Cortical Mechanisms of Visual Hypersensitivity in Women at Risk for Chronic Pelvic Pain

Abstract

Multisensory hypersensitivity (MSH), which refers to persistent discomfort across sensory modalities, is a risk factor for chronic pain. Developing a better understanding of the neural contributions of disparate sensory systems to MSH may clarify its role in the development of chronic pain. We recruited a cohort of women ( n =147) enriched with participants with menstrual pain at risk for developing chronic pain. Visual sensitivity was measured using a periodic pattern-reversal stimulus during EEG. Self-reported visual unpleasantness ratings were also recorded. Bladder pain sensitivity was evaluated with an experimental bladder-filling task associated with early clinical symptoms of chronic pelvic pain. Visual stimulation induced unpleasantness was associated with bladder pain and evoked primary visual cortex excitation; however, the relationship between unpleasantness and cortical excitation was moderated by bladder pain. Thus, future studies aimed at reversing the progression of MSH into chronic pain should prioritize targeting of cortical mechanisms responsible for maladaptive sensory input integration.

Figure 1.. Visual stimulation task presented during EEG recording and designed to elicit an SSVEP.

a) Participants viewed an alternating blue-yellow checkerboard pattern with positive and negative reversals across five different intensities of brightness modulated with monotonically increasing lux (i.e., brightness intensity). b) Checkerboards alternated at 25Hz and were presented for 20 seconds before an unpleasantness rating for each brightness intensity. Block order was randomized across participants. c) Participants’ unpleasantness ratings were measured using the Gracely Box Scale with textual descriptors.

Figure 2.. Multilevel modeling allows for comprehensive analysis of MSH accounting menstrual pain, somatic symptoms, bladder pain.

In level 1, participant unpleasantness ratings (U) from visual stimulation were modeled as a function of brightness intensity and cortical excitation from 25Hz power spectral density (PSD) estimates. Each participant and electrode were modeled individually, allowing for random intercepts and slopes. Ellipsis indicate all participants are included in this model. Intercepts, brightness slopes, and PSD slopes were modeled separately in level 2 as a function of participants’ prior menstrual pain, somatic symptoms, and bladder pain. This was modeled separately for each electrode but across participants. Moderating effects are demonstrated with arrows depicting high vs. low reported pain/symptoms. Therefore, level 2 brightness and PSD slopes depict positive moderating effects; however, negative moderating effects are also possible (not shown). Data presented are fictional and shown for illustrative purposes. MSH = multisensory hypersensitivity.

Figure 3.. The unpleasant checkerboard stimuli presented at 25Hz evoked widespread robust SSVEPs focused at Oz.

Left. Broadband PSD averaged across the five presented brightness intensities for all participants shows a clear peak at the 25Hz SSVEP alternating checkerboard frequency. Grey shading denotes 95% confidence interval. Middle. Topographically plotted intercepts demonstrated elevated PSD estimates toward occipital electrode sites. Right. Topographically plotted regression slopes show scalp-wide positive slopes, especially at occipital sites and Oz, demonstrating an increase in SSVEP PSD estimates with increasing brightness intensities. All topographic sites for intercept and slope effects were significant after correcting for multiple comparisons (p_FDR < .001).

Figure 4.. The relationships between visual unpleasantness and brightness intensity/cortical excitation were moderated by menstrual pain, somatic symptoms and bladder pain.

a) Partial regression scatter plots depict the positive relationship between bladder pain and participants’ mean unpleasantness ratings averaged across brightness intensities accounting for menstrual pain and somatic symptoms. b) Topographic plots of regression slopes testing the intercepts from the brightness and PSD models. Oz was our a priori electrode of interest. Raw (grey) and averaged (red) slopes across all participants plotted below demonstrate that increases in brightness intensity and 25Hz PSD resulted in concomitant increases in participant unpleasantness ratings when accounting for one another. c) Scalp topographies of moderating slopes from second level multilevel modeling results. Given that positive relationships were observed between unpleasantness ratings and brightness/PSD in b, positive slopes here depict an increasing positive relationship between moderating variables, while negative slopes depict an increasing negative relationship. Menstrual pain ratings moderated the positive relationship between unpleasantness ratings and brightness, but not 25 Hz PSD at Oz (a priori chosen) and several other exploratory electrode sites. Somatic symptoms did not moderate these relationships at Oz; however, somatic symptoms moderated brightness and PSD slopes at a right posterior site (CP6; p_FDR < .05 corrected), despite conflicting directions of moderation. In contrast, bladder pain moderated the positive relationship between unpleasantness and PSD, but not brightness. Level two regression parameter notation n denotes both the brightness (n=1) and PSD (n=2) slope models. PSD = power spectral density; FDR = false discovery rate.

Figure 5.. Visceral sensitivity predicts increased visual unpleasantness at equivalent excitation of primary visual cortex.

Conceptual line plots demonstrating the moderating effect of bladder pain on the relationship between unpleasantness ratings and cortical excitation measured via 25Hz power spectral density (PSD) estimates (i.e., SSVEP amplitudes) at electrode Oz. This moderating effect implies that when visual cortex is minimally excited by visual stimulation, bladder pain has minimal effect on perceived unpleasantness. However, individuals with greater bladder pain report more unpleasantness when cortical excitation is high. Primary visual cortical excitation is not greater in individuals with heightened bladder pain; rather, downstream interpretation of this signal is likely amplified in women with greater bladder pain.