Supplementary data for: Prepulse inhibition of the blink reflex in functional neurological disorder and fibromyalgia
Nováková, Lucia; Sojka, Petr; Voženílek, David; Sieger, Tomáš; Hasíková, Lenka; Šenolt, Ladislav; Závada, Jakub; Edwards, Mark J.; Serranová, Tereza
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- Zenodo
- Language
- en
Abstract
Supplementary data for the article "Prepulse inhibition of the blink reflex in functional neurological disorder and fibromyalgia" Abstract: Prepulse inhibition reflects subcortical sensory integration, where a low-intensity peripheral stimulus (prepulse) reduces the amplitude of a reflex response to a subsequent high-intensity stimulus. As a measure of pre-attentive sensory gating, prepulse inhibition has been found to be altered in small cohorts of patients with functional disorders, including functional motor disorder and fibromyalgia, suggesting a shared deficit in sensory information processing. However, prior studies have not demonstrated consistent associations between prepulse inhibition abnormalities and clinical measures. We hypothesized that widespread pain and somatic symptoms in somatic symptom disorders may result from a general deficit in the interpretation of bodily signals, potentially linked to abnormalities in sensory filtering as measured by prepulse inhibition. In this study, we examined 140 participants across four age- and sex-matched groups: 35 patients clinically categorized with functional motor disorder without fibromyalgia, 35 with both functional motor disorder and fibromyalgia, 35 with fibromyalgia only, and 35 healthy controls. A weak electrical stimulus to the index finger served as the prepulse, delivered 100 ms before supraorbital nerve stimulation to elicit the R2 component of the blink reflex. Prepulse inhibition was calculated as the percent reduction in R2 amplitude. Across all groups, lower prepulse was significantly associated with higher scores on the Fibromyalgia Severity Scale, consisting of Widespread Pain Index and Symptom Severity Scale. In patients with functional motor disorder, no association was found between prepulse inhibition size and objectively rated motor symptom severity. These findings suggest that impaired early sensory processing at subcortical level is related to “fibromyalgianess” in people with functional motor disorder and fibromyalgia. Abnormal prepulse inhibition may serve as an objective transdiagnostic marker of fibromyalgia symptomatology or fibromyalgianess, including widespread pain and other non-motor symptoms in functional disorders, highlighting a potential role of sensory gating deficits in the pathophysiology of fibromyalgia-spectrum manifestations.
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Supplementary material Methods Table S1 Medication use FM (n=35) FMD+FM (n=35) FMD (n=35) HC (n=35) Selective Serotonin Reuptake Inhibitors 11 8 10 5 Serotonin-Norepinephrine Reuptake Inhibitors 7 5 1 1 Serotonin Antagonist and Reuptake Inhibitors 9 7 5 1 Noradrenergic and Specific Serotonergic AD 2 3 0 0 Tricyclic AD 2 0 0 0 Anticonvulsants 2 1 0 0 Dopaminergic Agents 4 2 2 0 Benzodiazepines 6 5 2 1 Opioids 10 5 1 0 Nonsteroidal Anti-inflammatory Drugs 22 21 6 1 Medical Cannabis 8 2 0 0 Pregabalin/Gabapentin 12 21 8 0 Abbreviations: AD = antidepressants; FM = fibromyalgia; FMD = functional motor disorder; FMD+FM = functional motor disorder and fibromyalgia ; HC = Healthy Controls
Results Demographic and clinical data Table S2 Demographic and clinical measures FMD+FM (n=35) FM (n=35) FMD (n=35) HC (n=35) Test statistics P-value Effect size Age 48.6 (8.3) 50.1 (7.8) 47.3 (13.4) 48.3 (8.3) F(3, 136) = 0.29 0.83 0.006 a Sex (F/M) 32/3 32/3 32/3 32/3 NA NA NA Duration (y) 7.40 (6.30) 12.50 (9.40) 5.70 (5.40) NA F(2, 102) = 8.35 <0.001 0.14 a FSS 20.82 (5.31) 23.89 (3.90) 10.51 (3.60) 2.86 (2.94) F(3, 136) = 200.59 <0.001 0.82 a WPI 12.09 (4.34) 14.20 (2.94) 4.28 (2.46) 1.26 (1.48) F(3, 136) = 150.22 <0.001 0.77 a SSS 8.74 (2.05) 9.69 (1.64) 6.26 (2.79) 1.60 (1.91) F(3, 136) = 101.95 <0.001 0.69 a S-FMDRS 15.17 (8.02) NA 9.71 (5.59) NA t(68) = 3.85 <0.002 0.92 b BDI-II 24.23 (11.26) 27.71 (13.00) 17.20 (11.63) 6.03 (6.71) F(3, 136) = 27.07 <0.001 0.38 a STAI-X2 49.94 (12.83) 50.80 (12.27) 44.20 (11.92) 33.23 (6.64) F(3, 136) = 18.70 <0.001 0.29 a Mean values (SD) are presented; P-values are nominal values corrected using the Holm-Bonferroni method. Abbreviations: BDI-II = Beck Depression Inventory-II; FM = Fibromyalgia; FMD = Functional Motor Disorder; FMD+FM = Functional Motor Disorder and Fibromyalgia; Fibromyalgia Severity Scale; HC = Healthy controls; S-FMDRS = Simplified Functional Movement Disorders Rating Scale; SSS = Symptom Severity Scale; STAI-X2 = State-Trait Anxiety Inventory – trait; WPI = Widespread Pain Index; aPartial η2; bCohen’s d. Note: Disease duration represents FMD duration in patients with FMD (with or without FM) and FM duration in patients with FM alone.
Correlation analyses In all subjects (n=140), prepulse inhibition size (PPI size) was negatively correlated with all fibromyalgia-related measures (i.e. FSS, WPI, SSS), as well as with depression (BDI-II) and anxiety (STAI-X2) scores. All fibromyalgia-related scales were positively correlated with both BDI-II and STAI-X2. In the subgroup comprising patients with FMD (n=70), motor symptom severity (S-FMDRS) was not correlated with PPI size. Of the fibromyalgia-related measures, the FSS and SSS were significantly correlated with S-FMDRS. Moreover, S-FMDRS was positively correlated with both BDIII and STAI-X2. See Figure S1 for further details.
Fig S1. Cross-correlations between prepulse inhibition size, fibromyalgia-related measures, affective symptoms, and motor symptom severity. Pearson correlation coefficients are shown; *** p < 0.001, ** p < 0.01, * p < 0.05. Abbreviations: BDI-II = Beck Depression Inventory-II; C = healthy controls; F = patients with fibromyalgia; FSS = Fibromyalgia Severity Scale; M = patients with functional motor disorder; O = patients with functional motor disorder and fibromyalgia; PPI size = Prepulse Inhibition size; S-FMDRS = Simplified Functional Movement Disorder Rating Scale; SSS = Symptom Severity Scale; STAI-X2 = State-Trait Anxiety Inventory trait; WPI = Widespread Pain Index.
Between-group comparison of prepulse inhibition size PPI size differed across the four groups as revealed by the ANOVA model with a significant effect of the group on the PPI size, F(3,136) = 15.47, p < 0.001, with a large effect size, η2 = 0.25 (Fig. S2 A). The Tukey post-hoc test indicated that the HC generally had a higher PPI size compared to all patient groups. The FMD with fibromyalgia had significantly lower PPI size than the FMD only group. There were no significant differences in PPI size between the FMD with fibromyalgia and fibromyalgia only groups nor between the FMD only and fibromyalgia only. However, when we adjusted the PPI size for FSS (as PPI size was strongly negatively correlated with FSS), PPI size no longer differed across the four groups, F(3,136) = 0.87, p = 0.46 (Fig. S2 B). Fig S2. Between-group comparison of prepulse inhibition size Prepulse inhibition size (PPI size) in patients with fibromyalgia alone (FM), with functional motor disorder and fibromyalgia (FMD+FM), with functional motor disorder alone (FMD), and healthy controls (HC). The PPI size (i.e. the difference between the mean blink reflex magnitude in the baseline trials and the trials with the prepulse) is expressed in %. A: PPI size differed between groups. B: PPI size adjusted for FSS did not differ across groups. *** p < 0.001, * p < 0.05.
