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Showing papers on "Summation published in 2011"


Journal ArticleDOI
01 Apr 2011-Pain
TL;DR: Results confirm prior studies that indicate that catastrophizing enhances pain via supraspinal processes rather than spinal processes, and caution is warranted when using pain ratings to infer temporal summation of spinal nociceptive processes.
Abstract: Pain catastrophizing is associated with enhanced temporal summation of pain (TS-Pain). However, because prior studies have found that pain catastrophizing is not associated with a measure of spinal nociception (nociceptive flexion reflex [NFR] threshold), this association may not result from changes in spinal nociceptive processes. The goal of the present study in healthy participants was to examine the relationship between trait (traditional) and state (situation-specific) pain catastrophizing and temporal summation of NFR (TS-NFR) and TS-Pain. A secondary goal was to replicate prior findings concerning relationships between catastrophizing and NFR threshold, electrocutaneous pain threshold, and sensory and affective ratings of electrocutaneous stimuli. All analyses controlled for depression symptoms, pain-related anxiety, and participant sex. As expected, multiple regression analyses indicated that neither trait nor situation-specific catastrophizing was associated with NFR threshold, but that situation-specific catastrophizing was associated with pain ratings. Multilevel linear growth models of TS data indicated that situation-specific catastrophizing was associated with TS-Pain but not TS-NFR. Trait catastrophizing was not related to TS-Pain or TS-NFR. Together, these results confirm prior studies that indicate that catastrophizing enhances pain via supraspinal processes rather than spinal processes. Moreover, because catastrophizing was associated with TS-Pain but not TS-NFR, caution is warranted when using pain ratings to infer temporal summation of spinal nociceptive processes.

75 citations


Journal ArticleDOI
01 Nov 2011-Pain
TL;DR: The results suggest that some, but not all, forms of pain reduction by distraction rely on descending pain inhibition, and that pain Reduction by distraction seems to preferentially affect mechanisms of basal nociceptive transmission, not of temporal summation.
Abstract: Distraction from pain reduces pain perception, and imaging studies have suggested that this may at least partially be mediated by activation of descending pain inhibitory systems. Here, we used the nociceptive flexor reflex (RIII reflex) to directly quantify the effects of different distraction strategies on basal spinal nociception and its temporal summation. Twenty-seven healthy subjects participated in 3 distraction tasks (mental imagery, listening to preferred music, spatial discrimination of brush stimuli) and, in a fourth task, concentrated on the painful stimulus. Results show that all 3 distraction tasks reduced pain perception, but only the brush task also reduced the RIII reflex. The concentration-on-pain task increased both pain perception and the RIII reflex. The extent of temporal summation of pain perception and the extent of temporal summation of the RIII reflex were not affected by any of the tasks. These results suggest that some, but not all, forms of pain reduction by distraction rely on descending pain inhibition. In addition, pain reduction by distraction seems to preferentially affect mechanisms of basal nociceptive transmission, not of temporal summation.

62 citations


Journal ArticleDOI
TL;DR: It is demonstrated that short-term plasticity is responsible for shaping MOC inhibition and, therefore, encodes the transfer function from efferent firing frequency to the gain of the cochlear amplifier.
Abstract: In the mammalian inner ear, the gain control of auditory inputs is exerted by medial olivocochlear (MOC) neurons that innervate cochlear outer hair cells (OHCs) OHCs mechanically amplify the incoming sound waves by virtue of their electromotile properties while the MOC system reduces the gain of auditory inputs by inhibiting OHC function How this process is orchestrated at the synaptic level remains unknown In the present study, MOC firing was evoked by electrical stimulation in an isolated mouse cochlear preparation, while OHCs postsynaptic responses were monitored by whole-cell recordings These recordings confirmed that electrically evoked IPSCs (eIPSCs) are mediated solely by α9α10 nAChRs functionally coupled to calcium-activated SK2 channels Synaptic release occurred with low probability when MOC-OHC synapses were stimulated at 1 Hz However, as the stimulation frequency was raised, the reliability of release increased due to presynaptic facilitation In addition, the relatively slow decay of eIPSCs gave rise to temporal summation at stimulation frequencies >10 Hz The combined effect of facilitation and summation resulted in a frequency-dependent increase in the average amplitude of inhibitory currents in OHCs Thus, we have demonstrated that short-term plasticity is responsible for shaping MOC inhibition and, therefore, encodes the transfer function from efferent firing frequency to the gain of the cochlear amplifier

51 citations


Journal ArticleDOI
TL;DR: It is shown that synaptic integration of temporally summating excitation and inhibition can establish diverse temporal filters of presynaptic input, and that GABAergic inhibition plays a critical role in establishing different temporal filtering properties.
Abstract: Temporal filtering is a fundamental operation of nervous systems. In peripheral sensory systems, the temporal pattern of spiking activity can encode various stimulus qualities, and temporal filtering allows postsynaptic neurons to detect behaviorally relevant stimulus features from these spike trains. Intrinsic excitability, short-term synaptic plasticity, and voltage-dependent dendritic conductances have all been identified as mechanisms that can establish temporal filtering behavior in single neurons. Here we show that synaptic integration of temporally summating excitation and inhibition can establish diverse temporal filters of presynaptic input. Mormyrid electric fish communicate by varying the intervals between electric organ discharges. The timing of each discharge is coded by peripheral receptors into precisely timed spikes. Within the midbrain posterior exterolateral nucleus, temporal filtering by individual neurons results in selective responses to a particular range of presynaptic interspike intervals. These neurons are diverse in their temporal filtering properties, reflecting the wide range of intervals that must be detected during natural communication behavior. By manipulating presynaptic spike timing with high temporal resolution, we demonstrate that tuning to behaviorally relevant patterns of presynaptic input is similar in vivo and in vitro. We reveal that GABAergic inhibition plays a critical role in establishing different temporal filtering properties. Further, our results demonstrate that temporal summation of excitation and inhibition establishes selective responses to high and low rates of synaptic input, respectively. Simple models of synaptic integration reveal that variation in these two competing influences provides a basic mechanism for generating diverse temporal filters of synaptic input.

46 citations


Journal ArticleDOI
TL;DR: Discrepancies were noted between TS-NFR and TS-pain which raise concerns about using pain ratings to infer changes in spinal nociceptive processes, and some individuals did not have reliable NFRs when the stimulation intensity was set at NFR threshold during TS- NFR testing; therefore, a higher intensity is needed.

41 citations


Journal ArticleDOI
26 Jul 2011-PLOS ONE
TL;DR: Findings indicated that tactile stimulation induced asynchronous parallel fiber excitatory inputs onto the dendrites of PCs, and failed to evoke strong EPSCs and spike firing in PCs, but induced the rapid activation of strong GABAA receptor-mediated inhibitory postsynaptic currents in the somata and dendrite of PCs in the cerebellar cortex Crus II in urethane-anesthetized mice.
Abstract: Background Sensory stimuli evoke responses in cerebellar Purkinje cells (PCs) via the mossy fiber-granule cell pathway. However, the properties of synaptic responses evoked by tactile stimulation in cerebellar PCs are unknown. The present study investigated the synaptic responses of PCs in response to an air-puff stimulation on the ipsilateral whisker pad in urethane-anesthetized mice. Methods and main results Thirty-three PCs were recorded from 48 urethane-anesthetized adult (6-8-week-old) HA/ICR mice by somatic or dendritic patch-clamp recording and pharmacological methods. Tactile stimulation to the ipsilateral whisker pad was delivered by an air-puff through a 12-gauge stainless steel tube connected with a pressurized injection system. Under current-clamp conditions (I = 0), the air-puff stimulation evoked strong inhibitory postsynaptic potentials (IPSPs) in the somata of PCs. Application of SR95531, a specific GABA(A) receptor antagonist, blocked IPSPs and revealed stimulation-evoked simple spike firing. Under voltage-clamp conditions, tactile stimulation evoked a sequence of transient inward currents followed by strong outward currents in the somata and dendrites in PCs. Application of SR95531 blocked outward currents and revealed excitatory postsynaptic currents (EPSCs) in somata and a temporal summation of parallel fiber EPSCs in PC dendrites. We also demonstrated that PCs respond to both the onset and offset of the air-puff stimulation. Conclusions These findings indicated that tactile stimulation induced asynchronous parallel fiber excitatory inputs onto the dendrites of PCs, and failed to evoke strong EPSCs and spike firing in PCs, but induced the rapid activation of strong GABA(A) receptor-mediated inhibitory postsynaptic currents in the somata and dendrites of PCs in the cerebellar cortex Crus II in urethane-anesthetized mice.

30 citations


Journal ArticleDOI
TL;DR: The results support the hypothesis that pooling of local motion information from amblyopic eyes is abnormal and highly sensitive to noise.

29 citations


Journal ArticleDOI
TL;DR: This model has three stages of summation: short-range summation within linear receptive fields, medium-range integration to compute contrast energy for multiple patches of the image, and long-range pooling of the contrast integrators by probability summation.
Abstract: Classical studies of area summation measure contrast detection thresholds as a function of grating diameter. Unfortunately, (i) this approach is compromised by retinal inhomogeneity and (ii) it potentially confounds summation of signal with summation of internal noise. The Swiss cheese stimulus of T. S. Meese and R. J. Summers (2007) and the closely related Battenberg stimulus of T. S. Meese (2010) were designed to avoid these problems by keeping target diameter constant and modulating interdigitated checks of first-order carrier contrast within the stimulus region. This approach has revealed a contrast integration process with greater potency than the classical model of spatial probability summation. Here, we used Swiss cheese stimuli to investigate the spatial limits of contrast integration over a range of carrier frequencies (1–16 c/deg) and raised plaid modulator frequencies (0.25–32 cycles/check). Subthreshold summation for interdigitated carrier pairs remained strong (~4 to 6 dB) up to 4 to 8 cycles/check. Our computational analysis of these results implied linear signal combination (following square-law transduction) over either (i) 12 carrier cycles or more or (ii) 1.27 deg or more. Our model has three stages of summation: short-range summation within linear receptive fields, medium-range integration to compute contrast energy for multiple patches of the image, and long-range pooling of the contrast integrators by probability summation. Our analysis legitimizes the inclusion of widespread integration of signal (and noise) within hierarchical image processing models. It also confirms the individual differences in the spatial extent of integration that emerge from our approach.

26 citations


Journal ArticleDOI
TL;DR: The summation algorithm over the population of area 7a neurons carries the signature of a winner-take-all operation, with spatial attention possibly influencing the temporal dynamics of stimulus competition, that is the moment that the "winner" takes "victory" over the "loser" stimulus.
Abstract: While neurons in posterior parietal cortex have been found to signal the presence of a salient stimulus among multiple items in a display, spatial summation within their receptive field in the absence of an attentional bias has never been investigated. This information, however, is indispensable when one investigates the mechanisms of spatial attention and competition between multiple visual objects. To examine the spatial summation rule in parietal area 7a neurons, we trained rhesus monkeys to fixate on a central cross while two identical stimuli were briefly displayed in a neuron's receptive field. The response to a pair of dots was compared with the responses to the same dots when they were presented individually. The scaling and power parameters of a generalized summation algorithm varied greatly, both across neurons and across combinations of stimulus locations. However, the averaged response of the recorded population of 7a neurons was consistent with a winner-take-all rule for spatial summation. A control experiment where a monkey covertly attended to both stimuli simultaneously suggests that attention introduces additional competition by facilitating the less optimal stimulus. Thus an averaging stage is introduced between ∼200 and 300 ms of the response to a pair of stimuli. In short, the summation algorithm over the population of area 7a neurons carries the signature of a winner-take-all operation, with spatial attention possibly influencing the temporal dynamics of stimulus competition, that is the moment that the “winner” takes “victory” over the “loser” stimulus.

24 citations


Journal ArticleDOI
TL;DR: It is proposed that the localized peak of inhibition at the excitatory field center could be mediated by local interneurons, while the more widespread surrounding inhibition may depend on supraspinal circuitry.
Abstract: Extracellular recording has shown that dorsal horn neurons can have an inhibitory surround outside their excitatory receptive field, but cannot reveal inhibitory inputs within the excitatory field, or show the underlying excitatory and inhibitory synaptic inputs that determine net output. To study the underlying components of receptive field organization, in vivo patch-clamp recording was used to compare the size and distribution of subthreshold, suprathreshold, and inhibitory fields, in neurons in the mouse superficial medullary dorsal horn that were characterized by their responses to noxious and innocuous mechanical facial stimulation. Subthreshold excitatory fields typically extended some distance beyond the borders of the suprathreshold field, and also commonly exhibited broader stimulus selectivity, in that the majority of nociceptive-specific neurons exhibited subthreshold responses to brush. Separate voltage-clamp recording of excitatory and inhibitory inputs using different holding potentials revealed that inhibition could be evoked from both within and outside the excitatory field. In nociceptive neurons, inhibition tended to be maximal at the excitatory receptive field center, and was usually greater for pinch than brush, although the selectivity for pinch versus brush was not as great as with excitatory responses. Based on current data on dorsal horn organization, we propose that the localized peak of inhibition at the excitatory field center could be mediated by local interneurons, while the more widespread surrounding inhibition may depend on supraspinal circuitry.

22 citations


Journal Article
TL;DR: Test site affects orofacial thermal thresholds substantially, whereas time variability and spatial summation on the tongue appear to be modest.
Abstract: Aim To investigate time-dependent variability and influence of test site and stimulation area size on intraoral cold detection, warmth detection, and heat pain thresholds. Methods Thirty healthy volunteers (15 women and 15 men) participated. Six extra- and intraoral sites were examined, and cold detection, warmth detection, and heat pain thresholds were measured. Time variability and influence of spatial summation were also studied at one site-the tip of the tongue-three times over a 6-week period. One-way ANOVA for repeated measures and paired sample t test compared mean values and SD within and between sites for all thresholds. Results Several between-site differences were significant (P .05). Conclusion Test site affects orofacial thermal thresholds substantially, whereas time variability and spatial summation on the tongue appear to be modest.

Journal ArticleDOI
TL;DR: The present study examines the biophysical properties and functional implications of Ih in hippocampal area CA3 interneurons with somata in strata radiatum and lacunosum-moleculare and finds that Ih did not confer theta-band resonance, but flattened the impedance–frequency relations instead.
Abstract: The present study examines the biophysical properties and functional implications of Ih in hippocampal area CA3 interneurons with somata in strata radiatum and lacunosum-moleculare. Characterization studies showed a small maximum h-conductance (2.6±0.3 nS, n=11), shal- low voltage dependence with a hyperpolarized half- maximal activation (V1/2=−91 mV), and kinetics character- ized by double-exponential functions. The functional consequences of Ih were examined with regard to temporal summation and impedance measurements. For temporal summation experiments, 5-pulse mossy fiber input trains were activated. Blocking Ih with 50 μM ZD7288 resulted in an increase in temporal summation, suggesting that Ih supports sensitivity of response amplitude to relative input timing. Impedance was assessed by applying sinusoidal current commands. From impedance measurements, we found that Ih did not confer theta-band resonance, but flattened the impedance-frequency relations instead. Dou- ble immunolabeling for hyperpolarization-activated cyclic nucleotide-gated proteins and glutamate decarboxylase 67 suggests that all four subunits are present in GABAergic interneurons from the strata considered for electrophysio- logical studies. Finally, a model of Ih was employed in computational analyses to confirm and elaborate upon the contributions of Ih to impedance and temporal summation.

Journal ArticleDOI
TL;DR: Results demonstrate a 31% increase in the parafoveal spatial summation area in older observers with no significant age-related change in the fovea.
Abstract: Previous studies have demonstrated an inverse relation between the size of the complete spatial summation area and ganglion cell density. We hypothesized that if this relation is dynamic, the spatial summation area at 6- nasal would expand to compensate for age-related losses of retinal ganglion cells but not in the fovea where age-related loss in ganglion cell density is not significant. This hypothesis was tested by measuring contrast thresholds with a series of Gabor patches varying in size. The spatial summation area was defined by the intersection of the segments of a two-branched, piece-wise linear function fitted to the data with slopes of j0.5 and 0 on a plot of log threshold vs. log area. Results demonstrate a 31% increase in the parafoveal spatial summation area in older observers with no significant age-related change in the fovea. The average foveal data show a significant increase in thresholds with age. Contrary to the foveal data, age comparisons of the parafoveal peak contrast thresholds display no significant difference above the summation area. Nevertheless, as expected from the increase in summation area, expressing the parafoveal thresholds as contrast energy reveals a significant difference for stimuli that are smaller than the maximal summation area.


Patent
24 Feb 2011
TL;DR: In this article, a device for evoking a temporal summation of pain in a subject is described, which comprises a stimulation element (SE) arranged generating a physical stimulation on a skin surface area of at least 20 cm 2 according to a control signal (CS), where the stimulation(PS) evokes pain in the subject.
Abstract: A device for evoking a temporal summation of pain in a subject. The device comprises a stimulation element (SE) arranged generating a physical stimulation on a skin surface area of at least 20 cm 2 according to a control signal (CS), where the stimulation(PS) evokes pain in the subject. A processor (PR) generates the control signal (CS) to the stimulation element (SE)so as to provide a repetitive stimulation pattern comprising at least repetitions of: a)applying stimulation for a period (SP) of 0.5-120 seconds,b)stopping stimulation for a period (TP) of 0.5- 20 seconds. Preferred periods are 1-3 seconds for both stimulation and intermediate stopping periods. The stimulation element may include an inflatable tourniquet arranged for providing a compressional stimulation of an arm or a leg. However, other types of stimulation elements may be used such as electric, heating, mechanical stimulation or the like may be used. The device is suited for providing a measure of temporal summation in a subject with different intensities, and this measure can be used for determining if the subject suffers from central nervous sensitization which is an important diagnosis with respect to effective analgesic treatment. In some embodiments, the device is arranged to collect pain responses during the stimulation and to calculate a measure of temporal summation of the subject accordingly, e.g. in the form of a rate of pain change (VAS) versus time (T).


Journal ArticleDOI
TL;DR: This work is the first to demonstrate the expression of IKCa channels in central neurons, its association with Cav3 channels and the role of this Cav3-IKCa complex in controlling the response of PCs to PF inputs.
Abstract: Cerebellar Purkinje cells are contacted by up to ~150,000 parallel fibers from granule cells, of which only a subset will convey sensory information at any given time. Purkinje cells must then possess the means to respond effectively to meaningful parallel fiber input over background noise. Previous work has shown that parallel fiber excitatory postsynaptic potential (EPSP) summation can be shaped by feedforward synaptic inhibition and the hyperpolarization-activated current IH[1,2]. We now report that parallel fiber EPSPs activate T-type calcium channels that are linked to intermediate conductance calcium-activated potassium (IKCa) channels in Purkinje cells. This novel complex exerts a frequency-dependent suppression of temporal summation, such that only high frequency parallel fiber inputs undergoing presynaptic facilitation can elicit spike output from Purkinje cells. Cerebellar slices were prepared from P18-30 rats and patch recordings obtained from PC somata at 32-35°C. PFs were activated using a monopolar stimulating electrode in the molecular layer or granule cell layer. Alternatively, the role of postsynaptic PC ion channels were selectively tested by injecting simulated EPSCs to evoke PF simulated EPSPs (simEPSPs) at the soma. PF EPSPs below threshold for spike discharge were followed by an after hyperpolarization (AHP) of up to 2.5 mV and 250 ms. Application of blockers against high voltage activated Ca2+ channels (Cd2+, Agatoxin IVA), SK channels (apamin), or BK channels (TEA, iberiotoxin, paxilline) did not significantly affect the rate of simEPSP decay. However, T-type Ca2+ channel blockers (Ni2+, Mibefradil, kurtoxin) caused a ~35% decrease in the rate of simEPSP decay. Moreover, these effects were reproduced by application of IKCa channel blockers (TRAM-34, charybdotoxin). Immunofluorescent labeling for IKCa protein confirmed its expression in Purkinje cells somata and dendrites. Ni2+ and TRAM-34 sensitive outward currents were found in outside-out patches from PC somata, confirming current clamp data showing a functional link between Cav3 and IKCa channels. The outward current was further blocked by BAPTA (10 mM) but not EGTA (10 mM) in the internal patch solution, indicating that the Ca2+-IKca channel interaction resides within a nanodomain. To examine the effect of this interaction on temporal summation, PFs were stimulated at varying frequencies. For frequencies up to 25 Hz, no temporal summation was observed in control conditions. However, blocking either Cav3 or IKca channels caused significant summation for 25 Hz stimulations. This effect was seen in both the presence and absence of feedforward-inhibition. Application of TRAM-34 greatly altered the frequency response of PC to 50 and 100 Hz PF stimulation during tonic firing. Finally, the Cav3-IKCa complex selectively suppresses non-facilitating inputs while allowing smaller-amplitude, facilitating inputs to generate output. Our current work is the first to demonstrate the expression of IKCa channels in central neurons, its association with Cav3 channels and the role of this Cav3-IKCa complex in controlling the response of PCs to PF inputs. The Cav3-IKCa complex creates a high pass filter that reduces the effectiveness of background activity and allows Purkinje cells to respond preferentially to parallel fiber input indicative of sensory input carried by mossy fibers.