Cognitive-behavioral therapy effects on alerting network activity and effective connectivity in panic disorder

  • Susanne NeufangEmail author
  • Maximilian J. Geiger
  • György A. Homola
  • Marina Mahr
  • Miriam A. Schiele
  • Andrea Gehrmann
  • Brigitte Schmidt
  • Agnieszka Gajewska
  • Johannes Nowak
  • Eva Meisenzahl-Lechner
  • Mirko Pham
  • Marcel Romanos
  • Atae Akhrif
  • Katharina Domschke
Original Paper


Given the particular relevance of arousal and alerting in panic disorder (PD), here the alerting network was investigated (1) contrasting patients with PD and healthy controls, (2) as a function of anxiety sensitivity constituting a dimensional measure of panic-related anxiety, and (3) as a possible correlate of treatment response. Using functional magnetic resonance imaging (fMRI), 45 out-patients with PD (f = 34) and 51 matched healthy controls were investigated for brain activation patterns and effective connectivity (Dynamic Causal Modeling, DCM) while performing the Attention Network Task (ANT). Anxiety sensitivity was ascertained by the Anxiety Sensitivity Index (ASI). Forty patients and 48 controls were re-scanned after a 6 weeks cognitive-behavioral treatment (CBT) or an equivalent waiting time, respectively. In the alerting condition, patients showed decreased activation in fronto-parietal pathways including the middle frontal gyrus and the superior parietal lobule (MFG, SPL). In addition, ASI scores were negatively correlated with connectivity emerging from the SPL, the SFB and the LC and going to the MFG in patients but not in healthy controls. CBT resulted in an increase in middle frontal and parietal activation along with increased connectivity going from the MFG to the SPL. This change in connectivity was positively correlated with reduction in ASI scores. There were no changes in controls. The present findings point to a pathological disintegration of the MFG in a fronto-parietal pathway in the alerting network in PD which was observed to be reversible by a successful CBT intervention.


Anxiety Arousal Alerting system Neuroimaging Effective connectivity Frontal cortex Locus coeruleus Fronto-coerulear connectivity 



This work was supported by grants from the Deutsche Forschungsgemeinschaft (DFG; SFB-TRR-58 project C02 to KD and SN) and the Interdisciplinary Center for Clinical Research (IZKF), University of Wuerzburg (N-262 to KD, SN and GH).

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interests.

Informed consent

Written informed consent was obtained from all participants. The study was approved by the local ethics committee at Wuerzburg University, Germany, and carried out in accordance with the declaration of Helsinki.

Supplementary material

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Susanne Neufang
    • 1
    • 2
    Email author
  • Maximilian J. Geiger
    • 3
    • 4
  • György A. Homola
    • 5
  • Marina Mahr
    • 3
  • Miriam A. Schiele
    • 3
    • 6
  • Andrea Gehrmann
    • 3
  • Brigitte Schmidt
    • 3
  • Agnieszka Gajewska
    • 3
  • Johannes Nowak
    • 7
  • Eva Meisenzahl-Lechner
    • 2
  • Mirko Pham
    • 5
  • Marcel Romanos
    • 1
  • Atae Akhrif
    • 1
  • Katharina Domschke
    • 3
    • 6
  1. 1.Center of Mental Health, Department of Child and Adolescent PsychiatryUniversity of WuerzburgWuerzburgGermany
  2. 2.Department of Psychiatry and PsychotherapyMedical Faculty Heinrich-Heine UniversityDuesseldorfGermany
  3. 3.Center of Mental Health, Department of Psychiatry, Psychosomatics and PsychotherapyUniversity of WuerzburgWuerzburgGermany
  4. 4.Epilepsy Center, Medical Center, Faculty of MedicineUniversity of FreiburgFreiburgGermany
  5. 5.Institute for Diagnostical and Interventional NeuroradiologyUniversity of WuerzburgWuerzburgGermany
  6. 6.Department of Psychiatry and Psychotherapy, Medical Centre, Faculty of MedicineUniversity of FreiburgFreiburgGermany
  7. 7.Institute for Diagnostical and Interventional RadiologyUniversity of WuerzburgWuerzburgGermany

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