Showing papers on "Summation published in 2019"

Primary Motor Cortex Transcranial Direct Current Stimulation Modulates Temporal Summation of the Nociceptive Withdrawal Reflex in Healthy Subjects.

Abstract: OBJECTIVE Transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) has shown efficacy in a number of chronic pain conditions. Despite attempts to dissect the analgesic mechanisms, it is unknown whether M1 tDCS modulates the central integration of spinal nociception. To test this, we investigated the top-down modulation of spinal excitability using temporal summation (TS) of the nociceptive withdrawal reflex (NWR). METHODS In this randomized, blinded, cross-over study, eight healthy subjects received electrically evoked TS of the NWR, which was delivered at 5 Hz at a threshold and a suprathreshold (1.1× threshold) to elicit TS resulting in different levels of pain. Subjects were asked to rate their pain after each stimulation. Changes in the TS of the NWR and pain ratings were investigated following 20 minutes of 2-mA anodal tDCS or sham stimulation applied over M1. RESULTS Baseline recordings showed that TS of the NWR was induced with both threshold and suprathreshold stimulation. Suprathreshold stimulation was also associated with a higher pain intensity rating. After brain stimulation, there was no effect over the lower-intensity TS of the NWR or pain ratings in both the tDCS and sham conditions. However, tDCS reduced TS of the NWR and associated pain ratings following higher-intensity suprathreshold stimulation. CONCLUSIONS These results indicate that M1 tDCS can indirectly modulate the central integration of suprathreshold nociceptive processing in the spinal cord. It is possible that the analgesic efficacy of tDCS is dependent on plasticity induced within pain pathways following repeated, high-intensity stimulation, which may explain the beneficial effects seen in chronic pain patients.

Acute alcohol effects on conditioned pain modulation, but not temporal summation of pain.

Abstract: Although pain reduction after alcohol administration has repeatedly been demonstrated, alcohol effects on advanced and clinically relevant dynamic pain paradigms are still unknown. As such, temporal summation of pain (TSP) and conditioned pain modulation (CPM) indicate mechanisms of endogenous pain modulation and involve certain neurotransmitter systems crucially influenced by alcohol. Our study is the first to investigate acute alcohol effects on TSP and CPM. We investigated 39 healthy subjects in a placebo-controlled within-subject design and targeted alcohol levels of 0.06% (dose 1) and 0.08% (dose 2). Pain threshold, TSP, and CPM were evaluated before and after an alcoholic or placebo drink. Temporal summation of pain was assessed as enhanced pain response to 5 repetitive contact heat stimuli (threshold +3°C). Conditioned pain modulation was tested as pain inhibition when a conditioning stimulus (46°C hot water) was applied concurrently to a test stimulus (contact heat; threshold + 3°C). Both alcohol doses boosted CPM, with a greater effect size for the higher dose. Conditioning stimulus ratings increased after alcohol intake but were not correlated with CPM, suggesting independence of these effects. Temporal summation of pain was not affected by alcohol, and alcohol effects on pain threshold were small and limited to the higher dose. Our findings suggest that analgesic alcohol effects might be mainly driven by an enhancement of endogenous pain inhibition. The frequent use of alcohol as self-medication in chronic pain might be motivated by alcohol temporarily restoring deficient CPM, thus leading to pain relief in the short run and alcohol-related problems in the long run.

Effects of manipulating the interstimulus interval on heat-evoked temporal summation of second pain across the age span.

Abstract: This study examined the effects of interstimulus interval (ISI) on heat-evoked temporal summation of second pain (TSSP) and tested whether greatest maintenance of TSSP would occur at longer ISIs in older adults Several lines of evidence support that TSSP is associated with central sensitization and is centrally mediated The participants were 198 community-dwelling adults divided into 3 age cohorts (18-39, 40-59, and 60-78 years of age) Six TSSP trials used a train of 10 contacts with a preheated probe that made repetitive contact with the volar forearm Participants completed 2 trials at each ISI of 25, 35, and 45 seconds The intraclass correlations for each pair of trials support the reliability of the current methodology Temporal summation of second pain scores declined in a time-dependent manner across ISI In addition, greater maintenance of TSSP at longer ISIs was observed in middle-aged and older age groups compared with the younger cohort Significant associations were found between TSSP and measures of recent pain Greater summation at longer ISIs in older adults would suggest slower decay of excitability in spinal neurons and infer increased risk for central sensitization with advancing age

Heterogeneities in intrinsic excitability and frequency-dependent response properties of granule cells across the blades of the rat dentate gyrus

Abstract: The dentate gyrus (DG), the input gate to the hippocampus proper, is anatomically segregated into three different sectors, namely the suprapyramidal blade, the crest region and the infrapyramidal blade Although there are well-established differences between these sectors in terms of neuronal morphology, connectivity patterns and activity levels, differences in electrophysiological properties of granule cells within these sectors have remained unexplored Here, employing somatic whole-cell patch-clamp recordings from the rat DG, we demonstrate that granule cells in these sectors manifest considerable heterogeneities in their intrinsic excitability, temporal summation, action potential characteristics and frequency-dependent response properties Across sectors, these neurons showed positive temporal summation of their responses to inputs mimicking excitatory postsynaptic currents, and showed little to no sag in their voltage responses to pulse currents Consistently, the impedance amplitude profile manifested low-pass characteristics and the impedance phase profile lacked positive phase values at all measured frequencies, voltages and for all sectors Granule cells in all sectors exhibited class I excitability, with broadly linear firing rate profiles, and granule cells in the crest region fired significantly less action potentials compared to those in the infrapyramidal blade Finally, we found weak pairwise correlations across the 18 different measurements obtained individually from each of the three sectors, providing evidence that these measurements are indeed reporting distinct aspects of neuronal physiology Together, our analyses show that granule cells act as integrators of afferent information, and emphasize the need to account for the considerable physiological heterogeneities in assessing their roles in information encoding and processing

Spatial summation of broadband contrast.

Abstract: Spatial summation of luminance contrast signals has historically been psychophysically measured with stimuli isolated in spatial frequency (i.e., narrowband). Here, we revisit the study of spatial summation with noise patterns that contain the naturalistic 1/fα distribution of contrast across spatial frequency. We measured amplitude spectrum slope (α) discrimination thresholds and verified if sensitivity to α improved according to stimulus size. Discrimination thresholds did decrease with an increase in stimulus size. These data were modeled with a summation model originally designed for narrowband stimuli (i.e., single detecting channel; Baker & Meese, 2011; Meese & Baker, 2011) that we modified to include summation across multiple-differently tuned-spatial frequency channels. To fit our data, contrast gain control weights had to be inversely related to spatial frequency (1/f); thus low spatial frequencies received significantly more divisive inhibition than higher spatial frequencies, which is a similar finding to previous models of broadband contrast perception (Haun & Essock, 2010; Haun & Peli, 2013). We found summation across spatial frequency channels to occur prior to summation across space, channel summation was near linear and summation across space was nonlinear. Our analysis demonstrates that classical psychophysical models can be adapted to computationally define visual mechanisms under broadband visual input, with the adapted models offering novel insight on the integration of signals across channels and space.

Using holographic illumination to study synaptic signal integration at individual dendritic spines

Abstract: The physiology of individual synapses on dendritic spines is important because isolated and widely distributed spines are active during sensory information processing in vivo. We used acute cortical brain slices from the rat to investigate synaptic signal integration at the level of individual synapses on dendritic spines in layer 5 pyramidal neurons. We monitored subthreshold synaptic signals using a combination of voltage-sensitive dye recordings, patch-electrode somatic recordings, and 2-photon glutamate uncaging with holographic illumination. We describe the capabilities and limitations of this approach and demonstrate that imaging with an organic voltage-sensitive dye is presently a unique way to monitor temporal summation of uncaging evoked quantal excitatory synaptic potentials locally, at the site of origin on thin basal dendrites. The results indicated that the ability of repetitive activation of individual excitatory synapses on spines to influence the electrical signaling in individual neurons is strictly limited to subthreshold responses. We show that the underlying mechanisms, which control the temporal summation of excitatory synaptic potential in single synapses, can now be investigated with described methodology.