Altered fMRI resting-state connectivity in individuals with fibromyalgia on acute pain stimulation.

BACKGROUND: Fibromyalgia is a chronic widespread pain condition, with patients commonly reporting other symptoms such as sleep difficulties, memory complaints and fatigue. The use of magnetic resonance imaging (MRI) in fibromyalgia has allowed for the detection of neural abnormalities, with alterations in brain activation elicited by experimental pain and alterations in resting state connectivity related to clinical pain. METHODS: In this study, we sought to monitor state changes in resting brain connectivity following experimental pressure pain in fibromyalgia patients and healthy controls. Twelve fibromyalgia patients and 15 healthy controls were studied by applying discrete pressure stimuli to the thumbnail bed during MRI. Resting-state functional MRI scanning was performed before and immediately following experimental pressure pain. We investigated changes in functional connectivity to the thalamus and the insular cortex. RESULTS: Acute pressure pain increased insula connectivity to the anterior cingulate and the hippocampus. Additionally, we observed increased thalamic connectivity to the precuneus/posterior cingulate cortex, a known part of the default mode network, in patients but not in controls. This connectivity was correlated with changes in clinical pain. CONCLUSIONS: These data reporting changes in resting-state brain activity following a noxious stimulus suggest that the acute painful stimuli may contribute to the alteration of the neural signature of chronic pain. WHAT DOES THIS STUDY/ADD?: In this study acute pain application shows an echo in functional connectivity and clinical pain changes in chronic pain.

Kinematic analysis of a Duchenne smile.

OBJECTIVE: Facial expressions are communicative motor outputs, whose kinematics likely are due to musculoskeletal anatomy, neuromotor activity and the well-being and internal states of the individual. However, little has been published on the kinematics of facial expression. This study quantified lip, eye and cheek movements during the production of a Duchenne smile involving movement of lips and tissues surrounding the eyes. DESIGN: The three-dimensional positions of 20 markers placed around the eyes, cheeks, lips and chins of 24 young adult female subjects were digitized while they performed smiles after practicing to feedback from an investigator trained in the facial action coding system (FACS). Displacement, velocity and acceleration variables were extracted and analyzed from the markers. RESULTS: Results demonstrated several consistencies across subjects including: (1) relatively high peak velocities, accelerations and displacements for lip and cheek markers in the vertical and anteroposterior dimensions, (2) relatively large movements of the lower lateral eye region compared with other eye regions. CONCLUSION: The results indicate that there is significant movement in the anteroposterior dimension that is not observable in frontal views of the face alone.

Resting state connectivity correlates with drug and placebo response in fibromyalgia patients.

Fibromyalgia is a chronic pain syndrome characterized by widespread pain, fatigue, and memory and mood disturbances. Despite advances in our understanding of the underlying pathophysiology, treatment is often challenging. New research indicates that changes in functional connectivity between brain regions, as can be measured by magnetic resonance imaging (fcMRI) of the resting state, may underlie the pathogenesis of this and other chronic pain states. As such, this parameter may be able to be used to monitor changes in brain function associated with pharmacological treatment, and might also be able to predict treatment response. We performed a resting state fcMRI trial using a randomized, placebo-controlled, cross-over design to investigate mechanisms of action of milnacipran (MLN), a selective serotonin and norepinephrine reuptake inhibitor (SNRI), in fibromyalgia patients. Our aim was to identify functional connectivity patterns at baseline that would differentially predict treatment response to MLN as compared to placebo. Since preclinical studies of MLN suggest that this medication works by augmenting antinociceptive processes, we specifically investigated brain regions known to be involved in pain inhibition. 15 fibromyalgia patients completed the study, consisting of 6 weeks of drug and placebo intake (order counterbalanced) with an interspersed 2 week wash out period. As a main finding we report that reductions in clinical pain scores during MLN were associated with decreased functional connectivity between pro-nociceptive regions and antinociceptive pain regions at baseline, specifically between the rostral part of the anterior cingulate cortex (ACC) and the insular cortex (IC), as well as between the periaqueductal gray (PAG) and the IC: patients with lower preexisting functional connectivity had the greatest reduction in clinical pain. This pattern was not observed for the placebo period. However a more robust placebo response was associated with lower baseline functional connectivity between the ACC and the dorsolateral prefrontal cortex. This study indicates that ACC-IC connectivity might play a role in the mechanism of action of MLN, and perhaps more importantly fcMRI might be a useful tool to predict pharmacological treatment response.

Functional connectivity of human chewing: an fcMRI study.

Mastication is one of the most important orofacial functions. The neurobiological mechanisms of masticatory control have been investigated in animal models, but less so in humans. This project used functional connectivity magnetic resonance imaging (fcMRI) to assess the positive temporal correlations among activated brain areas during a gum-chewing task. Twenty-nine healthy young-adults underwent an fcMRI scanning protocol while they chewed gum. Seed-based fcMRI analyses were performed with the motor cortex and cerebellum as regions of interest. Both left and right motor cortices were reciprocally functionally connected and functionally connected with the post-central gyrus, cerebellum, cingulate cortex, and precuneus. The cerebellar seeds showed functional connections with the contralateral cerebellar hemispheres, bilateral sensorimotor cortices, left superior temporal gyrus, and left cingulate cortex. These results are the first to identify functional central networks engaged during mastication.

Brain activity and human unilateral chewing: an FMRI study.

Brain mechanisms underlying mastication have been studied in non-human mammals but less so in humans. We used functional magnetic resonance imaging (fMRI) to evaluate brain activity in humans during gum chewing. Chewing was associated with activations in the cerebellum, motor cortex and caudate, cingulate, and brainstem. We also divided the 25-second chew-blocks into 5 segments of equal 5-second durations and evaluated activations within and between each of the 5 segments. This analysis revealed activation clusters unique to the initial segment, which may indicate brain regions involved with initiating chewing. Several clusters were uniquely activated during the last segment as well, which may represent brain regions involved with anticipatory or motor events associated with the end of the chew-block. In conclusion, this study provided evidence for specific brain areas associated with chewing in humans and demonstrated that brain activation patterns may dynamically change over the course of chewing sequences.

Posterior insular molecular changes in myofascial pain.

Temporomandibular disorders (TMD) include craniocervical pain conditions with unclear etiologies. Central changes are suspected; however, few neuroimaging studies of TMD exist. Single-voxel proton magnetic resonance spectroscopy ((1)H-MRS) was used before and after pressure-pain testing to assess glutamate (Glu), glutamine (Gln), N-acetylaspartate (NAA), and choline (Cho) levels in the right and left posterior insulae of 11 individuals with myofascial TMD and 11 matched control individuals. Glu levels were significantly lower in all individuals after pain testing. Among those with TMD, left-insular Gln levels were related to reported pain, left posterior insular NAA and Cho levels were significantly higher at baseline than in control individuals, and NAA levels were significantly correlated with pain-symptom duration, suggesting adaptive changes. The results suggest that significant central cellular and molecular changes can occur in individuals with TMD.