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We developed a general method to generate populations of artificial spike trains (ASTs) that match the statistics of recorded neurons. The method is based on computing a Gaussian local rate function of the recorded spike trains, which results in rate templates from which ASTs are drawn as gamma distributed processes with a refractory period. Multiple instances of spike trains can be sampled from the same rate templates. Importantly, we can manipulate rate-covariances between spike trains by performing simple algorithmic transformations on the rate templates, such as filtering or amplifying specific frequency bands, and adding behavior related rate modulations. The method was examined for accuracy and limitations using surrogate data such as sine wave rate templates, and was then verified for recorded spike trains from cerebellum and cerebral cortex. We found that ASTs generated with this method can closely follow the firing rate and local as well as global spike time variance and power spectrum. The method is primarily intended to generate well-controlled spike train populations as inputs for dynamic clamp studies or biophysically realistic multicompartmental models. Such inputs are essential to study detailed properties of synaptic integration with well-controlled input patterns that mimic the in vivo situation while allowing manipulation of input rate covariances at different time scales.

Purpose To demonstrate an inexpensive smartphone-based fundus camera device (MII Ret Cam) and technique with ability to capture peripheral retinal pictures. Methods A fundus camera was designed in the form of a device that has slots to fit a smartphone (built-in camera and flash) and 20-D lens. With the help of the device and an innovative imaging technique, high-quality fundus videos were taken with easy extraction of images. Results The MII Ret Cam and innovative imaging technique was able to capture high-quality images of peripheral retina such as ora serrata and pars plana apart from central fundus pictures. Conclusions Our smartphone-based fundus camera can help clinicians to monitor diseases affecting both central and peripheral retina. It can help patients understand their disease and clinicians convincing their patients regarding need of treatment especially in cases of peripheral lesions. Imaging peripheral retina has not been demonstrated in existing smartphone-based fundus imaging techniques. The device can also be an inexpensive tool for mass screening.

Neural coding through inhibitory projection pathways remains poorly understood. We analyze the transmission properties of the Purkinje cell (PC) to cerebellar nucleus (CN) pathway in a modeling study using a data set recorded in awake mice containing respiratory rate modulation. We find that inhibitory transmission from tonically active PCs can transmit a behavioral rate code with high fidelity. We parameterized the required population code in PC activity and determined that 20% of PC inputs to a full compartmental CN neuron model need to be rate-comodulated for transmission of a rate code. Rate covariance in PC inputs also accounts for the high coefficient of variation in CN spike trains, while the balance between excitation and inhibition determines spike rate and local spike train variability. Overall, our modeling study can fully account for observed spike train properties of cerebellar output in awake mice, and strongly supports rate coding in the cerebellum., Author summary Detailed computer simulations of biological neurons can make an important contribution to our understanding of how the brain works. In this paper we use such a model of a neuron that represents the output from the cerebellum. We can show that the inhibition this neuron type receives from Purkinje cells in the cerebellar cortex is well suited to pass a detailed time course of movement control to the output of the cerebellum. Importantly we find that this type of coding requires a population of Purkinje cells that pass the same temporal coding of spike rate to the output neurons in the cerebellar nuclei.

Sir, Diffuse unilateral subacute neuroretinitis (DUSN) is a rare form of ocular larva migrans associated with damage to outer retinal layers and retinal pigment epithelium (RPE) by motile parasitic worms such as Ancylostoma caninum, Toxocara canis, Ascaris lumbricoides, Baylisacaris procyonis, and Dirofilaria spp.[1,2,3,4] We report a case of DUSN in a 37-year-old male, who presented with sudden onset of decreased vision in OS since one week. His best corrected visual acuity (BCVA) was 6/6, N6 (OD) and 4/60, N36 (OS). The OD examination was unremarkable. Fundus examination of OS revealed mild vitritis, multiple RPE de-pigmented patches, multifocal evanescent gray-white lesions in outer retina along with multifocal neurosensory detachment (NSD) involving macula. A glistening white, non-segmented motile worm approximately 2 disc diameter (~3000 μm) with tapered ends was located in supero-temporal quadrant outside temporal arcade [Fig. 1a] with track marks in inferior quadrant [Fig. 1b]. Snake-like wriggling movements of worm increased on light stimulation by fundus photography [Fig. ​[Fig.1c1c–d]. Fluorescein fundus angiography (FFA) revealed multiple RPE leaks with window defects and pooling of dye in NSD's [Fig. 2]. Spectral domain-optical coherence tomography (SD-OCT) demonstrated NSD's over macula and surrounding area with unhealthy RPE [Fig 3a]. Figure 1 Fundus picture showing the location and track marks of live subretinal worm Figure 2 Fundus fluorescein angiography showing punctuate hyerfluorescent areas which leak as the phases of angiograph proceed suggestive of unhealthy retinal pigment epithelium Figure 3 Spectral domain OCT showing pre laser appearance of subretinal worm along with sequential events post laser photocoagulation starting from early inflammation and late scarring Argon laser barrage (Zeiss Inc.; 45 spots, 200 mW, 200 μ, 350 ms) of 532 nm was performed in an attempt to restrict mobility of worm [Fig. 4a]. The worm showed increased movements in an attempt to come out of barraged area [Fig. ​[Fig.4b4b–d]. When it succeeded [Fig. 4e], it was killed directly by laser (15 spots, same settings; Fig. 4f). Although, the effect of laser barrage may take 1-2 weeks, continuous evaluation on experimental basis was done to gauge its effectiveness by limiting further worm migration, for which we had restricted favorable result, as the worm could migrate out of the barraged area only after 15 minutes of coiling and uncoiling effort. Pre-laser 3D SD-OCT revealed the worm as subretinal coiled hyper-echogenic structure [Fig. 3b] while immediately post-laser, it showed intense laser reaction in form of hypoechogenic areas [Fig. 3c]. Single dose of oral albendazole 400 mg along with tapered dose of oral prednisolone (starting from 60 mg/day) and diethylcarbazine 100 mg three times/day were given for 3 weeks. Figure 4 Fundus photograph showing worm movements (coiling and uncoiling) during the process of laser photocoagulation along with complete destruction of worm on follow-up revealed by scar formation Next day, a small streak of blood was seen along the vessel in region of worm [Fig. 4g]. SD-OCT findings showed minimal increase in OCT thickness compared to the previous day, which could be due to inflammatory reaction [Fig. 3d]. Though investigation including blood and stool was negative. On day 10 of post-laser, BCVA was stagnant at 4/60. Fundus examination demonstrated minimal vitritis, faded laser spots and dead worm (Interrupted white line; Black arrowhead in Fig. 4h). 3D SD-OCT revealed sub retinal fibrosis in lasered region [Fig. 3e]. On day 25, BCVA was unchanged. The vitritis resolved with complete disintegration of worm [Fig. 4i]. SD-OCT shows fibrotic scar [Fig. ​[Fig.3f3f–g] along with normal foveal contour with damaged photoreceptor and RPE [Fig. 3h]. The patient was lost to follow-up following this visit. Direct killing of worm with laser has been associated with significant increase in intraocular inflammation.[2] In other parts of body, systemic treatment may be associated with fever, myalgia and headache.[5] There has only been a single correspondence regarding post-laser OCT analysis of worm.[6] We have utilized 3D SD-OCT imaging technique to analyze post-laser worm degradation along with retinal inflammation secondary to worm toxins and laser. In conclusion, our report adds to an existing data[2,3,4] for laser photocoagulation being used as first line of management for cases of DUSN, in which live worm can be identified. OCT is an additional tool other than fundus photograph, which may be helpful in understanding the amount of photoreceptor and RPE destruction caused by worm, which may not be visible on fundus photographs. It can be proposed as another vital non-invasive modality in our armamentarium along with fundus photographs to image the eyes with DUSN.

PURPOSE To describe the effect of unilateral intravitreal injection of 0.7-mg dexamethasone implant on the other eye. METHODS Interventional case report and literature review. RESULTS A 54-year-old woman with bilateral, refractory, clinically significant macular edema was given an intravitreal injection of 0.7-mg dexamethasone sustained release implant in the right eye. The central foveal thickness improved in both the eyes with recurrence of edema after 16 weeks in both the eyes. CONCLUSION An intravitreal dexamethasone injection seems to have bilateral effect after unilateral injection.

Multielectrode recordings from awake behaving mice revealed rhythmic modulation both in Purkinje cell (PC) simple spike (SS) activity and the cerebellar nuclei (CN) neuron activity that is phase locked to the breathing rhythm. In the present work we were interested in studying how the different levels of background SS activity may affect the transfer of rhythmic SS modulation from PCs to the CN using a multicompartmental CN neuron model. We created a population of fifty artificial gamma distributed PC spike trains and gave them to the CN neuron model as inputs with 5nS conductance strength [1]. The mean firing rate for a given input was based on the rate histogram distribution constructed from our experimental PC recordings in awake mice, and ranged from 28 to 170 Hz. An identical slow fluctuation in the background firing rate for all 50 inputs was used, reflecting a high correlation of rates observed in vivo as quantified using a Bayesian rate estimation method [2]. The breathing associated rhythmic modulation estimated from a peri-event time histogram of a PC recording was normalized to a % change from mean rate and convolved with baseline firing rate at the timing of recorded breaths. The synaptic strength of the mossy fiber excitatory inputs was tuned so that the model output gave the best match to both the statistical properties and behavior related modulation of the experimental CN recordings. This match turned out to be excellent, as the mean ISI (recording 29.47, model 29.49), CV (1.072 vs. 0.926), and CV2 (0.74 vs. 0.75) were near identical. The mean breathing related rhythmic modulation in the CN simulation turned out to be higher (60 %) than in the applied PC input trains (12 %). We then separated the breathing modulations obtained in the model output based on whether they occurred at low or high background firing rate. We observed a decrease in modulation depth from 70% to 30% when the baseline firing rate was high in the CN. Similar results were observed in experimental recordings (a decrease from 60% to 30%) which also correlated with an decrease in PC firing rate and a decrease in rhythmicity of breathing during such episodes. To probe the cause of the inverse relationship between CN background rate and breathing modulation depth we used a PC input consisting of a 100 s ramp increase in rate with a fixed breathing modulation depth. This simulation revealed a linear inverse firing rate transformation between PC and CN rates, which also explains the dependence of breathing modulation on background rate. Essentially, since at high rates the absolute breathing related PC rate modulation is higher, this gets translated to greater relative rate modulation of CN neurons at their resulting low mean firing rate. Based on our findings we conclude that the background firing rate of PCs strongly affects the behavioral modulation of the output from the CN. This effect may be important in the cerebellar control or coordination of rhythmic motor behaviors such as breathing, licking, swallowing, and whisking.

Purkinje cells (PCs) in the mammalian cerebellum express high-frequency spontaneous activity with average spike rates between 30 and 200 Hz. Cerebellar nuclear (CN) neurons receive converging input from many PCs, resulting in a continuous barrage of inhibitory inputs. It has been hypothesized that pauses in PC activity trigger increases in CN spiking activity. A prediction derived from this hypothesis is that pauses in PC simple-spike activity represent relevant behavioral or sensory events. Here, we asked whether pauses in the simple-spike activity of PCs related to either fluid licking or respiration, play a special role in representing information about behavior. Both behaviors are widely represented in cerebellar PC simple-spike activity. We recorded PC activity in the vermis and lobus simplex of head-fixed mice while monitoring licking and respiratory behavior. Using cross-correlation and Granger causality analysis, we examined whether short interspike intervals (ISIs) had a different temporal relationship to behavior than long ISIs or pauses. Behavior-related simple-spike pauses occurred during low-rate simple-spike activity in both licking- and breathing-related PCs. Granger causality analysis revealed causal relationships between simple-spike pauses and behavior. However, the same results were obtained from an analysis of surrogate spike trains with gamma ISI distributions constructed to match rate modulations of behavior-related Purkinje cells. Our results therefore suggest that the occurrence of pauses in simple-spike activity does not represent additional information about behavioral or sensory events that goes beyond the simple-spike rate modulations.

Cerebellar Purkinje cells in mice show strong activity modulation related to rhythmic licking behavior [1]. Here we examine whether this modulation may preferentially be related to long inter-spike intervals (ISIs), i.e. pauses in spike activity. A preferential use of spike pauses for event coding of Purkinje cells has previously been suggested [2,3]. We analyzed the lick modulation of Purkinje cell spike trains by several methods. First, we used peri-lick time histograms constructed separately by spikes initiating ISIs of different duration (Fig. ​(Fig.1B1B,​,1C).1C). We found that short and long ISIs showed lick modulation, but licks of intermediate duration did not. Next we conducted a wavelet-based frequency resolved Granger causality analysis [4] to determine whether ISIs of different duration were caused by licks and/or were causal in the control of lick timing. We found there was a peak at 6 Hz from lick to spike in 12 cells, and a smaller peak also at 6 Hz from spike to lick in 5 out of those 12 cells. The peaks for plots (scaled to a possible maximum of 1.0) ranged from 0.1 to 0.8 for lick to spike causality and from 0.1 to 0.3 for spike to lick causality. Again, we found that short (0-10 ms) and long (40 ms and above) were preferentially involved in lick coding. To better understand the ISI duration dependence of lick coding we constructed controlled artificial spike trains from gamma ISI distributions [5], each matching slow spontaneous and lick-triggered spike rate fluctuations. The surrogate data show the same results as the biological ones in terms of preferential short and long ISI involvement in lick modulation. However, causality from spike data to licks was not observed in the artificial data. From these results we infer that any relation between specific ISI durations and lick modulation is due to the statistical properties of rate modulated spike trains, and can be mimicked by a simple gamma - distributed process. We also found that even the spike of single Purkinje cells can be predictive of lick events, suggesting Purkinje cell activity is involved in the control of lick timing. Figure 1 Peri-lick spike histogram broken up by ISI duration. A) The schematic showing the regular lick occurrence with an average lickinterval around 160ms. B) Peri-lick spike histogram for a Purkinje cell recording. The time at which the tongue touches the lick ...

Background Malaria infection among child travellers need special attention as it rarely occurs in non endemic countries. Most studies dealt with risks in the paediatric population, but there is a need to justify age class choices and its direct implication of analysis for severity risk factors. In this study we demonstrated that analysing the multi factorial and caregiver dependent feedbacks for children 6months had severity risks of OR 3.4 (95% CI: 1.39-8.30) and being born in endemic countries confirmed a protective factor against severity in all 3 groups analysed. However, evaluation of

Background Harmonic locking has been observed between breathing and heart beat rhythms, in hippocampal slices between interneurons firing at gamma and pyramidal neurons firing at beta frequencies with missed gamma beats and in model networks between theta and gamma rhythms. Existence and stability criteria for harmonic locking modes were derived for two reciprocally pulse coupled oscillators based on their first and second order phase resetting curves (PRCs). These methods were then tested using two reciprocally inhibitory Wang and Buzsaki model neurons. Methods PRCs were generated in an open loop configuration and applied to the analysis of the circuit under the assumption that after each perturbation the trajectory returns near its limit cycle and that the synaptic inputs received in the closed loop circuit remain similar to those used to generate the PRCs [1]. Figure 1A shows how an assumed firing pattern can be used to produce a map, which can then be linearized for a stability analysis. The dots indicate a variable number of spikes in the faster neuron 1. The periodicity criteria in this case are ts1 [n] = tr2 [n], ts21 [n] = tr11 [n], ts22 [n] = tr12 [n] with the intervals defined as shown in the figure. The periodicity criteria can be rewritten in from Seventeenth Annual Computational Neuroscience Meeting: CNS*2008 Portland, OR, USA. 19–24 July 2008