Efficacy of rTMS in a mouse model of posttraumatic stress disorder

Abstract

Posttraumatic stress disorder (PTSD) is associated with brain changes that commonly involve the fear network including the prefrontal cortex (PFC), hippocampus and amygdala. Neurostimulation can been recommended as an adjunct to psychotherapy in order to facilitate extinction of fear in PTSD. Repetitive transcranial magnetic stimulation (rTMS) can thus target the PFC to provide promising treatment responses. However, preclinical rodent-based studies need to be performed to enhance the comprehension and empirical-driven efficacy of rTMS. We used a focal 40-mm coil to apply a high frequency/intensity rTMS pattern (5 daily sessions) to the ventromedial PFC (vmPFC) in a mouse model of PTSD. This procedure was assessed against fluoxetine (SSRI treatment). Through spatially precise stereotaxic framing, one session of rTMS (750 pulses) was able to focally increase c-Fos functional maps in the vmPFC immediately after stimulation. When used as a chronic treatment (5 daily sessions for 3750 pulses) in a foot-shock PTSD model, rTMS counteracted PTSD-related behavioural deficit in the object recognition task 6 days after the last treatment session and enhanced extinction dynamics in a reexposure task (4 days afterward) compared to sham treatment. Reexposure-associated c-Fos activity was found increased in the infralimbic cortex, the basolateral amygdala and the CA1 of ventral hippocampus of mice exposed to the trauma and treated with rTMS. In conclusion, chronic rTMS treatment reversed PTSD-induced impairments by acting on distributed networks of fear neurocircuitry that self-sustained 10 days post-treatment in the infralimbic cortex, the basolateral amygdala and the ventral CA1.