Human Studies

A fundamental organizing principle in the somatosensory and motor systems is somatotopy, where specific body parts are represented separately and adjacently to other body parts, resulting in a body map. Different terminals of the sensorimotor network show varied somatotopic layouts, in which the relative position, distance and overlap between body-part representations differ. Since somatotopy is best characterized in the primary somatosensory (S1) and motor (M1) cortices, these terminals have been the main focus of research on somatotopic remapping following loss of sensory input (e.g. arm amputation). Cortical remapping is generally considered to be driven by the layout of the underlying somatotopy, such that neighboring body-part representations tend to activate the deprived brain region. Here, we challenge the assumption that somatotopic layout restricts remapping, by comparing patterns of remapping in humans born without one hand (hereafter, one-handers, n=26) across multiple terminals of the sensorimotor pathway. We first report that in the cerebellum of one-handers, the deprived hand region represents multiple body parts. Importantly, the representations of some of these body parts do not neighbor the deprived hand region. We further replicate our previous finding, showing a similar pattern of remapping in the deprived hand region of the cerebral cortex in one-handers. Finally, we report preliminary results of a similar remapping pattern in the putamen of one-handers. Since these three sensorimotor terminals (cerebellum, cerebrum, putamen) contain different somatotopic layouts, the parallel remapping they undergo demonstrates that the mere spatial layout of body-part representations may not exclusively dictate remapping in the sensorimotor systems.When a hand is missing, the brain region that typically processes information from that hand may instead process information from other body-parts, a phenomenon termed remapping. It is commonly thought that only body-parts whose information is processed in regions neighboring the hand region could "take up" the resources of this now deprived region. Here we demonstrate that information from multiple body-parts is processed in the hand regions of both the cerebral cortex and cerebellum. The native brain regions of these body-parts have varying levels of overlap with the hand region across multiple terminals in the sensorimotor hierarchy, and do not necessarily neighbor the hand region. We therefore propose that proximity between brain regions does not limit brain remapping.

Fibromyalgia (FM) is characterized by pain and fatigue, particularly during physical activity. Transcutaneous electrical nerve stimulation (TENS) activates endogenous pain inhibitory mechanisms. We evaluated if using TENS during activity would improve movement-evoked pain and other patient-reported outcomes in women with FM.

Recent resting-state fMRI studies associated extensive musical training with increased insula-based connectivity in large-scale networks involved in salience, emotion, and higher-order cognitive processes. Similar changes have also been found in chronic pain patients, suggesting that both types of experiences can have comparable effects on insula circuitries. Based on these observations, the current study asked the question whether, and if so in what way, different forms of experience-dependent neuroplasticity may interact. Here we assessed insula-based connectivity during fMRI resting-state between musicians and non-musicians both with and without chronic pain, and correlated the results with clinical pain duration and intensity. As expected, insula connectivity was increased in chronic pain non-musicians relative to healthy non-musicians (with cingulate cortex and supplementary motor area), yet no differences were found between chronic pain non-musicians and healthy musicians. In contrast, musicians with chronic pain showed decreased insula connectivity relative to both healthy musicians (with sensorimotor and memory regions) and chronic pain non-musicians (with the hippocampus, inferior temporal gyrus, and orbitofrontal cortex), as well as lower pain-related inferences with daily activities. Pain duration correlated positively with insula connectivity only in non-musicians, whereas pain intensity exhibited distinct relationships across groups. We conclude that although music-related sensorimotor training and chronic pain, taken in isolation, can lead to increased insula-based connectivity, their combination may lead to higher-order plasticity (metaplasticity) in chronic pain musicians, engaging brain mechanisms that can modulate the consequences of maladaptive experience-dependent neural reorganization (i.e., pain chronification).

A prospective observational study.

It has long been thought that severe chronic pain conditions, such as Complex Regional Pain Syndrome (CRPS), are not only associated with, but even maintained by a reorganisation of the somatotopic representation of the affected limb in primary somatosensory cortex (S1). This notion has driven treatments that aim to restore S1 representations, such as sensory discrimination training and mirror therapy. However, this notion is based on both indirect and incomplete evidence obtained with imaging methods with low spatial resolution. Here, we used functional MRI to characterize the S1 representation of the affected and unaffected hand in humans (of either sex) with unilateral CRPS. The cortical area, location, and geometry of the S1 representation of the CRPS hand were largely comparable to those of the healthy hand and controls. We found no differential relation between affected vs. unaffected hand map measures and clinical measures (pain severity, upper limb disability, disease duration). Thus, if any map reorganization occurs, it does not appear to be directly related to pain and disease severity. These findings compel us to reconsider the cortical mechanisms underlying CRPS and the rationale for interventions that aim to "restore" somatotopic representations to treat pain.This study shows that the spatial map of the fingers in S1 is largely preserved in chronic CRPS. These findings challenge the treatment rationale for restoring somatotopic representations in CRPS patients.

The over-prescription and overuse of opioid analgesics for chronic non-cancer pain (CNCP) is a growing issue. Synthesis of evidence about the barriers and enablers to reducing long-term opioid prescribing and use will enable the development of tailored interventions to address both problems.

To define the clinicopathologic features of amphiphysin-immunoglobulin G (IgG)-mediated neuropathy.