Generalized Anxiety Disorder is not just in your head: a threat-based fMRI study of the brain and spinal cord

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Date
2021-01-29
Authors
Kolesar, Tiffany A.
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Abstract
Generalized Anxiety Disorder (GAD) is a highly prevalent anxiety disorder, characterized by chronic, excessive worry. Physical symptoms are prevalent in GAD, but physiological data are often inconsistent. The goal of the present research is to investigate the neural responses to threat in GAD versus healthy controls (HC). To achieve this goal, we collected data from the largest span of the central nervous system to-date, using functional magnetic resonance imaging (fMRI). This work was broken down into the following three aims: to identify neural activity differences between GAD and HC groups in response to threat in Aim 1) the brain, Aim 2) the cervical spinal cord, and Aim 3) the thoracic spinal cord. All three aims use data acquired from a single sample of 16 participants with GAD and 14 HC. The thesis begins with an introduction to relevant topics including GAD, physiology, and MRI technology. Aim 1) is addressed in two parts. Aim 1a is an in-depth systematic review and meta-analysis on previous neuroimaging research to identify the known neural correlates of GAD, yielding results from the dorsolateral prefrontal cortex, anterior cingulate cortex, amygdala, hippocampus, and culmen of the cerebellum, among others. Aim 1b includes a brain fMRI study in which GAD and HC participants view emotion-evoking images. First, region-of-interest analyses are conducted using regions identified in the systematic review, but results are not significant for these analyses. A follow-up whole brain analysis yields significant results for the main effect of group, corroborating many of the findings from the systematic review. Aims 2 and 3 are considered together in an identical fMRI task as Aim 1b, this time looking at the cervical and thoracic spinal cord. Spinal cord results include increased activity in ventral rostral cervical cord (innervating the neck, shoulders, and trapezius muscles) and mediolateral thoracic cord (innervating the adrenal medulla and gut) for the GAD group as compared to HC. These results provide neurological evidence for increased muscle tension and autonomic activity in the gut and adrenal glands for those with GAD. This work provides the most comprehensive fMRI study of the neurophysiological underpinnings of GAD to-date.
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Keywords
Generalized Anxiety Disorder, Functional magnetic resonance imaging, Brain, Spinal cord
Citation
Kolesar TA, Bilevicius E, Wilson AD, Kornelsen J. Systematic review and meta-analyses of neural structural and functional differences in generalized anxiety disorder and healthy controls using magnetic resonance imaging. Neuroimage Clin. 2019;24:102016. doi: 10.1016/j.nicl.2019.102016. Epub 2019 Oct 14. PMID: 31835287; PMCID: PMC6879983.