Systematic review and meta-analyses of neural structural and functional differences in generalized anxiety disorder and healthy controls using magnetic resonance imaging.

OBJECTIVE: To compare structure, functional connectivity (FC) and task-based neural differences in subjects with generalized anxiety disorder (GAD) compared to healthy controls (HC). METHODS: The Embase, Ovid Medline, PsycINFO, Scopus, and Web of Science databases were searched from inception until March 12, 2018. Two reviewers independently screened titles, abstracts, and full-text articles. Data were extracted from records directly contrasting GAD and HC that included structure (connectivity and local indices such as volume, etc.), FC, or task-based magnetic resonance imaging data. Meta-analyses were conducted, as applicable, using AES-SDM software. RESULTS: The literature search produced 4,645 total records, of which 85 met the inclusion criteria for the systematic review. Records included structural (n = 35), FC (n = 33), and task-based (n = 42) findings. Meta-analyses were conducted on voxel-based morphometry and task-based results. DISCUSSION: The systematic review confirms and extends findings from previous reviews. Although few whole-brain resting state studies were conducted, key nodes of resting state networks have altered physiology: the hippocampus (default network), ACC and amygdala (salience network), have reduced volume, and the dlPFC (central executive network) and ACC have reduced FC with the amygdala in GAD. Nodes in the sensorimotor network are also altered with greater pre- and postcentral volume, reduced supplementary motor area volume, and reduced FC in anterior and increased FC in posterior cerebellum. CONCLUSIONS: Despite limitations due to sample size, the meta-analyses highly agree with the systematic review and provide evidence of widely distributed neural differences in subjects with GAD, compared to HC. Further research optimized for meta-analyses would greatly improve large-scale comparisons.

Neural Responses to Consciously and Unconsciously Perceived Emotional Faces: A Spinal fMRI Study.

Emotional stimuli modulate activity in brain areas related to attention, perception, and movement. Similar increases in neural activity have been detected in the spinal cord, suggesting that this understudied component of the central nervous system is an important part of our emotional responses. To date, previous studies of emotion-dependent spinal cord activity have utilized long presentations of complex emotional scenes. The current study differs from this research by (1) examining whether emotional faces will lead to enhanced spinal cord activity and (2) testing whether these stimuli require conscious perception to influence neural responses. Fifteen healthy undergraduate participants completed six spinal functional magnetic resonance imaging (fMRI) runs in which three one-minute blocks of fearful, angry, or neutral faces were interleaved with 40-s rest periods. In half of the runs, the faces were clearly visible while in the other half, the faces were displayed for only 17 ms. Spinal fMRI consisted of half-Fourier acquisition single-shot turbo spin-echo (HASTE) sequences targeting the cervical spinal cord. The results indicated that consciously perceived faces expressing anger elicited significantly more activity than fearful or neutral faces in ventral (motoric) regions of the cervical spinal cord. When stimuli were presented below the threshold of conscious awareness, neutral faces elicited significantly more activity than angry or fearful faces. Together, these data suggest that the emotional modulation of spinal cord activity is most impactful when the stimuli are consciously perceived and imply a potential threat toward the observer.