Clinical and Neurophysiological Effects of Progressive Movement Imagery Training for Pathological Pain.

Movement limitation is a common characteristic of chronic pain such that pain prevents the very movement and activity that is most likely to promote recovery. This is particularly the case for pathological pain states such as complex regional pain syndrome (CRPS). One clinical approach to CRPS that has growing evidence of efficacy involves progressive movement imagery training. Graded Motor Imagery (GMI) targets clinical and neurophysiological effects through a stepwise progression through implicit and explicit movement imagery training, mirror therapy and then functional tasks. Here we review experiences from over 20 years of clinical and research experience with GMI. We situate GMI in terms of its historical underpinnings, the benefits and outstanding challenges of its implementation, its potential application beyond CRPS. We then review the neuropathological targets of GMI and current thought on its effects on neurophysiological biomarkers. PERSPECTIVE: This article provides an overview of our experiences with graded motor imagery training over the last 20 years focussing on the treatment of CRPS. It does both cover the theoretical underpinnings for this treatment approach, biomarkers which indicate potential changes driven by GMI, and experiences for achieving optimal treatment results.

Using motor imagery practice for improving motor performance - A review.

Motor imagery practice is a current trend, but there is a need for a systematic integration of neuroscientific advances in the field. In this review, we describe the technique of motor imagery practice and its neural representation, considering different fields of application. The current practice of individualized motor imagery practice schemes often lacks systematization and is mostly based on experience. We review literature related to motor imagery practice in order to identify relevant modulators of practice effects like previous experience in motor training and motor imagery practice, the type of motor task to be trained, and strategies to increase sensory feedback during physical practice. Relevant discrepancies are identified between neuroscientific findings and practical consideration of these findings. To bridge these gaps, more effort should be directed at analyzing the brain network activities related to practically relevant motor imagery practice interventions.

Modifications in fMRI Representation of Mental Rotation Following a 6 Week Graded Motor Imagery Training in Chronic CRPS Patients.

Complex regional pain syndrome (CRPS) is a neuropathic pain condition that is difficult to treat. For behavioral interventions, graded motor imagery (GMI) showed relevant effects, but underlying neural substrates in patient groups have not been investigated yet. A previous study investigating differences in the representation of a left/right hand judgment task demonstrated less recruitment of subcortical structures, such as the putamen, in CRPS patients than in healthy controls. In healthy volunteers, the putamen activity increased after a hand judgment task training. In order to test for longitudinal effects of GMI training, we investigated 20 CRPS patients in a wait-list crossover design with 3 evaluation time points. Patients underwent a 6 week GMI treatment and a 6 week waiting period in a randomized group assignment and treatment groups were evaluated by a blinded rater. When compared to healthy matched controls at baseline, CRPS patients showed less functional activation in areas processing visual input, left sensorimotor cortex, and right putamen. Only GMI treatment, but not the waiting period showed an effect on movement pain and hand judgment task performance. Regression analyses revealed positive associations of movement pain with left anterior insula activation at baseline. Right intraparietal sulcus activation change during GMI was associated with a gain in performance of the hand judgment task. The design used here is reliable for investigating the functional representation of the hand judgment task in an intervention study. PERSPECTIVE: Twenty chronic CRPS patients underwent a 6 week GMI intervention in a randomized wait-list crossover design. functional MRI was tested pre and post for the hand lateralization task which improved over GMI but not over WAITING. Performance gain was positively related to right parietal functional MRI activation.

Intermittent theta burst stimulation over right somatosensory larynx cortex enhances vocal pitch-regulation in nonsingers.

While the significance of auditory cortical regions for the development and maintenance of speech motor coordination is well established, the contribution of somatosensory brain areas to learned vocalizations such as singing is less well understood. To address these mechanisms, we applied intermittent theta burst stimulation (iTBS), a facilitatory repetitive transcranial magnetic stimulation (rTMS) protocol, over right somatosensory larynx cortex (S1) and a nonvocal dorsal S1 control area in participants without singing experience. A pitch-matching singing task was performed before and after iTBS to assess corresponding effects on vocal pitch regulation. When participants could monitor auditory feedback from their own voice during singing (Experiment I), no difference in pitch-matching performance was found between iTBS sessions. However, when auditory feedback was masked with noise (Experiment II), only larynx-S1 iTBS enhanced pitch accuracy (50-250 ms after sound onset) and pitch stability (>250 ms after sound onset until the end). Results indicate that somatosensory feedback plays a dominant role in vocal pitch regulation when acoustic feedback is masked. The acoustic changes moreover suggest that right larynx-S1 stimulation affected the preparation and involuntary regulation of vocal pitch accuracy, and that kinesthetic-proprioceptive processes play a role in the voluntary control of pitch stability in nonsingers. Together, these data provide evidence for a causal involvement of right larynx-S1 in vocal pitch regulation during singing.

Motor imagery training: Kinesthetic imagery strategy and inferior parietal fMRI activation.

Motor imagery (MI) is the mental simulation of action frequently used by professionals in different fields. However, with respect to performance, well-controlled functional imaging studies on MI training are sparse. We investigated changes in fMRI representation going along with performance changes of a finger sequence (error and velocity) after MI training in 48 healthy young volunteers. Before training, we tested the vividness of kinesthetic and visual imagery. During tests, participants were instructed to move or to imagine moving the fingers of the right hand in a specific order. During MI training, participants repeatedly imagined the sequence for 15 min. Imaging analysis was performed using a full-factorial design to assess brain changes due to imagery training. We also used regression analyses to identify those who profited from training (performance outcome and gain) with initial imagery scores (vividness) and fMRI activation magnitude during MI at pre-test (MIpre ). After training, error rate decreased and velocity increased. We combined both parameters into a common performance index. FMRI activation in the left inferior parietal lobe (IPL) was associated with MI and increased over time. In addition, fMRI activation in the right IPL during MIpre was associated with high initial kinesthetic vividness. High kinesthetic imagery vividness predicted a high performance after training. In contrast, occipital activation, associated with visual imagery strategies, showed a negative predictive value for performance. Our data echo the importance of high kinesthetic vividness for MI training outcome and consider IPL as a key area during MI and through MI training.

Transcutaneous auricular vagal nerve stimulation (taVNS) might be a mechanism behind the analgesic effects of auricular acupuncture.

BACKGROUND: Randomized clinical trials (RCT) demonstrated that auricular acupuncture (AA) is effective in treatment of acute and chronic pain, although the mechanisms behind AA are not elucidated. METHODS: The data concerning the localization of AA points, which are commonly used to treat pain, were extracted from the meta-analysis of 17 RCTs and evaluated using the anatomical map of auricular afferent nerve supply. RESULTS: Fifteen out of 20 specific AA points, used in the treatment of pain, are situated in areas innervated mostly by the auricular branch of the vagal nerve (ABVN), whereas sham stimulation was applied at the helix of the auricle, innervated by cervical nerves. CONCLUSION: Considering the clinical data relating to the anatomy of neural pathways and experimental findings of the mechanisms of transcutaneous auricular vagal nerve stimulation, the analgesic effects of AA may be explained by stimulation of ABVN.

Preliminary findings of cerebral responses on transcutaneous vagal nerve stimulation on experimental heat pain.

Transcutaneous vagal nerve stimulation (TVNS) is a promising complementary method of pain relief. However, the neural networks associated with its analgesic effects are still to be elucidated. Therefore, we conducted two functional magnetic resonance imaging (fMRI) sessions, in a randomized order, with twenty healthy subjects who were exposed to experimental heat pain stimulation applied to the right forearm using a Contact Heat-Evoked Potential Stimulator. While in one session TVNS was administered bilaterally to the concha auriculae with maximal, non-painful intensity, the stimulation device was switched off in the other session (placebo condition). Pain thresholds were measured before and after each session. Heat stimulation elicited fMRI activation in cerebral pain processing regions. Activation magnitude in the secondary somatosensory cortex, posterior insula, anterior cingulate and caudate nucleus was associated with heat stimulation without TVNS. During TVNS, this association was only seen for the right anterior insula. TVNS decreased fMRI signals in the anterior cingulate cortex in comparison with the placebo condition; however, there was no relevant pain reducing effect over the group as a whole. In contrast, TVNS compared to the placebo condition showed an increased activation in the primary motor cortex, contralateral to the site of heat stimulation, and in the right amygdala. In conclusion, in the protocol used here, TVNS specifically modulated the cerebral response to heat pain, without having a direct effect on pain thresholds.

Theoretical Considerations for Chronic Pain Rehabilitation.

Conventional rehabilitation of patients with chronic pain is often not successful and is frustrating for the treatment team. However, theoretical developments and substantial advances in our understanding of the neurological aspects of chronic pain are changing these experiences. Modern theoretical models of pain consider pain to be a perceptual inference that reflects a "best guess" that protective action is required. This article argues that keen observation and open and respectful clinician-patient and scientist-clinician relationships have been critical for the emergence of effective rehabilitation approaches and will be critical for further improvements. The role in modern pain rehabilitation of reconceptualizing the pain itself-by "Explaining Pain," careful and intentional observation of the person in pain, and the strategic and constant communication of safety-is emphasized. It also is suggested that better understanding of the neural mechanisms underpinning chronic pain has directly informed the development of new therapeutic approaches, which are being further refined and tested. Conventional pain treatment (where the clinician strives to find the pain-relieving medication or exercise) or pain management (where the clinician helps the patient to manage life despite unabating pain) is being replaced by pain rehabilitation, where a truly biopsychosocial approach allows clinicians to provide patients with the knowledge, understanding, and skills to reduce both their pain and disability. A brief overview is provided of the key aspects of modern pain rehabilitation and the considerations that should lead our interaction with patients with chronic pain.

Verum and sham acupuncture exert distinct cerebral activation in pain processing areas: a crossover fMRI investigation in healthy volunteers.

Although acupuncture is effective for treating pain, its site-specificity is questioned. The aim was to compare the cerebral responses of needling applied to an acupuncture point to the needling of a sham point, using functional magnetic resonance imaging (fMRI). Twenty-one healthy male volunteers were enrolled. Manual stimulation of the acupuncture (ST44) and sham points on the dorsum of the left foot was applied during fMRI in a crossover manner. fMRI data analysis was performed contrasting the ST44 and the sham conditions. Stimulation intensity, subjective discrimination of the needling site and the incidence of "Qi" sensation were additionally recorded. Stimulation of ST44 acupoint, in comparison to the sham procedure, was associated with an increased fMRI-activation in the primary somatosensory, the inferior parietal and the prefrontal cortex and the posterior insula. Sham needling was associated with increased activation in the anterior cingulate cortex and the anterior insula. Verum acupuncture increased the activity of discriminative somatosensory and cognitive pain processing areas of the brain, whereas sham needling activated the areas responsible for affective processing of pain. This may explain favorable effects of verum acupuncture in clinical studies about treatment of chronic pain patients.

Kinesthetic imagery of musical performance.

Musicians use different kinds of imagery. This review focuses on kinesthetic imagery, which has been shown to be an effective complement to actively playing an instrument. However, experience in actual movement performance seems to be a requirement for a recruitment of those brain areas representing movement ideation during imagery. An internal model of movement performance might be more differentiated when training has been more intense or simply performed more often. Therefore, with respect to kinesthetic imagery, these strategies are predominantly found in professional musicians. There are a few possible reasons as to why kinesthetic imagery is used in addition to active training; one example is the need for mental rehearsal of the technically most difficult passages. Another reason for mental practice is that mental rehearsal of the piece helps to improve performance if the instrument is not available for actual training as is the case for professional musicians when they are traveling to various appearances. Overall, mental imagery in musicians is not necessarily specific to motor, somatosensory, auditory, or visual aspects of imagery, but integrates them all. In particular, the audiomotor loop is highly important, since auditory aspects are crucial for guiding motor performance. All these aspects result in a distinctive representation map for the mental imagery of musical performance. This review summarizes behavioral data, and findings from functional brain imaging studies of mental imagery of musical performance.

Graded motor imagery and the impact on pain processing in a case of CRPS.

OBJECTIVE: Graded motor imagery (GMI) shows promising results for patients with complex regional pain syndrome (CRPS). METHODS: In a case with chronic unilateral CRPS type I, we applied GMI for 6 weeks and recorded clinical parameters and cerebral activation using functional magnetic resonance imaging (fMRI; pre-GMI, after each GMI block, and after 6 mo). Changes in fMRI activity were mapped during movement execution in areas associated with pain processing. A healthy participant served as a control for habituation effects. RESULTS: Pain intensity decreased over the course of GMI, and relief was maintained at follow-up. fMRI during movement execution revealed marked changes in S1 and S2 (areas of discriminative pain processing), which seemed to be associated with pain reduction, but none in the anterior insula and the anterior cingulate cortex (areas of affective pain processing). After mental rotation training, the activation intensity of the posterior parietal cortex was reduced to one third. DISCUSSION: Our case report develops a design capable of differentiating cerebral changes associated with behavioral therapy of CRPS type I study.

Task-dependent interaction between parietal and contralateral primary motor cortex during explicit versus implicit motor imagery.

Both mental rotation (MR) and motor imagery (MI) involve an internalization of movement within motor and parietal cortex. Transcranial magnetic stimulation (TMS) techniques allow for a task-dependent investigation of the interhemispheric interaction between these areas. We used image-guided dual-coil TMS to investigate interactions between right inferior parietal lobe (rIPL) and left primary motor cortex (M1) in 11 healthy participants. They performed MI (right index-thumb pinching in time with a 1 Hz metronome) or hand MR tasks, while motor evoked potentials (MEPs) were recorded from right first dorsal interosseous. At rest, rIPL conditioning 6 ms prior to M1 stimulation facilitated MEPs in all participants, whereas this facilitation was abolished during MR. While rIPL conditioning 12 ms prior to M1 stimulation had no effect on MEPs at rest, it suppressed corticomotor excitability during MI. These results support the idea that rIPL forms part of a distinct inhibitory network that may prevent unwanted movement during imagery tasks.

The brain's relevance detection network operates independently of stimulus modality.

Brain regions associated with the processing of emotional stimuli are often also associated with the processing of social stimuli. Therefore, this network consisting of the amygdala, the anterior insula, the superior temporal sulcus (STS), and the orbitofrontal cortex (OFC) may rather be involved in more general relevance detection which should be independent of the sensory modality of the stimuli. In the current study, we used functional MRI to measure brain activations while participants either viewed pictures that varied in their emotional and social content or listened to sounds that varied along the same dimensions. The amygdala, the anterior insula, the STS, and the OFC showed increased activation during processing of emotional as well as social stimuli independent of the sensory modality in which the stimuli were presented. Moreover, social emotional stimuli elicited more pronounced activity in this network than stimuli with solely emotional or social content. These results indicate that the proposed network involved in relevance detection works independently of the source of relevance (emotional or social information mediated by the stimulus) and modality.

The truth about lying: inhibition of the anterior prefrontal cortex improves deceptive behavior.

Recent neuroimaging studies have indicated a predominant role of the anterior prefrontal cortex (aPFC) in deception and moral cognition, yet the functional contribution of the aPFC to deceptive behavior remains unknown. We hypothesized that modulating the excitability of the aPFC by transcranial direct current stimulation (tDCS) could reveal its functional contribution in generating deceitful responses. Forty-four healthy volunteers participated in a thief role-play in which they were supposed to steal money and then to attend an interrogation with the Guilty Knowledge Test. During the interrogation, participants received cathodal, anodal, or sham tDCS. Remarkably, inhibition of the aPFC by cathodal tDCS did not lead to an impairment of deceptive behavior but rather to a significant improvement. This effect manifested in faster reaction times in telling lies, but not in telling the truth, a decrease in sympathetic skin-conductance response and feelings of guilt while deceiving the interrogator and a significantly higher lying quotient reflecting skillful lying. Increasing the excitability of the aPFC by anodal tDCS did not affect deceptive behavior, confirming the specificity of the stimulation polarity. These findings give causal support to recent correlative data obtained by functional magnetic resonance imaging studies indicating a pivotal role of the aPFC in deception.

When seeing outweighs feeling: a role for prefrontal cortex in passive control of negative affect in blindsight.

Affective neuroscience has been strongly influenced by the view that a 'feeling' is the perception of somatic changes and has consequently often neglected the neural mechanisms that underlie the integration of somatic and other information in affective experience. Here, we investigate affective processing by means of functional magnetic resonance imaging in nine cortically blind patients. In these patients, unilateral postgeniculate lesions prevent primary cortical visual processing in part of the visual field which, as a result, becomes subjectively blind. Residual subcortical processing of visual information, however, is assumed to occur in the entire visual field. As we have reported earlier, these patients show significant startle reflex potentiation when a threat-related visual stimulus is shown in their blind visual field. Critically, this was associated with an increase of brain activity in somatosensory-related areas, and an increase in experienced negative affect. Here, we investigated the patients' response when the visual stimulus was shown in the sighted visual field, that is, when it was visible and cortically processed. Despite the fact that startle reflex potentiation was similar in the blind and sighted visual field, patients reported significantly less negative affect during stimulation of the sighted visual field. In other words, when the visual stimulus was visible and received full cortical processing, the patients' phenomenal experience of affect did not closely reflect somatic changes. This decoupling of phenomenal affective experience and somatic changes was associated with an increase of activity in the left ventrolateral prefrontal cortex and a decrease of affect-related somatosensory activity. Moreover, patients who showed stronger left ventrolateral prefrontal cortex activity tended to show a stronger decrease of affect-related somatosensory activity. Our findings show that similar affective somatic changes can be associated with different phenomenal experiences of affect, depending on the depth of cortical processing. They are in line with a model in which the left ventrolateral prefrontal cortex is a relay station that integrates information about subcortically triggered somatic responses and information resulting from in-depth cortical stimulus processing. Tentatively, we suggest that the observed decoupling of somatic responses and experienced affect, and the reduction of negative phenomenal experience, can be explained by a left ventrolateral prefrontal cortex-mediated inhibition of affect-related somatosensory activity.

Acupuncture reveals no specific effect on primary auditory cortex: a functional magnetic resonance imaging study.

Although acupuncture is effective in the treatment of several clinical conditions, its specificity has been questioned. We studied the effects of needle stimulation applied to 'ear-specific' acupuncture point GB43 on activations in primary auditory cortex using functional magnetic resonance imaging in comparison with sham acupuncture. Twenty healthy volunteers participated in this cross-over investigation. Multi-subject analysis showed no significant activations in the gyrus of Heschl during stimulation of the GB43 point or a sham point. In single-subject analysis, activation within the primary auditory cortex was seen in two out of 20 volunteers. We found no evidence for specificity of acupuncture point GB43 in relation to primary auditory activation, previously suggested by two independent research groups.

Regulation of anterior insular cortex activity using real-time fMRI.

Recent advances in functional magnetic resonance imaging (fMRI) data acquisition and processing techniques have made real-time fMRI (rtfMRI) of localized brain areas feasible, reliable and less susceptible to artefacts. Previous studies have shown that healthy subjects learn to control local brain activity with operant training by using rtfMRI-based neurofeedback. In the present study, we investigated whether healthy subjects could voluntarily gain control over right anterior insular activity. Subjects were provided with continuously updated information of the target ROI's level of activation by visual feedback. All participants were able to successfully regulate BOLD-magnitude in the right anterior insular cortex within three sessions of 4 min each. Training resulted in a significantly increased activation cluster in the anterior portion of the right insula across sessions. An increased activity was also found in the left anterior insula but the percent signal change was lower than in the target ROI. Two different control conditions intended to assess the effects of non-specific feedback and mental imagery demonstrated that the training effect was not due to unspecific activations or non feedback-related cognitive strategies. Both control groups showed no enhanced activation across the sessions, which confirmed our main hypothesis that rtfMRI feedback is area-specific. The increased activity in the right anterior insula during training demonstrates that the effects observed are anatomically specific and self-regulation of right anterior insula only is achievable. This is the first group study investigating the volitional control of emotionally relevant brain region by using rtfMRI training and confirms that self-regulation of local brain activity with rtfMRI is possible.

Volition and imagery in neurorehabilitation.

New interventional approaches have been proposed in the last few years to treat the motor deficits resulting from brain lesions. Training protocols represent the gold-standard of these approaches. However, the degree of motor recovery experienced by most patients remains incomplete. It would be important to improve our understanding of the mechanisms underlying functional recovery. This chapter examines the role of two possible mechanisms that could operate to improve motor function in this setting: volition and motor imagery. It is argued that both represent possible strategies to enhance training effects.

Motor imagery.

We describe general concepts about motor imagery and differences to motor execution. The problem of controlling what the subject actually does during imagery is emphasized. A major part of the chapter is dealing with mental training by imagery and the usage of motor imagination in athletes, musicians and during rehabilitation. Data of altered representations of the body after loss of afferent information and motor representation due to limb amputation or complete spinal cord injury are demonstrated and discussed. Finally we provide an outlook on additional work about motor imagery important for further understanding of the topic.

Modulation of slow cortical potentials by transcranial magnetic stimulation in humans.

We studied the effects of transcranial magnetic stimulation (TMS) on slow cortical potentials (SCPs) of the brain elicited during performance of a feedback and reward task. Ten healthy participants were trained to self-regulate their SCP amplitude using visual feedback and reward for increased or decreased amplitudes. Subjects participated in 27 runs (each comprising 70 trials) under three different conditions: single-pulse TMS delivered with the coil centered over Cz (vertex), over a lateral scalp position (LSP), which increased task difficulty, and in the absence of stimulation. Cz stimulation led to a non-significant enhancement of negative SCPs, while LSP stimulation led to a significant increase of positive SCPs. These results are consistent with the idea that enhanced task difficulty, as in LSP stimulation, enhances cognitive processing load leading to an increase of positive SCPs. Additionally, the data raise the hypothesis that TMS delivered to bilateral midcentral regions could modulate the amplitude of negative SCPs.