Nicholas Fallon

Structural alterations in brainstem of fibromyalgia syndrome patients correlate with sensitivity to mechanical pressure

Fibromyalgia syndrome is a chronic pain disorder characterised by widespread pain and tenderness in muscles and deep tissues. Current theories regarding the pathophysiological origins of fibromyalgia syndrome point towards central sensitisation and a decreased capacity of descending nociceptive controls. Morphological alterations to subcortical brain regions may contribute to such pathophysiological mechanisms, and to pain and other symptoms seen in fibromyalgia. Therefore, we evaluated geometric differences in subcortical structures in fibromyalgia patients relative to healthy people using a novel method of shape analysis. Sixteen female fibromyalgia patients and 15 age and sex matched, healthy control subjects underwent high-resolution T1-weighted magnetic resonance image scanning. Data was analysed using shape analysis of 15 subcortical regions and standard voxel-based morphometry analysis. Fibromyalgia syndrome patients, relative to healthy control participants, exhibited alterations to the shape of the left lateral aspect of the lower brainstem (medulla). The mean total volume of the brainstem was also found to be significantly reduced in the patient group compared to healthy control subjects, and this brainstem volume reduction in patient group significantly correlated with clinical manual tender point scale scores. Voxel-based morphometry analysis revealed that patients also demonstrated decreased local grey matter volumes in the brainstem (pons) and left precuneus, and increased grey matter volumes in bilateral primary somatosensory cortices. Results suggest that the volume reduction and associated geometric shape alterations seen in the brainstem of the patient group may contribute to sensitivity to pressure pain in fibromyalgia syndrome. This finding may be due to structure-related deficiencies in regions subserving descending nociceptive control.

Emotional modulation of experimental pain: a source imaging study of laser evoked potentials

Negative emotions have been shown to augment experimental pain. As induced emotions alter brain activity, it is not clear whether pain augmentation during noxious stimulation would be related to neural activation existing prior to onset of a noxious stimulus or alternatively, whether emotional stimuli would only alter neural activity during the period of nociceptive processing. We analyzed the spatio-temporal patterns of laser evoked potentials (LEPs) occurring prior to and during the period of cortical processing of noxious laser stimuli during passive viewing of negative, positive, or neutral emotional pictures. Independent component analysis (ICA) was applied to series of source activation volumes, reconstructed using local autoregressive average model (LAURA). Pain was the strongest when laser stimuli were associated with negative emotional pictures. Prior to laser stimulus and during the first 100 ms after onset of laser stimulus, activations were seen in the left and right medial temporal cortex, cerebellum, posterior cingulate, and rostral cingulate/prefrontal cortex. In all these regions, positive or neutral pictures showed stronger activations than negative pictures. During laser stimulation, activations in the right and left anterior insula, temporal cortex and right anterior and posterior parietal cortex were stronger during negative than neutral or positive emotional pictures. Results suggest that negative emotional stimuli increase activation in the left and right anterior insula and temporal cortex, and right posterior and anterior parietal cortex only during the period of nociceptive processing. The role of background brain activation in emotional modulation of pain appears to be only permissive, and consisting in attenuation of activation in structures maintaining the resting state of the brain.

Differential effects of hunger and satiety on insular cortex and hypothalamic functional connectivity.

The insula cortex and hypothalamus are implicated in eating behaviour, and contain receptor sites for peptides and hormones controlling energy balance. The insula encompasses multi‐functional subregions, which display differential anatomical and functional connectivities with the rest of the brain. This study aimed to analyse the effect of fasting and satiation on the functional connectivity profiles of left and right anterior, middle, and posterior insula, and left and right hypothalamus. It was hypothesized that the profiles would be altered alongside changes in homeostatic energy balance. Nineteen healthy participants underwent two 7‐min resting state functional magnetic resonance imaging scans, one when fasted and one when satiated. Functional connectivity between the left posterior insula and cerebellum/superior frontal gyrus, and between left hypothalamus and inferior frontal gyrus was stronger during fasting. Functional connectivity between the right middle insula and default mode structures (left and right posterior parietal cortex, cingulate cortex), and between right hypothalamus and superior parietal cortex was stronger during satiation. Differences in blood glucose levels between the scans accounted for several of the altered functional connectivities. The insula and hypothalamus appear to form a homeostatic energy balance network related to cognitive control of eating; prompting eating and preventing overeating when energy is depleted, and ending feeding or transferring attention away from food upon satiation. This study provides evidence of a lateralized dissociation of neural responses to energy modulations.

Modulation of pain by emotional sounds: a laser-evoked potential study.

Previous studies have shown increases in experimental pain during induction of a negative emotion with visual stimuli, verbal statements or unpleasant odours. The goal of the present study was to analyse the spatio‐temporal activation patterns underlying pain augmentation during negative emotional sounds.

Ipsilateral cortical activation in fibromyalgia patients during brushing correlates with symptom severity.

OBJECTIVE To evaluate cortical activation patterns during mechanical-tactile stimulation in fibromyalgia syndrome (FMS) patients and to correlate cortical activation changes with clinical symptoms. METHODS Nineteen female FMS patients and 18 matched, healthy control subjects underwent EEG examination during brushing stimulation of the right forearm. Participants rated any pain experienced and underwent a manual tender point scale (MTPS) examination. Amplitude changes of cortical rhythms during brushing were analysed in alpha (8-13 Hz) and beta (16-24 Hz) frequency bands. RESULTS Thirteen patients reported pain during brushing. Independent t-test comparison of event related desynchronisation (ERD) during brushing revealed a cluster of electrodes over ipsilateral (right) central-parietal region which demonstrated ERD in patients only. Clinical MTPS scores correlated with beta-band ERD in this cluster of electrodes. Beamformer analysis revealed a widespread array of source activations in patients, including bilateral insula and primary and secondary somatosensory cortices. Control subject source activations were limited to contralateral (left) hemisphere. CONCLUSIONS Results indicate ipsilateral cortical activations in FMS patients, but not in healthy controls, during brushing. Ipsilateral ERD during brushing is associated with MTPS score suggesting abnormal processing of somatosensory input which may contribute to clinical pain. SIGNIFICANCE Altered functioning in FMS may reflect physiological changes in response to afferent somatosensory information manifesting in chronic pain.

Functional Connectivity with the Default Mode Network Is Altered in Fibromyalgia Patients.

Fibromyalgia syndrome (FMS) patients show altered connectivity with the network maintaining ongoing resting brain activity, known as the default mode network (DMN). The connectivity patterns of DMN with the rest of the brain in FMS patients are poorly understood. This study employed seed-based functional connectivity analysis to investigate resting-state functional connectivity with DMN structures in FMS. Sixteen female FMS patients and 15 age-matched, healthy control subjects underwent T2-weighted resting-state MRI scanning and functional connectivity analyses using DMN network seed regions. FMS patients demonstrated alterations to connectivity between DMN structures and anterior midcingulate cortex, right parahippocampal gyrus, left superior parietal lobule and left inferior temporal gyrus. Correlation analysis showed that reduced functional connectivity between the DMN and the right parahippocampal gyrus was associated with longer duration of symptoms in FMS patients, whereas augmented connectivity between the anterior midcingulate and posterior cingulate cortices was associated with tenderness and depression scores. Our findings demonstrate alterations to functional connectivity between DMN regions and a variety of regions which are important for pain, cognitive and emotional processing in FMS patients, and which may contribute to the development or maintenance of chronic symptoms in FMS.

Effects of motor response expectancy on cortical processing of noxious laser stimuli.

Previous studies have shown pain reductions during motor cortex stimulation or voluntary movements. To shed more light on cortical changes associated with decreases in pain during heightened level of motor preparedness in absence of movement, we decided to analyse the effects of motor readiness on EEG laser-evoked potentials (LEPs) by manipulating the expectancy of motor responses. Noxious laser stimuli were administered to the right hand in absence of any movements during periods associated with either high or no expectancy of motor response (HMRE or NMRE, respectively). Subjects reported greater pain intensity during NMRE than HMRE trials. The N1 component of LEPs, peaking at 141 ms and generated in the contralateral operculo-insular cortex, was larger during HMRE than NMRE periods. The amplitude of the N1 component during NMRE correlated with pain intensity. The P2 component peaked earlier during HMRE (336 ± 30ms) than NMRE (356 ± 29 ms, P<0.05) condition and its amplitude showed statistically significant positive correlation with subjective pain intensity. Results suggest that pain reduction during high motor expectancy may be related to summation of effects of motor readiness and nociceptive processing in operculo-insular cortex. Subjective pain intensity appears to be formed at an early, sensory stage of processing of laser stimulus in the absence of motor task and only later, during the period in which multiple behavioural challenges are evaluated, if motor readiness is heightened.

Pleasant and Unpleasant Odors Influence Hedonic Evaluations of Human Faces: An Event-Related Potential Study.

Odors can alter hedonic evaluations of human faces, but the neural mechanisms of such effects are poorly understood. The present study aimed to analyze the neural underpinning of odor-induced changes in evaluations of human faces in an odor-priming paradigm, using event-related potentials (ERPs). Healthy, young participants (N = 20) rated neutral faces presented after a 3 s pulse of a pleasant odor (jasmine), unpleasant odor (methylmercaptan), or no-odor control (clean air). Neutral faces presented in the pleasant odor condition were rated more pleasant than the same faces presented in the no-odor control condition, which in turn were rated more pleasant than faces in the unpleasant odor condition. Analysis of face-related potentials revealed four clusters of electrodes significantly affected by odor condition at specific time points during long-latency epochs (600−950 ms). In the 620−640 ms interval, two scalp-time clusters showed greater negative potential in the right parietal electrodes in response to faces in the pleasant odor condition, compared to those in the no-odor and unpleasant odor conditions. At 926 ms, face-related potentials showed greater positivity in response to faces in the pleasant and unpleasant odor conditions at the left and right lateral frontal-temporal electrodes, respectively. Our data shows that odor-induced shifts in evaluations of faces were associated with amplitude changes in the late (>600) and ultra-late (>900 ms) latency epochs. The observed amplitude changes during the ultra-late epoch are consistent with a left/right hemisphere bias towards pleasant/unpleasant odor effects. Odors alter evaluations of human faces, even when there is a temporal lag between presentation of odors and faces. Our results provide an initial understanding of the neural mechanisms underlying effects of odors on hedonic evaluations.

Altered theta oscillations in resting EEG of fibromyalgia syndrome patients

Fibromyalgia syndrome (FM) is a chronic pain disorder characterized by widespread pain, sleep disturbance, fatigue and cognitive/affective symptoms. Functional imaging studies have revealed that FM and other chronic pain syndromes can affect resting brain activity. This study utilized electroencephalographic (EEG) recordings to investigate the relative power of ongoing oscillatory activity in the resting brain.

Unpleasant odors increase aversion to monetary losses.

Loss aversion is the tendency to prefer avoiding losses over acquiring gains of equal nominal values. Unpleasant odors not only influence affective state but have also been shown to activate brain regions similar to those mediating loss aversion. Therefore, we hypothesized a stronger loss aversion in a monetary gamble task if gambles were associated with an unpleasant as opposed to pleasant odor. In thirty human subjects, unpleasant (methylmercaptan), pleasant (jasmine), and neutral (clean air) odors were presented for 4 s. At the same time, uncertain gambles offering an equal chance of gain or loss of a variable amount of money, or a prospect of an assured win were displayed. One hundred different gambles were presented three times, each time paired with a different odor. Loss aversion, risk aversion, and logit sensitivity were evaluated using non-linear fitting of individual gamble decisions. Loss aversion was larger when prospects were displayed in the presence of methylmercaptan compared to jasmine or clean air. Moreover, individual differences in changes in loss aversion to the unpleasant as compared to pleasant odor correlated with odor pleasantness but not with odor intensity. Skin conductance responses to losses during the outcome period were larger when gambles were associated with methylmercaptan compared to jasmine. Increased loss aversion while perceiving an unpleasant odor suggests a dynamic adjustment of loss aversion toward greater sensitivity to losses. Given that odors are biological signals of hazards, such adjustment of loss aversion may have adaptive value in situations entailing threat or danger.