Multisine frequency modulation of intra-epidermal electric pulse sequences: A novel tool to study nociceptive processing

Berg, Boudewijn van den; Kasting, Mindy; Schouten, Alfred C.; Helm, F.C.T. van der; Buitenweg, Jan R.

doi:10.1016/j.jneumeth.2021.109106

Cited by 2 publications

(8 citation statements)

References 33 publications

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“…Earlier nociceptive and pain studies did occasionally report M1 activation, suggesting that this activation could be related to suppression of movement or pain-evoked movements (Apkarian et al 2005 ). Both explanations seem unlikely in this study, as participants generally experience intra-epidermal SSEPs as non-painful (van den Berg et al 2021 ). Earlier nociceptive and pain studies using EEG and MEG did consistently report sources in S1 and S2.…”

Section: Discussionmentioning

confidence: 78%

“…A major obstacle for accurate source localization was the low signal-to-noise ratio of the signal caused by both the low stimulus amplitude required to preferentially stimulate nociceptive afferents and the division of bandwidth over multiple stimulation frequencies to probe system (non)linearity. For a more elaborate discussion of parameters involved in the signal-to-noise ratio, please refer to (van den Berg et al 2021 ). As a result, individual source estimates (not reported) suffered from noise and were not accurately depicting a single source location.…”

Section: Discussionmentioning

confidence: 99%

“…The results presented in this work are based on data from two experiments. The first set of experiments on 10 participants were reported in (van den Berg et al 2021 ). Another set of experiments on 12 participants was recorded to extend the original dataset for improved signal-to-noise ratio and source localization.…”

Section: Methodsmentioning

confidence: 99%

“…Stimulation consisted of frequency modulated sequences of square wave cathodic electric pulses, using the same method as was used earlier in (van den Berg et al 2021 ). Stimulation was controlled by a microcontroller connected to the trigger input of the stimulator.…”

Section: Methodsmentioning

confidence: 99%

“…In a recent study, we showed that it is also possible to evoke nociceptive SSEPs using frequency modulation of intra-epidermal pulses to further downregulate saliency effects (i.e. by decreasing the maximum distance between pulses and avoiding the rapid variations in pulse rate associated with blocks of pulses), and to enable multisine frequency modulation for probing system properties such as system delay, linearity and order (van den Berg et al 2021 ). Frequency analysis showed significant peaks at stimulation frequencies (3–7 Hz), but did not find any significant harmonic or intermodulation frequencies that would confirm nonlinearity of nociceptive processing.…”

Section: Introductionmentioning

confidence: 99%

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Nociceptive Intra-epidermal Electric Stimulation Evokes Steady-State Responses in the Secondary Somatosensory Cortex

2022

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Recent studies have established the presence of nociceptive steady-state evoked potentials (SSEPs), generated in response to thermal or intra-epidermal electric stimuli. This study explores cortical sources and generation mechanisms of nociceptive SSEPs in response to intra-epidermal electric stimuli. Our method was to stimulate healthy volunteers (n = 22, all men) with 100 intra-epidermal pulse sequences. Each sequence had a duration of 8.5 s, and consisted of pulses with a pulse rate between 20 and 200 Hz, which was frequency modulated with a multisine waveform of 3, 7 and 13 Hz (n = 10, 1 excluded) or 3 and 7 Hz (n = 12, 1 excluded). As a result, evoked potentials in response to stimulation onset and contralateral SSEPs at 3 and 7 Hz were observed. The SSEPs at 3 and 7 Hz had an average time delay of 137 ms and 143 ms respectively. The evoked potential in response to stimulation onset had a contralateral minimum (N1) at 115 ms and a central maximum (P2) at 300 ms. Sources for the multisine SSEP at 3 and 7 Hz were found through beamforming near the primary and secondary somatosensory cortex. Sources for the N1 were found near the primary and secondary somatosensory cortex. Sources for the N2-P2 were found near the supplementary motor area. Harmonic and intermodulation frequencies in the SSEP power spectrum remained below a detectable level and no evidence for nonlinearity of nociceptive processing, i.e. processing of peripheral firing rate into cortical evoked potentials, was found.

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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Nociceptive Intra-epidermal Electric Stimulation Evokes Steady-State Responses in the Secondary Somatosensory Cortex

2022

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How to make calibration less painful—A proposition for an automatic, reliable and time‐efficient procedure

Świder,

Moratti,

Bruña

2024

Psychophysiology

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In behavioral and neurophysiological pain studies, multiple types of calibration methods are used to quantify the individual pain sensation stimuli. Often, studies lack a detailed calibration procedure description, data linearity, and quality quantification and omit required control for sex pain differences. This hampers study repetition and interexperimental comparisons. Moreover, typical calibration procedures require a high number of stimulations, which may cause discomfort and stimuli habituation among participants. To overcome those shortcomings, we present an automatic calibration procedure with a novel stimuli estimation method for intraepidermal stimulation. We provide an in‐depth data analysis of the collected self‐reports from 70 healthy volunteers (37 males) and propose a method based on a dynamic truncated linear regression model (tLRM). We compare its estimates for the sensation (t) and pain (T) thresholds and mid‐pain stimulation (MP), with those calculated using traditional estimation methods and standard linear regression models. Compared to the other methods, tLRM exhibits higher R2 and requires 36% fewer stimuli applications and has significantly higher t intensity and lower T and MP intensities. Regarding sex differences, t and T were found to be lower for females compared to males, regardless of the estimation method. The proposed tLRM method quantifies the calibration procedure quality, minimizes its duration and invasiveness, and provides validation of linearity between stimuli intensity and subjective scores, making it an enabling technique for further studies. Moreover, our results highlight the importance of control for sex in pain studies.

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Multisine frequency modulation of intra-epidermal electric pulse sequences: A novel tool to study nociceptive processing

Cited by 2 publications

References 33 publications

Nociceptive Intra-epidermal Electric Stimulation Evokes Steady-State Responses in the Secondary Somatosensory Cortex

Nociceptive Intra-epidermal Electric Stimulation Evokes Steady-State Responses in the Secondary Somatosensory Cortex

How to make calibration less painful—A proposition for an automatic, reliable and time‐efficient procedure

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