ABSTRACT
Decades of research notwithstanding, there remains an urgent need to uncover the neurobiology
of stress and anxiety and develop effective biomarkers for these conditions. The salience network (SN),
a major intrinsic neural network anchored in the frontal lobe, consistently exhibits hyperactive functioning
in stress and anxiety. This SN hyperactivity has been recognized as a novel brain network pathology, but
its underlying mechanism remains elusive.
EEG alpha (8-12 Hz) oscillations, dominating intrinsic neural rhythmic activity, play a critical role in
cortical inhibition. Particularly, prevalent posterior-to-frontal (P¿F) alpha projection (i.e., alpha directional
connectivity) transmits alpha inhibitory influence from the occipitoparietal cortex (a primary alpha source)
to the frontal lobe. By driving bottom-up cortical inhibition and gating sensory propagation that triggers
the SN, alpha P¿F connectivity can serve to downregulate the SN. Prominently featured in
“thalamocortical dysrhythmia” or “oscillopathy” models of neuropsychiatric disorders, alpha dysrhythmia
(particularly, deficient alpha P¿F connectivity) has been increasingly observed in stress and anxiety,
motivating our hypothesis that deficient alpha P¿F connectivity underlies SN hyperactivity in stress and
anxiety.
Leveraging an integrative methodology of simultaneous EEG-fMRI combined with experimental
anxiety induction via stress exposure, this project (N = 140) will establish a mechanistic role of alpha
P¿F hypoconnectivity in the genesis and maintenance of SN hyperactivity in stress and anxiety. This
discovery will further identify an accessible, low-cost EEG biomarker for SN hyperactivity and for stress
and anxiety in general. Finally, this discovery will isolate a new treatment target that is highly responsive
to non-invasive brain stimulation (NIBS), motivating an R01 to normalize alpha P¿F connectivity as a
novel intervention for stress and anxiety.