A Phase-Locked Loop Epilepsy Network Emulator.

Most seizure forecasting employs statistical learning techniques that lack a representation of the network interactions that give rise to seizures. We present an epilepsy network emulator (ENE) that uses a network of interconnected phase-locked loops (PLLs) to model synchronous, circuit-level oscillations between electrocorticography (ECoG) electrodes. Using ECoG data from a canine-epilepsy model (Davis et al. 2011) and a physiological entropy measure (approximate entropy or ApEn, Pincus 1995), we demonstrate the entropy of the emulator phases increases dramatically during ictal periods across all ECoG recording sites and across all animals in the sample. Further, this increase precedes the observable voltage spikes that characterize seizure activity in the ECoG data. These results suggest that the ENE is sensitive to phase-domain information in the neural circuits measured by ECoG and that an increase in the entropy of this measure coincides with increasing likelihood of seizure activity. Understanding this unpredictable phase-domain electrical activity present in ECoG recordings may provide a target for seizure detection and feedback control.

Postmenopausal osteoporosis: Our experience.

INTRODUCTION: There is very little published literature about experience with osteoporosis treatment from our country. MATERIALS AND METHODS: It is a retrospective analysis of first 50 patients enrolled in our clinic for osteoporosis. Postmenopausal women with T score of less than -2.5 or history suggestive fragility fracture with supportive bone mineral density (BMD) were included. Patients having hypercalcemia, abnormal renal function, myeloma and on long-term steroids were also excluded. RESULTS: Nearly 34% subjects were below the age of 60 years, 47% of subjects were between 60 and 70 years, whereas 18% were above 70 years. Nearly 6% had family history of osteoporosis s or history of osteoporotic fractures. Nearly 20% subjects had fracture prior to starting of any treatment. A total of 86% (40/46) had evidence of Vitamin D (VD) deficiency. Nearly 80% of patients were treated with bisphosphonates, 12% were treated with injectable bisphosphonates, and 8% were treated with teriperatide. Nearly 16% patients had duration of more than 5 years of experience with bisphosphonates. Follow up BMD was available in 25 subjects. BMD had improved significantly in 68% of subjects. In 24% the BMD was stable (the change was less than least significant change (LSC)). In 8% BMD had shown a significant decline while being on treatment. CONCLUSION: Postmenopausal osteoporosis occurs in relatively younger women in our country. Majority of them are VD deficient. Oral bisphosphonates is the most common used drug; it is fairly well tolerated and effective.

Distortion-product otoacoustic emissions in the common marmoset (Callithrix jacchus): parameter optimization.

Distortion-product otoacoustic emissions (DPOAEs) were measured in a New World primate, the common marmoset (Callithrix jacchus). We determined the optimal primary-tone frequency ratio (f(2)/f(1)) to generate DPOAEs of maximal amplitude between 3 and 24 kHz. The optimal f(2)/f(1), determined by varying f(2)/f(1) from 1.02 to 1.40 using equilevel primary tones, decreased with increasing f(2) frequency between 3 and 17 kHz, and increased at 24 kHz. The optimal f(2)/f(1) ratio increased with increasing primary-tone levels from 50 to 74 dB SPL. When all stimulus parameters were considered, the mean optimal f(2)/f(1) was 1.224-1.226. Additionally, we determined the effect of reducing L(2) below L(1). Decreasing L(2) below L(1) by 0, 5, and 10 dB (f(2)/f(1)=1.21) minimally affected DPOAE strength. DPOAE levels were stronger in females than males and stronger in the right ear than the left, just as in humans. This study is the first to measure OAEs in the marmoset, and the results indicate that the effect of varying the frequency ratio and primary-tone level difference on marmoset DPOAEs is similar to the reported effects in humans and Old World primates.

Continuous detection of weak sensory signals in afferent spike trains: the role of anti-correlated interspike intervals in detection performance.

An important problem in sensory processing is deciding whether fluctuating neural activity encodes a stimulus or is due to variability in baseline activity. Neurons that subserve detection must examine incoming spike trains continuously, and quickly and reliably differentiate signals from baseline activity. Here we demonstrate that a neural integrator can perform continuous signal detection, with performance exceeding that of trial-based procedures, where spike counts in signal- and baseline windows are compared. The procedure was applied to data from electrosensory afferents of weakly electric fish (Apteronotus leptorhynchus), where weak perturbations generated by small prey add approximately 1 spike to a baseline of approximately 300 spikes s(-1). The hypothetical postsynaptic neuron, modeling an electrosensory lateral line lobe cell, could detect an added spike within 10-15 ms, achieving near ideal detection performance (80-95%) at false alarm rates of 1-2 Hz, while trial-based testing resulted in only 30-35% correct detections at that false alarm rate. The performance improvement was due to anti-correlations in the afferent spike train, which reduced both the amplitude and duration of fluctuations in postsynaptic membrane activity, and so decreased the number of false alarms. Anti-correlations can be exploited to improve detection performance only if there is memory of prior decisions.

Nonrenewal statistics of electrosensory afferent spike trains: implications for the detection of weak sensory signals.

The ability of an animal to detect weak sensory signals is limited, in part, by statistical fluctuations in the spike activity of sensory afferent nerve fibers. In weakly electric fish, probability coding (P-type) electrosensory afferents encode amplitude modulations of the fish's self-generated electric field and provide information necessary for electrolocation. This study characterizes the statistical properties of baseline spike activity in P-type afferents of the brown ghost knifefish, Apteronotus leptorhynchus. Short-term variability, as measured by the interspike interval (ISI) distribution, is moderately high with a mean ISI coefficient of variation of 44%. Analysis of spike train variability on longer time scales, however, reveals a remarkable degree of regularity. The regularizing effect is maximal for time scales on the order of a few hundred milliseconds, which matches functionally relevant time scales for natural behaviors such as prey detection. Using high-order interval analysis, count analysis, and Markov-order analysis we demonstrate that the observed regularization is associated with memory effects in the ISI sequence which arise from an underlying nonrenewal process. In most cases, a Markov process of at least fourth-order was required to adequately describe the dependencies. Using an ideal observer paradigm, we illustrate how regularization of the spike train can significantly improve detection performance for weak signals. This study emphasizes the importance of characterizing spike train variability on multiple time scales, particularly when considering limits on the detectability of weak sensory signals.

Neural basis of hearing in real-world situations.

In real-world situations animals are exposed to multiple sound sources originating from different locations. Most vertebrates have little difficulty in attending to selected sounds in the presence of distractors, even though sounds may overlap in time and frequency. This chapter selectively reviews behavioral and physiological data relevant to hearing in complex auditory environments. Behavioral data suggest that animals use spatial hearing and integrate information in spectral and temporal domains to determine sound source identity. Additionally, attentional mechanisms help improve hearing performance when distractors are present. On the physiological side, although little is known of where and how auditory objects are created in the brain, studies show that neurons extract behaviorally important features in parallel hierarchically arranged pathways. At the highest levels in the pathway these features are often represented in the form of neural maps. Further, it is now recognized that descending auditory pathways can modulate information processing in the ascending pathway, leading to improvements in signal detectability and response selectivity, perhaps even mediating attention. These issues and their relevance to hearing in real-world conditions are discussed with respect to several model systems for which both behavioral and physiological data are available.

Detection of auditory signals by frog inferior collicular neurons in the presence of spatially separated noise.

Detection of auditory signals by frog inferior collicular neurons in the presence of spatially separated noise. J. Neurophysiol. 80: 2848-2859, 1998. Psychophysical studies have shown that the ability to detect auditory signals embedded in noise improves when signal and noise sources are widely separated in space; this allows humans to analyze complex auditory scenes, as in the cocktail-part effect. Although these studies established that improvements in detection threshold (DT) are due to binaural hearing, few physiological studies were undertaken, and very little is known about the response of single neurons to spatially separated signal and noise sources. To address this issue we examined the responses of neurons in the frog inferior colliculus (IC) to a probe stimulus embedded in a spatially separated masker. Frogs perform auditory scene analysis because females select mates in dense choruses by means of auditory cues. Results of the extracellular single-unit recordings demonstrate that 22% of neurons (A-type) exhibited improvements in signal DTs when probe and masker sources were progressively separated in azimuth. In contrast, 24% of neurons (V-type) showed the opposite pattern, namely, signal DTs were lowest when probe and masker were colocalized (in many instances lower than the DT to probe alone) and increased when the two sound sources were separated. The remaining neurons demonstrated a mix of these two types of patterns. An intriguing finding was the strong correlation between A-type masking release patterns and phasic neurons and a weaker correlation between V-type patterns and tonic neurons. Although not decisive, these results suggest that phasic units may play a role in release from masking observed psychophysically. Analysis of the data also revealed a strong and nonlinear interaction among probe, masker, and masker azimuth and that signal DTs were influenced by two factors: 1) the unit's sensitivity to probe in the presence of masker and 2) the criterion level for estimating DT. For some units, it was possible to examine the interaction between these two factors and gain insights into the variation of DTs with masker azimuth. The implications of these findings are discussed in relation to signal detection in the auditory system.

Neural ensemble coding of target identity in echolocating bats.

Most insectivorous bats use echolocation to determine the identity of flying insects. Among the many target features that are so extracted, the insect's wingbeat pattern and frequency appear to serve as useful cues for identification. Biosonar pulses impinging on the fluttering wings of an insect are returned as echoes whose amplitudes vary with time, thus providing a characteristic signature of the insect. It has been shown previously that neurons in the inferior colliculus, a midbrain auditory nucleus, of the little brown bat respond to sound stimuli that mimic echoes from fluttering targets. To examine the manner in which target identity is represented in the inferior colliculus, an ensemble coding analysis using a filter-based approach was undertaken. The analysis indicates that a discrete subset of neurons in the inferior colliculus, the onset units, are strongly tuned to wingbeat frequencies of targets that the bat hunts, and that ensemble response reaches a maximum at a distinct phase of the prey capture maneuver: the late approach stage. On the basis of the analysis it is hypothesized that inferior colliculus neurons may play an important role in target detection-identification processing. Although ensemble coding of temporally sequenced information has not been analyzed in the auditory system so far, this study indicates that this method of coding may provide the information necessary to detect and identify targets during prey capture.

Comparison of phenobarbitone, phenytoin with sodium valproate: randomized, double-blind study.

OBJECTIVE: To compare the efficacy and side effects of phenobarbitone (PB), phenytoin (PHT) and sodium valproate (SVP) in controlling generalized tonic-clonic convulsions (GTC). DESIGN: Randomized, double blind clinical trial. SETTING: Out-Patients in a tertiary care hospital. PATIENTS: 151 children with GTC, aged 4-12 yrs, from Madras city were enrolled. At the end of 2 yrs, 127 children remained in the study. INTERVENTION: Each child was given one active drug and 2 placebo tablets. Clinical, hematological and biochemical evaluations were done every month. Serum drug levels were assessed periodically. MAIN OUTCOME MEASURES: Recurrence of convulsion and side effects. RESULTS: The proportion of children with recurrence did not differ among the 3 groups. More than one side effect was observed in 16 (32%) children on PB, 20 (40%) children on PHT and 9 (19%) children on SVP and this difference was statistically significant (p < 0.05). Hyperactivity was the major side effect of PB, observed in 22% of children. CONCLUSION: All 3 drugs were equally effective in controlling seizures. Side effects were minimal with SVP followed by PB. Though side effects were more frequent with PHT, most of them disappeared on adjusting drug dosage. Least expensive phenobarbitone may be preferred as the first drug of choice but, only for pre-school children. SVP is advised for school going children.

Vestibular compensation in the horizontal vestibulo-ocular reflex of the goldfish.

Vestibular compensation is the process whereby vestibular system function is restored following unilateral removal of the vestibular receptors (hemilabyrinthectomy). Vestibular compensation was studied in the horizontal vestibulo-ocular reflex (VOR) of the goldfish. Spontaneous VOR (spontaneous nystagmus) was not observed in the goldfish following recovery from the surgery for hemilabyrinthectomy (a period of about 30 min). However, hemilabyrinthectomy resulted in an acute decrease in the gain of the horizontal VOR to approx. 50% of normal, and an increase in phase lead for mid-range frequencies (0.05 to 0.5 Hz). After 1 week of compensation, VOR gain had increased toward normal, and phase lead had returned to normal levels for mid-range frequencies, but increased above normal at low frequencies. After 1 month of compensation, horizontal VOR gain had recovered its normal value for head rotational velocity up to 60 deg/s, but it appeared to saturate for higher head velocity, and phase lead had decreased to normal, and even slightly below normal, at low frequencies. The results suggest that the goldfish is capable of almost completely recovering both the gain and phase of the horizontal VOR following 1 month of compensation for hemilabyrinthectomy. The extent of compensation in the horizontal VOR of the goldfish is greater than that which has been reported for mammals.

Evidence for a cooperative learning mechanism in the vestibulo-ocular reflex.

The vestibulo-ocular reflex (VOR) stabilizes vision by producing eye rotations that counterbalance head rotations. It receives input from a pair of vestibular receptors, and becomes unbalanced when input from one side is removed, producing spontaneous eye rotation in the absence of head rotation (SVOR). SVOR can be eliminated by the process of vestibular compensation. In mammals, SVOR elimination occurs over a period of days, and follows an exponential time course. We show that SVOR elimination in goldfish occurs in a matter of minutes, and its time course is not exponential but is characterized by a sigmoid function suggesting a cooperative mechanism. This time course is reproduced in a stochastic neural network model that has nonspecific reinforcement related to the level of VOR imbalance.

A vigorous mutant sugarcane (Saccharum sp.) clone Co 527.

A vigorous fast growing mutant which ends vegetative growth sixty days earlier than the parent variety Co 527 was isolated from gamma irradiated vegetative buds. The mutant initially segregated but stabilized in the vM4 generation. Its growth rate was almost fifty per cent higher than Co 527 beginning in the early stages of growth. It produced a significantly higher early shoot population which enabled it to yield a higher number of millable canes at maturity. Economic characters like sucrose content and juice purity remained unaffected. This mutant had a chromosomal basis in that the number was 2 to 3 lower than in the parent variety.