Prestimulus Theta Oscillations and Connectivity Modulate Pain Perception

Abstract

The perception of pain is strongly influenced by cognitive processes, such as expectations toward the efficacy of pain medication. It is reasonable to assume that such processes, among other sources of fluctuation, are reflected in ongoing brain activity, which in turn influences perceptual processing. To identify specific prestimulus EEG activity, and connectivity patterns related to subsequent pain perception in humans, we contrasted painful with nonpainful sensations delivered at the individual threshold level determined by the psychophysical QUEST estimation method (Watson and Pelli, 1983). The 64-channel EEG was recorded using active electrodes during a constant stimulation procedure. The power contrast between trials sorted by rating revealed a signal decrease of 8% before stimulus onset in theta-band (4-7 Hz) at T7/FT7 as well as increased theta-power by 6% at T8/FT8. Gamma-band power was increased (12%, 28-32 Hz) at frontocentral sites (all p < 0.05). Changes in theta-band power are covarying with subsequent pain perception, as well as lowered frontolateral theta-band connectivity for painful percepts. A decrease in frontoparietal connectivity for painful sensations was also identified in the gamma-band (28-32 Hz). A single-trial logistic regression revealed significant information content in the EEG signal at temporal electrode T7 in theta-band (p < 0.01) and frontal electrode F1 in gamma-band (all p < 0.02). The observed patterns suggest top-down modulation of the theta-band effects by a frontocentral network node. These findings contribute to the understanding of ongoing subjective pain sensitivity, potentially relevant to both clinical diagnostics and pain management.

Significance statement: The perceived intensity of a constant stimulus is known to vary considerably across multiple presentations. Here, we used state-of-the-art psychophysical methods in an EEG experiment to identify the specific neuronal activity before stimulus onset that reflects the subsequent perception of pain. We found specific oscillatory activity at the bilateral insular cortices as well as connectivity patterns that reflect and correlate with subsequent ratings. These results further the understanding of pain perception and are potentially relevant for the decoding of ongoing pain sensitivity and pain management.

Keywords: EEG; pain; prestimulus; psychophysics; theta-band; threshold.

Figure 1.

Experimental procedure. Top, Forty trials of thresholding were followed by 4–6 blocks of 30 trials each with constant stimulation, depending on data quality. Bottom, Schematics of a single trial: jittered 3–5 s waiting period (intertrial interval, ISI) followed by stimulation and the visual analog scale for pain rating after 250 ms.

Figure 2.

Power effects in the theta-band (4–7 Hz). a, Time-frequency plot of the difference between pain and no-pain trials averaged across electrodes T7/TF7 (top) and T8/TF8 (bottom). Solid outline indicates the prestimulus effect identified by permutation testing (t_min = −3.06, t_max = 2.77, all p < 0.05, FDR corrected). Dotted outline indicates the data region used as significant regression predictor in single-trial analysis (b = 0.61, p < 0.011). b, The topographies show relative power differences (dB) between pain and no-pain trials in the prestimulus time range (top) and poststimulus time range (bottom). *Electrodes showing significant effects.

Figure 3.

Power effects in the log gamma-band (28–32 Hz). a, Time-frequency plot of the relative power difference (dB) between pain and no-pain trials averaged across electrodes Fz, F1, FC1, and FCz. Solid outline indicates the prestimulus effect identified by permutation testing (t_max = 3.67, p < 0.05, FDR corrected). Dotted outline indicates the data region used as significant regression predictor in single-trial analysis (electrode F1, b = −0.93, p < 0.045). b, Topographies show relative power differences (dB) between pain and no-pain trials in the prestimulus time range (top) and poststimulus time range (bottom). *Electrodes showing significant effects.

Figure 4.

Connectivity effects. Time-frequency plots of different electrode pairs reflect changes in PLV between pain and no-pain trials. Topo-plots represent the locations of the plotted electrode pairs. Red represents an increase in connectivity. Blue represents a decrease. The matching category is indicated on the bottom right of each topo-plot. Depicted are visualizations of PLV differences from seed electrodes. a, PLV differences in the theta-band (4–7 Hz) and prestimulus time window (−0.8 to 0 s). b, PLV differences in the theta-band (4–7 Hz) and poststimulus time window (0–0.4 s). c, PLV differences in the gamma-band (28–32 Hz) for the prestimulus time window (−0.8 to 0 s). Time-frequency points within the solid lines are significant at p < 0.05 (cluster corrected).

Figure 5.

eLORETA generators for the scalp power differences in the theta-band. a, Differential activity in bilateral insular cortex (t_max = 0.104, t_min = −0.058). b, Differential source activity in the precuneus/posterior cingulate area (t_max = 0.103). Yellow/red: increase, blue: decrease.

Figure 6.

eLORETA generator for the scalp power differences in the gamma-band revealing a single effect in the contralateral insular cortex (t_max = 0.182). Yellow/red: increase, blue: decrease.