Ultrastructural reversible changes in fish neuromuscular junctions after chronic exercise

Neuromuscular junctions (NJs) of fin muscles of teleostean fishes, Lebistes reticulatus, were ultrastructurally analyzed during 60 min of chronic exercise and a subsequent period of 90 min of induced recovery. NJs from 30-min-exercised fishes showed an almost complete depletion of synaptic vesicles (SVs), corresponding to 83% of SV consumption; 76% of axon terminals were branched at the end of this period. During the recovery period, it was possible to observe the reversibility of the changes induced by the exercise and the transitory events that lead to the reacquirement of the normal NJ morphology. After 15 min of rest, SV population increased to a value of 54.6 SVs/micron2 and the percentage of branched axons was 66.5%. At 60 min of recovery the number of SVs reached a value of 84.6 SVs/micron2. The SV population was fully reestablished at 80 min of rest, while the percentage of branched axons was found within normal ranges after 90 min of recovery. These results demonstrate that chronic exercise induced physiological depletion of NJ SVs and other axon terminal morphological changes, as well as that postexercise rest induces the reestablishment of the normal NJ morphology.     

Normal intracortical excitability in developmental stuttering.

Persistent developmental stuttering (PDS) shares clinical features with task-specific dystonias. In these dystonias, intracortical inhibition is abnormally weak. We therefore sought to determine intracortical inhibition and intracortical facilitation in PDS. In 18 subjects with PDS since childhood (mean age, 39.4 [SD 13.0] years) and 18 speech-fluent controls (43.6 [14.3] years), we investigated resting and active motor thresholds as well as intracortical inhibition and facilitation of the optimal representation of the abductor digiti minimi of the dominant hand using transcranial magnetic stimulation. In PDS, the resting and active motor thresholds were increased, whereas intracortical inhibition and facilitation were normal. Normal intracortical excitability makes a pathophysiological analogy between focal dystonia and PDS less likely. The enhanced motor threshold suggests reduced motor cortical neuronal membrane excitability in PDS.     

Different effects of unilateral versus bilateral subthalamic nucleus stimulation on walking and reaching in Parkinson's disease.

The purpose of this study was to determine the effects of unilateral versus bilateral subthalamic nucleus (STN) stimulation on quantitative measures of walking and reaching in Parkinson's disease (PD). We used kinematic measures and the Unified Parkinson's Disease Rating Scale (UPDRS) motor subscale (subscale III) to evaluate the movement of 6 people with PD who had bilateral STN stimulators implanted for at least 6 months and withheld their anti-parkinson medication for at least 8 hours. Subjects were studied with both stimulators off, one on, and both on. Kinematic data were collected as subjects walked, reached to a target, and were rated using the UPDRS motor subscale. STN stimulation improved walking speed and stride length, with the greatest benefit from bilateral stimulation. Reaching speed was improved by unilateral STN stimulation alone, with no additive effect of bilateral stimulation. UPDRS motor subscale ratings paralleled the kinematic findings. STN stimulation did not restore PD subjects' movements to the level of age-matched controls. Overall, these results provide further evidence that the basal ganglia pathways involved in control of walking and reaching may be distinct. We speculate that basal ganglia may influence walking through bilateral pedunculopontine projections and reaching through ipsilateral thalamocortical projections. Our findings also suggest that maximal improvement of walking requires bilateral rather than unilateral STN stimulation.     

Reversible shifts in the Ca2+-dependent release of aspartate and glutamate from hippocampal slices with changing glucose concentrations

It is known that low glucose concentrations increase the aspartate and decrease the glutamate content of brain tissue both in vivo and in vitro. To see whether these changes occur in the transmitter compartment or not, the release of aspartate and glutamate evoked by electrical-field stimulation or by high K+ was followed in slices of rat hippocampus superfused with 5 or 0.2 mM glucose. Superfusion with 0.2 mM glucose increased the evoked release of aspartate about ten times and that of glutamate about threefold. This shift in the ratio of aspartate to glutamate released was accompanied by a similar increase in the relative amount of aspartate contained in the slices. The high evoked release of aspartate and glutamate was well maintained, provided 0.5 mM glutamine was added to the medium. Changing the concentration of glucose after the first period of stimulation rapidly altered the relative amounts of aspartate and glutamate released but not the enhanced release of glutamate. The large evoked release of both aspartate and glutamate in 0.2 mM glucose was almost entirely Ca2+-dependent. The relative amounts of aspartate and glutamate released by 50 mM K+ also changed when the glucose concentration was reduced. Results suggest two effects of low glucose concentrations: an increase in the overflow of synaptically released glutamate due to a decreased uptake and an increase in the proportion of aspartate to glutamate formed and released from the transmitter pool. These observations are consistent with the interpretation that these two transmitters can be released in different proportions from the same terminals.     

Impaired modulation of motor cortex excitability by homonymous and heteronymous muscle afferents in focal hand dystonia.

A decrease of heteronymous median nerve-evoked inhibition of corticospinal projections to forearm extensor muscles was reported in a group of 10 dystonic patients by Bertolasi and colleagues in 2003. Here we tested the excitability of corticomotoneuronal connections to both wrist extensor (ECR) and flexor (FCR) muscles after conditioning stimulation of median and also radial nerve at rest in a group of 25 patients with focal hand dystonia compared to 20 healthy subjects. We also investigated the effect of the wrist dystonic posture, either in flexion or in extension, on the afferent modulation of ECR and FCR motor evolved potentials (MEPs). The heteronymous (median-induced) but also homonymous (radial-induced) inhibitions (interstimuli intervals 13-21 ms) of ECR MEP size observed in healthy subjects were decreased in patients. In addition, homonymous (median-induced) facilitation of FCR MEP size was also decreased in patients while heteronymous inhibition (radial-induced) was not. Neither the involvement of the target muscle in the dystonic posture nor the origin of the afferent volley (from a dystonic muscle) influenced the degree of impairment of afferent modulation of the MEP. These findings support the view that a global abnormal somatosensory coupling in focal hand dystonia may contribute to an inadequate motor command to wrist muscles.     

Real-time refinement of subthalamic nucleus targeting using Bayesian decision-making on the root mean square measure.

The subthalamic nucleus (STN) is a major target for treatment of advanced Parkinson's disease patients undergoing deep brain stimulation surgery. Microelectrode recording (MER) is used in many cases to identify the target nucleus. A real-time procedure for identifying the entry and exit points of the STN would improve the outcome of this targeting procedure. We used the normalized root mean square (NRMS) of a short (5 seconds) MER sampled signal and the estimated anatomical distance to target (EDT) as the basis for this procedure. Electrode tip location was defined intraoperatively by an expert neurophysiologist to be before, within, or after the STN. Data from 46 trajectories of 27 patients were used to calculate the Bayesian posterior probability of being in each of these locations, given RMS-EDT pair values. We tested our predictions on each trajectory using a bootstrapping technique, with the rest of the trajectories serving as a training set and found the error in predicting the STN entry to be (mean +/- SD) 0.18 +/- 0.84, and 0.50 +/- 0.59 mm for STN exit point, which yields a 0.30 +/- 0.28 mm deviation from the expert's target center. The simplicity and computational ease of RMS calculation, its spike sorting-independent nature and tolerance to electrode parameters of this Bayesian predictor, can lead directly to the development of a fully automated intraoperative physiological procedure for the refinement of imaging estimates of STN borders.     

Abnormal sensorimotor integration is related to disease severity in Parkinson's disease: a TMS study.

Hyperexcitability of the motor system has been reported in Parkinson's disease (PD). We evaluate how cutaneous afferents modulate motor excitability in PD patients and whether abnormal modulation is correlated to parkinsonian symptoms. Digital stimulation causes abnormal enhancement of motor responses in patients. This effect may be one of the features of motor hyperexcitability in PD. Cutaneomotor hyperexcitability correlates with clinical scores, suggesting that abnormal processing of cutaneous inputs might contribute to the pathogenesis of parkinsonian symptoms.     

Primary orthostatic tremor is an exaggeration of a physiological response to instability.

Primary orthostatic tremor (POT) is a rare disorder characterised by an intense sense of unsteadiness upon standing and a 16-Hz tremor in which the timing between tremor bursts in different muscles (unilateral and bilateral) remains constant. Hitherto, similar EMG activity has not been described in healthy subjects and it has been postulated that the oscillations seen in POT are primarily pathological. In this study, EMG was recorded from tibialis anterior in healthy subjects who were made unsteady through vestibular galvanic stimulation or leaning backwards. Under these conditions, a peak at approximately 16 Hz was seen in the coherence between the left and right tibialis anterior. This bilateral coherence was absent when the subjects activated the same muscles when not unsteady. These data indicate the existence of a physiological system involved in organising postural responses under circumstances of imbalance and characterised by a highly synchronised output at approximately 16 Hz. In addition, the results suggest that the core abnormality in POT may be an exaggerated sense of unsteadiness when standing still, which then elicits activity from a 16-Hz oscillator normally engaged in postural responses.     

Electrophysiologic target localization in posteroventral pallidotomy

Summary The current interest in stereotactic posteroventral pallidotomy (PVP) for treating Parkinson's disease and the variability of published results have raised questions regarding techniques for target localization. In our technique the probe is guided to the optimum target at the most ventral pallidum and ansa lenticularis by macroelectrode stimulation of the internal capsule and optic tract from within the globus pallidus, with the thresholds providing a relative measure of the electrode proximity to these structures. We have characterized these localizing macroelectrode stimulation parameters in 57 posteroventral pallidotomies with consistent anatomic lesion placement, excellent outcome, and no complications.Using a 1.8 × 2.0 mm radiofrequency electrode for macroelectrode stimulation (RFG-3C, Radionics Inc.), minimum voltages (thresholds) to activate motor (at a frequency of 2 Hz) or visual (at a frequency of 100 Hz) responses as well as impedance measurements were obtained at the final target (Tf) and at distances proximal to Tf along the electrode trajectory. The visual and motor threshold voltages at Tf via our standard approach angles (50 ° above base plane, 20 ° from the sagittal plane), had a range of 1.0 to 1.5 V, and 2.0 to 3.5 V respectively. We also found that as the probe approaches Tf there is a significant decrease in voltage thresholds for motor (P<.0001) and visual (P<.0001) responses in an individual patient indicating that the probe is converging on these structures. Increases in impedance between Tf, 2–3 mm, and 4–5 mm proximal to Tf were also statistically significant (P<.0001). Microelectrode recording of electrophysiological neuronal activity at various points along the trajectory towards the target showed distinct firing patters providing identification of the globus pallidus externus and internus, ansa lenticularis, and optic tract.Macroelectrode electrophysiological stimulation within the target volume, inducing threshold responses in the internal capsule and optic tract, provides for accurate localization of the most effective PVP target in the ansa lenticularis. In unresponsive patients, the utilization of microelectrode recording for the identification of the pallidal borders and the optic tract improves safety.     

Activity of lateral vestibular nucleus neurons during locomotion in the decerebrate Guinea pig

Summary The influence of locomotor activity upon neurons in the lateral vestibular nucleus was investigated in precollicularly-postmamillary decerebrate guinea pigs. Out of 95 recorded neurons, 24 were identified as vestibulospinal and 71 had no descending projections. Locomotor activity occurred either spontaneously or was prompted by electrical stimulation of the mesencephalic locomotor region. Natural vestibular stimulation was supplied by tilting the animal about its longitudinal axis. Locomotor rhythmic limb muscle activity was accompanied by an increase in the firing frequency in the vast majority of investigated neurons. The increase in frequency was observed at the beginning of ipsilateral forelimb extensor muscle activity. Only in a few non-vestibulospinal neurons was the spontaneous activity depressed during locomotion. An increase in evoked responses was observed in almost all vestibulospinal neurons and in two thirds of the neurons without descending projections. A decrease in evoked responses was observed in one quarter of non-vestibulospinal neurons. During locomotion, the mean and maximal frequencies of evoked neuronal impulse activity changed, but the phase lag of these changes was not altered significantly. The results suggest an enhancement of vestibulospinal influences during locomotion, thus providing a high level of tonus in antigravitational muscles. This is interpreted as a mechanism to ensure that equilibrium is maintained during motion in different gaits and postures.