Name: psychophysically-anchored, robust thresholding in studying pain-related lateralization of oscillatory prestimulus activity
Uploaded: 2017-01-21T14:00:00
Description: Watch this Scientific Journal Video about Psychophysically-anchored, Robust Thresholding in Studying Pain-related Lateralization of Oscillatory Prestimulus Activity at JoVE.com

This work has been funded by the Transregional Collaborative Research Centre TRR169 &#34;Crossmodal Learning: Adaptivity, Prediction and Interaction&#34; / German Research Foundation (DFG). The authors thank Stephanie Shields for the helpful comments on the manuscript.

The experiment has been approved by the ethics commission of the Hamburg medical association (PV4509).
1. Participant Selection
<ol>
	<li>Beyond standard selection criteria, such as fitness for pain stimulation, head implants or pre-existing neurological conditions, make sure the participants are not suffering from acute or chronic pain, are not taking any pain medication, and have no known history of substance abuse. Participants should also not have taken part in any pharmacological studie...

<ol>
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Here we used the well theoretically founded QUEST method to efficiently estimate a robust psychophysical threshold between non-pain and pain perception. Using constant stimulation at this threshold enables an analysis of perceptual decisions independent of changes in stimulus magnitude. While we examined threshold intensity at the transition point between innocuous and noxious sensation domains, other points along the pain scale (e.g.,&#160;50 on a 100-point pain scale) can also be anchored with the here present...

When conducting behavioral experiments involving human participants, it is important to be able to closely control the intensities of presented stimuli. Using stimuli of equal intensity for all participants, however, will in some settings introduce the bias of subjective perception. For some perceptual qualities such as pain, there are high inter- and intra-individual variations in perceived intensity at a constant stimulus level1,2. For experiments that assume equal subjective percepts, it is thus a necessity to match the subjectively perceived intensity across participants. This is also important when examining perception at threshold level, e.g., between painful and nonpainful stimulation. Psychophysics research has addressed these kind of problems for decades, and today there are sophisticated but easy-to-use methods available to achieve robust psychophysical anchoring.
A simple, classical method of mapping the intensity of a stimulus to an individual sensation magnitude is the staircase method3. Hereby, the intensity of successive stimuli is increased or decreased, until there is a change in the participant&#39;s response relating to the desired threshold or position on the subjective sensation scale. Repeating this process&#160;number of times, yields a plausible estimate of the reversal point. Classical methods, however, fail to make use of all the information contained in each rating trial. This leads to an unnecessarily high number of trials required to reach convergence. Methods such as (linear) regression or function fitting might fail, if the assumptions for the relationship between stimulus intensity and sensation magnitude are wrong or do not hold for the tested stimulus range. The adaptive procedures not only yield a robust point estimate for a certain subjective intensity, but do so more efficiently. Especially for longer experiments, which heavily rely on accurate estimation of a threshold or sensation magnitude, it is necessary for the psychophysical method to be both robust and at the same time efficient with respect to the number of required trials. This is especially important in fields such as pain research, where the total exposure to painful stimulation should be kept as low as possible for the participants&#39; benefit.
Although the classical staircase methods are still widely used, e.g. in quantitative sensory testing, the use of more advanced estimation methods that make better use of the acquired information across trials is steadily increasing. In the case of the maximum likelihood estimation method QUEST4,5 used here, this is probably due to the readily available implementation in the popular Matlab PsychToolbox6 suite. The modern, revised version of this procedure is superior to classical estimation methods both in robustness and the low number of trials required to arrive at a sufficient estimate, if used with the right settings7.
The rationale behind the QUEST procedure is to fit a Weibull function to the incoming data to model the psychophysical transformation between stimulus intensity and sensation magnitude. The parameters for the psychophysical Weibull function are in part given by the experimenter, e.g. the steepness of the function or the offset due to the false positive rate and responder inconsistency. The positioning of the parameter of interest along the intensity dimension is approximated by the procedure using Bayesian maximum likelihood estimation. Hereby, a probability distribution is assumed over the location of the target parameter, i.e. the threshold intensity. Given a sensible prior assumption for such a distribution, the algorithm will determine the most informative intensity that the participant should respond to. For the current implementation of the procedure, this is the mean of the prior probability distribution8. For each successive trial, the prior probability distribution is in essence multiplied with the likelihood of the participant&#39;s given response at the tested stimulation level, as characterized by the Weibull function. Every response will be used to continuously update the probability distribution estimate for the threshold parameter. This procedure is repeated until a satisfying estimate is produced. The procedure is more efficient than a simple regression because it makes immediate use of the collected responses to determine which stimulation intensity to test next. Also, the procedure will specifically probe around the point of interest, e.g. a threshold or certain sensation intensity. Using only testing data from such a limited range in regression would lead to an unstable estimate, making adaptive procedures more robust in settings where only relatively low numbers of trials are feasible.
Such robust psychophysical anchoring can be used to measure changes in pain sensitivity over time, modulatory effects in hyperalgesia/allodynia research or analgesic effects in pharmacological interventions, amongst other settings. Another interesting prospect of being able to anchor stimuli to the intensity just at the threshold between two sensory continua is to examine subjective perception across the transition from non-painful to painful sensation9,10,11. This scenario is very interesting because if the pain threshold has been robustly estimated, pain and no-pain conditions can be contrasted in electroencephalographic (EEG) activity, for example, without changing the physical stimulus intensity12. This allows for the observation of pain-specific perceptual processes under constant stimulus conditions by examining the difference in brain activity between trials rated as painful and non-painful.
We will demonstrate how to use the readily available implementation of adaptive estimation in PsychToolbox to robustly determine the individual pain threshold in an EEG experiment where the contrast between pain and no-pain activity is examined for lateralization effects, depending on the stimulation site. Since the stimulation intensity can be kept constant after the thresholding procedure, it is not necessary to account for EEG activity co-varying with stimulus intensity in the subsequent analysis.

<table border="0" cellpadding="0" cellspacing="0" width="835">
	<tbody>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">EasyCap electrode cap</td>
			<td style="width:241px;">EasyCap, Woerthsee-Etterschlag, Germany</td>
			<td style="width:211px;">CUCHW-58</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">actiCap active Ag/Cl EEG electrode set</td>
			<td style="width:241px;">BrainProducts GmbH, Gliching, Germany</td>
			<td style="width:211px;">-</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">SuperVisc EEG eletrode gel</td>
			<td style="width:241px;">EasyCap, Woerthsee-Etterschlag, Germany</td>
			<td style="width:211px;">V16</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">BrainAmp EEG amplifier</td>
			<td style="width:241px;">BrainProducts GmbH, Gliching, Germany</td>
			<td style="width:211px;">BrainAmp Standard</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">PsychToolbox-3</td>
			<td style="width:241px;">Mario Kleiner / Open Source</td>
			<td style="width:211px;">-</td>
			<td>Available at http://psychtoolbox.org/</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Matlab</td>
			<td style="width:241px;">MathWorks, Natick, MA</td>
			<td style="width:211px;">Matlab R2015b</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">DigiTimer DS7A constant current electrical stimulator</td>
			<td style="width:241px;">DigiTimer Ltd., Hertfordshire, United Kingdom</td>
			<td style="width:211px;">DS7A</td>
			<td></td>
		</tr>
	</tbody>
</table>

psychophysically-anchored, robust thresholding in studying pain-related lateralization of oscillatory prestimulus activity

In perceptual studies, it is often important to objectively assess the equality of delivered stimulation across participants or to quantify the intra-individual sensation magnitude that is evoked by stimulation over multiple trials. This requires a robust mapping of stimulus magnitude to perceived intensity and is commonly achieved by psychophysical estimation methods such as the staircase procedure. Newer, more efficient procedures like the QUEST algorithm fit a psychophysical function to the data in real time while at the same time maximizing the efficiency of data collection. A robust estimate of the threshold intensity between painful and nonpainful perceptions can then be used to reduce the influence of variations in sensory input in subsequent analyses of oscillatory brain activity. By stimulating at a constant threshold intensity determined by an adaptive estimation procedure, the variance in the ratings can be directly attributed to perceptual processes. Oscillatory activity can then be contrasted between &#34;pain&#34; and &#34;no-pain&#34; trials directly, yielding activity that closely relates to perceptual classification processes in nociception.

Using a rating scale split into one half for nonpainful and one half for painful sensations (Figure 1a), constant stimulation can be applied over many trials while still yielding ratings across the scale midpoint (Figure 1b). This way, changes in sensory input can be avoided, and the rating outcome can be directly related to intrinsic perceptual classification processes related to pain.
<img alt...

Watch this Scientific Journal Video about Psychophysically-anchored, Robust Thresholding in Studying Pain-related Lateralization of Oscillatory Prestimulus Activity at JoVE.com

Psychophysically-anchored, Robust Thresholding in Studying Pain-related Lateralization of Oscillatory Prestimulus Activity

Psychophysical methods such as the QUEST estimation procedure can efficiently yield robust estimates of the stimulation intensity at which nonpainful sensations transition into painful sensations. By stimulating repeatedly at the threshold intensity, the variability in rating responses can directly be attributed to perceptual classifications in subsequent analyses.

In perceptual studies, it is often important to objectively assess the equality of delivered stimulation across participants or to quantify the ...

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