The modification of cortical reorganization and chronic pain by sensory feedback

Recent neuroscientific evidence has revealed that the adult brain is capable of substantial plastic change in areas such as the primary somatosensory cortex that were formerly thought to be modifiable only during early experience. We discuss research on phantom limb pain as well as chronic back pain that revealed functional reorganization in both the somatosensory and the motor system in these chronic pain states. In phantom limb pain patients, cortical reorganization is correlated with the amount of phantom limb pain; in low back pain patients the amount of reorganizational change increases with chronicity. We present a model of the development of chronic pain that assumes an important role of somatosensory pain memories. In phantom limb pain, we propose that those patients who experienced intense pain prior to the amputation will later likely develop enhanced cortical reorganization and phantom limb pain. We show that cortical plasticity related to chronic pain can be reduced by behavioral interventions that provide feedback to the brain areas that were altered by somatosensory pain memories.     

Motor cortex representation of the upper-limb in individuals born without a hand

The body schema is an action-related representation of the body that arises from activity in a network of multiple brain areas. While it was initially thought that the body schema developed with experience, the existence of phantom limbs in individuals born without a limb (amelics) led to the suggestion that it was innate. The problem with this idea, however, is that the vast majority of amelics do not report the presence of a phantom limb. Transcranial magnetic stimulation (TMS) applied over the primary motor cortex (M1) of traumatic amputees can evoke movement sensations in the phantom, suggesting that traumatic amputation does not delete movement representations of the missing hand. Given this, we asked whether the absence of a phantom limb in the majority of amelics means that the motor cortex does not contain a cortical representation of the missing limb, or whether it is present but has been deactivated by the lack of sensorimotor experience. In four upper-limb amelic subjects we directly stimulated the arm/hand region of M1 to see 1) whether we could evoke phantom sensations, and 2) whether muscle representations in the two cortices were organised asymmetrically. TMS applied over the motor cortex contralateral to the missing limb evoked contractions in stump muscles but did not evoke phantom movement sensations. The location and extent of muscle maps varied between hemispheres but did not reveal any systematic asymmetries. In contrast, forearm muscle thresholds were always higher for the missing limb side. We suggest that phantom movement sensations reported by some upper limb amelics are mostly driven by vision and not by the persistence of motor commands to the missing limb within the sensorimotor cortex. We propose that prewired movement representations of a limb need the experience of movement to be expressed within the primary motor cortex.     

Action observation treatment: a novel tool in neurorehabilitation

This review focuses on a novel rehabilitation approach known as action observation treatment (AOT). It is now a well-accepted notion in neurophysiology that the observation of actions performed by others activates in the perceiver the same neural structures responsible for the actual execution of those same actions. Areas endowed with this action observation–action execution matching mechanism are defined as the mirror neuron system. AOT exploits this neurophysiological mechanism for the recovery of motor impairment. During one typical session, patients observe a daily action and afterwards execute it in context. So far, this approach has been successfully applied in the rehabilitation of upper limb motor functions in chronic stroke patients, in motor recovery of Parkinson''s disease patients, including those presenting with freezing of gait, and in children with cerebral palsy. Interestingly, this approach also improved lower limb motor functions in post-surgical orthopaedic patients. AOT is well grounded in basic neuroscience, thus representing a valid model of translational medicine in the field of neurorehabilitation. Moreover, the results concerning its effectiveness have been collected in randomized controlled studies, thus being an example of evidence-based clinical practice.     

Increased Muscle Activation Following Motor Imagery During the Rehabilitation of the Anterior Cruciate Ligament

Motor imagery (MI) is the mental representation of an action without any concomitant movement. MI has been used frequently after peripheral injuries to decrease pain and facilitate rehabilitation. However, little is known about the effects of MI on muscle activation underlying the motor recovery. This study aimed to assess the therapeutic effects of MI on the activation of lower limb muscles, as well as on the time course of functional recovery and pain after surgery of the anterior cruciate ligament (ACL). Twelve patients with a torn ACL were randomly assigned to a MI or control group, who both received a series of physiotherapy. Electromyographic activity of the quadriceps, pain, anthropometrical data, and lower limb motor ability were measured throughout a 12-session therapy. The data provided evidence that MI elicited greater muscle activation, even though imagery practice did not result in pain decrease. Muscle activation increase might originate from a redistribution of the central neuronal activity, as there was no anthropometric change in lower limb muscles after imagery practice. This study confirmed the effectiveness of integrating MI in a rehabilitation process by facilitating muscular properties recovery following motor impairment. MI may thus be considered a reliable adjunct therapy to help injured patients to recover motor functions after reconstructive surgery of ACL.     

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.     

A Functional Magnetic Resonance Imaging Study of Pathophysiological Changes Responsible for Mirror Movements in Parkinson’s Disease

Mirror movements correspond to involuntary movements observed in the limb contralateral to the one performing voluntary movement. They can be observed in Parkinson’s disease (PD) but their pathophysiology remains unclear. The present study aims at identifying their neural correlates in PD using functional magnetic resonance imaging. Ten control subjects and 14-off drug patients with asymmetrical right-sided PD were included (8 with left-sided mirror movements during right-hand movements, and 6 without mirror movements). Between-group comparisons of BOLD signal were performed during right-hand movements and at rest (p<0.005 uncorrected). The comparison between PD patients with and without mirror movements showed that mirror movements were associated with an overactivation of the insula, precuneus/posterior cingulate cortex bilaterally and of the left inferior frontal cortex and with a deactivation of the right dorsolateral prefrontal cortex, medial prefrontal cortex, and pre-supplementary motor area and occipital cortex. These data suggest that mirror movements in Parkinson’s disease are promoted by: 1- a deactivation of the non-mirroring inhibitory network (dorsolateral prefrontal cortex, pre-supplementary motor area); 2- an overactivation of prokinetic areas (notably the insula). The concomitant overactivation of a proactive inhibitory network (including the posterior cingulate cortex and precuneus) could reflect a compensatory inhibition of mirror movements.     

Phantom pain reduction by low-frequency and low-intensity electromagnetic fields

Although various treatments have been presented for phantom pain, there is little proof supporting the benefits of pharmacological treatments, surgery or interventional techniques, electroconvulsive therapy, electrical nerve stimulation, far infrared ray therapy, psychological therapies, etc. Here, we report the preliminary results for phantom pain reduction by low-frequency and intensity electromagnetic fields under clinical circumstances. Our method is called as Electromagnetic-Own-Signal-Treatment (EMOST). Fifteen people with phantom limb pain participated. The patients were treated using a pre-programmed, six sessions. Pain intensity was quantified upon admission using a 0–10 verbal numerical rating scale. Most of the patients (n = 10) reported a marked reduction in the intensity of phantom limb pain. Several patients also reported about improvement in their sleep and mood quality, or a reduction in the frequency of phantom pain after the treatments. No improvements in the reduction of phantom limb pain or sleep and mood improvement were reported in the control group (n = 5). Our nonlinear electromagnetic EMOST method may be a possible therapeutic application in the reduction of phantom limb pain. Here, we also suggest that some of the possible effects of the EMOST may be achieved via the redox balance of the body and redox-related neural plasticity.     

Phantom pain reduction by low-frequency and low-intensity electromagnetic fields

Although various treatments have been presented for phantom pain, there is little proof supporting the benefits of pharmacological treatments, surgery or interventional techniques, electroconvulsive therapy, electrical nerve stimulation, far infrared ray therapy, psychological therapies, etc. Here, we report the preliminary results for phantom pain reduction by low-frequency and intensity electromagnetic fields under clinical circumstances. Our method is called as Electromagnetic-Own-Signal-Treatment (EMOST). Fifteen people with phantom limb pain participated. The patients were treated using a pre-programmed, six sessions. Pain intensity was quantified upon admission using a 0-10 verbal numerical rating scale. Most of the patients (n?=?10) reported a marked reduction in the intensity of phantom limb pain. Several patients also reported about improvement in their sleep and mood quality, or a reduction in the frequency of phantom pain after the treatments. No improvements in the reduction of phantom limb pain or sleep and mood improvement were reported in the control group (n?=?5). Our nonlinear electromagnetic EMOST method may be a possible therapeutic application in the reduction of phantom limb pain. Here, we also suggest that some of the possible effects of the EMOST may be achieved via the redox balance of the body and redox-related neural plasticity.     

下肢康复训练方法的研究现状

下肢运动功能障碍严重影响了患者的日常生活及步行的功能,严重时会造成偏瘫等现象,越来越多的研究者致力于寻找新的有效的下肢康复训练方法。目前临床常用的下肢康复训练方法有肌电生物反馈与综合康复训练结合法、针灸联合康复训练法、电刺激疗法和步态训练法。本文针对近年来下肢康复训练方法的多样性进行了系统回顾及总结,尤其对早期介入的减重步态训练康复模式进行了综述及展望。     

Inter-Individual Difference in the Effect of Mirror Reflection-Induced Visual Feedback on Phantom Limb Awareness in Forearm Amputees

Objective

To test whether the phantom limb awareness could be altered by observing mirror reflection-induced visual feedback (MVF) in unilateral forearm amputees.

Methods

Ten unilateral forearm amputees were asked to perform bilateral (intact and phantom) synchronous wrist motions with and without MVF. During wrist motion, electromyographic activities in the extensor digitorum longus (EDL) and flexor carpi radialis muscles (FCR) were recorded with bipolar electrodes. Degree of wrist range of motion (ROM) was also recorded by electrogoniometry attached to the wrist joint of intact side. Subjects were asked to answer the degree of attainment of phantom limb motion using a visual analog scale (VAS: ranging from 0 (hard) to 10 (easy)).

Results

VAS and ROM were significantly increased by utilizing MVF, and the extent of an enhancement of the VAS and wrist ROM was positively correlated (r = 0.72, p<0.05). Although FCR EMG activity also showed significant enhancement by MVF, this was not correlated with the changes of VAS and ROM. Interestingly, while we found negative correlation between EDL EMG activity and wrist ROM, MVF generally affected to be increasing both EDL EMG and ROM.

Conclusions

Although there was larger extent of variability in the effect of MVF on phantom limb awareness, MVF has a potential to enhance phantom limb awareness, in case those who has a difficulty for the phantom limb motion. The present result suggests that the motor command to the missing limb can be re-activated by an appropriate therapeutic strategy such as mirror therapy.     

Bias in amputation research; impact of subjects missed from a prospective study

For research findings to be generalized, a sample must be representative of the actual population of interest. Lower limb amputation is most frequently performed in older patients with vascular disease, a population that is often under-represented in research. The aim of this study was to explore the impact of selection bias by comparing characteristics from a sample included in a prospective study of phantom pain with the actual population who underwent amputation. Only 27% of all potential patients were referred during the first year of the prospective study. The referred patients were 8 years younger (p<0.001) and less likely to have had amputation because of a vascular condition, diabetes or infection (p = 0.003) than those not referred. There was also a significant difference in one year survival between the groups; 67% of referred patients survived compared with just 40% of non-referred patients (p = 0.004). The biased population in the phantom pain study may have resulted in an underestimation of phantom pain in the original study and subsequent protective factors should be considered within the context of the younger population reported. Selection bias is common in amputation research, and research methods to minimize its impact must be given greater attention.     

Mirror symmetric bimanual movement priming can increase corticomotor excitability and enhance motor learning

Repetitive mirror symmetric bilateral upper limb may be a suitable priming technique for upper limb rehabilitation after stroke. Here we demonstrate neurophysiological and behavioural after-effects in healthy participants after priming with 20 minutes of repetitive active-passive bimanual wrist flexion and extension in a mirror symmetric pattern with respect to the body midline (MIR) compared to an control priming condition with alternating flexion-extension (ALT). Transcranial magnetic stimulation (TMS) indicated that corticomotor excitability (CME) of the passive hemisphere remained elevated compared to baseline for at least 30 minutes after MIR but not ALT, evidenced by an increase in the size of motor evoked potentials in ECR and FCR. Short and long-latency intracortical inhibition (SICI, LICI), short afferent inhibition (SAI) and interhemispheric inhibition (IHI) were also examined using pairs of stimuli. LICI differed between patterns, with less LICI after MIR compared with ALT, and an effect of pattern on IHI, with reduced IHI in passive FCR 15 minutes after MIR compared with ALT and baseline. There was no effect of pattern on SAI or FCR H-reflex. Similarly, SICI remained unchanged after 20 minutes of MIR. We then had participants complete a timed manual dexterity motor learning task with the passive hand during, immediately after, and 24 hours after MIR or control priming. The rate of task completion was faster with MIR priming compared to control conditions. Finally, ECR and FCR MEPs were examined within a pre-movement facilitation paradigm of wrist extension before and after MIR. ECR, but not FCR, MEPs were consistently facilitated before and after MIR, demonstrating no degradation of selective muscle activation. In summary, mirror symmetric active-passive bimanual movement increases CME and can enhance motor learning without degradation of muscle selectivity. These findings rationalise the use of mirror symmetric bimanual movement as a priming modality in post-stroke upper limb rehabilitation.     

Complex Regional Pain Syndrome Type I Affects Brain Structure in Prefrontal and Motor Cortex

The complex regional pain syndrome (CRPS) is a rare but debilitating pain disorder that mostly occurs after injuries to the upper limb. A number of studies indicated altered brain function in CRPS, whereas possible influences on brain structure remain poorly investigated.We acquired structural magnetic resonance imaging data from CRPS type I patients and applied voxel-by-voxel statistics to compare white and gray matter brain segments of CRPS patients with matched controls. Patients and controls were statistically compared in two different ways: First, we applied a 2-sample ttest to compare whole brain white and gray matter structure between patients and controls. Second, we aimed to assess structural alterations specifically of the primary somatosensory (S1) and motor cortex (M1) contralateral to the CRPS affected side. To this end, MRI scans of patients with left-sided CRPS (and matched controls) were horizontally flipped before preprocessing and region-of-interest-based group comparison. The unpaired ttest of the “non-flipped” data revealed that CRPS patients presented increased gray matter density in the dorsomedial prefrontal cortex. The same test applied to the “flipped” data showed further increases in gray matter density, not in the S1, but in the M1 contralateral to the CRPS-affected limb which were inversely related to decreased white matter density of the internal capsule within the ipsilateral brain hemisphere. The gray-white matter interaction between motor cortex and internal capsule suggests compensatory mechanisms within the central motor system possibly due to motor dysfunction. Altered gray matter structure in dorsomedial prefrontal cortex may occur in response to emotional processes such as pain-related suffering or elevated analgesic top-down control.     

Treatment of phantom limb pain with combined EMG and thermal biofeedback: a case report

Phantom pain is a frequent consequence of the amputation of an extremity and causes considerable discomfort and disruption of daily activities. This study describes a patient with extreme phantom limb pain following amputation of the right upper limb. The treatment consisted of 6 sessions of EMG biofeedback followed by 6 sessions of temperature biofeedback. The patient did not use a prosthesis and had not received previous treatment for chronic pain. Results demonstrated complete elimination of phantom limb pain after treatment, which was maintained at a 3- and 12-month follow-up. Pain relief covaried with increase in skin temperature at stump and perceptual telescoping (retraction of phantom limb into stump).     

Involuntary movements of the lower extremity following dorsal root entry zone lesions in a man treated for phantom limb pain

A patient developed continuous patterned involuntary movements of abduction-adduction, flexion-extension of his right lower extremity following surgical placement of spinal dorsal root entry zone lesions for the treatment of phantom limb pain. The stereotype movements were monitored by video and electromyographic recording of quadriceps femoris and hamstring muscles. Administration of para-chlorophenylbutyric acid (baclofen) dramatically stopped the involuntary movements and electromyographic silence ensued. Voluntary muscle movements were preserved. The theoretical implications of this unique movement disorder and central patterning of motor activity within the spinal cord are discussed.     

虚拟场景的下肢康复训练系统的设计与实现

大多数的脑卒中患者在下肢运动方面有障碍,给其生活带来了极大的不便,进行及时有效的康复训练是恢复下肢运动功能的关键。传统的下肢康复训练过程中重复性高,患者的参与度低和互动性差。为了解决该问题,本研究设计了一种基于虚拟场景的下肢康复训练系统。该系统实现了结合虚拟现实技术进行下肢康复训练和评估,采集和处理足底压力数据,控制虚拟场景中虚拟元素,显示训练的时间、得分和训练过程中足底压力的最大值、平均值。该系统由下位机硬件和上位机软件构成。硬件系统包括力传感模块和数据采集模块;软件系统是由虚拟场景模块和人机交互模块构成。基于SPSS软件的分析数据结果表明,系统不仅可以准确的采集足底脚掌与脚跟的压力值,而且组内相关系数均大于0.9,系统具有很好的可靠性。本研究的虚拟场景的趣味性很高,能有效地提高患者训练的积极性,并有利于医生制定针对性的康复计划。     

Stroke rehabilitation reaches a threshold

Motor training with the upper limb affected by stroke partially reverses the loss of cortical representation after lesion and has been proposed to increase spontaneous arm use. Moreover, repeated attempts to use the affected hand in daily activities create a form of practice that can potentially lead to further improvement in motor performance. We thus hypothesized that if motor retraining after stroke increases spontaneous arm use sufficiently, then the patient will enter a virtuous circle in which spontaneous arm use and motor performance reinforce each other. In contrast, if the dose of therapy is not sufficient to bring spontaneous use above threshold, then performance will not increase and the patient will further develop compensatory strategies with the less affected hand. To refine this hypothesis, we developed a computational model of bilateral hand use in arm reaching to study the interactions between adaptive decision making and motor relearning after motor cortex lesion. The model contains a left and a right motor cortex, each controlling the opposite arm, and a single action choice module. The action choice module learns, via reinforcement learning, the value of using each arm for reaching in specific directions. Each motor cortex uses a neural population code to specify the initial direction along which the contralateral hand moves towards a target. The motor cortex learns to minimize directional errors and to maximize neuronal activity for each movement. The derived learning rule accounts for the reversal of the loss of cortical representation after rehabilitation and the increase of this loss after stroke with insufficient rehabilitation. Further, our model exhibits nonlinear and bistable behavior: if natural recovery, motor training, or both, brings performance above a certain threshold, then training can be stopped, as the repeated spontaneous arm use provides a form of motor learning that further bootstraps performance and spontaneous use. Below this threshold, motor training is "in vain": there is little spontaneous arm use after training, the model exhibits learned nonuse, and compensatory movements with the less affected hand are reinforced. By exploring the nonlinear dynamics of stroke recovery using a biologically plausible neural model that accounts for reversal of the loss of motor cortex representation following rehabilitation or the lack thereof, respectively, we can explain previously hard to reconcile data on spontaneous arm use in stroke recovery. Further, our threshold prediction could be tested with an adaptive train-wait-train paradigm: if spontaneous arm use has increased in the "wait" period, then the threshold has been reached, and rehabilitation can be stopped. If spontaneous arm use is still low or has decreased, then another bout of rehabilitation is to be provided.     

Activity of pre-entral neurones in conscious monkeys: effects of deafferentation and cerebellar ablation.

After limb deafferentation, there was no gross alteration in the initiation and performance of a sound-triggered ballistic movement. The pattern of neuronal discharge in the arm area of the motor cortex was not significantly modified. In the absence of cerebellum, the reaction time of motor cortex cells was about 150 msec longer than the reaction time observed in normal and deafferented animals. This was associated with an equal retardation in the onset of ENG changes in the limb muscles. This observation is compatible with the idea that the motor cortex is normally situated downstream to the cerebellum in the initiation of some movements. However, the motor cortex is necessary for the initiation and execution of simple sound-triggered movements since its removal results in a permanent inability to perform the task. Finally, in the absence of peripheral feedback, the pattern of motor output to the agonistic and antagonistic muscles was initiated normally and thus appeared to be preprogrammed centrally. The importance of the motor cortex as a "reflex center" in the control of slower movements is obviously not challenged by these observations since the motor task that we have used depends very little or not at all on sensory feedback (Stark, 1968). What these results indicate, however, is that the execution of some voluntary fast ballistic movements can be entirely preprogrammed independently of peripheral and cerebellar influences, and that the program, which is mainly concerned with generating velocity signals, appears to require the integrity of the motor cortex for its execution.