[PET imaging for better understanding of normal and pathological neurotransmission]. / L'imagerie TEP pour une meilleure compréhension de la neurotransmission normale et pathologique.

Positron emission tomography imaging is still an expanding field of preclinical and clinical investigations exploring the brain and its normal and pathological functions. In addition to technological improvements in PET scanners, the availability of suitable radiotracers for unexplored pharmacological targets is a key factor in this expansion. Many radiotracers (or radiopharmaceuticals, when administered to humans) have been developed by multidisciplinary teams to visualize and quantify a growing numbers of brain receptors, transporters, enzymes and other targets. The development of new PET radiotracers still represents an exciting challenge, given the large number of neurochemical functions that remain to be explored. In this article, we review the development context of the first preclinical radiotracers and their passage to humans. The main current contributions of PET radiotracers are described in terms of imaging neuronal metabolism, quantification of receptors and transporters, neurodegenerative and neuroinflammatory imaging. The different approaches to functional imaging of neurotransmission are also discussed. Finally, the contributions of PET imaging to the research and development of new brain drugs are described.

TITLE: L'imagerie TEP pour une meilleure compréhension de la neurotransmission normale et pathologique. ABSTRACT: La neuroimagerie des récepteurs cérébraux a commencé au début des années 1980. Aujourd'hui, quelque quarante ans plus tard, l'imagerie par tomographie d'émission de positons (TEP) est toujours un domaine en expansion dans les études précliniques et cliniques cherchant à explorer le cerveau et son fonctionnement normal et pathologique. Outre les améliorations apportées aux caméras TEP et à l'analyse d'images, la disponibilité de radiotraceurs est un facteur déterminant de cette expansion. De nombreux radiotraceurs (ou radiopharmaceutiques, lorsque injectés chez l'Homme) ont été mis au point par des équipes pluridisciplinaires pour visualiser et quantifier un nombre croissant de récepteurs, transporteurs, enzymes et autres cibles moléculaires du cerveau. Le développement de nouveaux radiotraceurs TEP représente un défi passionnant, du fait du grand nombre de cibles et de fonctions neurochimiques qui restent encore à explorer. Dans cet article, nous resituons le contexte de développement des premiers radiotraceurs précliniques et leur passage à l'Homme. Les principales contributions actuelles des radiotraceurs TEP sont décrites en termes d'imagerie du métabolisme neuronal, de quantification des récepteurs et des transporteurs, d'imagerie neurodégénérative et neuroinflammatoire. Les différentes approches d'imagerie fonctionnelle de la neurotransmission sont également abordées. Enfin, les apports de l'imagerie TEP à la recherche et au développement de nouveaux médicaments du cerveau sont décrits.

Functional brain imaging in neuropsychology over the past 25 years.

OBJECTIVE: Outline effects of functional neuroimaging on neuropsychology over the past 25 years. METHOD: Functional neuroimaging methods and studies will be described that provide a historical context, offer examples of the utility of neuroimaging in specific domains, and discuss the limitations and future directions of neuroimaging in neuropsychology. RESULTS: Tracking the history of publications on functional neuroimaging related to neuropsychology indicates early involvement of neuropsychologists in the development of these methodologies. Initial progress in neuropsychological application of functional neuroimaging has been hampered by costs and the exposure to ionizing radiation. With rapid evolution of functional methods-in particular functional MRI (fMRI)-neuroimaging has profoundly transformed our knowledge of the brain. Its current applications span the spectrum of normative development to clinical applications. The field is moving toward applying sophisticated statistical approaches that will help elucidate distinct neural activation networks associated with specific behavioral domains. The impact of functional neuroimaging on clinical neuropsychology is more circumscribed, but the prospects remain enticing. CONCLUSIONS: The theoretical insights and empirical findings of functional neuroimaging have been led by many neuropsychologists and have transformed the field of behavioral neuroscience. Thus far they have had limited effects on the clinical practices of neuropsychologists. Perhaps it is time to add training in functional neuroimaging to the clinical neuropsychologist's toolkit and from there to the clinic or bedside. (PsycINFO Database Record

Twenty years of functional near-infrared spectroscopy: introduction for the special issue.

Papers from four different groups were published in 1993 demonstrating the ability of functional near infrared spectroscopy (fNIRS) to non-invasively measure hemoglobin concentration responses to brain function in humans. This special issue commemorates the first 20years of fNIRS research. The 9 reviews and 49 contributed papers provide a comprehensive survey of the exciting advances driving the field forward and of the myriad of applications that will benefit from fNIRS.

Functional neuroimaging of migraine.

This review summarizes the history of migraine imaging and key findings of studies on functional neuroimaging in migraine and describes how these data have changed our view of the disorder. Functional neuroimaging during migraine attacks and also interictally has initiated the description of "the migraine brain". These studies have led to the demonstration of cortical spreading depression in migraine with aura, the crucial role for the brainstem during migraine attacks, and cortical hypersensitivity in migraineurs modulated by the trigeminal pathway, explaining sensory sensitization such as photophobia and osmophobia.

The myeloarchitectonic studies on the human cerebral cortex of the Vogt-Vogt school, and their significance for the interpretation of functional neuroimaging data.

The human cerebral cortex contains numerous myelinated fibres, many of which are concentrated in tangentially organized layers and radially oriented bundles. The spatial organization of these fibres is by no means homogeneous throughout the cortex. Local differences in the thickness and compactness of the fibre layers, and in the length and strength of the radial bundles renders it possible to recognize areas with a different myeloarchitecture. The neuroanatomical subdiscipline aimed at the identification and delineation of such areas is known as myeloarchitectonics. There is another, closely related neuroanatomical subdiscipline, named cytoarchitectonics. The aims and scope of this subdiscipline are the same as those of myeloarchitectonics, viz. parcellation. However, this subdiscipline focuses, as its name implies, on the size, shape and arrangement of the neuronal cell bodies in the cortex, rather than on the myelinated fibres. At the beginning of the twentieth century, two young investigators, Oskar and Cécile Vogt founded a centre for brain research, aimed to be devoted to the study of the (cyto + myelo) architecture of the cerebral cortex. The study of the cytoarchitecture was entrusted to their collaborator Korbinian Brodmann, who gained great fame with the creation of a cytoarchitectonic map of the human cerebral cortex. Here, we focus on the myeloarchitectonic studies on the cerebral cortex of the Vogt-Vogt school, because these studies are nearly forgotten in the present attempts to localize functional activations and to interprete findings in modern neuroimaging studies. Following introductory sections on the principles of myeloarchitectonics, and on the achievements of three myeloarchitectonic pioneers who did not belong to the Vogt-Vogt school, the pertinent literature is reviewed in some detail. These studies allow the conclusion that the human neocortex contains about 185 myeloarchitectonic areas, 70 frontal, 6 insular, 30 parietal, 19 occipital, and 60 temporal. It is emphasized that the data available, render it possible to compose a myeloarchitectonic map of the human neocortex, which is at least as reliable as any of the classic architectonic maps. During the realization of their myeloarchitectonic research program, in which numerous able collaborators were involved, the Vogts gradually developed a general concept of the organization of the cerebral cortex. The essence of this concept is that this structure is composed of about 200 distinct, juxtaposed 'Rindenfelder' or 'topistische Einheiten', which represent fundamental structural as well as functional entities. The second main part of this article is devoted to a discussion and evaluation of this 'Vogt-Vogt concept'. It is concluded that there is converging quantitative cytoarchitectonic, receptor architectonic, myeloarchitectonic, hodological, and functional evidence, indicating that this concept is essentially correct. The third, and final part of this article deals with the problem of relating particular cortical functions, as determined with neuroimaging techniques, to particular cortical structures. At present, these 'translation' operations are generally based on adapted, three-dimensional versions of Brodmann's famous map. However, it has become increasingly clear that these maps do not provide the neuroanatomical precision to match the considerable degree of functional segregation, suggested by neuroimaging studies. Therefore, we strongly recommend an attempt at combining and synthesizing the results of Brodmann's cytoarchitectonic analysis, with those of the detailed myeloarchitectonic studies of the Vogt-Vogt school. These studies may also be of interest for the interpretation of the myeloarchitectonic features, visualized in modern in vivo mappings of the human cortex.

The serendipitous discovery of the brain's default network.

One of the most unexpected findings by functional neuroimaging has been the discovery of the brain's default network - a set of brain regions that is spontaneously active during passive moments. The default network's discovery was a fortunate accident that occurred due to the inclusion of rest control conditions in early PET and functional MRI studies. At first, the network was ignored. Later, its presence was shunned as evidence of an experimental confound. Finally, it emerged as a mainstream target of focused study. Here, I describe a personal perspective of the default network's serendipitous discovery.