Detection of high-frequency oscillations by hybrid depth electrodes in standard clinical intracranial EEG recordings

High-frequency oscillations (HFOs) have been proposed as a novel marker for epileptogenic tissue, spurring tremendous research interest into the characterization of these transient events. A wealth of continuously recorded intracranial electroencephalographic (iEEG) data is currently available from patients undergoing invasive monitoring for the surgical treatment of epilepsy. In contrast to data recorded on research-customized recording systems, data from clinical acquisition systems remain an underutilized resource for HFO detection in most centers. The effective and reliable use of this clinically obtained data would be an important advance in the ongoing study of HFOs and their relationship to ictogenesis. The diagnostic utility of HFOs ultimately will be limited by the ability of clinicians to detect these brief, sporadic, and low amplitude events in an electrically noisy clinical environment. Indeed, one of the most significant factors limiting the use of such clinical recordings for research purposes is their low signal to noise ratio, especially in the higher frequency bands. In order to investigate the presence of HFOs in clinical data, we first obtained continuous intracranial recordings in a typical clinical environment using a commercially available, commonly utilized data acquisition system and "off the shelf" hybrid macro-/micro-depth electrodes. These data were then inspected for the presence of HFOs using semi-automated methods and expert manual review. With targeted removal of noise frequency content, HFOs were detected on both macro- and micro-contacts, and preferentially localized to seizure onset zones. HFOs detected by the offline, semi-automated method were also validated in the clinical viewer, demonstrating that (1) this clinical system allows for the visualization of HFOs and (2) with effective signal processing, clinical recordings can yield valuable information for offline analysis. © 2014 Kondylis, Wozny, Lipski, Popescu, DeStefino, Esmaeili, Raghu, Bagic and Richardson

Why Can't Rodents Vomit? A Comparative Behavioral, Anatomical, and Physiological Study

The vomiting (emetic) reflex is documented in numerous mammalian species, including primates and carnivores, yet laboratory rats and mice appear to lack this response. It is unclear whether these rodents do not vomit because of anatomical constraints (e.g., a relatively long abdominal esophagus) or lack of key neural circuits. Moreover, it is unknown whether laboratory rodents are representative of Rodentia with regards to this reflex. Here we conducted behavioral testing of members of all three major groups of Rodentia; mouse-related (rat, mouse, vole, beaver), Ctenohystrica (guinea pig, nutria), and squirrel-related (mountain beaver) species. Prototypical emetic agents, apomorphine (sc), veratrine (sc), and copper sulfate (ig), failed to produce either retching or vomiting in these species (although other behavioral effects, e.g., locomotion, were noted). These rodents also had anatomical constraints, which could limit the efficiency of vomiting should it be attempted, including reduced muscularity of the diaphragm and stomach geometry that is not well structured for moving contents towards the esophagus compared to species that can vomit (cat, ferret, and musk shrew). Lastly, an in situ brainstem preparation was used to make sensitive measures of mouth, esophagus, and shoulder muscular movements, and phrenic nerve activity-key features of emetic episodes. Laboratory mice and rats failed to display any of the common coordinated actions of these indices after typical emetic stimulation (resiniferatoxin and vagal afferent stimulation) compared to musk shrews. Overall the results suggest that the inability to vomit is a general property of Rodentia and that an absent brainstem neurological component is the most likely cause. The implications of these findings for the utility of rodents as models in the area of emesis research are discussed. © 2013 Horn et al

Imaging Neural Activity Using Thy1-GCaMP Transgenic Mice

The ability to chronically monitor neuronal activity in the living brain is essential for understanding the organization and function of the nervous system. The genetically encoded green fluorescent protein-based calcium sensor GCaMP provides a powerful tool for detecting calcium transients in neuronal somata, processes, and synapses that are triggered by neuronal activities. Here we report the generation and characterization of transgenic mice that express improved GCaMPs in various neuronal subpopulations under the control of the Thy1 promoter. In vitro and in vivo studies show that calcium transients induced by spontaneous and stimulus-evoked neuronal activities can be readily detected at the level of individual cells and synapses in acute brain slices, as well as chronically in awake, behaving animals. These GCaMP transgenic mice allow investigation of activity patterns in defined neuronal populations in the living brain and will greatly facilitate dissecting complex structural and functional relationships of neural networks.Poitras Center for Affective Disorders Researc

Responses of neurons in the rostral ventrolateral medulla to whole body rotations: comparisons in decerebrate and conscious cats

The responses to vestibular stimulation of brain stem neurons that regulate sympathetic outflow and blood flow have been studied extensively in decerebrate preparations, but not in conscious animals. In the present study, we compared the responses of neurons in the rostral ventrolateral medulla (RVLM), a principal region of the brain stem involved in the regulation of blood pressure, to whole body rotations of conscious and decerebrate cats. In both preparations, RVLM neurons exhibited similar levels of spontaneous activity (median of ∼17 spikes/s). The firing of about half of the RVLM neurons recorded in decerebrate cats was modulated by rotations; these cells were activated by vertical tilts in a variety of directions, with response characteristics suggesting that their labyrinthine inputs originated in otolith organs. The activity of over one-third of RVLM neurons in decerebrate animals was altered by stimulation of baroreceptors; RVLM units with and without baroreceptor signals had similar responses to rotations. In contrast, only 6% of RVLM neurons studied in conscious cats exhibited cardiac-related activity, and the firing of just 1% of the cells was modulated by rotations. These data suggest that the brain stem circuitry mediating vestibulosympathetic reflexes is highly sensitive to changes in body position in space but that the responses to vestibular stimuli of neurons in the pathway are suppressed by higher brain centers in conscious animals. The findings also raise the possibility that autonomic responses to a variety of inputs, including those from the inner ear, could be gated according to behavioral context and attenuated when they are not necessary

Different Neuronal Activity Patterns Induce Different Gene Expression Programs

A vast number of different neuronal activity patterns could each induce a different set of activity-regulated genes. Mapping this coupling between activity pattern and gene induction would allow inference of a neuron's activity-pattern history from its gene expression and improve our understanding of activity-pattern-dependent synaptic plasticity. In genome-scale experiments comparing brief and sustained activity patterns, we reveal that activity-duration history can be inferred from gene expression profiles. Brief activity selectively induces a small subset of the activity-regulated gene program that corresponds to the first of three temporal waves of genes induced by sustained activity. Induction of these first-wave genes is mechanistically distinct from that of the later waves because it requires MAPK/ERK signaling but does not require de novo translation. Thus, the same mechanisms that establish the multi-wave temporal structure of gene induction also enable different gene sets to be induced by different activity durations

Synthesis and Biological Evaluation of a Selective N- and P/Q-Type Calcium Channel Agonist

The acute effect of the potent cyclin-dependent kinase (cdk) inhibitor (<i>R</i>)-roscovitine on Ca²⁺ channels inspired the development of structural analogues as a potential treatment for motor nerve terminal dysfunction. On the basis of a versatile chlorinated purine scaffold, we have synthesized ca. 20 derivatives and characterized their N-type Ca²⁺ channel agonist action. Agents that showed strong agonist effects were also characterized in a kinase panel for their off-target effects. Among several novel compounds with diminished cdk activity, we identified a new lead structure with a 4-fold improved N-type Ca²⁺ channel agonist effect and a 22-fold decreased cdk2 activity as compared to (<i>R</i>)-roscovitine. This compound was selective for agonist activity on N- and P/Q-type over L-type calcium channels