The role of spinal manipulation in addressing disordered sensorimotor integration and altered motor control

This review provides an overview of some of the growing body of research on the effects of spinal manipulation on sensory processing, motor output, functional performance and sensorimotor integration. It describes a body of work using somatosensory evoked potentials (SEPs), transcranial magnetic nerve stimulation, and electromyographic techniques to demonstrate neurophysiological changes following spinal manipulation. This work contributes to the understanding of how an initial episode(s) of back or neck pain may lead to ongoing changes in input from the spine which over time lead to altered sensorimotor integration of input from the spine and limbs.     

Design,Fabrication, and Administration of the Hand Active Sensation Test (HASTe)

The concept of personalizing neurologic rehabilitation, based on individual impairments, has experienced a recent surge. In parallel, the number of outcome measures of upper extremity motor performance has grown. However, clinicians and researchers lack practical, quantitative measures of the hand’s natural role as a receptor of the environment. The Hand Active Sensation Test (HASTe), developed by Williams and colleagues in 2006, is a valid and reliable measure of haptic performance. Though not available commercially, the HASTe can be fabricated from inexpensive materials, and it has been used successfully to identify impairments in haptic touch in individuals with stroke. (Williams, 2006). This paper presents the methods of design and fabrication of the HASTe testing kit, as well as a visual screen to be used during administration, and instructions for the tests administration and scoring.     

Human glial-restricted progenitor transplantation into cervical spinal cord of the SOD1 mouse model of ALS

Cellular abnormalities are not limited to motor neurons in amyotrophic lateral sclerosis (ALS). There are numerous observations of astrocyte dysfunction in both humans with ALS and in SOD1(G93A) rodents, a widely studied ALS model. The present study therapeutically targeted astrocyte replacement in this model via transplantation of human Glial-Restricted Progenitors (hGRPs), lineage-restricted progenitors derived from human fetal neural tissue. Our previous findings demonstrated that transplantation of rodent-derived GRPs into cervical spinal cord ventral gray matter (in order to target therapy to diaphragmatic function) resulted in therapeutic efficacy in the SOD1(G93A) rat. Those findings demonstrated the feasibility and efficacy of transplantation-based astrocyte replacement for ALS, and also show that targeted multi-segmental cell delivery to cervical spinal cord is a promising therapeutic strategy, particularly because of its relevance to addressing respiratory compromise associated with ALS. The present study investigated the safety and in vivo survival, distribution, differentiation, and potential efficacy of hGRPs in the SOD1(G93A) mouse. hGRP transplants robustly survived and migrated in both gray and white matter and differentiated into astrocytes in SOD1(G93A) mice spinal cord, despite ongoing disease progression. However, cervical spinal cord transplants did not result in motor neuron protection or any therapeutic benefits on functional outcome measures. This study provides an in vivo characterization of this glial progenitor cell and provides a foundation for understanding their capacity for survival, integration within host tissues, differentiation into glial subtypes, migration, and lack of toxicity or tumor formation.     

Electrophysiological Analysis of Transmission Via Spinal Pathways After Vertebral Trauma

Complex electrophysiological examination of the state of spinal neuronal mechanisms was carried out in patients after complicated vertebral trauma (n = 52). Electromyographic responses of the muscles of the upper and lower limbs evoked by stimulation of the peripheral nerves, effects of magnetic stimulation (MS) of the brain cortex (transcranial MS, TMS) and spinal roots, and somatosensory evoked potentials (SSEPs) were recorded. Partial disorders of the motor functions of the lower limbs were observed in 21 patients. Subjects with complete absence of movements of the limbs demonstrated two variants of the patterns of electrophysiological phenomena. In 21 patients, evoked potentials were entirely absent, while reduced MS-evoked motor responses (MS MRs) and SSEPs could be observed in 10 subjects. The presence of these potentials was indicative of partial preservation of the cerebrospinal pathways after damage to the spinal cord. Thus, estimation of the results of complex electrophysiological examination allows one to objectively verify the state and dynamics of transmission via the spinal pathways, to make justified the tactics of treatment, and to estimate the efficacy of the measures directed toward recovery of the lost functions of spinal mechanisms.     

Action Possibility Judgments of People with Varying Motor Abilities Due to Spinal Cord Injury

Predictions about one''s own action capabilities as well as the action capabilities of others are thought to be based on a simulation process involving linked perceptual and motor networks. Given the central role of motor experience in the formation of these networks, one''s present motor capabilities are thought to be the basis of their perceptual judgments about actions. However, it remains unknown whether the ability to form these action possibility judgments is affected by performance related changes in the motor system. To determine if judgments of action capabilities are affected by long-term changes in one''s own motor capabilities, participants with different degrees of upper-limb function due to their level (cervical vs. below cervical) of spinal cord injury (SCI) were tested on a perceptual-motor judgment task. Participants observed apparent motion videos of reciprocal aiming movements with varying levels of difficulty. For each movement, participants determined the shortest movement time (MT) at which they themselves and a young adult could perform the task while maintaining accuracy. Participants also performed the task. Analyses of MTs revealed that perceptual judgments for participant''s own movement capabilities were consistent with their actual performance- people with cervical SCI had longer judged and actual MTs than people with below cervical SCI. However, there were no between-group differences in judged MTs for the young adult. Although it is unclear how the judgments were adjusted (altered simulation vs. threshold modification), the data reveal that people with different motor capabilities due to SCI are not completely biased by their present capabilities and can effectively adjust their judgments to estimate the actions of others.     

Epidemiology: Spinal manipulation utilization

The objectives of this article are to (1) describe spinal manipulation use by time, place, and person, and (2) identify predictors of the use of spinal manipulation. We conducted a systematic review of the English-language literature published from January 1, 1980 through June 30, 2011. Of 822 citations identified, 213 were deemed potentially relevant; 75 were included after further consideration. Twenty-one additional articles were identified from reference lists. The literature is heavily weighted toward North America, Europe, and Australia and thus largely precludes inferences about spinal manipulation use in other parts of the world. In the regions covered by the literature, chiropractors, osteopaths, and physical therapists are most likely to deliver spinal manipulation, often in conjunction with other conservative therapies. Back and neck pain are the most frequent indications for receiving spinal manipulation; non-musculoskeletal conditions comprise a very small percentage of indications. Although spinal manipulation is more commonly used in adults than children, evidence suggests that spinal manipulation may be more likely used for non-musculoskeletal ailments in children than in adults. Patient satisfaction with spinal manipulation is very high.     

Rat models of upper extremity impairment in stroke

Stroke remains the leading cause of adult disability, with upper extremity motor impairments being the most prominent functional deficit in surviving stroke victims. The development of animal models of upper extremity dysfunction after stroke has enabled investigators to examine the neural mechanisms underlying rehabilitation-dependent motor recovery as well as the efficacy of various adjuvant therapies for enhancing recovery. Much of this research has focused on rat models of forelimb motor function after experimentally induced ischemic or hemorrhagic stroke. This article provides a review of several different methods for inducing stroke, including devascularization, photothrombosis, chemical vasoconstriction, and hemorrhagia. We also describe a battery of sensorimotor tasks for assessing forelimb motor function after stroke. The tasks range from measures of gross motor performance to fine object manipulation and kinematic movement analysis, and we offer a comparison of the sensitivity for revealing motor deficits and the amount of time required to administer each motor test. In addition, we discuss several important methodological issues, including the importance of testing on multiple tasks to characterize the nature of the impairments, establishing stable baseline prestroke motor performance measures, dissociating the effects of acute versus chronic testing, and verifying lesion location and size. Finally, we outline general considerations for conducting research using rat models of stroke and the role that these models should play in guiding clinical trials.     

Cortical control of grasp in non-human primates

The skilled use of the hand for grasping and manipulation of objects is a fundamental feature of the primate motor system. Grasping movements involve transforming the visual information about an object into a motor command appropriate for the coordinated activation of hand and finger muscles. The cerebral cortex and its descending projections to the spinal cord are known to play a crucial role for the control of grasp. Recent studies in non-human primates have provided some striking new insights into the respective contribution of the parietal and frontal motor cortical areas to the control of grasp. Also, new approaches allowed investigating the coupling of grasp-related activity in different cortical areas for the control of the descending motor command.     

Randomised controlled trial to compare surgical stabilisation of the lumbar spine with an intensive rehabilitation programme for patients with chronic low back pain: the MRC spine stabilisation trial

Objectives To assess the clinical effectiveness of surgical stabilisation (spinal fusion) compared with intensive rehabilitation for patients with chronic low back pain.Design Multicentre randomised controlled trial.Setting 15 secondary care orthopaedic and rehabilitation centres across the United Kingdom.Participants 349 participants aged 18-55 with chronic low back pain of at least one year''s duration who were considered candidates for spinal fusion.Intervention Lumbar spine fusion or an intensive rehabilitation programme based on principles of cognitive behaviour therapy.Main outcome measure The primary outcomes were the Oswestry disability index and the shuttle walking test measured at baseline and two years after randomisation. The SF-36 instrument was used as a secondary outcome measure.Results 176 participants were assigned to surgery and 173 to rehabilitation. 284 (81%) provided follow-up data at 24 months. The mean Oswestry disability index changed favourably from 46.5 (SD 14.6) to 34.0 (SD 21.1) in the surgery group and from 44.8 (SD14.8) to 36.1 (SD 20.6) in the rehabilitation group. The estimated mean difference between the groups was –4.1 (95% confidence interval –8.1 to –0.1, P = 0.045) in favour of surgery. No significant differences between the treatment groups were observed in the shuttle walking test or any of the other outcome measures.Conclusions Both groups reported reductions in disability during two years of follow-up, possibly unrelated to the interventions. The statistical difference between treatment groups in one of the two primary outcome measures was marginal and only just reached the predefined minimal clinical difference, and the potential risk and additional cost of surgery also need to be considered. No clear evidence emerged that primary spinal fusion surgery was any more beneficial than intensive rehabilitation.     

Is spinal neuromuscular function asymmetrical in adolescents with idiopathic scoliosis compared to those without scoliosis?: A narrative review of surface EMG studies

Adolescent idiopathic scoliosis (AIS) is a three-dimensional spinal deformity occurring between ages of 10–18 years. We aimed to present a reasoned synthesis of the published evidence for and against asymmetrical paraspinal muscle activation in AIS. PubMed and Embase databases were searched using terms: adolescent idiopathic scoliosis AND electromyogra* (EMG). Identified studies (n = 94) were screened for eligibility. We identified 16 studies, from which 136 EMG outcome measures contributed to the review.For EMG onset, one of two studies provided evidence of earlier muscle activation on the convex compared to concave side of the spine, particularly in those with progressive AIS. For EMG amplitude, 43 outcome measures provided evidence of convex > concave activation, 85 outcomes supported no difference between sides, and 8 outcomes supported concave > convex activation. Greater activity on the convex than concave side was more commonly demonstrated at the scoliosis curve apex level, in people with single right thoracic [progressive] curves, during postural tasks.Further research is needed to determine the relationships between muscle activity asymmetry and spinal curve parameters in a variety of motor tasks. Recommendations are provided to improve methodological quality for future studies of spinal neuromuscular function in AIS, as well as more comprehensive and transparent reporting of methods and results.     

Internal models and intermittency: A theoretical account of human tracking behavior

This paper concerns the use of tracking studies to test a theoretical account of the information processing performed by the human CNS during control of movement. The theory provides a bridge between studies of reaction time and continuous tracking. It is proposed that the human CNS includes neuronal circuitry to compute inverse internal models of the multiple input, multiple output, dynamic, nonlinear relationships between outgoing motor commands and their resulting perceptual consequences. The inverse internal models are employed during movement execution to transform preplanned trajectories of desired perceptual consequences into appropriate outgoing motor commands to achieve them. A finite interval of time is required by the CNS to preplan the desired perceptual consequences of a movement and it does not commence planning a new movement until planning of the old one has been completed. This behavior introduces intermittency into the planning of movements. In this paper we show that the gain and phase frequency response characteristics of the human operator in a visual pursuit tracking task can be derived theoretically from these assumptions. By incorporating the effects of internal model inaccuracy and of speed-accuracy trade-off in performance, it is shown that various aspects of experimentally measured tracking behavior can be accounted for.     

Corollary Discharge Failure in an Oculomotor Task Is Related to Delusional Ideation in Healthy Individuals

Predicting the sensory consequences of saccadic eye movements likely plays a crucial role in planning sequences of saccades and in maintaining visual stability despite saccade-caused retinal displacements. Deficits in predictive activity, such as that afforded by a corollary discharge signal, have been reported in patients with schizophrenia, and may lead to the emergence of positive symptoms, in particular delusions of control and auditory hallucinations. We examined whether a measure of delusional thinking in the general, non-clinical population correlated with measures of predictive activity in two oculomotor tasks. The double-step task measured predictive activity in motor control, and the in-flight displacement task measured predictive activity in trans-saccadic visual perception. Forty-one healthy adults performed both tasks and completed a questionnaire to assess delusional thinking. The quantitative measure of predictive activity we obtained correlated with the tendency towards delusional ideation, but only for the motor task, and not the perceptual task: Individuals with higher levels of delusional thinking showed less self-movement information use in the motor task. Variation of the degree of self-generated movement knowledge as a function of the prevalence of delusional ideation in the normal population strongly supports the idea that corollary discharge deficits measured in schizophrenic patients in previous researches are not due to neuroleptic medication. We also propose that this difference in results between the perceptual and the motor tasks may point to a dissociation between corollary discharge for perception and corollary discharge for action.     

PTEN regulates AMPA receptor-mediated cell viability in iPS-derived motor neurons

Excitatory transmission in the brain is commonly mediated by the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors. In amyotrophic lateral sclerosis (ALS), AMPA receptors allow cytotoxic levels of calcium into neurons, contributing to motor neuron injury. We have previously shown that oculomotor neurons resistant to the disease process in ALS show reduced AMPA-mediated inward calcium currents compared with vulnerable spinal motor neurons. We have also shown that PTEN (phosphatase and tensin homolog deleted on chromosome 10) knockdown via siRNA promotes motor neuron survival in models of spinal muscular atrophy (SMA) and ALS. It has been reported that inhibition of PTEN attenuates the death of hippocampal neurons post injury by decreasing the effective translocation of the GluR2 subunit into the membrane. In addition, leptin can regulate AMPA receptor trafficking via PTEN inhibition. Thus, we speculate that manipulation of AMPA receptors by PTEN may represent a potential therapeutic strategy for neuroprotective intervention in ALS and other neurodegenerative disorders. To this end, the first step is to establish a fibroblast–iPS–motor neuron in vitro cell model to study AMPA receptor manipulation. Here we report that iPS-derived motor neurons from human fibroblasts express AMPA receptors. PTEN depletion decreases AMPA receptor expression and AMPA-mediated whole-cell currents, resulting in inhibition of AMPA-induced neuronal death in primary cultured and iPS-derived motor neurons. Taken together, our results imply that PTEN depletion may protect motor neurons by inhibition of excitatory transmission that represents a therapeutic strategy of potential benefit for the amelioration of excitotoxicity in ALS and other neurodegenerative disorders.     

Alternative communication systems for people with severe motor disabilities: a survey

We have now sufficient evidence that using electrical biosignals in the field of Alternative and Augmented Communication is feasible. Additionally, they are particularly suitable in the case of people with severe motor impairment, e.g. people with high-level spinal cord injury or with locked-up syndrome. Developing solutions for them implies that we find ways to use sensors that fit the user's needs and limitations, which in turn impacts the specifications of the system translating the user's intentions into commands. After devising solutions for a given user or profile, the system should be evaluated with an appropriate method, allowing a comparison with other solutions. This paper submits a review of the way three bioelectrical signals - electromyographic, electrooculographic and electroencephalographic - have been utilised in alternative communication with patients suffering severe motor restrictions. It also offers a comparative study of the various methods applied to measure the performance of AAC systems.     

Human Glial-Restricted Progenitor Transplantation into Cervical Spinal Cord of the SOD1G93A Mouse Model of ALS

Cellular abnormalities are not limited to motor neurons in amyotrophic lateral sclerosis (ALS). There are numerous observations of astrocyte dysfunction in both humans with ALS and in SOD1^G93A rodents, a widely studied ALS model. The present study therapeutically targeted astrocyte replacement in this model via transplantation of human Glial-Restricted Progenitors (hGRPs), lineage-restricted progenitors derived from human fetal neural tissue. Our previous findings demonstrated that transplantation of rodent-derived GRPs into cervical spinal cord ventral gray matter (in order to target therapy to diaphragmatic function) resulted in therapeutic efficacy in the SOD1^G93A rat. Those findings demonstrated the feasibility and efficacy of transplantation-based astrocyte replacement for ALS, and also show that targeted multi-segmental cell delivery to cervical spinal cord is a promising therapeutic strategy, particularly because of its relevance to addressing respiratory compromise associated with ALS. The present study investigated the safety and in vivo survival, distribution, differentiation, and potential efficacy of hGRPs in the SOD1^G93A mouse. hGRP transplants robustly survived and migrated in both gray and white matter and differentiated into astrocytes in SOD1^G93A mice spinal cord, despite ongoing disease progression. However, cervical spinal cord transplants did not result in motor neuron protection or any therapeutic benefits on functional outcome measures. This study provides an in vivo characterization of this glial progenitor cell and provides a foundation for understanding their capacity for survival, integration within host tissues, differentiation into glial subtypes, migration, and lack of toxicity or tumor formation.     

Inferior olive mirrors joint dynamics to implement an inverse controller

To produce smooth and coordinated motion, our nervous systems need to generate precisely timed muscle activation patterns that, due to axonal conduction delay, must be generated in a predictive and feedforward manner. Kawato proposed that the cerebellum accomplishes this by acting as an inverse controller that modulates descending motor commands to predictively drive the spinal cord such that the musculoskeletal dynamics are canceled out. This and other cerebellar theories do not, however, account for the rich biophysical properties expressed by the olivocerebellar complex’s various cell types, making these theories difficult to verify experimentally. Here we propose that a multizonal microcomplex’s (MZMC) inferior olivary neurons use their subthreshold oscillations to mirror a musculoskeletal joint’s underdamped dynamics, thereby achieving inverse control. We used control theory to map a joint’s inverse model onto an MZMC’s biophysics, and we used biophysical modeling to confirm that inferior olivary neurons can express the dynamics required to mirror biomechanical joints. We then combined both techniques to predict how experimentally injecting current into the inferior olive would affect overall motor output performance. We found that this experimental manipulation unmasked a joint’s natural dynamics, as observed by motor output ringing at the joint’s natural frequency, with amplitude proportional to the amount of current. These results support the proposal that the cerebellum—in particular an MZMC—is an inverse controller; the results also provide a biophysical implementation for this controller and allow one to make an experimentally testable prediction.     

Kinesiological research: The use of surface electromyography for assessing the effects of spinal manipulation

Decreasing an elevated muscle tone is an often cited benefit of spinal manipulation. Spinal manipulation is theorized to disrupt an assumed pain-spasm-pain cycle that sufferers of low back pain may be experiencing. The current research has mostly investigated the short term influence of a single spinal manipulation on paraspinal muscle activity either at rest (e.g. standing or prone) or during simple movements (e.g. forward bend). The higher quality experiments to date have typically reported both reductions in muscle activity during lying prone or during the fully flexed position of forward bend. The only study measuring the long term influence of spinal manipulation has failed to document any change in muscle activity as measured with surface electromyography. Both manually delivered manipulations and manipulations delivered via a mechanical adjusting device have been associated with changes in muscle activation. Changes in muscle activity at muscles distant from the spinal joints manipulated (e.g. muscles in the upper limbs) have been documented following a single spinal manipulation however rather than the typical reduction in muscle activity an increase in resting activation has been reported. The state of muscle dysfunction (e.g. palpably tender or subjectively taut) may be a factor in achieving a myoelectric response to spinal manipulation. Currently, the clinical significance of short term changes in electromyographic amplitude following manipulation is unknown.     

Toward an objective interpretation of surface EMG patterns: a voluntary response index (VRI).

Individuals with incomplete spinal cord injuries (SCI) retain varying degrees of voluntary motor control. The complexity of the motor control system and the nature of the recording biophysics have inhibited efforts to develop objective measures of voluntary motor control. This paper proposes the definition and use of a voluntary response index (VRI) calculated from quantitative analysis of surface electromyographic (sEMG) data recorded during defined voluntary movement as a sensitive measure of voluntary motor control in such individuals. The VRI is comprised of two numeric values, one derived from the total muscle activity recorded for the voluntary motor task (magnitude), and the other from the sEMG distribution across the recorded muscles (similarity index (SI)). Calculated as a vector, the distribution of sEMG from the test subject is compared to the average vector calculated from sEMG recordings of the same motor task from 10 neurologically intact subjects in a protocol called brain motor control assessment (BMCA). To evaluate the stability of the VRI, a group of five healthy subjects were individually compared to the prototype, average healthy-subject vectors for all of the maneuvers. To evaluate the sensitivity of this method, the VRI was obtained from two SCI subjects participating in other research studies. One was undergoing supported treadmill ambulation training, and the other a controlled withdrawal of anti-spasticity medications. The supported treadmill training patient's VRI, calculated from pre- and post-training BMCA recordings, reflected the qualitative changes in sEMG patterns and functional improvement of motor control. The VRI of the patient followed by serial BMCA during medication withdrawal also reflected changes in the motor control as a result of changes in anti-spasticity medication. To validate this index for clinical use, serial studies using larger numbers of subjects with compromised motor control should be performed.     

Multivariate patterns in object-selective cortex dissociate perceptual and physical shape similarity

Prior research has identified the lateral occipital complex (LOC) as a critical cortical region for the representation of object shape in humans. However, little is known about the nature of the representations contained in the LOC and their relationship to the perceptual experience of shape. We used human functional MRI to measure the physical, behavioral, and neural similarity between pairs of novel shapes to ask whether the representations of shape contained in subregions of the LOC more closely reflect the physical stimuli themselves, or the perceptual experience of those stimuli. Perceptual similarity measures for each pair of shapes were obtained from a psychophysical same-different task; physical similarity measures were based on stimulus parameters; and neural similarity measures were obtained from multivoxel pattern analysis methods applied to anterior LOC (pFs) and posterior LOC (LO). We found that the pattern of pairwise shape similarities in LO most closely matched physical shape similarities, whereas shape similarities in pFs most closely matched perceptual shape similarities. Further, shape representations were similar across participants in LO but highly variable across participants in pFs. Together, these findings indicate that activation patterns in subregions of object-selective cortex encode objects according to a hierarchy, with stimulus-based representations in posterior regions and subjective and observer-specific representations in anterior regions.     

The long-term prognosis of pre-term infants

The dramatic increases in the survival rate of prematurely born, very low birth weight infants (<1500 g) have created concern about the possible sequelae experienced by these children, in terms of both severe problems and less severe learning and behavior problems. The methodological difficulties involved in answering questions about the outcomes of these children, including the choice of appropriate outcome measures, the analysis of individual variation, the problems associated with dropouts, the relevant comparison groups, the importance of survival rate, and the question of correcting for the degree of prematurity, are considered. In spite of the difficulties in interpreting the studies, the research indicates that many premature children have learning disabilities, particularly in the perceptual and visual motor functioning and some aspects of language and reading. In addition, ethical issues related to prematurity are discussed, including parents’ rights, decision-making, and cost and treatment. Finally, some solutions are proposed involving the use of risk indices for the early detection of developmental problems.