Self-organised transients in a neural mass model of epileptogenic tissue dynamics

Stimulation of human epileptic tissue can induce rhythmic, self-terminating responses on the EEG or ECoG. These responses play a potentially important role in localising tissue involved in the generation of seizure activity, yet the underlying mechanisms are unknown. However, in vitro evidence suggests that self-terminating oscillations in nervous tissue are underpinned by non-trivial spatio-temporal dynamics in an excitable medium. In this study, we investigate this hypothesis in spatial extensions to a neural mass model for epileptiform dynamics. We demonstrate that spatial extensions to this model in one and two dimensions display propagating travelling waves but also more complex transient dynamics in response to local perturbations. The neural mass formulation with local excitatory and inhibitory circuits, allows the direct incorporation of spatially distributed, functional heterogeneities into the model. We show that such heterogeneities can lead to prolonged reverberating responses to a single pulse perturbation, depending upon the location at which the stimulus is delivered. This leads to the hypothesis that prolonged rhythmic responses to local stimulation in epileptogenic tissue result from repeated self-excitation of regions of tissue with diminished inhibitory capabilities. Combined with previous models of the dynamics of focal seizures this macroscopic framework is a first step towards an explicit spatial formulation of the concept of the epileptogenic zone. Ultimately, an improved understanding of the pathophysiologic mechanisms of the epileptogenic zone will help to improve diagnostic and therapeutic measures for treating epilepsy.

Mechanisms of nanoparticle-mediated photomechanical cell damage

Laser-assisted killing of gold nanoparticle targeted macrophages was investigated. Using pressure transient detection, flash photography and transmission electron microscopy (TEM) imaging, we studied the mechanism of single cell damage by vapor bubble formation around gold nanospheres induced by nanosecond laser pulses. The influence of the number of irradiating laser pulses and of particle size and concentration on the threshold for acute cell damage was determined. While the single pulse damage threshold is independent of the particle size, the threshold decreases with increasing particle size when using trains of pulses. The dependence of the cell damage threshold on the nanoparticle concentration during incubation reveals that particle accumulation and distribution inside the cell plays a key role in tissue imaging or cell damaging.

Quantitative assessment of nociceptive processes in conscious dogs by use of the nociceptive withdrawal reflex

OBJECTIVE: To investigate the feasibility of evoking the nociceptive withdrawal reflex (NWR) from fore and hind limbs in conscious dogs, score stimulus-associated behavioral responses, and assess the canine NWR response to suprathreshold stimulations. ANIMALS: 8 adult Beagles. PROCEDURE: Surface electromyograms evoked by transcutaneous electrical stimulation of ulnaris and digital plantar nerves were recorded from the deltoideus, cleidobrachialis, biceps femoris, and tibialis cranialis muscles. Train-of-five pulses (stimulus(train)) were used; reflex threshold (I(t train)) was determined, and recruitment curves were obtained at 1.2, 1.5, and 2 x I(t train). Additionally, a single pulse (stimulus(single)) was given at 1, 1.2, 1.5, 2, and 3 x I(t train). Latency and amplitude of NWRs were analyzed. Severity of behavioral reactions was subjectively scored. RESULTS: Fore- and hind limb I(t train) values (median; 25% to 75% interquartile range) were 2.5 mA (2.0 to 3.6 mA) and 2.1 mA (1.7 to 2.9 mA), respectively. At I(t train), NWR latencies in the deltoideus, cleidobrachialis, biceps femoris, and cranial tibialis muscles were not significantly different (19.6 milliseconds [17.1 to 20.5 milliseconds], 19.5 milliseconds [18.1 to 20.7 milliseconds], 20.5 milliseconds [14.7 to 26.4 milliseconds], and 24.4 milliseconds [17.1 to 40.5 milliseconds], respectively). Latencies obtained with stimulus(train) and stimulus(single) were similar. With increasing stimulation intensities, NWR amplitude increased and correlated positively with behavioral scores. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, the NWR can be evoked from limbs and correlates with behavioral reactions. Results suggest that NWR evaluation may enable quantification of nociceptive system excitability and efficacy of analgesics in individual dogs.

Inhibitory control of the human dorsolateral prefrontal cortex during the anti-saccade paradigm--a transcranial magnetic stimulation study

In the anti-saccade paradigm, subjects are instructed not to make a reflexive saccade to an appearing lateral target but to make an intentional saccade to the opposite side instead. The inhibition of reflexive saccade triggering is under the control of the dorsolateral prefrontal cortex (DLPFC). The critical time interval at which this inhibition takes place during the paradigm, however, is not exactly known. In the present study, we used single-pulse transcranial magnetic stimulation (TMS) to interfere with DLPFC function in 15 healthy subjects. TMS was applied over the right DLPFC either 100 ms before the onset of the visual target (i.e. -100 ms), at target onset (i.e. 0 ms) or 100 ms after target onset (i.e. +100 ms). Stimulation 100 ms before target onset significantly increased the percentage of anti-saccade errors to both sides, while stimulation at, or after, target onset had no significant effect. All three stimulation conditions had no significant influence on saccade latency of correct or erroneous anti-saccades. These findings show that the critical time interval at which the DLPFC controls the suppression of a reflexive saccade in the anti-saccade paradigm is before target onset. In addition, the results suggest the view that the triggering of correct anti-saccades is not under direct control of the DLPFC.

Information processing in long delay memory-guided saccades: further insights from TMS

The performance of memory-guided saccades with two different delays (3 s and 30 s of memorisation) was studied in eight subjects. Single pulse transcranial magnetic stimulation (TMS) was applied simultaneously over the left and right dorsolateral prefrontal cortex (DLPFC) 1 s after target presentation. In both delays, stimulation significantly increased the percentage of error in amplitude of memory-guided saccades. Furthermore, the interfering effect of TMS was significantly higher in the short delay compared to that of the long delay paradigm. The results are discussed in the context of a mixed model of spatial working memory control including two components: First, serial information processing with a predominant role of the DLPFC during the early period of memorisation and, second, parallel information processing, which is independent from the DLPFC, operating during longer delays.

Visual vector inversion during memory antisaccades--a TMS study

In the memory antisaccade task, subjects are instructed to look at an imaginary point precisely at the opposite side of a peripheral visual stimulus presented short time previously. To perform this task accurately, the visual vector, i.e., the distance between a central fixation point and the peripheral stimulus, must be inverted from one visual hemifield to the other. Recent data in humans and monkeys suggest that the posterior parietal cortex (PPC) might be critically involved in the process of visual vector inversion. In the present study, we investigated the temporal dynamics of visual vector inversion in the human PPC by using transcranial magnetic stimulation (TMS). In six healthy subjects, single pulse TMS was applied over the right PPC during a memory antisaccade task at four different time intervals: 100 ms, 217 ms, 333 ms, or 450 ms after target onset. The results indicate that for rightward antisaccades, i.e., when the visual target was presented in the left screen-half, TMS had a significant effect on saccade gain when applied 100 ms after target onset, but not later. For leftward antisaccades, i.e., when the visual target was presented in the right screen-half, a significant TMS effect on gain was found for the 333 ms and 450 ms conditions, but not for the earlier ones. This double dissociation of saccade gain suggests that the initial process of vector inversion can be disrupted 100 ms after onset of the visual stimulus and that TMS interfered with motor saccade planning based on an inversed vector signal at 333 ms and 450 ms after stimulus onset.

Optimization of Schwinger pair production in colliding laser pulses

Recent studies of Schwinger pair production have demonstrated that the asymptotic particle spectrum is extremely sensitive to the applied field profile. We extend the idea of the dynamically assisted Schwinger effect from single pulse profiles to more realistic field configurations to be generated in an all-optical experiment searching for pair creation. We use the quantum kinetic approach to study the particle production and employ a multi-start method, combined with optimal control theory, to determine a set of parameters for which the particle yield in the forward direction in momentum space is maximized. We argue that this strategy can be used to enhance the signal of pair production on a given detector in an experimental setup.

Transcranial magnetic stimulation (TMS) inhibits cortical dendrites

One of the leading approaches to non-invasively treat a variety of brain disorders is transcranial magnetic stimulation (TMS). However, despite its clinical prevalence, very little is known about the action of TMS at the cellular level let alone what effect it might have at the subcellular level (e.g. dendrites). Here, we examine the effect of single-pulse TMS on dendritic activity in layer 5 pyramidal neurons of the somatosensory cortex using an optical fiber imaging approach. We find that TMS causes GABAB-mediated inhibition of sensory-evoked dendritic Ca(2+) activity. We conclude that TMS directly activates fibers within the upper cortical layers that leads to the activation of dendrite-targeting inhibitory neurons which in turn suppress dendritic Ca(2+) activity. This result implies a specificity of TMS at the dendritic level that could in principle be exploited for investigating these structures non-invasively.

Late Quaternary planktonic foraminifera of ODP Hole 175-1087A

Planktonic foraminiferal assemblages from the upper Pleistocene part of Hole 1087A (0 to 12.1 meters below seafloor) are investigated to assess the role of global and local climate changes on surface circulation in the southern Benguela region. The benthic stable isotope record indicates that the studied interval is representative of the last four climatic cycles, that is, down to marine isotope Stage (MIS) 12. The species assemblages bear a clear transitional to subpolar character, with Neogloboquadrina pachyderma (d), Globorotalia inflata, and Globigerina bulloides, in order of decreasing abundance, as the dominant taxa. This species association presently characterizes the mixing domain of old upwelled and open ocean waters, seaward of the Benguela upwelling cells. Abundance variation of the dominant foraminiferal species roughly follows a glacial-interglacial pattern down to MIS 8, suggesting an alternation of upwelling strength and associated seaward extension of the belt of upwelled water as a response to global climate changes. This pattern is interrupted from ~250 ka down to MIS 12, where the phase relationship with global climate is ill defined and might be interpreted as a local response of the southern Benguela region to the mid-Brunhes event. Of particular interest is a single pulse of newly upwelled waters at the location of Site 1087 during early MIS 9 as indicated by a peak abundance of sinistral N. pachyderma (s). Variable input of warm, salty Indian Ocean thermocline waters into the southeast Atlantic, a key component of the Atlantic heat conveyor, is indicated by abundance changes of the tropical taxon Globorotalia menardii. From this tracer, we suggest that interocean exchange was hardly interrupted throughout the last 460 k.y., but was most effective at glacial terminations, particularly during Terminations I and II, as well as during the upper part of MIS 12. This maximum input of Indian Ocean waters around the southern tip of Africa is associated with the reseeding of G. menardii in the tropical Atlantic.

Processing of ultra-wideband low-frequency signals, for application in Foliage Penetration (FOPEN) Synthetic Aperture Radar (SAR) systems

Foliage Penetration (FOPEN) radar systems were introduced in 1960, and have been constantly improved by several organizations since that time. The use of Synthetic Aperture Radar (SAR) approaches for this application has important advantages, due to the need for high resolution in two dimensions. The design of this type of systems, however, includes some complications that are not present in standard SAR systems. FOPEN SAR systems need to operate with a low central frequency (VHF or UHF bands) in order to be able to penetrate the foliage. High bandwidth is also required to obtain high resolution. Due to the low central frequency, large integration angles are required during SAR image formation, and therefore the Range Migration Algorithm (RMA) is used. This project thesis identifies the three main complications that arise due to these requirements. First, a high fractional bandwidth makes narrowband propagation models no longer valid. Second, the VHF and UHF bands are used by many communications systems. The transmitted signal spectrum needs to be notched to avoid interfering them. Third, those communications systems cause Radio Frequency Interference (RFI) on the received signal. The thesis carries out a thorough analysis of the three problems, their degrading effects and possible solutions to compensate them. The UWB model is applied to the SAR signal, and the degradation induced by it is derived. The result is tested through simulation of both a single pulse stretch processor and the complete RMA image formation. Both methods show that the degradation is negligible, and therefore the UWB propagation effect does not need compensation. A technique is derived to design a notched transmitted signal. Then, its effect on the SAR image formation is evaluated analytically. It is shown that the stretch processor introduces a processing gain that reduces the degrading effects of the notches. The remaining degrading effect after processing gain is assessed through simulation, and an experimental graph of degradation as a function of percentage of nulled frequencies is obtained. The RFI is characterized and its effect on the SAR processor is derived. Once again, a processing gain is found to be introduced by the receiver. As the RFI power can be much higher than that of the desired signal, an algorithm is proposed to remove the RFI from the received signal before RMA processing. This algorithm is a modification of the Chirp Least Squares Algorithm (CLSA) explained in [4], which adapts it to deramped signals. The algorithm is derived analytically and then its performance is evaluated through simulation, showing that it is effective in removing the RFI and reducing the degradation caused by both RFI and notching. Finally, conclusions are drawn as to the importance of each one of the problems in SAR system design.

Enrichment for murine keratinocyte stem cells based on cell surface phenotype

The identification and physical isolation of epithelial stem cells is critical to our understanding of their growth regulation during homeostasis, wound healing, and carcinogenesis. These stem cells remain poorly characterized because of the absence of specific molecular markers that permit us to distinguish them from their progeny, the transit amplifying (TA) cells, which have a more restricted proliferative potential. Cell kinetic analyses have permitted the identification of murine keratinocyte stem cells (KSCs) as slowly cycling cells that retain [3H]thymidine ([3H]Tdr) label, termed label-retaining cells (LRCs), whereas TA cells are visualized as rapidly cycling cells after a single pulse of [3H]Tdr, termed pulse-labeled cells (PLCs). Here, we report on the successful separation of KSCs from TA cells through the combined use of in vivo cell kinetic analysis and fluorescence-activated cell sorting. Specifically, we demonstrate that murine dorsal keratinocytes characterized by their high levels of α6 integrin and low to undetectable expression of the transferrin receptor (CD71) termed α6briCD71dim cells, are enriched for epithelial stem cells because they represent a minor (≈8%) and quiescent subpopulation of small blast-like cells, with a high nuclear:cytoplasmic ratio, containing ≈70% of label-retaining cells, the latter being a well documented characteristic of stem cells. Conversely, TA cells could be enriched in a phenotypically distinct subpopulation termed α6briCD71bri, representing the majority (≈60%) of basal keratinocytes that are actively cycling, and importantly contain ≈70% of [3H]Tdr pulse-labeled cells. Importantly, immunostaining of dorsal skin revealed the presence of CD71dim cells in the hair follicle bulge region, a well documented location for KSCs.

Does interhemispheric competition mediate motion-induced blindness? A transcranial magnetic stimulation study

Motion-induced blindness (MIB) is a phenomenon, perhaps related to perceptual rivalry, where stationary targets disappear and reappear in a cyclic mode when viewed against a background (mask) of coherent, apparent 3-D motion. Since MIB has recently been shown to share similar temporal properties with binocular rivalry, we probed the appearance-disappearance cycle of MIB using unilateral, single-pulse transcranial magnetic stimulation (TMS)-a manipulation that has previously been shown to influence binocular rivalry. Effects were seen for both hemispheres when the timing of TMS was determined prospectively on the basis of a given subject's appearance-disappearance cycle, so that it occurred on average around 300 ms before the time of perceptual switch. Magnetic stimulation of either hemisphere shortened the time to switch from appearance to disappearance and vice versa. However, TMS of left posterior parietal cortex more selectively shortened the disappearance time of the targets if delivered in phase with the disappearance cycle, but lengthened it if TMS was delivered in the appearance phase after the perceptual switch. Opposite effects were seen in the right hemisphere, although less marked than the left-hemisphere effects. As well as sharing temporal characteristics with binocular rivalry, MIB therefore seems to share a similar underlying mechanism of interhemispheric modulation. Interhemispheric switching may thus provide a common temporal framework for uniting the diverse, multilevel phenomena of perceptual rivalry.

Numerical modelling of dispersion managed soliton transmission

This thesis presents the results of numerical modelling of the propagation of dispersion managed solitons. The theory of optical pulse propagation in single mode optical fibre is introduced specifically looking at the use of optical solitons for fibre communications. The numerical technique used to solve the nonlinear Schrödinger equation is also introduced. The recent developments in the use of dispersion managed solitons are reviewed before the numerical results are presented. The work in this thesis covers two main areas; (i) the use of a saturable absorber to control the propagation of dispersion managed solutions and (ii) the upgrade of the installed standard fibre network to higher data rates through the use of solitons and dispersion management. Saturable absorbe can be used to suppress the build up of noise and dispersive radiation in soliton transmission lines. The use of saturable absorbers in conjunction with dispersion management has been investigated both as a single pulse and for the transmission of a 10Gbit/s data pattern. It is found that this system supports a new regime of stable soliton pulses with significantly increased powers. The upgrade of the installed standard fibre network to higher data rates through the use of fibre amplifiers and dispersion management is of increasing interest. In this thesis the propagation of data at both 10Gbit/s and 40Gbit/s is studied. Propagation over transoceanic distances is shown to be possible for 10Gbit/s transmission and for more than 2000km at 40Gbit/s. The contribution of dispersion managed solitons in the future of optical communications is discussed in the thesis conclusions.

The use of driven equilibrium conditions in the measurement of NMR relaxation times

The further development of the use of NMR relaxation times in chemical, biological and medical research has perhaps been curtailed by the length of time these measurements often take. The DESPOT (Driven Equilibrium Single Pulse Observation of T1) method has been developed, which reduces the time required to make a T1 measurement by a factor of up to 100. The technique has been studied extensively herein and the thesis contains recommendations for its successful experimental application. Modified DESPOT type equations for use when T2 relaxation is incomplete or where off-resonance effects are thought to be significant are also presented. A recently reported application of the DESPOT technique to MR imaging gave good initial results but suffered from the fact that the images were derived from spin systems that were not driven to equilibrium. An approach which allows equilibrium to be obtained with only one non-acquisition sequence is presented herein and should prove invaluable in variable contrast imaging. A DESPOT type approach has also been successfully applied to the measurement of T1. T_1's can be measured, using this approach significantly faster than by the use of the classical method. The new method also provides a value for T1 simultaneously and therefore the technique should prove valuable in intermediate energy barrier chemical exchange studies. The method also gives rise to the possibility of obtaining simultaneous T1 and T1 MR images. The DESPOT technique depends on rapid multipulsing at nutation angles, normally less than 90^o. Work in this area has highlighted the possible time saving for spectral acquisition over the classical technique (90^o-5T_1)_n. A new method based on these principles has been developed which permits the rapid multipulsing of samples to give T_1 and M_0 ratio information. The time needed, however, is only slightly longer than would be required to determine the M_0 ratio alone using the classical technique. In ^1H decoupled ^13C spectroscopy the method also gives nOe ratio information for the individual absorptions in the spectrum.

Mode-locking in 25-km fibre laser

We demonstrate mode-locking and single-pulse generation in fibre laser with record-setting cavity length of 25 km. Substantial increase in the pulse round trip duration leads to ultra-low repetition rate of 8.097 kHz and pulse energy of 3.7 uJ.