Repetitive transcranial magnetic stimulation directed to a seizure focus localized by high-density EEG: A case report.

We demonstrate feasibility of using high-density EEG to map a neocortical seizure focus in conjunction with delivery of magnetic therapy. Our patient had refractory seizures affecting the left leg. A five-day course of placebo stimulation followed a month later by active rTMS was directed to the mapped seizure dipole. Active rTMS resulted in reduced EEG spiking, and shortening of seizure duration compared to placebo. Seizure frequency, however, improved similarly in both placebo and active treatment stages. rTMS-evoked EEG potentials demonstrated that a negative peak at 40 ms - believed to represent GABAergic inhibition - was enhanced by stimulation.

Tracking generalized tonic-clonic seizures with a wrist accelerometer linked to an online database.

PURPOSE: Clinical management of epilepsy and current epilepsy therapy trials rely on paper or electronic diaries often with inaccurate self-reported seizure frequency as the primary outcome. This is the first study addressing the feasibility of detecting and recording generalized tonic-clonic seizures (GTCS) through a biosensor linked to an online seizure database. METHOD: A prospective trial was conducted with video-EEG (vEEG) in an epilepsy monitoring unit. Patients wore a wristwatch accelerometer that detected shaking and transmitted events via Bluetooth® to a bedside electronic tablet and then via Wi-Fi to an online portal. The watch recorded the date, time, audio, duration, frequency and amplitude of events. Events logged by the watch and recorded in a bedside paper diary were measured against vEEG, the "gold standard." RESULTS: Thirty patients were enrolled and 62 seizures were recorded on vEEG: 31 convulsive and 31 non-convulsive. Twelve patients had a total of 31 convulsive seizures, and of those, 10 patients had 13 GTCS. The watch captured 12/13 (92.3%) GTCS. Watch audio recordings were consistent with seizures in 11/12 (91.6%). Data were successfully transferred to the bedside tablet in 11/12 (91.6%), and to the online database in 10/12 (83.3%) GTCS. The watch recorded 81 false positives, of which 42/81 (51%) were cancelled by the patients. Patients and caregivers verbally reported 15/62 seizures (24.2% sensitivity) but no seizures were recorded on paper logs. CONCLUSION: Automatic detection and recording of GTCS to an online database is feasible and may be more informative than seizure logging in a paper diary.

Differences in neural circuitry guiding behavioral responses to polarized light presented to either the dorsal or ventral retina in Drosophila.

Linearly polarized light (POL) serves as an important cue for many animals, providing navigational information, as well as directing them toward food sources and reproduction sites. Many insects detect the celestial polarization pattern, or the linearly polarized reflections off of surfaces, such as water. Much progress has been made toward characterizing both retinal detectors and downstream circuit elements responsible for celestial POL vision in different insect species, yet much less is known about the neural basis of how polarized reflections are detected. We previously established a novel, fully automated behavioral assay for studying the spontaneous orientation response of Drosophila melanogaster populations to POL stimuli presented to either the dorsal, or the ventral halves of the retina. We identified separate retinal detectors mediating these responses: the 'Dorsal Rim Area' (DRA), which had long been implicated in celestial POL vision, as well as a previously uncharacterized 'ventral polarization area' (VPA). In this study, we investigate whether DRA and VPA use the same or different downstream circuitry, for mediating spontaneous behavioral responses. We use homozygous mutants, or molecular genetic circuit-breaking tools (silencing, as well as rescue of synaptic activity), in combination with our behavioral paradigm. We show that responses to dorsal versus ventral stimulation involve previously characterized optic lobe neurons, like lamina monopolar cell L2 and medulla cell types Dm8/Tm5c. However, using different experimental conditions, we show that important differences exist between the requirement of these cell types downstream of DRA versus VPA. Therefore, while the neural circuits underlying behavioral responses to celestial and reflected POL cues share important building blocks, these elements play different functional roles within the network.

Walking Drosophila align with the e-vector of linearly polarized light through directed modulation of angular acceleration.

Understanding the mechanisms that link sensory stimuli to animal behavior is a central challenge in neuroscience. The quantitative description of behavioral responses to defined stimuli has led to a rich understanding of different behavioral strategies in many species. One important navigational cue perceived by many vertebrates and insects is the e-vector orientation of linearly polarized light. Drosophila manifests an innate orientation response to this cue ('polarotaxis'), aligning its body axis with the e-vector field. We have established a population-based behavioral paradigm for the genetic dissection of neural circuits guiding polarotaxis to both celestial as well as reflected polarized stimuli. However, the behavioral mechanisms by which flies align with a linearly polarized stimulus remain unknown. Here, we present a detailed quantitative description of Drosophila polarotaxis, systematically measuring behavioral parameters that are modulated by the stimulus. We show that angular acceleration is modulated during alignment, and this single parameter may be sufficient for alignment. Furthermore, using monocular deprivation, we show that each eye is necessary for modulating turns in the ipsilateral direction. This analysis lays the foundation for understanding how neural circuits guide these important visual behaviors.

Genetic dissection reveals two separate retinal substrates for polarization vision in Drosophila.

BACKGROUND: Linearly polarized light originates from atmospheric scattering or surface reflections and is perceived by insects, spiders, cephalopods, crustaceans, and some vertebrates. Thus, the neural basis underlying how this fundamental quality of light is detected is of broad interest. Morphologically unique, polarization-sensitive ommatidia exist in the dorsal periphery of many insect retinas, forming the dorsal rim area (DRA). However, much less is known about the retinal substrates of behavioral responses to polarized reflections. SUMMARY: Drosophila exhibits polarotactic behavior, spontaneously aligning with the e-vector of linearly polarized light, when stimuli are presented either dorsally or ventrally. By combining behavioral experiments with genetic dissection and ultrastructural analyses, we show that distinct photoreceptors mediate the two behaviors: inner photoreceptors R7+R8 of DRA ommatidia are necessary and sufficient for dorsal polarotaxis, whereas ventral responses are mediated by combinations of outer and inner photoreceptors, both of which manifest previously unknown features that render them polarization sensitive. CONCLUSIONS: Drosophila uses separate retinal pathways for the detection of linearly polarized light emanating from the sky or from shiny surfaces. This work establishes a behavioral paradigm that will enable genetic dissection of the circuits underlying polarization vision.

Induction of neutralization antibodies in mice by Dengue-2 envelope DNA vaccines.

BACKGROUND: Dengue (DEN) viruses have become a public health problem that affects approximately 100 million people worldwide each year. Prevention measures rely on vector control programs, which are inefficient. Therefore, a vaccine is urgently needed. METHODS: The main goal of our laboratory is to develop an efficient tetravalent DEN DNA vaccine. In this study, we constructed four DEN-2 DNA vaccines expressing prM/env genes, using the homologous leader sequence (VecD2, VRD2E) or the tissue plasminogen activator (tPA) secretory signal (VecD2tpa, VRD2tpa). In vitro expression was tested by transient transfections and Western blot. The immunogenicity and protective efficacy of the vaccine candidates was evaluated in BALB/c mice, using intramuscular (IM) and intradermal (ID) vaccination routes. RESULTS: Envelope (E) protein expression was detected in transfected COS-7 or 293T cells. We found statistical differences in the antibody responses induced by these vaccine candidates. In addition, the strongest antibody responses and protection were observed when the vaccines were delivered intramuscularly. Moreover, the tPA leader sequence did not significantly improve the vaccine immunogenicity since VecD2 and VecD2tpa induced similar antibody responses. CONCLUSIONS: We demonstrated that most of our DNA vaccine candidates could induce antibody responses and partial protection against DEN-2 virus in mice. These results provide valuable information for the design and construction of a tetravalent DEN DNA vaccine.

Neural circuitry: seeing the parts that make the picture.

What are the neural correlates of vision? A recent study on Drosophila has described the incredible neuronal diversity in the fly visual system, and traced the circuits that underlie color vision.