Is prepulse modification altered by continuous theta burst stimulation? DAT1 genotype and motor threshold interact on prepulse modification following brain stimulation.
Previous studies suggest an inhibitory top-down control of the amygdala by the prefrontal cortex (PFC). Both brain regions play a role in the modulation of prepulse modification (PPM) of the acoustic startle response by a pre-stimulus. Repetitive transcranial magnetic stimulation (rTMS) can modulate the activity of the PFC and might thus affect PPM. This study tested the effect of inhibitory rTMS on PPM accounting for a genetic variant of the dopamine transporter gene (DAT1). Healthy participants (N = 102) were stimulated with continuous theta burst stimulation (cTBS, an intense form of inhibitory rTMS) or sham treatment over the right PFC. Afterwards, during continuous presentation of a background white noise a louder noise burst was presented either alone (control startle) or preceded by a prepulse. Participants were genotyped for a DAT1 variable number tandem repeat (VNTR) polymorphism. Two succeeding sessions of cTBS over the right PFC (2 × 600 stimuli with a time lag of 15 min) attenuated averaged prepulse inhibition (PPI) in participants with a high resting motor threshold. An attenuation of PPI induced by prepulses with great distances to the pulse (480, 2000 ms) was observed following active cTBS in participants that were homozygous carriers of the 10-repeat-allele of the DAT1 genotype and had a high resting motor threshold. Our results confirm the importance of the prefrontal cortex for the modulation of PPM. The effects were observed in participants with a high resting motor threshold only, probably because they received a higher dose of cTBS. The effects in homozygous carriers of the DAT1 10-repeat allele confirm the relevance of dopamine for PPM. Conducting an exploratory study we decided against the use of a correction for multiple testing.
Department of Psychiatry and Psychotherapy, University of Münster, Albert-Schweitzer-Campus 1, Gebäude A9, 48149, Münster, Germany. swantje.notzon@ukmuenster.de.
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Notzon
School of Health, Münster University of Applied Sciences, Leonardo Campus 8, 48149, Münster, Germany.
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Vennewald
Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Margarete-Höppel-Platz 1, 97080, Würzburg, Germany.
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Gajewska
Department of Psychiatry and Psychotherapy, University of Münster, Albert-Schweitzer-Campus 1, Gebäude A9, 48149, Münster, Germany.
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Klahn
kbo-Inn-Salzach-Hospital, Gabersee 7, 83512, Wasserburg am Inn, Germany.
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Diemer
Catholic University of Applied Sciences North Rhine-Westphalia, Münster, Piusallee 89, 48147, Münster, Germany.
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Winter
Department of Psychiatry and Psychotherapy, University of Münster, Albert-Schweitzer-Campus 1, Gebäude A9, 48149, Münster, Germany.
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Fohrbeck
Department of Psychiatry and Psychotherapy, University of Münster, Albert-Schweitzer-Campus 1, Gebäude A9, 48149, Münster, Germany.
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Arolt
Department of Biological Psychology, Clinical Psychology and Psychotherapy, University of Würzburg, Marcusstraße 9-11, 97070, Würzburg, Germany.
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Pauli
Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Margarete-Höppel-Platz 1, 97080, Würzburg, Germany.|Department of Psychiatry and Psychotherapy, University of Freiburg, Hauptstrasse 5, 79104, Freiburg, Germany.
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Domschke
Department of Psychiatry and Psychotherapy, University of Münster, Albert-Schweitzer-Campus 1, Gebäude A9, 48149, Münster, Germany.|kbo-Inn-Salzach-Hospital, Gabersee 7, 83512, Wasserburg am Inn, Germany.|Department of Psychiatry und Psychotherapy, Ludwig Maximilians University, Munich, Germany.
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Zwanzger
D000328:Adult; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D019054:Evoked Potentials, Motor / Q000502:physiology*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D018598:Minisatellite Repeats; D011110:Polymorphism, Genetic; D017397:Prefrontal Cortex / Q000502:physiology*; D065808:Prepulse Inhibition / Q000502:physiology*; D013216:Reflex, Startle / Q000502:physiology*; D013826:Theta Rhythm / Q000502:physiology*; D050781:Transcranial Magnetic Stimulation / Q000379:methods*; D055815:Young Adult
D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human
Acoustic startle response; DAT1 genotype; Prepulse facilitation; Prepulse inhibition; Prepulse modification; Repetitive transcranial magnetic stimulation (rTMS); Theta burst stimulation (TBS)