New neuroimaging techniques have led to significant advancements in our understanding of cerebral mechanisms of primary insomnia. However, the neuronal low-frequency oscillation remains largely uncharacterized in chronic primary insomnia (CPI). In this study, the amplitude of low-frequency fluctuation (ALFF), a data-driven method based on resting-state functional MRI, was used to examine local intrinsic activity in 27 patients with CPI and 27 age-, sex-, and education-matched healthy controls. We examined neural activity in two frequency bands, slow-4 (between 0.027 and 0.073 Hz) and slow-5 (0.010-0.027 Hz), because blood-oxygen level dependent (BOLD) fluctuations in different low-frequency bands may present different neurophysiological manifestations that pertain to a spatiotemporal organization. The ALFF associated with the primary disease effect was widely distributed in the cerebellum posterior lobe (CPL), dorsal and ventral prefrontal cortex, anterior cingulate cortex, precuneus, somatosensory cortex, and several default-mode sub-regions. Several brain regions (i.e., the right cerebellum, anterior lobe, and left putamen) exhibited an interaction between the frequency band and patient group. In the slow-5 band, increased ALFF of the right postcentral gyrus/inferior parietal lobule (PoCG/IPL) was enhanced in association with the sleep quality (ρ = 0.414, P = 0.044) and anxiety index (ρ = 0.406, P = 0.049) of the CPI patients. These findings suggest that during chronic insomnia, the intrinsic functional plasticity primarily responds to the hyperarousal state, which is the loss of inhibition in sensory-informational processing. Our findings regarding an abnormal sensory input and intrinsic processing mechanism might provide novel insight into the pathophysiology of CPI. Furthermore, the frequency factor should be taken into consideration when exploring ALFF-related clinical manifestations.
Keywords: ACC, anterior cingulate cortex; ALFF, amplitude of low-frequency fluctuation; ANOVA, analysis of variance; Amplitude of low-frequency fluctuations; CPI, chronic primary insomnia; CPL, cerebellum posterior lobe; Chronic primary insomnia; FC, functional connectivity; Functional magnetic resonance imaging, resting state; Functional plasticity; Fus/CAL, fusiform gyrus/cerebellum anterior lobe; HC, healthy control; MFG/SFG, middle/superior frontal gyrus; MOG, middle occipital gyrus; MRI, magnetic resonance imaging; PCC, posterior cingulate cortex; PCUN, precuneus; PSQI, Pittsburgh Sleep Quality Index; PoCG/IPL, postcentral gyrus/inferior parietal lobule; SPECT, single-photon emission computed tomography; SPM, statistical parametric mapping; STAI-s, State Trait Anxiety Inventory-state; STAI-t, State Trait Anxiety Inventory-trait; STG, superior temporal gyrus; fMRI, functional MRI; fO/AI, frontal operculum/anterior insula; mPFC, medial prefrontal gyrus; mTL, medial temporal lobe; rs-fMRI, resting-state fMRI.