Registration is not as simple as equating the origin of similar coordinate systems, Rather, registration must accommodate a diversity of atlas types, spatial scales, and extents of coverage, Registration is also needed to compare one brain atlas with another, The success of any brain atlas depends on how well the anatomies of individual subjects match the representation of anatomy in the atlas, Although registration can bring the individual into correspondence with the atlas, and a common coordinate system enables the pooling of activation data and multisubject comparisons, the accuracy and utility of the atlas are equally dependent on the anatomical template itself [84], The Talairach templates were based on post mortem sections of a 60-year-old female subject's brain, which clearly did not reflect the in vivo anatomy of subjects in activation studies, The atlas plates were also compromised by having a variable slice separation (3 to 4 mm), and data from orthogonal planes were inconsistent, To address these limitations, a composite MRI dataset was constructed from several hundred young normal subjects (239 males, 66 females; age: 23,4 + 4,1 yrs) whose scans were individually registered into the Talairach system by linear transformation, intensity normalized, and averaged on a voxel-by-voxel basis [31,32], Although the resulting average brain has regions where individual structures are blurred out because of spatial variability in the population [31,32], the effect of anatomical variability in different brain areas is illustrated qualitatively by this map. Meanwhile, automated methods were rapidly being developed to register new MRI and PET data into a common space. These algorithms could be used to optimally align new MR data with the template by maximizing a measure of intensity similarity, such as 3D cross-correlation [17,18,19], ratio image uniformity [131], or mutual information [127,130]. Any alignment transformation defined for one modality, such as MRI, can be identically applied to another modality, such as PET, if a previous cross-modality intrasubject registration has been performed [132]. For the first time then, PET data could be mapped into stereotaxic space via a correlated MR dataset [32,132]. Registration algorithms therefore made it feasible to automatically map data from a variety of modalities into an atlas coordinate space based directly on the Talairach reference system.

transformation to a common 3D coordinate space, is only valid if homologous cortical regions in different subjects have been brought into register by spatial normalization transformation. Extreme variations in cortical patterns, observed in normal subjects and exacerbated in disease states by additional pathologic influence, suggest that caution is necessary in selecting the transformation system to support cross-subject and cross-group comparisons of cortically based observations or functional maps. The most severe challenge occurs when the topology itself is undergoing considerable dynamic change because of development or degeneration, for example. Direct digital subtraction of stereotaxic functional maps in studies of disease states, such as dementia, may lead to spurious results: maps of apparent significance may reflect differences that are anatomic, rather than functional, in character [66,133]. These difficulties have led to the suggestion that direct reference to the sulci that frame architectonic fields may present a more reliable basis for functional mapping than reference to a single standard or idealized brain [82,98,106,112,114,129].

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