Altered visual cortex excitability in premenstrual dysphoric disorder: evidence from magnetoencephalographic gamma oscillations and perceptual suppression

Abstract

Premenstrual dysphoric disorder (PMDD) is a psychiatric condition characterized by extreme mood shifts, anxiety, and irritability during the premenstrual period. Abnormal sensitivity to allopregnanolone, a neurosteroid that normally potentiates inhibition, and an increased ratio of neural excitation-to-inhibition (E/I) have been linked to the pathophysiology of PMDD. We hypothesized that in subjects with PMDD these factors will lead to an altered frequency of magnetoencephalographic (MEG) visual gamma oscillations, altered modulation of their power by the strength of excitatory drive and to an altered perceptual spatial suppression. We examined women with PMDD and age-matched control women twice: during the asymptomatic follicular and symptomatic luteal phases of the menstrual cycle (MC). MEG gamma oscillations were recorded while modulating excitatory drive to the visual cortex by increasing drift rate of high-contrast visual gratings. Perceptual suppression was assessed as a degree of impairment of the discrimination of visual motion direction with increasing stimulus size. In women with PMDD, the gamma response (GR) peak frequency and its modulation by the drift rate were normal, whereas modulation of the GR power was significantly altered. A moderate increase in drift rate had an unusually strong facilitating effect on the GR power in PMDD, regardless of the MC phase. In contrast, the effect of increasing drift rate, which normally suppresses GR power, was attenuated in PMDD in the luteal phase and predicted symptom severity estimated on the same day. Perceptual spatial suppression did not differ between the groups, but decreased from the follicular to the luteal phase only in PMDD subjects. The atypical GR power modulation suggests that neuronal excitability in the visual cortex is constitutively elevated in women with PMDD, and that their E/I ratio is additionally shifted toward excitation during the luteal phase, possibly due to an abnormal sensitivity to neurosteroids. However, the unchanged frequency of GR and normal spatial suppression in women with PMDD speak against the dysfunction of their inhibitory neurons, at least those involved in generation of visual gamma oscillations.