Showing papers on "Summation published in 2007"

Brain activity related to temporal summation of C-fiber evoked pain.

Abstract: Temporal summation of "second pain" (TSSP) is considered to be the result of C-fiber-evoked responses of dorsal horn neurons, termed 'windup'. This phenomenon is dependent on stimulus frequency (0.33 Hz) and relevant for central sensitization and chronic pain. Previous brain imaging studies have only been used to characterize neural correlates of second pain but not its temporal summation. We utilized functional magnetic resonance imaging (fMRI) in healthy volunteers to measure brain responses associated with TSSP. Region of interest analysis was used to assess TSSP related brain activation. Eleven pain-free normal subjects underwent fMRI scanning during repetitive heat pulses to the right foot at 0.33 and 0.17 Hz. Stimulus intensities were adjusted to each individual's heat sensitivity to achieve comparable TSSP ratings of moderate pain in all subjects. As predicted, experimental pain ratings showed robust TSSP during 0.33 Hz but not 0.17 Hz stimuli. fMRI statistical maps identified several brain regions with stimulus and frequency dependent activation consistent with TSSP, including contralateral thalamus (THAL), S1, bilateral S2, anterior and posterior insula (INS), mid-anterior cingulate cortex (ACC), and supplemental motor areas (SMA). TSSP ratings were significantly correlated with brain activation in somatosensory areas (THAL, S1, left S2), anterior INS, and ACC. These results show that neural responses related to TSSP are evoked in somatosensory processing areas (THAL, S2), as well as in multiple areas that serve other functions related to pain, such as cognition (ACC, PFC), affect (INS, ACC, PAG), pre-motor activity (SMA, cerebellum), and pain modulation (rostral ACC).

Attention alters spatial integration in macaque V1 in an eccentricity-dependent manner

Abstract: Attention can selectively enhance neuronal responses and exclude external noise, but the neuronal computations that underlie these effects remain unknown. At the neuronal level, noise exclusion might result in altered spatial integration properties. We tested this proposal by recording neuronal activity and length tuning in neurons of the primary visual cortex of the macaque when attention was directed toward or away from stimuli presented in each neuron's classical receptive field. For cells with central-parafoveal receptive fields, attention reduced spatial integration, as demonstrated by a reduction in preferred stimulus length and in the size of the spatial summation area. Conversely, in cells that represented more peripheral locations, attention increased spatial integration by increasing the cell's summation area. This previously unknown dichotomy between central and peripheral vision could support accurate analysis of attended foveal objects and target selection for impending eye movements to peripheral objects.

α2-Noradrenergic receptors activation enhances excitability and synaptic integration in rat prefrontal cortex pyramidal neurons via inhibition of HCN currents

Abstract: Stimulation of α2-noradrenergic (NA) receptors within the PFC improves working memory performance. This improvement is accompanied by a selective increase in the activity of PFC neurons during delay periods, although the cellular mechanisms responsible for this enhanced response are largely unknown. Here we used current and voltage clamp recordings to characterize the response of layer V–VI PFC pyramidal neurons to α2-NA receptor stimulation. α2-NA receptor activation produced a small hyperpolarization of the resting membrane potential, which was accompanied by an increase in input resistance and evoked firing. Voltage clamp analysis demonstrated that α2-NA receptor stimulation inhibited a caesium and ZD7288-sensitive hyperpolarization-activated (HCN) inward current. Suppression of HCN current by α2-NA stimulation was not dependent on adenylate cyclase but instead required activation of a PLC–PKC linked signalling pathway. Similar to direct blockade of HCN channels, α2-NA receptor stimulation produced a significant enhancement in temporal summation during trains of distally evoked EPSPs. These dual effects of α2-NA receptor stimulation – membrane hyperpolarization and enhanced temporal integration – together produce an increase in the overall gain of the response of PFC pyramidal neurons to excitatory synaptic input. The net effect is the suppression of isolated excitatory inputs while enhancing the response to a coherent burst of synaptic activity.

Thalamic filtering of retinal spike trains by postsynaptic summation.

Abstract: At many synapses in the central nervous system, spikes within high-frequency trains have a better chance of driving the postsynaptic neuron than spikes occurring in isolation. We asked what mechanism accounts for this selectivity at the retinogeniculate synapse. The amplitude of synaptic potentials was remarkably constant, ruling out a major role for presynaptic mechanisms such as synaptic facilitation. Instead, geniculate spike trains could be predicted from retinal spike trains on the basis of postsynaptic summation. This simple form of integration explains the response differences between a geniculate neuron and its main retinal driver, and thereby determines the flow of visual information to cortex.

Local and Global Effects of Ih Distribution in Dendrites of Mammalian Neurons

Abstract: The hyperpolarization-activated cation current I h exhibits a steep gradient of channel density in dendrites of pyramidal neurons, which is associated with location independence of temporal summation of EPSPs at the soma. In striking contrast, here we show by using dendritic patch-clamp recordings that in cerebellar Purkinje cells, the principal neurons of the cerebellar cortex, I h exhibits a uniform dendritic density, while location independence of EPSP summation is observed. Using compartmental modeling in realistic and simplified dendritic geometries, we demonstrate that the dendritic distribution of I h only weakly affects the degree of temporal summation at the soma, while having an impact at the dendritic input location. We further analyze the effect of I h on temporal summation using cable theory and derive bounds for temporal summation for any spatial distribution of I h. We show that the total number of I h channels, not their distribution, governs the degree of temporal summation of EPSPs. Our findings explain the effect of I h on EPSP shape and temporal summation, and suggest that neurons are provided with two independent degrees of freedom for different functions: the total amount of I h (controlling the degree of temporal summation of dendritic inputs at the soma) and the dendritic spatial distribution of I h (regulating local dendritic processing).

Integration of Asynchronously Released Quanta Prolongs the Postsynaptic Spike Window

Abstract: Classically, the release of glutamate in response to a presynaptic action potential causes a brief increase in postsynaptic excitability. Previous reports indicate that at some central synapses, a single action potential can elicit multiple, asynchronous release events. This raises the possibility that the temporal dynamics of neurotransmitter release may determine the duration of altered postsynaptic excitability. In response to physiological challenges, the magnocellular neurosecretory cells (MNCs) in the paraventricular nucleus of the hypothalamus (PVN) exhibit robust and prolonged increases in neuronal activity. Although the postsynaptic conductances that may facilitate this form of activity have been investigated thoroughly, the role of presynaptic release has been largely overlooked. Because the specific patterns of activity generated by MNCs require the activation of excitatory synaptic inputs, we sought to characterize the release dynamics at these synapses and determine whether they contribute to prolonged excitability in these cells. We obtained whole-cell recordings from MNCs in brain slices of postnatal day 21-44 rats. Stimulation of glutamatergic inputs elicited large and prolonged postsynaptic events that resulted from the summation of multiple, asynchronously released quanta. Asynchronous release was selectively inhibited by the slow calcium buffer EGTA-AM and potentiated by brief high-frequency stimulus trains. These trains caused a prolonged increase in postsynaptic spike activity that could also be eliminated by EGTA-AM. Our results demonstrate that glutamatergic terminals in PVN exhibit asynchronous release, which is important in generating large postsynaptic depolarizations and prolonged spiking in response to brief, high-frequency bursts of presynaptic activity.

Pain additivity, diffuse noxious inhibitory controls, and attention: a functional measurement analysis.

Abstract: This study utilized the methodology of Functional Measurement theory to investigate the additivity of painful and non-painful thermally induced experiences at one body site with those produced by brief noxious and innocuous electrical stimuli at another. Forty healthy young subjects were tested, using a Peltier thermode to induce tonic pain and an electrocutaneous stimulator for presenting phasic pain, under conditions of either full attention or visual/cognitive distraction (counting numerous light signals) in order to evaluate whether the summed effects are attributable to refocused attention. Six levels of intensity were combined in a factorial design for both tonic and phasic pain. Subjects indicated the overall strength of their dual perception on a visual analog scale. Stimuli showed complex patterns of interaction. Two stimuli were generally rated as greater than one, but the summation was far from additive and greatly influenced by the intensity of the stronger stimulus, suggesting inhibitory action. In general, tonic heat pain strongly affected the perception of phasic electrocutaneous pain whereas the reverse was only partly true. Distraction had a very small effect, suggesting that the ‘‘pain inhibits pain’’ phenomenon attributable to diffuse noxious inhibitory controls (DNIC) is not due to attentional processes. Our data also relate to issues regarding spatial summation across dermatomes and to adaptation level effects in pain, in which a strong painful experience serves as an anchor or comparison point by which others are judged. The psychophysical findings provide a perceptual foundation for clinical phenomena in which patients face with comorbid pain disorders.

Age Interacts with Stimulus Frequency in the Temporal Summation of Pain

Abstract: Objective. There is growing interest in the impact of aging on the plasticity of pain responses. Up-regulation characterizes pain responses in clinical situations, and consequently aging effects on the development and resolution of increased sensitivity have important implications for the experience of pain in those older age groups who are more likely to suffer from chronic conditions. This study examined temporal summation of pain at different stimulus frequencies to gain further insights into the effect of age on pain plasticity. Design. In a group of younger and a group of older subjects, trains of five brief electrical stimuli were applied to the skin over the sural nerve at frequencies ranging between 0.2 and 2.0 Hz. Nociceptive reflexes were recorded throughout the application of stimuli. Single pulses and the fifth pulse of each series were rated for pain intensity with a visual analog scale. Results. The younger subjects demonstrated temporal summation at frequencies of stimulation that were consistent with previous reports, namely 0.33 to 2.0 Hz. The older group had a greater mean rating of the fifth pulse relative to a single pulse at all frequencies of stimulation. The behavior of the nociceptive reflex to repeated stimuli was equivalent for the two age groups, only summating at a frequency of 2.0 Hz. Conclusions. The temporal summation of low-frequency stimuli in the older subjects suggests that aging impacts on the capacity of the nociceptive system to down-regulate subsequent to sensitization.

Area summation in human vision at and above detection threshold

Abstract: The initial image-processing stages of visual cortex are well suited to a local (patchwise) analysis of the viewed scene. But the world’s structures extend over space as textures and surfaces, suggesting the need for spatial integration. Most models of contrast vision fall shy of this process because (i) the weak area summation at detection threshold is attributed to probability summation (PS) and (ii) there is little or no advantage of area well above threshold. Both of these views are challenged here. First, it is shown that results at threshold are consistent with linear summation of contrast following retinal inhomogeneity, spatial filtering, nonlinear contrast transduction and multiple sources of additive Gaussian noise. We suggest that the suprathreshold loss of the area advantage in previous studies is due to a concomitant increase in suppression from the pedestal. To overcome this confound, a novel stimulus class is designed where: (i) the observer operates on a constant retinal area, (ii) the target area is controlled within this summation field, and (iii) the pedestal is fixed in size. Using this arrangement, substantial summation is found along the entire masking function, including the region of facilitation. Our analysis shows that PS and uncertainty cannot account for the results, and that suprathreshold summation of contrast extends over at least seven target cycles of grating.

Spatial Summation, End Inhibition and Side Inhibition in the Middle Temporal Visual Area (MT)

Abstract: We investigated the responses of single neurons in the middle temporal area (MT) of anesthetized marmoset monkeys to sine-wave gratings of various lengths and widths. For the vast majority of MT cells maximal responses were obtained on presentation of gratings of specific dimensions, which were typically asymmetrical along the length and width axes. The strength of end inhibition was dependent on the width of the stimulus, with many cells showing clear end inhibition only when wide gratings were used. Conversely, the strength of side inhibition was dependent on stimulus length. Furthermore, for over one third of MT cells length summation properties could not be defined without consideration of stimulus width and vice versa. These neurons, which we refer to as "length-width inseparable" (LWI) cells, were rare in layer 4. The majority of LWI neurons was strongly inhibited by wide-field stimuli and responded preferentially to gratings that were elongated, along either the length or width dimensions. However, rather than forming a homogeneous and entirely distinct group, LWI cells represented the upper end of a continuum of complexity in spatial summation response properties, which characterized the population of MT cells. Only a minority of MT neurons (22.3%) showed no evidence of inhibition by wide-field stimuli, with this type of response being common among layer 5 cells. These results demonstrate distinct patterns of spatial selectivity in MT, supporting the notion that neurons in this area can perform various roles in terms of grouping and segmentation of motion signals.

Noninvasive assessment of the facilitation of the nociceptive withdrawal reflex by repeated electrical stimulations in conscious dogs.

Abstract: Objective—To investigate the facilitation of the nociceptive withdrawal reflex (NWR) by repeated electrical stimuli and the associated behavioral response scores in conscious, nonmedicated dogs as a measure of temporal summation and analyze the influence of stimulus intensity and frequency on temporal summation responses. Animals—8 adult Beagles. Procedures—Surface electromyographic responses evoked by transcutaneous constant-current electrical stimulation of ulnaris and digital plantar nerves were recorded from the deltoideus, cleidobrachialis, biceps femoris, and cranial tibial muscles. A repeated stimulus was given at 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, and 1.1 × It (the individual NWR threshold intensity) at 2, 5, and 20 Hz. Threshold intensity and relative amplitude and latency of the reflex were analyzed for each stimulus configuration. Behavioral reactions were subjectively scored. Results—Repeated sub-It stimuli summated and facilitated the NWR. To elicit temporal summation, significantly lower int...

Comparing neural response telemetry amplitude growth functions with loudness growth functions: preliminary results.

Abstract: Comparisons of the subjective loudness growth function and the objective evoked compound action potential (ECAP) amplitude growth function indicate that both functions are exponential in nature. This implies that a more accurate estimate of the ECAP threshold would be obtained using exponential regression of the amplitude growth function instead of the currently used linear regression. The perceptual threshold and the ECAP threshold seem to approach each other when the stimulation rate is lowered to reduce temporal summation effects. The effect of the stimulation rate on the perceptual threshold will have to be taken into account when trying to use the ECAP threshold for predicting the perceptual threshold.

Dissociation of nociceptive modulation of a human jaw reflex from the influence of stress

Abstract: In human beings, inhibitory jaw reflexes can be depressed by painful stimulation of remote parts of the body. Since similar effects can be produced by the stress of anticipating pain, we wished to investigate whether the effects of remote painful stimuli are dependent on stress. EMG recordings were made from a masseter muscle while subjects maintained activity in the muscle at ∼12.5% of maximum using visual feedback. The protocols involved three sequences: (1) “standard controls” in which reflexes were evoked by electrical test stimuli applied to the upper lip; (2) “standard conditioning” in which painful electrical conditioning stimuli were applied over the sural nerve 100 ms before the test stimuli; (3) “random sequences” in which test-only and conditioning-test combinations were employed in a double-blind, random, order. Data are presented as means ± SEMs. In the standard controls, the stimuli evoked clear inhibitory reflexes (latency 37 ± 1.3 ms, duration 62 ± 5.6 ms; n = 10) in all the subjects. During standard conditioning, the reflex magnitude was reduced significantly (by 50.0 ± 8.5%, P = 0.0002, one-sample t-test). When the test-only and conditioning-test responses were extracted from the random sequences, there was also a significant reduction in the reflex magnitude following conditioning (by 34.6 ± 5.5%, P = 0.0002, one-sample t-test) albeit less so than between the standard sequences (P = 0.03, paired t-test). A second series of experiments suggested that these lesser effects during the random sequences were not substantially due to any loss of temporal summation of the conditioning mechanisms. The evidence for this was that application of pairs of conditioning stimuli did not produce a significantly greater effect than single conditioning stimuli within a random sequence (39.9 ± 9.6% as opposed to 32.7 ± 9.1% reductions in the reflex, P = 0.117, paired t-test). Therefore since any stress in the random sequences would not have been “tied” to the conditioned responses alone, the effects of remote painful stimuli on this inhibitory jaw reflex cannot be entirely secondary to stress.

Controlling for spatial variability in single site recordings in an in vitro hippocampal preparation with a spontaneous rhythm

Abstract: An important consideration in analyzing the time-frequency rhythms of hippocampal local field potentials is to what extent changes in time of a single site signal actually reflect spatial summation of two wholly separate signals. Signals observed could be the result of the spatial summation of different activities. For example, the duration of activities observed could be due to two shorter durations overlapping. More broadly, it is a source of concern if the hippocampal rhythms do not have well defined spatial properties (preferably fairly homogenous) since a single signal has no control for this variable. To that end, we examine the behaviour of a spontaneous hippocampal rhythm over time as it varies spatially within an intact whole hippocampus preparation. We also examine the response to a high frequency stimulation protocol of 80 Hz. Using four simultaneous rostral to caudal recordings of two to five minutes, we characterize this changing rhythmic activity according to clustered patterns of activity in its time-frequency distribution. Our data set consists of 40 extracellular recordings. The frequency distribution change in response to stimulation was observed. We calculate the spatial variance of the data for each unit of time. This allows us to link the time-frequency data to a level of spatial variance. The variance of the signal in time was defined to be the variance in the mean frequencies of the signal resultant from partitioning each time-frequency epoch into thirds. That is, a sliding 0.5 second temporal resolution was divided into thirds and the variance in the mean frequencies calculated. The change in the signal in time was then compared to the change in signal in space to determine whether there were any significant correlations. There is a distinct relationship between the variance among simultaneous rostral caudal recordings and the non-stationarity present in each of those spatially distinct recordings. The peak values nearly follow the y = -x line. Functional biological rhythms in the hippocampus are commonly both non-stationary and coherent, making this inverse relationship more intuitive. Consider that the hippocampal recording has two components, one of which is stationary background noise and one of which is the nonstationary signal of interest. Our finding, then, is that the noise is uncorrelated spatially and signal is correlated spatially. In this case, when the signal is low, the non-stationarity would be low and the spatial variance would be high. This is a very useful property for single site recordings because it means that the more physiologically interesting (nonstationary) the recording, the less we need to be concerned that spatial summation is a problem.

Spatial Attention Can Enhance or Impair Visual Temporal Resolution

Abstract: Transient attention impairs observers’temporal resolution in a cued location. This detrimental effect of attention was ascribed to inhibitory connections from parvocellular to magnocellular neurons (1). Alternatively, the difficulty might arise because attention facilitates the temporal summation of two successive stimuli. The current study examined this hypothesis by manipulating the luminance polarity of the stimuli against a background. Attention should not modulate temporal summation of two anti-polar stimuli because these are processed in separate channels. Indeed, observers judged the temporal order of two successive stimuli better in the cued location than in the uncued location when the stimuli were opposite in polarity, but temporal resolution was worse in the cued location when the stimuli had the same polarity. Thus, attentional effects on temporal resolution may be attributed to temporal summation rather than parvocellular inhibition of magnocellular activity.

What do pressure pipes tell us about spatial summation in pain processing.

Abstract: Psychophysics is one of the oldest domains of research in the life sciences at large, and in pain research in particular. Its elegance is in its simplicity. Where else would a very ‘low tech’ device made of pipes conveying pressurized air merit an editorial in the central Journal of the field? The study by Staud et al., 2007 is, indeed, of a very simple design, examining characteristics of spatial summation of pressure pain in healthy controls and in patients with Fibromyalgia (FM). Although spatial summation of mechanical pain has already been explored by others (Greenspan et al., 1997; Defrin et al., 2003; Lautenbacher et al., 2005), the present study is distinct in using a novel device, which enables the production of a well-controlled pressure pain, free of biases characteristic of other stimulators, and in including patients in addition to the healthy controls studied previously. Some of the results of this study could have been intuitively predicted by the reader; one could expect that a larger stimulation area would induce a more intense pain, and that FM patients would report more intense pain than controls for similar stimuli. For these results, the value of this study is mainly in showing the relatively easy and simple test setup. The importance of the article is in the less predictable findings. The fact that two separate stimuli at distance of 8 cm cause more pain than same stimuli at 4 cm apart is not obvious, since pain inhibitory mechanisms are expected to come into action once a certain distance between two stimuli is opened, as recently shown for thermal/mechanical stimuli by Pud et al. (2005). The critical distance under which summation prevails, and above which mutual inhibition prevails, is of great interest, both from the pure physiological point of view, and more importantly, from the pathophysiological one. This distance indicates the spatial balance point between pain augmenting forces, such as summation mechanisms, and pain inhibiting forces such as diffuse noxious inhibitory control (DNIC). It, thus, can make a useful parameter in characterizing the normal and abnormal