Cortisol and Reduced Interhemispheric Coupling Between the Left Prefrontal and the Right Parietal Cortex

SIR: Neuroimaging and electrophysiological studies have demonstrated a relationship between hypoactivation of the left prefrontal cortex and depression.¹ There is also strong evidence for the involvement of the right parietal cortex in this unipolar disorder.

Davidson¹ proposes an interhemispheric circuit consisting of the left prefrontal and right parietal area to be dysfunctional in depression. Depression is often accompanied by defective feedback of the hypothalamic-pituitary-adrenal axis, resulting in elevated levels of the steroid hormone cortisol.²

Interestingly, steroid hormones are involved in interhemispheric transmission.³ A valid method for quantifying interhemispheric transmission or functional connectivity is EEG spectral coherence analysis, which measures phase consistency at paired locations.⁴ A reliable measure for cortisol reaching the target tissues in the brain can be taken from saliva.⁵ We investigated the relationship between salivary cortisol and EEG spectral coherence over the left prefrontal and the right parietal cortex.

Thirty nonclinical, right-handed subjects (15 females) ages 20 to 28 years participated. Written informed consent was obtained. To control for circadian hormonal rhythms, the sessions were conducted between 1:30 p.m. and 4:30 p.m. Salivary sampling was followed by a 10-minute EEG baseline recording from the F₃, F₄, P₃, P₄ electrodes, which were referenced to the right mastoid. Cortisol levels were determined by radioimmunoassay. Baseline cortisol did not (P<0.25) and normally does not differ between the sexes.⁵ Artifact-free EEG signal (bandpass filter: 1–30 Hz) was extracted through a Hamming window, and a fast Fourier transformation was used to derive estimates of spectral power (μV²). Squared correlation coefficients (coherences) were determined for the four electrodes in the 4–7 Hz (θ), 8–13 Hz (α), and 14–30 Hz (β) frequency domains.

Correlational analyses showed significant inverse relations between cortisol and the F₃–P₄ coherence in the fast α (r=–0.43, P<0.01) and β (r=–0.39, P<0.03) EEG frequency bands. Thus, already in this nonclinical subject group, higher cortisol was accompanied by reductions in interhemispheric transmission between the left prefrontal and right parietal cortex. Our data might suggest a sensitive interhemispheric decoupling mechanism by which pathological levels of the steroid hormone cortisol could be implicated in depression.