Yoshihiko Koga

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.

Preliminary Clinical Evaluation of Toxicity and Efficacy of A New Astaxanthin-rich Haematococcus pluvialis Extract

Astaxanthin (Ax), a carotenoid ubiquitously distributed in microorganisms, fish, and crustaceans, has been known to be a potent antioxidant and hence exhibit various physiological effects. We attempted in these studies to evaluate clinical toxicity and efficacy of long-term administration of a new Ax product, by measuring biochemical and hematological blood parameters and by analyzing brain function (using CogHealth and P300 measures). Ax-rich Haematococcus pluvialis extracts equivalent to 4, 8, 20 mg of Ax dialcohol were administered to 73, 38, and 16 healthy adult volunteers, respectively, once daily for 4 weeks to evaluate safety. Ten subjects with age-related forgetfulness received an extract equivalent to 12 mg in a daily dosing regimen for 12 weeks to evaluate efficacy. As a result, no abnormality was observed and efficacy for age-related decline in cognitive and psychomotor functions was suggested.

Effects of krill oil containing n-3 polyunsaturated fatty acids in phospholipid form on human brain function: a randomized controlled trial in healthy elderly volunteers.

Background Krill oil, rich in n-3 (omega-3) polyunsaturated fatty acids (PUFAs) incorporated in phosphatidylcholine, has been reported to have many effects on physiological function. However, there are few studies using psychophysiological methods published that describe the effects of krill oil on brain function. We investigated the influence of ingestion of krill oil on cognitive function in elderly subjects by using near-infrared spectroscopy and electroencephalography. Methods A randomized, double-blind, parallel-group comparative study design was adopted. Forty-five healthy elderly males aged 61–72 years were assigned to receive 12 weeks of treatment with: medium-chain triglycerides as placebo; krill oil, which is rich in n-3 PUFAs incorporated in phosphatidylcholine; or sardine oil, which is abundant in n-3 PUFAs incorporated in triglycerides. Changes in oxyhemoglobin concentrations in the cerebral cortex during memory and calculation tasks were measured. The P300 component of event-related potentials was also measured during a working memory task. Results During the working memory task, changes in oxyhemoglobin concentrations in the krill oil and sardine oil groups were significantly greater than those in the medium-chain triglyceride group at week 12. The differential value for P300 latency in the krill oil group was significantly lower than that in the medium-chain triglyceride group at week 12. With regard to the calculation task, changes in oxyhemoglobin concentrations in the krill oil group were significantly greater than those in the medium-chain triglyceride group at week 12. Conclusion This study provides evidence that n-3 PUFAs activate cognitive function in the elderly. This is especially the case with krill oil, in which the majority of n-3 PUFAs are incorporated into phosphatidylcholine, causing it to be more effective than sardine oil, in which n-3 PUFAs are present as triglycerides.

An event-related potential study on the impairment of automatic processing of auditory input in schizophrenia

SummaryMismatch negativity (MMN) and P300 to auditory stimuli was carried out using global field power (GFP) in 25 schizophrenics and 25 normal controls. The peak latencies of MMN and P300 were significantly longer in schizophrenics than in normal controls, and the differences in MMN were marked in the frontal regions. The peak amplitudes of MMN and P300 were significantly smaller in schizophrenics. The scalp distribution of MMN to 1050 Hz tone differed between the two groups, although that to 1100 Hz was similar to each other. The results indicate an impairment in the automatic discrimination process of auditory input in schizophrenics.

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.

Arachidonic Acid Supplementation Decreases P300 Latency and Increases P300 Amplitude of Event-Related Potentials in Healthy Elderly Men

In the present study, we examined the effects of arachidonic acid (ARA) on age-related event-related potential (ERP) changes in 25 healthy elderly men. This study was performed using a double-blind crossover design. The subjects were administered 600 mg/day of ARA-enriched triglyceride (SUNTGA40S; containing 240 mg ARA) in capsules or the same amount of olive oil in capsules as an inactive placebo for 1 month. ERPs were measured before capsule administration and after 1 month of administration, and P300 latency and amplitude were also measured. In subjects administered 240 mg/day ARA, P300 latency was significantly shorter, and P300 amplitude was significantly higher than in those administered olive oil capsules, and they exhibited a significant increase in ARA content in serum phospholipids. These findings suggest that supplementation of ARA can improve cognitive function in healthy elderly men.

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.

Effects of Essence of Chicken on Cognitive Brain Function: A Near-Infrared Spectroscopy Study

The aim of this study was to investigate the effects of the essence of chicken on brain function by near-infrared spectroscopy. Twelve healthy elderly subjects took the essence of chicken or a placebo for 7 d in a double-blind cross-over design study. Changes in oxy-hemoglobin concentrations in the bilateral prefrontal areas of the brain were measured while the subjects performed the simple reaction task, the Groton Maze Learning Test, and the working memory task. In the latter case, there were significant interactions in the changes in oxy-hemoglobin concentrations between treatment and period of intake according to two-way repeated ANOVA. The changes in oxy-hemoglobin concentrations significantly increased in several regions of the prefrontal areas of the brain in those taking essence of chicken for 7 d. These results suggest that essence of chicken is useful as a nutritional supplement to enhance or maintain brain function in the elderly.

Clinical application of single-pulse transcranial magnetic stimulation for the treatment of depression

Abstract  Transcranial magnetic stimulation (TMS) has been recently suggested for the treatment of patients with major depression. Based on the results of the authors’ pilot study showing a possible antidepressive effect of single‐pulse TMS, a clinical trial was conducted involving patients with major depression. For the present study single‐photon emission computed tomography (SPECT) was recorded for six of the target patients to study the effects of TMS on the local blood flow volume. Twenty‐three inpatients meeting the Diagnostic and Statistical Manual of Mental Disorders (4th edn; DSM‐IV) criteria for major depression were invited to participate in the study. Depressive symptoms were rated using the Hamilton Rating Scale for Depression (HAM‐D). Patients were given 10 stimuli over the frontal area of both sides for a total of 20 stimuli in a session. The subjects had daily TMS session for 5 days as an add‐on therapy. In addition, six patients had their quantitative 99mTc‐ethyl cysteinate dimer SPECT images measured before and after TMS treatment. Compared with the value 2 days prior to the start of TMS therapy (24.2 ± 4.9), the average HAM‐D scale dropped significantly to 15.3 ± 6.6 on the day after completion of such therapy. The results of SPECT showed that the regional cerebral blood flow (rCBF) of the bilateral frontal region had increased in four out of six patients when comparing before and after treatment. The present study shows that single‐pulse TMS, which is widely used as a neurological test method, possesses a wide range of antidepressive effects without inducing adverse reactions. The results suggest that although repetitive TMS is steadily becoming the mainstay technique today, single‐pulse TMS also possesses sufficient antidepressive effects.