Cortical reintegration after facial allotransplantation.

Neural plasticity of the brain or its ability to reorganize following injury has likely coincided with the successful clinical correction of severe deformity by facial transplantation since 2005. In this study, we present the cortical reintegration outcomes following syngeneic hemifacial vascularized composite allograft (VCA) in a small animal model. Specifically, changes in the topographic organization and unit response properties of the rodent whisker-barrel somatosensory system were assessed following hemifacial VCA. Clear differences emerged in the barrel-cortex system when comparing naïve and hemiface transplanted animals. Neurons in the somatosensory cortex of transplanted rats had decreased sensitivity albeit increased directional sensitivity compared with naïve rats and evoked responses in transplanted animals were more temporally dispersed. In addition, receptive fields were often topographically mismatched with the indication that the mismatched topography reorganized within adjacent barrel (same row-arc bias following hemifacial transplant). These results suggest subcortical changes in the thalamus and/or brainstem play a role in hemifacial transplantation cortical plasticity and demonstrate the discrete and robust data that can be derived from this clinically relevant small animal VCA model for use in optimizing postsurgical outcomes.NEW & NOTEWORTHY Robust rodent hemifacial transplant model was used to record functional changes in somatosensory cortex after transplantation. Neurons in the somatosensory cortex of face transplant recipients had decreased sensitivity to stimulation of whiskers with increased directional sensitivity vs. naive rats. Transplant recipient cortical unit response was more dispersed in temporary vs. naive rats. Despite histological similarities to naive cortices, transplant recipient cortices had a mix of topographically appropriate and inappropriate whiskered at barrel cortex relationships.

Effect of whisker geometry on contact force produced by vibrissae moving at different velocities.

Rats and mice are able to perform a variety of subtle tactile discriminations with their mystacial vibrissae. Increasingly, the design and interpretation of neurophysiological and behavioral studies are inspired by and linked to a more precise understanding of the detailed physical properties of the whiskers and their associated hair follicles. Here we used a piezoelectric sensor (bimorph) to examine how contact forces are influenced by the geometry of individual whisker hairs. For a given point along a whisker, bimorph signals are linearly related to whisker movement velocity. The slope of this linear function, called velocity sensitivity (VS), diminishes nonlinearly as whisker diameter decreases. Whiskers differ in overall length, thickness, and proximal-distal taper. Thus VS varies along an individual whisker and among different whiskers on the mystacial pad. Thinner, shorter whiskers, such as those located rostrally in rats and those in mice, have lower overall VSs, rendering them potentially less effective for mediating discriminations that rely on subtle velocity cues. The nonlinear effect of diameter combined with the linear effect of arc length produces radial distance tuning curves wherein small differences in the proximal-distal location of impacts yields larger differences in signal magnitude. Such position-dependent cues could contribute to the localization of objects near the face. Proximal-to-distal changes in contact location during whisking sweeps could also provide signals that aid texture discrimination.NEW & NOTEWORTHY This study describes the geometry of facial whiskers distributed across the mystacial pad with emphasis on velocity encoding of object strikes. Findings indicate how the shapes, lengths, and thicknesses of individual hairs can contribute to sophisticated vibrissa-based tactile discrimination.

Response properties of whisker-associated primary afferent neurons following infraorbital nerve transection with microsurgical repair in adult rats.

The rodent whisker/trigeminal system, characterized by high spatial and temporal resolution, provides an experimental model for developing new therapies for improving sensory functions of damaged peripheral nerves. Here, we use controlled whisker stimulation and single-unit recordings of trigeminal ganglion cells to examine in detail the nature and time course of functional recovery of mechanoreceptive afferents following nerve transection with microsurgical repair of the infraorbital nerve (ION) branch of the trigeminal nerve in adult rats. Response measures include rapid vs. slow adaptation, firing rate, interspike intervals, latency, and angular (directional) tuning. Whisker-evoked responses, readily observable by 3 wk post-transection, recover progressively for at least the next 5 wk. All cells in transected animals, as in control cases, responded to deflections of single whiskers only, but topography within the ganglion was clearly disrupted. The time course and extent of recovery of quantitative response measures were receptor dependent. Cells displaying slowly adapting (SA) properties recovered more quickly than rapidly adapting (RA) populations, and for some response measures-notably evoked firing rates-closely approached or attained control levels by 8 wk post-transection. Angular tuning of RA cells was slightly better than control units, whereas SA tuning did not differ from control values. Nerve conduction times and refractory periods, examined separately using electrical stimulation of the ION, were slower than normal in all transected animals and poorly reflected recovery of whisker-evoked response latencies and interspike intervals. Results underscore the need for multiple therapeutic strategies that target different aspects of functional restitution following peripheral nerve injury.

Assessment of fine motor control in individuals with Parkinson's disease using force tracking with a secondary cognitive task.

BACKGROUND AND PURPOSE: Motor symptoms of Parkinson's disease (PD) are typically assessed using clinical scales such as the Unified Parkinson's Disease Rating Scale, but clinical scales are insensitive to subtle changes early in the disease process. The goal of this project was to use current sensing technology to develop a quantitative assessment tool to document fine motor deficits in PD based on the ability to control grip force output. The assessment was designed to challenge deficits commonly encountered as a result of PD, including dual-task performance of a motor task and a cognitive task simultaneously. METHODS: Two force sensors were used to measure the isometric pinch grip force between the thumb and index finger in 30 individuals with PD and 30 control participants of similar age without disability. Participants performed a target force tracking task with each of two different target waveforms (sinusoidal or pseudorandom) under each of three different cognitive load conditions (none, subtract 1, and subtract 3). Dependent variables calculated from the force sensor data included root mean square error, tremor integral, and lag. RESULTS: In general, individuals with PD showed significantly less accuracy in generating the target forces as shown by larger root mean square error compared with controls (P < 0.001). They also showed greater amounts of tremor and lag compared with controls (P = 0.001 and <0.001, respectively). Deficits were more pronounced during the cognitive multitasking component of the test. DISCUSSION AND CONCLUSIONS: These results will serve as a preliminary work for the development of a clinical biomarker for PD that may help to identify subtle deficits in fine motor control early in the disease process and facilitate tracking of disease progression with time.

The synergistic effect of treadmill running on stem-cell transplantation to heal injured skeletal muscle.

Muscle-derived stem-cell (MDSC) transplantation presents a promising method for the treatment of muscle injuries. This study investigated the ability of exercise to enhance MDSC transplantation into the injured muscle. Mice were divided into four groups: contusion + phosphate-buffered saline (C + PBS; n = 14 muscles), C + MDSC transplantation (n = 12 muscles), C + PBS + treadmill running (C + PBS + TM; n = 17 muscles), and C + MDSC + TM (n = 13 muscles). One day after injury, the TM groups began running for 1 or 5 weeks. Two days after injury, muscles of C + MDSC and C + MDSC + TM groups were injected with MDSCs. One or 5 weeks later, the number and differentiation of transplanted MDSCs, myofiber regeneration, collagen I formation, and vascularity were assessed histologically. In vitro, MDSCs were subjected to mechanical stimulation, and growth kinetics were quantified. In vitro, mechanical stimulation decreased the MDSC population doubling time (18.6 +/- 1.6 h) and cell division time (10.9 +/- 0.7 h), compared with the controls (population doubling time: 23.0 +/- 3.4 h; cell division time: 13.3 +/- 1.1 h) (p = 0.01 and 0.03, respectively). In vivo, 5 weeks of TM increased the myogenic contribution of transplanted MDSCs, compared with the controls (p = 0.02). C + MDSC, C + PBS + TM, and C + MDSC + TM demonstrated decreased fibrosis at 5 weeks, compared with the C + PBS controls (p = 0.00, p = 0.03, and p = 0.02, respectively). Results suggest that the mechanical stimulation favors MDSC proliferation, both in vitro and in vivo, and that exercise enhances MDSC transplantation after injury.

A model for functional recovery and cortical reintegration after hemifacial composite tissue allotransplantation.

BACKGROUND: The ability to achieve optimal functional recovery is important in both face and hand transplantation. The purpose of this study was to develop a functional rat hemifacial transplant model optimal for studying both functional outcome and cortical reintegration in composite tissue allotransplantation. METHODS: Five syngeneic transplants with motor and sensory nerve appositions (group 1) and five syngeneic transplants without nerve appositions (group 2) were performed. Five allogeneic transplants were performed with motor and sensory nerve appositions (group 3). Lewis (RT1) rats were used for syngeneic transplants and Brown-Norway (RT1) donors and Lewis (RT1) recipients were used for allogeneic transplants. Allografts received cyclosporine A monotherapy. Functional recovery was assessed by recordings of nerve conduction velocity and cortical neural activity evoked by facial nerve and sensory (tactile) stimuli, respectively. RESULTS: All animals in groups 1 and 3 showed evidence of motor function return on nerve conduction testing, whereas animals in group 2, which did not have nerve appositions, did not show electrical activity on electromyographic analysis (p < 0.001). All animals in groups 1 and 3 showed evidence of reafferentation on recording from the somatosensory cortex after whisker stimulation. Animals in group 2 did not show a cortical response on stimulation of the whiskers (p < 0.001). CONCLUSION: The authors have established a hemiface transplant model in the rat that has several modalities for the comprehensive study of motor and sensory recovery and cortical reintegration after composite tissue allotransplantation.

Motor modulation of afferent somatosensory circuits.

A prominent feature of thalamocortical circuitry in sensory systems is the extensive and highly organized feedback projection from the cortex to the thalamic neurons that provide stimulus-specific input to the cortex. In lightly sedated rats, we found that focal enhancement of motor cortex activity facilitated sensory-evoked responses of topographically aligned neurons in primary somatosensory cortex, including antidromically identified corticothalamic cells; similar effects were observed in ventral posterior medial thalamus (VPm). In behaving rats, thalamic responses were normally smaller during whisking but larger when signal transmission in brainstem trigeminal nuclei was bypassed or altered. During voluntary movement, sensory activity may be globally suppressed in the brainstem, whereas signaling by cortically facilitated VPm neurons is simultaneously enhanced relative to other VPm neurons receiving no such facilitation.

Thalamocortical conduction times and stimulus-evoked responses in the rat whisker-to-barrel system.

Studies of the rodent whisker system indicate that somatosensory cortical circuitry operates at a millisecond timescale to transform sensory afferent signals from the thalamus. We measured axon conduction times and whisker-evoked responses of 48 thalamocortical (TC) neurons in the rat whisker-to-barrel pathway. Conduction times were derived from spike-triggered averages of local field potentials evoked in layer 4 cortical whisker-related barrels by the spontaneous firing of individual topographically aligned neurons in the ventral posterior medial thalamus. Conduction times varied fourfold, from 0.31 to 1.34 ms, and faster conducting TC neurons responded earlier and more robustly to controlled whisker deflections. Early arrival of highly responsive TC inputs, thought to contact inhibitory barrel neurons preferentially, could prime the cortical network, rendering it more selective for later-arriving signals.

Voluntary upper-extremity movements in patients with unilateral peripheral vestibular hypofunction.

BACKGROUND AND PURPOSE: People with peripheral vestibular pathology demonstrate motor impairments when responding and adapting to postural platform perturbations and during performance of sit-to-stand and locomotor tasks. This study investigated the influence of unilateral peripheral vestibular hypofunction on voluntary arm movement. SUBJECTS AND METHODS: Subjects without known neurological impairments and subjects with vestibular impairments performed 3 voluntary arm movements: an overhead reach to a target, a sideward reach to a target, and a forward flexion movement through 90 degrees. Subjects performed these tasks under precued and choice reaction time conditions. During all tasks, body segment motion was measured. Head velocity measurements were calculated for the side task only. RESULTS: Subjects with vestibular loss restricted upper body segment motion within the frontal and transverse planes for the 90-degree and overhead tasks. Average angular head velocity was lower for the group with vestibular hypofunction. Task uncertainty (the introduction of a choice reaction time paradigm) differentially influenced the groups regarding head velocity at target acquisition. DISCUSSION AND CONCLUSION: Individuals with vestibular loss altered their performance of voluntary arm movements. Such alterations may have served to minimize the functional consequences of gaze instability.

Texture discrimination and unit recordings in the rat whisker/barrel system.

We have developed a semi-automated technique for acquiring neurophysiological data during whisker-based tactile discriminative behavior. Water-deprived, blindfolded rats are tethered by means of a harness vest that permits them to contact a rough (250 micrometer grooves) or smooth discriminandum with only their vibrissae. Discriminanda are mounted on a motor-driven carousel, and the rat indicates its choice (rough, smooth) by licking either a right or left water port located near the carousel. A narrow light beam detects general proximity of the animal's nose to the discriminandum, although actual whisker contact is monitored by a SuperVHS camera and measured offline using field-by-field videographic analysis. Rats can be trained within 3-6 weeks at which time they perform 100-150 trials/day at a level of 80% correct. Unit recording from the somatosensory cortex reveals that neurons increase their firing upon whisker contact of a discriminandum and that firing remains elevated during several hundred milliseconds of ongoing contact, even with the smooth surface. Nevertheless, despite the animal's ability to distinguish the rough and smooth surfaces, overall neuronal firing rates were indistinguishable for the two surfaces. In some cases, temporal firing patterns differed, although not in a consistent way across recording sites.