Neural mechanisms underlying attentional bias modification in fibromyalgia patients: a double-blind ERP study.

There is a growing interest in the potential benefits of attentional bias modification (ABM) training in chronic pain patients. However, studies examining the effectiveness of ABM programs in fibromyalgia patients have demonstrated inconclusive effects on both behavioral indices and clinical symptoms. Additionally, underlying neural dynamics of ABM effects could yield new insights but remain yet unexplored. Current study, therefore, aims to investigate the effects of ABM training on known neural electrophysiological indicators of attentional bias to pain (P2, N2a). Thirty-two fibromyalgia patients were enrolled and randomly assigned to an ABM training (N = 16) or control (N = 16) condition (2 weeks duration). Within the ABM training condition participants performed five sessions consisting of a modified version of the dot-probe task in which patients were trained to avoid facial pain expressions, whereas in the control group participants performed five sessions consisting of a standard version of the dot-probe task. Potential ABM training effects were evaluated by comparing a single pre- and post-treatment session, in which event-related potentials (ERPs) were recorded in response to both facial expressions and target stimuli. Furthermore, patients filled out a series of self-report questionnaires assessing anxiety, depression, pain-related worrying, fear of pain, fatigue and pain status. After training, results indicated an overall reduction of the amplitude of the P2 component followed by an enhancement of N2a amplitude for the ABM condition compared to control condition. In addition, scores on anxiety and depression decreased in patients assigned to the training condition. However, we found no effects derived from the training on pain-related and fatigue status. Present study offers new insights related to the possible neural mechanisms underlying the effect of ABM training in fibromyalgia. Clinical trial (TRN: NCT05905159) retrospectively registered (30/05/2023).

Unveiling the Role of Contingent Negative Variation (CNV) in Migraine: A Review of Electrophysiological Studies in Adults and Children.

Migraine has been considered a chronic neuronal-based pain disorder characterized by the presence of cortical hyperexcitability. The Contingent Negative Variation (CNV) is the most explored electrophysiological index in migraine. However, the findings show inconsistencies regarding its functional significance. To address this, we conducted a review in both adults and children with migraine without aura to gain a deeper understanding of it and to derive clinical implications. The literature search was conducted in the PubMed, SCOPUS and PsycINFO databases until September 2022m and 34 articles were retrieved and considered relevant for further analysis. The main results in adults showed higher CNV amplitudes (with no habituation) in migraine patients. Electrophysiological abnormalities, particularly focused on the early CNV subcomponent (eCNV), were especially prominent a few days before the onset of a migraine attack, normalizing during and after the attack. We also explored various modulatory factors, including pharmacological treatments-CNV amplitude was lower after the intake of drugs targeting neural hyperexcitability-and other factors such as psychological, hormonal or genetic/familial influences on CNV. Although similar patterns were found in children, the evidence is particularly scarce and less consistent, likely due to the brain's maturation process during childhood. As the first review exploring the relationship between CNV and migraine, this study supports the role of the CNV as a potential neural marker for migraine pathophysiology and the prediction of pain attacks. The importance of further exploring the relationship between this neurophysiological index and childhood migraine is critical for identifying potential therapeutic targets for managing migraine symptoms during its development.

Pain E-motion Faces Database (PEMF): Pain-related micro-clips for emotion research.

A large number of publications have focused on the study of pain expressions. Despite the growing knowledge, the availability of pain-related face databases is still very scarce compared with other emotional facial expressions. The Pain E-Motion Faces Database (PEMF) is a new open-access database currently consisting of 272 micro-clips of 68 different identities. Each model displays one neutral expression and three pain-related facial expressions: posed, spontaneous-algometer and spontaneous-CO2 laser. Normative ratings of pain intensity, valence and arousal were provided by students of three different European universities. Six independent coders carried out a coding process on the facial stimuli based on the Facial Action Coding System (FACS), in which ratings of intensity of pain, valence and arousal were computed for each type of facial expression. Gender and age effects of models across each type of micro-clip were also analysed. Additionally, participants' ability to discriminate the veracity of pain-related facial expressions (i.e., spontaneous vs posed) was explored. Finally, a series of ANOVAs were carried out to test the presence of other basic emotions and common facial action unit (AU) patterns. The main results revealed that posed facial expressions received higher ratings of pain intensity, more negative valence and higher arousal compared with spontaneous pain-related and neutral faces. No differential effects of model gender were found. Participants were unable to accurately discriminate whether a given pain-related face represented spontaneous or posed pain. PEMF thus constitutes a large open-source and reliable set of dynamic pain expressions useful for designing experimental studies focused on pain processes.

Working memory dysfunction in fibromyalgia is associated with genotypes of the catechol- O-methyltransferase gene: an event-related potential study.

Recent findings have associated different COMT genotypes with working memory capacity in patients with fibromyalgia. Although it is thought that the COMT gene may influence neural correlates (P2 and P3 ERP components) underlying working memory impairment in this chronic-pain syndrome, it has not yet been explored. Therefore, the aim of the present research was to investigate the potential effect of the COMT gene in fibromyalgia patients on ERP working memory indices (P2 and P3 components). For this purpose, 102 participants (51 patients and 51 healthy control participants) took part in the experiment. Event-related potentials and behavioral responses were recorded while participants performed a spatial n-back task. Participants had to decide if the stimulus coincided or not in the same location as the one presented one (1-back condition) or two (2-back condition) trials before. Genotypes of the COMT gene were determined through a saliva sample from all participants. Present results significantly showed lower working memory performance (p < 0.05) in patients with fibromyalgia as compared to control participants (higher rate of errors and slower reaction times). At neural level, we found that patients exhibited enhanced frontocentral and parieto-occipital P2 amplitudes compared to control participants (p < 0.05). Interestingly, we also observed that only fibromyalgia patients carrying the Val/Val genotype of the COMT gene showed higher frontocentral P2 amplitudes than control participants (p < 0.05). Current results (behavioral outcomes and P2 amplitudes) confirmed the presence of an alteration in working memory functioning in fibromyalgia. The enhancement of frontocentral P2 could be reflecting that these patients would manifest an inefficient way of activating executive attention processes, in carriers of the Val/Val genotype of COMT. To our knowledge, the present findings are the first linking neural indices of working memory dysfunctions and COMT genotypes in fibromyalgia. Applying a subgroup of patient's strategy based on this genetic marker could be useful to establish more tailored therapeutical approaches.

Electrophysiological indices of pain expectation abnormalities in fibromyalgia patients.

Fibromyalgia is a chronic pain syndrome characterized by dysfunctional processing of nociceptive stimulation. Neuroimaging studies have pointed out that pain-related network functioning seems to be altered in these patients. It is thought that this clinical symptomatology may be maintained or even strengthened because of an enhanced expectancy for painful stimuli or its forthcoming appearance. However, neural electrophysiological correlates associated with such attentional mechanisms have been scarcely explored. In the current study, expectancy processes of upcoming laser stimulation (painful and non-painful) and its further processing were explored by event-related potentials (ERPs). Nineteen fibromyalgia patients and twenty healthy control volunteers took part in the experiment. Behavioral measures (reaction times and subjective pain perception) were also collected. We manipulated the pain/no pain expectancy through an S1-S2 paradigm (cue-target). S1 (image: triangle or square) predicted the S2 appearance (laser stimulation: warmth or pinprick sensation). Laser stimuli were delivered using a CO2 laser device. Temporal and spatial principal component analyses were employed to define and quantify the ERP component reliability. Statistical analyses revealed the existence of an abnormal pattern of pain expectancy in patients with fibromyalgia. Specifically, our results showed attenuated amplitudes at posterior lCNV component in anticipation of painful stimulation that was not found in healthy participants. In contrast, although larger P2 amplitudes to painful compared to innocuous events were shown, patients did not show any amplitude change in this laser-evoked response as a function of pain predictive cues (as occurred in the healthy control group). Additionally, analyses of the subjective perception of pain and reaction time indicated that laser stimuli preceded by pain cues were rated as more painful than those signaling non-pain expectancy and were associated with faster responses. Differences between groups were not found. The present findings suggest the presence of dysfunction in pain expectation mechanisms in fibromyalgia that eventually may make it difficult for patients to correctly interpret signs that prevent pain symptoms. Furthermore, the abnormal pattern in pain expectancy displayed by fibromyalgia patients could result in ineffective pain coping strategies. Understanding the neural correlates of pain processing and its modulatory factors is crucial to identify treatments for chronic pain syndromes.

Neural correlates of the attentional bias towards pain-related faces in fibromyalgia patients: An ERP study using a dot-probe task.

BACKGROUND: One of the major cognitive deficits in fibromyalgia has been linked to the hypervigilance phenomenon. It is mainly reflected as a negative bias for allocating attentional resources towards both threatening and pain-related information. Although the interest in its study has recently grown, the neural temporal dynamics of the attentional bias in fibromyalgia still remains an open question. METHOD: Fifty participants (25 fibromyalgia patients and 25 healthy control subjects) performed a dot-probe task. Two types of facial expressions (pain-related and neutral) were employed as signal stimuli. Then, as a target stimulus, a single dot replaced the location of one of these two faces. Event-related potentials (ERP) in response to facial expressions and target stimulation (i.e., dot) were recorded. Reaction time (RT) and accuracy measures in the experimental task were collected as behavioural outcomes. RESULTS: Temporal dynamics of brain electrical activity were analysed on two ERP components (P2 and N2a) sensitive to the facial expressions meaning. Pain-related faces elicited higher frontal P2 amplitudes than neutral faces for the whole sample. Interestingly, an interaction effect between group and facial expressions was also found showing that pain-related faces elicited enhanced P2 amplitudes (at fronto-central regions, in this case) compared to neutral faces only when the group of patients was considered. Furthermore, higher P2 amplitudes were observed in response to pain-related faces in patients with fibromyalgia compared to healthy control participants. Additionally, a shorter latency of P2 (at centro-parietal regions) was also detected for pain-related facial expressions compared to neutral faces. Regarding the amplitude of N2a, it was lower for patients as compared to the control group. Non-relevant effects of the target stimulation on the ERPs were found. However, patients with fibromyalgia exhibited slower RT to locate the single dot for incongruent trials as compared to congruent and neutral trials. CONCLUSIONS: Data suggest the presence of an attentional bias in fibromyalgia that it would be followed by a deficit in the allocation of attentional resources to further process pain-related information. Altogether the current results suggest that attentional biases in fibromyalgia might be explained by automatic attentional mechanisms, which seem to be accompanied by an alteration of more strategic or controlled attentional components.

Altered Subprocesses of Working Memory in Patients with Fibromyalgia: An Event-Related Potential Study Using N-Back Task.

OBJECTIVE: Cognitive dysfunction in fibromyalgia has become a key symptom considered by patients as more disabling than pain itself. Experimental evidence from neuropsychological and neuroimaging studies indicates that such cognitive impairments are especially robust when patients need to set in motion working memory processes, suggesting the existence of an altered functioning underlying the cerebral cortices of the frontoparietal memory network. However, the temporal dynamics of working memory subprocesses have not yet been explored in fibromyalgia. SUBJECTS: Thirty-six right-handed women participated in the experiment, comprising 18 patients with fibromyalgia and 18 healthy controls. METHODS: Event-related potentials (ERPs) and behavioral responses were recorded while participants were engaged in a two-back working memory task. Principal component analyses were used to define and quantify the ERP components associated with working memory processes. RESULTS: Patients with fibromyalgia exhibited worse performance than the control group, as revealed by their number of errors in the working memory task. Moreover, both scalp parieto-occipital P2 and parieto-occipital P3 amplitudes were lower for patients than for healthy control participants. Regression analyses revealed that lower P3 amplitudes were observed in those patients with fibromyalgia reporting higher pain ratings. CONCLUSIONS: The present results suggest that both encoding of information (as reflected by P2) and subsequently context updating and replacement (as seen in lower P3 amplitudes), as a part of working memory subprocesses, are impaired in fibromyalgia. Studying the temporal dynamics of working memory through the use of ERP methodology is a helpful approach to detect specific impaired cognitive mechanisms in this chronic pain syndrome. These new data could be used to develop more specific treatments adapted for each patient.

Fear of pain moderates the relationship between self-reported fatigue and methionine allele of catechol-O-methyltransferase gene in patients with fibromyalgia.

Previous research has shown a consistent association among genetic factors, psychological symptoms and pain associated with fibromyalgia. However, how these symptoms interact to moderate genetic factors in fibromyalgia has rarely been studied to date. The present research investigates whether psychological symptoms can moderate the effects of catechol-O-methyltransferase on pain and fatigue. A total of 108 women diagnosed with fibromyalgia and 77 healthy control participants took part in the study. Pain, fatigue, and psychological symptoms (anxiety, depression, pain catastrophizing, fear of pain and fear of movement) were measured by self-report questionnaires. Two types of statistical analyses were performed; the first was undertaken to explore the influences of COMT genotypes on clinical symptoms by comparing patients with fibromyalgia and healthy controls. In the second analysis, moderation analyses to explore the role of psychological symptoms as potential factors that moderate the relationship between pain/fatigue and COMT genotypes were performed. The main results indicated that patients carrying the Met/Met genotype reported significantly higher levels of fatigue than heterozygote carriers (i.e., Met/Val genotype) and higher levels of fatigue, but not significantly different, than Val homozygote carriers. Among patients with fibromyalgia carrying methionine alleles (i.e., Met/Met + Met/Val carriers), only those who scored high on medical fear of pain, experienced an intensified feeling of fatigue. Thus, the present research suggests that fear of pain, as a psychological symptom frequently described in fibromyalgia may act as a moderating factor in the relationship between the Met allele of the COMT gene and the increase or decrease in self-reported fatigue. Although further research with wider patient samples is needed to confirm the present findings, these results point out that the use of psychological interventions focused on affective symptomatology might be a useful tool to reduce the severity of fibromyalgia.

Effects of COMT Genotypes on Working Memory Performance in Fibromyalgia Patients.

Growing research has reported the presence of a clear impairment of working memory functioning in fibromyalgia. Although different genetic factors involving dopamine availability (i.e, the COMT gene) have been associated with the more severe presentation of key symptoms in fibromyalgia, scientific evidence regarding the influence of COMT genotypes on cognitive impairment in these patients is still lacking. To this end, 167 participants took part in the present investigation. Working memory performance was assessed by the application of the SST (Spatial Span Test) and LNST (Letter and Number Sequence Test) belonging to the Weschler Memory Scale III. Significant working memory impairment was shown by the fibromyalgia patients. Remarkably, our results suggest that performance according to different working memory measures might be influenced by different genotypes of the COMT gene. Specifically, fibromyalgia patients carrying the Val/Val genotype exhibited significantly worse outcomes for the span of SST backward, SST backward score, SST total score and the Working Memory Index (WMI) than the Val/Val healthy carriers. Furthermore, the Val/Val patients performed worse on the SST backward and SST score than heterozygotes. Our findings are the first to show a link between the COMT gene and working memory dysfunction in fibromyalgia, supporting the idea that higher COMT enzyme activity would contribute to more severe working memory impairment in fibromyalgia.