Diminished appetitive startle modulation following targeted inhibition of prefrontal cortex.
From an evolutionary perspective the startle eye-blink response forms an integral part of the human avoidance behavioral repertoire and is typically diminished by pleasant emotional states. In major depressive disorder (MDD) appetitive motivation is impaired, evident in a reduced interference of positive emotion with the startle response. Given the pivotal role of frontostriatal neurocircuitry in orchestrating appetitive motivation, we hypothesized that inhibitory transcranial magnetic stimulation (TMS) would reduce appetitive neuromodulation in a manner similar to MDD. Based on a pre-TMS functional MRI (fMRI) experiment we selected the left dorsolateral and dorsomedial prefrontal cortices as target regions for subsequent sham-controlled inhibitory theta-burst TMS (TBS) in 40 healthy male volunteers. Consistent with our hypothesis, between-group comparisons revealed a TBS-induced inhibition of appetitive neuromodulation, manifest in a diminished startle response suppression by hedonic stimuli. Collectively, our results suggest that functional integrity of left dorsolateral and dorsomedial prefrontal cortex is critical for mediating a pleasure-induced down-regulation of avoidance responses which may protect the brain from a depressogenic preponderance of defensive stress.
1] Department of Psychiatry, University of Bonn, 53105 Bonn, Germany [2] Division of Medical Psychology, University of Bonn, 53105 Bonn, Germany.
René
R
Hurlemann
1] Department of Psychiatry, University of Bonn, 53105 Bonn, Germany [2] Division of Medical Psychology, University of Bonn, 53105 Bonn, Germany.
Stephan
S
Arndt
1] Department of Psychiatry, University of Bonn, 53105 Bonn, Germany [2] Department of Psychiatry &Behavioral Medicine, The Johns Hopkins Hospital, Baltimore, Maryland, 21287, USA.
Thomas E
TE
Schlaepfer
Beta Clinic, 53227 Bonn, Germany.
Juergen
J
Reul
1] Department of Psychiatry, University of Bonn, 53105 Bonn, Germany [2] German Center for Neurodegenerative Diseases (DZNE), 53175 Bonn, Germany.
Wolfgang
W
Maier
1] Department of Psychiatry, University of Bonn, 53105 Bonn, Germany [2] Division of Medical Psychology, University of Bonn, 53105 Bonn, Germany.
Dirk
D
Scheele
D000328:Adult; D001070:Appetitive Behavior / Q000502:physiology; D001931:Brain Mapping; D003865:Major Depressive Disorder / Q000503:physiopathology*; D004644:Emotions / Q000502:physiology* / Q000528:radiation effects; D064368:Healthy Volunteers; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009474:Neurons / Q000502:physiology* / Q000528:radiation effects; D017397:Prefrontal Cortex / Q000503:physiopathology / Q000528:radiation effects; D013216:Reflex, Startle / Q000502:physiology* / Q000528:radiation effects; D013826:Theta Rhythm; D050781:Transcranial Magnetic Stimulation