Heartbeat-evoked neural response abnormalities in generalized anxiety disorder during peripheral adrenergic stimulation.

What are the neural mechanisms underlying abnormalities in the processing of interoceptive signals (i.e., signals originating from within the body) in general anxiety disorder (GAD)? Here we examined whether the peripheral adrenergic modulation of cardiovascular signaling differentially affects the heartbeat evoked potential (HEP), an electrophysiological marker of cardiac interoception, during concurrent electroencephalogram and functional magnetic resonance imaging (EEG-fMRI) scanning. Analyzable EEG data were collected in 24 females with GAD and 24 healthy comparison females (HC) during the administration of intravenous bolus infusions of isoproterenol (0.5 and2.0 micrograms, μg) and saline in a double-blinded and randomized fashion. During the 0.5 μg isoproterenol infusion the GAD group exhibited significantly larger changes in HEP amplitude in an opposite direction compared to the HC group. In addition, the GAD group showed significantly larger HEP amplitudes than HC during saline infusions, when cardiovascular tone did not increase. No significant group differences in HEP were identified during the 2 μg isoproterenol infusion. Using analyzable blood oxygenation level dependent fMRI data from participants with concurrent HEP-neuroimaging data (21 GAD and 22 HC), we found that the aforementioned HEP effects correlated neither with insular cortex activation nor with activation of the ventromedial prefrontal cortex. These findings confirm dysfunctional cardiac interoception in GAD and indicate that bottom-up and top-down mechanisms at the electrophysiological level are involved independently from blood oxygen level-dependent neural responses.