Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026: 06/14/17

Τετάρτη 14 Ιουνίου 2017

Benefits of an individualized perioperative plan for children with autism spectrum disorder

Summary

Background

Perioperative care for children with autism spectrum disorder may be challenging. Previous investigators recommend development of an individualized perioperative management plan with caregiver involvement.

Aim

The primary goal was to determine the usefulness of an individualized plan based on the decision to provide preoperative sedation stratified by autism spectrum severity level. Secondary goals were to assess the effectiveness of the plan based on subjective assessment of patient behavior at induction of anesthesia and caregiver satisfaction.

Methods

We developed an individualized plan for each child with autism spectrum disorder scheduled for anesthesia. Children were categorized by autism spectrum disorder severity level. With institutional ethics approval, we conducted a retrospective chart review to document need for preoperative sedation, sedation stratified by autism spectrum disorder severity level, behavior at induction, and caregiver satisfaction.

Results

Between 2012 and 2014, we successfully prepared a plan for 246 (98%) of 251 surgical or diagnostic procedures in 224 patients. Severity level was distributed as 45% Severity Level 1 and Asperger's, 25% Severity Level 2, and 30% Severity Level 3. The majority (90%) of cases were scheduled as day surgery. Preoperative sedation increased with increasing severity level: Severity Level 1 (21%) or Asperger's (31%), Severity Level 2 (44%), and Severity Level 3 (56%). The odds ratio for sedation use was 5.5 [CI: 2.6-11.5, P<.001] with Severity Level 3 vs Severity Level 1 patients. Cooperation at induction of anesthesia was 90% overall with preoperative sedation administered to 94 (38%) of the entire cohort. Cooperation was greatest in Severity Level 1 (98%) and Asperger's patients (93%) and somewhat less (85%) in patients in Severity Levels 2 and 3. The plan was helpful to guide sedation choices as cooperation did not differ between sedated and unsedated children at any severity level (overall χ²=2.87 P=.09).

Satisfaction among caregivers contacted was 98%.

Conclusion

The results suggest that an individualized plan is helpful in the perioperative management of children with autism spectrum disorder and that knowledge of autism spectrum disorder severity level may be helpful in determining the need for preoperative sedation.

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Introduction of color-flow injection test to confirm intravascular location of peripherally placed intravenous catheters

Summary

Background

The incidence of infiltration and extravasation when using peripheral intravenous catheters is high in pediatric patients. Due to the lack of a gold standard test to confirm intravascular location of a peripherally placed intravenous catheter, we introduce a novel method, the color-flow injection test to assess the intravascular location of these catheters. For the color-flow injection test, 1 mL of normal saline was injected within 2 seconds in the distal intravenous catheter and changes in color-flow via ultrasonography were observed at the proximal draining veins. The primary objective of the study was to demonstrate feasibility of the color-flow injection test.

Methods

A prospective study was conducted on children <18 years old undergoing general anesthesia. All peripheral intravenous catheters were subject to the color-flow injection test and standard confirmation tests.

Results

Out of the 100 patients enrolled, 22 patients came to the operating room with preexisting peripheral intravenous catheters. Intraoperatively, 105 attempts were made on 78 patients of which 27 catheters were considered as infiltrated during their placement. A final set of 100 catheters were considered for intraoperative usage after they had passed at least one of the standard confirmatory tests. For the color-flow injection test, the ideal sites for ultrasound evaluation of proximal draining veins were the axillary veins and femoral veins. The color-flow injection test was positive in 93 of the 100 catheters with color-flow changes noticed in the proximal veins during the saline injection. Of the 100 catheters, infiltration around seven catheter sites were observed within 2 hours of intraoperative usage and the color-flow injection test was negative in these seven catheters. The color-flow injection test was also negative in the 27 catheters that had infiltrated during their placement. The color-flow injection test was sensitive at 100% [95% confidence interval (CI)=95-100] and specific at 100% (95% CI=56-100) to indicate intravascular location.

Conclusion

We were able to confirm intravascular location of peripheral intravenous catheters using the color-flow injection test in pediatric patients. The test can lead to early recognition of malfunctioning peripheral intravenous catheters and decrease rate of infiltration-extravasation injuries associated with their use.

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Plant genetics: Branching out for crop improvement

Nature Reviews Genetics 18, 393 (2017). doi:10.1038/nrg.2017.48

Author: Darren J. Burgess

Inflorescence architecture is the arrangement of flowers and their underlying stem branching patterns, and it has important effects on the yield of the fruits or grains from agricultural plants. A new study dissects key genetic underpinnings of tomato inflorescence branching, which not only provides insight

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Associating cellular epigenetic models with human phenotypes

Nature Reviews Genetics 18, 441 (2017). doi:10.1038/nrg.2017.32

Authors: Tuuli Lappalainen & John M. Greally

Epigenetic association studies have been carried out to test the hypothesis that environmental perturbations trigger cellular reprogramming, with downstream effects on cellular function and phenotypes. There have now been numerous studies of the potential molecular mediators of epigenetic changes by epigenome-wide association studies (EWAS). However,

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Plant genetics: Spatial transcriptomics in plants

Nature Reviews Genetics 18, 394 (2017). doi:10.1038/nrg.2017.41

Author: Liesbet Lieben

Spatial transcriptomics combines histological imaging and RNA sequencing to simultaneously quantify and localize gene expression. Giacomello et al. have now optimized this technique for plant tissues, which pose specific challenges compared with mammalian tissues, such as the presence of cell walls, vacuoles, chloroplasts and

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Cancer genomics: Tracking cancer evolution

Nature Reviews Genetics 18, 391 (2017). doi:10.1038/nrg.2017.43

Author: Carolina Perdigoto

Understanding tumour heterogeneity and evolution is essential for the early detection of disease recurrence and the efficient treatment of cancer. Two recent studies published in Nature and in the New England Journal of Medicine prospectively tracked the evolutionary dynamics of early-stage non-small-cell lung

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Stem cells: The different flavours of iPS cells

Nature Reviews Genetics 18, 394 (2017). doi:10.1038/nrg.2017.42

Author: Katharine H. Wrighton

The use of induced pluripotent stem (iPS) cells for studying genetic variants that underlie human diseases is complicated by the fact that individual iPS cell lines are genetically and phenotypically heterogeneous. Kilpinen et al. now provide a detailed overview of the genetic and phenotypic

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Technology: Nucleic acid detection — it's elementary with SHERLOCK!

Nature Reviews Genetics 18, 392 (2017). doi:10.1038/nrg.2017.40

Author: Dorothy Clyde

Point-of-care (POC) diagnostic tools should be sensitive, specific, simple to use, rapid, portable and low cost; however, satisfying all these criteria in a single device without compromise is challenging. Now, a new study reports a CRISPR-based diagnostic platform for detecting nucleic acids that has the

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The evolutionary significance of polyploidy

Nature Reviews Genetics 18, 411 (2017). doi:10.1038/nrg.2017.26

Authors: Yves Van de Peer, Eshchar Mizrachi & Kathleen Marchal

Polyploidy, or the duplication of entire genomes, has been observed in prokaryotic and eukaryotic organisms, and in somatic and germ cells. The consequences of polyploidization are complex and variable, and they differ greatly between systems (clonal or non-clonal) and species, but the process has often

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Genetic testing: The diagnostic power of RNA-seq

Nature Reviews Genetics 18, 392 (2017). doi:10.1038/nrg.2017.39

Author: Katharine H. Wrighton

Whole-exome sequencing (WES) and whole-genome sequencing (WGS) can only identify rare Mendelian genetic diseases in up to 50% of cases; our ability to interpret the functional and clinical importance of the genetic variants they identify is limited. Here, Cummings et al. show that analysing

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Comparative transcriptomics in human and mouse

Nature Reviews Genetics 18, 425 (2017). doi:10.1038/nrg.2017.19

Authors: Alessandra Breschi, Thomas R. Gingeras & Roderic Guigó

Cross-species comparisons of genomes, transcriptomes and gene regulation are now feasible at unprecedented resolution and throughput, enabling the comparison of human and mouse biology at the molecular level. Insights have been gained into the degree of conservation between human and mouse at the level of

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Functional variomics and network perturbation: connecting genotype to phenotype in cancer

Nature Reviews Genetics 18, 395 (2017). doi:10.1038/nrg.2017.8

Authors: Song Yi, Shengda Lin, Yongsheng Li, Wei Zhao, Gordon B. Mills & Nidhi Sahni

Proteins interact with other macromolecules in complex cellular networks for signal transduction and biological function. In cancer, genetic aberrations have been traditionally thought to disrupt the entire gene function. It has been increasingly appreciated that each mutation of a gene could have a subtle but

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Is a Chest Radiograph Required After Removal of Chest Tubes in Children?

Our objective was to determine the clinical value of obtaining a chest radiograph after removal of a chest tube. We conducted a retrospective chart review of pediatric general surgical patients with a chest tube in place after a thoracic procedure over a 3-year time period. Postremoval films were considered to be of value if they led to a change in clinical management. Of 468 patients who had a thoracic procedure, 281 patients had a chest tube and a postremoval film. In 263 patients (93.6%) there was no change in the postremoval film result compared with baseline.

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Prevalence of and risk factors for HBV infection in a metropolitan Southern Italian area: Evidence for the effectiveness of universal Hepatitis B vaccination.

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Detection of New Delhi Metallo-β-Lactamase Variants NDM-4, NDM-5, and NDM-7 in Enterobacter aerogenes Isolated from a Neonatal Intensive Care Unit of a North India Hospital: A First Report

Microbial Drug Resistance , Vol. 0, No. 0.

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Effect of eye position during human visual-vestibular integration of heading perception

Visual and inertial stimuli provide heading discrimination cues. Integration of these multisensory stimuli has been demonstrated to depend on their relative reliability. However, the reference frame of visual stimuli is eye centered while inertial is head centered and it remains unclear how these are reconciled with combined stimuli. Seven human subjects completed a heading discrimination task consisting of a 2s translation with a peak velocity of 16 cm/s. Eye position was varied between 0°, and ±25° left/right. Experiments were done using inertial motion, visual motion, or a combined visual-inertial motion. Visual motion coherence varied between 35-100%. Subjects reported if their perceived heading was left or right of the midline using a forced choice task. With the inertial stimulus the eye position had an effect such that the point of subjective equality (PSE) shifted 4.6 ± 2.4° in the gaze direction. With the visual stimulus the PSE shift was 10.2 ± 2.2° opposite the gaze direction consistent with retinotopic coordinates. Thus with eccentric eye positions, the perceived inertial and visual headings were offset about 15°. During the visual-inertial conditions the PSE varied consistently with the relative reliability of these stimuli such that at low visual coherence the PSE was similar to that of the inertial stimulus and at high coherence it was closer to the visual stimulus. On average, the inertial stimulus was weighted near Bayesian ideal predictions, but there was significant deviation from ideal in individual subjects. These findings support visual and inertia cue integration occurring in independent coordinate systems.

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Activity of primate V1 neurons during the gap saccade task

When a saccadic eye movement is made toward a visual stimulus, the variability in accompanying V1 activity is related to saccade latency in both human (Bompas et al., 2015) and non-human (Lee et al., 2010) primates. In order to understand the nature of this relationship, we examined the functional link between V1 activity and the initiation of visually guided saccades during the gap saccade task, in which a brief temporal gap is interposed between the turning off of a fixation stimulus and the appearance of a saccadic target. The insertion of such a gap robustly reduces saccade latency (Saslow, 1967), and facilitates the occurrence of extremely short latency (express) saccades (Fischer and Boch, 1983). Here, we recorded single-cell activity from macaque V1 while monkeys performed the gap saccade task. In parallel with the gap effect on saccade latency, the neural latency (time of first spike) of V1 response elicited by the saccade target became shorter, and the firing rate increased as the gap duration increased. Similarly, neural latency was shorter and firing rate was higher before express saccades relative to regular latency saccades. In addition to these post-target changes, the level of spontaneous spike activity during the pre-target period was negatively correlated with both neural and saccade latencies. These results demonstrate that V1 activity correlates with the gap effect, and indicate that the trial-to-trial variability in the state of V1 underlies the variability of neural and behavioral latencies.

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High frequency epidural stimulation across the respiratory cycle evokes phrenic short-term potentiation after incomplete cervical spinal cord injury

C2 spinal hemilesion (C2Hx) paralyzes the ipsilateral diaphragm, but recovery is possible through activation of "crossed spinal" synaptic inputs to ipsilateral phrenic motoneurons. We tested the hypothesis that high frequency epidural stimulation (HF-ES) would potentiate ipsilateral phrenic output after subacute and chronic C2Hx. HF-ES (300 Hz) was applied to the ventrolateral C4 or T2 spinal cord ipsilateral to C2Hx in anesthetized and mechanically ventilated adult rats. Stimulus duration was 60-sec and currents ranged from 100-1000 µA. Bilateral phrenic nerve activity and ipsilateral hypoglossal nerve activity were recorded before and after HF-ES. Higher T2 stimulus currents potentiated ipsilateral phasic inspiratory activity at both 2- and 12-wks post-C2Hx, while higher stimulus currents delivered at C4 potentiated ipsilateral phasic phrenic activity only at 12-wks (P=0.028). Meanwhile, tonic output in the ipsilateral phrenic nerve reached 500% of baseline values at the high currents with no difference between 2- and 12-wks. HF-ES did not trigger inspiratory burst frequency changes. Similar responses occurred following T2 HF-ES. Increases in contralateral phrenic and XII nerve output were induced by C4 and T2 HF-ES at higher currents, but the relative magnitude of these changes was small compared to the ipsilateral phrenic response. We conclude that following incomplete cervical SCI, HF-ES of the ventrolateral mid-cervical or thoracic spinal cord can potentiate efferent phrenic motor output with little impact on inspiratory burst frequency. However, the substantial increases in tonic output indicate that the uninterrupted 60-sec stimulation paradigm used here is unlikely to be useful for respiratory muscle activation after spinal injury.

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Interhemispheric interactions between trunk muscle representations of the primary motor cortex

Unilateral arm movements require trunk stabilization through bilateral contraction of axial muscles. Interhemispheric interactions between primary motor cortices (M1) could enable such coordinated contractions but these mechanisms are largely unknown. Using transcranial magnetic stimulation (TMS), we characterized interhemispheric interactions between M1 representations of the trunk stabilizing muscle erector spinae at 1^st lumbar vertebra (ES L1) during a right isometric shoulder flexion. These interactions were compared to those of Anterior Deltoid (AD), the main agonist in this task, and the first dorsal interosseous (FDI). TMS over the right M1 elicited ipsilateral silent periods (iSP) in all three muscles on the right side. In ES L1 - but not AD or FDI-, ipsilateral motor evoked potential (iMEP) could precede the iSP or replaced it. iMEP amplitude was not significantly different whether ES L1 was used to stabilize the trunk or was voluntarily contracted. TMS at the cervicomedullary junction showed that the size of CMEP was unchanged during the iSP but increased during iMEP, suggesting that the iSP is due to intracortical mechanisms, but not the iMEP. Using a dual coil paradigm with two coils over the left and right M1, interhemispheric inhibition could be evoked at interstimulus interval of 6ms in ES L1 and 8ms in AD and FDI. Together these results suggest that interhemispheric inhibition is dominant when axial muscles are involved in a stabilizing task. The ipsilateral facilitation could be evoked by ipsilateral or subcortical pathways and could be used depending on the role axial muscles play in the task.

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Perspectives on classical controversies about the motor cortex

Primary motor cortex has been studied for more than a century, yet a consensus on its functional contribution to movement control is still out of reach. In particular, there remains controversy as to the level of control produced by motor cortex ("low level" movement dynamics vs. "high-level" movement kinematics) and the role of sensory feedback. Here we present different perspectives on the two following questions: What does activity in motor cortex reflect? And, how do planned motor commands interact with incoming sensory feedback during movement? The four authors each present their independent views on how they think the primary motor cortex (M1) controls movement. At the end we present a dialogue in which the authors synthesize their views and suggest possibilities for moving the field forward. While there is not yet a consensus on the role of M1 or sensory feedback in the control of upper limb movements, such dialogues are essential to take us closer to one.

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Accumulation of methylglyoxal increases the advanced glycation end products levels in DRG and contributes to lumbar disc herniation-induced persistent pain

Lumbar disc herniation (LDH) with discogenic low back pain and sciatica is a common and complicated musculoskeletal disorder. The underlying mechanisms are poorly understood and there are no effective therapies for LDH-induced pain. In the present study, we found that the patients who suffered from LDH-induced pain had elevated plasma methylglyoxal (MG) levels. In rats, implantation of autologous nucleus pulposus (NP) to the left lumbar 5 spinal nerve root, which mimicked LDH, induced mechanical allodynia and increased MG level in plasma and dorsal root ganglion (DRG) and enhanced the excitability of small DRG neurons (< 30μm in diameter). Intrathecal injection of MG also induced mechanical allodynia and its application to DRG neurons ex vivo increased the number of action potentials evoked by depolarizing current pulses. Furthermore, inhibition of MG accumulation by aminoguanidine attenuated the enhanced excitability of small DRG neurons and the mechanical allodynia induced by NP implantation. In addition, NP implantation increased levels of advanced glycation end products (AGEs) in DRG, and intrathecal injection of MG-derived AGEs induced the mechanical allodynia and DRG neuronal hyperactivity. Intrathecal injection of MG also significantly increased the expression of AGEs in DRG. Importantly, scavenging of MG by aminoguanidine also attenuated the increase in AGEs induced by NP implantation. These results suggested that LDH-induced MG accumulation contributed to persistent pain by increasing AGE levels. Thus, generation of AGEs from MG may represent a target for treatment of LDH-induced pain.

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Prevention and reversal of latent sensitization of dorsal horn neurons by glial blockers in a model of low back pain in male rats

In an animal model of non-specific low back pain, recordings from dorsal horn neurons were made to investigate the influence of glial cells in the central sensitization process. To induce a latent sensitization of the neurons, nerve growth factor (NGF) was injected into the multifidus muscle; the manifest sensitization to a second NGF injection 5 days later was used as a read-out. The sensitization manifested in increased resting activity and in an increased proportion of neurons responding to stimulation of deep somatic tissues. To block microglial activation, minocycline was continuously administered intrathecally starting 1 day before or 2 days after the first NGF injection. The glia inhibitor fluorocitrate that also blocks astrocyte activation was administrated 2 days after the first injection. Minocycline applied before the first NGF injection reduced the manifest sensitization after the second NGF injection to control values. The proportion of neurons responsive to stimulation of deep tissues was reduced from 50% to 17.7% (P<0.01). No significant changes occurred when minocycline was applied after the first injection. In contrast, fluorocitrate administrated after the first NGF injection reduced significantly the proportion of neurons with deep input (15.8%, P<0.01). A block of glia activation had no significant effect on the increased resting activity. The data suggest that blocking microglial activation prevented the NGF-induced latent spinal sensitization while blocking astrocyte activation reversed it. The induction of spinal neuronal sensitization in this pain model appears to depend on microglia activation, while its maintenance is regulated by activated astrocytes.

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Excitability and firing behavior of single slow motor axons transmitting natural repetitive firing of human motoneurons

Excitability of motor axons is critically important for realizing their main function - transmitting motoneuron firing to muscle fibres. The present study was designed to explore excitability recovery and firing behavior in single slow axons transmitting human motoneuron firing during voluntary muscle contractions. The abductor digiti minimi, flexor carpi ulnaris, and tibialis anterior were investigated during threshold stimulation of corresponding motor nerves. Motor unit (MU) firing index in response to testing volleys evoking M-responses was used as a physiological measure of axonal excitability and its changes throughout a target interspike interval (ISI) were explored. It was shown that axons displayed an early irresponsive period (within the first ~ 2 - 5 ms of a target ISI) that followed by a responsive period (for the next 5 - 17 ms of the ISI), in which MUs fired axonal doublets, and a later irresponsive period. At the beginning of the responsive period, M-responses showed small latency delays. However, since at that ISI moment, MUs displayed excitability recovery with high firing index, slight latency changes, may be considered as a functionally insignificant phenomenon. The duration of axonal doublet ISIs did not depend on motoneuron firing frequencies (range: 4.3 - 14.6 imp/s). The question of whether or not traditionally described axonal recovery excitability cycle is realistic in natural motor control is discussed. In conclusion, the present approach, exploring, for the first time, excitability recovery in single slow axons during motoneuron natural activation, can provide further insight into axonal firing behavior in normal and diseases.

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The visual encoding of purely proprioceptive intermanual tasks is due to the need of transforming joint signals, not to their inter-hemispheric transfer

To perform goal-oriented hand movement humans combine multiple sensory signals (e.g. vision and proprioception) that can be encoded in various reference frames (body-centered and/or exo-centered). In a previous study we showed that when aligning a hand to a remembered target orientation the brain encodes both target and response in visual space when the target is sensed by one hand and the response is performed by the other, even though both are sensed only through proprioception. Here we ask whether such visual encoding is due i) to the necessity of transferring sensory information across the brain hemispheres or ii) to the necessity, due to the arms' anatomical mirror symmetry, of transforming the joint signals of one limb into the reference frame of the other. To answer this question we asked subjects to perform purely proprioceptive tasks in different conditions: Intra - the same arm sensing the target and performing the movement; Inter/Parallel - one arm sensing the target and the other reproducing its orientation; and Inter/Mirror - one arm sensing the target and the other mirroring its orientation. Performance was very similar between Intra and Inter/Mirror (conditions not requiring joint-signal transformations) while both differed from Inter/Parallel. Manipulation of the visual scene in a virtual-reality paradigm showed visual encoding of proprioceptive information only in the latter conditions. These results suggest that the visual encoding of purely proprioceptive tasks is not due to inter-hemispheric transfer of the proprioceptive information per se, but to the necessity of transforming joint signals between mirror-symmetric limbs.

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Physiological Properties of Brain Machine Interface Input Signals

Brain machine interfaces (BMIs), also called brain computer interfaces (BCIs), decode neural signals and use them to control some type of external device. Despite many experimental successes and terrific demonstrations in animals and humans, a high-performance, clinically-viable device has not yet been developed for widespread usage. There are many factors that impact clinical viability and BMI performance. Arguably the first of these is the selection of brain signals used to control BMIs. Here, we summarize the physiological characteristics and performance-including movement-related information, longevity, and stability-of multiple types of input signals that have been used in invasive BMIs to date. These include intracortical spikes as well as field potentials obtained inside the cortex, at the surface of the cortex (electrocorticography), and at the surface of the dura mater (epidural signals). We also discuss the potential for future enhancements in input signal performance, both by improving hardware and by leveraging the knowledge of the physiological characteristics of these signals to improve decoding and stability.

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Comparison of the VTA and LC response to methylphenidate: a concomitant behavioral and neuronal study of adolescent male rats

Methylphenidate (MPD), also known as Ritalin, is a psychostimulant used to treat attention hyperactivity disorder. However, it is increasingly being misused by normal adolescents for recreation and academic advantage. Therefore, it is important to elucidate the behavioral and neurophysiological effects of MPD in normal subjects. MPD inhibits the reuptake of catecholamines, mainly found in the ventral tegmental area (VTA) and locus coeruleus (LC). The VTA and LC normally mediate attention, motivation, and drug reward behaviors. Selective neuronal connections between the VTA and LC have been identified implicating regular interaction between the structures. The objective of this study was to compare the neuronal responses of the VTA and LC to MPD in normal adolescent rats. Animals were implanted with permanent electrodes in the VTA and LC, and neuronal units were recorded following acute and repetitive (chronic) saline, 0.6, 2.5, or 10.0 mg/kg MPD exposure. Animals displayed either behavioral sensitization or tolerance to all three doses of MPD. Acute MPD exposure elicited excitation in the majority of all VTA and LC units. Chronic MPD exposure elicited a further increase in VTA and LC neuronal activity in animals exhibiting behavioral sensitization and an attenuation in VTA and LC neuronal activity in animals exhibiting behavioral tolerance demonstrating neurophysiological sensitization and tolerance, respectively. The similar pattern in VTA and LC unit activity suggest that the two structures are linked in their response to MPD. These results may help determine the exact mechanism of action of MPD resulting in optimized treatment of patients.

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Diffusion weighted tractography in the common marmoset monkey at 9.4 T

The common marmoset (Callithrix jacchus) is a small New World primate that is becoming increasingly popular in the neurosciences as an animal model of preclinical human disease. With several major disorders characterized by alterations in neural white matter (e.g., multiple sclerosis, Alzheimer's, schizophrenia) proposed to be transgenically modelled using marmosets, the ability to reliably isolate and characterize major white matter fiber tracts with MRI will be of utility for evaluating structural brain changes related to disease processes and symptomatology. Here, we propose protocols for isolating major white matter fiber tracts in the common marmoset using in vivo ultra-high field MRI (9.4 T) diffusion weighted imaging (DWI) data. Using a high angular resolution DWI (256 diffusion encoding directions) sequence collected on four anesthetized marmosets, we provide guidelines for manually drawing fiber tracking regions of interest based on easily identified anatomical landmarks in DWI native space. These fiber tract isolation protocols are expected to be experimentally useful for visualization and quantification of individual white matter fiber tracts in both control and experimental groups of marmosets (e.g., transgenic models). As disease models in the marmoset advance, determining how macroscopic white matter anatomy is altered as a function of disease state will be relevant in bridging the existing translational gap between preclinical rodent models and human patients.

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Supramodal Representation of Temporal Priors Calibrates Interval Timing

Human timing behaviors are consistent with Bayesian inference, according to which both previous knowledge (prior) and current sensory information determine final responses. However, it is unclear whether the brain represents temporal priors exclusively for individual modalities or in a supramodal manner when temporal information comes from different modalities at different times. Here we asked participants to reproduce time intervals in either a unisensory or a multisensory context. In unisensory tasks, sample intervals drawn from a uniform distribution were presented in a single visual or auditory modality. In multisensory tasks, sample intervals from the two modalities were randomly mixed; visual and auditory intervals were drawn from two adjacent uniform distributions, with the conjunction of the two being equal to the distribution in the unisensory tasks. In the unisensory tasks, participants' reproduced times exhibited classic central-tendency biases: shorter intervals were overestimated and longer intervals were underestimated. In the multisensory tasks, reproduced times were biased towards the mean of the whole distribution rather than the means of intervals in individual modalities. The Bayesian model with a supramodal prior (distribution of time intervals from both modalities) outperformed the model with modality-specific priors in describing participants' performance. With a generalized model assuming the prior to be a weighted combination of unimodal priors, we further obtained the relative contribution of visual intervals and auditory intervals in forming the prior for each participant. These findings suggest a supramodal mechanism for encoding priors in temporal processing, although the extent of influence of one modality upon another differs individually.

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Different roles for inhibition in the rhythm-generating respiratory network

Unraveling the interplay of excitation and inhibition within rhythm-generating networks remains a fundamental issue in neuroscience. We use a biophysical model to investigate the different roles of local and long-range inhibition in the respiratory network, a key component of which is the pre-Bötzinger complex inspiratory microcircuit. Increasing inhibition within the microcircuit results in a limited number of out-of-phase neurons before rhythmicity and synchrony degenerate. Thus, unstructured local inhibition is destabilizing and cannot support the generation of more than one rhythm. A two-phase rhythm requires restructuring the network into two microcircuits coupled by long-range inhibition in the manner of a half-center. In this context, inhibition leads to greater stability of the two out-of-phase rhythms. We support our computational results with in vitro recordings from mouse pre-Bötzinger complex. Partial excitation block leads to increased rhythmic variability, but this recovers following blockade of inhibition. Our results support the idea that local inhibition in the pre-Bötzinger complex is present to allow for descending control of synchrony or robustness to adverse conditions like hypoxia. We conclude that the balance of inhibition and excitation determines the stability of rhythmogenesis, but with opposite roles within and between areas. These different inhibitory roles may apply to a variety of rhythmic behaviors that emerge in widespread pattern generating circuits of the nervous system.

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Wakefulness suppresses retinal-wave-related neural activity in visual cortex

In the developing visual system before eye opening, spontaneous retinal waves trigger bursts of neural activity in downstream structures, including visual cortex. At the same ages when retinal waves provide the predominant input to the visual system, sleep is the predominant behavioral state. However, the interactions between behavioral state and retinal-wave-driven activity have never been explicitly examined. Here, we characterized unit activity in visual cortex during spontaneous sleep-wake cycles in 9- and 12-day-old rats. At both ages, cortical activity occurred in discrete rhythmic bursts, approximately 30-60 s apart, mirroring the timing of retinal waves. Interestingly, when pups spontaneously woke up and moved their limbs in the midst of a cortical burst, the activity was suppressed. Finally, experimentally evoked arousals also suppressed intra-burst cortical activity. All together, these results indicate that active wake interferes with the activation of the developing visual cortex by retinal waves. They also suggest that sleep-wake processes can modulate visual cortical plasticity at earlier ages than has been previously considered.

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Prevalence of and risk factors for HBV infection in a metropolitan Southern Italian area: Evidence for the effectiveness of universal Hepatitis B vaccination.

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Subclinical white matter lesions and medial temporal lobe atrophy are associated with EEG slowing in a memory clinic cohort

As the world's population ages, the identification of subjects at increased risk of Alzheimer's dementia and the early detection of Alzheimer's disease (AD) are key topics in research and are also of increasing relevance in clinical care and patient counselling. Newly refined diagnostic criteria for AD now better define clinical phenotype and integrate neuroimaging and cerebrospinal fluid biomarkers into the diagnostic process. They cover the full staging of the disease from the subjective cognitive impairment (SCI) and mild cognitive impairment (MCI) to clinically obvious dementia (Dubois et al., 2014).

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