Effects of stimulus-driven synchronization on sensory perception

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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. These measures were obtained across a number of paired sites – two unilateral and one bilateral – and several conditions of adapting stimuli were delivered both prior to and concurrently with the TOJ and TDT tasks. The pairs of conditioning stimuli were synchronized and periodic, synchronized and non-periodic, or asynchronous and non-periodic.</p> <p>Results</p> <p>In the absence of any additional stimuli, TOJ and TDT results obtained from the study were comparable across a number of pairs of stimulus sites – unilateral as well as bilateral. In the presence of a 25 Hz conditioning sinusoidal stimulus which was delivered both before, concurrently and after the TOJ task, there was a significant change in the TOJ measured when the two stimuli were located unilaterally on digits 2 and 3. However, in the presence of the same 25 Hz conditioning stimulus, the TOJ obtained when the two stimuli were delivered bilaterally was not impacted. TDT measures were not impacted to the same degree by the concurrent stimuli that were delivered to the unilateral or bilateral stimulus sites. This led to the speculation that the impact that the conditioning stimuli – which were sinusoidal, periodic and synchronous – had on TOJ measures was due to the synchronization of adjacent cortical ensembles in somatosensory cortex, and that the synchronization of these cortical ensembles could have been responsible for the degradation in temporal order judgment. In order to more directly test this hypothesis, the synchronized 25 Hz conditioning stimuli that were delivered during the initial TOJ test were replaced with <it>asynchronous </it>non-periodic 25 Hz conditioning stimuli, and these asynchronous conditioning stimuli did not impact the TOJ measures.</p> <p>Conclusion</p> <p>The results give support to the theory that synchronization of cortical ensembles in SI could significantly impact the topography of temporal perception, and these findings are speculated to be linked mechanistically to previously reported co-activation plasticity studies. Additionally, the impact that such synchronizing conditioning stimuli have on TOJ – which can be measured relatively quickly – could provide an effective means to assess the functional connectivity of neurologically compromised subject populations.</p

Stimulus-dependent spatial patterns of response in SI cortex

BACKGROUND: Recently we reported that vibrotactile flutter stimulation of a skin locus at different amplitudes evokes an optical response confined to the same local region of the primary somatosensory cortex (SI), where its overall magnitude varies proportionally to the flutter amplitude. In this report, we characterize the impact of the flutter amplitude on the spatial patterns of activity evoked within the responding SI region. RESULTS: In order to characterize the spatial pattern of activity within the responding SI region, images of the flutter-evoked SI optical response were segmented and analyzed with spatial frequency analysis. The analysis revealed that: (1) dominant spatial frequencies in the optical intrinsic signal emerge within the responding SI region within 3–5 sec of stimulus onset; (2) the stimulus-evoked activity is spatially organized in a form of several roughly parallel, anterior-posteriorly extended waves, spaced 0.4–0.5 mm apart; (3) the waves themselves exhibit spatial periodicities along their long axis; and (4) depending on the flutter stimulus amplitude, these periodicities can range from fine 0.15 mm "ripples" at 50 μm amplitude to well-developed 0.5 mm fluctuations at the amplitude of 400 μm. CONCLUSION: The observed spatiointensive fractionation on a sub-macrocolumnar scale of the SI response to skin stimulation might be the product of local competitive interactions within the stimulus-activated SI region and may be a feature that could yield novel insights into the functional interactions that take place in SI cortex

Amplitude-dependency of response of SI cortex to flutter stimulation

BACKGROUND: It is established that increasing the amplitude of a flutter stimulus increases its perceived intensity. Although many studies have examined this phenomenon with regard to the responding afferent population, the way in which the intensity of a stimulus is coded in primary somatosensory cortex (SI) remains unclear. RESULTS: Optical intrinsic signal (OIS) imaging was used to study the evoked responses in SI of anesthetized squirrel monkeys by 25 Hz sinusoidal vertical skin displacement stimulation. Stimuli were 10 sec duration with a 50 sec inter-stimulus interval. Stimulus amplitude ranged from 50 to 400 microns and different amplitudes were interleaved. Control levels of activity were measured in the absence of stimulation, and used to compare with activation levels evoked by the different stimulus amplitudes. Stimulation of a discrete skin site on the forelimb evoked a prominent increase in absorbance within the forelimb representational region in cytoarchitectonic areas 3b and 1 of the contralateral hemisphere. An increase in stimulus amplitude led to a proportional increase in the magnitude of the absorbance increase in this region of areas 3b and 1 while surrounding cortex underwent a decrease in absorbance. Correlation maps revealed that as stimulus amplitude is increased, the spatial extent of the activated region in SI remains relatively constant, and the activity within this region increases progressively. Additionally, as stimulus amplitude is increased to suprathreshold levels, activity in the surround of the activated SI territory decreases, suggesting an increase in inhibition of neuronal activity within these regions. CONCLUSION: Increasing the amplitude of a flutter stimulus leads to a proportional increase in absorbance within the forelimb representational region of SI. This most likely reflects an increase in the firing rate of neurons in this region of SI. The relatively constant spatial extent of this stimulus-evoked increase in absorbance suggests that an increase in the amplitude of a 25 Hz skin stimulus does not evoke a larger area of SI neuronal activation due to an amplitude-dependent lateral inhibitory effect that spatially funnels the responding SI neuronal population

Neurosensory Assessments of Concussion

ABSTRACT 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. Sensory-based performance tasks utilizing vibrotactile stimuli applied to tips of the index and middle fingers were administered to test an individual's amplitude discrimination, temporal order judgment, and duration discrimination capacity in the presence and absence of illusion-inducing conditioning stimuli. Comparison of the performances in the presence and abse..

RNA SHAPE Analysis of Small RNAs and Riboswitches

We describe structural analysis of RNAs by SHAPE chemical probing. RNAs are treated with 1-methyl-7-nitroisatoic anhydride (1M7), a reagent that detects local nucleotides flexibility, and N-methylisatoic anhydride (NMIA) and 1-methyl-6-nitroisatoic anhydride (1M6), reagents which together detect higher-order and non-canonical interactions. Chemical adducts are detected as stops during reverse transcriptase-mediated primer extension. Probing information can be used to infer conformational changes and ligand binding, and to develop highly accurate models of RNA secondary 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, showing 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 SI). Such findings have led to characterizations of SI as a network which preserves, rather than transforms, the excitatory drive it receives from subcortical levels. Inconsistent with this perspective are images and neurophysiological recordings of SI neurons in lightly anesthetized primates. These studies show that an extreme anterior position within SI (area 3a) receives input originating predominantly from unmyelinated nociceptors, distinguishing it from posterior SI (areas 3b and 1), long recognized as receiving input predominantly from myelinated afferents, including nociceptors. Of particular importance, interactions between these subregions during maintained nociceptive stimulation are accompanied by an altered SI response to myelinated and unmyelinated nociceptors. A revised view of pain coding within SI cortex is discussed, and potentially significant clinical implications are emphasized

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. Materials and Methods A cross-sectional study consisting of 84 Active Duty service members in two groups (healthy control – HC and individuals experiencing persistent mTBI symptoms) completed neurocognitive tests and the RRA. The RRA task requires a high level of mobility and resembles military training activities in a maneuver that includes combat rolls, fast transitions, obstacle avoidance, and visual search. Observational and inertial sensor data were compared between groups and performance across four trial times was compared within groups. Correlations between RRA results and neurocognitive test scores were analyzed. Results Simple observational measures (time, errors) did not differ between groups. Spectral power analysis of the inertial sensor data showed significant differences in motor performance between groups. Within group one-way ANOVAs showed that in HC trial 1, time was significantly different than trials 2,3 and 4 (F(3,47) = 4.60, p < 0.01, Tukey HSD p < 0.05) while the mTBI group showed no significant difference in time between trials. During testing individuals with mTBI were less likely to complete the multiple test trials or required additional rest between trials than HCs (χ2 = 10.78, p < 0.01). Small but significant correlations were seen with two neurocognitive tests of attention and RRA performance time. Conclusion While observational scores were not sensitive to group differences, inertial sensor data showed motor performance on the forward run, combat roll, and backward run differed significantly between groups. The RRA task appeared challenging and provoked symptoms in the mTBI group, causing 8 of 33 mTBI participants to stop the task or require additional rest between trials while none of the HC participants had to stop. Individuals with mTBI demonstrated slower learning of the complex motor sequence compared to HCs who had significant improvement after one trial of RRA. Complex novel training maneuvers like RRA may aid clinicians in informing return to duty decisions

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 some apparent discrepancies between modeled and accepted structures. Recent studies by Das and colleagues [Kladwang et al., Biochemistry 50:8049 (2011) and Nat. Chem. 3:954 (2011)], focused on analyzing six small RNAs, yielded poorer RNA secondary structure predictions than expected based on prior benchmarking efforts. To understand the features that led to these divergent results, we re-examined four RNAs yielding the poorest results in this recent work – tRNAPhe, the adenine and cyclic-di-GMP riboswitches, and 5S rRNA. Most of the errors reported by Das and colleagues reflected non-standard experiment and data processing choices, and selective scoring rules. For two RNAs, tRNAPhe and the adenine riboswitch, secondary structure predictions are nearly perfect if no experimental information is included but were rendered inaccurate by the Das and colleagues SHAPE data. When best practices were used, single-sequence SHAPE-directed secondary structure modeling recovered ~93% of individual base pairs and greater than 90% of helices in the four RNAs, essentially indistinguishable from the mutate-and-map approach with the exception of a single helix in the 5S rRNA. The field of experimentally-directed RNA secondary structure prediction is entering a phase focused on the most difficult prediction challenges. We outline five constructive principles for guiding this field forward

FEATURE SELECTION AND EXTRACTION USING AN UNSUPERVISED BIOLOGICALLY-SUGGESTED APPROXIMATION TO GEBELEIN'S MAXIMAL CORRELATION

Feature selection and extraction are critical steps in many areas where pattern recognition techniques are applied. Feature selection and extraction are based on identifying and maximizing dependency relations. Gebelein's Maximal Correlation (GMC) is the most general form of dependence in that it does not make any statistical assumptions concerning the nature of the dependencies. Unfortunately, benefiting from such a useful measure in practice is generally impossible as there are only a few cases for which explicit formulae are available to calculate it. In this paper, we point out a parallel between GMC and the SINBAD algorithms, developed originally as a model of feature extraction for neurons in the cerebral cortex. We use SINBAD as a robust approximation to GMC to perform feature selection and extraction on a number of artificial and real datasets. We show that SINBAD estimates of GMC compare favorably to other well known feature selection and extraction methods based on mutual information, kernel canonical correlation analysis and principal component analysis