Stereopsychopharmacology: past, present and future

Stereoisomers have been used for more than a century to study the role of three-dimensional (spatial) features in biological processes. Configuration and conformation are spatial features of primary interest for effects of drugs. The role of configuration has been studied mainly by comparing effects of optical isomers (enantiomers), whereas the role of conformation has been investigated primarily using geometrical isomers and semi-rigid molecules. Spatial features have been shown to play a role in many effects of stereoisomers on noradrenergic, dopaminergic, serotonergic, cholinergic, opioid and GABAergic mechanisms. Further information on psychopharmacological effects of stereoisomers may lead to a better understanding of mental disorders and to improvements in drugs used to treat them.     

Brain-machine interfaces: past, present and future

Since the original demonstration that electrical activity generated by ensembles of cortical neurons can be employed directly to control a robotic manipulator, research on brain-machine interfaces (BMIs) has experienced an impressive growth. Today BMIs designed for both experimental and clinical studies can translate raw neuronal signals into motor commands that reproduce arm reaching and hand grasping movements in artificial actuators. Clearly, these developments hold promise for the restoration of limb mobility in paralyzed subjects. However, as we review here, before this goal can be reached several bottlenecks have to be passed. These include designing a fully implantable biocompatible recording device, further developing real-time computational algorithms, introducing a method for providing the brain with sensory feedback from the actuators, and designing and building artificial prostheses that can be controlled directly by brain-derived signals. By reaching these milestones, future BMIs will be able to drive and control revolutionary prostheses that feel and act like the human arm.     

Suicide prevention: past, present and future

Efforts to prevent suicide are reviewed. Recent studies have shown that suicide prevention centers may be effective in preventing suicide, at least among females. However, in recent years, more attention has been directed toward the possibility that restricting access to methods for suicide may be an effective way for preventing suicide. In addition, there is a growing body of research on which medications and which techniques of psychotherapy may be most effective in decreasing the risk of suicide in depressed patients.     

Italian neurology: past, present and future

This short history of the Italian Society of Neurology focuses on its founders and leading personalities. The article also considers the present and the future of Italian neurology, emphasising in particular the scientific impact of Italian neurological research on the main international journals and the activities undertaken to increase the role of neurologists.     

帕金森病的昨天、今天和明天

帕金森病（Parkinson disease，PD）日益成为公共卫生关注的焦点，在我国，它影响了近1．7％的65岁以上的老年人。回顾PD的历史，有几个里程碑需要铭记。1817年Parkinson首次详述了PD的典型临床表征。1895年Brissaud从病理上提出中脑可能是PD的解剖基础。1912年Lewy发现黑质内嗜伊红包涵体，即Lewy小体是PD的重要病理特征。1960年Ehringer和Homykiewicz发现纹状体多巴胺（dopamine，DA）神经递质水平下降是产生PD运动症状的主要因素。1961年Birkmayer和Hornykiewicz首次应用左旋多巴治疗PD，但最终将其成功推向临床的要归功于Cotzias。     

Friedreich's ataxia: past, present and future

Friedreich's ataxia (FRDA) is an autosomal recessive inherited disorder characterized by progressive gait and limb ataxia, dysarthria, areflexia, loss of vibratory and position sense, and a progressive motor weakness of central origin. Additional features include hypertrophic cardiomyopathy and diabetes. Large GAA repeat expansions in the first intron of the FXN gene are the most common mutation underlying FRDA. Patients show severely reduced levels of a FXN-encoded mitochondrial protein called frataxin. Frataxin deficiency is associated with abnormalities of iron metabolism: decreased iron-sulfur cluster (ISC) biogenesis, accumulation of iron in mitochondria and depletion in the cytosol, enhanced cellular iron uptake. Some models have also shown reduced heme synthesis. Evidence for oxidative stress has been reported. Respiratory chain dysfunction aggravates oxidative stress by increasing leakage of electrons and the formation of superoxide. In vitro studies have demonstrated that Frataxin deficient cells not only generate more free radicals, but also show a reduced capacity to mobilize antioxidant defenses. The search for experimental drugs increasing the amount of frataxin is a very active and timely area of investigation. In cellular and in animal model systems, the replacement of frataxin function seems to alleviate the symptoms or even completely reverse the phenotype. Therefore, drugs increasing the amount of frataxin are attractive candidates for novel therapies. This review will discuss recent findings on FRDA pathogenesis, frataxin function, new treatments, as well as recent animal and cellular models. Controversial aspects are also discussed.     

Simple schizophrenia: past, present, and future

The diagnostic category called simple schizophrenia has disappeared from official American nosology but has been retained in ICD-9. The diagnosis has a long history, was one of the traditional schizophrenic subtypes identified by Bleuler, and was later accepted by Kraepelin. The authors provide a historical overview of the concept, review its modern successors, and provide recommendations for its inclusion in DSM-IV as a proposed diagnostic category needing further study.     

Clinical linguistics: Its past,present and future

Historiography is a growing area of research within the discipline of linguistics, but so far the subfield of clinical linguistics has received virtually no systematic attention. This article attempts to rectify this by tracing the development of the discipline from its pre-scientific days up to the present time. As part of this, I include the results of a survey of articles published in Clinical Linguistics & Phonetics between 1987 and 2008 which shows, for example, a consistent primary focus on phonetics and phonology at the expense of grammar, semantics and pragmatics. I also trace the gradual broadening of the discipline from its roots in structural linguistics to its current reciprocal relationship with speech and language pathology and a range of other academic disciplines. Finally, I consider the scope of clinical linguistic research in 2011 and assess how the discipline seems likely develop in the future.     

Clinical linguistics: its past, present and future

Historiography is a growing area of research within the discipline of linguistics, but so far the subfield of clinical linguistics has received virtually no systematic attention. This article attempts to rectify this by tracing the development of the discipline from its pre-scientific days up to the present time. As part of this, I include the results of a survey of articles published in Clinical Linguistics & Phonetics between 1987 and 2008 which shows, for example, a consistent primary focus on phonetics and phonology at the expense of grammar, semantics and pragmatics. I also trace the gradual broadening of the discipline from its roots in structural linguistics to its current reciprocal relationship with speech and language pathology and a range of other academic disciplines. Finally, I consider the scope of clinical linguistic research in 2011 and assess how the discipline seems likely develop in the future.     

Immunotherapy of neuroblastoma: present, past and future

Neuroblastoma is a neuroectodermal tumor of childhood with poor prognosis and low survival in patients with advanced-stage disease who respond to conventional therapies but unfortunately, often present relapse. Therefore, the search for novel therapeutic strategies is warranted and represents the objective of many investigators. Among the new, innovative approaches, immunotherapy has attracted much interest. However, until recently, little information was available about the immunogenicity of human neuroblastoma.     

Visual hallucinatory syndromes: past, present, and future

In 1936, two clinical reviews, one by de Morsier, the other by L'Hermitte and de Ajuriaguerra, formulated an approach to visual hallucinations that continues to this day. Breaking with previous traditions, the papers championed visual hallucinations as worthy of study in their own right, de-emphasizing the clinical significance of their visual contents and distancing them from visual illusions. De Morsier described a set of visual hallucinatory syndromes based on the wider neurological and psychiatric context, many of which remain relevant today; however, one-the Charles Bonnet Syndrome-sparked 70 years of controversy over the role of the eye. Here, the history of visual hallucinatory syndromes and the eye dispute is reviewed, together with advances in perceptual neuroscience that question core assumptions of our current approach. From a neurobiological perspective, three syndromes emerge that relate to specific dysfunctions of afferent, cholinergic and serotonergic visual circuitry and promise future therapeutic advances.     

Electroconvulsive therapy: past, present, and future]

Although electroconvulsive therapy (ECT) was first introduced to treat schizophrenia in 1938, it is widely used for the treatment of various major psychiatric disorders, including depression. In western countries, its safety has been improved with the introduction of techniques such as succinylcholine muscle relaxation, barbiturate anesthesia, oxygenation and brief-pulse stimulation. Although the first use of ECT in Japan was reported in 1939, few modifications of the ECT technique have been made since then. From the 1980s, in collaboration with anesthesiologists, ECT with anesthesia and muscle relaxation (modified ECT) has been administered in numerous general hospitals. Moreover, brief-pulse ECT devices were approved in 2002. Rapid progress in ECT practices is expected in Japan. Before administering ECT, informed consent should be obtained from the patient, except when the patient lacks capacity to consent. The major problems in ECT are cognitive side effects and high relapse rates. Furthermore, its mechanisms of action are still unknown. These problems must be solved in the near future.