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Systems Phenomics

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Population Neuroscience

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Abstract

The molecular machinery described in the preceding three chapters represents both the blueprint (genes) and the mechanics (epigenetics, transcriptomics, proteomics) for the emergence of system-level phenotypes: the functional and structural properties of the human brain. As with any other biological system in our bodies, brain phenotypes arise from a combination of genetic and environmental influences, which are expressed via multiple molecular pathways throughout our lives. Ultimately, inter-individual variability in these structural and functional brain properties underlies differences between individuals in their behavioural traits. In this chapter, we will focus on the use of magnetic resonance imaging (MRI) for quantifying brain phenotypes. We will start with a few general comments about functional and structural brain imaging, explain the basic principles of MRI and then move on to describe various ways in which we can measure structural and functional brain phenotypes. Given our interest in the ultimate “product” of our brains, namely behaviour, we will also provide a brief overview of tools suitable for out-of-scanner assessment of cognitive abilities and mental health in population-based imaging studies.

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Notes

  1. 1.

    We use the term “behaviour” in a broad sense, encompassing not only observable actions but also cognition, emotions and mental health.

  2. 2.

    Voxel (or volumetric pixel) is a volume element of the (3D) MR image (pixels refer to picture elements of (2D) video images).

  3. 3.

    1.5 T equals 15,000 Gauss. For comparison, the Earth’s magnetic field is about 0.5 Gauss.

  4. 4.

    For hydrogen, this “resonant” frequency is about 64 MHz at 1.5 T.

  5. 5.

    The switching of the gradient coils generates the knocking noise heard during scanning.

  6. 6.

    Proton density refers to the number of hydrogen nuclei per unit of tissue volume.

  7. 7.

    Lattice is an array of points repeating periodically in three dimensions.

  8. 8.

    Individual hydrogen nuclei precess at slightly different rates, leading to their magnetic moments eventually pointing in different directions (“dephasing”).

  9. 9.

    MT imaging is used most often in patients with neurological disorders affecting white matter, such as multiple sclerosis (Filippi and Rocca 2007).

  10. 10.

    Let me explain the reason for quotation marks here. As pointed out in this section, it is unlikely that the BOLD signal reflects neural activity understood as neurons generating action potentials, that is, firing. For this reason, the term “activation” can be used only as a metaphor. For this reason, we prefer to use terms—such as “BOLD response” or “fMRI response”—that do not imply a particular neurophysiological process.

  11. 11.

    A vertex is a corner point of a polygon; polygons constitute a representation of a (cortical) surface.

  12. 12.

    The “prior” is shorthand for “a prior probability distribution”. In this context, the priors bring existing knowledge to assist a particular classification algorithm.

  13. 13.

    The target is usually a population average generated in a standardized (atlas) space.

  14. 14.

    The standard Hotelling T2 test is used to detect and characterize such differences (Davatzikos et al. 1996; Thompson and Toga 1997).

  15. 15.

    The Jacobian is the determinant of the Jacobian matrix, which characterizes spatial relationships between vectors in (the three-dimensional) Euclidean space.

  16. 16.

    Typically, one uses a standard two-sample t test of the log-Jacobian values to identify areas of significant local difference in volume between two populations.

  17. 17.

    Typically, we use r = 20 mm but our findings remain the same for r = 15 mm or r = 25 mm (Toro et al. 2008a).

  18. 18.

    Note that we are not interested here in the repeatability of average (group) “activation” maps.

  19. 19.

    The most common type of ICC used in this context is the third ICC (Shrout and Fleiss 1979).

  20. 20.

    The magnitude of the BOLD response is typically assessed in a particular contrast (difference) between two conditions.

  21. 21.

    Test–retest reliability: poor—ICCs <0.4; fair—0.4–0.75; excellent—>0.75 (Fleiss 1986).

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  1. Rotman Research Institute, Baycrest, Bathurst Street 3560, Toronto, ON, M6A 2E1, Canada

    Tomáš Paus

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Paus, T. (2013). Systems Phenomics. In: Population Neuroscience. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-36450-1_7

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