Cortisol Inversely Related to Prefrontal Gamma Coherence in Healthy Human Subjects

SIR: Here we report a significant relationship between baseline salivary cortisol levels and interhemispheric coherence in the gamma band (30–50 Hz) of the electroencephalographic spectrum.

Interhemispheric coherence analysis of the EEG is considered to reflect functional corticocortical connections between the two hemispheres of the brain by quantifying the phase consistency between two regions of the brain.¹ In pathological states, such as dementia in Alzheimer's disease (AD), neurodegeneration is accompanied by decreases in higher-frequency oscillations (>30 Hz) and functional connections (i.e., coherence).² Furthermore, dementia is often also accompanied by a hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, resulting in chronically elevated cortisol levels.³ Interestingly, elevated cortisol levels result in reductions of the neurotransmitter acetylcholine (Ach) in the brain, and in AD the depletion of Ach, likely caused by high levels of cortisol, contributes severely to the brain atrophy.⁴ To our knowledge, no studies have addressed the relationship between cortisol and gamma coherence in normal subjects, which is possibly indicative of the predisposition to develop AD.

This relationship was investigated in 33 right-handed subjects ages 18 to 29 years. Salivary samples were collected between 2:00 p.m. and 4:00 p.m. in resting conditions, followed by an 8-minute baseline EEG recording from the F₃ and F₄ electrode positions, according to the International 10-20 System. Data were corrected for ocular and muscular artifacts. The cortisol level in saliva is a valid measure of unbound hormone fraction, and only unbound cortisol reaches the target tissues in the brain.⁵ The gamma band in the EEG spectrum was extracted and the averaged power density was calculated. Additionally, coherence between the F₃ and F₄ electrode was calculated for the fast EEG band.² Salivary cortisol levels were determined without extraction by using a radioimmunoassay employing a polyclonal anticortisol antibody (K7348) Following chromatographic verification of its purity, 1,2-[³H](N)-hydrocortisone (NET 185, NEN-Dupont, Dreiech, Germany) was used as a tracer. Statistical analysis revealed no significant relationship between cortisol and the power amplitude in the gamma frequency band (r=0.085, df=0.085, not significant). There was, however, a significant negative correlation (r=–0.40, df=33, P<0.02 ) between cortisol and the gamma coherence over the prefrontal areas.

In sum, our data showed a significant inverse relationship between cortisol levels and coherence in the gamma frequency band in normal subjects. Higher levels of cortisol were accompanied by reductions in EEG gamma coherence. Alzheimer's disease patients tend to show increased levels of cortisol in a far more extreme range, and these are argued to contribute to brain atrophy, thus decreasing gamma coherence.³ This demonstration of such an inverse relationship between cortisol and gamma coherence in young healthy subjects suggests that the mechanism is highly sensitive. Higher premorbid cortisol levels may have a predictive value for the neurodegeneration of the brain.