Neuroanatomical correlates of therapeutic efficacy of low-frequency right prefrontal transcranial magnetic stimulation in treatment-resistant depression


Shinsuke Kito, MD, PhD, Department of Neuropsychiatry, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan. Email:


Aims:  Low-frequency transcranial magnetic stimulation (TMS) to the right prefrontal cortex has been shown to be effective in treatment-resistant depression. The aim of the present study was to investigate changes in regional cerebral blood flow (rCBF) after low-frequency right prefrontal stimulation (LFRS), and neuroanatomical correlates of therapeutic efficacy of LFRS in treatment-resistant depression.

Methods:  Twenty-six patients with treatment-resistant depression received five 60-s 1-Hz trains over the right prefrontal cortex, and 12 treatment sessions were administered during 3 weeks. Brain scans were acquired before and after LFRS using single photon emission computed tomography with 99mTc-ethyl cysteinate dimer. Severity of depression was assessed on the Hamilton Depression Rating Scale (HDRS).

Results:  Significant decreases in rCBF after LFRS were seen in the prefrontal cortex, orbitofrontal cortex, subgenual cingulate cortex, globus pallidus, thalamus, anterior and posterior insula, and midbrain in the right hemisphere. Therapeutic efficacy of LFRS was correlated with decreases in rCBF in the right prefrontal cortex, bilateral orbitofrontal cortex, right subgenual cingulate cortex, right putamen, and right anterior insula.

Conclusion:  The antidepressant effects of LFRS in treatment-resistant depression may be associated with decreases in rCBF in the orbitofrontal cortex and the subgenual cingulate cortex via the right prefrontal cortex.