Tony A. Fields

Increased Fast ripple to ripple Ratios Correlate with Reduced Hippocampal Volumes and Neuron Loss in Temporal Lobe Epilepsy Patients

Purpose: To determine whether hippocampal sclerosis might form an anatomical substrate for pathological high‐frequency oscillations in patients with temporal lobe epilepsy (TLE).

Analysis of Seizure Onset on the Basis of Wideband EEG Recordings

Summary:  Seventy‐five seizure onsets recorded with depth electrodes in the frequency band from 0.1 to 70 Hz were analyzed in 19 patients with intractable temporal lobe epilepsy. It was shown that 89% of low‐voltage fast‐type seizures contained an initial slow wave, whereas hypersynchronous‐type seizures did not show an initial slow wave. Voltage depth profile analysis illustrated that the peak amplitude of the initial slow‐wave onset was in white matter, whereas the peak amplitude of hypersynchronous onset was in deep temporal areas (hippocampus, entorhinal cortex, or amygdala). The difference in voltage depth profiles suggests that these two types of seizure onsets have different mechanisms of generation. The absence of phase reversal of the initial slow wave in white matter or at the border of deep temporal areas indicates a possible nonneuronal mechanism of generation.

Three-dimensional surface maps link local atrophy and fast ripples in human epileptic hippocampus.

There is compelling evidence that pathological high‐frequency oscillations (HFOs), called fast ripples (FR, 150–500Hz), reflect abnormal synchronous neuronal discharges in areas responsible for seizure genesis in patients with mesial temporal lobe epilepsy (MTLE). It is hypothesized that morphological changes associated with hippocampal atrophy (HA) contribute to the generation of FR, yet there is limited evidence that hippocampal FR‐generating sites correspond with local areas of atrophy.

Three-dimensional hippocampal atrophy maps distinguish two common temporal lobe seizure-onset patterns.

Purpose:  Current evidence suggests that the mechanisms underlying depth electrode–recorded seizures beginning with hypersynchronous (HYP) onset patterns are functionally distinct from those giving rise to low‐voltage fast (LVF) onset seizures. However, both groups have been associated with hippocampal atrophy (HA), indicating a need to clarify the anatomic correlates of each ictal onset type. We used three‐dimensional (3D) hippocampal mapping to quantify HA and determine whether each onset group exhibited a unique distribution of atrophy consistent with the functional differences that distinguish the two onset morphologies.

Ictal onset patterns of local field potentials, high frequency oscillations, and unit activity in human mesial temporal lobe epilepsy.

To characterize local field potentials, high frequency oscillations, and single unit firing patterns in microelectrode recordings of human limbic onset seizures.

A lack of effect from transcranial magnetic stimulation (TMS) on the vagus nerve stimulator (VNS)

OBJECTIVE The effects of transcranial magnetic stimulation (TMS) on vagus nerve stimulation (VNS) are unknown. Understanding these effects is important before exposing individuals with an implanted VNS to TMS, as could occur in epilepsy or depression TMS research. To explore this issue, the TMS-induced current in VNS leads and whether TMS has an effect on the VNS pulse generator was assessed. METHODS Ex vivo measurement of current in VNS leads during single-pulse TMS and pulse generator function before, during, and after single-pulse TMS was assessed. RESULTS At the highest intensity and with the TMS coil held approximately 5 mm from the VNS wires, a 200 nA, 1.0 ms current was induced by TMS. This translates to an induced charge density of 3.3 nC/cm2/phase. The function of the pulse generator was unaffected by single-pulse TMS, even when its case was directly stimulated by the coil. CONCLUSIONS TMS-induced current in VNS electrodes was not only well outside of the range known to be injurious to peripheral nerve, but also below the activation threshold of nerve fibers. SIGNIFICANCE Using single-pulse TMS in individuals with VNS should not result in nerve stimulation or damage. Furthermore, single-pulse TMS does not affect the VNS pulse generators function.

Novel Cell and Tissue Acquisition System (CTAS): Microdissection of Live and Frozen Brain Tissues

We developed a novel, highly accurate, capillary based vacuum-assisted microdissection device CTAS - Cell and Tissue Acquisition System, for efficient isolation of enriched cell populations from live and freshly frozen tissues, which can be successfully used in a variety of molecular studies, including genomics and proteomics. Specific diameter of the disposable capillary unit (DCU) and precisely regulated short vacuum impulse ensure collection of the desired tissue regions and even individual cells. We demonstrated that CTAS is capable of dissecting specific regions of live and frozen mouse and rat brain tissues at the cellular resolution with high accuracy. CTAS based microdissection avoids potentially harmful physical treatment of tissues such as chemical treatment, laser irradiation, excessive heat or mechanical cell damage, thus preserving primary functions and activities of the dissected cells and tissues. High quality DNA, RNA, and protein can be isolated from CTAS-dissected samples, which are suitable for sequencing, microarray, 2D gel-based proteomic analyses, and Western blotting. We also demonstrated that CTAS can be used to isolate cells from native living tissues for subsequent recultivation of primary cultures without affecting cellular viability, making it a simple and cost-effective alternative for laser-assisted microdissection.