Basis For Functional Specialization Research Articles

Functional anatomy of the human brain

Attempts to understand the varied structure–function relationships within the human brain have a long history. Through the use of a variety of techniques, including analysis of behavioural and cognitive change due to brain injury and a variety of cytological staining techniques, functional maps of the brain have been built up over many years, providing the neuroanatomical basis for functional specialization of the cerebral cortex and other brain structures. In the 1980s, positron emission tomography (PET), which measures function-related changes in regional cerebral blood flow, closely followed in the early 1990s by functional magnetic resonance imaging (fMRI), which measures blood-oxygen level-dependent signals, revolutionized the field. These techniques brought non-invasive high-spatial-resolution approaches to brain structure–function studies for the first time, enabling measurement of region-specific changes of brain activity correlated with particular cognitive, motor or sensory tasks. The three reviews that follow illustrate the extraordinarily wide spectrum of research that has been stimulated by the new neuroimaging techniques. Karl Zilles shows how the detailed architectonic maps that have been built up by means of cell body- or myelin-staining techniques are incompatible in important respects with the new data arising from fMRI studies. He describes in exquisite detail the regional and laminar distribution within the human cerebral cortex of various transmitter receptors, signalling molecules that play crucial roles in cortical functions. Their regional organization is clearly more relevant to the new fMRI-based insights than the cytoarchitectonic observations on which cortical maps have previously been based. Although neuroanatomical maps provide the basis for understanding the location of different brain functions, it is clear that the human brain is a dynamic structure with considerable ability to maintain and recover cognitive functions after focal cortical damage. This resilience suggests that there may not be a one-to-one mapping between neuronal structures and cognitive functions, and that multiple neuronal systems might be capable of producing the same behavioural response. Uta Noppeney, Karl Friston and Cathy Price describe how fMRI can be used to explore structure–function relationships in terms of neuronal mechanisms that can mediate behavioural compensation after focal cortical damage. Finally, Klaas Stephan argues that classical approaches towards brain structure–function relationships are not sufficient to provide an understanding of the operational principles of a dynamic system such as the brain but must be complemented by models based on general system theory. Although this approach essentially relates functional neuroimaging to computational neuroscience, the article provides helpful insights that are accessible to the non-mathematician. Neural systems models of the type introduced here may in due course provide sufficiently sensitive diagnostic tools to discriminate between different forms of closely related psychological disorders. These three articles arise from a symposium of the Anatomical Society of Great Britain and Ireland entitled ‘Functional anatomy of the human brain’, held in London in January 2004. A second group of reviews from this symposium will follow in a future issue of the Journal.

Metabolism and function of coenzyme Q

Coenzyme Q (CoQ) is present in all cells and membranes and in addition to be a member of the mitochondrial respiratory chain it has also several other functions of great importance for the cellular metabolism. This review summarizes the findings available to day concerning CoQ distribution, biosynthesis, regulatory modifications and its participation in cellular metabolism. There are a number of indications that this lipid is not always functioning by its direct presence at the site of action but also using e.g. receptor expression modifications, signal transduction mechanisms and action through its metabolites. The biosynthesis of CoQ is studied in great detail in bacteria and yeast but only to a limited extent in animal tissues and therefore the informations available is restricted. However, it is known that the CoQ is compartmentalized in the cell with multiple sites of biosynthesis, breakdown and regulation which is the basis of functional specialization. Some regulatory mechanisms concerning amount and biosynthesis are established and nuclear transcription factors are partly identified in this process. Using appropriate ligands of nuclear receptors the biosynthetic rate can be increased in experimental system which raises the possibility of drug-induced upregulation of the lipid in deficiency. During aging and pathophysiological conditions the tissue concentration of CoQ is modified which influences cellular functions. In this case the extent of disturbances is dependent on the localizaion and the modified distribution of the lipid at cellular and membrane levels.