Mariela Rance

Brain correlates of stress-induced analgesia

&NA; Stress‐induced analgesia (SIA) refers to a reduced pain response after stress exposure, which is mediated by descending pain‐inhibitory circuits and may be an indicator of adequate centrally mediated pain control. We used functional magnetic resonance imaging to assess brain mechanisms of SIA in 21 healthy participants. Using a block design series of mildly painful pressure stimuli were applied to the left medial phalanx of the second digit during functional magnetic resonance imaging. Mental arithmetic combined with increasing levels of noise was used as a stressor. Verbal ratings, changes in blood pressure and heart rate confirmed the validity of the stress induction. Post‐stress pain thresholds and pain tolerance were significantly higher and post‐stress pain and unpleasantness ratings were significantly lower compared to pre‐stress levels. SIA led to an increase of the blood‐level‐dependent oxygenation response in the primary somatosensory cortex, bilaterally in the anterior insula, and secondary somatosensory cortex. The increase in pain tolerance correlated significantly with activation in the rostral anterior cingulate cortex and pain unpleasantness with activation in the dorsal anterior cingulate cortex. SIA seems to activate similar brain networks as placebo analgesia or analgesia mediated by diffuse noxious inhibitory controls and involved sensory, affective and cognitive modulatory circuits.

Treatment-related changes in brain activation in patients with fibromyalgia syndrome

Little is known about the effects of successful treatment on brain function in chronic pain. This study examined changes in pain-evoked brain activation following behavioral extinction training in fibromyalgia patients. Using functional magnetic resonance imaging, brain activation to painful mechanical stimuli applied to the 2nd phalanx of the left 2nd digit (m. flexor digitorum) was assessed in 10 patients with fibromyalgia syndrome (FM) before and after behavioral extinction training. The behavioral treatment significantly reduced interference from pain in the FM patients. Mechanical pain threshold and pain tolerance increased significantly after treatment. Activation in the insula shifted bilaterally from a more anterior site before treatment to a more posterior location after treatment. The pre- to post-treatment reduction in both interference related to pain and pain severity were significantly associated with bilateral activation in pain-evoked activity in the posterior insula, the ipsilateral caudate nucleus/striatum, the contralateral lenticular nucleus, the left thalamus and the primary somatosensory cortex contralateral to the stimulated side. These data show a relation between successful behavioral treatment and higher activation bilaterally in the posterior insula and in the contralateral primary somatosensory cortex. Future studies should compare responders and non-responders for differential treatment effects and examine in more detail the mechanisms underlying these changes.

Real time fMRI feedback of the anterior cingulate and posterior insular cortex in the processing of pain

Self‐regulation of brain activation using real‐time functional magnetic resonance imaging has been used to train subjects to modulate activation in various brain areas and has been associated with behavioral changes such as altered pain perception. The aim of this study was to assess the comparability of upregulation versus downregulation of activation in the rostral anterior cingulate cortex (rACC) and left posterior insula (pInsL) and its effect on pain intensity and unpleasantness. In a first study, we trained 10 healthy subjects to separately upregulate and downregulate the blood oxygenation level‐dependent response in the rACC or pInsL (six trials on 4 days) in response to painful electrical stimulation. The participants learned to significantly downregulate activation in pInsL and rACC and upregulate pInsL but not rACC. Success in the modulation of one region and direction of the modulation was not significantly correlated with success in another condition, indicating that the ability to control pain‐related brain activation is site‐specific. Less covariation between the areas in response to the nociceptive stimulus was positively correlated with learning success. Upregulation or downregulation of either region was unrelated to pain intensity or unpleasantness; however, our subjects did not learn rACC upregulation, which might be important for pain control. A significant increase in pain unpleasantness was found during upregulation of pInsL when covariation with the rACC was low. These initial results suggest that the state of the network involved in the processing of pain needs to be considered in the modulation of pain‐evoked activation and its behavioral effects. Hum Brain Mapp 35:5784–5798, 2014.

Differential central pain processing following repetitive intramuscular proton/prostaglandin E2 injections in female fibromyalgia patients and healthy controls

BACKGROUND While the etiology of fibromyalgia syndrome (FMS) remains unclear, it is assumed that both peripheral and central components are involved. AIMS/METHODS To investigate central activation patterns following chemically-induced muscle pain we repetitively injected protons (low pH) and prostaglandin E(2) (PGE(2)) in isotonic solution into the left extensor carpi radialis brevis muscle of female FMS patients and female healthy control subjects (HC). The injection of protons/PGE(2) has the advantage that it is not prone to tachyphylaxis compared to capsaicin and hypotonic saline solution. During the repetitive injections continuous pain ratings were recorded and functional magnetic resonance imaging measurements were conducted. RESULTS Injection of protons/PGE(2) led to activation of the anterior and medial cingulate cortices, contralateral primary sensory cortex, bilateral insula and thalamus, left basal ganglia, left orbitofrontal cortex and the cerebellum in FMS patients. In HC, activations were found only in the anterior, medial, and posterior cingulate cortices, and the primary somatosensory cortex. The contrast between the groups revealed significantly stronger activation for FMS patients in the left anterior insula. Peak pain ratings were comparable between HC and FMS patients, but pain duration (sustained pain) was prolonged in FM. CONCLUSION Repetitive proton/PGE(2)-induced excitation of muscle tissue led to a more prolonged perception of pain and more wide-spread activation in pain-related brain areas in FMS, especially in the left (ipsilateral) insula, whereas acute protons/PGE(2)-induced pain processing was similar in the two groups. These data provide further evidence for enhanced central pain processing in FMS patients.Background: While the etiology of fibromyalgia syndrome (FMS) remains unclear, it is assumed that both peripheral and central components are involved.

An augmented reality home-training system based on the mirror training and imagery approach

Mirror training and movement imagery have been demonstrated to be effective in treating several clinical conditions, such as phantom limb pain, stroke-induced hemiparesis, and complex regional pain syndrome. This article presents an augmented reality home-training system based on the mirror and imagery treatment approaches for hand training. A head-mounted display equipped with cameras captures one hand held in front of the body, mirrors this hand, and displays it in real time in a set of four different training tasks: (1) flexing fingers in a predefined sequence, (2) moving the hand into a posture fitting into a silhouette template, (3) driving a “Snake” video game with the index finger, and (4) grasping and moving a virtual ball. The system records task performance and transfers these data to a central server via the Internet, allowing monitoring of training progress. We evaluated the system by having 7 healthy participants train with it over the course of ten sessions of 15-min duration. No technical problems emerged during this time. Performance indicators showed that the system achieves a good balance between relatively easy and more challenging tasks and that participants improved significantly over the training sessions. This suggests that the system is well suited to maintain motivation in patients, especially when it is used for a prolonged period of time.

The Importance of Synchrony and Temporal Order of Visual and Tactile Input for Illusory Limb Ownership Experiences – An fMRI Study Applying Virtual Reality

In the so-called rubber hand illusion, synchronous visuotactile stimulation of a visible rubber hand together with ones own hidden hand elicits ownership experiences for the artificial limb. Recently, advanced virtual reality setups were developed to induce a virtual hand illusion (VHI). Here, we present functional imaging data from a sample of 25 healthy participants using a new device to induce the VHI in the environment of a magnetic resonance imaging (MRI) system. In order to evaluate the neuronal robustness of the illusion, we varied the degree of synchrony between visual and tactile events in five steps: in two conditions, the tactile stimulation was applied prior to visual stimulation (asynchrony of −300 ms or −600 ms), whereas in another two conditions, the tactile stimulation was applied after visual stimulation (asynchrony of +300 ms or +600 ms). In the fifth condition, tactile and visual stimulation was applied synchronously. On a subjective level, the VHI was successfully induced by synchronous visuotactile stimulation. Asynchronies between visual and tactile input of ±300 ms did not significantly diminish the vividness of illusion, whereas asynchronies of ±600 ms did. The temporal order of visual and tactile stimulation had no effect on VHI vividness. Conjunction analyses of functional MRI data across all conditions revealed significant activation in bilateral ventral premotor cortex (PMv). Further characteristic activation patterns included bilateral activity in the motion-sensitive medial superior temporal area as well as in the bilateral Rolandic operculum, suggesting their involvement in the processing of bodily awareness through the integration of visual and tactile events. A comparison of the VHI-inducing conditions with asynchronous control conditions of ±600 ms yielded significant PMv activity only contralateral to the stimulation site. These results underline the temporal limits of the induction of limb ownership related to multisensory body-related input.

Neurofeedback of the difference in activation of the anterior cingulate cortex and posterior insular cortex: two functionally connected areas in the processing of pain

The aim of this study was the analysis of the effect of a learned increase in the dissociation between the rostral anterior cingulate cortex (rACC) and the left posterior insula (pInsL) on pain intensity and unpleasantness and the contribution of each region to the effect, exploring the possibility to influence the perception of pain with neurofeedback methods. We trained ten healthy subjects to increase the difference in the blood oxygenation level-dependent response between the rACC and pInsL to painful electric stimuli. Subjects learned to increase the dissociation with either the rACC (state 1) or the pInsL (state 2) being higher. For feedback we subtracted the signal of one region from the other and provided feedback in four conditions with six trials each yielding two different states: [rACC—pInsL increase (state 1), rACC—pInsL decrease (state 2), pInsL—rACC increase (state 2), pInsL—rACC decrease (state 1)]. Significant changes in the dissociation from trial one to six were seen in all conditions. There were significant changes from trial one to six in the pInsL in three of the four conditions, the rACC showed no significant change. Pain intensity or unpleasantness ratings were unrelated to the dissociation between the regions and the activation in each region. Learning success in the conditions did not significantly correlate and there was no significant correlation between the two respective conditions of one state, i.e., learning to achieve a specific state is not a stable ability. The pInsL seems to be the driving force behind changes in the learned dissociation between the regions. Despite successful differential modulation of activation in areas responsive to the painful stimulus, no corresponding changes in the perception of pain intensity or unpleasantness emerged. Learning to induce different states of dissociation between the areas is not a stable ability since success did not correlate overall or between two conditions of the the same state.

Do Mirror Glasses Have the Same Effect on Brain Activity as a Mirror Box? Evidence from a Functional Magnetic Resonance Imaging Study with Healthy Subjects

Since its original proposal, mirror therapy has been established as a successful neurorehabilitative intervention in several neurological disorders to recover motor function or to relieve pain. Mirror therapy seems to operate by reactivating the contralesional representation of the non-mirrored limb in primary motor- and somatosensory cortex. However, mirror boxes have some limitations which prompted the use of additional mirror visual feedback devices. The present study evaluated the utility of mirror glasses compared to a mirror box. We also tested the hypothesis that increased interhemispheric communication between the motor hand areas is the mechanism by which mirror visual feedback recruits the representation of the non-mirrored limb. Therefore, mirror illusion capacity and brain activations were measured in a within-subject design during both mirror visual feedback conditions in counterbalanced order with 20 healthy subjects inside a magnetic resonance imaging scanner. Furthermore, we analyzed task-dependent functional connectivity between motor hand representations using psychophysiological interaction analysis during both mirror tasks. Neither the subjective quality of mirror illusions nor the patterns of functional brain activation differed between the mirror tasks. The sensorimotor representation of the non-mirrored hand was recruited in both mirror tasks. However, a significant increase in interhemispheric connectivity between the hand areas was only observed in the mirror glasses condition, suggesting different mechanisms for the recruitment of the representation of the non-mirrored hand in the two mirror tasks. We conclude that the mirror glasses might be a promising alternative to the mirror box, as they induce similar patterns of brain activation. Moreover, the mirror glasses can be easy applied in therapy and research. We want to emphasize that the neuronal mechanisms for the recruitment of the affected limb representation might differ depending on conceptual differences between MVF devices. However, our findings need to be validated within specific patient groups.

Which method should be used for brain connectivity analysis

One possible way to examine brain connectivity is to study correlations between signals recorded from different areas. The recent trends couple the signal processing based on data-driven mathematical methods with graph analysis performed on the connectivity matrix. The connectivity matrices can be evaluated by using several methods, and different toolboxes are available. The aim of the proposed platform is to create an embedded environment where it is possible to study brain connectivity through different methods and at the same time to compare the results. For this purpose different procedures are developed: from frequency and lag selection in the case of time or frequency varying analyses, to binary graph creation and binary and weighted graph comparisons. This software is realized with a high level of modularity, making it possible to integrate new analysis methods and clustering approaches.