Brain Research Reviews最新文献

Late-life depressive syndromes often arise in the context of predementia, dementia syndromes, and Alzheimer's disease (AD). Conversely, patients with a history of mood disorders are at higher risk of developing cognitive impairment. The high rate of co-occurrence of these two disorders is becoming a major health problem in older subjects for both their epidemiological impact and the negative outcomes in terms of disability and increased mortality. In this perspective, it is possible to speculate on the presence of a mirror relationship between depressive and cognitive disorders in late-life. Indeed, although a causal contribution of genetic, environmental, and social factors is widely recognized in these disorders, the neurobiological links still remain largely unknown. l-glutamic acid and γ-aminobutyric acid are the principal excitatory and inhibitory neurotransmitters in the central nervous system, respectively, and increasing evidence suggests that alterations in this neurotransmitter system may contribute to the neurobiology linking depression and cognitive impairment. In the present review article, we examined the neurobiological bases of the relationship between late-life depressive syndromes and AD, with a particular attention to glutamatergic pathway signalling like a bridge connecting these two conditions. In addition, attempts have been made to explain changes in glutamatergic pathway, depression in older age, and dementia through the analysis of signal transduction mechanisms associated with these disabling disorders.

Our brain does not process incoming sensory stimuli mechanistically. Instead the current brain state modulates our reaction to a stimulus. This modulation can be investigated by cognitive paradigms such as the attentional blink, which reveal that identical visual target stimuli are correctly reported only on about half the trials. Support for the notion that the fluctuating state of the brain determines stimulus detection comes from electrophysiological investigations of brain oscillations, which have shown that different parameters of ongoing oscillatory alpha activity (~ 10 Hz) can predict whether a visual stimulus will be perceived or not. The present article reviews recent findings on the role of prestimulus alpha oscillatory activity for visual perception and incorporates these results into a neurocognitive model that is able to account for various findings in temporal attention paradigms, specifically the attentional blink.

Perceptual filling-in occurs when structures of the visual system interpolate information across regions of visual space where that information is physically absent. It is a ubiquitous and heterogeneous phenomenon, which takes place in different forms almost every time we view the world around us, such as when objects are occluded by other objects or when they fall behind the blind spot. Yet, to date, there is no clear framework for relating these various forms of perceptual filling-in. Similarly, whether these and other forms of filling-in share common mechanisms is not yet known. Here we present a new taxonomy to categorize the different forms of perceptual filling-in. We then examine experimental evidence for the processes involved in each type of perceptual filling-in. Finally, we use established theories of general surface perception to show how contextualizing filling-in using this framework broadens our understanding of the possible shared mechanisms underlying perceptual filling-in. In particular, we consider the importance of the presence of boundaries in determining the phenomenal experience of perceptual filling-in.

The ingestion of alcohol/ethanol during pregnancy can result in abnormal fetal development in both humans and a variety of experimental animal models. Depending on the pattern of consumption, the dose, and the period of exposure to ethanol, a myriad of structural and functional deficits can be observed. These teratogenic effects are thought to result from the ethanol-induced dysregulation of a variety of intracellular pathways ultimately culminating in toxicity and cell death. For instance, ethanol exposure can lead to the generation of reactive oxygen species (ROS) and produce an imbalance in the intracellular redox state, leading to an overall increase in oxidative stress. In the present review we will provide an up-to-date summary on the effects of prenatal/neonatal ethanol exposure on the levels of oxidative stress in the central nervous system (CNS) of experimental models of fetal alcohol spectrum disorders (FASD). We will also review the evidence for the use of antioxidants as potential therapeutic strategies for the treatment of some of the neuropathological deficits characteristic of both rodent models of FASD and children afflicted with these disorders. We conclude that an imbalance in the intracellular redox state contributes to the deficits seen in FASD and suggest that antioxidants are potential candidates for the development of novel therapeutic strategies for the treatment of these developmental disorders.

Neuropathic pain is currently being treated by a range of therapeutic interventions that above all act to lower neuronal activity in the somatosensory system (e.g. using local anesthetics, calcium channel blockers, and opioids). The present review highlights novel and often still largely experimental treatment approaches based on insights into pathological mechanisms, which impact on the spinal nociceptive network, thereby opening the ‘gate’ to higher brain centers involved in the perception of pain. Cellular and molecular mechanisms such as ectopia, sensitization of nociceptors, phenotypic switching, structural plasticity, disinhibition, and neuroinflammation are discussed in relation to their involvement in pain hypersensitivity following either peripheral neuropathies or spinal cord injury. A mechanism-based treatment approach may prove to be successful in effective treatment of neuropathic pain, but requires more detailed insights into the persistence of cellular and molecular pain mechanisms which renders neuropathic pain unremitting. Subsequently, identification of the therapeutic window-of-opportunities for each specific intervention in the particular peripheral and/or central neuropathy is essential for successful clinical trials. Most of the cellular and molecular pain mechanisms described in the present review suggest pharmacological interference for neuropathic pain management. However, also more invasive treatment approaches belong to current and/or future options such as neuromodulatory interventions (including spinal cord stimulation) and cell or gene therapies, respectively.

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.

The vestibular system provides the brain with sensory signals about three-dimensional head rotations and translations. These signals are important for postural and oculomotor control, as well as for spatial and bodily perception and cognition, and they are subtended by pathways running from the vestibular nuclei to the thalamus, cerebellum and the “vestibular cortex.” The present review summarizes current knowledge on the anatomy of the thalamocortical vestibular system and discusses data from electrophysiology and neuroanatomy in animals by comparing them with data from neuroimagery and neurology in humans. Multiple thalamic nuclei are involved in vestibular processing, including the ventroposterior complex, the ventroanterior–ventrolateral complex, the intralaminar nuclei and the posterior nuclear group (medial and lateral geniculate nuclei, pulvinar). These nuclei contain multisensory neurons that process and relay vestibular, proprioceptive and visual signals to the vestibular cortex. In non-human primates, the parieto-insular vestibular cortex (PIVC) has been proposed as the core vestibular region. Yet, vestibular responses have also been recorded in the somatosensory cortex (area 2v, 3av), intraparietal sulcus, posterior parietal cortex (area 7), area MST, frontal cortex, cingulum and hippocampus. We analyze the location of the corresponding regions in humans, and especially the human PIVC, by reviewing neuroimaging and clinical work. The widespread vestibular projections to the multimodal human PIVC, somatosensory cortex, area MST, intraparietal sulcus and hippocampus explain the large influence of vestibular signals on self-motion perception, spatial navigation, internal models of gravity, one's body perception and bodily self-consciousness.

This article provides a survey of major methodological and analytic developments in the use of functional neuroimaging to study complex structural and functional brain activity and connectivity, including data analysis methods devised to distill network properties from high-dimensional and multimodal datasets. The goal of this survey is to provide those in the broader neuroscientific community with an understanding of these developments sufficient to facilitate an informed reading of the literature, and a thoughtful approach to their use in the investigation of questions in their own areas of interest. Practical methodological considerations for assessing and designing functional neuroimaging studies are provided, as are examples of the types of questions that can be addressed by various techniques.