Integrating Imaging and Genetics in Cognitive Research May 8th - 11th, 2007 Amsterdam, the Netherlands

Scientific Background

Great technological and theoretical progress has been made over the last decades in two separate areas of research on individual differences in human cognition: brain imaging and genetics.

In brain imaging, new tools have been developed to map differences in cognitive abilities to structural differences in gray and white matter (Hulshoff Pol et al., 2006; Posthuma et al., 2002; Thompson et al., 2001) and, more recently, to developmental trajectories of brain growth (Shaw et al., 2006). In parallel, functional imaging in subjects with schizophrenia, autism, and ADHD has been used to test how the affected brain responds to various cognitive demands, and how this response differs from that of the unaffected brain (e.g. Egan et al., 2001; Meyer-Lindenbergh et al., 2005).
In human genetics, recent attempts to explain the molecular genetic basis of cognitive ability have yielded promising genomic loci (Butcher et al., 2005; Buyske et al., 2006; Dick et al., 2006; Luciano et al., 2006; Posthuma et al., 2005; Wainwright et al., 2006). Building on the fruits of the Human Genome Project already a number of candidate genes have been successfully associated with cognitive traits (e.g. Burdick et al., 2006; Gosso et al., 2006a,b; Harris et al., 2006; Tsai et al., 2004).
With a few exciting exceptions, these two fields – imaging and genetics – have operated largely independently. As discussed above, the exceptions, where subjects are submitted to MRI measurements after being genotyped on candidate genes, have been unanimously successful. Weinberger and colleagues have shown how genetic variation in the COMT and BDNF genes is directly associated with variation in brain activity during working memory and attentional control and episodic memory tasks respectively (Blasi et al, 2005; Egan et al, 2003; Goldberg & Weinberger, 2004). Likewise Hariri and others (Hariri et al, 2002; Pezawas et al., 2005; Canli et al., 2006) have shown how the 5HTTLPR genotype modulates amygdalar and prefrontal processing of emotional stimuli. These studies clearly demonstrate that integration of imaging with genetics (i.e. Imaging Genomics) is beneficial to cognitive neuroscience: pinpointing genes helps understand the neurobiological pathways underlying individual differences in (ab)normal brain functioning, whereas the use of brain imaging greatly increases the power of genetic association studies.

The main goal of this Advance Study Initiative, therefore, is to stimulate increased collaboration between ‘brain imagers’ and ‘geneticists’ working in the area of cognitive neuroscience.

  • Blasi G, Mattay VS, Bertolino A, Elvevag B, Callicott JH, Das S, Kolachana BS, Egan MF, Goldberg TE, Weinberger DR. Effect of catechol-O-methyltransferase val158met genotype on attentional control. J Neurosci. 2005, 25(20):5038-45.
  • Burdick KE, Lencz T, Funke B, Finn et al. Genetic variation in DTNBP1 influences general cognitive ability. Hum Mol Genet. 2006, 15(10):1563-8.
  • Butcher LM, Meaburn E, Knight J et al: Snps, microarrays and pooled DNA: identification of four loci associated with mild mental impairment in a sample of 6000 children. Hum Mol Genet 2005; 14: 1315– 1325.
  • Buyske, S., Bates, M.E., Gharani, et al. (2006). Cognitive Traits Link to Human Chromosomal Regions. Behav Genet, 36:65-76
  • Canli T, Qiu M, Omura K, et al. Neural correlates of epigenesis. Proc Natl Acad Sci U S A. 2006, 103(43):16033-8.
  • Dick, D.M., Aliev, F., Bierut, L., et al. Linkage Analyses of IQ in the Collaborative Study on the Genetics of Alcoholism (COGA) Sample. Behav Genet. 2006, 36, 77-86
  • Egan MF, Goldberg TE, Kolachana BS et al. Effect of COMT Val108/158Met genotype on frontal lobe function and risk for schizophrenia. Proc Natl Acad Sci USA 2001; 98: 6917–22
  • Egan MF, Kojima M, Callicott JH, Goldberg TE, Kolachana BS, Bertolino A, Zaitsev E, Gold B, Goldman D, Dean M, Lu B, Weinberger DR. The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell. 2003, 112(2):257-69.
  • Goldberg TE, Weinberger DR. Genes and the parsing of cognitive processes. Trends Cogn Sci. 2004, 8(7):325-35.
  • Gosso MF, de Geus EJC, van Belzen MJ, et al.The SNAP-25 gene is associated with cognitive ability: Evidence from a family based study in two independent Dutch cohorts. Mol Psychiat. 2006a 11(9):878-886
  • Gosso, M.F., van Belzen, M., de Geus, E.J.C. et al.Family based association testing provides further evidence for a role of the CHRM2 gene in cognition. Genes Brain Behavior. 2006b, 5(8), 577-584.
  • Hariri AR, Mattay VS, Tessitore A, Kolachana B, Fera F, Goldman D, Egan MF, and Weinberger DR. Serotonin Transporter Genetic Variation and the Response of the Human Amygdala. Science 2002 297: 400-403
  • Harris, S. E., Fox, H., Wright, A. F., Hayward, C., Starr, J. M., Whalley, L. J., & Deary, I. J. (2006). The brain derived neurotrophic factor polymorphism is associated with age-related change in reasoning skills. Molecular Psychiatry, 11, 505-513.
  • Hulshoff Pol HE, Schnack HG, Posthuma D, et al. A genetic neural network involved in human intelligence. Journal of Neuroscience. 2006, 26(40):10235-42
  • Luciano M, Wright MJ Duffy MA et al (2006). Genome-wide scan of IQ finds significant linkage to a quantitative trait locus on 2q. Behav Genet, 36(1):45-55
  • Meyer-Lindenberg AS, Olsen RK, Kohn PD, et al. (2005). Regionally specific disturbance of dorsolateral prefrontal-hippocampal functional connectivity in schizophrenia. Arch Gen Psychiatry. 62(4):379-86.
  • Pezawas L, Meyer-Lindenberg A, Drabant EM. Et al. 5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression. Nat Neurosci. 2005, 8(6):828-34.
  • Posthuma D, De Geus EJ, Baare WF, Hulshoff Pol HE, Kahn RS, Boomsma DI: The association between brain volume and intelligence is of genetic origin. Nat Neurosci 2002; 5: 83–84.
  • Posthuma D, Luciano M, Geus EJ et al: A genomewide scan for intelligence identifies quantitative trait loci on 2q and 6p. Am J Hum Genet 2005; 77: 318– 326.
  • Shaw P, Greenstein D, Lerch J, et al Intellectual ability and cortical development in children and adolescents. Nature. 2006, 440(7084):676-9.
  • Thompson PM, Cannon TD, Narr KL, et al. Genetic influences on brain structure. Nat Neurosci. 2001, 4(12):1253-8.
  • Tsai SJ, Hong CJ, Yu YW, Chen TJ: Association study of a brainderived neurotrophic factor (BDNF) val66met polymorphism and personality trait and intelligence in healthy young females. Neuropsychobiology 2004; 49: 13– 16.
  • Wainwright, M.A., Wright, M.J., Luciano, M., Montgomery, G.W., Geffen, G.M., & Martin, N.G. A Linkage Study of Academic Skills Defined by the Queensland Core Skills Test. Behav Genet. 2006, 36, 56-64.