title: Panic Anxiety in Humans with Bilateral Amygdala Lesions: Pharmacological Induction via Cardiorespiratory Interoceptive Pathways.
abstract: We previously demonstrated that carbon dioxide inhalation could induce panic anxiety in a group of rare lesion patients with focal bilateral amygdala damage. To further elucidate the amygdala-independent mechanisms leading to aversive emotional experiences, we retested two of these patients (B.G. and A.M.) to examine whether triggering palpitations and dyspnea via stimulation of non-chemosensory interoceptive channels would be sufficient to elicit panic anxiety. Participants rated their affective and sensory experiences following bolus infusions of either isoproterenol, a rapidly acting peripheral β-adrenergic agonist akin to adrenaline, or saline. Infusions were administered during two separate conditions: a panic induction and an assessment of cardiorespiratory interoception. Isoproterenol infusions induced anxiety in both patients, and full-blown panic in one (patient B.G.). Although both patients demonstrated signs of diminished awareness for cardiac sensation, patient A.M., who did not panic, reported a complete lack of awareness for dyspnea, suggestive of impaired respiratory interoception. These findings indicate that the amygdala may play a role in dynamically detecting changes in cardiorespiratory sensation. The induction of panic anxiety provides further evidence that the amygdala is not required for the conscious experience of fear induced via interoceptive sensory channels.
  
  
  CONCLUSIONS
  We found that monozygotic twins with focal bilateral amygdala lesions report panic anxiety in response to intravenous infusions of isoproterenol, a β-adrenergic agonist similar to adrenaline. Heightened anxiety was evident in both twins, with one twin experiencing a panic attack. The twin who did not panic displayed signs of impaired cardiorespiratory interoception, including a complete absence of dyspnea sensation. These findings highlight that the amygdala is not strictly required for the experience of panic anxiety, and suggest that neural systems beyond the amygdala are also involved. Determining these additional systems could provide key neural modulation targets for future anxiolytic treatments.
authors.affiliation: Laureate Institute for Brain Research, Tulsa, Oklahoma 74136, Oxley College of Health Sciences, University of Tulsa, Tulsa, Oklahoma 74104, UCLA Department of Psychiatry, Semel Institute for Neuroscience and Human Behavior, Los Angeles, California 90095, skhalsa@laureateinstitute.org.
authors.forename: Sahib S
authors.initials: SS
authors.lastname: Khalsa
authors.affiliation: Laureate Institute for Brain Research, Tulsa, Oklahoma 74136, Oxley College of Health Sciences, University of Tulsa, Tulsa, Oklahoma 74104, California Institute of Technology, Pasadena, California 91125, and.
authors.forename: Justin S
authors.initials: JS
authors.lastname: Feinstein
authors.affiliation: UCLA Neuroscience Program, Los Angeles, California 90095.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: UCLA Department of Psychiatry, Semel Institute for Neuroscience and Human Behavior, Los Angeles, California 90095.
authors.forename: Jamie D
authors.initials: JD
authors.lastname: Feusner
authors.affiliation: California Institute of Technology, Pasadena, California 91125, and.
authors.forename: Ralph
authors.initials: R
authors.lastname: Adolphs
authors.affiliation: Department of Psychiatry, University of Bonn, Bonn, Germany.
authors.forename: Rene
authors.initials: R
authors.lastname: Hurlemann
mesh_terms: D000318:Adrenergic beta-Agonists; D000328:Adult; D000344:Afferent Pathways / Q000187:drug effects / Q000503:physiopathology*; D000679:Amygdala / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D006321:Heart / Q000294:innervation* / Q000503:physiopathology; D006801:Humans; D065812:Interoception; D007545:Isoproterenol; D008168:Lung / Q000294:innervation / Q000503:physiopathology; D008297:Male; D016584:Panic Disorder / Q000139:chemically induced / Q000473:pathology*
chemical_list: D000318:Adrenergic beta-Agonists; D007545:Isoproterenol
keywords: amygdala lesion; anxiety; emotion; heartbeat; interoception; respiration