Online consumer testing beyond central location tests: A case study for brewed coffee.

Due to the constraints of the COVID-19 pandemic, conducting sensory evaluations requiring direct interactions became challenging. In response, researchers have been motivated to devise non-face-to-face testing methods as alternatives. This study aimed to compare two non-face-to-face home-use tests (HUT) with the traditional face-to-face central location test (CLT). Both HUTs involved online recruitment and sample delivery to participants' homes. One HUT provided a written protocol with no direct interaction (contactless HUT; C-HUT), whereas the other included an online meeting with a researcher for live guidance (online HUT; O-HUT). Four coffee samples were evaluated on the basis of liking and sensory and emotional attributes. The comparison between CLT and O-HUT showed RV coefficients of 0.92, 0.93, and 0.98 (P < 0.05) for liking and sensory and emotional attributes, respectively. In addition, based on the RV coefficient, the CLT results showed a significantly greater similarity to those of O-HUT compared to those of C-HUT. The O-HUT also outperformed the C-HUT in its ability to significantly discriminate between samples. Hence, real-time interactions between researchers and participants, as facilitated by O-HUT, may be more suitable in certain scenarios compared to C-HUT, which relies solely on a written protocol. Overall, these findings suggest that C-HUT and O-HUT are suitable methods for collecting sensory data and overcoming geographic and face-to-face contact limitations, providing greater flexibility, and reducing the time and cost associated with traditional sensory evaluations.

Effects of Simulated Airplane Cabin Noise on In-Flight Meal Perception in the Brain Using Electroencephalography.

Auditory distractions can impair the sensory evaluation of food; however, the specific impact of airplane cabin noise on the sensory perception of in-flight meals remains poorly studied. Here, we investigated the effects of airplane cabin noise on the visual processing of in-flight meal stimuli using electroencephalography (EEG) in twenty healthy male subjects. Resting-state EEG and event-related potential (ERP) responses to in-flight meal images were acquired during quiet and simulated cabin noise conditions. Participants reported mild discomfort and some loss of appetite when exposed to airplane cabin noise. The analysis of resting-state EEG showed an increase in the absolute power of theta and beta frequency bands in the left superior parietal and left frontal/right central regions under simulated cabin noise conditions, compared to quiet conditions. The ERP results showed that the amplitude of responses evoked by visual meal images in the superior parietal area was reduced in the noise condition compared to the quiet condition. Our findings suggest that airplane cabin noise disrupts the visual perception and attentional processing of in-flight food stimuli. These neural changes imply an impact on integrating sensory information, resulting in altered sensory evaluations of food during in-flight dining experiences.

High-definition tDCS over primary motor cortex modulates brain signal variability and functional connectivity in episodic migraine.

OBJECTIVE: This study investigated how high-definition transcranial direct current stimulation (HD-tDCS) over the primary motor cortex (M1) affects brain signal variability and functional connectivity in the trigeminal pain pathway, and their association with changes in migraine attacks. METHODS: Twenty-five episodic migraine patients were randomized for ten daily sessions of active or sham M1 HD-tDCS. Resting-state blood-oxygenation-level-dependent (BOLD) signal variability and seed-based functional connectivity were assessed pre- and post-treatment. A mediation analysis was performed to test whether BOLD signal variability mediates the relationship between treatment group and moderate-to-severe headache days. RESULTS: The active M1 HD-tDCS group showed reduced BOLD variability in the spinal trigeminal nucleus (SpV) and thalamus, but increased variability in the rostral anterior cingulate cortex (rACC) compared to the sham group. Connectivity decreased between medial pulvinar-temporal pole, medial dorsal-precuneus, and the ventral posterior medial nucleus-SpV, but increased between the rACC-amygdala, and the periaqueductal gray-parahippocampal gyrus. Changes in medial pulvinar variability mediated the reduction in moderate-to-severe headache days at one-month post-treatment. CONCLUSIONS: M1 HD-tDCS alters BOLD signal variability and connectivity in the trigeminal somatosensory and modulatory pain system, potentially alleviating migraine headache attacks. SIGNIFICANCE: M1 HD-tDCS realigns brain signal variability and connectivity in migraineurs closer to healthy control levels.

Exploring HD-tDCS Effect on µ-opioid Receptor and Pain Sensitivity in Temporomandibular Disorder: A Pilot Randomized Clinical Trial Study.

This study explored the association between experimentally-induced pain sensitivity and µ-opioid receptor (µOR) availability in patients with temporomandibular disorder (TMD) and further investigated any changes in the pain and µOR availability following high-definition transcranial direct current stimulation (HD-tDCS) over the primary motor cortex (M1) with pilot randomized clinical trials. Seven patients with TMD completed either active (n = 3) or sham treatment (n = 4) for 10 daily sessions and underwent positron emission tomography (PET) scans with [11C]carfentanil, a selective µOR agonist, a week before and after treatment. PET imaging consisted of an early resting and late phase with the sustained masseteric pain challenge by computer-controlled injection of 5% hypertonic saline. We also included 12 patients with TMD, obtained from our previous study, for baseline PET analysis. We observed that patients with more sensitivity to pain, indicated by lower infusion rate, had less µOR availability in the right amygdala during the late phase. Moreover, active M1 HD-tDCS, compared to sham, increased µOR availability post-treatment in the thalamus during the early resting phase and the amygdala, hippocampus, and parahippocampal gyrus during the late pain challenge phase. Importantly, increased µOR availability post-treatment in limbic structures including the amygdala and hippocampus was associated with decreased pain sensitivity. The findings underscore the role of the µOR system in pain regulation and the therapeutic potential of HD-tDCS for TMD. Nonetheless, large-scale studies are necessary to establish the clinical significance of these results. TRIAL REGISTRATION: ClinicalTrial.gov (NCT03724032) PERSPECTIVE: This study links pain sensitivity and µ-opioid receptors in patients with TMD. HD-tDCS over M1 improved µOR availability, which was associated with reduced pain sensitivity. Implications for TMD pain management are promising, but larger clinical trials are essential for validation.

Comparison of Check-All-That-Apply (CATA), Rate-All-That-Apply (RATA), Flash Profile, Free Listing, and Conventional Descriptive Analysis for the Sensory Profiling of Sweet Pumpkin Porridge.

With significant progress in the use of rapid descriptive methodologies as alternatives to conventional descriptive analysis (DA), several consumer-based approaches have emerged. In this study, we compared four such methodologies-check-all-that-apply (CATA), rate-all-that-apply (RATA), flash profile (FP), and free listing (FL)-for sensory profiling to DA, using six sweet pumpkin porridges. The DA involved eight trained panelists, whereas each consumer evaluation engaged 60 untrained consumers. Overall, the performance of the consumer methods was similar to the DA, and it could effectively profile differences in consumer perceptions of sensory attributes, as evident from high regressor vector (RV) values (>0.89). RATA exhibited the highest similarity to the DA (Rv = 0.96), featuring quicker and less tedious processes compared with FP or FL. Novel combined methods for sensory characterization using the strengths of these four approaches are warranted. This includes leveraging the simplicity and versatility of CATA or RATA coupled with the capacity of FP or FL to capture spontaneous perceptions of products by consumers.

Effect of High-Definition Transcranial Direct Current Stimulation on Headache Severity and Central µ-Opioid Receptor Availability in Episodic Migraine.

Objective: The current understanding of utilizing HD-tDCS as a targeted approach to improve headache attacks and modulate endogenous opioid systems in episodic migraine is relatively limited. This study aimed to determine whether high-definition transcranial direct current stimulation (HD-tDCS) over the primary motor cortex (M1) can improve clinical outcomes and endogenous µ-opioid receptor (µOR) availability for episodic migraineurs. Methods: In a randomized, double-blind, and sham-controlled trial, 25 patients completed 10-daily 20-min M1 HD-tDCS, repeated Positron Emission Tomography (PET) scans with a selective agonist for µOR. Twelve age- and sex-matched healthy controls participated in the baseline PET/MRI scan without neuromodulation. The primary endpoints were moderate-to-severe (M/S) headache days and responder rate (≥50% reduction on M/S headache days from baseline), and secondary endpoints included the presence of M/S headache intensity and the use of rescue medication over 1-month after treatment. Results: In a one-month follow-up, at initial analysis, both the active and sham groups exhibited no significant differences in their primary outcomes (M/S headache days and responder rates). Similarly, secondary outcomes (M/S headache intensity and the usage of rescue medication) also revealed no significant differences between the two groups. However, subsequent analyses showed that active M1 HD-tDCS, compared to sham, resulted in a more beneficial response predominantly in higher-frequency individuals (>3 attacks/month), as demonstrated by the interaction between treatment indicator and baseline frequency of migraine attacks on the primary outcomes. These favorable outcomes were also confirmed for the secondary endpoints in higher-frequency patients. Active treatment also resulted in increased µOR concentration compared to sham in the limbic and descending pain modulatory pathway. Our exploratory mediation analysis suggests that the observed clinical efficacy of HD-tDCS in patients with higher-frequency conditions might be potentially mediated through an increase in µOR availability. Conclusion: The 10-daily M1 HD-tDCS can improve clinical outcomes in episodic migraineurs with a higher baseline frequency of migraine attacks (>3 attacks/month). This improvement may be, in part, facilitated by the increase in the endogenous µOR availability. Clinical Trial Registration: www.ClinicalTrials.gov, identifier - NCT02964741.

Classifying migraine using PET compressive big data analytics of brain's µ-opioid and D2/D3 dopamine neurotransmission.

Introduction: Migraine is a common and debilitating pain disorder associated with dysfunction of the central nervous system. Advanced magnetic resonance imaging (MRI) studies have reported relevant pathophysiologic states in migraine. However, its molecular mechanistic processes are still poorly understood in vivo. This study examined migraine patients with a novel machine learning (ML) method based on their central µ-opioid and dopamine D2/D3 profiles, the most critical neurotransmitters in the brain for pain perception and its cognitive-motivational interface. Methods: We employed compressive Big Data Analytics (CBDA) to identify migraineurs and healthy controls (HC) in a large positron emission tomography (PET) dataset. 198 PET volumes were obtained from 38 migraineurs and 23 HC during rest and thermal pain challenge. 61 subjects were scanned with the selective µ-opioid receptor (µOR) radiotracer [11C]Carfentanil, and 22 with the selective dopamine D2/D3 receptor (DOR) radiotracer [11C]Raclopride. PET scans were recast into a 1D array of 510,340 voxels with spatial and intensity filtering of non-displaceable binding potential (BPND), representing the receptor availability level. We then performed data reduction and CBDA to power rank the predictive brain voxels. Results: CBDA classified migraineurs from HC with accuracy, sensitivity, and specificity above 90% for whole-brain and region-of-interest (ROI) analyses. The most predictive ROIs for µOR were the insula (anterior), thalamus (pulvinar, medial-dorsal, and ventral lateral/posterior nuclei), and the putamen. The latter, putamen (anterior), was also the most predictive for migraine regarding DOR D2/D3 BPND levels. Discussion: CBDA of endogenous µ-opioid and D2/D3 dopamine dysfunctions in the brain can accurately identify a migraine patient based on their receptor availability across key sensory, motor, and motivational processing regions. Our ML-based findings in the migraineur's brain neurotransmission partly explain the severe impact of migraine suffering and associated neuropsychiatric comorbidities.

Management of Episodic Migraine with Neuromodulation: A Case Report.

Migraine is a highly prevalent neurovascular disorder that affects approximately 15% of the global population. Migraine attacks are a complex cascade of neurologic events that lead to debilitating symptoms and are often associated with inhibitory behavior. The constellation of severe signs and symptoms during the ictal phase (headache attack) makes migraine the third most common cause of disability globally in both sexes under the age of 50. Misuse of pharmaceuticals, such as opiates, can lead to devastating outcomes and exacerbation of pain and headache attacks. A safe and well-tolerated non-pharmacological research approach is high-definition transcranial direct current stimulation over the M1.

Functional Magnetic Resonance Imaging Signal Variability Is Associated With Neuromodulation in Fibromyalgia.

OBJECTIVES: Although primary motor cortex (M1) transcranial direct current stimulation (tDCS) has an analgesic effect in fibromyalgia (FM), its neural mechanism remains elusive. We investigated whether M1-tDCS modulates a regional temporal variability of blood-oxygenation-level-dependent (BOLD) signals, an indicator of the brain's flexibility and efficiency and if this change is associated with pain improvement. MATERIALS AND METHODS: In a within-subjects cross-over design, 12 female FM patients underwent sham and active tDCS on five consecutive days, respectively. Each session was performed with an anode placed on the left M1 and a cathode on the contralateral supraorbital region. The subjects also participated in resting-state functional magnetic resonance imaging (fMRI) at baseline and after sham and active tDCS. We compared the BOLD signal variability (SDBOLD), defined as the standard deviation of the BOLD time-series, between the tDCS conditions. Baseline SDBOLD was compared to 15 healthy female controls. RESULTS: At baseline, FM patients showed reduced SDBOLD in the ventromedial prefrontal cortex (vmPFC), lateral PFC, and anterior insula and increased SDBOLD in the posterior insula compared to healthy controls. After active tDCS, compared to sham, we found an increased SDBOLD in the left rostral anterior cingulate cortex (rACC), lateral PFC, and thalamus. After sham tDCS, compared to baseline, we found a decreased SDBOLD in the dorsomedial PFC and posterior cingulate cortex/precuneus. Interestingly, after active tDCS compared to sham, pain reduction was correlated with an increased SDBOLD in the rACC/vmPFC but with a decreased SDBOLD in the posterior insula. CONCLUSION: Our findings suggest that M1-tDCS might revert temporal variability of fMRI signals in the rACC/vmPFC and posterior insula linked to FM pain. Changes in neural variability would be part of the mechanisms underlying repetitive M1-tDCS analgesia in FM.

Structural and functional thalamocortical connectivity study in female fibromyalgia.

Dysfunctional thalamocortical interactions have been suggested as putative mechanisms of ineffective pain modulation and also suggested as possible pathophysiology of fibromyalgia (FM). However, it remains unclear which specific thalamocortical networks are altered and whether it is related to abnormal pain perception in people with FM. Here, we conducted combined vertex-wise subcortical shape, cortical thickness, structural covariance, and resting-state functional connectivity analyses to address these questions. FM group exhibited a regional shape deflation of the left posterior thalamus encompassing the ventral posterior lateral and pulvinar nuclei. The structural covariance analysis showed that the extent of regional deflation of the left posterior thalamus was negatively covaried with the left inferior parietal cortical thickness in the FM group, whereas those two regions were positively covaried in the healthy controls. In functional connectivity analysis with the left posterior thalamus as a seed, FM group had less connectivity with the periaqueductal gray compared with healthy controls, but enhanced connectivity between the posterior thalamus and bilateral inferior parietal regions, associated with a lower electrical pain threshold at the hand dorsum (pain-free point). Overall, our findings showed the structural thalamic alteration interacts with the cortical regions in a functionally maladaptive direction, leading the FM brain more responsive to external stimuli and potentially contributing to pain amplification.

Dopaminergic Regulation of Reward System Connectivity Underpins Pain and Emotional Suffering in Migraine.

PURPOSE: It has been suggested that reward system dysfunction may account for emotion and pain suffering in migraine. However, there is a lack of evidence whether the altered reward system connectivity is directly associated with clinical manifestations, including negative affect and ictal pain severity and, at the molecular level, the dopamine (DA) D2/D3 receptors (D2/3Rs) signaling implicated in encoding motivational and emotional cues. PATIENTS AND METHODS: We acquired resting-state functional MRI from interictal episodic migraine (EM) patients and age-matched healthy controls, as well as positron emission tomography (PET) with [11C]raclopride, a selective radiotracer for DA D2/3Rs, from a subset of these participants. The nucleus accumbens (NAc) was seeded to measure functional connectivity (FC) and DA D2/3Rs availability based on its essential involvement in pain-related aversive/reward functions. Associations of the brain measures with positive/negative affect and ictal pain severity were also assessed. RESULTS: Compared with controls, the EM group showed weaker right NAc connectivity with areas implicated in pain and emotional regulation, such as the amygdala, rostral anterior cingulate cortex, hippocampus, and thalamus; but showed stronger left NAc connectivity with the dorsolateral prefrontal cortex and lingual gyrus. Moreover, among the altered NAc connectivities, only right NAc-amygdala connectivity was inversely correlated with DA D2/3Rs availability in migraine patients (diagnostic group-by-D2/3Rs interaction p < 0.007). At a clinical level, such weaker NAc-amygdala connectivity was associated with lower interictal positive affect and greater ictal pain severity over the head and facial extension area (pain area and intensity number summation, PAINS). CONCLUSION: Together, our findings suggest that altered reward system connectivity, specifically between the NAc and amygdala, might be affected by endogenous DA D2/3Rs signaling, and such process might be a neural mechanism that underlies emotional and pain suffering in episodic migraineurs.

Differential alteration of fMRI signal variability in the ascending trigeminal somatosensory and pain modulatory pathways in migraine.

BACKGROUND: The moment-to-moment variability of resting-state brain activity has been suggested to play an active role in chronic pain. Here, we investigated the regional blood-oxygen-level-dependent signal variability (BOLDSV) and inter-regional dynamic functional connectivity (dFC) in the interictal phase of migraine and its relationship with the attack severity. METHODS: We acquired resting-state functional magnetic resonance imaging from 20 migraine patients and 26 healthy controls (HC). We calculated the standard deviation (SD) of the BOLD time-series at each voxel as a measure of the BOLD signal variability (BOLDSV) and performed a whole-brain voxel-wise group comparison. The brain regions showing significant group differences in BOLDSV were used to define the regions of interest (ROIs). The SD and mean of the dynamic conditional correlation between those ROIs were calculated to measure the variability and strength of the dFC. Furthermore, patients' experimental pain thresholds and headache pain area/intensity levels during the migraine ictal-phase were assessed for clinical correlations. RESULTS: We found that migraineurs, compared to HCs, displayed greater BOLDSV in the ascending trigeminal spinal-thalamo-cortical pathways, including the spinal trigeminal nucleus, pulvinar/ventral posteromedial (VPM) nuclei of the thalamus, primary somatosensory cortex (S1), and posterior insula. Conversely, migraine patients exhibited lower BOLDSV in the top-down modulatory pathways, including the dorsolateral prefrontal (dlPFC) and inferior parietal (IPC) cortices compared to HCs. Importantly, abnormal interictal BOLDSV in the ascending trigeminal spinal-thalamo-cortical and frontoparietal pathways were associated with the patient's headache severity and thermal pain sensitivity during the migraine attack. Migraineurs also had significantly lower variability and greater strength of dFC within the thalamo-cortical pathway (VPM-S1) than HCs. In contrast, migraine patients showed greater variability and lower strength of dFC within the frontoparietal pathway (dlPFC-IPC). CONCLUSIONS: Migraine is associated with alterations in temporal signal variability in the ascending trigeminal somatosensory and top-down modulatory pathways, which may explain migraine-related pain and allodynia. Contrasting patterns of time-varying connectivity within the thalamo-cortical and frontoparietal pathways could be linked to abnormal network integrity and instability for pain transmission and modulation.

Threat Prediction from Schemas as a Source of Bias in Pain Perception.

Our sensory impressions of pain are generally thought to represent the noxious properties of an agent but can be influenced by the predicted level of threat. Predictions can be sourced from higher-order cognitive processes, such as schemas, but the extent to which schemas can influence pain perception relative to bottom-up sensory inputs and the underlying neural underpinnings of such a phenomenon are unclear. Here, we investigate how threat predictions generated from learning a cognitive schema lead to inaccurate sensory impressions of the pain stimulus. Healthy male and female participants first detected a linear association between cue values and stimulus intensity and rated pain to reflect the linear schema when compared with uncued heat stimuli. The effect of bias on pain ratings was reduced when prediction errors (PEs) increased, but pain perception was only partially updated when measured against stepped increases in PEs. Cognitive, striatal, and sensory regions graded their responses to changes in predicted threat despite the PEs (p < 0.05, corrected). Individuals with more catastrophic thinking about pain and with low mindfulness were significantly more reliant on the schema than on the sensory evidence from the pain stimulus. These behavioral differences mapped to variability in responses of the striatum and ventromedial prefrontal cortex. Thus, this study demonstrates a significant role of higher-order schemas in pain perception and indicates that pain perception is biased more toward predictions and less toward nociceptive inputs in individuals who report less mindfulness and more fear of pain.SIGNIFICANCE STATEMENT This study demonstrates that threat predictions generated from cognitive schemas continue to influence pain perception despite increasing prediction errors arising in pain pathways. Individuals first formed a cognitive schema of linearity in the relationship between the cued threat value and the stimulus intensity. Subsequently, the linearity was reduced gradually, and participants partially updated their evaluations of pain in relation to the stepped increases in prediction errors. Individuals who continued to rate pain based more on the predicted threat than on changes in nociceptive inputs reported high pain catastrophizing and less mindful-awareness scores. These two affects mapped to activity in the ventral and dorsal striatum, respectively. These findings direct us to a significant role of top-down processes in pain perception.

Disrupted Resting State Network of Fibromyalgia in Theta frequency.

Fibromyalgia (FM), chronic widespread pain, exhibits spontaneous pain without external stimuli and is associated with altered brain activities during resting state. To understand the topological features of brain network in FM, we employed persistent homology which is a multiple scale network modeling framework not requiring thresholding. Spontaneous magnetoencephalography (MEG) activity was recorded in 19 healthy controls (HCs) and 18 FM patients. Barcode, single linkage dendrogram and single linkage matrix were generated based on the proposed modeling framework. In theta band, the slope of decrease in the number of connected components in barcodes showed steeper in HC, suggesting FM patients had decreased global connectivity. FM patients had reduced connectivity within default mode network, between middle/inferior temporal gyrus and visual cortex. The longer pain duration was correlated with reduced connectivity between inferior temporal gyrus and visual cortex. Our findings demonstrated that the aberrant resting state network could be associated with dysfunction of sensory processing in chronic pain. The spontaneous nature of FM pain may accrue to disruption of resting state network.

Increased Low- and High-Frequency Oscillatory Activity in the Prefrontal Cortex of Fibromyalgia Patients.

Recent human neuroimaging studies have suggested that fibromyalgia (FM), a chronic widespread pain disorder, exhibits altered thalamic structure and function. Since the thalamus has extensive reciprocal connection with the cortex, structural and functional thalamic alterations in FM might be linked to aberrant thalamocortical oscillation. This study investigated the presence of abnormal brain rhythmicity in low- and high-frequency bands during resting state in patients with FM and their relationship to clinical pain symptom. Spontaneous magnetoencephalography (MEG) activity was recorded in 18 females with FM and 18 age- and sex-matched healthy control (HC) subjects. The most remarkable finding was that FM patients had general increases in theta, beta and gamma power along with a slowing of the dominant alpha peak. Increased spectral powers in the theta-band were primarily localized to the left dorsolateral prefrontal (DLPFC) and orbitofrontal cortex (OFC). Beta and gamma over-activation were localized to insular, primary motor and primary and secondary somatosensory (S2) cortices, as well as the DLPFC and OFC. Furthermore, enhanced high-frequency oscillatory activities in the DLPFC and OFC were associated with higher affective pain scores in patients with FM. Our results demonstrate that FM patients feature enhanced low- and high-frequency oscillatory activity in the brain areas related to cognitive and emotional modulation of pain. Increased low- and high-frequency activity of the prefrontal cortex may contribute to persistent perception of pain in FM. Therapeutic intervention based on manipulating neural oscillation to restore normal thalamocortical rhythmicity may be beneficial to pain relief in FM.

Augmented Pain Processing in Primary and Secondary Somatosensory Cortex in Fibromyalgia: A Magnetoencephalography Study Using Intra-Epidermal Electrical Stimulation.

The aim of this study was to investigate augmented pain processing in the cortical somatosensory system in patients with fibromyalgia (FM). Cortical evoked responses were recorded in FM (n = 19) and healthy subjects (n = 21) using magnetoencephalography after noxious intra-epidermal electrical stimulation (IES) of the hand dorsum (pain rating 6 on a numeric rating scale, perceptually-equivalent). In addition, healthy subjects were stimulated using the amplitude corresponding to the average stimulus intensity rated 6 in patients with FM (intensity-equivalent). Quantitative sensory testing was performed on the hand dorsum or thenar muscle (neutral site) and over the trapezius muscle (tender point), using IES (thresholds, ratings, temporal summation of pain, stimulus-response curve) and mechanical stimuli (threshold, ratings). Increased amplitude of cortical responses was found in patients with FM as compared to healthy subjects. These included the contralateral primary (S1) and bilateral secondary somatosensory cortices (S2) in response to intensity-equivalent stimuli and the contralateral S1 and S2 in response to perceptually-equivalent stimuli. The amplitude of the contralateral S2 response in patients with FM was positively correlated with average pain intensity over the last week. Quantitative sensory testing results showed that patients with FM were more sensitive to painful IES as well as to mechanical stimulation, regardless of whether the stimulation site was the hand or the trapezius muscle. Interestingly, the slope of the stimulus-response relationship as well as temporal summation of pain in response to IES was not different between groups. Together, these results suggest that the observed pain augmentation in response to IES in patients with FM could be due to sensitization or disinhibition of the cortical somatosensory system. Since the S2 has been shown to play a role in higher-order functions, further studies are needed to clarify the role of augmented S2 response in clinical characteristics of FM.

Disinhibition of the primary somatosensory cortex in patients with fibromyalgia.

Fibromyalgia (FM) is a chronic widespread pain condition linked to central sensitization. Altered excitability of sensorimotor cortex has been proposed as an underlying pathology of FM. This study aimed to investigate intracortical excitability of the primary somatosensory cortex (S1) and its potential role in clinical pain in patients with FM. Somatosensory evoked magnetic fields were recorded in 17 right-handed females with FM and 21 age-, sex-, and handedness-matched healthy control subjects. Paired-pulse median nerve stimulation was delivered to the left and right wrist. We assessed the peak-to-peak amplitudes of the N20m-P35m and peak amplitude of each N20m and P35m component. Paired-pulse suppression (PPS) of the second response was quantified as the ratio of the amplitudes of the second to the first response. Patients with FM displayed significantly higher PPS ratio for the N20m-P35m in both hemispheres, indicating reduced intracortical inhibition in the S1. Notably, PPS ratio for the P35m was higher in patients with FM than in healthy controls, whereas no differences were apparent in PPS ratio for the N20m in both hemispheres. For both the N20m-P35m and the P35m in the left hemisphere, PPS ratios were positively associated with the sensory pain on the short-form McGill Pain Questionnaire. This study demonstrated that intracortical inhibition in the S1 is compromised bilaterally in patients with FM, and the extent of disinhibition can be closely associated with increased clinical pain. Our results suggest that changes of intracortical inhibition of the S1 may contribute to the pathophysiology of FM pain.

Impaired pre-attentive auditory processing in fibromyalgia: A mismatch negativity (MMN) study.

OBJECTIVE: Fibromyalgia (FM) patients often show deficits in cognitive functions such as attention and working memory. We assumed that pre-attentive information processing, a crucial element in human perception and cognition, would be altered in FM patients. Thus, the objective of this study was to determine whether FM patients exhibit alterations in pre-attentive processing as assessed by auditory mismatch negativity (MMN). METHODS: Auditory evoked magnetic fields were recorded in FM patients (n=18) and healthy control subjects (n=21) during a duration-deviant auditory oddball paradigm. The magnetic mismatch negativity (MMNm) was obtained by subtracting responses to standard tones from responses to deviant tones. Pressure pain thresholds over the thenar and trapezius muscles were determined using an algometer. RESULTS: MMNm peak amplitudes in right hemispheres were attenuated, and the directional asymmetry coefficient of the MMNm amplitude was lower in FM patients, indicating a more leftward asymmetry than in healthy control subjects. Smaller right MMNm amplitude was associated with lower pressure pain thresholds of thenar muscles in FM patients. CONCLUSIONS: Our results suggested that pre-attentive processing of auditory information is impaired in FM patients. SIGNIFICANCE: This study provided neurophysiological evidence of impaired pre-attentive sensory change detection in FM.

Altered white matter integrity in the corpus callosum in fibromyalgia patients identified by tract-based spatial statistical analysis.

OBJECTIVE: Although recent imaging studies of fibromyalgia (FM) have converged on a dysfunction of central pain processing as the primary pathophysiologic cause of the disorder, microstructural changes of the white matter (WM) suggestive of abnormalities in the anatomic connectivity of the brain have not been extensively examined. The aim of this study was to investigate WM integrity and its possible relationship to pain symptoms in women with FM. METHODS: Nineteen FM patients and 21 age-, sex-, and education-matched healthy control subjects were included in the study and underwent diffusion-weighted imaging. Group differences in WM integrity, which were assessed via fractional anisotropy (FA), was investigated by applying tract-based spatial statistics. RESULTS: As compared with the healthy control group, the FM group showed a single cluster with lower FA in the left body of the corpus callosum, which was found to be connected to the bilateral sensorimotor cortices (P < 0.05, corrected for multiple comparisons). Furthermore, FA values in the cluster were negatively associated with sensory pain, as measured by the Short-Form McGill Pain Questionnaire, as well as with the relative magnitude of sensory pain versus affective pain (calculated by dividing the sensory score by the affective score). CONCLUSION: Findings of the current study demonstrated that patients with FM had disrupted WM microstructure in the body of the corpus callosum, which was associated with clinical pain intensity. Our results suggest that abnormal interhemispheric transfer might contribute to the heightened pain perception. Our findings further strengthen the hypothesis of centrally augmented pain processing in patients with FM.

Ascending beta oscillation from finger muscle to sensorimotor cortex contributes to enhanced steady-state isometric contraction in humans.

OBJECTIVE: ß-Band corticomuscular coherence is suggested as an electrophysiological mechanism that contributes to sensorimotor functioning in the maintenance of steady-state contractions. Converging evidence suggests that not only the descending corticospinal pathway but the ascending sensory feedback pathway is involved in the generation of ß-band corticomuscular coherence. The present study aimed to investigate which pathway, descending vs. ascending, contributes more to the stability of muscle contraction, especially for human intrinsic hand muscles. METHODS: In this study, we assessed directed transfer function (DTF) between magnetoencephalography signals over the sensorimotor cortex (SMC) and rectified electromyographic (EMG) signals recorded during steady-state isometric contraction of the right thumb muscle (flexor pollicis brevis, FPB) or right little finger muscle (flexor digiti minimi brevis, FDMB) in 15 right-handed healthy subjects. RESULTS: ß-Band DTF was statistically significant in both descending (SMC→EMG) and ascending (EMG→SMC) directions, and mean phase delays for each direction were in agreement with the conduction time for the descending corticospinal and ascending sensory feedback pathways. The strengths of the ß-band DTF (EMG→SMC direction) were greater in the FPB muscle than in the FDMB muscle, while the strengths of the ß-band DTF (SMC→EMG direction) were not different between the two muscles. Moreover, the ß-band DTF (EMG→SMC direction) was greater in the "Stable" period than in the "Less Stable" period within the FDMB muscle. Greater DTF (EMG→SMC direction) was positively associated with the stability of muscle contraction. CONCLUSIONS: Our findings suggest that ascending ß-band oscillatory activity may promote a steady-state isometric contraction by efficiently transmitting sensory feedback from finger muscles to the sensorimotor cortex. SIGNIFICANCE: The results show the differential contribution of the ascending part of the corticomuscular network depending on the functional organization.