dendritic input and its regulation by dendritic inhibition. We find that two of the decompositions produce much larger estimates of synergy and shared information than the others, as well as large levels of unique misinformation. When within-neuron differences in the components are examined, the five methods produce more similar results for all but the shared information component, for which two methods produce a different statistical conclusion from the others. There are some differences in the expression of unique information asymmetry among the methods. It is significantly larger, on average, under dendritic inhibition. Three of the methods support a previous conclusion that apical amplification is reduced by dendritic inhibition. The second study used a detailed compartmental model to produce action potentials for many combinations of the numbers of basal and apical synaptic inputs. Decompositions of the entire data set produce similar differences to those in the first study. Two analyses of decompositions are conducted on subsets of the data. In the first, the decompositions reveal a bifurcation in unique information asymmetry. For three of the methods, this suggests that apical drive switches to basal drive as the strength of the basal input increases, while the other two show changing mixtures of information and misinformation. Decompositions produced using the second set of subsets show that all five decompositions provide support for properties of cooperative context-sensitivity-to varying extents.

Variations in Pupil Size Related to Memory for Recently Presented Words and Event Related Potentials.

Pupillometry has been found to be correlated with activity of cholinergic and noradrenergic neuromodulator systems. These systems regulate the level of cortical arousal and therefore perception, attention, and memory. Here, we tested how different types of pupil size variance (prestimulus baseline and prestimulus hippus power) may correlate with behavioral and event-related potentials (ERPs). We recorded pupil size and ERPs while participants were presented with a series of words and then asked whether the words had been in the initial list when they were later presented intermixed with unpresented words. We found that a smaller prestimulus baseline pupil size during the study phase was associated with better memory performance. Study items also evoked a larger P3 response at presentation and a greater old/new memory ERP effect at test when prestimulus pupil size was small rather than large. Prestimulus hippus power was found to be a between-subjects factor affecting the robustness of memory encoding with less power being associated with a greater old/new memory ERP effect. These results provide evidence relating memory and ERPs to variables defined on pupil size that are thought to reflect varying states of parasympathetic and sympathetic arousal.

Apical amplification-a cellular mechanism of conscious perception?

We present a theoretical view of the cellular foundations for network-level processes involved in producing our conscious experience. Inputs to apical synapses in layer 1 of a large subset of neocortical cells are summed at an integration zone near the top of their apical trunk. These inputs come from diverse sources and provide a context within which the transmission of information abstracted from sensory input to their basal and perisomatic synapses can be amplified when relevant. We argue that apical amplification enables conscious perceptual experience and makes it more flexible, and thus more adaptive, by being sensitive to context. Apical amplification provides a possible mechanism for recurrent processing theory that avoids strong loops. It makes the broadcasting hypothesized by global neuronal workspace theories feasible while preserving the distinct contributions of the individual cells receiving the broadcast. It also provides mechanisms that contribute to the holistic aspects of integrated information theory. As apical amplification is highly dependent on cholinergic, aminergic, and other neuromodulators, it relates the specific contents of conscious experience to global mental states and to fluctuations in arousal when awake. We conclude that apical dendrites provide a cellular mechanism for the context-sensitive selective amplification that is a cardinal prerequisite of conscious perception.

Scoliosis Management for Primary Care Practitioners.

For many families, the possibility that their child may have scoliosis causes great anxiety because their child may be deformed for life, may need to wear a brace for years, or may need to undergo a large and dangerous operation. For most families, these fears are groundless. Up to 3% of the population has a spinal curvature, most of which are small curves that may not need referral or repeated imaging. Many adolescents with scoliosis do well and do not need to wear a brace or have surgery.

Apical drive-A cellular mechanism of dreaming?

Dreams are internally generated experiences that occur independently of current sensory input. Here we argue, based on cortical anatomy and function, that dream experiences are tightly related to the workings of a specific part of cortical pyramidal neurons, the apical integration zone (AIZ). The AIZ receives and processes contextual information from diverse sources and could constitute a major switch point for transitioning from externally to internally generated experiences such as dreams. We propose that during dreams the output of certain pyramidal neurons is mainly driven by input into the AIZ. We call this mode of functioning "apical drive". Our hypothesis is based on the evidence that the cholinergic and adrenergic arousal systems, which show different dynamics between waking, slow wave sleep, and rapid eye movement sleep, have specific effects on the AIZ. We suggest that apical drive may also contribute to waking experiences, such as mental imagery. Future studies, investigating the different modes of apical function and their regulation during sleep and wakefulness are likely to be richly rewarded.

Impact of scoliosis surgery on pulmonary function in patients with muscular dystrophies and spinal muscular atrophy.

BACKGROUND: Scoliosis is a common complication of severe neuromuscular diseases. The aim of this study is to determine the impact of posterior spinal fusion on pulmonary function parameters in patients with severe neuromuscular disease at our medical center. METHODS: Retrospective chart review of all patients with severe neuromuscular disease who had posterior spinal fusion between 2012 and 2017 at Texas Children's Hospital. Patients with growing rods, brain injury or malformation, and/or spina bifida were excluded. Pulmonary function measures before and after spinal surgery were determined. RESULTS: A total of 20 eligible patients were identified, 7 with Duchenne muscular dystrophy, 6 with spinal muscular atrophy, 3 with merosin deficient muscular dystrophy, 2 with Charcot-Marie-Tooth, 1 with central core disease, and 1 with dystroglycanopathy. The mean change in vital capacity from pre- to postspine surgery was a loss of 0.63 L for the spinal muscular atrophy patients, a loss of 0.36 L for the Duchenne muscular dystrophy patients, and a gain of 0.23 L for the merosin deficient patients. The difference between spinal muscular atrophy and merosin deficient patients was statistically significant (P = .02) CONCLUSION: In this single-center retrospective study, we found that after spine surgery for scoliosis, all patients with spinal muscular atrophy and most patients with Duchenne muscular dystrophy lost vital capacity, while the patients with merosin deficient muscular dystrophy gained vital capacity. These differences were not associated with differences is respiratory strength, body mass index, or surgical outcomes.

Tension Band Plate (TBP)-guided Hemiepiphysiodesis in Blount Disease: 10-Year Single-center Experience With a Systematic Review of Literature.

BACKGROUND: Primary treatment for Blount disease has changed in the last decade from osteotomies or staples to tension band plate (TBP)-guided hemiepiphysiodesis. However, implant-related issues have been frequently reported with Blount cases. The purpose of our study is to evaluate the surgical failure rates of TBP in Blount disease and characterize predictors for failure. METHODS: We performed an Institutional Review Board-approved retrospective chart-review of pediatric patients with Blount disease to evaluate the results of TBP from 2008 to 2017 and a systematic literature review. Blount cases defined as pathologic tibia-vara with HKA (hip-knee-ankle) axis and MDA (metaphyseal-diaphyseal angle) deviations ≥11 degrees were included in the analysis. Surgical failure was categorized as mechanical and functional failure. We studied both patient and implant-related characteristics and compared our results with a systematic review. RESULTS: In 61 limbs of 40 patients with mean follow-up of 38 months, we found 41% (25/61) overall surgical failure rate and 11% (7/61) mechanical failure rate corresponding to 11% to 100% (range) and 0% to 50% (range) in 8 other studies. Statistical comparison between our surgical failure and nonfailure groups showed significant differences in deformity (P=0.001), plate material (P=0.042), and obesity (P=0.044) in univariate analysis. The odds of surgical failure increased by 1.2 times with severe deformity and 5.9 times with titanium TBP in the multivariate analysis after individual risk-factor adjustment. All 7 mechanical failures involved breakage of cannulated screws on the metaphyseal side. CONCLUSIONS: Most of the studies have reported high failure rates of TBP in Blount cases. Besides patient-related risk factors like obesity and deformity, titanium TBP seems to be an independent risk factor for failure. Solid screws were protective for mechanical failure, but not for functional failure. In conclusion, efficacy of TBP still needs to be proven in Blount disease and implant design may warrant reassessment. LEVEL OF EVIDENCE: Level III-retrospective comparative study with a systematic review.

Computational Modeling of Genetic Contributions to Excitability and Neural Coding in Layer V Pyramidal Cells: Applications to Schizophrenia Pathology.

Pyramidal cells in layer V of the neocortex are one of the most widely studied neuron types in the mammalian brain. Due to their role as integrators of feedforward and cortical feedback inputs, they are well-positioned to contribute to the symptoms and pathology in mental disorders-such as schizophrenia-that are characterized by a mismatch between the internal perception and external inputs. In this modeling study, we analyze the input/output properties of layer V pyramidal cells and their sensitivity to modeled genetic variants in schizophrenia-associated genes. We show that the excitability of layer V pyramidal cells and the way they integrate inputs in space and time are altered by many types of variants in ion-channel and Ca2+ transporter-encoding genes that have been identified as risk genes by recent genome-wide association studies. We also show that the variability in the output patterns of spiking and Ca2+ transients in layer V pyramidal cells is altered by these model variants. Importantly, we show that many of the predicted effects are robust to noise and qualitatively similar across different computational models of layer V pyramidal cells. Our modeling framework reveals several aspects of single-neuron excitability that can be linked to known schizophrenia-related phenotypes and existing hypotheses on disease mechanisms. In particular, our models predict that single-cell steady-state firing rate is positively correlated with the coding capacity of the neuron and negatively correlated with the amplitude of a prepulse-mediated adaptation and sensitivity to coincidence of stimuli in the apical dendrite and the perisomatic region of a layer V pyramidal cell. These results help to uncover the voltage-gated ion-channel and Ca2+ transporter-associated genetic underpinnings of schizophrenia phenotypes and biomarkers.

Apical Function in Neocortical Pyramidal Cells: A Common Pathway by Which General Anesthetics Can Affect Mental State.

It has been argued that general anesthetics suppress the level of consciousness, or the contents of consciousness, or both. The distinction between level and content is important because, in addition to clarifying the mechanisms of anesthesia, it may help clarify the neural bases of consciousness. We assess these arguments in the light of evidence that both the level and the content of consciousness depend upon the contribution of apical input to the information processing capabilities of neocortical pyramidal cells which selectively amplify relevant signals. We summarize research suggesting that what neocortical pyramidal cells transmit information about can be distinguished from levels of arousal controlled by sub-cortical nuclei and from levels of prioritization specified by interactions within the thalamocortical system. Put simply, on the basis of the observations reviewed, we hypothesize that when conscious we have particular, directly experienced, percepts, thoughts, feelings and intentions, and that general anesthetics affect consciousness by interfering with the subcellular processes by which particular activities are selectively amplified when relevant to the current context.

Feed efficiency of tropically adapted cattle when fed in winter or spring in a temperate location.

Earlier work has shown that young tropically adapted cattle do not gain weight as rapidly as temperately adapted cattle during the winter in Oklahoma. The objective for this study was to determine whether efficiency of gains was also affected in tropically adapted cattle and whether efficiency was consistent over different seasons. Over 3 yr, 240 straightbred and crossbred steers (F1 and 3-way crosses) of Angus, Brahman, or Romosinuano breeding, born in Brooksville, FL, were transported to El Reno, OK in October and fed in 2 phases to determine performance, individual intake, and efficiency. Phase 1 (WIN) began in November after a 28-d recovery from shipping stress and phase 2 (SS) began in March, 28 d following completion of WIN each year. The diet for WIN was a grower diet (14% CP, 1.10 Mcal NEg/kg) and that for the SS was a feedlot diet (12.8% CP; 1.33 Mcal NEg/kg). After a 14-d adjustment to diet and facilities, intake trials were conducted over a period of 56 to 162 d for determination of intake and gain for efficiency. Body weights were recorded at approximately 14-d intervals, and initial BW, median BW, and ADG were determined from individual animal regressions of BW on days on feed. Individual daily DMI was then regressed by phase on median BW and ADG, and residuals of regression were recorded as residual feed intake (RFI). Similarly, daily gain was regressed by phase on median BW and DMI, and errors of regression were recorded as residual gain (RADG). Gain to feed (G:F) was also calculated. The statistical model to evaluate ADG, DMI, and efficiency included fixed effects of dam age (3 to 4, 5, 6 to 10, and >10 yr), harvest group (3 per year), age on test, and a nested term DT (ST × XB), where DT is the proportion tropical breeding of dam (0, 0.5, or 1), ST is the proportion tropical breeding of sire (1 or 0), and XB whether the calf was straightbred or crossbred. Year of record, sire (ST × XB), and pen were random effects. Preweaning ADG and BW increased (P < 0.05) with level of genetic tropical influence, but during the WIN, ADG and efficiency estimated by G:F and RADG declined (P < 0.05). Tropical influence had little effect on RFI during the WIN, or on most traits during SS. In general, during SS, crossbred steers gained faster and were more efficient by G:F and RADG (P < 0.05) than straightbred steers. Simple correlations, both Pearson and Spearman, between RFI in WIN and RFI in SS were 0.51 (P < 0.001), whereas that for RADG was 0.17 (P < 0.01).

Partial information decomposition as a unified approach to the specification of neural goal functions.

In many neural systems anatomical motifs are present repeatedly, but despite their structural similarity they can serve very different tasks. A prime example for such a motif is the canonical microcircuit of six-layered neo-cortex, which is repeated across cortical areas, and is involved in a number of different tasks (e.g. sensory, cognitive, or motor tasks). This observation has spawned interest in finding a common underlying principle, a 'goal function', of information processing implemented in this structure. By definition such a goal function, if universal, cannot be cast in processing-domain specific language (e.g. 'edge filtering', 'working memory'). Thus, to formulate such a principle, we have to use a domain-independent framework. Information theory offers such a framework. However, while the classical framework of information theory focuses on the relation between one input and one output (Shannon's mutual information), we argue that neural information processing crucially depends on the combination of multiple inputs to create the output of a processor. To account for this, we use a very recent extension of Shannon Information theory, called partial information decomposition (PID). PID allows to quantify the information that several inputs provide individually (unique information), redundantly (shared information) or only jointly (synergistic information) about the output. First, we review the framework of PID. Then we apply it to reevaluate and analyze several earlier proposals of information theoretic neural goal functions (predictive coding, infomax and coherent infomax, efficient coding). We find that PID allows to compare these goal functions in a common framework, and also provides a versatile approach to design new goal functions from first principles. Building on this, we design and analyze a novel goal function, called 'coding with synergy', which builds on combining external input and prior knowledge in a synergistic manner. We suggest that this novel goal function may be highly useful in neural information processing.

Cognitive functions of intracellular mechanisms for contextual amplification.

Evidence for the hypothesis that input to the apical tufts of neocortical pyramidal cells plays a central role in cognition by amplifying their responses to feedforward input is reviewed. Apical tufts are electrically remote from the soma, and their inputs come from diverse sources including direct feedback from higher cortical regions, indirect feedback via the thalamus, and long-range lateral connections both within and between cortical regions. This suggests that input to tuft dendrites may amplify the cell's response to basal inputs that they receive via layer 4 and which have synapses closer to the soma. ERP data supporting this inference is noted. Intracellular studies of apical amplification (AA) and of disamplification by inhibitory interneurons targeted only at tufts are reviewed. Cognitive processes that have been related to them by computational, electrophysiological, and psychopathological studies are then outlined. These processes include: figure-ground segregation and Gestalt grouping; contextual disambiguation in perception and sentence comprehension; priming; winner-take-all competition; attention and working memory; setting the level of consciousness; cognitive control; and learning. It is argued that theories in cognitive neuroscience should not assume that all neurons function as integrate-and-fire point processors, but should use the capabilities of cells with distinct sites of integration for driving and modulatory inputs. Potentially 'unifying' theories that depend upon these capabilities are reviewed. It is concluded that evolution of the primitives of AA and disamplification in neocortex may have extended cognitive capabilities beyond those built from the long-established primitives of excitation, inhibition, and disinhibition.

Implications of Information Theory for Computational Modeling of Schizophrenia.

Information theory provides a formal framework within which information processing and its disorders can be described. However, information theory has rarely been applied to modeling aspects of the cognitive neuroscience of schizophrenia. The goal of this article is to highlight the benefits of an approach based on information theory, including its recent extensions, for understanding several disrupted neural goal functions as well as related cognitive and symptomatic phenomena in schizophrenia. We begin by demonstrating that foundational concepts from information theory-such as Shannon information, entropy, data compression, block coding, and strategies to increase the signal-to-noise ratio-can be used to provide novel understandings of cognitive impairments in schizophrenia and metrics to evaluate their integrity. We then describe more recent developments in information theory, including the concepts of infomax, coherent infomax, and coding with synergy, to demonstrate how these can be used to develop computational models of schizophrenia-related failures in the tuning of sensory neurons, gain control, perceptual organization, thought organization, selective attention, context processing, predictive coding, and cognitive control. Throughout, we demonstrate how disordered mechanisms may explain both perceptual/cognitive changes and symptom emergence in schizophrenia. Finally, we demonstrate that there is consistency between some information-theoretic concepts and recent discoveries in neurobiology, especially involving the existence of distinct sites for the accumulation of driving input and contextual information prior to their interaction. This convergence can be used to guide future theory, experiment, and treatment development.

The coherent organization of mental life depends on mechanisms for context-sensitive gain-control that are impaired in schizophrenia.

There is rapidly growing evidence that schizophrenia involves changes in context-sensitive gain-control and probabilistic inference. In addition to the well-known cognitive disorganization to which these changes lead, basic aspects of vision are also impaired, as discussed by other papers on this Frontiers Research Topic. The aim of this paper is to contribute to our understanding of such findings by examining five central hypotheses. First, context-sensitive gain-control is fundamental to brain function and mental life. Second, it occurs in many different regions of the cerebral cortex of many different mammalian species. Third, it has several computational functions, each with wide generality. Fourth, it is implemented by several neural mechanisms at cellular and circuit levels. Fifth, impairments of context-sensitive gain-control produce many of the well-known symptoms of schizophrenia and change basic processes of visual perception. These hypotheses suggest why disorders of vision in schizophrenia may provide insights into the nature and mechanisms of impaired reality testing and thought disorder in psychosis. They may also cast light on normal mental function and its neural bases. Limitations of these hypotheses, and ways in which they need further testing and development, are outlined.