Christoph Naegeli1, Thomas Zeffiro2, Marco Piccirelli3, Assia Jaillard4, Anina Weilenmann1, Katayun Hassanpour1, Matthis Schick1, Michael Rufer5, Scott P Orr6, Christoph Mueller-Pfeiffer7. 1. Department of Psychiatry and Psychotherapy, University Hospital Zurich, University of Zurich, Zurich, Switzerland. 2. Neurometrika, Potomac, Maryland; Department of Radiology, University of Maryland, Baltimore, Maryland. 3. Department of Neuroradiology, Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland. 4. Unité IRM 3T Recherche, Pôle Recherche CHU de Grenoble, Grenoble Cedex, France. 5. Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland. 6. Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. 7. Department of Psychiatry and Psychotherapy, University Hospital Zurich, University of Zurich, Zurich, Switzerland. Electronic address: christoph.mueller-pfeiffer@access.uzh.ch.
Abstract
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.
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). PTSDparticipants 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 PTSDparticipants (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.
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