Non-invasive 4D transcranial functional ultrasound and ultrasound localization microscopy for multimodal imaging of neurovascular response.

A long-standing goal of neuroimaging is the non-invasive volumetric assessment of whole brain function and structure at high spatial and temporal resolutions. Functional ultrasound (fUS) and ultrasound localization microscopy (ULM) are rapidly emerging techniques that promise to bring advanced brain imaging and therapy to the clinic with the safety and low-cost advantages associated with ultrasound. fUS has been used to study cerebral hemodynamics at high temporal resolutions while ULM has been used to study cerebral microvascular structure at high spatial resolutions.

Methodological Problems With Online Concussion Testing.

Reaction time testing is widely used in online computerized concussion assessments, and most concussion studies utilizing the metric have demonstrated varying degrees of difference between concussed and non-concussed individuals. The problem with most of these online concussion assessments is that they predominantly rely on consumer grade technology. Typical administration of these reaction time tests involves presenting a visual stimulus on a computer monitor and prompting the test subject to respond as quickly as possible via keypad or computer mouse.

Quantification of Mild Traumatic Brain Injury via Cortical Metrics: Analytical Methods.

Mild traumatic brain injuries are difficult to diagnose or assess with commonly used diagnostic methods. However, the functional state of cerebral cortical networks can be rapidly and effectively probed by measuring tactile-based sensory percepts (called cortical metrics), which are designed to exercise various components of cortical machinery. In this study, such cortical metrics were obtained from 52 college students before and after they experienced sports-related concussions by delivering vibrotactile stimuli to the index and middle fingertips.

Clinical Utility and Analysis of the Run-Roll-Aim Task: Informing Return-to-Duty Readiness Decisions in Active-Duty Service Members.

Introduction: The Assessment of Military Multitasking Performance (AMMP1) consists of six dual-task and multitask military-relevant performance-based assessments which were developed to provide assistance in making return-to-duty decisions after concussion or mild traumatic brain injury (mTBI.) The Run-Roll-Aim (RRA) task, one component of the AMMP, was developed to target vulnerabilities following mTBI including attention, visual function, dynamic stability, rapid transition, and vestibular function. One aim of this study was to assess the known-group and construct validity of the RRA, and additionally to further explore reliability limitations reported previously.

Contributions of Nociresponsive Area 3a to Normal and Abnormal Somatosensory Perception.

Traditionally, cytoarchitectonic area 3a of primary somatosensory cortex (SI) has been regarded as a proprioceptive relay to motor cortex. However, neuronal spike-train recordings and optical intrinsic signal imaging, obtained from nonhuman sensorimotor cortex, show that neuronal activity in some of the cortical columns in area 3a can be readily triggered by a C-nociceptor afferent drive. These findings indicate that area 3a is a critical link in cerebral cortical encoding of secondary/slow pain.

Hand-to-Face Remapping But No Differences in Temporal Discrimination Observed on the Intact Hand Following Unilateral Upper Limb Amputation.

Unilateral major limb amputation causes changes in sensory perception. Changes may occur within not only the residual limb but also the intact limb as well as the brain. We tested the hypothesis that limb amputation may result in the detection of hand sensation during stimulation of a non-limb-related body region.

Neurosensory Assessments of Concussion.

The purpose of this research was to determine if cortical metrics-a unique set of sensory-based assessment tools-could be used to characterize and differentiate concussed individuals from nonconcussed individuals. Cortical metrics take advantage of the somatotopic relationship between skin and cortex, and the protocols are designed to evoke interactions between adjacent cortical regions to investigate fundamental mechanisms that mediate cortical-cortical interactions. Student athletes, aged 18 to 22 years, were recruited into the study through an athletic training center that made determinations of postconcussion return-to-play status.

Percept of the duration of a vibrotactile stimulus is altered by changing its amplitude.

There have been numerous studies conducted on time perception. However, very few of these have involved tactile stimuli to assess a subject's capacity for duration discrimination. Previous optical imaging studies in non-human primates demonstrated that increasing the duration of a vibrotactile stimulus resulted in a consistently longer and more well defined evoked SI cortical response.

Activity of somatosensory-responsive neurons in high subdivisions of SI cortex during locomotion.

Responses of neurons in the primary somatosensory cortex during movements are poorly understood, even during such simple tasks as walking on a flat surface. In this study, we analyzed spike discharges of neurons in the rostral bank of the ansate sulcus (areas 1-2) in 2 cats while the cats walked on a flat surface or on a horizontal ladder, a complex task requiring accurate stepping. All neurons (n = 82) that had receptive fields (RFs) on the contralateral forelimb exhibited frequency modulation of their activity that was phase locked to the stride cycle during simple locomotion.

SHAPE analysis of small RNAs and riboswitches.

We describe structural analysis of small RNAs by SHAPE chemical probing. RNAs are treated with 1-methyl-7-nitroisatoic anhydride, a reagent that detects local nucleotide flexibility; and N-methylisatoic anhydride and 1-methyl-6-nitroisatoic anhydride, reagents which together detect higher-order and noncanonical interactions. Chemical adducts are quantified as stops during reverse transcriptase-mediated primer extension.

Möbius-strip-like columnar functional connections are revealed in somato-sensory receptive field centroids.

Receptive fields of neurons in the forelimb region of areas 3b and 1 of primary somatosensory cortex, in cats and monkeys, were mapped using extracellular recordings obtained sequentially from nearly radial penetrations. Locations of the field centroids indicated the presence of a functional system in which cortical homotypic representations of the limb surfaces are entwined in three-dimensional Möbius-strip-like patterns of synaptic connections. Boundaries of somatosensory receptive field in nested groups irregularly overlie the centroid order, and are interpreted as arising from the superposition of learned connections upon the embryonic order.

Single-molecule correlated chemical probing of RNA.

Complex higher-order RNA structures play critical roles in all facets of gene expression; however, the through-space interaction networks that define tertiary structures and govern sampling of multiple conformations are poorly understood. Here we describe single-molecule RNA structure analysis in which multiple sites of chemical modification are identified in single RNA strands by massively parallel sequencing and then analyzed for correlated and clustered interactions. The strategy thus identifies RNA interaction groups by mutational profiling (RING-MaP) and makes possible two expansive applications.

Attenuated Glial K(+) Clearance Contributes to Long-Term Synaptic Potentiation Via Depolarizing GABA in Dorsal Horn Neurons of Rat Spinal Cord.

It has been reported that long-term enhancement of superficial dorsal horn (DHs) excitatory synaptic transmission underlies central sensitization, secondary hyperalgesia, and persistent pain. We tested whether impaired clearance of K(+) and glutamate by glia in DHs may contribute to initiation and maintenance of the CNS pain circuit and sensorimotor abnormalities. Transient exposure of the spinal cord slice to fluorocitrate (FC) is shown to be accompanied by a protracted decrease of the DHs optical response to repetitive electrical stimulation of the ipsilateral dorsal root, and by a similarly protracted increase in the postsynaptic response of the DHs like LTP.

Principles for understanding the accuracy of SHAPE-directed RNA structure modeling.

Accurate RNA structure modeling is an important, incompletely solved, challenge. Single-nucleotide resolution SHAPE (selective 2'-hydroxyl acylation analyzed by primer extension) yields an experimental measurement of local nucleotide flexibility that can be incorporated as pseudo-free energy change constraints to direct secondary structure predictions. Prior work from our laboratory has emphasized both the overall accuracy of this approach and the need for nuanced interpretation of modeled structures.

Role of primary somatosensory cortex in the coding of pain.

The intensity and submodality of pain are widely attributed to stimulus encoding by peripheral and subcortical spinal/trigeminal portions of the somatosensory nervous system. Consistent with this interpretation are studies of surgically anesthetized animals, demonstrating that relationships between nociceptive stimulation and activation of neurons are similar at subcortical levels of somatosensory projection and within the primary somatosensory cortex (in cytoarchitectural areas 3b and 1 of somatosensory cortex, SI). Such findings have led to characterizations of SI as a network that preserves, rather than transforms, the excitatory drive it receives from subcortical levels.

QuShape: rapid, accurate, and best-practices quantification of nucleic acid probing information, resolved by capillary electrophoresis.

Chemical probing of RNA and DNA structure is a widely used and highly informative approach for examining nucleic acid structure and for evaluating interactions with protein and small-molecule ligands. Use of capillary electrophoresis to analyze chemical probing experiments yields hundreds of nucleotides of information per experiment and can be performed on automated instruments. Extraction of the information from capillary electrophoresis electropherograms is a computationally intensive multistep analytical process, and no current software provides rapid, automated, and accurate data analysis.

Columnar distribution of activity dependent gabaergic depolarization in sensorimotor cortical neurons.

Background: GABA, the major inhibitory neurotransmitter in CNS, has been demonstrated to paradoxically produce excitation even in mature brain. However activity-dependent form of GABA excitation in cortical neurons has not been observed. Here we report that after an intense electrical stimulation adult cortical neurons displayed a transient GABA excitation that lasted for about 30s.

Selection of vocal features for Parkinson's Disease diagnosis.

Parkinson's Disease (PD) is a neurodegenerative motor system disorder, which also causes vocal impairments for most of its patients. A number of recent exploratory studies have evaluated the feasibility of detecting voice disorders by applying data mining tools to acoustic features extracted from speech recordings of patients. Selection of a minimal yet descriptive set of features is crucial for improving the classifier generalisation capability and interpretability of the classification model as well as for reducing the burden of data preprocessing.

Neocortical layer 4 as a pluripotent function linearizer.

A highly effective kernel-based strategy used in machine learning is to transform the input space into a new "feature" space where nonlinear problems become linear and more readily solvable with efficient linear techniques. We propose that a similar "problem-linearization" strategy is used by the neocortical input layer 4 to reduce the difficulty of learning nonlinear relations between the afferent inputs to a cortical column and its to-be-learned upper layer outputs. The key to this strategy is the presence of broadly tuned feed-forward inhibition in layer 4: it turns local layer 4 domains into functional analogs of radial basis function networks, which are known for their universal function approximation capabilities.

Dynamic representations of the somatosensory cortex.

Neural representation of somatosensory events undergoes major transformation in the primary somatosensory cortex (SI) from its original, more or less isomorphic, form found at the level of peripheral receptors. A large body of SI optical imaging, neural recording and psychophysical studies suggests that SI representation of stimuli encountered in everyday life is a product of dynamic processes that involve competitive interactions at multiple levels of cortical organization. Such interactions take place among neighboring neurons, among local groups of minicolumns, among neighboring macrocolumns, between SI and SII, between Pacinian and non-Pacinian channels, and bilaterally between homotopic somatosensory regions of the opposite hemispheres.

Area 3a neuron response to skin nociceptor afferent drive.

Area 3a neurons are identified that respond weakly or not at all to skin contact with a 25-38 degrees C probe, but vigorously to skin contact with the probe at > or =49 degrees C. Maximal rate of spike firing associated with 1- to 7-s contact at > or =49 degrees C occurs 1-2 s after probe removal from the skin. The activity evoked by 5-s contact with the probe at 51 degrees C remains above-background for approximately 20 s after probe retraction.

Empiricist word learning.

At first, Bloom's theory appears inimical to empiricism, since he credits very young children with highly sophisticated cognitive resources (e.g., a theory of mind and a belief that real kinds have essences), and he also attacks the empiricist's favoured learning theory, namely, associationism.

Effects of stimulus-driven synchronization on sensory perception.

Background: A subject's ability to differentiate the loci of two points on the skin depends on the stimulus-evoked pericolumnar lateral inhibitory interactions which increase the spatial contrast between regions of SI cortex that are activated by stimulus-evoked afferent drive. Nevertheless, there is very little known about the impact that neuronal interactions - such as those evoked by mechanical skin stimuli that project to and coordinate synchronized activity in adjacent and/or near-adjacent cortical columns - could have on sensory information processing.

Methods: The temporal order judgment (TOJ) and temporal discriminative threshold (TDT) of 20 healthy adult subjects were assessed both in the absence and presence of concurrent conditions of tactile stimulation.