Effects of Connectivity-based rTMS and State-Dependency on Amygdala Activation

Effects of Connectivity-based rTMS and State-Dependency on Amygdala Activation

Posttraumatic stress disorder (PTSD) is a highly debilitating disease with response rates to pharmacological treatment rarely exceeding 60%. Preliminary attempts have been made to use repetitive transcranial magnetic stimulation (rTMS) as a non-pharmacological treatment alternative, but thus far rTMS approaches have demonstrated only modest efficacy. A major factor contributing to these limited effects stems from the depth penetration of TMS, which is not sufficient to directly modulate deep subcortical structures, such as the amygdala, that are affected in PTSD. Moreover, while rTMS effects have been shown to be state-dependent, (i.e. vary substantially according to the neural state during stimulation), this important factor is rarely considered during the clinical application of rTMS. The current study addresses both of these limitations to improve the therapeutic efficacy of rTMS for PTSD. Here we will develop a protocol to test if connectivity-based rTMS is able to modulate amygdala activity through the functional connections with medial prefrontal cortex, taking advantage of state-dependency to enhance rTMS effects by actively engaging the amygdala through a fear perception task. BOLD activation in the amygdala and its connectivity with the frontal cortex will constitute the primary outcomes to test rTMS efficacy. Heart rate variability and skin galvanic responses, acquired during the presentation of fearful faces, will be used as continuous moderators of task engagement during rTMS. If successful, this study will pave the way for a large-scale study to investigate whether state-dependent, connectivity-based rTMS of the amygdala can improve rTMS efficacy as a clinical treatment for PTSD.

Inclusion Criteria:

• Age Restrictions: Young Group (from 18 to 35 years old)
• Use of effective method of birth control for women of childbearing capacity.
• Willing to provide informed consent.

Exclusion Criteria:

• Current or recent (within the past 6 months) history of substance abuse or dependence.
• Current serious medical illness.
• History of seizure, epilepsy, stroke, brain surgery, head injury, cranial metal implants, known structural brain lesion, devices that may be affected by rTMS or MRI (pacemaker, medication pump, cochlear implant, implanted brain stimulator)
• Inability or unwilling to give informed consent.
• Diagnosed any Axis I DSM-IV disorder (MINI, DSM-IV).
• Clinically defined neurological disorder.
• Increased risk of seizure for any reason, including prior diagnosis of increased intracranial pressure, or currently taking medication that lowers the seizure threshold.
• Claustrophobia (MRI scanner).
• Pregnancy.