Psychological Medicine

Original Articles

Altered cingulate and amygdala response towards threat and safe cues in attention deficit hyperactivity disorder

S. J. Maiera1a2 c1, A. Szalkowskia1, S. Kamphausena3, B. Feigea1, E. Perlova1, R. Kalischa4, G. A. Jacoba1a5, A. Philipsena1, O. Tüschera1a6  and L. Tebartz van Elsta1 

a1 Department of Psychiatry and Psychotherapy, University Medical Centre Freiburg, Germany

a2 Faculty of Biology, Institute of Biology III, University of Freiburg, Germany

a3 Department of Psychiatry and Psychotherapy, University Medical Centre Tuebingen, Germany

a4 Institute for Systems Neuroscience, University Medical Centre Hamburg-Eppendorf (UKE), Hamburg, Germany

a5 Department of Clinical Psychology and Psychotherapy, University of Freiburg, Germany

a6 Department of Psychiatry and Psychotherapy, University Medical Centre Mainz, Germany


Background Emotional dysregulation is becoming increasingly recognized as an important feature of attention deficit hyperactivity disorder (ADHD). In this study, two experiments were conducted investigating the neural response to either verbally instructed fear (IF) or uninstructed (classically conditioned) fear (UF) using the skin conductance response (SCR) and functional magnetic resonance imaging (fMRI).

Method In the conditioning phase of the UF experiment (17 ADHD and 17 healthy controls), subjects experienced an unconditioned stimulus (UCS, unpleasant electrodermal stimulation) paired with a former neutral conditioned stimulus (CS+), whereas a control stimulus (CS−) was never paired with the UCS. In the subsequent test phase, only the CS+ and the CS− were presented. In the IF experiment (13 ADHD and 17 healthy controls), subjects were only told that an independently experienced UCS might occur together with the CS+ but not the CS− during testing. No UCS was presented.

Results Groups did not detectably differ in SCR or neural responses to UF. In IF, ADHD patients showed a trend-line decreased SCR and significantly decreased activation of the dorsal anterior cingulate cortex (dACC), a region prominently involved in fear responding, to the CS+. This was accompanied by higher amygdala activation to the CS−.

Conclusions During IF, ADHD patients showed deficits in regions centrally involved in fear learning and expression in terms of diminished CS+-related dACC and increased CS−-related amygdala signals. This suggests an impaired processing of verbally transmitted aversive information, which is central for conveying fear information in social contexts. This result extends the growing literature on emotional alterations in ADHD.

(Received May 10 2012)

(Revised February 06 2013)

(Accepted February 12 2013)

(Online publication March 19 2013)

Key words

  • ADHD;
  • amygdala;
  • anterior cingulate cortex;
  • fear conditioning;
  • fear learning;
  • functional MRI;
  • instructed fear;
  • uninstructed fear


  These authors contributed equally to this work.