Using imaging to target the prefrontal cortex for transcranial magnetic stimulation studies in treatment-resistant depression

Structural imaging studies of the brains of patients with treatment-resistant depression (TRD) have found several abnormalities, including smaller hippocampus, orbitofrontal cortex, or prefrontal cortex. Transcranial magnetic stimulation (TMS) is a noninvasive means of modulating brain activity, and has shown antidepressant treatment efficacy. The initial methods used for targeting the prefrontal cortex are most likely insufficient. Herwig et al found that a common rule-based approach (the 5-cm rule) resulted in approximately one third of subjects receiving stimulation over the premotor, and not the prefrontal, cortex. The work of Kozel et al, replicated by Mosimann et al, showed that increasing prefrontal cortical atrophy was correlated with TMS nonresponse. These studies have raised the question of whether there might be prefrontal location methods that result in higher TMS antidepressant efficacy. Measurement of distance from skull to cortex (ds-c) provides information about both normal and pathological cortical atrophy. It has been proposed that ds-c can be used to adjust the dosage of TMS. The ds-c can be measured manually after a scan or with automated software. We are currently involved in a four-site NIMH-sponsored trial (Optimization of TMS in Depression - OPT-TMS), testing whether daily prefrontal repetitive TMS (rTMS) has antidepressant efficacy All subjects receive a baseline MRI scan with fiducials marking the motor and putative prefrontal cortex. We report the results concerning atrophy (intensity) and location in the first 20 subjects in this trial (estimated final sample: 240).