Neuroimaging of Anxiety Disorders

Neuroimaging has transformed our understanding of anxiety disorders by revealing both structural and functional alterations within brain circuits that mediate emotional regulation, threat detection and executive control. Key regions include the amygdala, prefrontal cortex (PFC), anterior cingulate cortex (ACC) and hippocampus, which together form a prefrontal-limbic network. Structural methods such as voxel-based morphometry have identified volume reductions in the ACC and inferior frontal gyrus across a range of anxiety presentations, while diffusion imaging has highlighted white-matter disruptions in tracts such as the uncinate fasciculus connecting limbic and prefrontal regions. Functional techniques, including resting-state functional connectivity and measures of spontaneous low-frequency fluctuations, have revealed aberrant coupling within the default mode, salience and executive networks. Dynamic analyses have further shown that temporal variability in local activity can distinguish patients from controls and correlate with symptom severity. Together, these findings point towards circuits whose dysregulation underpins excessive worry, hypervigilance and impaired top-down control, offering potential biomarkers for early diagnosis, tracking of symptom trajectories and personalised treatment strategies.

Research from Nature Portfolio

Recent studies have shown that trait and state aspects of anxiety can be dissociated by their distinct neural signatures. Stable trait anxiety is associated with alterations in the structural covariance of the default mode network, notably an increase in dorsal nodes and decrease in ventral nodes, alongside enhanced functional connectivity within frontal regions. By contrast, transient state anxiety correlates with heightened connectivity of the salience network and ventral default mode nodes without accompanying structural changes. These results demonstrate that different dimensions of anxiety engage separate neuroanatomical and functional pathways, suggesting tailored targets for diagnostic markers and interventions depending on whether anxiety is a persistent disposition or a situation-driven response.

Neuroimaging of Anxiety Disorders publication trend

The graph below shows the total number of articles in neuroimaging of anxiety disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Resting-state functional connectivity: Correlation of spontaneous brain activity between regions when a subject is not engaged in a task, used to infer network organisation.

Fractional amplitude of low-frequency fluctuation (fALFF): A measure of the relative intensity of spontaneous neural oscillations in the 0.01–0.1 Hz band, indicative of local functional activity.

Amplitude of low-frequency fluctuation (ALFF): The absolute power of spontaneous low-frequency oscillations, reflecting regional brain activity.

Voxel-based morphometry (VBM): A neuroimaging analysis technique that detects local differences in gray matter volume across subjects.

Salience network: A functional network anchored in the anterior insula and dorsal ACC that detects and filters behaviourally relevant stimuli.

Default mode network (DMN): A network active during rest and self-referential thought, including medial prefrontal, posterior cingulate and lateral parietal regions.

References

1. Abnormal regional activity in the prefrontal‐limbic circuit at rest: Potential imaging markers and treatment predictors in drug‐naive anxiety disorders. CNS Neuroscience & Therapeutics (2023).
2. Trait and state anxiety are mapped differently in the human brain. Scientific Reports (2020).
3. Dynamic changes of amplitude of low‐frequency fluctuations in patients with generalized anxiety disorder. Human Brain Mapping (2019).
4. The Common Traits of the ACC and PFC in Anxiety Disorders in the DSM-5: Meta-Analysis of Voxel-Based Morphometry Studies. PLOS ONE (2014).
5. White matter abnormalities in adolescents with generalized anxiety disorder: a diffusion tensor imaging study. BMC Psychiatry (2014).
6. Aberrant Functional Network Connectivity as a Biomarker of Generalized Anxiety Disorder. Frontiers in Human Neuroscience (2017).