Shinsuke Kito

Regional Cerebral Blood Flow Changes after Low-Frequency Transcranial Magnetic Stimulation of the Right Dorsolateral Prefrontal Cortex in Treatment-Resistant Depression

Several studies have proved that low-frequency transcranial magnetic stimulation (TMS) of the right dorsolateral prefrontal cortex (DLPFC) showed an antidepressant effect, although its mechanism is still not completely elucidated. The aim of the present study was to clarify the alteration in neuroanatomical function elicited by low-frequency TMS of the right DLPFC in treatment-resistant depression and to detect the difference between responders and nonresponders to TMS. Single-photon emission computed tomography with 99mTc-ethyl cysteinate dimer was performed in 14 right-handed male patients with treatment-resistant unipolar depression before and after low-frequency TMS of the right DLPFC. Five 60-second 1-Hz trains were applied and 12 treatment sessions were administered within a 3-week period (total pulses, 3,600). The Hamilton Rating Scale for Depression was administered and the regional cerebral blood flow (rCBF) was analyzed using statistical parametric mapping (SPM2). After TMS treatment in 14 patients, the score on the Hamilton Rating Scale for Depression decreased significantly, and considerable decreases in rCBF were seen in the bilateral prefrontal, orbitofrontal, anterior insula, right subgenual cingulate, and left parietal cortex, but no significant increase in rCBF occurred. Additionally, as compared with 8 nonresponders, 6 responders showed significant increases in rCBF at baseline in the left hemisphere including the prefrontal and limbic-paralimbic regions. These results suggest that the antidepressant effect of low-frequency TMS of the right DLPFC is associated with a decrease in rCBF in the limbic-paralimbic regions via the ipsilateral subgenual cingulate, and increased rCBF at baseline in the left hemisphere may be involved in the response to low-frequency TMS treatment.

Cerebral blood flow ratio of the dorsolateral prefrontal cortex to the ventromedial prefrontal cortex as a potential predictor of treatment response to transcranial magnetic stimulation in depression

BACKGROUND There is growing evidence that high-frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex is effective in the treatment of depression. Brain imaging studies have shown that rTMS alters regional brain activity with improvement of depression. However, a predictor of treatment response to rTMS has not yet been identified. OBJECTIVE The aim of this study was to estimate regional cerebral blood flow in the frontal regions and investigate the correlation with treatment response to high-frequency rTMS over the left dorsolateral prefrontal cortex in depression. METHODS Twenty-four patients with depression received high-frequency rTMS over the left dorsolateral prefrontal cortex and were assessed with the Hamilton Depression Rating Scale. Brain scans were acquired before rTMS using (99m)Tc-ethyl cysteinate dimer single photon emission computed tomography (SPECT), and cerebral blood flow in 16 brain regions was estimated using a fully automated region of interest (ROI) analysis software. Two principal components were extracted from cerebral blood flow in 16 brain regions by factor analysis with maximum likelihood method and Promax rotation with Kaiser normalization. RESULTS Sixteen brain regions were divided into two groups: dorsolateral prefrontal cortex (superior frontal, medial frontal, middle frontal, and inferior frontal regions); ventromedial prefrontal cortex (anterior cingulate, subcallosal, orbital, and rectal regions). Treatment response to rTMS was correlated with cerebral blood flow ratio of the dorsolateral prefrontal cortex to the ventromedial prefrontal cortex (DLPFC/VMPFC CBF ratio, r = -0.60, P = 0.002). CONCLUSIONS The findings of this study suggest that depressed patients with a lower DLPFC/VMPFC CBF ratio may show a better response to high-frequency rTMS over the left dorsolateral prefrontal cortex.

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

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.

Cerebral blood flow in the ventromedial prefrontal cortex correlates with treatment response to low‐frequency right prefrontal repetitive transcranial magnetic stimulation in the treatment of depression

Aims:  Low‐frequency right prefrontal repetitive transcranial magnetic stimulation (rTMS) is effective in treating depression, and its antidepressant effects have proven to correlate with decreases in cerebral blood flow (CBF) in the orbitofrontal cortex and subgenual cingulate cortex. However, a predictor of treatment response to low‐frequency right prefrontal rTMS in depression has not been identified yet. The aim of this study was to estimate regional CBF in the frontal regions and investigate the correlation with treatment response to low‐frequency right prefrontal rTMS in depression.

Changes in hypothalamic–pituitary–thyroid axis following successful treatment with low-frequency right prefrontal transcranial magnetic stimulation in treatment-resistant depression

Hypothalamic-pituitary-thyroid (HPT) axis abnormalities have been reported in some patients with major depression. To knowledge, however, the effects of low-frequency right prefrontal transcranial magnetic stimulation (TMS) on the HPT axis have not yet been elucidated. The goal of this study was to evaluate alterations in the HPT axis associated with the therapeutic efficacy of TMS treatments. Twenty patients with treatment-resistant depression received five 60-s 1-Hz trains over the right dorsolateral prefrontal cortex. Twelve treatment sessions were administered within a 3-week period (total pulses, 3600). Responders were defined as a > or =50% decrease in the Hamilton Depression Rating Scale (HDRS) score. Serum levels of thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) were measured, respectively, at pre- and post-treatment. There were no significant changes in fT3 and fT4 levels measured at either pre- or post-treatment in either responders or nonresponders; however, TSH levels of responders elevated significantly after TMS treatments. In addition, there was a significant negative correlation between TSH levels at pretreatment and decrease (%) in the HDRS score. These findings suggest that the HPT axis is associated with antidepressant effects of low-frequency right prefrontal TMS, and indicate that lower TSH levels at pre-treatment are correlated with better therapeutic efficacy.

A 6-month follow-up case report of regional cerebral blood flow changes in treatment-resistant depression after successful treatment with bilateral transcranial magnetic stimulation.

We report a patient with treatment-resistant depression who responded dramatically to bilateral transcranial magnetic stimulation (TMS) and present a 6-month follow-up of changes in regional cerebral blood flow. A 59-year-old man with 4 recurrences of depression came to our outpatient clinic. His current episode had persisted for at least 10 months, although he received several antidepressants. After successful TMS treatment, as compared with normal comparisons, the areas of hypoperfusion in the anterior and subgenual cingulate cortices were almost unchanged but were normalized at month 6. The areas of hyperperfusion in the orbitofrontal cortex were reduced considerably at week 4 and disappeared at month 6. Although there are limitations of a case report, the findings of this case suggest that treatment response to bilateral TMS may be associated with the anterior cingulate, subgenual cingulate, and orbitofrontal cortices.

Transcranial Magnetic Stimulation Modulates Resting EEG Functional Connectivity Between the Left Dorsolateral Prefrontal Cortex and Limbic Regions in Medicated Patients With Treatment-Resistant Depression

High-frequency left prefrontal repetitive transcranial magnetic stimulation (rTMS) has been shown to have efficacy in treatment-resistant depression. However, the effects of rTMS on functional connectivity are still not clear. To examine changes in functional connectivity before and after rTMS, resting EEG of 14 patients with treatment-resistant depression was recorded twice at baseline and at week 4, respectively. The EEG data were analyzed using the standardized low-resolution brain electromagnetic tomography (sLORETA). The results reveal that high-frequency left prefrontal rTMS modulates resting EEG functional connectivity between the left dorsolateral prefrontal cortex and limbic regions, including the subgenual cingulate cortex and parahippocampal gyrus.

S7-5. Repetitive transcranial magnetic stimulation (rTMS) modulates resting EEG functional connectivity in patients with treatment-resistant depression

Aims Repetitive transcranial magnetic stimulation (rTMS) is a neuromodulation technique for treating patients with depression who do not respond to medications. However, the effects of rTMS on functional connectivity are still not clear. The aims of this study were to examine changes in resting EEG functional connectivity before and after rTMS treatments. Methods Resting EEG of patients with treatment-resistant depression was recorded for approximately 5 min twice at baseline and at week 4 respectively. The patients received high-frequency left prefrontal rTMS, 5 days a week, for 4 weeks. To examine changes in resting EEG functional connectivity, the EEG data were analyzed using the functional independent component analysis (fICA) and functional wire connectivity analysis (fWCA) in the standardized low-resolution brain electromagnetic tomography (sLORETA). Results fICA showed that rTMS enhanced the anti-correlated gamma band activities between the left dorsolateral prefrontal cortex (DLPFC) and precuneus. fWCA revealed that there was significant increased functional connectivity in middle beta band between the left DLPFC and parahippocampal gyrus, and between the subgenual cingulate cortex and parahippocampal gyrus. Conclusion These findings suggest that rTMS might modulate neural networks between the left DLPFC and posterior cingulate, and between the left DLPFC and limbic regions.

Successful treatment with blonanserin for drug-induced hyperprolactinemia in chronic schizophrenia patients: a six-month follow-up of two cases.

To the Editor: Some antipsychotics cause elevations in serum prolactin (PRL) levels, which can lead to galactorrhea, infertility, menstrual disorders, sexual dysfunction, and reduction in bone mineral density, although recent atypical antipsychotics do so less often than conventional ones. We present two cases of chronic schizophrenia with risperidone-induced hyperprolactinemia, of whom one, especially, had sexual dysfunction. Their elevated PRL levels were normalized after switching to blonanserin.

Study on the Disruption of Cerebral White Matter Integrity in Schizophrenia with MR-DTI Tractography

We have analyzed cerebral white matter using magnetic resonance diffusion tensor imaging (MR-DTI) to find available indices for the quantitative evaluation of schizophrenia. Diffusion tensor images were acquired for patients with schizophrenia and healthy comparison subjects, group-matched for age, sex, and handedness. Fiber tracking was performed on the inferior longitudinal and inferior fronto-occipital fasciculi for the comparison between the patient and comparison groups. We have calculated the cross-sectional area on the starting coronal plane of tracking and the mean and standard deviation of the fractional anisotropy and the apparent diffusion coefficient along tracked fibers. These five indices were compared in the patient and comparison group and in the right and left hemispheres. As a result, in the inferior longitudinal fasciculus we found the standard deviation of the right apparent diffusion coefficient had significant difference between the patient and comparison groups. In the inferior fronto-occipital fasciculus the mean and standard deviation of the apparent diffusion coefficient had significant differences. These results suggest that we may evaluate the disruption in white matter integrity in schizophrenic patients quantitatively by comparing the indices having significant differences in the patient and comparison groups.