Single-trial Averaging Research Articles

Individual Difference in Cooperation and Reciprocal Choice: Findings From the Prisoner’s Dilemma

Following nociceptive heat or laser stimulation, an early contralateral and later vertex potential can be recorded. Although more indicative of the nociceptive input, the acquisition of the contralateral N1 after contact heat stimulation (contact heat-evoked potentials [CHEPs]) remains difficult. An advantage of contact heat is that the baseline skin temperature preceding peak stimulation can be controlled. Increasing the baseline temperature may represent a novel strategy to improve the acquisition of CHEPs without resulting in more subjective pain to stimulation. A study was undertaken in 23 healthy subjects to examine the effects of increasing the baseline temperature but not the perceived intensity of contact heat stimulation. A combined standard averaging and single-trial analysis was performed to disclose how changes in averaged waveforms related to latency jitter and individual trial amplitudes. By increasing the baseline temperature, the acquisition of N1 was improved among subjects with a low-amplitude response (greater than −4 μV) following 35°C baseline temperature stimulation (P < .05). Based on standard averaging, N2/P2 amplitudes were also significantly increased with and without an accompanying change in the rating of perceived pain when the baseline temperature was increased (P < .05). In contrast, automated single-trial averaging revealed no significant difference in N2 amplitude when the baseline temperature was increased to 42°C and the peak temperature reduced. These findings suggest that 2 mechanisms underlie the improved acquisition of CHEPs: increased synchronization of afferent volley, yielding larger-amplitude evoked potentials in response to the same rating of intensity; and reduced inter-trial variability.

Single-trial averaging improves the physiological interpretation of contact heat evoked potentials

Laser and contact heat evoked potentials (LEPs and CHEPs, respectively) provide an objective measure of pathways and processes involved in nociception. The majority of studies analyzing LEP or CHEP outcomes have done so based on conventional, across-trial averaging. With this approach, evoked potential components are potentially confounded by latency jitter and ignore relevant information contained within single trials. The current study addressed the advantage of analyzing nociceptive evoked potentials based on responses to noxious stimulations within each individual trial. Single-trial and conventional averaging were applied to data previously collected in 90 healthy subjects from 3 stimulation locations on the upper limb. The primary analysis focused on relationships between single and across-trial averaged CHEP outcomes (i.e., N2P2 amplitude and N2 and P2 latencies) and subject characteristics (i.e., age, sex, height, and rating of perceived intensity), which were examined by way of linear mixed model analysis. Single-trial averaging lead to larger N2P2 amplitudes and longer N2 and P2 latencies. Age and ratings of perceived intensity were the only subject level characteristics associated with CHEPs outcomes that significantly interacted with the method of analysis (conventional vs single-trial averaging). The strength of relationships for age and ratings of perceived intensity, measured by linear fit, were increased for single-trial compared to conventional across-trial averaged CHEP outcomes. By accounting for latency jitter, single-trial averaging improved the associations between CHEPs and physiological outcomes and should be incorporated as a standard analytical technique in future studies.

Improving the acquisition of nociceptive evoked potentials without causing more pain

Following nociceptive heat or laser stimulation, an early contralateral and later vertex potential can be recorded. Although more indicative of the nociceptive input, the acquisition of the contralateral N1 after contact heat stimulation (contact heat-evoked potentials [CHEPs]) remains difficult. An advantage of contact heat is that the baseline skin temperature preceding peak stimulation can be controlled. Increasing the baseline temperature may represent a novel strategy to improve the acquisition of CHEPs without resulting in more subjective pain to stimulation. A study was undertaken in 23 healthy subjects to examine the effects of increasing the baseline temperature but not the perceived intensity of contact heat stimulation. A combined standard averaging and single-trial analysis was performed to disclose how changes in averaged waveforms related to latency jitter and individual trial amplitudes. By increasing the baseline temperature, the acquisition of N1 was improved among subjects with a low-amplitude response (greater than −4μV) following 35°C baseline temperature stimulation (P<.05). Based on standard averaging, N2/P2 amplitudes were also significantly increased with and without an accompanying change in the rating of perceived pain when the baseline temperature was increased (P<.05). In contrast, automated single-trial averaging revealed no significant difference in N2 amplitude when the baseline temperature was increased to 42°C and the peak temperature reduced. These findings suggest that 2 mechanisms underlie the improved acquisition of CHEPs: increased synchronization of afferent volley, yielding larger-amplitude evoked potentials in response to the same rating of intensity; and reduced inter-trial variability.

Optimizing the Measurement of Contact Heat Evoked Potentials

Our aim was to determine whether single trial averaging could improve quantification of contact heat evoked potentials measured from fixed position contact heat stimulation. Event-related brain potentials were measured in response to contact heat stimuli applied to the arm and the leg of 10 subjects via a circular thermode, using fixed and varied thermode positions at 41 degrees C and 51 degrees C. Contact heat evoked potentials were successfully recorded from varied position stimulation of the leg at 51 degrees C in 80% of subjects, but from only 60% of subjects using a fixed position. Contact heat evoked potentials were only identified in a small number of subjects when stimulating at 41 degrees C. The amplitude of the N2-P2 complex and pain intensity ratings were larger for the varied compared with the fixed thermode position and were also larger when stimulating the arm. Automated single trial analysis of the data resulted in larger amplitude of the N2-P2 complex than standard averaging. In conclusion, we have demonstrated that the reduced contact heat evoked potentials amplitude seen for fixed location stimulation can be improved with single-trial averaging.

Effects of single-trial averaging on spatial extent of brain activation detected by fMRI are subject and task dependent

AimThe effects of single-trial averaging on the spatial extent of event-related fMRI activation may vary between subjects and tasks. The purpose of this study was to evaluate this variability using a visual task and a word generation task.Patients, materials, and methodsFive Chinese right-handed male volunteers participated in the experiment. Experiments were conducted using a 1.5 T clinical MRI scanner with a T2*-weighted single-shot gradient-echo EPI sequence. Each task contained 150 trials that were separated into 5 runs. For each voxel, time courses averaged across different numbers of randomly selected trials, were obtained. They were applied for determining the voxels with significant activations, using a students’ t-test (p<0.001, uncorrected).ResultsConsistent with previous findings, the number of the activated voxels increased monotonically with the number of trials combined. The ascending rate and the maximum number of the activated voxels were different, however, between tasks and among subjects.ConclusionsThe effects of single-trial averaging were found to vary significantly between tasks and subjects. Therefore, we strongly advise to carefully consider such variability when using the spatial extent of activation as a measure in a group or a task comparison.

The effects of single-trial averaging on the temporal resolution of functional MRI

Computer simulations and event-related functional MRI (ER-fMRI) experiments were performed to investigate the effects of single-trial averaging and the corresponding contrast-to-noise ratio (CNR) on the minimal resolvable hemodynamic timing difference between brain areas. Three ER-fMRI sessions with temporally delayed (250, 500 and 1,000 ms) visual stimulations between two hemifields, each with 70 repeated single trials, were examined on two subjects. From the computer simulation, the temporal resolution improved as the CNR increased, which reached 500 and 100 ms for CNRs of 1.55 and 6.44, respectively. In the ER-fMRI experiments, the measured CNR increased as more single trials were averaged. The detectability of temporal differences was positively correlated (P<.05) with the CNR in all sessions for one subject but only in the 1,000-ms session for the other subject. Temporal resolution of 1,000 ms was achieved when more than 10 trials were averaged. The 500- and 250-ms delays might be differentiable when more than 20 trials were averaged, but the results were subject-dependent. This study demonstrated that the CNR could be significantly improved by single-trial averaging, which led to an improved temporal resolution of ER-fMRI. Temporal resolution in the range of hundreds of milliseconds was subject-dependent, which might be attributed to the intrinsic spatial variations in the timing of the blood oxygenation level-dependent (BOLD) response.