Limbic dysregulation is associated with lowered heart rate variability and increased trait anxiety in healthy adults.
OBJECTIVE
We tested whether dynamic interaction between limbic regions supports a control systems model of excitatory and inhibitory components of a negative feedback loop, and whether dysregulation of those dynamics might correlate with trait differences in anxiety and their cardiac characteristics among healthy adults.


METHODS
Sixty-five subjects received fMRI scans while passively viewing angry, fearful, happy, and neutral facial stimuli. Subjects also completed a trait anxiety inventory, and were monitored using ambulatory wake ECG. The ECG data were analyzed for heart rate variability, a measure of autonomic regulation. The fMRI data were analyzed with respect to six limbic regions (bilateral amygdala, bilateral hippocampus, Brodmann Areas 9, 45) using limbic time-series cross-correlations, maximum BOLD amplitude, and BOLD amplitude at each point in the time-series.


RESULTS
Diminished coupling between limbic time-series in response to the neutral, fearful, and happy faces was associated with greater trait anxiety, greater sympathetic activation, and lowered heart rate variability. Individuals with greater levels of trait anxiety showed delayed activation of Brodmann Area 45 in response to the fearful and happy faces, and lowered Brodmann Area 45 activation with prolonged left amygdala activation in response to the neutral faces.


CONCLUSIONS
The dynamics support limbic regulation as a control system, in which dysregulation, as assessed by diminished coupling between limbic time-series, is associated with increased trait anxiety and excitatory autonomic outputs. Trait-anxious individuals showed delayed inhibitory activation in response to overt-affect stimuli and diminished inhibitory activation with delayed extinction of excitatory activation in response to ambiguous-affect stimuli.
Department of Biomedical Engineering, Stony Brook University, Stony Brook, New York 11794-8181, USA. lstrey@stonybrook.edu
Lilianne R
LR
Mujica-Parodi
Mayuresh
M
Korgaonkar
Bosky
B
Ravindranath
Tsafrir
T
Greenberg
Dardo
D
Tomasi
Mark
M
Wagshul
Babak
B
Ardekani
David
D
Guilfoyle
Shilpi
S
Khan
Yuru
Y
Zhong
Ki
K
Chon
Dolores
D
Malaspina
D000293:Adolescent; D000328:Adult; D000679:Amygdala / Q000503:physiopathology; D001008:Anxiety Disorders / Q000503:physiopathology*; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology*; D001342:Autonomic Nervous System Diseases / Q000503:physiopathology*; D001931:Brain Mapping; D004562:Electrocardiography; D005246:Feedback / Q000502:physiology; D005260:Female; D006339:Heart Rate / Q000502:physiology; D006624:Hippocampus / Q000503:physiopathology; D006801:Humans; D008032:Limbic System / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009433:Neural Inhibition / Q000502:physiology; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000503:physiopathology; D055815:Young Adult