Kenneth J. Pope

Cognitive tasks augment gamma EEG power

OBJECTIVE Gamma EEG oscillations are low amplitude rhythms in the 30-100 Hz range that correlate with cognitive task execution. They are usually reported using time-locked averaging of EEG during repetitive tasks. We tested the hypothesis that continuous gamma EEG would be measurable during mental tasks. METHODS We investigated sustained human gamma EEG oscillations induced by 8 cognitive tasks (Visual Checkerboard, Expectancy, Reading, Subtraction, Music, Expectancy, Word learning, Word recall, and a Video Segment) in 20 subjects using standard digital EEG recording and power spectral analysis. RESULTS All of the cognitive tasks augmented gamma power relative to a control condition (eyes open watching a blank computer screen). This enhancement was statistically significant at more than one scalp site for all tasks except checkerboard. The Expectancy, Learning, Reading and Subtraction tasks expressed the most impressive gamma response, up to 5 fold above the control condition and there was some task-related specificity of the distribution of increased gamma power, especially in posterior cortex with visual tasks. CONCLUSIONS Widespread gamma activation of cortical EEG can easily be demonstrated during mental activity. SIGNIFICANCE These results establish the feasibility of measuring high frequency EEG rhythms with trans-cranial recordings, demonstrate that sustained gamma EEG activity correlates with mentation, and provides evidence consistent with the temporal binding model.

Thinking activates EMG in scalp electrical recordings.

OBJECTIVE Fast electrical rhythms in the gamma range (30-100Hz) in scalp (but not intracranial) recordings are predominantly due to electromyographic (EMG) activity. We hypothesized that increased EMG activity would be augmented by mental tasks in proportion to task difficulty and the requirement of these tasks for motor or visuo-motor output. METHODS EEG was recorded in 98 subjects whilst performing cognitive tasks and analysed to generate power spectra. In four other subjects, neuromuscular blockade was achieved pharmacologically providing EMG-free spectra of EEG at rest and during mental tasks. RESULTS In comparison to the paralysed condition, power of scalp electrical recordings in the gamma range varied in distribution, being maximal adjacent to cranial or cervical musculature. There were non-significant changes in mean gamma range activity due to mental tasks in paralysed subjects. In normal subjects, increases in scalp electrical activity were observed during tasks, without relationship to task difficulty, but with tasks involving limb- or eye-movement having higher power. CONCLUSIONS Electrical rhythms in the gamma frequency range recorded from the scalp are inducible by mental activity and are largely due to EMG un-related to cognitive effort. EMG varies with requirements for somatic or ocular movement more than task difficulty. SIGNIFICANCE Severe restrictions exist on utilizing scalp recordings for high frequency EEG.

Removal of EEG noise and artifact using blind source separation.

Summary: A study was performed to investigate and compare the relative performance of blind signal separation (BSS) algorithms at separating common types of contamination from EEG. The study develops a novel framework for investigating and comparing the relative performance of BSS algorithms that incorporates a realistic EEG simulation with a known mixture of known signals and an objective performance metric. The key finding is that although BSS is an effective and powerful tool for separating and removing contamination from EEG, the quality of the separation is highly dependant on the type of contamination, the degree of contamination, and the choice of BSS algorithm. BSS appears to be most effective at separating muscle and blink contamination and less effective at saccadic and tracking contamination. For all types of contamination, principal components analysis is a strong performer when the contamination is greater in amplitude than the brain signal whereas other algorithms such as second-order blind inference and Infomax are generally better for specific types of contamination of lower amplitude.

Persistent abnormality detected in the non-ictal electroencephalogram in primary generalised epilepsy.

Objectives: Gamma oscillations (30–100 Hz gamma electroencephalographic (EEG) activity) correlate with high frequency synchronous rhythmic bursting in assemblies of cerebral neurons participating in aspects of consciousness. Previous studies in a kainic acid animal model of epilepsy revealed increased intensity of gamma rhythms in background EEG preceding epileptiform discharges, leading the authors to test for intensified gamma EEG in humans with epilepsy. Methods: 64 channel cortical EEG were recorded from 10 people with primary generalised epilepsy, 11 with partial epilepsy, and 20 controls during a quiescent mental state. Using standard methods of EEG analysis the strength of EEG rhythms (fast Fourier transformation) was quantified and the strengths of rhythms in the patient groups compared with with controls by unpaired t test at 1 Hz intervals from 1 Hz to 100 Hz. Results: In patients with generalised epilepsy, there was a threefold to sevenfold increase in power of gamma EEG between 30 Hz and 100 Hz (p<0.01). Analysis of three unmedicated patients with primary generalised epilepsies revealed an additional 10-fold narrow band increase of power around 35 Hz–40 Hz (p<0.0001). There were no corresponding changes in patients with partial epilepsy. Conclusions: Increased gamma EEG is probably a marker of the underlying ion channel or neurotransmitter receptor dysfunction in primary generalised epilepsies and may also be a pathophysiological prerequisite for the development of seizures. The finding provides a new diagnostic approach and also links the pathophysiology of generalised epilepsies to emerging concepts of neuronal correlates of consciousness.

Cell swelling, seizures and spreading depression: An impedance study

The cellular processes that take place during the transition from pre-seizure state to seizure remain to be defined. In this study in awake, paralyzed rats, we used an electrical impedance measure of changes in extra-cellular intracranial volume to estimate changes in cell size in acute models of epilepsy. Animals were prepared with extradural electroencephalographic (EEG)/impedance electrodes and a venous catheter. On a subsequent day, animals were paralyzed, ventilated and treated with picrotoxin, kainic acid or fluorocitrate in doses that usually induce epileptiform discharges. We now report that increases in baseline impedance were induced by kainic acid and smaller increases by picrotoxin. We also demonstrated that epileptiform discharges were preceded by small, accelerated increases in impedance. Increases in baseline impedance were highly correlated with increases in power of non-ictal high frequency EEG activity. Seizures were accompanied by increases in impedance and all treatments induced transient, relatively large, increases in impedance often associated with unilateral reductions in low frequency EEG, likely periods of spreading depression. We conclude: cerebral cells swell in convulsant models of epilepsy, that there are pre-ictal accelerations in cell swelling, and that spreading depression-like events are frequently associated with seizures.

Nicotine as an Antiepileptic Agent in ADNFLE: An N-of-One Study: NICOTINE IN ADNFLE

Summary:  Purpose: To test nicotine patch treatment for a patient with a defined mutation for autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) whose seizures were refractory to standard antiepileptic therapy.

Picrotoxin-induced generalised convulsive seizure in rat: changes in regional distribution and frequency of the power of electroencephalogram rhythms.

OBJECTIVES It is unknown how generalised discharges in primary generalised epilepsy (PGE) develop from background brain electrical activity or how widespread these discharged are throughout the brain. Here we address this by determining which neural structures and rhythms lead to and participate in generalised discharges in the picrotoxin rat model of PGE. METHODS Rats with chronically implanted electrodes were infused with picrotoxin until a seizure occurred. This process we refer to as acute epileptogenesis. The electroencephalogram (EEG) was recorded and spectral analysis applied off-line to determine changes in the spectral power of contributing frequencies in 13 brain regions. RESULTS Two types of generalised discharge occurred, spindles and seizure, which were present in all brain regions studied. None of the frequencies (1-100 Hz) were significantly increased in background EEG before either spindles or seizure. Within the generalised discharges, power changes revealed significant increases in 6-8 Hz, most powerful in ventrolateral thalamus and neocortex. Gamma frequencies were increased significantly in neocortical structures during spindles with further increases in most structures at seizure onset. 1 Hz was significantly increased in parietal cortex during spindles with differential increases at seizure onset. CONCLUSIONS We conclude that gamma, 1 and 6-8 Hz frequencies do not appear to contribute to picrotoxin epileptogenesis but do play a role in generalised seizures. The distribution of these frequencies during discharges suggests that the spindles are thalamocortical events and that the seizure is a cortical event with downstream effects on other brain regions.

Cell swelling precedes seizures induced by inhibition of astrocytic metabolism

It is currently unknown what processes take place at the interface between non-ictal and ictal activity during seizure initiation. In this study, using paralysed awake rats, we focally inhibited astrocytic metabolism with fluorocitrate (FC), causing seizures. We measured changes in electroencephalogram (EEG) (0-300 Hz), and extracellular ion-concentrations during ictal onsets defining possible relationships with impedance-determined cell swelling. In animals showing ictal activity (69%) there were spike-wave discharges, spike-wave discharges followed by spreading depression and spreading depression without any discharges. In a high proportion of spike-wave discharges (>95%), just prior to the first spike-wave discharge, there was a decrease in the volume of the extracellular space. Following the initiation of cell swelling and prior to discharges, there were increases in high-frequency (150-300 Hz) EEG activity, increases in extracellular potassium- and decreases in extracellular calcium-concentrations. We suggest that EEG and ionic changes are not causative of cell swelling. Cell swelling due to metabolic failure in astrocytes at the injected site may release excitatory amino acids. At the same time, our results suggest ion homeostasis is not maintained and increased neuronal excitability and synchronisation occur. These could be the drivers changing normal brain activity into ictal activity.

Physiological and pathological spindling phenomena have similar regional EEG power distributions

Sleep spindles in human and in rat are known to have a thalamocortical substrate. It has also been suggested that absence epilepsy spike and wave discharges may be generated by a similar mechanism. In addition, we have previously reported a possible thalamocortical origin of the EEG spindling rhythmic discharges associated with myoclonic jerks in the picrotoxin rat model of primary generalised epilepsy. To investigate whether pathological and physiological brain rhythms have common mechanisms of generation, we analysed four electroencephalographic (EEG) spindling activities in the rat. These were the non-convulsive spindle discharges induced by picrotoxin (picrotoxin spindles), naturally occurring absence epilepsy spike and wave discharges (absence spindles), spindle discharges during natural sleep (sleep spindles) and spindling activity that occurs under barbiturate anaesthesia (barbiturate spindles). We used power spectral analysis to define and compare the strength and brain distribution of EEG power during the spindling activities in 12 forebrain and 7 brainstem regions. There were brain-wide differences in power for each of the different spindle types with the pathological rhythms of the epilepsies containing more power than the physiological rhythms. There were also similar differences in the expression of spindles related to the region examined and no thalamic emphasis. These results provide evidence for a similar regional EEG power distribution for all four types of spindling activity and thus for the different spindles being expressions of a single phenomenon.

Surface Laplacian of scalp electrical signals and independent component analysis resolve EMG contamination of electroencephalogram

The serious impact of electromyogram (EMG) contamination of electroencephalogram (EEG) is well recognised. The objective of this research is to demonstrate that combining independent component analysis with the surface Laplacian can eliminate EMG contamination of the EEG, and to validate that this processing does not degrade expected neurogenic signals. The method involves sequential application of ICA, using a manual procedure to identify and discard EMG components, followed by the surface Laplacian. The extent of decontamination is quantified by comparing processed EEG with EMG-free data that was recorded during pharmacologically induced neuromuscular paralysis. The combination of the ICA procedure and the surface Laplacian, with a flexible spherical spline, results in a strong suppression of EMG contamination at all scalp sites and frequencies. Furthermore, the ICA and surface Laplacian procedure does not impair the detection of well-known, cerebral responses; alpha activity with eyes-closed; ERP components (N1, P2) in response to an auditory oddball task; and steady state responses to photic and auditory stimulation. Finally, more flexible spherical splines increase the suppression of EMG by the surface Laplacian. We postulate this is due to ICA enabling the removal of local muscle sources of EMG contamination and the Laplacian transform being insensitive to distant (postural) muscle EMG contamination.