Locus Coeruleus Activity Mediates Hyperresponsiveness in Posttraumatic Stress Disorder

BACKGROUND: Patients with posttraumatic stress disorder (PTSD) are hyperresponsive to unexpected or potentially threatening environmental stimuli. Research in lower animals and humans suggests that sensitization of the locus coeruleus-norepinephrine system may underlie behavioral and autonomic hyperresponsiveness in PTSD. However, direct evidence linking locus coeruleus system hyperactivity to PTSD hyperresponsiveness is sparse. METHODS: Psychophysiological recording and functional magnetic resonance imaging were used during passive listening to brief, 95-dB sound pressure level, white noise bursts presented intermittently to determine whether behavioral and autonomic hyperresponsiveness to sudden sounds in PTSD is associated with locus coeruleus hyperresponsiveness. RESULTS: Participants with PTSD (n = 28) showed more eye-blink reflexes and larger heart rate, skin conductance, and pupil area responses to loud sounds (multivariate p = .007) compared with trauma-exposed participants without PTSD (n = 26). PTSD participants exhibited larger responses in locus coeruleus (t = 2.60, region of interest familywise error corrected), intraparietal sulcus, caudal dorsal premotor cortex, and cerebellar lobule VI (t >= 4.18, whole-brain familywise error corrected). Caudal dorsal premotor cortex activity was associated with both psychophysiological response magnitude and levels of exaggerated startle responses in daily life in PTSD participants (t >= 4.39, whole-brain familywise error corrected). CONCLUSIONS: Behavioral and autonomic hyperresponsiveness in PTSD may arise from a hyperactive alerting/orienting system in which processes related to attention and motor preparation localized to lateral premotor cortex, intraparietal sulcus, and posterior superior cerebellar cortex are modulated by atypically high phasic noradrenergic influences originating in the locus coeruleus.