Is prepulse modification altered by continuous theta burst stimulation? DAT1 genotype and motor threshold interact on...

Area of Science:

• Neuroscience
• Genetics
• Psychology

Background:

• The prefrontal cortex (PFC) exerts inhibitory top-down control over the amygdala.
• Both the PFC and amygdala are involved in modulating prepulse inhibition (PPI) of the acoustic startle reflex.
• Repetitive transcranial magnetic stimulation (rTMS) can alter PFC activity and potentially influence PPI.

Purpose of the Study:

• To investigate the effect of inhibitory rTMS on PFC activity and its impact on PPI.
• To examine how a genetic variant of the dopamine transporter gene (DAT1) influences the rTMS modulation of PPI.
• To explore the interaction between PFC stimulation, DAT1 genotype, and PPI in healthy participants.

Main Methods:

• Healthy participants (N=102) received continuous theta burst stimulation (cTBS), a form of inhibitory rTMS, or sham treatment over the right PFC.
• Participants underwent acoustic startle response testing with and without a prepulse stimulus.
• Genetic analysis was performed for the DAT1 variable number tandem repeat (VNTR) polymorphism.

Main Results:

• Two sessions of cTBS over the right PFC attenuated averaged PPI in participants with a high resting motor threshold.
• Active cTBS led to reduced PPI for prepulses with longer inter-stimulus intervals (480, 2000 ms) in homozygous carriers of the DAT1 10-repeat allele with high resting motor thresholds.
• These effects were specific to participants with high resting motor thresholds, suggesting a dose-dependent response to cTBS.

Conclusions:

• The prefrontal cortex plays a crucial role in modulating prepulse inhibition (PPI).
• The dopamine system, as indicated by the DAT1 genotype, is relevant for PPI modulation.
• Inhibitory rTMS effects on PPI are influenced by both genetic factors (DAT1) and stimulation intensity (resting motor threshold).