Showing papers on "Summation published in 2015"

Neural correlates of temporal summation of second pain in the human brainstem and spinal cord

Abstract: Temporal summation of second pain (TSSP) occurs when painful stimuli are presented repetitively (≥ 0.33 Hz) and results from a C-fibre evoked enhancement (or "wind-up") of the dorsal horn neurons. Based on electrophysiological studies in intact animals, windup is considered a purely central phenomenon. With advancements in functional MRI (fMRI), we can now probe the central mechanisms of this pain response in humans. The aim of this study is to characterize the fMRI responses in the healthy human brainstem and spinal cord that correspond to TSSP. Functional MRI of healthy female adults (N = 15) was conducted while brief, repetitive heat pain stimuli were applied to the right thenar eminence (C6 dermatome), and TSSP (0.33 Hz) and control (0.17 Hz) heat pain paradigms were employed. The stimulus intensity was adjusted to each participant's heat pain sensitivity. Data were analyzed by means of a general linear model, and region-of-interest analyses. As predicted, participants demonstrated significant behavioural summation of pain in the TSSP condition. FMRI results identified enhanced activity in the spinal cord dorsal horn at C6 in response to the TSSP condition. Additionally, multiple areas of the brainstem (RVM and PAG) showed greater responses with the TSSP condition. These results suggest that, in humans, increased pain perception in the TSSP condition is reflected by greater responses in the dorsal horn and in regions known to play a role in the descending modulation of pain, which may modulate the spinal cord response.

Standard Automated Perimetry: Determining Spatial Summation and Its Effect on Contrast Sensitivity Across the Visual Field.

Abstract: Purpose To establish Ricco's critical area (Ac) using the 30-2 Humphrey visual field analyzer (HVFA) and thereby identify Goldmann test sizes that are within or outside complete spatial summation at all visual field testing locations. We also determined the suitability of using age normative data for different test sizes. Finally, by modifying current output measures (dB values), we provide a new method that allows comparison of contrast sensitivity when testing with different Goldmann test sizes within complete spatial summation. Methods We used the HVFA in full threshold mode and measured thresholds for all five Goldmann test sizes in 12 observers. Normative data of Heijl et al. were used for age transformation and comparison. Results All the data converted to a 50-year-old equivalent lie within 1 SD of expected variance for all test locations of the 30-2 paradigm. We established Ac values at all locations of the 30-2 paradigm and showed a systematic increase in Ac as a function of increased visual field eccentricity, consistent with previous studies. Age does not appear to affect Ac or the slope of partial summation for a wide range of visual field eccentricities tested using the HVFA. By equating spatial summation, we propose a new metric, dB*, that returns a uniform sensitivity value for different test sizes that are operating within complete spatial summation (i.e., follow Ricco's law). Conclusions We established that converting to age-equivalent thresholds and application of dB* principle advantageously allows comparison of data sets across age and test size at different locations of the visual field. By identifying the Ac across the visual field, it is now possible to systematically determine threshold changes across the 30-2 locations in ocular disease and further characterize the importance of testing within complete spatial summation in standard automated perimetry.

Spatial summation across the central visual field: implications for visual field testing.

Abstract: In the present study, we measured the extent of spatial summation in the detection of image contrast within the central 40° visual field. Contrast detection thresholds (in 28 observers) were measured for a spot of light of 10 different sizes [area: 0.03-1.92(°)(2)] at different retinal meridians (0°, 45°, 90°, 135°, 180°, 225°, 270°, and 315°) and eccentricities (0°, 5°, 10°, 15°, and 20°). Contrast detection thresholds were significantly affected by the size of the stimulus with sensitivity improving with stimulus size consistent with Ricco's law. Summation curves were similar across different spatial meridians, but the extent of spatial summation increased with retinal eccentricity consistent with previous reports. The size of the stimulus was also shown to affect contrast detection thresholds in the periphery. In particular, contrast detection thresholds decreased more rapidly with increasing eccentricity for a smaller target than a larger one. This difference in performance is accounted for by the accompanying change in Ac with eccentricity. In Experiment 2, we show that spatial uncertainty affected contrast detection, particularly at eccentric locations greater than 5°, such that cueing the location of the stimulus improved contrast thresholds. Spatial uncertainty improved overall performance but did not affect the estimates of the critical areas of summation. The results of the present study indicate that, due to spatial summation, detection performance is highly dependent on the size of the stimulus, its eccentric location, and spatial uncertainty. Future perimetric methodologies must consider these factors to improve detection sensitivity.

Cell-specific activity-dependent fractionation of layer 2/3→5B excitatory signaling in mouse auditory cortex.

Abstract: Auditory cortex (AC) layer 5B (L5B) contains both corticocollicular neurons, a type of pyramidal-tract neuron projecting to the inferior colliculus, and corticocallosal neurons, a type of intratelencephalic neuron projecting to contralateral AC. Although it is known that these neuronal types have distinct roles in auditory processing and different response properties to sound, the synaptic and intrinsic mechanisms shaping their input–output functions remain less understood. Here, we recorded in brain slices of mouse AC from retrogradely labeled corticocollicular and neighboring corticocallosal neurons in L5B. Corticocollicular neurons had, on average, lower input resistance, greater hyperpolarization-activated current (Ih), depolarized resting membrane potential, faster action potentials, initial spike doublets, and less spike-frequency adaptation. In paired recordings between single L2/3 and labeled L5B neurons, the probabilities of connection, amplitude, latency, rise time, and decay time constant of the unitary EPSC were not different for L2/3→corticocollicular and L2/3→corticocallosal connections. However, short trains of unitary EPSCs showed no synaptic depression in L2/3→corticocollicular connections, but substantial depression in L2/3→corticocallosal connections. Synaptic potentials in L2/3→corticocollicular connections decayed faster and showed less temporal summation, consistent with increased Ih in corticocollicular neurons, whereas synaptic potentials in L2/3→corticocallosal connections showed more temporal summation. Extracellular L2/3 stimulation at two different rates resulted in spiking in L5B neurons; for corticocallosal neurons the spike rate was frequency dependent, but for corticocollicular neurons it was not. Together, these findings identify cell-specific intrinsic and synaptic mechanisms that divide intracortical synaptic excitation from L2/3 to L5B into two functionally distinct pathways with different input–output functions.

Spatiotemporal Summation of Perimetric Stimuli in Early Glaucoma.

Abstract: PURPOSE: To investigate achromatic temporal summation under the conditions of standard automated perimetry (SAP), using a Goldmann III (GIII) stimulus and a stimulus scaled to the local area of complete spatial summation (Ricco's area) in open-angle glaucoma (OAG) patients and healthy age-similar control participants. METHODS: Twenty patients with OAG (mean age, 63 years; mean MD, -3.3 dB) and 15 healthy controls (mean age, 64 years) were recruited. Contrast thresholds were measured for seven stimulus durations (1-24 frames, 1.8-191.9 ms) using a near-GIII stimulus (0.48° diameter) and stimuli scaled to the local Ricco's area, in four oblique meridians at 8.8° eccentricity in the visual field. The upper limit of complete temporal summation (critical duration) was estimated using iterative two-phase regression analysis. RESULTS: Median critical duration values were significantly longer (P < 0.05) in the OAG group for the near-GIII (107.2 ms; interquartile range [IQR], 38.0-190.5) and Ricco's area-scaled (83.2 ms, 41.7-151.4) stimuli, compared to those in healthy subjects (near-GIII, 34.7 ms; 18.2-47.9; Ricco's area-scaled, 49.0 ms; 25.1-64.6). The greatest difference in contrast thresholds between healthy and OAG subjects (i.e., disease signal) was found when stimuli were scaled to Ricco's area and shorter than or equal to the critical duration in healthy observers. CONCLUSIONS: Temporal summation is altered in glaucoma. The stimulus duration and area of conventional SAP may be suboptimal for identifying early functional damage. Simultaneously modulating stimulus duration, area, and luminance during the examination may improve the diagnostic capability of SAP and expand the dynamic range of current instruments.

High dendritic expression of Ih in the proximity of the axon origin controls the integrative properties of nigral dopamine neurons

Abstract: Key points The hyperpolarization-activated cation current Ih is expressed in dopamine neurons of the substantia nigra, but the subcellular distribution of the current and its role in synaptic integration remain unknown. We used cell-attached patch recordings to determine the localization profile of Ih along the somatodendritic axis of nigral dopamine neurons in slices from young rats. Ih density is higher in axon-bearing dendrites, in a membrane area close to the axon origin, than in the soma and axon-lacking dendrites. Dual current-clamp recordings revealed a similar contribution of Ih to the waveform of single excitatory postsynaptic potentials throughout the somatodendritic domain. The Ih blocker ZD 7288 increased the temporal summation in all dendrites with a comparable effect in axon- and non-axon dendrites. The strategic position of Ih in the proximity of the axon may influence importantly transitions between pacemaker and bursting activities and consequently the downstream release of dopamine. Abstract Dendrites of most neurons express voltage-gated ion channels in their membrane. In combination with passive properties, active currents confer to dendrites a high computational potential. The hyperpolarization-activated cation current Ih present in the dendrites of some pyramidal neurons affects their membrane and integration properties, synaptic plasticity and higher functions such as memory. A gradient of increasing h-channel density towards distal dendrites has been found to be responsible for the location independence of excitatory postsynaptic potential (EPSP) waveform and temporal summation in cortical and hippocampal pyramidal cells. However, reports on other cell types revealed that smoother gradients or even linear distributions of Ih can achieve homogeneous temporal summation. Although the existence of a robust, slowly activating Ih current has been repeatedly demonstrated in nigral dopamine neurons, its subcellular distribution and precise role in synaptic integration are unknown. Using cell-attached patch-clamp recordings, we find a higher Ih current density in the axon-bearing dendrite than in the soma or in dendrites without axon in nigral dopamine neurons. Ih is mainly concentrated in the dendritic membrane area surrounding the axon origin and decreases with increasing distances from this site. Single EPSPs and temporal summation are similarly affected by blockade of Ih in axon- and non-axon-bearing dendrites. The presence of Ih close to the axon is pivotal to control the integrative functions and the output signal of dopamine neurons and may consequently influence the downstream coding of movement.

Race effects on temporal summation to heat pain in youth.

Abstract: Racial differences in pain responsiveness have been demonstrated in adults. However, it is unclear whether racial differences are also present in youth and whether they extend to experimental pain indices assessing temporal summation of second pain (TSSP). Temporal summation of second pain provides an index of pain sensitivity and may be especially relevant in determining risk for chronic pain. This study assessed pain tolerance and TSSP to evoked thermal pain in 78 healthy youth (age range, 10-17), 51% of whom were African American and 49% were non-Hispanic white. Multilevel models revealed within-individual increases in pain ratings during the temporal summation task in non-Hispanic white youth that were consistent with TSSP. Pain ratings did not change significantly during the temporal summation task in African-American youth. Baseline evoked pain ratings were significantly higher in African-American compared with non-Hispanic white youth. These findings suggest that enhanced responsiveness to evoked thermal pain in African Americans is present in adolescence but is unlikely to be related to elevated TSSP. These results may have implications for understanding racial differences in chronic pain experience in adulthood.

Is temporal summation of pain and spinal nociception altered during normal aging

Abstract: This study examines the effect of normal aging on temporal summation (TS) of pain and the nociceptive flexion reflex (RIII). Two groups of healthy volunteers, young and elderly, received transcutaneous electrical stimulation applied to the right sural nerve to assess pain and the nociceptive flexion reflex (RIII-reflex). Stimulus intensity was adjusted individually to 120% of RIII-reflex threshold, and shocks were delivered as a single stimulus or as a series of 5 stimuli to assess TS at 5 different frequencies (0.17, 0.33, 0.66, 1, and 2 Hz). This study shows that robust TS of pain and RIII-reflex is observable in individuals aged between 18 and 75 years and indicates that these effects are comparable between young and older individuals. These results contrast with some previous findings and imply that at least some pain regulatory processes, including TS, may not be affected by normal aging, although this may vary depending on the method.

Estimating the critical duration for temporal summation of standard achromatic perimetric stimuli

Abstract: Purpose: To estimate the critical duration of temporal summation for achromatic Goldmann III stimuli under the conditions of standard automated perimetry (SAP) and quantify response variability for short duration stimuli. Methods: Contrast thresholds were gathered using the method of constant stimuli for seven circular (0.48° diameter) incremental stimuli of varying duration (sum-of-frames equivalent: 8.3-198.3 msec), at an eccentricity of 8.8° along the four principal meridians of the visual field in two healthy, psychophysically experienced observers. Stimuli were presented on a high-resolution CRT display with a background luminance of 10 cd/m2. Psychometric functions were fitted using a probit model and non-parametric local linear analysis. The critical duration was estimated using iterative two-phase regression analysis, the results also being compared with values produced using previously published methods of analysis. Results: The median critical duration estimated using iterative two-phase regression analysis was 27.7 msec (IQR 22.5-29.8). A slight steepening of the psychometric function slope (lower variability) was observed for longer stimulus durations, using both probit and local-linear analysis techniques, but this was not statistically significant. Conclusions: Critical duration estimates in this study are substantially shorter than those previously reported for a Goldmann III stimulus under the conditions of SAP. Further work is required to firmly establish the relationship between measurement variability and the degree of local temporal and spatial summation.

Imbalance of excitation and inhibition at threshold level in the auditory cortex

Abstract: The interplay of cortical excitation and inhibition is a fundamental feature of cortical information processing. Excitation and inhibition in single cortical neurons are balanced in their response to optimal sensory stimulation due to thalamocortical feedforward microcircuitry. It is unclear whether the balance between cortical excitation and inhibition is maintained at the threshold stimulus level. Using in vivo whole-cell patch-clamp recording of thalamocortical recipient neurons in the primary auditory cortex of mice, we examined the tone-evoked excitatory and inhibitory postsynaptic currents at threshold levels. Similar to previous reports, tone induced excitatory postsynaptic currents when the membrane potentials were held at – 70 mV and inhibitory postsynaptic currents when the membrane potentials were held at 0 mV on single cortical neurons. This coupled excitation and inhibition is not demonstrated when threshold-level tone stimuli are presented. In most cases, tone induced only excitatory postsynaptic potential. The best frequencies of excitatory and inhibitory responses were often different and thresholds of inhibitory responses were mostly higher than those of excitatory responses. Our data suggest that the excitatory and inhibitory inputs to single cortical neurons are imbalanced at the threshold level. This imbalance may result from the inherent dynamics of thalamocortical feedforward microcircuitry.

The Effect of Age on the Temporal Summation of Achromatic Perimetric Stimuli.

Abstract: Purpose: To examine the temporal summation of a Goldmann III–sized stimulus under the conditions of standard automated perimetry in healthy participants of varying age. Methods: Twenty-seven healthy individuals of varying age (24–80 years) were tested. Achromatic contrast thresholds were measured for seven 0.48° diameter (near Goldmann III) spot stimuli of varying presentation duration (1–24 frames, 1.8–191.9 ms) at 8.8° eccentricity in the visual field along the 45°, 135°, 225°, and 315° meridians. All stimuli were displayed on a CRT display with a background set to 10 cd/m2. Iterative two-phase regression analysis was used to estimate the critical duration from each localized temporal summation function. Results: A significant decrease in contrast sensitivity for all stimulus durations examined in this study was observed with increasing age in both the superior and inferior hemifield (P < 0.001). Despite this, no significant change in the critical duration was observed as a function of age in either the superior (r2 = 9.1 × 10−9, P = 0.99) or inferior hemifield (r2 = 2.4 × 10−5, P = 0.98). Conclusions: Age-related changes in the visual system, although leading to a reduction in contrast sensitivity, are not accompanied by a change in temporal summation for a detection task with an achromatic 0.48° diameter spot stimulus. This is important to know when proceeding to examine temporal summation changes in diseases like glaucoma.

Fourth-root summation of contrast over area: No end in sight when spatially inhomogeneous sensitivity is compensated by a witch's hat.

Abstract: Measurements of area summation for luminance-modulated stimuli are typically confounded by variations in sensitivity across the retina. Recently we conducted a detailed analysis of sensitivity across the visual field (Baldwin et al, 2012) and found it to be well-described by a bilinear “witch’s hat” function: sensitivity declines rapidly over the first 8 cycles or so, more gently thereafter. Here we multiplied luminance-modulated stimuli (4 c/deg gratings and “Swiss cheeses”) by the inverse of the witch’s hat function to compensate for the inhomogeneity. This revealed summation functions that were straight lines (on double log axes) with a slope of -1/4 extending to ≥33 cycles, demonstrating fourth-root summation of contrast over a wider area than has previously been reported for the central retina. Fourth-root summation is typically attributed to probability summation, but recent studies have rejected that interpretation in favour of a noisy energy model that performs local square-law transduction of the signal, adds noise at each location of the target and then sums over signal area. Modelling shows our results to be consistent with a wide field application of such a contrast integrator. We reject a probability summation model, a quadratic model and a matched template model of our results under the assumptions of signal detection theory. We also reject the high threshold theory of contrast detection under the assumption of probability summation over area.

Estimating the time course of population excitatory postsynaptic potentials in motoneurons of spastic stroke survivors.

Abstract: Hyperexcitable motoneurons are likely to contribute to muscle hypertonia after a stroke injury; however, the origins of this hyperexcitability are not clear. One possibility is that the effective duration of the Ia excitatory postsynaptic potential (EPSP) is prolonged, increasing the potential for temporal summation of EPSPs, making action potential initiation easier. Accordingly, the purpose of this study was to quantify the time course of EPSPs in motoneurons of stroke survivors. The experimental protocol, which was based on parameters derived from simulation, involved sequential subthreshold electrical stimuli delivered to the median nerve of hemispheric stroke survivors. The resulting H-reflex responses were recorded in the flexor carpi radialis muscle. H-reflex response probability was then used to quantify the time course of the underlying EPSPs in the motoneuron pool. A population EPSP was estimated based on the probability of evoking an H reflex from the second electrical stimulus in the absence of a reflex response to the first stimulus. The accuracy of this time-course estimate was quantified using a computer simulation that explored a range of feasible EPSP parameters. Our experimental results showed that in all five hemispheric stroke survivors the rate of decay of the population EPSP was consistently slower in spastic compared with the contralateral motoneuron pools. We propose that one potential mechanism for hyperexcitability of motoneurons in spastic stroke survivors may be linked to this prolongation of the Ia EPSP time course. Our subthreshold double-stimulation approach also provides a noninvasive tool for quantifying the time course of EPSPs in both healthy and pathological conditions.

Temporal summation of muscle pain evoked by very fast pressure sequences and rotation

Abstract: Background: Pressure evoked temporal summation of pain has been described with slow repetitions ( 1 Hz). This study examined temporal summation of pain by repeated computer-controlled pressure stimulation at high repetition rates with and without simultaneous active probe rotations for potential better efficiency.Methods: In 15 healthy subjects, 15 pressure stimuli (300 and 500 ms durations) were delivered at the pressure pain threshold intensity with and without rotation of a rounded probe (1 cm2) at three repetition frequencies (1.5, 1, 0.5 Hz). The pressure pain intensity was continuously rated on a visual analogue scale (VAS) and scores after each stimulus were extracted and normalized to the first score.Results: The peak VAS score was larger for rotational (p < 0.001), longer stimulus duration (p < 0.02), and lower frequencies (p < 0.05) compared with non-rotational, shorter stimulus duration, and highe...

O042. Phase-dependent defective functional activity of the default mode network and facilitated temporal processing of nociceptive stimuli in cluster headache

Abstract: Background In cluster headache (CH) during the active period we described a facilitated temporal summation (TS) of nociceptive signals at spinal level linked to a defective suprapinal control of pain and followed by a normalization of the values during the remission period [1]. TS of sensory neuronal responses to nociceptive stimuli is a form of central plasticity that shifts the sensory information from tactile to nociceptive before transmitting the nociceptive information to brain areas mediating pain sensation. This feature of the sensory system results pivotal in physiological nociception, for discrimination between innocuous and potentially dangerous stimulation, as well as in pathological nociception, for induction and maintenance of the central sensitization, subsequently resulting in pain chronification [2]. In this study we sought to determine which brain sites are involved in the modulation of temporal processing of pain sensation in CH subjects during both the active and remission period. We utilized functional magnetic resonance imaging (fMRI) to compare the Blood Oxygenation Level Dependent (BOLD) signal changes related to the temporal summation threshold (TST) of the nociceptive withdrawal reflex (NWR). We used the single NWR response as control stimulus.

Flicker-Defined Forms in the Ternus Display.

Abstract: Odic and Pratt (2008, Perception, 37, 1790-1804) proposed that the type of movement seen in the bistable Ternus display depends on the elements' temporal summation of contrast relative to the background. To test this theory, participants viewed a flicker-defined Ternus display where the elements had no temporal summation of contrast. Participants also viewed a luminance-defined control condition. Five interstimulus intervals (ISIs) (0, 20, 40, 60, and 80 ms) and two stimulus durations (SDs) (200 and 400 ms) were used in each condition. If temporal summation of contrast does not influence perceived group and end-to-end movement in flicker-defined forms, it was expected that the frequency of their reports would be equal to those in the luminance- defined control condition at the same ISIs and SDs. As predicted, the main effect of condition was not significant and participants reported both percepts at expected rates in both conditions, contrary to the predictions of Odic and Pratt (2008).

Effect of Contrast on Visual Spatial Summation in Different Cell Categories in Cat Primary Visual Cortex.

Abstract: Multiple cell classes have been found in the primary visual cortex, but the relationship between cell types and spatial summation has seldom been studied. Parvalbumin-expressing inhibitory interneurons can be distinguished from pyramidal neurons based on their briefer action potential durations. In this study, we classified V1 cells into fast-spiking units (FSUs) and regular-spiking units (RSUs) and then examined spatial summation at high and low contrast. Our results revealed that the excitatory classical receptive field and the suppressive non-classical receptive field expanded at low contrast for both FSUs and RSUs, but the expansion was more marked for the RSUs than for the FSUs. For most V1 neurons, surround suppression varied as the contrast changed from high to low. However, FSUs exhibited no significant difference in the strength of suppression between high and low contrast, although the overall suppression decreased significantly at low contrast for the RSUs. Our results suggest that the modulation of spatial summation by stimulus contrast differs across populations of neurons in the cat primary visual cortex.

Temporal summation in a neuromimetic micropillar laser

Abstract: Neuromimetic systems are systems mimicking the functionalities orarchitecture of biological neurons and may present an alternativepath for efficient computing and information processing. We demonstratehere experimentally temporal summation in a neuromimetic micropillarlaser with integrated saturable absorber. Temporal summation is theproperty of neurons to integrate delayed input stimuli and to respondby an all-or-none kind of response if the inputs arrive in a sufficientlysmall time window. Our system alone may act as a fast optical coincidence detector and paves the way to fast photonic spike processing networks.