Muscle Spasms after Spinal Cord Injury Stem from Changes in Motoneuron Excitability and Synaptic Inhibition, Not Synaptic Excitation.

Muscle spasms are common in chronic spinal cord injury (SCI), posing challenges to rehabilitation and daily activities. Pharmacological management of spasms mostly targets suppression of excitatory inputs, an approach known to hinder motor recovery. To identify better targets, we investigated changes in inhibitory and excitatory synaptic inputs to motoneurons as well as motoneuron excitability in chronic SCI. We induced either a complete or incomplete SCI in adult mice of either sex and divided those with incomplete injury into low or high functional recovery groups. Their sacrocaudal spinal cords were then extracted and used to study plasticity below injury, with tissue from naive animals as a control. Electrical stimulation of the dorsal roots elicited spasm-like activity in preparations of chronic severe SCI but not in the control. To evaluate overall synaptic inhibition activated by sensory stimulation, we measured the rate-dependent depression of spinal root reflexes. We found inhibitory inputs to be impaired in chronic injury models. When synaptic inhibition was blocked pharmacologically, all preparations became clearly spastic, even the control. However, preparations with chronic injuries generated longer spasms than control. We then measured excitatory postsynaptic currents (EPSCs) in motoneurons during sensory-evoked spasms. The data showed no difference in the amplitude of EPSCs or their conductance among animal groups. Nonetheless, we found that motoneuron persistent inward currents activated by the EPSCs were increased in chronic SCI. These findings suggest that changes in motoneuron excitability and synaptic inhibition, rather than excitation, contribute to spasms and are better suited for more effective therapeutic interventions.Significance Statement Neural plasticity following spinal cord injury is crucial for recovery of motor function. Unfortunately, this process is blemished by maladaptive changes that can cause muscle spasms. Pharmacological alleviation of spasms without compromising the recovery of motor function has proven to be challenging. Here, we investigated changes in fundamental spinal mechanisms that can cause spasms post-injury. Our data suggest that the current management strategy for spasms is misdirected toward suppressing excitatory inputs, a mechanism that we found unaltered after injury, which can lead to further motor weakness. Instead, this study shows that more promising approaches might involve restoring synaptic inhibition or modulating motoneuron excitability.

Estimates of persistent inward currents in lower limb motoneurons are larger in females than in males.

Noninvasive recordings of motor unit (MU) spike trains help us understand how the nervous system controls movement and how it adapts to various physiological conditions. The majority of participants in human and nonhuman animal physiology studies are male, and it is assumed that mechanisms uncovered in these studies are shared between males and females. However, sex differences in neurological impairment and physical performance warrant the study of sex as a biological variable in human physiology and performance. To begin addressing this gap in the study of biophysical properties of human motoneurons, we quantified MU discharge rates and estimates of persistent inward current (PIC) magnitude in both sexes. We decomposed MU spike trains from the tibialis anterior (TA), medial gastrocnemius (MG), and soleus (SOL) using high-density surface electromyography and blind source separation algorithms. Ten participants of each sex performed slow triangular (10 s up and down) isometric contractions to a peak of 30% of their maximum voluntary contraction. We then used linear mixed-effects models to determine if peak discharge rate and estimates of PICs were predicted by the fixed effects of sex, muscle, and their interaction. Despite a lack of sex-differences in peak discharge rates across all muscles, estimates of PICs were larger [χ2(1) = 6.26, P = 0.012] in females [4.73 ± 0.242 pulses per second (pps)] than in males (3.81 ± 0.240 pps). These findings suggest that neuromodulatory drive, inhibitory input, and/or biophysical properties of motoneurons differ between the sexes and may contribute to differences in MU discharge patterns.NEW & NOTEWORTHY Sex-related differences in motoneuron analyses have emerged with greater inclusion of female participants, however, mechanisms for these differences remain unclear. Estimates of persistent inward currents (i.e., ΔF) in motoneurons of the lower limb muscles were larger in females than in males. This suggests neuromodulatory drive, monoaminergic signaling, intrinsic motoneuron properties, and/or descending motor commands may differ between the sexes, which provides a potential mechanism underlying previously reported sex-related differences in motoneuron discharge patterns.

A single-arm pilot of a web-based intervention to improve itch-related quality of life.

BACKGROUND: Many patients with chronic itch and atopic dermatitis (AD) or psoriasis do not receive/use available medical and psychosocial treatments properly due to system, provider and/or patient factors. OBJECTIVE: An educational website (ITCH-RELIEF) to improve itch-related quality of life (QoL) for adults with AD or psoriasis and chronic itch was developed and assessed. ITCH RELIEF stands for Interactive Toolbox of Comprehensive Health Resources to Enhance Living with Itch - Educational Facilitation (for Adults). METHODS: Single-arm pre- and post-test design with 1-month follow-up (N = 137 at baseline). RESULTS: There was statistically and clinically significant improvement in the primary outcome of itch-related QoL impairment as assessed by the ItchyQoL from baseline [M = 78.9, 95% confidence interval (CI) = 75.9, 81.9] to follow up (M = 75.4, CI = 72.4, 78.5), P = 0.007, as well as statistically significant improvement in several itch-related secondary outcomes (all Ps < 0.05). CONCLUSIONS: This study demonstrated initial effectiveness of an online intervention to improve itch-related QoL among individuals with AD or psoriasis and chronic itch. Future studies should address limitations by randomizing more heterogeneous participants, utilizing a longer follow-up and assessing medication use.

Estimates of persistent inward currents are reduced in upper limb motor units of older adults.

Ageing is a natural process causing alterations in the neuromuscular system, which contributes to reduced quality of life. Motor unit (MU) contributes to weakness, but the mechanisms underlying reduced firing rates are unclear. Persistent inward currents (PICs) are crucial for initiation, gain control and maintenance of motoneuron firing, and are directly proportional to the level of monoaminergic input. Since concentrations of monoamines (i.e. serotonin and noradrenaline) are reduced with age, we sought to determine if estimates of PICs are reduced in older (>60 years old) compared to younger adults (<35 years old). We decomposed MU spike trains from high-density surface electromyography over the biceps and triceps brachii during isometric ramp contractions to 20% of maximum. Estimates of PICs (ΔFrequency; or simply ΔF) were computed using the paired MU analysis technique. Regardless of the muscle, peak firing rates of older adults were reduced by ∼1.6 pulses per second (pps) (P = 0.0292), and ΔF was reduced by ∼1.9 pps (P < 0.0001), compared to younger adults. We further found that age predicted ΔF in older adults (P = 0.0261), resulting in a reduction of ∼1 pps per decade, but there was no relationship in younger adults (P = 0.9637). These findings suggest that PICs are reduced in the upper limbs of older adults during submaximal isometric contractions. Reduced PIC magnitude represents one plausible mechanism for reduced firing rates and function in older individuals, but further work is required to understand the implications in other muscles and during a variety of motor tasks. KEY POINTS: Persistent inward currents play an important role in the neural control of human movement and are influenced by neuromodulation via monoamines originating in the brainstem. During ageing, motor unit firing rates are reduced, and there is deterioration of brainstem nuclei, which may reduce persistent inward currents in alpha motoneurons. Here we show that estimates of persistent inward currents (ΔF) of both elbow flexor and extensor motor units are reduced in older adults. Estimates of persistent inward currents have a negative relationship with age in the older adults, but not in the young. This novel mechanism may play a role in the alteration of motor firing rates that occurs with ageing, which may have consequences for motor control.

Nonlinear Input-Output Functions of Motoneurons.

All movements are generated by the activation of motoneurons, and hence their input-output properties define the final step in processing of all motor commands. A major challenge to understanding this transformation has been the striking nonlinear behavior of motoneurons conferred by the activation of persistent inward currents (PICs) mediated by their voltage-gated Na+ and Ca2+ channels. In this review, we focus on the contribution that these PICs make to motoneuronal discharge and how the nonlinearities they engender impede the construction of a comprehensive model of motor control.

Estimates of persistent inward currents in tibialis anterior motor units during standing ramped contraction tasks in humans.

Persistent inward currents (PICs) play an essential role in setting motor neuron gain and shaping motor unit firing patterns. Estimates of PICs in humans can be made using the paired motor unit analysis technique, which quantifies the difference in discharge rate of a lower threshold motor unit at the recruitment onset and offset of a higher threshold motor unit (ΔF). Because PICs are highly dependent on the level of neuromodulatory drive, ΔF represents an estimate of level of neuromodulation at the level of the spinal cord. Most of the estimates of ΔF are performed under constrained, isometric, seated conditions. In the present study, we used high-density surface EMG arrays to discriminate motor unit firing patterns during isometric seated conditions with torque or EMG visual feedback and during unconstrained standing anterior-to-posterior movements with root mean square EMG visual feedback. We were able to apply the paired motor unit analysis technique to the decomposed motor units in each of the three conditions. We hypothesized that ΔF would be higher during unconstrained standing anterior-to-posterior movements compared with the seated conditions, reflecting an increase in the synaptic input to motoneurons drive while standing. In agreement with previous work, we found that there was no evidence of a difference in ΔF between the seated and standing postures, although slight differences in the initial and peak discharge rates were observed. Taken together, our results suggest that both the standing and seated postures are likely not sufficiently different, both being "upright" postures, to result in large changes in neuromodulatory drive.NEW & NOTEWORTHY In the present study, we show that the discharge rate of a lower threshold motor unit at the recruitment onset and offset of a higher threshold motor unit (ΔF) is similar between standing and seated conditions in human tibialis anterior motor units, suggesting that at least for these two upright postures neuromodulatory drive is similar. We also highlight a proposed technological development in using high-density EMG arrays for real-time muscle activity feedback to accomplish standing ramped contraction tasks and demonstrate the validity of the paired motor unit analysis technique during these conditions.

Slowly activating outward membrane currents generate input-output sub-harmonic cross frequency coupling in neurons.

A major challenge in understanding spike-time dependent information encoding in the neural system is the non-linear firing response to inputs of the individual neurons. Hence, quantitative exploration of the putative mechanisms of this non-linear behavior is fundamental to formulating the theory of information transfer in the neural system. The objective of this simulation study was to evaluate and quantify the effect of slowly activating outward membrane current, on the non-linearity in the output of a one-compartment Hodgkin-Huxley styled neuron. To evaluate this effect, the peak conductance of the slow potassium channel (gK-slow) was varied from 0% to 200% of its normal value in steps of 33%. Both cross- and iso-frequency coupling between the input and the output of the simulated neuron was computed using a generalized coherence measure, i.e., n:m coherence. With increasing gK-slow, the amount of sub-harmonic cross-frequency coupling, where the output frequencies (1-8 Hz) are lower than the input frequencies (15-35 Hz), increased progressively whereas no change in iso-frequency coupling was observed. Power spectral and phase-space analysis of the neuronal membrane voltage vs. slow potassium channel activation variable showed that the interaction of the slow channel dynamics with the fast membrane voltage dynamics generates the observed sub-harmonic coupling. This study provides quantitative insights into the role of an important membrane mechanism i.e. the slowly activating outward current in generating non-linearities in the output of a neuron.

Scaling of Motor Output, From Mouse to Humans.

Appropriate scaling of motor output from mouse to humans is essential. The motoneurons that generate all motor output are, however, very different in rodents compared with humans, being smaller and much more excitable. In contrast, feline motoneurons are more similar to those in humans. These scaling differences need to be taken into account for the use of rodents for translational studies of motor output.

Inability to increase the neural drive to muscle is associated with task failure during submaximal contractions.

We investigated changes in motor unit (MU) behavior and vasti-muscle contractile properties during sustained submaximal fatiguing contractions with a new time-domain tracking technique to understand the mechanisms responsible for task failure. Sixteen participants performed a nonfatiguing 15-s isometric knee extension at 50% of the maximum voluntary (MVC) torque, followed by a 30% MVC sustained contraction until exhaustion. Two grids of 64 surface electromyography electrodes were placed over vastus medialis and lateralis. Signals were decomposed into MU discharge times and the MUs from the 30% MVC sustained contraction were followed until task failure by overlapping decomposition intervals. These MUs were then tracked between 50% and 30% MVC. During the sustained fatiguing contraction, MUs of the two muscles decreased their discharge rate until ∼40% of the endurance time, referred to as the reversal time, and then increased their discharge rate until task failure. This reversal in firing behavior predicted total endurance time and was matched by opposite changes in twitch force (increase followed by a decrease). Despite the later increase in MU firing rates, peak discharge rates at task failure did not reach the frequency attained during a nonfatiguing 50% MVC contraction. These results show that changes in MU firing properties are influenced by adjustments in contractile properties during the course of the contraction, allowing the identification of two phases. Nevertheless, the contraction cannot be sustained, possibly because of progressive motoneuron inhibition/decreased excitability, as the later increase in firing rate saturates at a much lower frequency compared with a higher-force nonfatiguing contraction.NEW & NOTEWORTHY Motor unit firing and contractile properties during a submaximal contraction until failure were assessed with a new tracking technique. Two distinct phases in firing behavior were observed, which compensated for changes in twitch area and predicted time to failure. However, the late increase in firing rate was below the rates attained in absence of fatigue, which points to an inability of the central nervous system to sufficiently increase the neural drive to muscle with fatigue.

Hyperexcitability precedes motoneuron loss in the Smn2B/- mouse model of spinal muscular atrophy.

Spinal motoneuron dysfunction and loss are pathological hallmarks of the neuromuscular disease spinal muscular atrophy (SMA). Changes in motoneuron physiological function precede cell death, but how these alterations vary with disease severity and motoneuron maturational state is unknown. To address this question, we assessed the electrophysiology and morphology of spinal motoneurons of presymptomatic Smn2B/- mice older than 1 wk of age and tracked the timing of motor unit loss in this model using motor unit number estimation (MUNE). In contrast to other commonly used SMA mouse models, Smn2B/- mice exhibit more typical postnatal development until postnatal day (P)11 or 12 and have longer survival (~3 wk of age). We demonstrate that Smn2B/- motoneuron hyperexcitability, marked by hyperpolarization of the threshold voltage for action potential firing, was present at P9-10 and preceded the loss of motor units. Using MUNE studies, we determined that motor unit loss in this mouse model occurred 2 wk after birth. Smn2B/- motoneurons were also larger in size, which may reflect compensatory changes taking place during postnatal development. This work suggests that motoneuron hyperexcitability, marked by a reduced threshold for action potential firing, is a pathological change preceding motoneuron loss that is common to multiple models of severe SMA with different motoneuron maturational states. Our results indicate voltage-gated sodium channel activity may be altered in the disease process.NEW & NOTEWORTHY Changes in spinal motoneuron physiologic function precede cell death in spinal muscular atrophy (SMA), but how they vary with maturational state and disease severity remains unknown. This study characterized motoneuron and neuromuscular electrophysiology from the Smn2B/- model of SMA. Motoneurons were hyperexcitable at postnatal day (P)9-10, and specific electrophysiological changes in Smn2B/- motoneurons preceded functional motor unit loss at P14, as determined by motor unit number estimation studies.

5-HT1D receptors inhibit the monosynaptic stretch reflex by modulating C-fiber activity.

The monosynaptic stretch reflex (MSR) plays an important role in feedback control of movement and posture but can also lead to unstable oscillations associated with tremor and clonus, especially when increased with spinal cord injury (SCI). To control the MSR and clonus after SCI, we examined how serotonin regulates the MSR in the sacrocaudal spinal cord of rats with and without a chronic spinal transection. In chronic spinal rats, numerous 5-HT receptor agonists, including zolmitriptan, methylergonovine, and 5-HT, inhibited the MSR with a potency highly correlated to their binding affinity to 5-HT1D receptors and not other 5-HT receptors. Selective 5-HT1D receptor antagonists blocked this agonist-induced inhibition, although antagonists alone had no action, indicating a lack of endogenous or constitutive receptor activity. In normal uninjured rats, the MSR was likewise inhibited by 5-HT, but at much higher doses, indicating a supersensitivity after SCI. This supersensitivity resulted from the loss of the serotonin transporter SERT with spinal transection, because normal and injured rats were equally sensitive to 5-HT after SERT was blocked or to agonists not transported by SERT (zolmitriptan). Immunolabeling revealed that the 5-HT1D receptor was confined to superficial lamina of the dorsal horn, colocalized with CGRP-positive C-fibers, and eliminated by dorsal rhizotomy. 5-HT1D receptor labeling was not found on large proprioceptive afferents or α-motoneurons of the MSR. Thus serotonergic inhibition of the MSR acts indirectly by modulating C-fiber activity, opening up new possibilities for modulating reflex function and clonus via pain-related pathways. NEW & NOTEWORTHY Brain stem-derived serotonin potently inhibits afferent transmission in the monosynaptic stretch reflex. We show that serotonin produces this inhibition exclusively via 5-HT1D receptors, and yet these receptors are paradoxically mostly confined to C-fibers. This suggests that serotonin acts by gating of C-fiber activity, which in turn modulates afferent transmission to motoneurons. We also show that the classic supersensitivity to 5-HT after spinal cord injury results from a loss of SERT, and not 5-HT1D receptor plasticity.

Locomotor-related V3 interneurons initiate and coordinate muscles spasms after spinal cord injury.

Spinal cord injury leads to a devastating loss of motor function and yet is accompanied by a paradoxical emergence of muscle spasms, which often involve complex muscle activation patterns across multiple joints, reciprocal muscle timing, and rhythmic clonus. We investigated the hypothesis that spasms are a manifestation of partially recovered function in spinal central pattern-generating (CPG) circuits that normally coordinate complex postural and locomotor functions. We focused on the commissural propriospinal V3 neurons that coordinate interlimb movements during locomotion and examined mice with a chronic spinal transection. When the V3 neurons were optogenetically activated with a light pulse, a complex coordinated pattern of motoneuron activity was evoked with reciprocal, crossed, and intersegmental activity. In these same mice, brief sensory stimulation evoked spasms with a complex pattern of activity very similar to that evoked by light, and the timing of these spasms was readily reset by activation of V3 neurons. Given that V3 neurons receive abundant sensory input, these results suggest that sensory activation of V3 neurons is alone sufficient to generate spasms. Indeed, when we silenced V3 neurons optogenetically, sensory evoked spasms were inhibited. Also, inhibiting general CPG activity by blocking N-methyl-d-aspartate (NMDA) receptors inhibited V3 evoked activity and associated spasms, whereas NMDA application did the opposite. Furthermore, overwhelming the V3 neurons with repeated optogenetic stimulation inhibited subsequent sensory evoked spasms, both in vivo and in vitro. Taken together, these results demonstrate that spasms are generated in part by sensory activation of V3 neurons and associated CPG circuits. NEW & NOTEWORTHY We investigated whether locomotor-related excitatory interneurons (V3) play a role in coordinating muscle spasm activity after spinal cord injury (SCI). Unexpectedly, we found that these neurons not only coordinate reciprocal motor activity but are critical for initiating spasms, as well. More generally, these results suggest that V3 neurons are important in initiating and coordinating motor output after SCI and thus provide a promising target for restoring residual motor function.

Progressive recruitment of contralesional cortico-reticulospinal pathways drives motor impairment post stroke.

KEY POINTS: Activation of the shoulder abductor muscles in the arm opposite a unilateral brain injury causes involuntary increases in elbow, wrist and finger flexion in the same arm, a phenomenon referred to as the flexion synergy. It has been proposed that flexion synergy expression is related to reduced output from ipsilesional motor cortex and corticospinal pathways. In this human subjects study, we provide evidence that the magnitude of flexion synergy expression is instead related to a progressive, task-dependent recruitment of contralesional cortex. We also provide evidence that recruitment of contralesional cortex may induce excessive activation of ipsilateral reticulospinal descending motor pathways that cannot produce discrete movements, leading to flexion synergy expression. We interpret these findings as an adaptive strategy that preserves low-level motor control at the cost of fine motor control. ABSTRACT: A hallmark of hemiparetic stroke is the loss of fine motor control in the contralesional arm and hand and the constraint to a grouped movement pattern known as the flexion synergy. In the flexion synergy, increasing shoulder abductor activation drives progressive, involuntary increases in elbow, wrist and finger flexion. The neural mechanisms underlying this phenomenon remain unclear. Here, across 25 adults with moderate to severe hemiparesis following chronic stroke and 18 adults without neurological injury, we test the overall hypothesis that two inter-related mechanisms are necessary for flexion synergy expression: increased task-dependent activation of the intact, contralesional cortex and recruitment of contralesional motor pathways via ipsilateral reticulospinal projections. First, we imaged brain activation in real time during reaching motions progressively constrained by flexion synergy expression. Using this approach, we found that cortical activity indeed shifts towards the contralesional hemisphere in direct proportion to the degree of shoulder abduction loading in the contralesional arm. We then leveraged the post-stroke reemergence of a developmental brainstem reflex to show that anatomically diffuse reticulospinal motor pathways are active during synergy expression. We interpret this progressive recruitment of contralesional cortico-reticulospinal pathways as an adaptive strategy that preserves low-level motor control at the cost of fine motor control.

To protect or not to protect: examining reasons for sun protection among young women at risk for skin cancer.

We aimed to further the understanding of the low rates of sun protection in young women at risk for skin cancer. Six-hundred-sixty-one daily diary entries were received via text message over 14 days from 56 young women at moderate to high risk of developing skin cancer. Women reported whether or not they used sun protection and also listed what their reasons were for using protection or not using sun protection each day. Multi-level modeling was used to examine the influence of study variables when predicting daily sun protection or lack of protection. The number of days in which sun protection was reported was positively associated with "habit" and "prevention" as reasons for protection and negatively associated with "not-needed" and "unprepared" as reasons for non-protection. Self-reported sun protection increased over the 14-day study period. Results of this study suggest the potential value of interventions aimed at motives for sun-protection behaviors.

Reflex wind-up in early chronic spinal injury: plasticity of motor outputs.

In this study we evaluate temporal summation (wind-up) of reflexes in select distal and proximal hindlimb muscles in response to repeated stimuli of the distal tibial or superficial peroneal nerves in cats 1 mo after complete spinal transection. This report is a continuation of our previous paper on reflex wind-up in the intact and acutely spinalized cat. To evaluate reflex wind-up in both studies, we recorded electromyographic signals from the following left hindlimb muscles: lateral gastrocnemius (LG), tibialis anterior (TA), semitendinosus (ST), and sartorius (Srt), in response to 10 electrical pulses to the tibial or superficial peroneal nerves. Two distinct components of the reflex responses were considered, a short-latency compound action potential (CAP) and a longer duration bout of sustained activity (SA). These two response types were shown to be differentially modified by acute spinal injury in our previous work (Frigon A, Johnson MD, Heckman CJ. J Physiol 590: 973-989, 2012). We show that these responses exhibit continued plasticity during the 1-mo recovery period following acute spinalization. During this early chronic phase, wind-up of SA responses returned to preinjury levels in one muscle, the ST, but remained depressed in all other muscles tested. In contrast, CAP response amplitudes, which were initially potentiated following acute transection, returned to preinjury levels in all muscles except for Srt, which continued to show marked increase. These findings illustrate that spinal elements exhibit considerable plasticity during the recovery process following spinal injury and highlight the importance of considering SA and CAP responses as distinct phenomena with unique underlying neural mechanisms.NEW & NOTEWORTHY This research is the first to assess temporal summation, also called wind-up, of muscle reflexes during the 1-mo recovery period following spinal injury. Our results show that two types of muscle reflex activity are differentially modulated 1 mo after spinal cord injury (SCI) and that spinal reflexes are altered in a muscle-specific manner during this critical period. This postinjury plasticity likely plays an important role in spasticity experienced by individuals with SCI.

Constitutive activity of 5-HT2C receptors is present after incomplete spinal cord injury but is not modified after chronic SSRI or baclofen treatment.

After spinal cord injury (SCI), reflexes become hyperexcitable, leading to debilitating muscle spasms and compromised motor function. Previous work has described adaptations in spinal systems that might underlie this hyperexcitability, including an increase in constitutively active 5-HT2C receptors in spinal motoneurons. That work, however, examined adaptations following complete transection SCI, whereas SCI in humans is usually anatomically and functionally incomplete. We therefore evaluated whether constitutive activity of 5-HT2C receptors contributes to reflex hyperexcitability in an incomplete compression model of SCI and to spasms in vitro and in vivo. Our results confirm that 5-HT2C receptor constitutive activity contributes to reflex excitability after incomplete SCI. We also evaluated whether constitutive activity could be altered by manipulation of neural activity levels after SCI, testing the hypothesis that it reflects homeostatic processes acting to maintain spinal excitability. We decreased neural activity after SCI by administering baclofen and increased activity by administering the selective serotonin reuptake inhibitor (SSRI) fluoxetine. We found that drug administration produced minimal alterations in in vivo locomotor function or reflex excitability. Similarly, we found that neither baclofen nor fluoxetine altered the contribution of constitutively active 5-HT2C receptors to reflexes after SCI, although the contribution of 5-HT2C receptors to reflex activity was altered after SSRIs. These results confirm the importance of constitutive activity in 5-HT2C receptors to spinal hyperexcitability following SCI in the clinically relevant case of incomplete SCI but suggest that this activity is not driven by homeostatic processes that act to maintain overall levels of spinal excitability.NEW & NOTEWORTHY After spinal cord injury (SCI), most people will develop muscle spasms below their level of injury that can severely impact function. In this work, we examine the adaptations that occur within the spinal cord after SCI that contribute to these motor dysfunctions. We also evaluate one hypothesis about how these adaptations develop, which will potentially lead to intervention strategies to improve functional outcomes in persons with SCI.

Refinement of measures to assess psychosocial constructs associated with skin cancer risk and protective behaviors of young adults.

The study's purpose was to select/refine measures assessing psychosocial constructs associated with skin cancer risk/protective behaviors. Cognitive interviewing was conducted with twenty participants locally, and a survey was conducted with 965 adults aged 18-25 years at moderate to high risk of developing skin cancer, recruited nationally online. Psychosocial measures assessed variables from the Integrative Model of Behavior Prediction. As a result of expert review and cognitive interviewing, items were removed, added, and/or made simpler, more personal, consistent, and less ambiguous. A factor analysis resulted in 14 scales and adequate model fit. Internal reliability and test-retest reliability was acceptable to good. Correlations among the psychosocial and behavioral variables were generally significant and in expected directions, demonstrating convergent validity. We have refined measures that assess important psychosocial constructs associated with skin cancer-related behaviors, that research participants can understand and complete successfully, and that are reliable and demonstrate evidence for validity.