A growing body of literature from recent years holds that sleep plays a crucial role in the development of learning. Evidence of sleep-dependent learning has now been demonstrated across a wide variety of mnemonic domain, including both declarative and non-declarative procedural or conditioned memories. The mechanisms of sleep-dependent memory enhancement involve particular cerebral activities associated with neuroplasticity during sleep. However, there remains controversy as to whether every mnemonic function classified into various domains benefits similarly from sleep or not. This work attempts to set the scene for a much more profound insight into mnemonic characteristics, including considerations for emotional modification.

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There are several advantages to using sleep deprivation for treatment of depression, including early response, a high efficacy rate (approximately 60%), few side effects, and efficacy for drug- resistant depression. On the other hand, relapse is common; there is substantial burden for patients and doctors; and no medical fee is obtained. Therefore, this treatment is not widely used in Japan. However, methods for increasing and sustaining the efficacy of sleep deprivation have been reported. It is possible to increase and sustain the efficacy of sleep deprivation in combination with medication (antidepressant drug, lithium, etc.), bright light therapy and/or sleep phase advance. Because we sometimes encounter patients who are resistant to general drug treatment, adding sleep deprivation to the treatment choices may overcome drug-resistant depression and shorten treatment duration.

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Behavioral and physiological processes exhibit circadian rhythms in most organisms including humans. These rhythms are driven by a system of self-sustained clocks and are entrained by external cues. The mammalian central oscillator, suprachiasmatic nucleus (SCN) incorporates environmental information and orchestrates slave oscillators in peripheral cells. The circadian clock system is composed of a hierarchy of oscillators that involve transcription and translation feedback loops of multiple clock genes. Advanced sleep phase type, delayed sleep phase type and non-entrained type of circadian rhythm sleep disorders (CRSD) are thought to at least partly result from malfunction/maladaptation of the circadian system. Dissection of human circadian clock system is indispensable to understand the pathophysiology of CRSD. However, it is laborious and costly to assess individual’s circadian rhythms precisely, since the subject is usually required to stay in a laboratory environment free from external cues and masking effects for over a couple of weeks. Therefore, more convenient measurements of circadian properties are demanded to reduce patients’ burden. In this review, we discuss the pathophysiology of CRSD and surrogate measurements for assessing individual’s circadian properties.

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Effects of the quality of nighttime sleep on children’s cognitive and emotional functions are reviewed. The existing studies show strong link between nighttime sleep and children’s higher cognitive functions, which are supposed to rely on neural network including prefrontal cortex as in adults. However, some studies indicate the possibility that influences of nighttime sleep vary according to developmental stage. Furthermore, it has been shown that detrimental effects of poor nighttime sleep can be ameliorated by higher socio-economic status. Therefore, it is indispensable to take into consideration children’s age and background information in evaluating the effects of nighttime sleep on children’s cognitive and emotional functions.

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Neuroimaging techniques such as positron emission tomography (PET) have been performed to elucidate the mechanism of action of electroconvulsive therapy (ECT). We showed that acute ECT increases the regional cerebral blood flow (CBF) in the brain stem, diencephalon, basal ganglia, and medial temporal lobes. We particularly emphasized the importance of the centrencephalon for seizure generalization. Furthermore, after 10-30 min of acute ECT, decreased CBF in the anterior cingulate cortex and the medial prefrontal cortex and increased CBF in the thalamus were observed. The CBF reduction in the frontal part of the brain may support the anticonvulsant theory of ECT by Sackeim. After a course of ECT sessions, the results of CBF and glucose metabolism were inconsistent, which could be attributed to the different measurement methods and the time elapsed after the last treatment. Recent studies have shown the effects of ECT on neurotransmitters. One study showed a decrease in the dopamine D2 receptor binding in the rostral cingulate gyrus after a course of ECT, which indicates a downregulation of the receptor. Another study showed a reduction in the 5-HT2 receptor binding in large portions of the cerebral cortex. However, their sample sizes were small, and further studies are required.

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Transcranial Magnetic Stimulation (TMS) is a non- invasive method of brain stimulation, inducing eddy current in cerebral cortex by the electromagnetic induction. The eddy current stimulates mainly interneurons, resulting in indirect stimulation of pyramidal neurons. Based on Motor Evoked Potential (MEP), single-and paired-pulse TMS can be used to investigate excitatory and inhibitory regulation mechanisms of motor cortex and also to measure central motor conduction time. Repetitive TMS (rTMS) could have long-lasting effects on neuronal activity, potentially reflecting enhanced neuroplasticity. Thus therapeutic application of rTMS has been studied in neuropsychiatric disorders. Since 1995, antidepressant effect of rTMS has been actively studied as clinical research. In 2008, FDA has finally approved the therapeutic use of rTMS for medication-resistant major depression. In recent meta-analyses of rTMS, it has been reported that antidepressant effects of rTMS could be smaller than those of Electroconvulsive Therapy (ECT), however almost same as those of antidepressants. As novel strategies of rTMS, Theta Burst Stimulation (TBS) and Quadro- Pulse Stimulation (QPS) are expect-ed to have more robust long-lasting effects on neuronal activity than conventional rTMS.

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Transcranial magnetic stimulation (TMS), can stimulate the brain cortex noninvasively. This method can be divided into two types. One is called single pulse stimulation, the other is repetitive TMS (rTMS). Many studies have been done to investigate the effect of TMS in the treatment of depression. TMS has been applied for clinical treatment of psychiatric diseases such as depression. This article will focus on the physical principle of magnetic stimulation and its effects and side effects on organisms. The actual procedure of TMS will also be mentioned. Furthermore, the mechanism of the effects of TMS on organisms will be discussed briefly from the view of electromagnetism. Our study illustrates an example of application of rTMS to the treatment of depression. TMS is a very safe treatment tool and its application is expected to improve and become widespread in the treatment of many psychiatric diseases besides depression.

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For various psychiatric diseases and symptoms, many clinical trials of rTMS (repetitive transcranial magnetic stimulation) treatment have been conducted. However, most of them were for depression, and meta- analyses were reported only for auditory hallucinations and positive/negative symptoms in schizophrenia and OCD (obsessive- compulsive disorder) as well as depression. In treating depression, rTMS shows lower efficacy and slower response time but higher tolerability compared with ECT (electroconvulsive therapy), and some studies reported comparable benefit of rTMS to antidepressant medications. For treating severely depressed patients, the US Food and Drug Administration approved an rTMS device under several strict conditions in 2008, and we are expecting increase of successfully treated patients and elucidation of the therapeutic mechanisms of rTMS. The meta- analyses show favorable therapeutic effects on auditory hallucinations, but do not show any significant therapeutic effects on positive/negative symptoms in schizophrenia and OCD.

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Modified electroconvulsive therapy (m-ECT) is a useful and biological treatment for patients with psychiatric disorders and neurological diseases. With more safety and validity and less side effect, the standardized procedure of m-ECT would be required. Substantial studies of m-ECT show positive associations between ictal-electroencephalogram (EEG) and therapeutic efficacy but, to our knowledge, there was no ECT algorithm using ictal-EEG. Here, we attempted to create a procedural algorithm of m- ECT using the evaluation scale for ictal-EEG. To evaluate the validity of the ECT algorithm, we did chart review to compare the ECT effectiveness between patients who received ECT with and without the algorithm. The results showed that the patients received ECT with the algorithm recovered in short period and by small number of ECT sessions compared to those without the algorithm. The preliminary study suggests that the algorithm may provide the efficient ECT to patients.

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