Characterization of the relationship between motor end-plate jitter and the safety factor

A mathematical model developed for a personal computer was used to simulate the jitter phenomenon in neuromuscular transmission in order to characterize the relationship between jitter and the safety factor. Four models of normal and abnormal neuromuscular transmission were investigated. In a human experiment, the mean consecutive difference (MCD) values for stimulated single-fiber electromyography at firing rates of 1, 2, 5, and 10 Hz were measured in 137 motor end-plates of myasthenic patients. Results of the computer simulations show that the relationship between jitter and the safety factor is exponential like. Variations in jitter are most prominent in end-plates with low safety factors. This relationship agrees with results of human end-plate studies. Changes in the MCD values caused by presynaptic depression or facilitation are linearly correlated to the initial jitter, whereas the logarithmic values of MCD are not. It is very important to keep in mind this nonlinear relationship when relating single-fiber jitter to the safety factor. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21:628–636, 1998.     

Golgi studies on Purkinje cell development in the frog during spontaneous metamorphosis. III. Axonal development

The development and organization of Purkinje cell axons and their collaterals was studied in the bullfrog using the Golgi-Kopsch method. In the tadpole, axonal collaterals are few and usually unbranched. In the adult, however, intracortical axonal collaterals of Purkinje cells are more numerous, and they form a meager supraganglionic plexus and a more extensive infraganglionic plexus. In contrast to the pattern seen in higher vertebrates, these plexuses have a tendency to be distributed along the length of the cerebellar plate in both tadpoles and froglets. In addition, collateral branches that form intracortical plexuses apparently increase throughout the course of cerebellar development in this species.     

Transcranial DC stimulation (tDCS): a tool for double-blind sham-controlled clinical studies in brain stimulation.

OBJECTIVE: Brain polarization in the form of transcranial direct current stimulation (tDCS), which influences motor function and learning processes, has been proposed as an adjuvant strategy to enhance training effects in Neurorehabilitation. Proper testing in Neurorehabilitation requires double-blind sham-controlled study designs. Here, we evaluated the effects of tDCS and sham stimulation (SHAM) on healthy subjects and stroke patients' self-report measures of attention, fatigue, duration of elicited sensations and discomfort. METHODS: tDCS or SHAM was in all cases applied over the motor cortex. Attention, fatigue, and discomfort were self rated by study participants using visual analog scales. Duration of perceived sensations and the ability to distinguish tDCS from Sham sessions were determined. Investigators questioning the patients were blind to the intervention type. RESULTS: tDCS and SHAM elicited comparably minimal discomfort and duration of sensations in the absence of differences in attention or fatigue, and could not be distinguished from SHAM by study participants nor investigators. CONCLUSIONS: Successful blinding of subjects and investigators and ease of application simultaneously with training protocols supports the feasibility of using tDCS in double-blind, sham-controlled randomized trials in clinical Neurorehabilitation. SIGNIFICANCE: tDCS could evolve into a useful tool, in addition to TMS, to modulate cortical activity in Neurorehabilitation.     

Axonal pathways linked to therapeutic and nontherapeutic outcomes during psychiatric deep brain stimulation

Objective:

The underlying hypothesis of our work is that specific clinical neuropsychiatric benefits can be achieved by selective activation of specific axonal pathways during deep brain stimulation (DBS). As such, the goal of this study was to develop a method for identifying axonal pathways whose activation is most likely necessary for achieving therapeutic benefits during DBS.

Experimental design:

Our approach combined clinical data, diffusion tensor tractography, and computer models of patient‐specific neurostimulation to identify particular axonal pathways activated by DBS and determine their correlations with individual clinical outcome measures. We used this method to evaluate a cohort of seven treatment‐resistant depression patients treated with DBS of the ventral anterior internal capsule and ventral striatum (VC/VS).

Principal observations:

Clinical responders exhibited five axonal pathways that were consistently activated by DBS. All five pathways coursed lateral and medial to the VS or dorsal and lateral to the nucleus accumbens; however, details of their specific trajectories differed. Similarly, one common pathway was identified across nonresponders.

Conclusions:

Our method and preliminary results provide important background for studies aiming to expand scientific characterization of neural circuitry associated with specific psychiatric outcomes from DBS. Furthermore, identification of pathways linked to therapeutic benefit provides opportunities to improve clinical selection of surgical targets and stimulation settings for DBS devices. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.

     

强直性肌营养不良的激发重复神经电刺激研究

对９例强直性肌营养不良患者行激发重复神经电刺激检查。１例ＡＲＮＳ前见序列复合肌肉动作电位波幅递减，８例ＡＲＮＳ后出现首位ＣＭＡＰ波幅降低，其中６例伴序列ＣＭＡＰｓ波幅递减。首位ＣＭＡＰ波幅降低出现率和平均降低程度随病程延长而加重。     

Axonal trees and cortical architecture.

In modern computer design considerable care is taken to arrange the components in such a way that wiring is kept to a minimum. Certain features of cortical structure--the mappings, stripes and blobs within areas, and areas themselves--are somewhat reminiscent of the layout of computer components, and suggest that the cortex may also be organized so as to economize on neuronal 'wiring'. One important difference between the brain and a computer is that the wiring in the brain takes the form of elaborate branched structures, namely axonal trees. In this article, it is argued that an assessment of the efficiency of cortical wiring must take account of the branching rules of these trees.     

Axonal degeneration in beriberi neuropathy.

Ultrastructural and teased-fiber studies were carried out on the sural nerves of nine patients with beriberi neuropathy Axonal degeneration was the most prominent feature, and large myelinated fibers were more affected than unmyelinated ones. An unusual change with accumulation of flattened sacs or tubuli was recognized in the axoplasm of myelinated fibers of untreated patients. Active regeneration was extensive in patients receiving vitamin B. Segmental demyelination, remyelination, and early onion bulbs were scarece in patients with a long and relapsing course before treatment.     

Single fibre electromyographic jitter in multiple sclerosis.

Recent histological and electrophysiological reports have given evidence for peripheral nervous system (PNS) involvement in multiple sclerosis. We have applied the single fibre electromyography (SFEMG) technique to 15 patients with multiple sclerosis. Six patients had clearly abnormal jitter and two of these had previously undiagnosed coexistent peripheral neuropathy. A further five patients had borderline abnormalities of SFEMG. The mean jitter for each patient was abnormal in 10 patients. This was clear evidence for PNS involvement in this disease. Theoretically, the site of the abnormality could be in the terminal nerve network or at the neuromuscular junction, but this technique cannot distinguish between these sites.     

Facioscapulohumeral dystrophy: jitter in facial muscles.

Motor end plate jitter was studied by single fibre EMG in the orbicularis oculi muscle of eight patients with facioscapulohumeral dystrophy activated by extramuscular nerve stimulation. The jitter was found to be slightly larger in comparison with the normal controls, although still within the normal limits in each patient. The findings are considered to indicate absence of any significant neuromuscular transmission disturbance, inflammatory or regenerative process, or reinnervation in progress. There was no evidence of muscle fibre conduction abnormality even in very weak muscle.     

Concentric needle electrode for neuromuscular jitter analysis

We used a concentric needle electrode (CNE) with 2 kHZ low-cut filter and a single fiber electrode (SFE) in the same subjects for neuromuscular jitter measurement in the extensor digitorum communis (EDC) and orbicularis oculi (OOc) muscles. At the same session, 20 jitter values were obtained from each subject with each electrode. For EDC (during voluntary contraction), mean jitter values with SFE and CNE were 23.4 +/- 8 micros and 23.3 +/- 8 micros in 10 normals; and 56.8 +/- 28 micros and 57.4 +/- 33 micros in 10 myasthenics. For OOc (during electrical stimulation), mean jitter values with SFE and CNE were 17.9 +/- 5 micros and 16.3 +/- 4 micros in 11 normal subjects, and 41.2 +/- 29 micros and 36.7 +/- 27 micros in 10 myasthenics. For both muscles, the numbers of individual abnormal jitter values with SFE and CNE were highly comparable. Both needles labeled the same patients as having "normal" or "abnormal" neuromuscular transmission. CNE may be an alternative to SFE in neuromuscular jitter analysis.     

Determining neuromuscular jitter using a monopolar electrode.

Neuromuscular jitter was determined in the extensor digitorum communis (EDC) of 41 healthy control subjects and 8 patients with myasthenia gravis (MG). Standard single-fiber electromyographic (SFEMG) techniques were used, except that a monopolar electrode (MPE) was substituted for a single-fiber electrode (SFE). In normals, mean jitter for 20 pairs was 22.4 +/- 2.8 microseconds and the mean jitter for an individual pair was 22 +/- 5.6 microseconds. In the age range tested (18 to 49 years), jitter did not change with increasing age. When MPE jitter studies were repeated in 16 normals, mean jitter usually varied by less than 10% (mean 7.4% +/- 6.2%) and remained normal. Jitter was significantly increased in MG compared to normals 73 +/- 56 microseconds versus 22 +/- 5.6 microseconds (F = 149.4, P less than 0.0001). Using an analog pain scale, the discomfort during electromyography using MPE and SFE was compared between the left and right arms in 35 normals. MPEs caused less discomfort than SFEs (P = 0.0031), and were preferred (71% versus 20%) to SFEs (chi 2 = 9.21, P = 0.01). Based on these results, we conclude that MPE determined jitter studies are reproducible, can distinguish between normals and MG, and are associated with less discomfort than SFE.     

Downward gaze in monkeys: stimulation and lesion studies.

Ten monkeys were stimulated unilaterally and bilaterally through bipolar electrodes placed stereotactically on each side of the midline under light barbiturate anaesthesia. Bilateral simultaneous stimulation elicited straight downward binocular movements from a core of tissue about 40 mm3 on each side which included the fields of Forel, zona incerta, subthalamic nucleus, oral pole of the red nucleus, fasciculus retroflexus and 'area tegmentalis'. Unilateral stimulation of the same points yielded downward eye movements in only 25 per cent of the instances. Upward deviation of the globes could be elicited by bilateral stimulation of tissue located more caudal, ventral and medial than that from which downward movements were obtained. Bilateral electrolytic lesions within the region outlined above caused significant defects in downward gaze both in saccadic and slow pursuit binocular movements. Passive bending of the head backwards, however, resulted in downward deviation of the globes (oculocephalic reflex). Optokinetic nystagmus and after-nystagmus downward were abolished. Oblique (45 degrees) optokinetic stimulation elicited a perverted response in the horizontal plane. Vestibulo-ocular reflexes elicited by bilateral warm irrigation of both ear canals with the monkey in the erect position, or by turning the animal while lying on one side, caused a strong tonic deviation upward with absence of nystagmus downward. Some of these monkeys showed additional alterations in upward gaze but they were less severe in intensity and duration than those of downward gaze. All eye deviations in the horizontal plane were consistently normal. Recovery occurred in all types of vertical binocular movements except in the rapid motions (saccades and quick phases of nystagmus) below the horizontal meridian. A unilateral lesion had no effect. The minimal damage producing downward gaze defects was about 1.7 mm in diameter, cetred in the prerubral fields, rostral and medial to the red nuclei with minimal involvement of the oral pole of these structures. The nuclei of Cajal, Darkschewitsch and interstitialis of the posterior commissure, as well as the fasciculus retroflexus and the posterior commissure, were spared by this lesion. The so-called rostral interstitial nucleus of the medial longitudinal fasciculus and the nucleus campi Foreli appear to be destroyed. These structures are known to receive an input from the paramedian pontine reticular formation and project on to the oculomotor nerve nucleus. These results demonstrate that the prerubral fields contain structures which are critical for rapid eye movements downward, and therefore an isolated downward gaze palsy is a strong indicator of a bilateral lesion of this zone. The findings in the few reported cases with this sign and available pathological analysis suggest that our conclusions from the experimental monkey apply to man as well. The concept of bilateral innervation for vertical eye movements is amply confirmed for the downward vectors...     

Axonal degeneration in sodium cyanate-induced neuropathy.

Two patients with sickle cell disease who had been maintained on sodium cyanante therapy for periods of 440 and 600 days on dosages up to 44 and 41 mg/kg per day developed a motor and sensory neuropathy. In both, definite abnormalities of myelinated and unmyelinated fibers were found. In one, the predominant abnormality of myelinated fibers was segmental demyelination and remyelination; in the other, there were histological features typical of axonal degeneration. It seems unlikely that the brunt of the metabolic derangement was on Schwann cells in the first case and on the nerve cell in the second. Probably, in both cases, the primary effect was on the nerve, with Schwann cell changes being concomitant or secondary. The clustered distribution of the segmental demyelination favors the latter.     

Axonal swellings in human intramuscular nerves.

The presence, morphology, distribution, and abundance of axonal swellings in intramuscular nerves were evaluated. Axonal swellings were present in intramuscular nerves in 42% of 127 muscle biopsies from patients with a variety of conditions. The incidence was highest in muscle from patients with peripheral neuropathy, but swellings were present in muscle from patients with motor neuron disease, primary muscle diseases, and some individuals without clinical or histological evidence of neuromuscular disease. The greatest number of swellings in intramuscular nerves was in muscle from patients with chronic inflammatory demyelinating neuropathy. Swellings were spherical or elliptical, 4-20 microns in diameter, 5-30 microns in length, and composed of neurofilaments. Swellings were present only in myelinated axons of intramuscular nerves, proximal to nodes of Ranvier or in internodal regions. Swellings were not associated with axonal degeneration. They were probably not transported. The formation or accumulation of swellings may reflect altered axonal dynamics common to a number of disease processes.