Carolina Sitges

Disrupted Functional Connectivity of the Pain Network in Fibromyalgia

Objective To investigate the impact of chronic pain on brain dynamics at rest. Methods Functional connectivity was examined in patients with fibromyalgia (FM) (n = 9) and healthy controls (n = 11) by calculating partial correlations between low-frequency blood oxygen level–dependent fluctuations extracted from 15 brain regions. Results Patients with FM had more positive and negative correlations within the pain network than healthy controls. Patients with FM displayed enhanced functional connectivity of the anterior cingulate cortex (ACC) with the insula (INS) and basal ganglia (p values between .01 and .05), the secondary somatosensory area with the caudate (CAU) (p = .012), the primary motor cortex with the supplementary motor area (p = .007), the globus pallidus with the amygdala and superior temporal sulcus (both p values < .05), and the medial prefrontal cortex with the posterior cingulate cortex (PCC) and CAU (both p values < .05). Functional connectivity of the ACC with the amygdala and periaqueductal gray (PAG) matter (p values between .001 and .05), the thalamus with the INS and PAG (both p values < .01), the INS with the putamen (p = .038), the PAG with the CAU (p = .038), the secondary somatosensory area with the motor cortex and PCC (both p values < .05), and the PCC with the superior temporal sulcus (p = .002) was also reduced in FM. In addition, significant negative correlations were observed between depression and PAG connectivity strength with the thalamus (r = −0.64, p = .003) and ACC (r = −0.60, p = .004). Conclusions These findings demonstrate that patients with FM display a substantial imbalance of the connectivity within the pain network during rest, suggesting that chronic pain may also lead to changes in brain activity during internally generated thought processes such as occur at rest. Abbreviations BOLD = blood oxygen level–dependent; FM = fibromyalgia; HC = healthy control; WHYMPI = West Haven-Yale Multidimensional Pain Inventory; fMRI = functional magnetic resonance imaging; ACC = anterior cingulate cortex; PCC = posterior cingulate cortex; AMYG = amygdala; CAU = caudate; PUT = putamen; INS = insula; M1 = primary motor area; SMA = supplementary motor area; SI = primary somatosensory area; SII = secondary somatosensory area; mPFC = medial prefrontal cortex; PAG = periaqueductal gray; STS = superior temporal sulcus; THA = thalamus

Abnormal affective modulation of somatosensory brain processing among patients with fibromyalgia

Objective: It is well established that subjective pain perception can be modulated by negative mood states and that patients with chronic pain are characterized by high levels of depression and anxiety. Nevertheless, very little is known about the effects of negative mood induction on brain processing of somatosensory information in fibromyalgia. The objective of the present study was to examine the influence of two emotional states (pleasant and unpleasant) on brain activity of patients with fibromyalgia (FM; n = 27) and with musculoskeletal (MSK) pain resulting from identifiable somatic lesions (n = 16). Methods: For this purpose, somatosensory-evoked potentials (SEPs) elicited by nonpainful pneumatic stimuli, delivered to the right and left hand following an oddball paradigm, were recorded when patients were viewing affective slides. Results: As compared with patients with MSK pain, patients with FM displayed overall larger P50 amplitude to tactile stimuli. In addition, significantly larger P50 and smaller N80 amplitudes were found within patients with FM when they were viewing the unpleasant rather than the pleasant slides. Conclusion: Our data suggest an abnormal processing of nonpainful somatosensory information in FM, especially when somatic signals are arising from the body within an aversive stimulus context. These findings provide further support for the use of biopsychosocial models for understanding FM and other chronic pain states. ACR = American College of Rheumatology; ANOVA = analysis of variance; BDI = Beck Depression Inventory; EEG = electroencephalogram; FM = fibromyalgia; fMRI=functional magnetic resonance imaging; IAPS = International Affective Picture System; MPI = West Haven–Yale Multidimensional Pain Inventory; MPQ = McGill Pain Questionnaire; MSK = musculoskeletal; SE = standard error of the mean; SEP = somatosensory-evoked potentials; STAI = State-Trait Anxiety Inventory.

Modular Organization of Brain Resting State Networks in Chronic Back Pain Patients

Recent work on functional magnetic resonance imaging large-scale brain networks under resting conditions demonstrated its potential to evaluate the integrity of brain function under normal and pathological conditions. A similar approach is used in this work to study a group of chronic back pain patients and healthy controls to determine the impact of long enduring pain over brain dynamics. Correlation networks were constructed from the mutual partial correlations of brain activitys time series selected from ninety regions using a well validated brain parcellation atlas. The study of the resulting networks revealed an organization of up to six communities with similar modularity in both groups, but with important differences in the membership of key communities of frontal and temporal regions. The bulk of these findings were confirmed by a surprisingly naive analysis based on the pairwise correlations of the strongest and weakest correlated healthy regions. Beside confirming the brain effects of long enduring pain, these results provide a framework to study the effect of other chronic conditions over cortical function.

Somatosensory activity modulation during observation of other's pain and touch

We examined whether somatosensory activity could be modulated by the observation of bodily experiences. For this purpose, somatosensory-evoked potentials elicited by non-painful stimulation were recorded when subjects were viewing a hand penetrated by a needle, touched by a cotton swab or at resting without stimulation. Participants were instructed to adopt an egocentric perspective when viewing the videos and to rate pain intensity and unpleasantness supposedly experienced by the model, as well as the unpleasantness induced by the video clips. Results indicated that pain videos were rated as more unpleasant than touch videos, and that observation of both pain and touch video clips led to a significant enhancement of P50 amplitudes as compared to viewing a hand without stimulation. Moreover, enhanced P50 amplitudes during observation of both pain and touch in others were associated with increased unpleasant ratings induced by the video clips, as well as with high scores in a perspective taking scale (IRI). These findings provide support for the involvement of an attentional bottom-up mechanism which could be responsible to enhance sensory processing of somatic information when observing bodily experiences in others irrespective of whether they are painful or not.

Temporal dissociation in the brain processing of pain and anger faces with different intensities of emotional expression

&NA; Facial expression is one of the most relevant nonverbal behaviors in the communication of pain. However, little is known about brain processing of pain expressions in comparison with other affective facial expressions. The present experiment aimed to examine the effects of pain expression intensity on affective ratings and brain dynamics by recording electroencephalography (EEG) from 20 female healthy volunteers 18–24 years of age. Participants were asked to rate the affective characteristics of 144 stimuli depicting facial expressions of pain and anger with 3 level of intensities (high, mild, and low), as well as neutral faces. Results indicated that pain faces were judged as more unpleasant and arousing than anger and neutral faces for all intensity levels. EEG results further showed that facial expressions of pain elicited more enhanced amplitudes of the visual evoked potentials than anger and neutral faces in the latency between 350 and 550 milliseconds after stimulus onset; whereas anger faces elicited greater P200 amplitudes than pain and neutral faces. In addition, more increased theta activity in the latency of 200 to 400 milliseconds after stimulus onset was observed to high‐intense as compared with low‐intense facial expressions. These findings indicate that brain activity elicited by affective faces is modulated by the intensity of facial expressions and suggest the involvement of different brain mechanisms during the processing and recognition of facial expressions of pain and anger in healthy volunteers. Facial expression is one of the most relevant nonverbal behaviors in the communication of pain. Here, neurophysiological evidence is provided regarding the differential processing of pain and anger faces with high and low intensities of emotional expression, which may provide a framework for future investigations of psychosocial factors involved in the maintenance of chronic pain.

Linear and nonlinear analyses of EEG dynamics during non-painful somatosensory processing in chronic pain patients

The aim of our study was to characterize brain dynamics of affective modulation of somatosensory processing in chronic pain. We hypothesized that chronic pain patients will show abnormal EEG activity under negative mood conditions compared to healthy controls. Nineteen patients with chronic pain and 21 healthy subjects participated in the experiment. Multiscale entropy, fractal dimension, event-related potentials, and fast Fourier transform were used to analyze EEG data. A significant enhancement of entropy was found in pain patients at P4 compared to P3. Analysis of fractal dimension also revealed significantly higher values at P4 than P3 when pain patients were viewing unpleasant pictures. By contrast, no significant differences due to hemisphere or affective condition were found on nonlinear measures for healthy controls. Analyses of somatosensory ERPs showed that P50 amplitudes elicited by pleasant pictures were more reduced in chronic pain patients than in healthy controls. Finally, we observed that EEG band power was lower in pain patients than in healthy controls, in particular for theta and beta bands over sensorimotor cortices and temporal regions when viewing pleasant images. These findings suggest that sustained pain seems to be accompanied by an abnormal activation and dynamic of brain networks related to emotional processing of somatosensory information in chronic pain. Furthermore, our findings suggest that both linear and nonlinear measures of EEG time series may contribute to the understanding of brain dysfunction in chronic pain.

Consideraciones acerca de las alteraciones de la actividad cerebral en pacientes con fibromialgia

La fibromialgia es un trastorno de dolor cronico osteomuscular de etiologia desconocida y caracterizado por dolor generalizado. La investigacion clinica y experimental ha demostrado que los pacientes con fibromialgia pueden presentar un aumento de la sensibilidad para el dolor en varias regiones corporales, junto con alteraciones neuroendocrinas y una activacion anormal de regiones cerebrales implicadas en el dolor. Los datos recientes han demostrado tambien que el procesamiento afectivo y cognitivo de la informacion relacionada con el dolor se encuentra alterado en la fibromialgia. En nuestra opinion, todos estos resultados sugieren la presencia de un procesamiento anormal del dolor en el sistema nervioso central, que podria ser responsable del mantenimiento del dolor cronico en estos pacientes.Fibromyalgia is a chronic musculoskeletal pain disorder of unknown etiology, characterized by widespread pain. Clinical and experimental research has demonstrated that patients with fibromyalgia may have enhanced pain sensitivity at several points of the body, together with neuroendocrine abnormalities, and abnormal activation of pain-related brain regions. Recent data have also shown that affective and cognitive processing of pain-related information could also be disturbed in fibromyalgia. In our opinion, all these findings suggest the existence of abnormal central pain processing, which could be responsible for the persistence of chronic pain in these patients.

Event-related brain responses as correlates of changes in predictive and affective values of conditioned stimuli.

Previous evidence suggests that the judged predictive strength of one cue may be influenced by the predictive strengths of other pretrained cues (prediction errors). In the present study, we examined affective ratings and event-related brain responses from 18 healthy participants during an aversive conditioning task in which affective values of previously trained conditioned stimuli were modified through a blocking procedure. The task was divided into two phases. During the training phase, single stimulus A (e.g., red square) was always followed by aversive picture stimuli, while single stimulus B (e.g., yellow square) was signaling the absence of aversive stimulation. During the blocking phase, compound stimuli consisted of the combination of one single trained stimulus (A or B) and one new somatosensory stimulus were also followed by the presence of aversive stimulation. Results indicated that single stimulus A elicited greater ERP amplitudes and theta power, and was rated as more unpleasant than single stimulus B during the training phase. Moreover, single stimulus B elicited greater ERP amplitudes than stimulus A, as well as greater theta power and more unpleasant ratings during the blocking as compared with the training phase. By contrast, no changes in ERP amplitudes and theta power were observed for stimulus A. Our findings provide neurophysiological and behavioral evidence for an increased affective processing of conditioned stimuli when compound stimuli were introduced, but only if the target CS was previously trained to signal the absence of aversive stimulation.

Corrigendum: Inhibitory Control Impairment on Somatosensory Gating Due to Aging: An Event-Related Potential Study

[This corrects the article DOI: 10.3389/fnhum.2018.00280.].

Inhibitory Control Impairment on Somatosensory Gating Due to Aging: An Event-Related Potential Study

The capacity to suppress irrelevant incoming input, termed sensory gating, is one of the most investigated inhibitory processes associated with cognitive impairments due to aging. The aim of this study was to examine the influence of aging on sensory gating by using somatosensory event-related potentials (ERPs) elicited by repetitive non-painful tactile stimulation (paired-pulsed task). Somatosensory ERPs were recorded in 20 healthy young adults and 20 healthy older adults while they received two identical pneumatic stimuli (S1 and S2) of 100 ms duration with an inter-stimulus interval of 550 ± 50 ms on both forefingers. The difference between the somatosensory ERPs amplitude elicited by S1 and S2 was computed as a sensory gating measure. The amplitude and the latency of P50, N100 and late positive complex (LPC) were analyzed as well as the source generators of the gating effect. Reduced sensory gating was found in older individuals for N100 at frontal and centro-parietal electrodes and for LPC at fronto-central electrodes. Source localization analyses also revealed a reduced current density during gating effect in the older group in frontal areas in N100 and LPC. Moreover, older individuals showed delayed latencies in N100. No significant gating effect differences were found between groups in P50. These findings suggest an age-related slowing of processing speed and a reduced efficiency of inhibitory mechanisms in response to repetitive somatosensory information during stimulus evaluation, and a preservation of processing speed and inhibitory control during early stimulus coding in aging.