Stephen D. Cranstoun

Electrical Stimulation of the Anterior Nucleus of the Thalamus for the Treatment of Intractable Epilepsy

Summary:  Purpose: Animal studies and sporadic case reports in human subjects have suggested that intermittent electrical stimulation of the anterior nucleus of the thalamus reduces seizure activity. We embarked on an open‐label pilot study to determine initial safety and tolerability of bilateral stimulation of the anterior nucleus of the thalamus (ANT), to determine a range of appropriate stimulation parameters, and to begin to gather pilot efficacy data.

A multi-feature and multi-channel univariate selection process for seizure prediction

OBJECTIVE To develop a prospective method for optimizing seizure prediction, given an array of implanted electrodes and a set of candidate quantitative features computed at each contact location. METHODS The method employs a genetic-based selection process, and then tunes a probabilistic neural network classifier to predict seizures within a 10 min prediction horizon. Initial seizure and interictal data were used for training, and the remaining IEEG data were used for testing. The method continues to train and learn over time. RESULTS Validation of these results over two workshop patients demonstrated a sensitivity of 100%, and 1.1 false positives per hour for Patient E, using a 2.4s block predictor, and a failure of the method on Patient B. CONCLUSIONS This study demonstrates a prospective, exploratory implementation of a seizure prediction method designed to adapt to individual patients with a wide variety of pre-ictal patterns, implanted electrodes and seizure types. Its current performance is limited likely by the small number of input channels and quantitative features employed in this study, and segmentation of the data set into training and testing sets rather than using all continuous data available. SIGNIFICANCE This technique theoretically has the potential to address the challenge presented by the heterogeneity of EEG patterns seen in medication-resistant epilepsy. A more comprehensive implementation utilizing all electrode sites, a broader feature library, and automated multi-feature fusion will be required to fully judge the methods potential for predicting seizures.

Depth of tissue sampling in the optic nerve head using laser Doppler flowmetry

Laser Doppler flowmetry (LDF) was performed on a simulated blood vessel in a model eye through optic nerve tissue sections in order to ascertain the ability to detect flow through them. LDF was performed using either near-infra-red or green laser light. Tissue section thickness ranged from 50 μm to 1000 μm. As expected, we found that our ability to detect flow with LDF decreased as we increased the thickness of optic nerve sections interposed between the LDF apparatus and the simulated blood vessel. We also found that the sampled depth of LDF increased with increasing separation of the optical detection fibre from the centre of the illuminated tissue volume. With adequate separation, we were able to detect flow with LDF through tissue sections of 1000 μm thickness using either near-infra-red or green laser light.

Evidence for self-organized criticality in human epileptic hippocampus

Self-organized criticality (SOC) is a property of complex dynamic systems that evolve to a critical state, capable of producing scale-free energy fluctuations. A characteristic feature of dynamical systems exhibiting SOC is the power-law probability distributions that describe the dynamics of energy release. We show experimental evidence for SOC in the epileptic focus of seven patients with medication-resistant temporal lobe epilepsy. In the epileptic focus the probability density of pathological energy fluctuations and the time between these energy fluctuations scale as (energy)−&dgr; and (time)−&ggr;, respectively. The power-laws characterizing the probability distributions from these patients are consistent with computer simulations of integrate-and-fire oscillator networks that have been reported recently. These findings provide insight into the neuronal dynamics of epileptic hippocampus and suggest a mechanism for interictal epileptiform fluctuations. The presence of SOC in human epileptic hippocampus may provide a method for identifying the network involved in seizure generation.

Long-range temporal correlations in epileptogenic and non-epileptogenic human hippocampus.

Epileptogenic human hippocampus generates spontaneous energy fluctuations with a wide range of amplitude and temporal variation, which are often assumed to be entirely random. However, the temporal dynamics of these fluctuations are poorly understood, and the question of whether they exhibit persistent long-range temporal correlations (LRTC) remains unanswered. In this paper we use detrended fluctuation analysis (DFA) to show that the energy fluctuations in human hippocampus show LRTC with power-law scaling, and that these correlations differ between epileptogenic and non-epileptogenic hippocampus. The analysis shows that the energy fluctuations exhibit slower decay of the correlations in the epileptogenic hippocampus compared with the non-epileptogenic hippocampus. The DFA-derived scaling exponents demonstrate that there are LRTC of energy fluctuations in human hippocampus, and that the temporal persistence of energy fluctuations is characterized by a bias for large (small) energy fluctuations to be followed by large (small) energy fluctuations. Furthermore, we find that in the period of time leading up to seizures there is no change in the scaling exponents that characterize the LRTC of energy fluctuations. The fact that the LRTC of energy fluctuations do not change as seizures approach provides evidence that the local neuronal network dynamics do not change in the period before seizures, and that seizures in mesial temporal lobe epilepsy may be triggered by an influence that is external to the hippocampus. The presence of LRTC with power-law scaling does not imply a specific mechanism, but the finding that temporal correlations decay more slowly in epileptogenic hippocampus provides electrophysiologic evidence that the underlying neuronal dynamics are different within the epileptogenic hippocampus compared with contralateral hippocampus. We briefly discuss possible neurobiological mechanisms for LRTC of the energy fluctuations in hippocampus.

Time-frequency spectral estimation of multichannel EEG using the Auto-SLEX method

In this paper, we apply a new time-frequency spectral estimation method for multichannel data to epileptiform electroencephalography (EEG). The method is based on the smooth localized complex exponentials (SLEX) functions which are time-frequency localized versions of the Fourier functions and, hence, are ideal for analyzing nonstationary signals whose spectral properties evolve over time. The SLEX functions are simultaneously orthogonal and localized in time and frequency because they are obtained by applying a projection operator rather than a window or taper. In this paper, we present the Auto-SLEX method which is a statistical method that 1) computes the periodogram using the SLEX transform, 2) automatically segments the signal into approximately stationary segments using an objective criterion that is based on log energy, and 3) automatically selects the optimal bandwidth of the spectral smoothing window. The method is applied to the intracranial EEG from a patient with temporal lobe epilepsy. This analysis reveals a reduction in average duration of stationarity in preseizure epochs of data compared to baseline. These changes begin up to hours prior to electrical seizure onset in this patient.

Blood pO2 and blood flow at the optic disc

A fundus camera-based phosphorometer to noninvasively and quasicontinuously measure the blood partial pressure of oxygen (pO(2,blood)) in the microvasculature of the pig optic nerve using the principle of the phosphorescence quenching by O(2) is described. A porphyrin dye is injected into the venous circulation and the decay of its phosphorescence emission is detected locally in the eye, after excitation with a flash of light. Combined with blood flow measurements by means of a laser Doppler flowmeter mounted on the phosphorometer, we demonstrate the capability of the instrument to determine the time course of optic nerve blood flow and pO(2,blood) in response to various physiological stimuli, such as hyperoxia and hypercapnia. This instrument appears to be a useful tool for the investigation of the oxygenation of the optic nerve.

Evaluation of a CRT-Based Test of Saturation Discrimination Using a Discrete Matching Technique

A computer controlled color CRT system was used to present color test stimuli varying in saturation along R-G and B-Y lines through the white point in color space. Subjects ordered stimuli according to color and saturation. Normals ordered the R-G series with few errors but showed a tendency toward increasing errors with increasing age on the B-Y series. Dichromat error scores showed a sensitivity to the exact orientation of the R-G stimulus line. The maximum rate of stimulus presentation was too slow to allow exploitation of color choice.

Self-organized criticality in the epileptic brain

Criticality is a property of complex dynamical systems that can produce large energy release. Examples in nature of such systems are earthquakes, avalanches and volcanoes. It has been recently demonstrated that networks of integrate-and-fire neurons also exhibit such critical behavior where the system energy is related to the degree of synchronized neuronal firing. We have examined electrographic recordings from human epileptic hippocampus and demonstrate that this tissue exhibits self-organized criticality. These findings may explain energy bursting recently found to occur prior to epileptic seizures in the hippocampus and may connect them to integrate-and-fire models.

Optic nerve and choroidal blood flow in humans by laser Doppler flowmetry

Laser Doppler flowmetry (LDF) was applied to measure blood flow in discrete regions of the optic nerve head (ONHBF) and in the foveal region of the choroid (ChBF) in humans. LDF is based on the Doppler effect. For its ocular application, a diode laser beam (wavelength equals 810 nm, 60 mW at the cornea) was delivered to the eye through a fundus camera. For ONHBF the beam was directed at regions of the optic disk with no apparent individual vessels. For ChBF in the foveal region subjects were asked to look directly at the beam. Light scattered by red blood cells in the tissue volume illuminated by the incident laser beam was detected at the fundus image plane of the camera by an optical fiber. Two analysis schemes of the Doppler signal were developed: one uses commercial skin blood flowmeters, the other a NeXT station (Motorola 68040 based) computer system. Responses of ONHBF and ChBF to various physiological and pharmacological stimuli were obtained and shown to be in agreement with previously published findings. LDF is a valid technique for obtaining non- invasive, continuous and sensitive recordings of ONHBF and foveal ChBF, the latter without the need to dilate the pupil.