EEG Cortical Neuroimaging during Human Full-Body Movement.

Studying how the human brain functions during full-body movement can increase our understanding of how to diagnose and treat neurological disorders. High-density electroencephalography (EEG) can record brain activity during body movement due to its portability and excellent time resolution. However, EEG is prone to movement artifact, and traditional EEG methods have poor spatial resolution. Combining EEG with independent component analysis (ICA) and inverse source modeling can improve spatial resolution. In my first study, I used EEG and ICA to investigate the biomechanical and neural interplay of performing a complicated cognitive task at different walking speeds. Young, healthy subjects stepped significantly wider when walking with the cognitive task compared to walking alone, but walking speed did not affect cognitive performance (i.e. reaction time and correct responses). EEG results mirrored cognitive performance, in that there were similar event-related desynchronizations in the somatosensory association cortex around encoding at all speeds. For my second study, I addressed the problem of movement artifact in EEG. I created an interface that blocked true electrocortical signals while recording only movement artifact. I quantified the spectral changes in the movement artifact EEG, tested various methods of removing the artifact, and compared their efficacies. Artifact spectral power varied across individuals, electrode locations, and walking speed. None of the cleaning methods removed all artifact. For my third study, I examined cortical spectral power fluctuations and effective connectivity during active and viewed full-body exercise with different combinations of arm and leg effort. Larger spectral fluctuations occurred in the cortex during rhythmic arm exercise compared to rhythmic leg exercise, which suggests that rhythmic arm movement is more cortically driven. The strength and direction of information flow was very similar between the active and viewed exercise conditions, with the right motor cortex being the hub of information flow. These studies provide insight into how the human brain functions during full-body movement and may have applications for rehabilitation after a brain injury or in brain monitoring for improving cognitive performance.PhDBiomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/116622/1/jekline_1.pd

AMPA Receptor Phosphorylation and Synaptic Colocalization on Motor Neurons Drive Maladaptive Plasticity below Complete Spinal Cord Injury.

Clinical spinal cord injury (SCI) is accompanied by comorbid peripheral injury in 47% of patients. Human and animal modeling data have shown that painful peripheral injuries undermine long-term recovery of locomotion through unknown mechanisms. Peripheral nociceptive stimuli induce maladaptive synaptic plasticity in dorsal horn sensory systems through AMPA receptor (AMPAR) phosphorylation and trafficking to synapses. Here we test whether ventral horn motor neurons in rats demonstrate similar experience-dependent maladaptive plasticity below a complete SCI in vivo. Quantitative biochemistry demonstrated that intermittent nociceptive stimulation (INS) rapidly and selectively increases AMPAR subunit GluA1 serine 831 phosphorylation and localization to synapses in the injured spinal cord, while reducing synaptic GluA2. These changes predict motor dysfunction in the absence of cell death signaling, suggesting an opportunity for therapeutic reversal. Automated confocal time-course analysis of lumbar ventral horn motor neurons confirmed a time-dependent increase in synaptic GluA1 with concurrent decrease in synaptic GluA2. Optical fractionation of neuronal plasma membranes revealed GluA2 removal from extrasynaptic sites on motor neurons early after INS followed by removal from synapses 2 h later. As GluA2-lacking AMPARs are canonical calcium-permeable AMPARs (CP-AMPARs), their stimulus- and time-dependent insertion provides a therapeutic target for limiting calcium-dependent dynamic maladaptive plasticity after SCI. Confirming this, a selective CP-AMPAR antagonist protected against INS-induced maladaptive spinal plasticity, restoring adaptive motor responses on a sensorimotor spinal training task. These findings highlight the critical involvement of AMPARs in experience-dependent spinal cord plasticity after injury and provide a pharmacologically targetable synaptic mechanism by which early postinjury experience shapes motor plasticity

Cognition in action: Imaging brain/body dynamics in mobile humans

We have recently developed a mobile brain imaging method (MoBI), that allows for simultaneous recording of brain and body dynamics of humans actively behaving in and interacting with their environment. A mobile imaging approach was needed to study cognitive processes that are inherently based on the use of human physical structure to obtain behavioral goals. This review gives examples of the tight coupling between human physical structure with cognitive processing and the role of supraspinal activity during control of human stance and locomotion. Existing brain imaging methods for actively behaving participants are described and new sensor technology allowing for mobile recordings of different behavioral states in humans is introduced. Finally, we review recent work demonstrating the feasibility of a MoBI system that was developed at the Swartz Center for Computational Neuroscience at the University of California, San Diego, demonstrating the range of behavior that can be investigated with this method. Copyright © 2011 by Walter de Gruyter, Berlin, Boston

Traumatic spinal cord injury; Theranostic applications of advanced MRI techniques

Imaging technology is an important part of the diagnosis and management of spinal trauma. However, many efforts have been made to develop new diagnostic biomarkers through advanced imaging techniques. Unfortunately, there is still no consensus for practical use of biomarkers in SCI patients. The authors conducted an all-encompassing literature review and relevant images were included as examples. Spinal cord and soft-tissue injuries are best evaluated by magnetic resonance imaging (MRI). However, advanced MRI techniques provide researchers with a noninvasive approach that allows evaluation of physiological and biochemical condition of the spinal cord and the brain at cellular and molecular level. The advent of new rehabilitation and treatment strategies could demand more precise and advanced techniques to approach the pathophysiology and anatomy of the spinal cord, offering more accurate and non-invasive support to research and clinical follow up

The current state-of-the-art of spinal cord imaging: methods.

A first-ever spinal cord imaging meeting was sponsored by the International Spinal Research Trust and the Wings for Life Foundation with the aim of identifying the current state-of-the-art of spinal cord imaging, the current greatest challenges, and greatest needs for future development. This meeting was attended by a small group of invited experts spanning all aspects of spinal cord imaging from basic research to clinical practice. The greatest current challenges for spinal cord imaging were identified as arising from the imaging environment itself; difficult imaging environment created by the bone surrounding the spinal canal, physiological motion of the cord and adjacent tissues, and small cross-sectional dimensions of the spinal cord, exacerbated by metallic implants often present in injured patients. Challenges were also identified as a result of a lack of "critical mass" of researchers taking on the development of spinal cord imaging, affecting both the rate of progress in the field, and the demand for equipment and software to manufacturers to produce the necessary tools. Here we define the current state-of-the-art of spinal cord imaging, discuss the underlying theory and challenges, and present the evidence for the current and potential power of these methods. In two review papers (part I and part II), we propose that the challenges can be overcome with advances in methods, improving availability and effectiveness of methods, and linking existing researchers to create the necessary scientific and clinical network to advance the rate of progress and impact of the research

Neurophysiological oscillatory markers of hypoalgesia in conditioned pain modulation

Introduction:Conditioned pain modulation (CPM) is an experimental procedure that consists of an ongoing noxious stimulus attenuating the pain perception caused by another noxious stimulus. A combination of the CPM paradigm with concurrent electrophysiological recordings can establish whether an association exists between experimentally modified pain perception and modulations of neural oscillations.Objectives:We aimed to characterize how CPM modifies pain perception and underlying neural oscillations. We also interrogated whether these perceptual and/or neurophysiological effects are distinct in patients affected by chronic pain.Methods:We presented noxious electrical stimuli to the right ankle before, during, and after CPM induced by an ice pack placed on the left forearm. Seventeen patients with chronic pain and 17 control participants rated the electrical pain in each experimental condition. We used magnetoencephalography to examine the anatomy-specific effects of CPM on the neural oscillatory responses to the electrical pain.Results:Regardless of the participant groups, CPM induced a reduction in subjective pain ratings and neural responses (beta-band [15-35 Hz] oscillations in the sensorimotor cortex) to electrical pain.Conclusion:Our findings of pain-induced beta-band activity may be associated with top-down modulations of pain, as reported in other perceptual modalities. Therefore, the reduced beta-band responses during CPM may indicate changes in top-down pain modulations.</p

Electrophysiological markers for neuropathic pain in spinal cord injured subjects

Physical disability following spinal cord injury (SCI) is the most striking problem noted by the general public. But for the affected subjects urogenital difficulties or depression and pain are often more burdensome. Pain after SCI can have various reasons but only neuropathic pain below the level of lesion (bNP) is thought to be caused by injury of the spinal nervous tissue. This type of pain is in the focus of this thesis. Once bNP has established it is mostly chronic and medication is generally ineffective. Currently, more and more treatments trying to restore function after SCI enter the clinical trial phase. Besides improving function, however, treatments increasing nerve growth in the spinal cord risk to induce or exacerbate bNP. Therefore, observation of bNP is a crucial factor in such interventional studies. A method to objectively supervise bNP has, however, not yet been established. The spinothalamic tract (STT) mainly transmits nociceptive and temperature information in the spinal cord. This tract was dysfunctional in SCI subjects suffering from bNP in clinical examinations. Nevertheless, STT dysfunction was not predictive for bNP and sensory differences between subjects with and without bNP could not be detected. In contrast to clinical examination which is always subjective and only offers limited resolution, electrophysiological measures allow for a more detailed and objective investigation. The novel electrophysiological method of contact heat evoked potentials (CHEP) measures STT function. Establishment of this method was the goal of the first study. The painful stimulation on locations along the spine allowed the calculation of the conduction velocity of the STT in healthy subjects. Furthermore the CHEP latency depended linearly on the heat pain threshold with 1° C higher threshold leading to approximately 10 ms longer latency. It was hypothesized that the rather low heating rate combined with the time-consuming passive heat spread from skin surface to nociceptors was responsible for this. The second study aimed at clarifying this dependence through comparison of the results of study 1 with those of a theoretical heat transfer model. According to this model, 1° C higher pain threshold leads to approximately 15 ms longer CHEP latency. The close similarity between the experimentally determined (study 1) and the computed dependence, proved the influence of the pain threshold on CHEP latency. Summary Electrophysiological markers for Neuropathic Pain in SCI Subjects 2 Subjects suffering from neuropathic pain (NP) in general and not only in SCI, have lowered EEG peak frequency. It was hypothesized in literature that the reduced EEG peak frequency emerged from thalamic deafferentiation and from the ensuing dysrhythmia in thalamocortical feedback loops. Therefore, the third study investigated EEG peak frequency in addition to STT function and compared both between SCI subjects with and without bNP and controls. The STT function (measured with CHEP) below the level of injury was distinctly impaired in SCI compared to control subjects. Furthermore, the EEG peak frequency was generally lower in the SCI subjects. While the CHEP measurements did not reveal differences between subjects with and without bNP, the EEG peak frequency was lowered in subjects with bNP. This difference, however, was only apparent after the linear dependence of EEG peak frequency from the level of SCI was taken into account. In consideration of this dependence, the EEG peak frequency could in future be helpful to supervise bNP both in studies aiming at restoring function or reducing pain after SCI. Currently, the clinical read-out parameter for STT function is pinprick sensation. In the fourth study this pinprick sensation was traced over the first year after SCI. Comparison of this STT function with the bNP state of the same subjects 2-5 years after SCI disclosed larger functional STT recovery in subjects suffering from bNP. Despite the different STT functional recovery, the initial and end measurements did not discriminate between subjects with and without bNP. This was in agreement with earlier studies. The results corroborate the above mentioned hypothesis that new therapies intending to promote sensorimotor recovery after SCI could simultaneously induce bNP by boosting recovery of spinothalamic function

Slow Potentials of the Sensorimotor Cortex during Rhythmic Movements of the Ankle

The objective of this dissertation was to more fully understand the role of the human brain in the production of lower extremity rhythmic movements. Throughout the last century, evidence from animal models has demonstrated that spinal reflexes and networks alone are sufficient to propagate ambulation. However, observations after neural trauma, such as a spinal cord injury, demonstrate that humans require supraspinal drive to facilitate locomotion. To investigate the unique nature of lower extremity rhythmic movements, electroencephalography was used to record neural signals from the sensorimotor cortex during three cyclic ankle movement experiments. First, we characterized the differences in slow movement-related cortical potentials during rhythmic and discrete movements. During the experiment, motion analysis and electromyography were used characterize lower leg kinematics and muscle activation patterns. Second, a custom robotic device was built to assist in passive and active ankle movements. These movement conditions were used to examine the sensory and motor cortical contributions to rhythmic ankle movement. Lastly, we explored the differences in sensory and motor contributions to bilateral, rhythmic ankle movements. Experimental results from all three studies suggest that the brain is continuously involved in rhythmic movements of the lower extremities. We observed temporal characteristics of the cortical slow potentials that were time-locked to the movement. The amplitude of these potentials, localized over the sensorimotor cortex, revealed a reduction in neural activity during rhythmic movements when compared to discrete movements. Moreover, unilateral ankle movements produced unique sensory potentials that tracked the position of the movement and motor potentials that were only present during active dorsiflexion. In addition, the spatiotemporal patterns of slow potentials during bilateral ankle movements suggest similar cortical mechanisms for both unilateral and bilateral movement. Lastly, beta frequency modulations were correlated to the movement-related slow potentials within medial sensorimotor cortex, which may indicate they are of similar cortical origin. From these results, we concluded that the brain is continuously involved in the production of lower extremity rhythmic movements, and that the sensory and motor cortices provide unique contributions to both unilateral and bilateral movemen