Altered Brain Signal Variability in Patients With Generalized Anxiety Disorder.

Generalized anxiety disorder (GAD) is characterized by a chronic, continuous symptom of worry and exaggerated startle response. Although functional abnormality in GAD has been widely studied using functional magnetic resonance imaging (fMRI), the dynamic signatures of GAD are not fully understood. As a vital index of brain function, brain signal variability (BSV) reflects the capacity of state transition of neural activities. In this study, we recruited 47 patients with GAD and 38 healthy controls (HCs) to investigate whether or not BSV is altered in patients with GAD by measuring the standard deviation of fMRI signal of each voxel. We found that patients with GAD exhibited decreased BSV in widespread regions including the visual network, sensorimotor network, frontoparietal network, limbic system, and thalamus, indicating an inflexible brain state transfer pattern in these systems. Furthermore, the correlation between BSV and trait anxiety score was prone to be positive in patients with GAD but negative in HCs. The opposite relationships between BSV and anxiety level in the two groups indicate that the brain with moderate anxiety level may stay in the most stable rather than in the flexible state. As the first study of BSV in GAD, we revealed extensively decreased BSV in patients with GAD similar to that in other mental disorders but with a non-linear relationship between BSV and anxiety level indicating a novel neurodynamic mechanism of the anxious brain.

Spatial complexity of brain signal is altered in patients with generalized anxiety disorder.

BACKGROUND: Is it healthy to be chaotic? Recent studies have argued that mental disorders are associated with more orderly neural activities, corresponding to a less flexible functional system. These conclusions were derived from altered temporal complexity. However, the relationship between spatial complexity and health is unknown, although spatial configuration is of importance for normal brain function. METHODS: Based on resting-state functional magnetic resonance imaging data, we used Sample entropy (SampEn) to evaluate the altered spatial complexity in patients with generalized anxiety disorder (GAD; n = 47) compared to healthy controls (HCs; n = 38) and the relationship between spatial complexity and anxiety level. RESULTS: Converging results showed increased spatial complexity in patients with GAD, indicating more chaotic spatial configuration. Interestingly, inverted-U relationship was revealed between spatial complexity and anxiety level, suggesting complex relationship between health and the chaos of human brain. LIMITATIONS: Anxiety-related alteration of spatial complexity should be verified at voxel level in a larger sample and compared with results of other indices to clarify the mechanism of spatial chaotic of anxiety. CONCLUSIONS: Altered spatial complexity in the brain of GAD patients mirrors inverted-U relationship between anxiety and behavioral performance, which may reflect an important characteristic of anxiety. These results indicate that SampEn is a good reflection of human health or trait mental characteristic.

Multiscale energy reallocation during low-frequency steady-state brain response.

Traditional task-evoked brain activations are based on detection and estimation of signal change from the mean signal. By contrast, the low-frequency steady-state brain response (lfSSBR) reflects frequency-tagging activity at the fundamental frequency of the task presentation and its harmonics. Compared to the activity at these resonant frequencies, brain responses at nonresonant frequencies are largely unknown. Additionally, because the lfSSBR is defined by power change, we hypothesize using Parseval's theorem that the power change reflects brain signal variability rather than the change of mean signal. Using a face recognition task, we observed power increase at the fundamental frequency (0.05 Hz) and two harmonics (0.1 and 0.15 Hz) and power decrease within the infra-slow frequency band (<0.1 Hz), suggesting a multifrequency energy reallocation. The consistency of power and variability was demonstrated by the high correlation (r > .955) of their spatial distribution and brain-behavior relationship at all frequency bands. Additionally, the reallocation of finite energy was observed across various brain regions and frequency bands, forming a particular spatiotemporal pattern. Overall, results from this study strongly suggest that frequency-specific power and variability may measure the same underlying brain activity and that these results may shed light on different mechanisms between lfSSBR and brain activation, and spatiotemporal characteristics of energy reallocation induced by cognitive tasks.