The human motor cortex contributes to gravity compensation to maintain posture and during reaching.

The neural control of posture and movement is interdependent. During voluntary movement, the neural motor command is executed by the motor cortex through the corticospinal tract and its collaterals and subcortical targets. Here we address the question of whether the control mechanism for the postural adjustments at nonmoving joints is also involved in overcoming gravity at the moving joints. We used single-pulse transcranial magnetic stimulation to measure the corticospinal excitability in humans during postural and reaching tasks. We hypothesized that the corticospinal excitability is proportional to background muscle activity and the gravity-related joint moments during both static postures and reaching movements. To test this hypothesis, we used visual targets in virtual reality to instruct five postures and three movements with or against gravity. We then measured the amplitude and gain of motor evoked potentials in multiple arm and hand muscles at several phases of the reaching motion and during static postures. The stimulation caused motor evoked potentials in all muscles that were proportional to the muscle activity. During both static postures and reaching movements, the muscle activity and the corticospinal contribution to these muscles changed in proportion with the postural moments needed to support the arm against gravity, supporting the hypothesis. Notably, these changes happened not only in antigravity muscles. Altogether, these results provide evidence that the changes in corticospinal excitability cause muscle cocontraction that modulates limb stiffness. This suggests that the motor cortex is involved in producing postural adjustments that support the arm against gravity during posture maintenance and reaching.NEW & NOTEWORTHY Animal studies suggest that the corticospinal tract and its collaterals are crucial for producing postural adjustments that accompany movement in limbs other than the moving limb. Here we provide evidence for a similar control schema for both arm posture maintenance and gravity compensation during movement of the same limb. The observed interplay between the postural and movement control signals within the corticospinal tract may help explain the underlying neural motor deficits after stroke.

Secondary endings of muscle spindles: Structure, reflex action, role in motor control and proprioception.

NEW FINDINGS: What is the topic of this review? We describe the structure and function of secondary sensory endings of muscle spindles, their reflex action and role in motor control and proprioception. What advances does it highlight? In most mammalian skeletal muscles, secondary endings of spindles are more or much more numerous than primary endings but are much less well studied. By focusing on secondary endings in this review, we aim to redress the balance, draw attention to what is not known and stimulate future research. ABSTRACT: Kinaesthesia and the control of bodily movement rely heavily on the sensory input from muscle spindles. Hundreds of these sensory structures are embedded in mammalian muscles. Each spindle has one or more sensory endings and its own complement of small muscle fibres that are activated by the CNS via fusimotor neurons, providing efferent control of sensory responses. Exactly how the CNS wields this influence remains the subject of much fascination and debate. There are two types of sensory endings, primary and secondary, with differing development, morphology, distribution and responsiveness. Spindle primary endings have received more attention than secondaries, although the latter usually outnumber them. This review focuses on the secondary endings. Their location within the spindle, their response properties, the projection of their afferents within the CNS and their reflex actions all suggest that secondaries have certain separate roles from the primaries in proprioception and motor control. Specifically, spindle secondaries seem more adapted than primaries to signalling slow and maintained changes in the relative position of bodily segments, thereby contributing to position sense, postural control and static limb positioning. By highlighting, in this way, the roles of secondary endings, a final aim of the review is to broaden understanding of muscle spindles more generally and of the important contributions they make to both sensory and motor mechanisms.

Time-Dependent Discrepancies between Assessments of Sensory Function after Incomplete Cervical Spinal Cord Injury.

We recently demonstrated that the electrical perceptual threshold (EPT) examination reveals spared sensory function at lower spinal segments compared with the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) examination in humans with chronic incomplete cervical spinal cord injury (SCI). Here, we investigated whether discrepancies in sensory function detected by both sensory examinations change over time after SCI. Forty-five participants with acute (<1 year), chronic (≥1-10 years), and extended-chronic (>10 years) incomplete cervical SCI and 30 control subjects were tested on dermatomes C2-T4 bilaterally. EPT values were higher in subjects with acute (2.5 ± 0.8 mA), chronic (2.2 ± 0.7 mA), or extended-chronic (2.8 ± 1.1 mA) SCI compared with controls (1.0 ± 0.1 mA). The EPT examination detected sensory impairments in spinal segments above (2.3 ± 0.9) and below (4.2 ± 2.6) the level detected by the ISNCSCI sensory examination in participants with acute and chronic SCI, respectively. Notably, both examinations detected similar levels of spared sensory function in the extended-chronic phase of SCI (0.8 ± 0.5). A negative correlation was found between differences in EPT and ISNCSCI sensory levels and time post-injury. These observations indicate that discrepancies between EPT and ISNCSCI sensory scores are time-dependent, with the EPT revealing impaired sensory function above, below, or at the same spinal segment as the ISNCSCI examination. We propose that the EPT is a sensitive tool to assess changes in sensory function over time after incomplete cervical SCI.

Muscle spindle and fusimotor activity in locomotion.

Mammals may exhibit different forms of locomotion even within a species. A particular form of locomotion (e.g. walk, run, bound) appears to be selected by supraspinal commands, but the precise pattern, i.e. phasing of limbs and muscles, is generated within the spinal cord by so-called central pattern generators. Peripheral sense organs, particularly the muscle spindle, play a crucial role in modulating the central pattern generator output. In turn, the feedback from muscle spindles is itself modulated by static and dynamic fusimotor (gamma) neurons. The activity of muscle spindle afferents and fusimotor neurons during locomotion in the cat is reviewed here. There is evidence for some alpha-gamma co-activation during locomotion involving static gamma motoneurons. However, both static and dynamic gamma motoneurons show patterns of modulation that are distinct from alpha motoneuron activity. It has been proposed that static gamma activity may drive muscle spindle secondary endings to signal the intended movement to the central nervous system. Dynamic gamma motoneuron drive appears to prime muscle spindle primary endings to signal transitions in phase of the locomotor cycle. These findings come largely from reduced animal preparations (decerebrate) and require confirmation in freely moving intact animals.

The interaction of cortico-spinal pathways and sacral sphincter reflexes in subjects with incomplete spinal cord injury: a pilot study.

AIMS: To reveal the effectiveness of corticospinal drive in facilitating the pudendal reflex in the anal sphincter muscle, as a surrogate marker for the urethral sphincter, in incomplete spinal cord injury (iSCI). METHODS: Three neurologically normal subjects and twenty-six subjects with incomplete, supra-sacral spinal cord injuries and symptoms of a neuropathic bladder were recruited. Incontinence was assessed using the International Consultation on Incontinence Modular Questionnaire (ICIQ). Electromyographic activity of the external anal sphincter was recorded. The pudendo-anal reflex (PAR) was elicited by electrical stimulation of the dorsal penile nerve (DPN). Motor cortical excitation was achieved using transcranial magnetic stimulation (TMS). RESULTS: Preliminary findings in normal and iSCI subjects showed facilitation of the PAR by prior TMS with an optimal interval of 20-40 msec. Of 23 iSCI subjects, 12 showed facilitation to TMS applied 30 msec before DPN stimulation. Eight of the 12, and a further five iSCI subjects, had an anal sphincter MEP in response to TMS alone. There was a weak tendency (r(2) = 0.22, P = 0.03) for those with higher ICIQ values to have larger PAR responses but no significant difference in ICIQ scores between those with (ICIQ = 4.9 ± 4.0 mean ± SD) and those without (ICIQ = 7.2 ± 4.7) cortical facilitation of the PAR. CONCLUSIONS: Cortical TMS was effective in facilitating the PAR in some iSCI subjects. The presence of cortical facilitation of the PAR was not related to the degree of urinary continence.

Induction of central nervous system plasticity by repetitive transcranial magnetic stimulation to promote sensorimotor recovery in incomplete spinal cord injury.

Cortical and spinal cord plasticity may be induced with non-invasive transcranial magnetic stimulation to encourage long term potentiation or depression of neuronal circuits. Such plasticity inducing stimulation provides an attractive approach to promote changes in sensorimotor circuits that have been degraded by spinal cord injury (SCI). If residual corticospinal circuits can be conditioned appropriately there should be the possibility that the changes are accompanied by functional recovery. This article reviews the attempts that have been made to restore sensorimotor function and to obtain functional benefits from the application of repetitive transcranial magnetic stimulation (rTMS) of the cortex following incomplete spinal cord injury. The confounding issues that arise with the application of rTMS, specifically in SCI, are enumerated. Finally, consideration is given to the potential for rTMS to be used in the restoration of bladder and bowel sphincter function and consequent functional recovery of the guarding reflex.

Quantitative testing in spinal cord injury: overview of reliability and predictive validity.

OBJECT: The objective of this study was to identify commonly used physiological outcome measures and summarize evidence on the reliability and predictive validity of quantitative measures used in monitoring persons with spinal cord injury (SCI). METHODS: A systematic search of PubMed through January 5, 2012, was conducted to identify publications using common outcome measures in persons with SCI and for studies that were specifically designed to evaluate the reliability and predictive validity of selected quantitative measures. Quantitative measures were defined as tests that quantify sensory and motor function, such as amount of force or torque, as well as thresholds, amplitudes, and latencies of evoked potentials that might be useful in studies and monitoring of patients with SCI. Reliability studies reporting interclass correlation coefficients (ICCs) or weighted κ coefficients were considered for inclusion. Studies explicitly evaluating correlation between measures and specific functional outcomes were considered for predictive validity. RESULTS: From a total of 121 potentially relevant citations, 6 studies of reliability and 4 studies of predictive validity for quantitative tests met the inclusion criteria. In persons with incomplete SCI, ICCs for both interrater and intrarater reliability of electrical perceptual threshold (EPT) were ≥ 0.7 above the sensory level of SCI but were less reliable below the sensory level. Interclass correlation coefficients for interrater and intrarater reliability of the Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP) components ranged from 0.84 to 0.98. For electromyography, the ICC was consistently high for within-day tests. The overall quality of reliability of the majority of studies was poor, due to the potential for selection bias and small sample sizes. No classic validation studies were found for the selected measures, and evidence regarding the predictive validity of the measures was limited. Somatosensory evoked potentials (SSEPs) may be correlated with ambulatory capacity, as well as the Barthel Index and motor index scores, but this correlation was limited for evaluation of bladder function recovery in 3 studies that assessed the correlation between baseline or initial SSEPs and a specific clinical outcome at a later follow-up time. All studies used convenience samples and the overall sample quality was low. CONCLUSIONS: Evidence on the reliability and validity of the quantitative measures selected for this review is limited, and the overall quality of existing studies is poor. There is some evidence for the reliability of the EPT, dermatomal SSEPs, and the GRASSP to suggest that they may be useful in longitudinal studies of patients with SCI. There is a need for high quality studies of reliability, responsiveness, and validity for quantitative measures to monitor the level and degree of SCI.

Reliability of cutaneous electrical perceptual threshold in the assessment of sensory perception in patients with spinal cord injury.

The electrical perceptual threshold (EPT) test complements the American Spinal Injury Association (ASIA) assessment of cutaneous sensory function by providing a quantitative assessment for each dermatome. The aim here was to establish the reliability of the EPT by examining inter- and intra-rater repeatability of test results in spinal cord injury (SCI). Twelve persons with incomplete spinal cord injury (iSCI; two stable at >20 months and 10 sub-acute at <9 months post-injury) and 12 control subjects took part. EPT was established at the ASIA sensory key points. A pulse of 0.5 ms in duration was applied three times per second. Threshold was determined by the method of limits. The strength of stimulation was augmented (0.1 mA.s(-1)) until the recipient reported sensation, then reduced until sensation was lost. EPT was taken as the lowest strength at which the subject reported sensation. Threshold was determined by two raters to establish intra- and inter-rater reliability. There were no significant differences in mean intra- or inter-rater EPT values at, above, or below the level of lesion (ASIA sensory level) for iSCI subjects. The intra-class correlation coefficient (ICC) was 0.56-0.80 for intra-rater and 0.52-0.91 for inter-rater classes, depending on the level tested. There was a significant correlation (Pearson's r = 0.93) between EPTs for four different dermatomes of control subjects assessed using two different types of stimulator. EPT provides an objective and quantitative measure of threshold for cutaneous sensory function. The method has good inter- and intra-rater reliability, and can be assessed using different stimulators.

Cortical control of erector spinae muscles during arm abduction in humans.

Abduction of one arm preferentially activates erector spinae muscles on the other side to stabilise the body. We hypothesise that the corticospinal drive to the arm abductors and the erector spinae may originate from the same hemisphere. In 18 subjects, transcranial magnetic stimulation (TMS) was applied using an angle double-cone coil placed symmetrically over the vertex. Motor evoked potentials (MEP) could not be evoked systematically seated at rest but could be evoked bilaterally in erector spinae muscles during unilateral arm abduction. TMS was applied at 110% and 120% motor threshold (MT) for the contralateral erector spinae muscle when an arm was abducted against resistance. The electromyographic (EMG) activity in the erector spinae at L4 vertebral level during contralateral arm abduction was significantly higher (P<0.05) than in the ipsilateral erector spinae. The mean (+/-S.E.M.) latencies of MEPs in the contralateral muscle to TMS at 120%MT (left 16.0+/-0.8 ms; right 17.0+/-0.8 ms) were significantly (P<0.05) longer than in the ipsilateral erector spinae (13.9+/-1.0 ms; 16.6+/-0.4 ms). In two of six subjects from the same group, it was possible to elicit MEPs by TMS applied selectively to one hemisphere using a figure-of-eight coil. MEPs ipsilateral to the TMS had longer latencies than contralateral MEPs. The study revealed an unexpectedly longer rather than shorter latency of the MEP recorded from the lumbar erector spinae muscles when co-activated during abduction of the opposite arm. A speculative explanation is that TMS might activate back muscles contralateral to arm abduction via an uncrossed, ipsilateral corticospinal tract that is slower conducting than the conventional crossed corticospinal tract. The study has implications for the design of measures to promote recovery and rehabilitation of motor function in disorders such as stroke and spinal cord injury.

Review of physiological motor outcome measures in spinal cord injury using transcranial magnetic stimulation and spinal reflexes.

This article reviews methods that have been developed as part of a clinical initiative on improving outcome measures for motor function assessment in subjects with spinal cord injury (SCI). Physiological motor outcome measures originally developed for limbs-transcranial magnetic stimulation (TMS) of the motor cortex to elicit motor-evoked potentials (MEPs) and mechanical stimulation to elicit spinal reflexes-have been extended to muscles of the trunk. The impetus for this development is the lack of a motor component in the American Spinal Injury Association clinical assessment for the thoracic myotomes. The application of TMS to the assessment of limb muscles is reviewed, followed by consideration of its application to the assessment of paravertebral and intercostal muscles. Spinal reflex testing of paravertebral muscles is also described. The principal markers for the thoracic SCI motor level that have emerged from this clinical initiative are (1) the threshold of MEPs in paravertebral muscles in response to TMS of the motor cortex, (2) the facilitation pattern and latency of MEPs in intercostal muscles during voluntary expiratory effort, and (3) the absence of long-latency reflex responses and the exaggeration of short-latency reflex responses in paravertebral muscles.

Quantitative sensory tests (perceptual thresholds) in patients with spinal cord injury.

This article was presented at the Premeeting Workshop on Outcome Measures at the American Spinal Injury Association (ASIA) Annual Scientific Meeting in Dallas, Texas, in May 2005. The article summarizes preliminary findings of three quantitative sensory tests that were evaluated as part of the International Spinal Research Trust Clinical Initiative study: perceptual thresholds to electrical, vibration, and thermal stimulation. The results gathered so far suggest that the three tests are simple, reproducible, and applicable in a clinical setting. The tests seem to add resolution and sensitivity to the standard clinical testing and could be useful adjuncts in longitudinal monitoring of spinal cord injury for research purposes.

The ability of physiological stimuli to generate the sympathetic skin response in human chronic spinal cord injury.

PURPOSE: Sympathetic sudomotor function in chronic spinal cord injury (SCI) has been evaluated to determine if recording the sympathetic skin response (SSR) provides evidence of integrity of the spinal component of the sympathetic pathways. METHODS: Thirty subjects with chronic SCI and 15 healthy normal subjects were studied. The SSR was elicited using two physiological (auditory and inspiratory gasp) stimuli. In addition, electrical (median and peroneal nerve) stimulation was also performed. Recordings were made from palmar and plantar sites. RESULTS: Palmar and plantar SSRs could be readily elicited in all control subjects by all stimuli. In the majority of SCI subjects, the presence or absence of the SSR was related to the American Spinal Injury Association (ASIA) impairment scale, which incorporates only motor and sensory assessments. The exceptions indicated preserved (or damaged) sympathetic spinal cord pathways. CONCLUSIONS: We conclude that the SSR, using either physiological or electrical stimuli, may be a reliable, non-invasive method of determining integrity of sympathetic cholinergic pathways in SCI, with potential for monitoring the effects of intervention and spinal repair.

Segmental recording of cortical motor evoked potentials from thoracic paravertebral myotomes in complete spinal cord injury.

STUDY DESIGN: A study of thoracic paravertebral muscle motor-evoked potentials using transcranial magnetic stimulation in spinal cord injury patients and control participants. OBJECTIVES: To develop a method to study the level and density of corticospinal lesions in thoracic spinal cord injury. SUMMARY OF BACKGROUND DATA: Cervical and lumbar spinal cord injury, unlike thoracic spinal cord injury, can be quantified by recording muscle motor-evoked potentials from limb muscles. For thoracic spinal cord injury, the use of paravertebral muscles is limited by complex innervation patterns and the greater difficulty in obtaining muscle motor-evoked potentials. METHODS: In 10 patients with complete midthoracic spinal cord injury (T4-T7) and 10 age-matched control participants, muscle motor-evoked potentials were recorded from all thoracic paravertebral muscles using transcranial magnetic stimulation with a double-cone stimulating coil over the vertex. RESULTS: In control participants, muscle motor-evoked potential responses evoked in all myotomes had progressively increasing latency in a rostrocaudal direction. Threshold was comparable in all segments. The duration of muscle motor-evoked potentials was unrelated to the spinal level. In spinal cord injury, responses were elicited in all segments above a lesion and in a varying range of segments below the lesion. In comparison with control participants, threshold was lower above and higher below the lesion (P < 0.001) in patients with spinal cord injury. Latency was longer than normal both above and below the lesion (P < 0.001). Duration was not significantly different from that in control participants at any level. CONCLUSIONS: Paravertebral muscle motor-evoked potentials can be elicited below the level of a complete spinal cord injury. Possible reasons for this include the multisegmental innervation of these muscles and the long muscle fiber conduction. Stretch reflex activation elicited by contraction of muscles above the lesion is thought to be an unlikely mechanism because of the latency of the response. Although the presence or absence of muscle motor-evoked potentials does not appear to be a sensitive indicator of the level of thoracic spinal cord injury lesion, analysis of muscle motor-evoked potentials reveals abnormal patterns that may assist in defining lesions. Finally, lower threshold above the lesion suggests corticospinal hyperexcitability of this pathway as a result of central plasticity after spinal cord injury.