Advances in anxiety research: Neurocognitive mechanisms and clinical applications

Recent epidemiological surveys of mental disorders in China indicate increasing public burden with that of anxiety disorders ranking the highest at a lifetime prevalence of 7.57%. Anxiety disorders primarily include subtypes of generalized anxiety disorder (GAD), panic disorder (PD), and social anxiety disorder (SAD); but regardless of practical diagnosis, its general pathogenesis and subtyping mechanisms are unclear. This article systematically reviews recent progress in this research area, especially for our team, focusing on theoretical models of the neurocognitive mechanism and clinical applications for new insights and research clues. Based on the (i) classical cognitive models, (ii) amygdala- and insula- centric neural models, and (iii) statical brain network models, we propose here an updated dynamic brain network model of anxiety and executive function. Specific features of this model are threefold. First, it highlights dynamic interactions among the salience, executive control, default, and perceptual networks, which underlies emotional and cognitive control. Second, neural oscillations among networks are responsible for the resource transformation and signal synchronization. Third, the noradrenergic system, particularly the locus coeruleus (LC)-norepinephrine (NE) system, regulates the above processes through neurotransmitters. The article also summarizes diagnostic and predictive indicators of anxiety disorders, including genetic signatures, cognitive characteristics, and neural biomarkers. In these predictive features, we especially highlight frequency-band-specific neural oscillatory patterns, and connectome-based dynamic brain network connectivity for predictions of personalized anxiety and other psychiatric disorders. They suggest an objective toolset that joins multimodal biomarkers for individualized symptom prediction and monitoring. Associated with these new observations, reviewed interventions and treatment methods in this paper include classical medication and psychological therapy, as well as noninvasive brain stimulations (NBS)of transcranial magnetic stimulation, transcranial direct current stimulation, transcranial alternating current stimulation, transcranial photo biomodulation, and neurofeedback. Though NBS has demonstrated significant therapeutic effects in anxiety and related disorders, specific parameters and protocols are still pending for future improvement. Besides new insights of personalized and targeted precision interventions and graded prevention, we further suggest to identify the neural mechanisms of anxiety across species from rodents and non-human primates, taking advantage of electrophysiology, optogenetics, and in vivo microscopic imaging for modeling common behaviors across species. On the clinical side, we propose to break the traditional classification and diagnosis system that are only based on symptomatology; but instead, to establish a multi-dimensional objective marker system based on the latest Dimensional Approaches to Research Classification and Research Domain Criteria (RDoC).