Imbalanced temporal states of cortical blood-oxygen-level-dependent signal variability during rest in episodic migraine.

BACKGROUND: Migraine has been associated with functional brain changes including altered connectivity and activity both during and between headache attacks. Recent studies established that the variability of the blood-oxygen-level-dependent (BOLD) signal is an important attribute of brain activity, which has so far been understudied in migraine. In this study, we investigate how time-varying measures of BOLD variability change interictally in episodic migraine patients. METHODS: Two independent resting state functional MRI datasets acquired on 3T (discovery cohort) and 1.5T MRI scanners (replication cohort) including 99 episodic migraine patients (n3T = 42, n1.5T=57) and 78 healthy controls (n3T = 46, n1.5T=32) were analyzed in this cross-sectional study. A framework using time-varying measures of BOLD variability was applied to derive BOLD variability states. Descriptors of BOLD variability states such as dwell time and fractional occupancy were calculated, then compared between migraine patients and healthy controls using Mann-Whitney U-tests. Spearman's rank correlation was calculated to test associations with clinical parameters. RESULTS: Resting-state activity was characterized by states of high and low BOLD signal variability. Migraine patients in the discovery cohort spent more time in the low variability state (mean dwell time: p = 0.014, median dwell time: p = 0.022, maximum dwell time: p = 0.013, fractional occupancy: p = 0.013) and less time in the high variability state (mean dwell time: p = 0.021, median dwell time: p = 0.021, maximum dwell time: p = 0.025, fractional occupancy: p = 0.013). Higher uptime of the low variability state was associated with greater disability as measured by MIDAS scores (maximum dwell time: R = 0.45, p = 0.007; fractional occupancy: R = 0.36, p = 0.035). Similar results were observed in the replication cohort. CONCLUSION: Episodic migraine patients spend more time in a state of low BOLD variability during rest in headache-free periods, which is associated with greater disability. BOLD variability states show potential as a replicable functional imaging marker in episodic migraine.

Altered spatio-temporal state patterns for functional dynamics estimation in first-episode drug-naive major depression.

Patients with major depressive disorder (MDD) display affective and cognitive impairments. Although MDD-associated abnormalities of brain function and structure have been explored in depth, the relationships between MDD and spatio-temporal large-scale functional networks have not been evaluated in large-sample datasets. We employed data from International Big-Data Center for Depression Research (IBCDR), and comparable 543 healthy controls (HC) and 314 first-episode drug-naive (FEDN) MDD patients were included. We used a multivariate pattern classification method to learn informative spatio-temporal functional states. Brain states of each participant were extracted for functional dynamic estimation using an independent component analysis. Then, a multi-kernel pattern classification method was developed to identify discriminative spatio-temporal states associated with FEDN MDD. Finally, statistical analysis was applied to intrinsic and clinical brain characteristics. Compared with HC, FEDN MDD patients exhibited altered spatio-temporal functional states of the default mode network (DMN), the salience network, a hub network (centered on the dorsolateral prefrontal cortex), and a relatively complex coupling network (visual, DMN, motor-somatosensory and subcortical networks). Multi-kernel classification models to distinguish patients from HC obtained areas under the receiver operating characteristic curves up to 0.80. Classification scores correlated with Hamilton Depression Rating Scale scores and age at MDD onset. FEDN MDD patients had multiple abnormal spatio-temporal functional states. Classification scores derived from these states were related to symptom severity. The assessment of spatio-temporal states may represent a powerful clinical and research tool to distinguish between neuropsychiatric patients and controls.