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Contrasting to the established role of the hypothalamic agouti-related protein (AgRP) neurons in feeding regulation, the neural circuit and signaling mechanisms by which they control energy expenditure remains unclear. Here, we report that energy expenditure is regulated by a subgroup of AgRP neurons that send non-collateral projections to neurons within the dorsal lateral part of dorsal raphe nucleus (dlDRN) expressing the melanocortin 4 receptor (MC4R), which in turn innervate nearby serotonergic (5-HT) neurons. Genetic manipulations reveal a bi-directional control of energy expenditure by this circuit without affecting food intake. Fiber photometry and electrophysiological results indicate that the thermo-sensing MC4R dlDRN neurons integrate pre-synaptic AgRP signaling, thereby modulating the post-synaptic serotonergic pathway. Specifically, the MC4R dlDRN signaling elicits profound, bi-directional, regulation of body weight mainly through sympathetic outflow that reprograms mitochondrial bioenergetics within brown and beige fat while feeding remains intact. Together, we suggest that this AgRP neural circuit plays a unique role in persistent control of energy expenditure and body weight, hinting next-generation therapeutic approaches for obesity and metabolic disorders.

The objective of the study was to investigate the efficacy of three energy densities 4, 10, and 50 J/cm 2 of pulsed Nd:YAG laser for the treatment of crushed sciatic nerve in Wister rats by evaluating changes in the sciatic functional index and the electrophysiology.A total of 180 Wistar rats were involved in the study. Rats were randomly assigned to five groups. Rats were subjected to the sciatic nerve crushing. Control negative (CONT-ve), which received no crushing; control positive (CONT+ve), which received crushing with no laser; and HILT-4, HILT-10, and HILT-50 groups, which received pulsed Nd:YAG laser (10 Hz, 360 mJ/cm 2 ) with energy densities 4, 10, and 50 J/cm 2 , respectively. The SFI, the amilitude of compound motor action potential (CMAP) and sciatic motor nerve conduction velocity (MNCV) were measured before and after seven, 14, and 21 days after crushing. For the SFI and electrophysiological analysis, repeated measures ANOVA is used, followed by Bonferroni's repeated-measures test. Statistical significance was set at p < 0.05. After one week, there was no significant difference in SFI, CMAP, and MNCV among the three laser groups with significant changes between them and CONT-ve and CONT+ve groups. There was a significant increase in either CMAP amplitude or MNCV after 14 days with significant decrease in the SFI after 21 days among all treatment groups. The pulsed Nd:YAG laser applied with energy densities 4, 10, and 50 J/cm 2 significantly decreased the SFI and increased the CMAP and MNCV of the crushed sciatic nerve in Wister rats. Among laser doses, the difference in the rate of recovery in the electrophysiology was found after two weeks while in the SFI after three weeks. The improvement after the nerve injury was time and dose dependent.

Background: Watchful waiting in patients with rectal cancer with complete clinical response after chemoradiation therapy has gained increased popularity to avoid morbidity and mortality associated with surgery. Irradiation of the pelvis causes bowel dysfunction, but the effect on anorectal sensory function remains obscure in this patient category., Objective: The aim of this study was to characterize the sensory pathways of the gut-brain axis in patients with rectal cancer treated solely with chemoradiation therapy (nonconventional regime/dose) compared with healthy volunteers., Design: This is an explorative study., Settings: Sensory evaluation by rectal distension was performed and cortical evoked potentials were recorded during rapid balloon distensions of the rectum and anal canal. Latencies and amplitudes of cortical evoked potentials were compared, and the relative amplitude of 5 spectral bands from recorded cortical evoked potentials was used as an additional proxy of neuronal processing., Patients: Patients with rectal cancer solely with chemoradiation therapy (n = 13) a median of 3.2 years ago (range, 2.3-5.6 y) and healthy volunteers (n = 13) were included., Main Outcome Measures: Cortical evoked potentials were measured., Results: Patients had 35% lower rectal capacity at a maximum tolerable volume (p = 0.007). We found no differences in rectal cortical evoked potential latencies (p = 0.09) and amplitudes (p = 0.38) between groups. However, spectral analysis of rectal cortical evoked potentials showed a decrease in θ (4-8 Hz) and an increase in β (12-32 Hz) band activity in patients (all p < 0.001). Anal cortical potentials showed an increase in α (8-12 Hz) and β and a decrease in γ (32-70 Hz) band activity (all p < 0.001) in patients compared with healthy volunteers., Limitations: This is an explorative study of limited size., Conclusions: Chemoradiation therapy for distal rectal cancer causes abnormal cortical processing of both anal and rectal sensory input. Such central changes may play a role in symptomatic patients, especially when refractory to local treatments. See Video Abstract at http://links.lww.com/DCR/B270. RESPUESTA NEURONAL ANORMAL A ESTÍMULOS RECTALES Y ANALES, EN PACIENTES TRATADOS POR CÁNCER RECTAL DISTAL, CON QUIMIORRADIOTERAPIA DE DOSIS ALTA, SEGUIDA DE ESPERA VIGILANTE: La espera vigilante en pacientes de cáncer rectal, con respuesta clínica completa después de la quimiorradiación, ha ganado una mayor popularidad en evitar la morbilidad y mortalidad asociadas con la cirugía. La irradiación de la pelvis causa disfunción intestinal, pero el efecto sobre la función sensorial ano-rectal sigue siendo no claro, en esta categoría de pacientes.El objetivo de este estudio, fue caracterizar las vías sensoriales del eje intestino-cerebro en pacientes con cáncer rectal, tratados únicamente con quimiorradiación (régimen / dosis no convencional), en comparación con voluntarios sanos.Es un estudio exploratorio.Se realizó una evaluación sensorial por distensión rectal y se registraron los potenciales evocados corticales, durante las distensiones rápidas con balón en recto y canal anal. Se compararon las latencias y amplitudes de los potenciales evocados corticales, y la amplitud relativa de cinco bandas espectrales registradas, de potenciales evocados corticales, se usaron como proxy adicional del procesamiento neuronal.Pacientes de cáncer rectal, únicamente con terapia de quimiorradiación (n = 13) mediana de 3.2 años (rango 2.3-5.6) y voluntarios sanos (n = 13).Potenciales evocados corticales.Pacientes tuvieron una capacidad rectal menor del 35%, al volumen máximo tolerable (p = 0.007). No encontramos diferencias en las latencias potenciales evocadas corticales rectales (p = 0.09) y amplitudes (p = 0.38) entre los grupos. Sin embargo, el análisis espectral de los potenciales evocados corticales rectales, mostró una disminución en theta (4-8 Hz) aumento en beta (12-32 Hz), y actividad en banda en pacientes (todos p <0.001). Los potenciales evocados corticales anales mostraron un aumento en alfa (8-12 Hz) y beta, disminución en gamma (32-70 Hz), y actividad en banda (todos p <0.001), en pacientes comparados a voluntarios sanos.Este es un estudio exploratorio de tamaño limitado.La quimiorradiación para el cáncer rectal distal, ocasiona procesos corticales sensoriales anormales anales y rectales. Tales cambios centrales pueden desempeñar un papel en pacientes sintomáticos, especialmente cuando son refractarios a tratamientos locales. Consulte Video Resumen en http://links.lww.com/DCR/B270.

Despite great progress in neuroscience, there are still fundamental unanswered questions about the brain, including the origin of subjective experience and consciousness. Some answers might rely on new physical mechanisms. Given that biophotons have been discovered in the brain, it is interesting to explore if neurons use photonic communication in addition to the well-studied electro-chemical signals. Such photonic communication in the brain would require waveguides. Here we review recent work (S. Kumar, K. Boone, J. Tuszynski, P. Barclay, and C. Simon, Scientific Reports 6, 36508 (2016)) suggesting that myelinated axons could serve as photonic waveguides. The light transmission in the myelinated axon was modeled, taking into account its realistic imperfections, and experiments were proposed both in vivo and in vitro to test this hypothesis. Potential implications for quantum biology are discussed.

Radiofrequency-based electrophysical agents (EPA) have been used in therapy practice over several decades (e.g., shortwave therapies). Currently, there is insufficient evidence supporting such devices operating below shortwave frequencies. This laboratory-based study investigated the skin physiological effects of 448 kHz capacitive resistive monopolar radiofrequency (CRMRF) and compared them to pulsed shortwave therapy (PSWT). In a randomised crossover study, seventeen healthy volunteers received four treatment conditions - High, Low and Placebo dose conditions receiving 15-min CRMRF treatment and a Control condition receiving no intervention. Fifteen participants also received high dose PSWT for comparison. Treatment was applied to the right lower medial thigh. Pre, post and 20-min follow-up measurements of skin temperature (SKT), skin blood flow (SBF) and nerve conduction velocity (NCV) were obtained using Biopac MP150 system. Group data were compared using the ANOVA model. Statistical significance was set at p ≤ 0.05 (0.8P, 95%CI). Significant increase and sustenance of SKT with both high and low dose CRMRF was demonstrated over the other groups (p < 0.001). PSWT increased SKT significantly (p < 0.001) but failed to sustain it over the follow-up. However, among the five conditions, only high dose CRMRF significantly increased and sustained SBF (p < 0.001). Overall, the CRMRF physiological responses were significantly more pronounced than that of PSWT. No significant changes in NCV were noted for any condition. Physiological changes associated with CRMRF were more pronounced when compared to PSWT, placebo or control. Any potential stronger therapeutic benefits of CRMRF need to be confirmed by comparative clinical studies.

Background: The development of hypersensitivity following spinal cord injury can result in incurable persistent neuropathic pain. Our objective was to examine the effect of red light therapy on the development of hypersensitivity and sensorimotor function, as well as on microglia/macrophage subpopulations following spinal cord injury., Methods: Wistar rats were treated (or sham treated) daily for 30 min with an LED red (670 nm) light source (35 mW/cm(2)), transcutaneously applied to the dorsal surface, following a mild T10 hemicontusion injury (or sham injury). The development of hypersensitivity was assessed and sensorimotor function established using locomotor recovery and electrophysiology of dorsal column pathways. Immunohistochemistry and TUNEL were performed to examine cellular changes in the spinal cord., Results: We demonstrate that red light penetrates through the entire rat spinal cord and significantly reduces signs of hypersensitivity following a mild T10 hemicontusion spinal cord injury. This is accompanied with improved dorsal column pathway functional integrity and locomotor recovery. The functional improvements were preceded by a significant reduction of dying (TUNEL(+)) cells and activated microglia/macrophages (ED1(+)) in the spinal cord. The remaining activated microglia/macrophages were predominantly of the anti-inflammatory/wound-healing subpopulation (Arginase1(+)ED1(+)) which were expressed early, and up to sevenfold greater than that found in sham-treated animals., Conclusions: These findings demonstrate that a simple yet inexpensive treatment regime of red light reduces the development of hypersensitivity along with sensorimotor improvements following spinal cord injury and may therefore offer new hope for a currently treatment-resistant pain condition.

Ulnar nerve entrapment at the elbow (UNE) is the second most common entrapment neuropathy of the arm. Conservative treatment is the treatment of choice in mild to moderate cases. Elbow splints and avoiding flexion of the involved elbow constitute majority of the conservative treatment; indeed, there is no other non-invasive treatment modality. The aim of this study was to investigate the efficacy of ultrasound (US) and low-level laser therapy (LLLT) in the treatment of UNE to provide an alternative conservative treatment method. A randomized single-blind study was carried out in 32 patients diagnosed with UNE. Short-segment conduction study (SSCS) was performed for the localization of the entrapment site. Patients were randomized into US treatment (frequency of 1 MHz, intensity of 1.5 W/cm(2), continuous mode) and LLLT (0.8 J/cm(2) with 905 nm wavelength), both applied five times a week for 2 weeks. Assessments were performed at baseline, at the end of the treatment, and at the first and third months by visual analog scale, hand grip strength, semmes weinstein monofilament test, latency change at SSCS, and patient satisfaction scale. Both treatment groups had significant improvements on clinical and electrophysiological parameters (p < 0.05) at first month with no statistically significant difference between them. Improvements in all parameters were sustained at the third month for the US group, while only changes in grip strength and latency were significant for the LLLT group at third month. The present study demonstrated that both US and LLLT provided improvements in clinical and electrophysiological parameters and have a satisfying short-term effectiveness in the treatment of UNE.

The aim of this study is to analyze the differences between early and delayed use of low-level laser therapy (LLLT) in functional and morphological recovery of the peripheral nerve. Thirty male Wistar rats were divided into three groups after the sciatic nerve was crushed: (1) control group without laser treatment, (2) early group with laser treatment started immediately after surgery and lasted 14 days, and (3) delayed group with laser treatment starting on the postoperative day 7 and lasted until day 21. A 650-nm diode laser (model: DH650-24-3(5), Huanic, China) with an output power of 25 mW exposed transcutaneously at three equidistant points on the surgical mark corresponding to the crushed nerve. The length of the laser application was calculated as 57 s to satisfy approximately 10 J/cm(2). A Sciatic Functional Index (SFI) was used to evaluate functional improvement in groups at pre- and post-surgery (on days 7, 14, and 21). Compound action potential (CAP) was measured after the sacrifice and histological examination was performed for all groups. SFI results showed that there was no significant difference between groups at different days (p > 0.05). On the other hand, the latency of CAP decreased significantly (p < 0.05) in the delayed group. Histological examination confirmed that the number of mononuclear cells was lower (p < 0.05) in both early and delayed groups. In conclusion, results supported the hypothesis that LLLT could accelerate the rate of recovery of injured peripheral nerves in this animal model. Though both laser groups had positive outcomes, delayed group showed better recovery.

In this article we evaluate the effects of ultrasound radiation and its causes on the rate of injured peripheral nerve regeneration by crushing the sciatic nerve of rats with hemostatic forceps. The rats were divided into three test and one control groups. The test groups were radiated using three different types of ultrasound parameters while the control group just received sham expose. The amount of nerve regeneration was measured via functional test by extracting sciatic functional index from rats paw prints. The results showed that one of the test group parameters had the best functional results compared to other groups. Obtaining this outcome, the investigations continued by 50 rats with crushed sciatic nerve. These rats again divided into two test and control groups while for the test group the best parameters were assigned. In different time intervals compound muscle action potential wave was recorded from five rats of each group. Then their sciatic nerves were extracted to measure the amount of ciliary neurotropic factor gene expression by real time polymerase chain reaction. Crush injury sets the sciatic functional index to about -90 and compound muscle action potential to 6.8 mV in both control and test groups. After the period of treatment with ultrasound, the sciatic functional index reached the value of -25 in control group and -10 in test group and compound muscle action potential value reached 11 in control and 18 in test group. The results of electrophysiological tests confirmed the results of functional tests. At the end of the second, third and fourth weeks, the outcomes of real time polymerase chain reaction showed that the expression of ciliary neurotropic factor gene in test group was higher than control group as well as the amount in test group was approximately 11, 2 and 6 times higher than test group in corresponding weeks. Hence we can conclude that increase in the expression of ciliary neurotropic factor gene, as a nerve growth factor, following ultrasound radiation, can be considered as the reason of the effect of ultrasound on the rate of injured nerve regeneration.

Introduction: The aim of this study was to evaluate the ultrasound (US) morphological changes of sural nerves (SNs) of uremic patients on hemodialysis., Methods: Sixty-six SNs in 33 uremic patients were examined by 22-MHZ high-frequency US and routine nerve conduction studies (NCS), and 76 SNs in 38 controls were also examined. Cross-sectional area (CSA) and maximal fascicular thickness (MFT) of the SNs were measured., Results: The inner parts of the SN were clearly identified in all participants. There were significant increases in CSA and MFT in the patient group (1.86 ± 0.53 mm(2) and 0.37 ± 0.08 mm, respectively) compared with the control group (1.38 ± 0.25 mm(2) and 0.32 ± 0.03 mm, respectively) (P < 0.001). Fifty-seven SNs (86.36%) had abnormal CSAs, and 51 SNs (77.27%) had abnormal MFTs in the patient group, which was higher than NCS abnormalities (66.67%)., Conclusions: A 22-MHZ US can show morphological changes in the SNs of uremic patients and may be a valuable tool., (Copyright © 2012 Wiley Periodicals, Inc.)

Objective: The purpose of this study was to evaluate effects of transcutaneous 650 and 808 nm laser irradiation (LI) to a single point overlying rat sciatic nerve; a comparison to four point LI and relevance to the clinical application of low-level laser therapy (LLLT) and laser acupuncture (LA)., Background Data: Transcutaneous LI inhibits somatosensory and motor conduction when delivered to four points overlying sciatic nerve; however, effects of the same total energy delivered to a single point over the nerve, equating to laser acupuncture, are undefined., Methods: Transcutaneous 808 nm, 450 mW, (13.5 or 54 J) continuous wave (cw) mode or 650 nm, 35 mW, (1.1 or 4.4 J), cw LI or sham LI, was applied for 30 or 120 sec to a single point overlying the midpoint of rat sciatic nerve. Somatosensory evoked potentials (SSEPs) and compound muscle action potentials (CMAPs) were then recorded after 10 and 20 min, and after 24 and 48 h., Results: 120 sec of 808 nm LI increased SSEP amplitudes only at 10 min, with no effect of 30 or 120 sec at other time points on SSEPs or on CMAPs. LI 650 nm for 30 or 120 sec did not alter SSEPs or CMAPs at any time point., Conclusions: Localized transcutaneous 808 LI to a single point overlying sciatic nerve increases SSEP amplitudes when compared with delivery of the same total energy to four points, which causes decreased SSEP amplitudes and conduction block. Therefore, the area and duration of delivery are important, independent variables with implications for clinical delivery of both LLLT and LA.

Purpose: To study how pressure pulses affect nerves through mechanisms that are neither thermal nor cavitational, and investigate how the effects are related to cumulative radiation-force impulse (CRFI). Applications include traumatic brain injury and acoustic neuromodulation., Methods: A simple neural model consisting of the giant axon of a live earthworm was exposed to trains of pressure pulses produced by an 825 kHz focused ultrasound transducer. The peak negative pressure of the pulses and duty cycle of the pulse train were controlled so that neither cavitation nor significant temperature rise occurred. The amplitude and conduction velocity of action-potentials triggered in the worm were measured as the magnitude of the pulses and number of pulses in the pulse trains were varied., Results: The functionality of the axons decreased when sufficient pulse energy was applied. The level of CRFI at which the observed effects occur is consistent with the lower levels of injury observed in this study relative to blast tubes. The relevant CRFI values are also comparable to CRFI values in other studies showing measureable changes in action-potential amplitudes and velocities. Plotting the measured action-potential amplitudes and conduction velocities from different experiments with widely varying exposure regimens against the single parameter of CRFI yielded values that agreed within 21% in terms of amplitude and 5% in velocity. A predictive model based on the assumption that the temporal rate of decay of action-potential amplitude and velocity is linearly proportional the radiation force experienced by the axon predicted the experimental amplitudes and conduction velocities to within about 20% agreement., Conclusions: The functionality of axons decreased due to noncavitational mechanical effects. The radiation force, possibly by inducing changes in ion-channel permeability, appears to be a possible mechanism for explaining the observed degradation. The CRFI is also a promising parameter for quantifying neural bioeffects during exposure to pressure waves, and for predicting axon functionality.

Aim: Peripheral nerve regeneration is often blocked by scar formation and misdirection of axon sprouts. The aim of this study is to evaluate electrophysiological and histopathological effects of low-dose radiation therapy on the prevention of intraneural scar formation in peripheral nerve injury., Material and Methods: In this experimental study, twenty rats were randomly divided into two groups. Left sciatic nerves were exposed and clipped by temporary aneurysm clip for 5 minutes in both groups. In all animals, electrophysiological recordings were performed between 22-24 hours after sciatic nerve injury. The control group was not given any treatment. In the experimental group, 700 cGy low-dose radiation was administered on the left sciatic nerves 24 hours after clipping. Six weeks after injury, electrophysiological recordings were performed in both groups and animals were sacrificed to evaluate the injured nerves histopathologically., Results: We observed that low-dose radiotherapy increased the amplitude and improved latency measurements in electrophysiological examinations. Histopathologically, more axonal degeneration and vacuolization was observed in the control group comparing with the experimental group. Endoneural space increased slightly more in the control group than the experimental group., Conclusion: It was observed that low-dose radiotherapy may prevent intraneural scar formation and may improve electrophysiological recovery in sciatic nerve injury performed in rats.

Low-intensity laser therapy (LILT) has been considered as a treatment modality in diabetic distal symmetric polyneuropathy (DSP). The aim of this study is to determine the effectiveness of LILT on DSP. We examined 107 subjects with type 2 diabetes for detection of DSP using the Michigan Neuropathy Screening Instrument (MNSI). Seventeen subjects were eligible to be enrolled in the study. Nerve conduction studies (NCS) were performed in all eligible subjects as an objective method to confirm neuropathy. The participants received LILT three times a week for ten sessions. NCSs were reevaluated after completion of the treatment. The absolute changes in NCS parameters were considered to establish the effectiveness of the treatment. Baseline demographics were similar in all participants. The mean differences of NCV parameters were considered for comparison. At the end of the study, the subjects showed a significant increase in neural potential amplitudes (p < 0.05). This study clearly demonstrated a significant positive effect of LILT on improvement of nerve conduction velocity on diabetic distal symmetric polyneuropathy (DSP). This finding supports the therapeutic potential of LILT in DSP.

Low-intensity ultrasound (LIU) can stimulate injured nerve regeneration but the mechanism is still unclear. We investigated the stimulating effect and its mechanism of continuous-wave LIU on neurotometic injury of sciatic nerve. The right sciatic nerves of 64 adult Wistar rats were first crushed and then exposed (32 rats) or sham-exposed (32 rats) to LIU at the crush site. The LIU had a spatial averaged and temporal averaged intensity of 0.25 W/cm(2) operated at 1.0 MHz for 1 min every other day. At various stages (the second, fourth, sixth and eighth weeks) after LIU exposure, the sciatic nerve function index (SFI), the sensory nerve conduction velocity (SNCV), the expression of nerve growth factor (NGF) and sample histology were studied. It was found that the density of nerve fibers with myelin sheath, SFI, SNCV and NGF expression of the treatment group were higher than that of control group (p < 0.05). It has been determined that LIU treatment can accelerate the regeneration and functional recovery of neurotometic injured sciatic nerve at earlier stages after injury, the upgraded expression of NGF induced by LIU may be the primary mechanism of the acceleration effects., (Copyright 2010. Published by Elsevier Inc.)

Charcot-Marie-Tooth (CMT) disease is the most common inherited neuropathy. The CMT1A type can be considered the typical phenotype of this disease. Although pain is not considered a relevant symptom in CMT patients by physicians and no study assessed it comprehensively, this symptom is frequently complained by patients. The objective of the present study was to investigate the nociceptive system in a sample of CMT1A patients suffering from pain by laser-evoked potentials (LEPs). Moreover, we also used a pain specific questionnaire in order to obtain patient-oriented data about their painful symptoms, the Neuropathic Pain Diagnostic Questionnaire (DN4). We evaluated 16 patients affected by CMT1A and 14 controls. All subjects underwent a standard LEP recording session (foot, hand, and face stimulation) and filled in the DN4. While the N2/P2 amplitude to foot stimulation was lower in CMT patients than in controls (p=0.003), no difference in LEP amplitude to both hand and face stimulation was found between patients and healthy subjects (p>0.05). This result is probably due to a length-dependent Adelta-fiber loss which involves mostly the longer fibers coming from the lower limb. In our patients, there was a significant association between a reduced N2/P2 amplitude to foot stimulation and a high DN4 score (p=0.03), meaning that patients with highly probable neuropathic pain had also low N2/P2 amplitude values to painful foot stimulation. This suggests that in our CMT1A patients neuropathic pain is probably related to a reduction of the Adelta afferents., (Copyright 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Transcranial direct current stimulation (tDCS) is an emerging technique of non-invasive brain stimulation that has been found useful in facilitating treatment of various neurological disorders, especially stroke. Currently available criteria for single application of several minutes-long stimulation at 1-2 mA have been considered safe. However, knowledge regarding safety parameters of repeated and long-term electrical stimulation is so far limited. Studies on the use of tDCS focus predominantly on the motor cortex. They demonstrate that weak direct current is capable of eliciting cortical excitability changes which occur during and after stimulation. The nature of these changes is specific for current polarity - anodal stimulation enhances excitability, and cathodal reduces it. Studies indicate that tDCS effects are generated by polarity-driven alterations of membrane potentials and efficacy modulations of specific neuronal receptors. According to interhemispheric competition models, possible mechanisms underlying functional improvements due to stimulation in patients with stroke are attributed to tDCS-induced modification of inappropriate interhemispheric inhibition.

In acute experiments using adult rabbits, we measured the paroxysmal discharge threshold (PADT) elicited by stimulation to the apical dendritic layer of the hippocampal CA1 region before and after low-power laser irradiation. Nd:YVO(4) laser irradiation (wavelength: 532 nm) was introduced into the same region as the stimulation site. The average PADT was 247 +/- 13 microA (n = 18) before laser irradiation, while after 5-min laser irradiation with 50, 75, and 100 mW, PADT was 333 +/- 40 (n = 4), 353 +/- 33 (n = 4) and 367 +/- 27 microA (n = 6), respectively. The latter two increments were statistically significant compared to the control (p < 0.05 and p < 0.01). After 10-min laser irradiation with 75 and 100 mW, PADT was 340 +/- 47 (n = 9) and 480 +/- 60 microA (n = 11; p < 0.01), respectively. Laser irradiation with a specific wavelength and average power offers the potential to suppress the generation of paroxysmal discharges in rabbit hippocampus CA1. Correlation analyses suggest that PADT increments are based on photochemical as well as photothermal effects of laser irradiation.

Background: Laser light is known to stimulate nerves. This study investigated alternative wavelengths for nerve stimulation., Materials and Methods: The sciatic nerves of rats were irradiated with four different lasers-a Ho:YAG (2100 nm), a Yb:glass fiber laser (1495 nm) and diode lasers (1450 nm and 1540 nm)., Results: All lasers evoked a visible leg twitch response, and electromyography confirmed muscle activation. The Yb:glass laser at 1495 nm delivered through a single mode fiber was found to be the most effective stimulus. The stimulation threshold for a 2 millisecond pulse from the Yb:glass laser was determined to be 3.7+/-2.8 mJ/cm(2)., Conclusions: The Yb:glass laser has the potential for use in neurostimulation, as an alternative to electrical stimulation.

Study Design: We evaluated the electrophysiological changes to the cauda equina after low-dose external irradiation in a postlaminotomy fibrosis model in rats., Objective: To clarify the immediate and long-term electrophysiological responses of antifibrotic radiation therapy in a fibrosis model., Summary of Background Data: Low-dose perioperative radiation therapy inhibits scar formation. However, its efficacy for preventing fibrosis-induced compressive neuropathy and its potential adverse effect on underlying neural structures have not been studied., Methods: Twenty-four rats were placed in 3 groups of 8: group I, sham operation (laminar exposure alone) with a single fraction of 700 cGy external irradiation given using a 9-MeV electron beam 24 hours postsurgery; group II, left L5 hemilaminectomy (laminotomy) alone; and group III, left L5 hemilaminectomy with the same radiation protocol as group 1. We recorded mixed-nerve-elicited somatosensory-evoked potentials (M-SSEP)- and dermal (D)-SSEP at the thoracolumbar junction, and L1-L2 interspinous ligament after percutaneously stimulating the posterior tibial nerve at the bilateral medial ankle and L5 dermatomal fields. We compared the potentials recorded immediately before, 30 minutes, 2 weeks, and 1, 2, and 3 months after surgery on the operated and nonoperated sides. We used gross dissection and histologic sections to evaluate the degree of perineural fibrosis and walking-track analysis for neurologic evaluation., Results: Pre- and postoperative (30 minutes and 2 weeks) M- and D-SSEP were not statistically different. In group II, the relative amplitude of D-SSEP (elicited from 5 dermatomes) 1, 2, and 3 months postsurgery was lower; however, the M-SSEP in all groups and D-SSEP of groups I and III remained constant. Histologic evaluation of radiation efficacy showed that the frequency and extent of peridural fibrosis was consistently lower in group II than in group III., Conclusion: Low-dose irradiation reduced peridural fibrosis and prevented fibrosis-induced radiculopathy. The radiation caused no adverse neuropathic complications.

The somatotopic map of the first nociceptive component in the primary somatosensory cortex (S1) is still unclear. In this study, a CO(2) laser was applied to the tail of the rat to induce nociception without the interference from large myelinated (A(beta)) fibers. Thus, only noxious fibers could be activated. Two-dimensional current-source-density analysis was used to analyze the evoked field potentials. Using this method, the nociceptive responses of A(delta)-fibers in S1 were verified, and the somatotopic map of the first nociceptive component in S1 was identified. We found that whether light touch or laser-induced nociception was applied to the tail of the rat, the responsive topography in S1 was consistent. Discrimination of these two modalities was achieved vertically in the same column; the deeper layer represented the nociceptive response while the superficial layer encoded the response to light touch. This is quite different from that of a primate brain.

High frequency alternating current (HFAC) waveforms reversibly block conduction in mammalian peripheral nerves. The initiation of the HFAC produces an onset response in the nerve before complete block occurs. An amplitude ramp, starting from zero amplitude, is ineffective in eliminating this onset response. In fact, it makes the onset worse. We postulated that initiating the ramp from a non-zero amplitude would produce a different effect on the onset. This was tested in an in-vivo rat sciatic nerve model. HFAC was applied at supra block threshold amplitudes and then reduced to a lower amplitude (0%, 25% 50 %, 75% and 90% of the suprathreshold amplitude). The amplitude was then increased again to the original supra block threshold amplitude. This normally produces a second period of onset response if increased as a step. However, an amplitude ramp was successful in eliminating this onset. This was always possible for the ramps up from 50%, 75 % and 90% block threshold amplitude, but never from 0% or 25% of the block threshold amplitude. This maneuver can potentially be used to maintain complete nerve block, transition to partial block and then resume complete block without initiating another onset.

The delivery of high frequency alternating currents (HFAC) to peripheral nerves has been shown to produce a rapid and reversible nerve conduction block at the site of the electrode, and holds therapeutic promise for diseases associated with undesired or pathological neural activity. It has been known since 1939 that the configuration of an electrode used for nerve block can impact the quality of the block, but to date no formal study of the impact of electrode design on high frequency nerve block has been performed. Using a mammalian small animal model, it is demonstrated that the contact separation distance for a bipolar nerve cuff electrode can impact two important factors related to high frequency nerve block: the amplitude of HFAC required to block the nerve (block threshold), and the degree to which the transient "onset response" which always occurs when HFAC is first applied to peripheral nerves, is present. This study suggests that a bipolar electrode with a separation distance of 1.0 mm minimizes current delivery while producing high frequency block with a minimal onset response in the rat sciatic nerve.

Objective: To study the effects of subthalamic nucleus (STN) stimulation on motor cortex excitability in Parkinson's disease (PD)., Methods: Fifteen patients were evaluated under off-medication, OFF- and ON-STN conditions, using the UPDRS. We studied the effects of STN stimulation on motor cortex excitability under three conditions (OFF, ON with chronic therapeutic parameters, ON HighV with a voltage set 10% under permanent side effects threshold), using transcranial magnetic stimulation. We measured the central motor conduction time (CMCT), rest and active motor threshold (MT), F-wave persistence and amplitude, silent period (SP), intracortical inhibition and facilitation at 3, 5 and 15 ms interstimulus intervals (ISI)., Results: The UPDRS motor score decreased from 44.4+/-14.0 under OFF, to 15.2+/-8.0 under ON-STN condition. The CMCT and MT did not change across STN conditions. The F-wave parameters were within normal range under STN stimulation. STN stimulation lengthened the SP and induced facilitation at 15 ms ISI compared to the OFF-STN condition., Conclusion: Therapeutic STN stimulation modulates cortical excitability in PD. High voltage STN stimulation could also act on spinal excitability., Significance: At the motor cortical level, STN stimulation may have a direct effect on intracortical interneurons, modifying the balance between excitation and inhibition.

To investigate the effect of somatostatin on the cross-excitation between adjacent primary afferent terminals in the rats, we recorded single unit activity from distal cut ends of dorsal cutaneous branches of the T10 and T12 spinal nerves in response to antidromic stimulation of the distal cut end of the T11 dorsal root in the presence and absence of somatostatin and its receptor antagonist applied to the receptive field of the recorded nerve. Afferent fibers were classified based upon their conduction velocity. Mean mechanical thresholds decreased and spontaneous discharge rates increased significantly in C and Adelta but not Abeta fibers of the T10 and T12 spinal nerves in both male and female rats following antidromic electrical stimulation (ADES) of the dorsal root from adjacent spinal segment (DRASS) indicating cross-excitation of thin fiber afferents. The cross-excitation was not significantly different between male and female rats. Microinjection of somatostatin into the receptive field of recorded units inhibited the cross-excitation. This inhibitory effect, in turn, was reversed by the somatostation receptor antagonist cyclo-somatostatin (c-SOM). Application of c-SOM alone followed by ADES of DRASS significantly decreased the mechanical thresholds and increased the discharge rates of C and Adelta fibers, indicating that endogenous release of somatostatin plays a tonic inhibitory role on the cross-excitation between peripheral nerves. These results suggest that somatostatin could inhibit the cross-excitation involved in peripheral hyperalgesia and have a peripheral analgesic effect.

Neural integrators and working memory rely on persistent activity, a widespread neural phenomenon potentially involving persistent sodium conductances. Using a unique combination of voltage-clamp, dynamic-clamp, and frequency-domain techniques, we have investigated the role of voltage-dependent conductances on the dendritic electrotonic structure of neurons of the prepositus hypoglossi nucleus (PHN), which is known to be involved in oculomotor integration. The PHN contains two main neuronal populations: type B neurons with a double afterhyperpolarization and type D neurons, which not only are oscillatory but also have a greater electrotonic length than that of type B neurons. The persistent sodium conductance is present in all PHN neurons, although its effect on the dynamic electrotonic structure is shown to significantly differ in the two major cell types present in the nucleus. The electrotonic differences are such that the persistent sodium conductance can be almost perfectly manipulated in a type B neuron using an on-line dynamic clamp to add or subtract virtual sodium ion channels. The dynamic-clamp results are confirmed by data-fitted models, which suggest that the persistent sodium conductance has two different roles depending on its somatic versus dendritic location: perisomatic conductances could play a major role in maintaining action potential discharge and dendritic conductances would be more involved in other computational properties, such as those involving remote synaptic processing or bistable events.

Objective: To identify the sensitivity and the patterns of change in sensory excitability that accompany an ischaemic insult., Methods: Sensory excitability studies were undertaken in 10 subjects (mean age 36), and monitored throughout ischaemia and following its release. Ischaemia was induced using a sphygmomanometer inflated to 200mm/Hg above the elbow., Results: During ischaemia there was reduction in threshold (P<0.001), associated with a significant increase in refractoriness (106+/-6.62%; P<0.001), reduction in superexcitability (30.4+/-0.42%; P<0.001), and 'fanning in' of threshold electrotonus, all indicative of axonal depolarization. Paraesthesiae were minimal during ischaemia, but became severe on release, at which stage numbness was prominent. Late subexcitability in sensory axons was completely abolished by a relatively shorter period of ischaemia than previously observed in motor axons., Conclusions: The present study has successfully developed a template for changes in sensory axonal excitability parameters that accompany ischaemia, and established their relative sensitivity to an ischaemic change. Further, it is proposed that the inhibition of the Na+/K+ pump, in the setting of increased persistent Na+ currents and abolition of late subexcitability may underlie the development of paraesthesiae during ischaemia., Significance: Changes in axonal excitability induced by ischaemia may serve as a tool to identify and interpret changes in axonal membrane potential recorded in neuropathic patients.

Impairment of ulnar sensory fibers at the wrist has recently been documented in moderate/severe carpal tunnel syndrome (CTS). This has been interpreted as a consequence of compressive forces transmitted to Guyon's canal by high pressure in the carpal tunnel or comorbidity between ulnar neuropathy and CTS. The main aim of the present study was to identify any ulnar nerve conduction impairment in the early stages of CTS. The relation between ulnar and median nerve conduction in all CTS severity stages was also assessed. Ulnar nerve sensory conduction at the wrist was investigated in 580 hands with CTS. Significant changes in ulnar nerve conduction were present even in the early stages of CTS. A significant, positive correlation was also found between CTS severity and conduction abnormalities of ulnar sensory fibers. These findings make the hypothesis of comorbidity weak. Based on the above results and on reports of high pressure in Guyon's canal in CTS, ulnar nerve conduction abnormalities may be caused in part by compressive forces progressively transmitted to the canal by increasing pressure in the carpal tunnel with increasing CTS severity. This does not exclude other causative factors such as subclinical traumatic damage acting on median and ulnar fibers.

In chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) the pathophysiology underlying permanent muscle weakness and sensory loss was studied in 22 stabilized long-term CIDP patients clinically characterized using isokinetic dynamometry, quantitative sensory testing, and neuropathy scores. Conduction velocity (CV), distal latency (DLAT), minimal F-wave latency (FLAT), compound muscle action potential (CMAP), and amplitude decay between distal and proximal stimulation sites were determined in the median, ulnar, peroneal, and tibial motor nerves and sensory CV and nerve action potentials in the median and sural nerves. Amplitude of CMAP and the DLAT were related to quantitative muscle strength, whereas CV, FLAT, amplitude decay, and dispersion were not consistently related to strength. Furthermore, CMAP and muscle strength were significantly more reduced distally than proximally. In conclusion, the electrophysiological signs of axonal loss and the associated length-dependent muscle weakness suggest secondary axonal loss in addition to primary demyelination in CIDP.

Objective: It has been shown that finger circumference negatively correlates with sensory nerve action potential amplitude (SNAP-A). Also fat people have lower sensory nerve amplitudes. Factors that cause electrodes displaced further away from underlying nerves, such as increased cutaneous and subcutaneous tissue, will lower SNAP-A. This study was designed to evaluate correlation between skin thickness and SNAP amplitude., Methods: Thirty-seven healthy 22-40-year-old subjects were selected. Nineteen (51.4%) were males and 18 (48.6%) were females, without significant difference between males and females regarding their ages. For all subjects, height and weight were measured. Anteroposterior and mediolateral diameters of the proximal phalanges of the index and little fingers and also finger circumferences were measured. Palmar digital skin thickness was measured in two ways: first with sonography machine, and second with skin fold caliper. Median and ulnar nerve sensory and motor conduction studies were performed., Results: In bivariate analysis, SNAP-A correlated negatively with female sex, height, anteroposterior diameter of the fingers, finger circumference and skin thickness measured by sonography, but in multiple regression analysis only skin thickness measured by sonography could predict SNAP-A., Conclusions: This study demonstrates that among physiological factors of sex, height, BMI and also finger size measures, skin thickness is the best predictor of SNAP-A., Significance: In clinical practice, this effect must be taken into account when making determination of abnormality based on sensory nerve amplitude.

Objective: To elucidate the frequency of peripheral nerve demyelination in multiple sclerosis (MS). There are a number of case reports describing MS patients associated with demyelinating neuropathy, but its frequency in a whole MS population is unknown., Methods: Extensive nerve conduction studies were prospectively performed in 60 consecutive patients with relapsing-remitting MS. Multiple excitability measurements using threshold tracking were also performed in median motor axons and superficial radial sensory axons., Results: Nerve conduction abnormalities suggestive of demyelination were found for 3 (5%) of the patients. Two of them developed clinically evident neuropathy, whereas the remaining one had only generalized areflexia in addition to MS symptoms/signs. In all the three, MS preceded demyelinating neuropathy by several years. Excitability testing showed that supernormality and threshold electrotonus at the tested sites (median motor axons at the wrist, and radial sensory axons at the mid-forearm) were similar in the normal and MS groups., Conclusions: MS patients do not generally have peripheral nerve demyelination, but approximately 5% of patients develop demyelinating neuropathy. The association could result from a common pathogenesis possibly due to epitope spreading during the long course of MS., Significance: Association of chronic inflammatory demyelinating polyneuropathy with MS is not frequent, but needs to be recognized as a treatable condition.

Activation of the climbing fiber input powerfully excites cerebellar Purkinje cells via hundreds of widespread dendritic synapses, triggering dendritic spikes as well as a characteristic high-frequency burst of somatic spikes known as the complex spike. To investigate the relationship between dendritic spikes and the spikelets within the somatic complex spike, and to evaluate the importance of the dendritic distribution of climbing fiber synapses, we made simultaneous somatic and dendritic patch-clamp recordings from Purkinje cells in cerebellar slices. Injection of large climbing fiber-like synaptic conductances at the soma using dynamic clamp was sufficient to reproduce the complex spike, independently of dendritic spikes, indicating that neither a dendritic synaptic distribution nor dendritic spikes are required. Furthermore, we found that dendritic spikes are not directly linked to spikelets in the complex spike, and that each dendritic spike is associated with only 0.24 +/- 0.09 extra somatic spikelets. Rather, we demonstrate that dendritic spikes regulate the pause in firing that follows the complex spike. Finally, using dual somatic and axonal recording, we show that all spikelets in the complex spike are axonally generated. Thus, complex spike generation proceeds relatively independently of dendritic spikes, reflecting the dual functional role of climbing fiber input: triggering plasticity at dendritic synapses and generating a distinct output signal in the axon. The encoding of dendritic spiking by the post-complex spike pause provides a novel computational function for dendritic spikes, which could serve to link these two roles at the level of the target neurons in the deep cerebellar nuclei.

The somatic voltage clamp technique has revolutionized understanding of synaptic physiology and the excitability of neurons. Although computer simulations have indicated that the somatic voltage clamp poorly controls voltage in the dendritic tree of neurons, where the majority of synaptic contacts are made, there has not been an experimental description of the performance of the somatic voltage clamp. Here, we directly quantify errors in the measurement of dendritic synaptic input by the somatic voltage clamp using simultaneous whole-cell recordings from the soma and apical dendrite of rat neocortical pyramidal neurons. The somatic voltage clamp did not control voltage at sites other than the soma and distorted measurement of the amplitude, kinetics, slope conductance and reversal potential of synaptic inputs in a dendritic distance-dependent manner. These errors question the use of the somatic voltage clamp as a quantitative tool in dendritic neurons.

Space constants and time constants characterize the spatial and temporal behavior of the membrane potential of a neuronal membrane with constant conductance. However, more realistic models of membrane potential assume that membrane conductance depends on the membrane potential and its history, and therefore, it is not clear that space and time constants can be defined for membranes with this property. However, through a consideration of the properties of trains of action potentials treated as traveling waves, space and time constants for the total membrane current during a propagated action potential can be derived and estimated. We show that the formal definitions of the space and time constants for the membranes with constant conductance can be extended to membranes with voltage-dependent conductance in which the behavior of each type of membrane is distinguished through the choice of the representation of the membrane conductance used in these definitions. In the case of a membrane with voltage-dependent conductance, the conductance to be used in the definitions of the space and time constants can be estimated from the extracellularly determined conduction speed of the propagated action potential.

Changes in the excitability of the neuron (amplitude, excitability threshold, rate of action potential transduction), as well as changes in the viscosity of the plasma membrane of the nerve and membranes of subcellular organelles, induced by the action of a weak magnetic field, have been studied by the methods of extracellular registration of membrane potential and combination scattering. It was found that only the threshold of excitability in intact nervous fibers increases by the action of this field. It was proven that the conformation of C40 carotenoids localized not only in plasma membranes but also in subcellular membranes of the neuron changes in a weak magnetic field. It is assumed that the changes in the excitability of the neuron by the action of weak magnetic field are due to changes in the orderliness of membrane lipids and the content of oxygen in the cytoplasm.

Measurements of muscle-fiber conduction velocity during voluntary contractions have been used in the diagnosis of neuromuscular diseases. However, the velocity of propagation of action potentials depends on the interspike interval of activation due to the velocity recovery function (VRF) of muscle fibers. The comparison of muscle-fiber conduction velocity estimates between individuals may thus be influenced by differences in motor unit discharge rate. This study investigates action potential properties of motor units of the sternocleidomastoid muscle during voluntary modulation of discharge rate with the purpose of assessing the effect of the VRF on motor unit properties in voluntary contractions. Nineteen healthy men trained to control a target motor unit with feedback of surface multichannel electromyographic (EMG) signals. The subjects performed three 30-s contractions of cervical flexion/rotation modulating the discharge rate of the target motor unit from 6.6 +/- 1.6 pps to 28.0 +/- 6.4 pps. Action potential conduction velocity was correlated to instantaneous discharge rate (R = 0.38 +/- 0.21). Action potential conduction velocity, peak-to-peak amplitude, and duration varied between minimum and maximum discharge rate (P < 0.01; percent change 12.3 +/- 5.0, -11.8 +/- 9.9, and -12.9 +/- 7.3). Thus, the properties of surface motor unit action potentials vary with modulation of discharge rate. This has implications for the use of conduction velocity values measured during voluntary contractions to differentiate patient populations from healthy individuals and for the development of normative data.

Periventricular leukomalacia (PVL) is the most frequent cause of spastic diplegia. The movement disorder is attributed to damage to the corticospinal tract, but there is increasing evidence of additional cortical dysfunction associated with PVL. Aim of the present study was to evaluate the integrity of the corticospinal tract and cortical inhibitory function using transcranial magnetic stimulation. Fifteen children with bilateral PVL and spastic diplegia and twenty-two healthy children underwent single-pulse stimulations to the right tibial anterior muscle. We compared central motor conduction time and amplitudes of motor evoked potentials as markers for corticospinal integrity and the postexcitatory silent period (SP), representing cortical inhibitory interneurons. The patients' parameters of corticospinal tract function did not differ significantly from those in the control children. In contrast, the SP was significantly shortened in children with PVL (mean 25.6 +/- 6.9 ms; controls: mean 47.6 +/- 23.2 ms, P = 0.018). This suggests cortical involvement with reduced cortical inhibitory function in PVL. This could be due to impaired functioning of the cortical interneurons themselves, or to decreased input from activating fibres, e.g. thalamocortical or cortico-cortical connections.

A theoretical study of possible neuromuscular incapacitation based on the application of high-intensity, ultrashort electric pulses is presented. The analysis is applied to a rat, but the approach is general and can be extended to any whole-animal and applies for any arbitrary pulse waveform. It is hypothesized that repeatable and reversible action potential blocks in nerves can be attained based on the electroporation mechanism. Our numerical studies are based on the Hodgkin-Huxley distributed circuit representation of nerves, and incorporate a nodal analysis for the time-dependent and volumetric perturbing potentials and internal electric fields in whole animals. The predictions are compared to actual 600-ns experimental reports on rats and shown to be in very good agreement. Effective strength-duration plots for neuromuscular incapacitation are also generated.

Objective: To elucidate the clinical and physiologic features of anomalous superficial radial innervation to the ulnar dorsum of hand., Methods: We performed superficial radial and ulnar dorsal cutaneous nerve conduction studies (NCS) in 100 patients without radial or ulnar neuropathy and in 71 patients with various ulnar neuropathies., Results: Of 100 patients, 16 had anomalous superficial radial innervation to ulnar dorsum of hand. Only 3 subjects had an absent ulnar dorsal cutaneous response without this variant. The anomaly was unilateral in 14 subjects and bilateral in 2, manifesting in 18 of 200 hands (9%). In the 71 patients with various ulnar neuropathies, failure to recognize the variant confounded clinical and NCS diagnoses., Conclusions: Anomalous superficial radial innervation to the ulnar dorsum of the hand is the most common cause of an absent ulnar dorsal cutaneous response in the population at large., Significance: It is important to recognize this variant to avoid erroneous diagnoses and inappropriate treatment, and to improve assessment of nerve injury and recovery. From a historical perspective, our findings are the first to adequately explain the degree of asymmetry observed by Jabre [Jabre JF. Ulnar nerve lesions at the wrist: new technique for recording from the sensory dorsal branch of the ulnar nerve. Neurology 1980;30:873-6.] in his seminal paper on the ulnar dorsal cutaneous response.

Intrinsic properties and rotation-evoked responses of trochlear motoneurons were investigated in the turtle using an in vitro preparation consisting of the brain stem with attached temporal bones that retain functional semicircular canals. Motoneurons were divided into two classes based on intrinsic properties. The first class exhibited higher impedance (123.0 +/- 11.0 MOmega), wider spikes (0.99 +/- 0.05 ms), a single spike afterhyperpolarization (AHP), little or no spike frequency adaptation (SFA), and anomalous rectification, characterized by an initial "sag" in membrane potential in response to hyperpolarizing current injection. The second class exhibited lower impedance (21.8 +/- 2.5 MOmega), narrower spikes (0.74 +/- 0.03 ms), a double AHP, substantial SFA, and little or no rectification. Vestibular responses were evoked by horizontal sinusoidal rotation (1/12-1/3 Hz; peak velocity: 30-100 degrees /s). Spiking in higher-impedance cells was recruited earlier in the response and exhibited a more limited dynamic range relative to that of lower impedance cells. Spiking evoked by injecting depolarizing current during rotation was blocked during contraversive motion and was consistent with a shunting inhibition. No morphological features were identified in neurobiotin-filled cells that correlated with the two physiological classes. Recovered motoneurons were multipolar but exhibited a less-complex dendritic morphology than ocular motoneurons of similarly sized mammals. The two physiologically defined cell classes have homologues in other vertebrates, suggesting that intrinsic membrane properties play an important role in oculomotor processing.

Thalidomide was recently reintroduced to treat several immune-mediated pathologies. Peripheral neuropathy is a significant side effect limiting its clinical use. Our aims include: (1) describing and identifying the incidence of clinical or electrophysiologic peripheral neuropathy in children, (2) determining whether peripheral neuropathy correlates with cumulative dose of thalidomide and with age, and (3) defining its reversibility rate. We studied 13 children manifesting immune-mediated pathologies treated with thalidomide at doses ranging from 25-100 mg/day. Clinical and neurophysiologic evaluation was performed before and after starting treatment. Seven children (53.8%) showed neurophysiologic signs of sensory peripheral axonal polyneuropathy. Five presented associated clinical symptoms, while the other two only presented subclinical, neurophysiologic signs of peripheral neuropathy. We found a significant correlation between the incidence of peripheral neuropathy and thalidomide cumulative dose (P = 0.02). We observed a lower incidence of peripheral neuropathy at a cumulative dose <20 gm, and a correlation with age (P < 0.01). The clinical and electrophysiologic recovery rate was 40%, and clinical improvement alone was observed in another 40%. Thalidomide induces dose-dependent and age-dependent peripheral neuropathy at a significant frequency in childhood (53.8%). In our experience a cumulative dosage at >20 gm and long-term administration for >10 months seem to increase the risk of peripheral neuropathy. We propose clinical and neurophysiologic follow-up every 3 months to identify and monitor possible side effects.

The aim of this prospective study was to assess whether extra discharges (EDs), sometimes following the compound muscle action potential, could be used as a neurophysiological indicator of overdose of acetylcholinesterase inhibitors (AChEIs) in patients with myasthenia gravis (MG). The characteristics and frequency of EDs were explored and the correlation of EDs with cholinergic side effects was also determined. Twenty-two MG patients (14 women, 8 men; 61 +/- 16 years of age) with daily AChEI treatment were examined. The mean disease duration was 10 years (range 2-62 years) and all patients had been treated with AChEI since MG onset. Both single and repetitive stimulation of the ulnar and accessory nerves were performed before and 60 min after oral pyridostigmine bromide (PB) administration and after additional edrophonium injection. Fatigue, side effects, and AChE activity in blood were assessed before and 60 min after PB intake. The daily dose of PB ranged from 150 to 900 mg/day. Fourteen patients (64%) experienced daily cholinergic adverse effects, and muscarinic side effects correlated with AChE activity. Eleven patients (50%) developed EDs after oral PB. Among the eight patients with daily nicotinic side effects, EDs were significantly (P < 0.05) more common. Additionally, older patients were more prone to develop cholinergic side effects and EDs. Thus, when EDs are found, patients should be asked about daily muscular symptoms, which may be related to AChEI treatment and not solely to MG.

Objective: Contact heat evoked potentials (CHEPs) provide an objective approach to investigate cerebral responses to thermal stimuli mediated by Adelta fibers. Skin denervation is often associated with reduced thermal sensibilities. We aimed to investigate the influences of skin denervation on CHEPs in neuropathic patients., Methods: CHEPs were recorded at the vertex area by applying contact heat stimuli of 51 degrees C on the distal leg of neuropathic patients with sensory symptoms and pathological evidence of skin denervation in the distal leg. Patterns and parameters of CHEPs in the neuropathic group were compared with those in the control group of age- and gender-matched subjects., Results: There were 25 neuropathic patients with reduced intraepidermal fiber (IENF) density (1.46+/-1.70fibers/mm, range: 0-5.32). In the control group, well-defined averaged tracings of CHEPs with an initial negative peak (N-wave) followed by a positive peak (P-wave) were consistently recorded in all 25 subjects. The peripheral conduction velocities of CHEPs were 9.92+/-4.06m/s (range: 6.06-16.60), in the range of Adelta fibers. The group of neuropathic patients had markedly reduced N-P amplitudes (p<0.0001) and prolonged N-wave latencies (p=0.049) compared to the control group. IENF density was the only neuropathic parameter correlated with N-P amplitude on multiple linear regression analysis (p=0.010) compared to large-fiber parameters., Conclusions: In neuropathic patients with pathological evidence of skin denervation, there were reduced amplitude and prolonged latencies in CHEPs mediated by Adelta fibers. The reduction of CHEP amplitude corresponded to the degree of skin denervation., Significance: CHEP offers electrophysiological evidence of thermal responses and provides an objective, non-invasive approach to assess the physiological counterparts of skin denervation in neuropathic patients.

The effects of various exposures (intensity, duration) of high-intensity focused ultrasound (HIFU) on sciatic nerve conduction were investigated in vivo in rats. The objective was to identify HIFU exposures that produce biological effects ranging from partial to complete conduction block, indicating potential use of HIFU as an alternative to current clinical methods of inducing nerve conduction block. In the study, 26 nerves were exposed and treated with 5-s applications of 5.7-MHZ HIFU with acoustic intensities of 390, 2,255, 3,310, and 7,890 W/cm(2) (spatial peak, temporal peak). Compound muscle action potentials (CMAPs), in response to electrical stimulation of the nerve proximal to the HIFU site, were recorded from the plantar foot muscles immediately before and after HIFU treatment and 2 and 4 h after treatment. Furthermore, a preliminary long-term investigation was performed on 27 nerves with the same four sets of HIFU parameters. CMAPs were measured at the survival endpoint for each animal (7 or 28 days after treatment). For nerves treated with the three lower exposures, CMAPs decreased initially within 4 h or 7 days after HIFU treatment and then recovered to their baseline level at 28 days after treatment. For the highest exposure, however, CMAPs remained absent even 28 days after treatment. These exposure-dependent effects of HIFU on nerve function suggest its future potential as a novel treatment for severe spasticity and pain.

Type 1 diabetes mellitus (T1DM) is associated with a peripheral neuropathy that reduces nerve conduction velocity. This may impair high motor-unit discharge frequencies (MUDF), decrease muscle activation, and curtail the ability to sustain repetitive contractile tasks. We examined (1) whether MUDF, the contractile properties of the knee extensors, and the conduction velocity of persons with T1DM differed from controls; (2) whether persons with T1DM can maintain adequate MUDF during a fatigue protocol; and (3) the relationship between these parameters and impaired glycemic control. We studied male and female subjects with T1DM and controls matched for age, height, weight, and gender. Single motor unit recordings were made from vastus lateralis during maximal and submaximal contractions and during a fatigue protocol. Glycemic control was assessed from blood glucose concentration and glycosylated hemoglobin (HbA1c). Control femoral conduction velocities were comparable to literature values and those of the T1DM subjects were slower. These values correlated with plasma glucose and HbA1c. T1DM subjects fatigued 45% sooner than controls, and time to fatigue and conduction velocity were correlated (r = 0.54, P < 0.05). Discharge frequencies tended to be slower during 50% maximal voluntary contractile force in the T1DM subjects at task failure. Persons with T1DM had slower conduction velocities and lower MUDF than their controls, which apparently leads to impaired activation of muscle and decreased endurance during isometric fatigue.

We hypothesized that the corticospinal system undergoes functional changes in long-term polio survivors. Central motor conduction times (CMCTs) to the four limbs were measured in 24 polio survivors using transcranial magnetic stimulation (TMS). Resting motor thresholds and CMCTs were normal. In 17 subjects whose legs were affected by polio and 13 healthy controls, single- and paired-pulse TMS was used to assess motor cortex excitability while recording from tibialis anterior (TA) muscles at rest and following maximal contraction until fatigue. In polio survivors the slope of the recruitment curve was normal, but maximal motor evoked potentials (MEPs) were larger than in controls. MEPs were depressed after fatiguing exercise. Three patients with central fatigue by twitch interpolation had a trend toward slower recovery. There was no association with symptoms of post-polio syndrome. These changes occurring after polio may allow the motor cortex to activate a greater proportion of the motor neurons innervating affected muscles.

Objective: The purpose of this study was to determine the efficacy of anodyne monochromatic infrared photo energy (MIRE) in-home treatments over a 90-day period to improve peripheral sensation and self-reported quality of life in individuals with diabetes., Research Design and Methods: This was a double-blind, randomized, sham-controlled clinical trail. We randomly assigned 69 individuals with diabetes and a vibration perception threshold (VPT) between 20 and 45 V to two treatment groups: active or sham treatment. Sixty patients (120 limbs) completed the study. Anodyne units were used at home every day for 40 min for 90 days. We evaluated nerve conduction velocities, VPT, Semmes-Weinstein monofilaments (SWM) (4-, 10-, 26-, and 60-g monofilaments), the Michigan Neuropathy Screening Instrument (MNSI), a 10-cm visual analog pain scale, and a neuropathy-specific quality of life instrument. We used a nested repeated-measures multiple ANOVA design. Two sites (great toe and fifth metatarsal) were tested on both the left and right feet of each patient, so two feet were nested within each patient and two sites were nested within each foot. To analyze the ordinal SWM scores, we used a nonparametric factorial analysis for longitudinal data., Results: There were no significant differences in measures for quality of life, MNSI, VPT, SWM, or nerve conduction velocities in active or sham treatment groups (P > 0.05)., Conclusions: Anodyne MIRE therapy was no more effective than sham therapy in the treatment of sensory neuropathy in individuals with diabetes.

Recent studies have reported abnormalities in short-term plasticity in patients with Huntington's disease (HD). However, is not known whether long-term potentiation (LTP)-like plasticity is also affected in these patients. We tested cortical and brainstem LTP-like plasticity in eight symptomatic HD patients and in 10 healthy age-matched controls. To probe motor cortex LTP-like plasticity we used paired associative stimulation (PAS), a technique that combines repetitive electric stimulation of the median nerve with subsequent transcranial magnetic stimulation (TMS) of the contralateral motor cortex at 25 ms. To investigate brainstem plasticity, we induced LTP-like phenomena in the trigeminal wide dynamic range neurons (WDR) of the blink reflex circuit by pairing an high-frequency train of electrical stimuli (HFS) over the right supraorbital nerve (SO) coincident with the R2 response elicited by a preceding SO stimulus. Our results demonstrate impairment of both cortical and brainstem LTP-like plasticity in symptomatic HD patients which is similar to LTP deficits previously reported in HD animal models. These findings might well represent the neurophysiological correlates of memory deficits often present in HD.