Pharmaco-EEG: A Study of Individualized Medicine in Clinical Practice

pharmacotherapy

Ronald J. Swatzyna, Gerald P. Kozlowski, and Jay D. Tarnow

Abstract

Pharmaco-electroencephalography (Pharmaco-EEG) studies using clinical EEG and quantitative EEG (qEEG) technologies have existed for more than 4 decades. This is a promising area that could improve psychotropic intervention using neurological data. One of the objectives in our clinical practice has been to collect EEG and quantitative EEG (qEEG) data. In the past 5 years, we have identified a subset of refractory cases (n = 386) found to contain commonalities of a small number of electrophysiological features in the following diagnostic categories: mood, anxiety, autistic spectrum, and attention deficit disorders, Four abnormalities were noted in the majority of medication failure cases and these abnormalities did not appear to significantly align with their diagnoses. Those were the following: encephalopathy, focal slowing, beta spindles, and transient discharges. To analyze the relationship noted, they were tested for association with the assigned diagnoses. Fisher’s exact test and binary logistics regression found very little (6%) association between particular EEG/qEEG abnormalities and diagnoses. Findings from studies of this type suggest that EEG/qEEG provides individualized understanding of pharmacotherapy failures and has the potential to improve medication selection.

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Concern Regarding the Mitsar Amplifier

The concern regarding the Mitsar amplifier expressed with so much vigor by those with competing interests has met the reality test of actual recorded data.  The concern expressed was over a theoretical time skewing error due to the data sampling of an older version of the Mitsar amplifier.

I suggested at the time that all the emotion was merely an example of someone yelling “the sky is falling”, like Chicken Little. There was no real problem, just lots of crying out and hand wringing.

I requested in an open international forum for anyone to send me a sample of the problem, and none could be produced. I suspected there was no real problem, as the sample issue was concerning a 500 sample/second device having a time skew… though this was in comparison to a database collected on a 100 sample per second device, with the waveforms interpolated from these samples.

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Thalamic Involvement in the Generation of the Alpha Rhythms

Alpha… it’s not a simple idling rhythm… let’s look at alpha generators:

The thalamic involvement in the generation of the alpha rhythm is being under-valued when looking at the LORETA images of alpha current source generators. The alpha power may come from the sources that LORETA identifies, but the thalamus is intimately involved in alpha rhythm generation, and this is not part of the LORETA image of the sources.

The polarization within the thalamus sets the base frequency of the alpha, but the cortical rhythm requires a complex multi-layer feedback loop from the thalamus to the cortex, and back to the thalamus. Without the cortex, there is a total disruption of the normal spatio-temporal distribution of the alpha wave’s spike trains within the thalamus, and cortical damage often disturbs coherence due to this mechanism.

The thalamus distributes the alpha posteriorly via specific sensory relays, which have a simple return circuit. Like the white matter relay from the lateral geniculate of the thalamus to the occipital lobe’s primary visual areas, and directly back. This thalamo-cortical-thalamic loop is relatively faster than the loop seen frontally. The frontal return circuitry is not simple, but the descending routes are complex and somewhat circuitous, taking more time, and thus it is common for the frontal lobe’s alpha to be at the slower end of the individual’s alpha frequency range. The frontal lobe has a return path through the striatum.

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qEEG Artifacting

The qEEG represents the statistical manipulation of the raw EEG, so an understanding of these manipulations should precede any discussion of the qEEGs clinical indications for protocols. Without such knowledge any given finding may be misinterpreted.

Following the careful recording of the EEG, the quantitative analysis is begun with the sampling of the data to be used in the analysis by the Fourier transform. The Fourier analysis assumes there are no transients (epileptic discharges, episodic voltage changes etc.) or state changes (light sleep, drug effect, mental task, etc.), so these must be avoided when selecting data for analysis in qEEG for eyes closed resting database comparison. There are some eyes open and task databases available more recently (Hudspeth, Sterman, Duffy etc.)

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