Broad Anatomical Regions Patient Control Comparisons

Figure 1 Evolution of brain Imaging studies of visceral perception.

pairwise associations. This bivariate correlational technique can be labeled functional connectivity analysis and can show important relationships between separate regions, but does not allow for directly testing the nature of these associations over time or across conditions, provides no information on how these associations may come about, and permits only rudimentary inferences regarding the characterization of neural networks. Effective connectivity analyses, on the other hand, employ sophisticated multivariate techniques such as partial least squares (84,85), principal components analysis (86), and structural equation modeling (86). These covariance-based methods permit examination of integrated neural systems (86), as well as the identification of spatial and temporal clustering of neuroimaging data. Thus, unlike its functional counterpart, effective connectivity analysis incorporates anatomical connections and considers neural interactions simultaneously to quantify explicitly the effect brain structures exert on one another in a network and provides a means to test theories regarding neural networks (87). A very simplified example of connectivity analysis is the structural equation model testing corticolimbic pontine interactions operating during noxious visceral stimulation discussed above (59). In this example, three brain regions were simultaneously examined for direct and indirect connections leading to increased activity in the dorsal brain stem and potentially increased descending pain-inhibitory action.

Shown is a schematic illustrating the evolution from the earlier, purely descriptive studies to hypothesis-driven designs and toward novel application of imaging technology and analysis.

Much more sophisticated connectivity analyses that include a much larger set of highly specific brain regions are now becoming possible and they go hand-in-hand with other advances in brain imaging, including increased spatial and temporal scanner resolution (36), use of radioligand tracers specific to molecules of interest (52), and the application of genetic analyses related to the development of specific brain circuitry (88). These new analytical tools should yield important breakthroughs in our understanding of central processes related to the pathophysiology of visceral pain disorders.

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