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 grating. Visual perceptual suppression was assessed as the degree of deterioration of motion direction discrimination with increasing stimulus size. In women with PMDD, the peak frequency of the gamma response (GR) 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 normally suppressive effect of a strong increase in drift rate was attenuated in PMDD during the luteal phase and predicted symptom severity assessed 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 this E/I imbalance is further exacerbated 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. Three key pointsO_LIAtypical modulation of visual gamma power by excitatory drive in women with PMDD suggests the presence of neuronal hyperexcitability, which is exacerbated during the symptomatic luteal phase, possibly due to altered sensitivity to neurosteroids. C_LIO_LIThe peak frequency of gamma oscillations does not differ between women with PMDD and control women and demonstrates the luteal phase-specific effect of the 1st scan in both groups, which suggest normal functioning of inhibitory neurons in the visual cortex in PMDD. C_LIO_LIThe presence of normal perceptual spatial suppression also speaks against inhibitory deficit in the visual cortex in PMDD. C_LI