Effects of polarization and apodization on laser induced optical breakdown threshold.

We investigated the influence of polarization and apodization on laser induced optical breakdown threshold in transparent and diffuse media using linearly and radially polarized light. We demonstrate a lower irradiance threshold for optical breakdown using radially polarized light. The dominance of radial polarization in higher-order multiphoton ionization has important medical applications where a lower irradiance threshold may allow reaching deeper layers inside the skin with less risk of collateral damage and thereby improving safety and efficacy of treatment.

Numerical prediction of frequency dependent 3D maps of mechanical index thresholds in ultrasonic brain therapy.

PURPOSE: Therapeutic ultrasound has been used in the brain for thrombolysis and high intensity focused ultrasound (HIFU) therapy. A low-frequency clinical study of sonothrombolysis, called the transcranial low-frequency ultrasound-mediated thrombolysis in brain ischemia (TRUMBI), has revealed an increased incidence of hemorrhage, which may have been caused by cavitation. The goal of this study is to determine if there is a comparable risk of generating cavitation during HIFU brain therapy at different frequencies. METHODS: Two approaches are used to transmit acoustic energy through the skull to the brain: low-frequency ultrasound, with a wavelength that is larger than the skull thickness, and high frequency ultrasound, that is sensitive to aberrations and must use corrective techniques. At high frequency, the mechanical index (MI) is lower, which translates to a higher cavitation threshold. In addition to the nonfocused geometry of the 300 kHz sonothrombolysis treatment device, two types of focused therapeutic transducers were modeled: a low frequency 220 kHz transducer and a 1 MHz transducer that required aberration correction with a time-reversal approach, representing the lowest and highest frequencies currently used. The acoustic field was modeled with a finite difference fullwave acoustic code developed for large scale computations, that is, capable of simulating the entire brain volume. Various MI thresholds and device geometries were considered to determine the regions of the brain that have an increased probability of cavitation events. RESULTS: For an equivalent energy deposition rate, it is shown that at a low frequency there is a significant volume of the brain that is above the MI thresholds. At a high frequency, the volume is over 3 orders of magnitude smaller, and it is entirely confined to a compact focal spot. CONCLUSIONS: The significant frequency dependence of the volumes with an increased probability of cavitation can be attributed to two factors: First, the volume encompassed by the focal region depends on the cube of the frequency. Second, the heat deposition increases with frequency. In conclusion, according to these simulations, the acoustic environment during HIFU brain therapy at 1 MHz is not conducive to a high probability of cavitation in extended regions of the brain.

Wavelength dependence of femtosecond laser ablation threshold of corneal stroma.

We measure the surface ablation threshold fluence of porcine corneal stroma for 100 fs laser pulses, with wavelengths between 800 nm and 1450 nm, generated by a Ti:sapphire-pumped optical parametric amplifier. The ablation threshold was found to vary only slightly within this wavelength range, between 1.5 and 2.2 J/cm(2). The data suggest a rapid increase of the ablation threshold for wavelengths up to about 1000 nm, followed by a plateau for longer wavelengths. This behavior is partly confirmed by a simple theoretical model of the ablation process. The influence of the wavelength on the physics of surface ablation is discussed on the basis of the model.

Efficient reduction of stimulus artefact in TMS-EEG by epithelial short-circuiting by mini-punctures.

OBJECTIVE: We aimed at comparing the effects of two different electrode-to-skin contact preparation techniques on the stimulus artefact induced by transcranial magnetic stimulation (TMS) in electroencephalography (EEG) signals. METHODS: Six healthy subjects participated in a combined navigated brain stimulation (NBS) and EEG study. Electrode contacts were first prepared in the standard way of rubbing the skin using a wooden stick with a cotton tip. The location of hand motor area and the motor threshold (MT) was determined for each subject. Then, the TMS-induced artefact was measured at 60%, 80%, 100% and 120% of the MT. Subsequently, the epithelium under the electrode contacts was electrically short-circuited by puncturing with custom-made needles and the stimulation sequences were replicated. The artefact was compared between the preparation techniques. RESULTS: The TMS-induced artefact was significantly reduced after puncturing. In addition, the size and duration of the artefact depended on the applied stimulation intensity. The reduction of the artefact was largest in electrodes at and close to the stimulation site. CONCLUSIONS: Mini-puncturing technique enables more accurate analysis of TMS-induced short-latency phenomena in EEG during NBS, and it may aid in the examination of the short distance neural connectivity beneath and close to the stimulation site. SIGNIFICANCE: This study describes a practical skin preparation method that significantly improves the utility of TMS-EEG method in studying short-latency cortical connectivity.

Reliability of transcranial magnetic stimulation for mapping swallowing musculature in the human motor cortex.

OBJECTIVE: Although transcranial magnetic stimulation (TMS) has been widely used to study motor cortex organization and excitability, the reliability of this technique has not been thoroughly investigated. Furthermore, previous reports of TMS reliability have been restricted to upper limb musculature. We sought to determine the test-retest reliability for TMS mapping of motor representations for swallowing musculature. METHODS: Twenty healthy volunteers were tested twice over two weeks using TMS to determine motor threshold, map area, map volume, maximal MEP site location and maximal MEP site size for the suprahyoid complex and pharyngeal musculature. RESULTS: Good test-retest reliability was found in both swallowing muscle sites for the following test parameters: motor map area, maximal MEP site location: lateral coordinate, maximal MEP site size and motor threshold (ICC=0.76-0.98). Moderate reliability was observed for motor map volume and maximal MEP site location: anterior-posterior coordinate (ICC=0.68-0.74). CONCLUSIONS: TMS assessments of motor representation size, location and excitability appear to be highly reproducible, although the reliability of these measures may vary according to the specific muscle under investigation. SIGNIFICANCE: These works provide much needed psychometric data to validate the use of TMS to assess the cortical representation of swallowing musculature.

Interference of short-interval intracortical inhibition (SICI) and short-interval intracortical facilitation (SICF).

OBJECTIVE: Short-interval intracortical inhibition (SICI) is a widely used paired-pulse transcranial magnetic stimulation (TMS) measure to assess inhibition in human motor cortex. However, facilitatory processes may contaminate SICI under certain conditions. Here, we specifically address the contribution of short-interval intracortical facilitation (SICF). METHODS: A SICF interstimulus interval (ISI) curve was obtained in nine healthy subjects according to an established paired-pulse TMS protocol [Ziemann U, Tergau F, Wassermann EM, Wischer S, Hildebrandt J, Paulus W. Demonstration of facilitatory I-wave interaction in the human motor cortex by paired transcranial magnetic stimulation. J Physiol (Lond) 1998a;511:181-190]. The individual ISI leading to SICF peak1, trough1, peak2, trough2 and peak3 was selected for the subsequent measurement of SICI intensity curves (SICI(peak1), SICI(trough1), SICI(peak2), SICI(trough2), SICI(peak3)) using intensity variation of the first stimulus (S1) from 50% to 120% of active motor threshold (AMT) in the first dorsal interosseous muscle. RESULTS: SICI(peak1) (mean ISI, 1.54ms) and SICI(trough1) (mean ISI, 1.97ms) showed a sigmoid SICI increase with S1 intensity. SICI(trough1) reached the strongest SICI and was therefore chosen for comparison with the other SICI curves. SICI(peak2) (mean ISI, 2.61ms) was U-shaped with a similar increase at low S1 intensities, but a decrease when S1 intensity exceeded 90% AMT. Correlation analyses suggested that this decrease was caused by SICF. SICI(trough2) (mean ISI, 3.50ms) and SICI(peak3) (mean ISI, 4.26ms) showed considerably less inhibition than SICI(trough1) over the whole range of S1 intensities. CONCLUSIONS: Findings show that commonly accepted protocols of testing SICI (ISI of 2-3ms, S1 intensity approximately 95% AMT) bear the risk of measuring net inhibition contaminated by SICF. SIGNIFICANCE: SICF may contribute to apparently reduced SICI in patients with neurological or psychiatric disorders.

Threshold level of p53 required for the induction of apoptosis in X-irradiated MOLT-4 cells.

PURPOSE: To determine the threshold level for the initiation of apoptosis by studying the quantitative aspect of p53 response to DNA damage in individual cells, to better understand the process in X-ray-induced p53-dependent apoptosis. METHODS AND MATERIALS: Time-sequential changes in p53 protein level were obtained for X-irradiated MOLT-4 cells using flow cytometry and analyzed. RESULTS: The changes in the cellular frequency distribution pattern of p53 content could be divided into two parts at a certain p53 level. The p53 vs. side-scatter in flow cytometry showed the sequential changes of p53 increase followed by an increase in cell death. On the basis of these results we determined a threshold level of p53 for the initiation of apoptosis. The level was estimated to be (1.08 +/- 0.05) x 10(5) molecules per cell, which was approximately threefold higher than the mean content of control cells. The minimum times for p53 level to reach this threshold level were independent of X-ray dose and 1.4-1.6 h. The times for the signal transduction from the p53 accumulation to disruption of the mitochondrial membrane potential, caspase-3 activation, and cell death were 1.6, 2.1, and 2.8 h, respectively. CONCLUSIONS: The threshold level of p53 for the initiation of apoptosis and the time sequence in the course of apoptotic events were determined in X-irradiated MOLT-4 cells.

Modulation of motor cortical excitability following rapid-rate transcranial magnetic stimulation.

OBJECTIVE: To investigate the effect of high frequency rTMS (25 Hz at 90-100% of resting motor threshold) on the excitability of the motor cortex of healthy human subjects. METHODS: Resting and active motor threshold, MEP recruitment curve (I/O curve), short interval intracortical inhibition (SICI) and facilitation (ICF), and the duration of the silent period (SP) were tested in the right first dorsal interosseous muscle (FDI) before and twice after the end of 1500 pulses in 16 normal young adult male volunteers. RESULTS: Twenty-five Hertz rTMS decreased motor thresholds, reduced the duration of the silent period and had a tendency to increase the slope of the I/O curve. Most of these effects lasted for the duration of the two post-testing sessions (at least 30 min) and had returned to normal by 2h. There were no significant effects on SICI/ICF. CONCLUSION: Twenty-five Hertz rTMS can produce a long lasting increase in cortical excitability in healthy subjects. SIGNIFICANCE: This method may prove useful for the study of normal human physiology and for therapeutic manipulation of brain plasticity.

Changes in measures of motor axon excitability with age.

OBJECTIVE: Threshold tracking is a novel technique that permits examination of the excitability of human axons in vivo. Protocols have been validated for sensory and motor axons, but there are limited data on the changes in the excitability of motor axons with age. This study aimed to determine such changes from the third to the eighth decades. METHODS: Sixty healthy subjects aged 22-79, 10 per decade, were studied using the TRONDXM4 protocol of the QTRAC threshold-tracking program to assess motor axon function. The median nerve was stimulated at the wrist and the compound muscle action potential was recorded from the thenar muscles. RESULTS: There was an increase in threshold in elderly subjects, associated with a decrease in slope of the stimulus-response curves. Strength-duration time constant and threshold electrotonus to depolarising and hyperpolarising currents of up to 40% did not change significantly with aging. The current-threshold relationship was similar across all decades for subthreshold depolarising currents, but the slope of the current-threshold relationship was significantly steeper the older the subjects for hyperpolarising currents, particularly those greater than 40% of threshold. There was also a significant decrease in supernormality in the recovery cycle with increasing age. CONCLUSIONS: The threshold of axons increases with age and the extent of supernormality decreases. There may also be greater inward rectification in motor axons, perhaps due to greater activity of I(H), the hyperpolarisation-activated conductance, though this is only significant with hyperpolarising currents greater than 40% of the threshold current. SIGNIFICANCE: Many indices of axonal excitability, such as strength-duration time constant, the relative refractory period, late subnormality, threshold electrotonus and the depolarising side of the current-threshold relationship, do not change significantly with age. For other indices, age-related changes may be due to a combination of non-neural factors that alter current access to the node of Ranvier, changes in the axon and its myelination and, possibly, changes in channel activity and/or changes in extracellular [K(+)](o).

Damage thresholds for cultured retinal pigment epithelial cells exposed to lasers at 532 nm and 458 nm.

The determination of safe exposure levels for lasers has come from damage assessment experiments in live animals, which typically involve correlating visually identifiable damage with laser dosimetry. Studying basic mechanisms of laser damage in animal retinal systems often requires tissue sampling (animal sacrifice), making justification and animal availability problematic. We determined laser damage thresholds in cultured monolayers of a human retinal pigment epithelial (RPE) cell line. By varying exposure duration and laser wavelength, we identified conditions leading to damage by presumed photochemical or thermal mechanisms. A comparison with literature values for ocular damage thresholds validates the in vitro model. The in vitro system described will facilitate molecular and cellular approaches for understanding laser-tissue interaction.

Effect of electrode surface area on thresholds for AC stimulation and ventricular fibrillation.

Unintended, weak AC stimulation (leakage currents) from medical devices can cause blood pressure collapse and ventricular fibrillation (VF), potentially even death. Yet, little is understood about AC cardiac stimulation. The objective of this paper is to establish the relationship between the stimulation and VF thresholds for electrode size and stimulation frequency. Twenty-four retired male breeder guinea pigs were anesthetized with isoflurane, a tracheotomy and thoracotomy were performed, and vitals were monitored using the lead II ECG and an optical plethysmograph. The circular flat ends of eleven stainless steel rods were used as electrodes with areas ranging from 0.1 to 26.79 mm2. In the first study, 60-Hz AC stimuli of 5 s duration were delivered with strengths from 25-3000 microA or until VF was induced. In the second group, the current thresholds at 20, 40, 80, and 160 Hz were determined at electrode areas of 0.2, 2.01, and 16.4 mm2. Reactions were categorized as having no effect, having some effect (EFFECT, typically blood pressure collapse), and inducing VF. On a log-log scale, electrode radii had a piecewise-linear relationship with the current thresholds for EFFECT (p < 0.005) and VF (p < 0.01). The liminal area determined by the piecewise-linear fit was 2.0 and 2.84 mm2 for EFFECT and VF, respectively. Above the liminal area, the threshold increased proportional to r(1.25) and r(0.95) (r = radius of electrode), for EFFECT and VF, respectively. Based on these experimental results, we present a theoretical framework to explain the electrode size-stimulation threshold variation for both low strength AC stimulation and VF initiation.

Influence of a 902.4 MHz GSM signal on the human visual system: investigation of the discrimination threshold.

The proximity of a mobile phone to the human eye raises the question as to whether radiofrequency (RF) electromagnetic fields (EMF) affect the visual system. A basic characteristic of the human eye is its light sensitivity, making the visual discrimination threshold (VDThr) a suitable parameter for the investigation of potential effects of RF exposure on the eye. The VDThr was measured for 33 subjects under standardized conditions. Each subject took part in two experiments (RF-exposure and sham-exposure experiment) on different days. In each experiment, the VDThr was measured continuously in time intervals of about 10 s for two periods of 30 min, having a break of 5 min in between. The sequence of the two experiments was randomized, and the study was single blinded. During the RF exposure, a GSM signal of 902.4 MHz (pulsed with 217 Hz) was applied to the subjects. The power flux density of the electromagnetic field at the subject location (in the absence of the subject) was 1 W/m(2), and numerical dosimetry calculations determined corresponding maximum local averaged specific absorption rate (SAR) values in the retina of SAR(1 g) = 0.007 W/kg and SAR(10 g) = 0.003 W/kg. No statistically significant differences in the VDThr were found in comparing the data obtained for RF exposure with those for sham exposure.

Wavelength dependence of ocular damage thresholds in the near-ir to far-ir transition region: proposed revisions to MPES.

This report summarizes the results of a series of infrared (IR) laser-induced ocular damage studies conducted over the past decade. The studies examined retinal, lens, and corneal effects of laser exposures in the near-IR to far-IR transition region (wavelengths from 1.3-1.4 mum with exposure durations ranging from Q-switched to continuous wave). The corneal and retinal damage thresholds are tabulated for all pulsewidth regimes, and the wavelength dependence of the IR thresholds is discussed and contrasted to laser safety standard maximum permissible exposure limits. The analysis suggests that the current maximum permissible exposure limits could be beneficially revised to (1) relax the IR limits over wavelength ranges where unusually high safety margins may unintentionally hinder applications of recently developed military and telecommunications laser systems; (2) replace step-function discontinuities in the IR limits by continuously varying analytical functions of wavelength and pulsewidth which more closely follow the trends of the experimental retinal (for point-source laser exposures) and corneal ED50 threshold data; and (3) result in an overall simplification of the permissible exposure limits over the wavelength range from 1.2-2.6 mum. A specific proposal for amending the IR maximum permissible exposure limits over this wavelength range is presented.

A dose threshold for a medium transfer bystander effect for a human skin cell line.

The existence of radiation-induced bystander effects mediated by diffusible factors is now accepted, but the mechanisms and precise behavior at low doses remain unclear. We exposed cells to gamma-ray doses in the range 0.04 mGy-5 Gy, harvested the culture medium, and transferred it to unirradiated reporter cells. Calcium fluxes and clonogenic survival were measured in the recipients. We show evidence for a dose threshold around 2 mGy for the human skin cell line used with a suggestion of increased survival below that dose. Similar experiments using direct gamma irradiation showed no reduction in survival until the dose exceeded 7 mGy. Preliminary data for neutrons where the gamma-ray dose was kept below the bystander threshold do not show a significant bystander effect in the dose range 1-33 mGy. A lack of a bystander response with neutrons occurred at around 1 Gy, where significant cell killing from direct irradiation was observed. The result may have implications for understanding the role of bystander effects at low doses.

Effects of aging on motor cortex excitability.

To determine whether aging is associated with changes in excitability of the cerebral cortex, we evaluated the excitability of the motor cortex with transcranial magnetic stimulation (TMS). We compared TMS related measures obtained in a group of young people with those of a group of old people. Motor evoked potential (MEP) amplitude was significantly smaller in older than in younger controls (1.3+/-0.8 mV versus 2.7+/-1.1 mV; p<0.0071). Mean cortical silent period (CSP) duration was shorter in older than in younger controls (87+/-29 ms versus 147+/-39 ms; p<0.0071). SP duration/MEP amplitude ratios were similar in both groups. Our results are consistent with an impaired efficiency of some intracortical circuits in old age.

Reliability of motor cortex transcranial magnetic stimulation in four muscle representations.

OBJECTIVE: Motor cortex plasticity may underlie motor recovery after stroke. Numerous studies have used transcranial magnetic stimulation (TMS) to investigate motor system plasticity. However, research on the reliability of TMS measures of motor cortex organization and excitability is limited. We sought to test the reliability of these TMS measurements. METHODS: Twenty healthy volunteers were tested twice over a two-week period using TMS to determine motor threshold, map topography, and stimulus-response curves for first dorsal interosseous (FDI), abductor pollicis brevis (APB), extensor digitorum communis (EDC), and flexor carpi radialis (FCR) muscles. RESULTS: We found moderate to good test-retest reliability TMS measurements of motor threshold (ICC=0.90-0.97), map area (ICC=0.63-0.86) and location (ICC=0.69-0.86), and stimulus-response curves (ICC=0.60-0.83). CONCLUSIONS: TMS assessments of motor representation size, location, and excitability are generally reliable measures, although their reliability may vary according to the muscle under investigation. SIGNIFICANCE: These results suggest that TMS measurements of motor cortex function are reliable enough to be potentially useful in investigation of motor system plasticity.

Distal excitability changes in motor axons in amyotrophic lateral sclerosis.

OBJECTIVE: Previous axonal excitability studies in amyotrophic lateral sclerosis (ALS) have suggested that impaired potassium channel function could be responsible for the generation of fasciculations, but the ectopic activity arises predominantly from the motor nerve terminals. This study tested the hypothesis that dysfunction of potassium channels is more pronounced in the more distal parts of axons. METHODS: Threshold electrotonus was used to compare accommodation at the motor point of abductor pollicis brevis, and at the wrist portion of the median nerve, between 22 patients with ALS and 19 normal subjects. As target responses for motor point stimulation, movement-related potentials were recorded using an accelerometer. RESULTS: Compared to normal subjects, ALS patients showed greater threshold changes to depolarizing conditioning currents at both the motor point and wrist, suggesting less accommodation by potassium currents. Differences in the threshold electrotonus curves between the normal and ALS groups were much more prominent at the motor point than at the wrist. CONCLUSIONS: In ALS, axonal potassium channels are impaired more prominently in distal portions of axons than at the nerve trunk, and this is consistent with evidence that fasciculations mostly arise from the nerve terminals. SIGNIFICANCE: Excitability testing at the motor point provides additional information about the pathophysiology of ALS.

TMS motor cortical brain mapping in patients with complex regional pain syndrome type I.

OBJECTIVE: The motor cortical representation in patients with complex regional pain syndrome type I (CRPS I) was determined under the assumption that the motor cortex undergoes representational adaptations in the course of CRPS. METHODS: A total of 14 patients with CRPS I and a group of healthy subjects without any known neurological symptoms participated in the study. The motor cortical representation, i.e. the size of representation (cm2), motor-evoked potentials (MEP), the calculated volume (cm2 mV), and the center of gravity (CoG) were measured by transcranial magnetic stimulation. Recordings were made of the long extensor muscles of the forearm of the affected and unaffected hand. RESULTS: Analyses of the results revealed a significant asymmetry between the two hemispheres: the motor cortical representation corresponding to the unaffected hand was significantly larger. While the CoG data did not differ statistically between the two hemispheres, the CoG coordinates corresponding to the affected hand indicated a larger variability. CONCLUSIONS: The presence of pain and other CRPS symptoms may induce lasting changes in motor cortical plasticity, as it also does in the sensory cortex. SIGNIFICANCE: This could be of importance in rehabilitative strategies for the sensory motor system in CRPS I patients.

Altered response to rTMS in patients with Alzheimer's disease.

OBJECTIVE: In this study, we tested the excitability of cortical motor areas in patients with Alzheimer's disease. Because repetitive transcranial magnetic stimulation (rTMS) modulates cortical excitability, possibly by inducing a short-term increase in synaptic efficacy, we used rTMS to investigate motor cortex excitability in patients with Alzheimer's disease. METHODS: We tested the changes in the size and threshold of motor evoked potential (MEP) and cortical silent period (CSP) duration evoked by focal rTMS delivered in 10 trains of 10 stimuli at 5Hz frequency and 120% rMth intensity in a group of patients with Alzheimer's disease, and age-matched controls. In a further session, rTMS was also delivered at 1Hz frequency (trains of 10 stimuli, 120% rMth). RESULTS: Whereas in control subjects, 5Hz-rTMS elicited normal MEPs that progressively increased in size during the train, in patients, it elicited MEPs that decreased in size. The increase in the duration of the CSP was similar in patients and healthy controls. One hertz rTMS left the MEP amplitude unchanged in patients and healthy controls. CONCLUSIONS: The lack of MEP facilitation reflects an altered response to 5Hz-rTMS in patients with Alzheimer's disease. SIGNIFICANCE: Our rTMS findings strongly suggest an altered cortical plasticity in excitatory circuits within motor cortex in patients with Alzheimer's disease.

H-reflex depression by propofol and sevoflurane is dependent on stimulus intensity.

OBJECTIVE: The H-reflex has been widely used to investigate effects of drugs on motoneuron excitability in humans. However, up to now no systematic investigation has been done to examine the effects at different stimulus intensities. Here, the M. soleus recruitment curves were compared under influence of propofol and sevoflurane with control conditions to investigate these stimulus intensity dependent effects. METHODS: The study was performed in 10 volunteers for propofol and sevoflurane each, aged 23-32 years. The M. soleus H-reflex was evoked by stimulation of the tibial nerve. Recruitment curves were gained by increasing the stimulation current stepwise from below the threshold of a minimal H-reflex up to a maximal (m-response. Measurements were performed under the influence of the respective drug (2mg/l propofol, 0.8 vol% sevoflurane) and compared to control measurements before and after drug administration. RESULTS: The relative amount of depression of the H-reflex at high stimulus intensities is for both drugs significantly (p<0.001, Friedman's test) lower than at low stimulus intensities. CONCLUSIONS: Stimulus dependent effects have to be taken into consideration when experimental settings to investigate the effects of drugs on the H-reflex are being designed. According to the size principle of motoneuron excitation, it can also be assumed that under the influence of propofol and sevoflurane larger motoneurons are not depressed in the same amount as smaller motoneurons. SIGNIFICANCE: Different drug effects on the H-reflex at different stimulus intensities are not only of methodological importance, but also indicate different drug effects on motoneurons of different sizes.