Opinion

Multiple sclerosis (MS) is generally considered to be an autoimmune, inflammatory disease. In this provocative Perspective, Stys and colleagues propose that non-inflammatory, primary progressive MS is the 'real' MS, and that inflammatory forms of the disorder reflect an aberrant immune reaction to ongoing cytodegeneration.

The conservation of processes associated with normal ageing across species suggests that model systems can contribute to our understanding of human brain ageing. In this Perspective article the authors review the insights into longevity emerging from model organisms and highlight the need for the new paradigms in gerontology to be applied to the CNS.

A growing field of research aims to examine the potential overlap between the characteristics and underlying mechanisms of drug addiction and obesity. Here, Fletcher and colleagues argue that there is not yet sufficient evidence to support a 'food addiction' model and call for caution in the application of this model to clinical and policy recommendations.

In recent decades, advances in technology have enabled the structure of the nervous system to be dissected in greater detail than ever before. In this Opinion article, Denk and colleagues outline why structural information is so important for our understanding of the function of neural circuits and describe new tools and approaches that are improving the structural information that we can acquire.

The study of speech production has largely been divided into investigations of lower-level articulatory motor control and of higher-level linguistic processing, with these research traditions rarely interacting. In this Opinion article, Hickok argues that these approaches have much to offer each other, and he presents a model of speech production that incorporates ideas from both research traditions and findings from neuroscientific studies of sensorimotor integration.

Despite its clinical relevance, direct electrical stimulation (DES) of the human brain is surprisingly poorly understood. Karnath and colleagues discuss the complex local and remote effects of DES on physiology and behaviour, and conclude that DES cannot be regarded as the gold standard for inferring causality between neuronal activity and behaviour.

Current theories of addiction all argue for a unitary account of drug addiction. Badiani and colleagues challenge this view by highlighting behavioural, cognitive and neurobiological differences between opiate addiction and psychostimulant addiction. They argue that these differences have important implications for addiction treatment, addiction theories and future research.

Both theoretical and experimental approaches have demonstrated that noise can improve information processing, but there is substantial scope for new biologically appropriate computational hypotheses and noise sources to be investigated. McDonnell and Ward propose a unifying framework for reconciling theory with experiment.

The immediate subjective effects of cocaine are central to its rewarding properties and addictive qualities; however, the mechanisms by which the drug causes these rapid effects were unclear. Wise and Kayatkin describe recent findings that show that cocaine-predictive cues can activate the dopaminergic reward system in less time than it takes for cocaine to reach and block dopamine transporters in the brain.

Collieret al. revisit the idea that age-related and Parkinson's disease-related changes in midbrain dopamine neurons are unrelated. They review studies showing that markers of cellular risk factors accumulate with age in a pattern that mimics the pattern of degeneration seen in Parkinson's disease and propose that ageing induces a pre-parkinsonian state.

Although inter-individual differences in performance are often considered to be 'noise', recent data show that they are linked to structural differences. Kanai and Rees argue that studying these links can help in understanding how structural variation influences the functional capacity of brain regions.

A great many aspects of neuronal physiology and pathology involve or affect the brain barriers. Recent insights into the role of the blood–brain barrier during development, and advances in our understanding of how it affects neurological disorders, have led to closer links between the two topics.

A subcortical pathway is assumed to mediate non-conscious visual processing of emotional stimuli. In this provocative Perspective, Pessoa and Adolphs argue that this pathway does not exist in primates and propose novel roles for the amygdala and the cortex in visual emotion processing.

Lightman and Conway-Campbell review findings showing that, superimposed on its well-known circadian rhythm, the HPA axis shows ultradian, oscillatory activity. They describe how the resulting pulsatile release of glucocorticoids maintains optimal responsiveness of the HPA axis and the brain processes regulated by these hormones.

In this Perspective, Vollenweider and Kometer discuss the clinical potential of psychedelic drugs for the treatment of various psychiatric disorders, and describe the molecular mechanisms by which classical hallucinogens and dissociative anaesthetics affect serotonin and glutamate systems. An interview with Franz X. Vollenweider for Neuropod is available for download.

The interrelationship between circadian and sleep rhythm abnormalities and neurological disease has long been recognized. Foster and colleagues now provide a conceptual framework regarding common mechanisms of neurological disease and circadian and sleep physiology, and propose new approaches for the treatment of neuropsychiatric and neurodegenerative diseases.

The traditional distinction between declarative and nondeclarative forms of memory is based on conscious versus non-conscious learning and recall. Katharina Henke argues that consciousness is a poor criterion and presents an alternative model of memory systems that is based on processing operations.

Two main features make budding yeast a key model organism for eukaryotic biology: its amenability to analysis and its conserved genome and cellular biology. Here, the authors highlight the valuable mechanistic insights into the cell-autonomous mechanisms of neurodegeneration that are emerging from studies inSaccharomyces cerevisiae.

Pulvermüller and Fadiga address the much discussed question of whether speech comprehension depends on activation of cortical motor areas. Reviewing data from neuroimaging, brain stimulation, lesion and computational studies, they conclude that action and perception circuits have interdependent roles in language comprehension.

Ensheathing glia are essential for the long-term survival of axons; however, the mechanisms by which they contribute to neuronal viability are unclear. Here, Nave proposes that long axons require continuous support from glia to meet their metabolic needs, especially when insulated by myelin.