title: Altered cingulate and amygdala response towards threat and safe cues in attention deficit hyperactivity disorder.
abstract: 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).
  
  
  METHODS
  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.
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Centre Freiburg, Germany.
authors.forename: S J
authors.initials: SJ
authors.lastname: Maier
authors.forename: A
authors.initials: A
authors.lastname: Szalkowski
authors.forename: S
authors.initials: S
authors.lastname: Kamphausen
authors.forename: B
authors.initials: B
authors.lastname: Feige
authors.forename: E
authors.initials: E
authors.lastname: Perlov
authors.forename: R
authors.initials: R
authors.lastname: Kalisch
authors.forename: G A
authors.initials: GA
authors.lastname: Jacob
authors.forename: A
authors.initials: A
authors.lastname: Philipsen
authors.forename: O
authors.initials: O
authors.lastname: Tüscher
authors.forename: L
authors.initials: L
authors.lastname: Tebartz van Elst
mesh_terms: D000328:Adult; D000679:Amygdala / Q000503:physiopathology*; D001289:Attention Deficit Disorder with Hyperactivity / Q000503:physiopathology*; D001921:Brain / Q000503:physiopathology; D016022:Case-Control Studies; D003214:Conditioning, Classical / Q000502:physiology*; D003463:Cues; D005239:Fear / Q000502:physiology*; D005260:Female; D059907:Functional Neuroimaging; D005712:Galvanic Skin Response; D006179:Gyrus Cinguli / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D055815:Young Adult