Skip to main content
Log in

Impaired engagement of the ventral attention system in neurofibromatosis type 1

  • Original Research
  • Published:
Brain Imaging and Behavior Aims and scope Submit manuscript

Abstract

Individuals with neurofibromatosis type 1 (NF1) exhibit significant impairments in attention across multiple domains. Very little is known about the contributing neural networks. We used task-based functional magnetic resonance imaging (fMRI) to examine dorsal and ventral attention networks during auditory oddball processing in children and adolescents with NF1 and typically developing controls. Significant differences in neural activation patterns were identified within brain regions supporting the ventral attention system. Children with NF1 demonstrated hypoactivation in the temporoparietal junction and the anterior cingulate cortex compared to typically developing children. Hypoactivation in the anterior cingulate cortex was associated with poorer selective attention and attentional control in children with NF1. Results indicate an abnormality in bottom-up attention networks in NF1 that may lead to inefficient and faulty suppression of stimulus-driven information outside the current attentional set that play a significant role in the NF1 behavioral phenotype.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Adviento, B., Corbin, I. L., Widjaja, F., Desachy, G., Enrique, N., Rosser, T., et al. (2014). Autism traits in the RASopathies. Journal of Medical Genetics, 51(1), 10–20.

    Article  CAS  PubMed  Google Scholar 

  • Ashburner, J. (2007). A fast diffeomorphic image registration algorithm. NeuroImage, 38(1), 95–113.

    Article  PubMed  Google Scholar 

  • Barton, B., & North, K. (2004). Social skills of children with neurofibromatosis type 1. Developmental Medicine & Child Neurology, 46(8), 553–563.

    Article  Google Scholar 

  • Billingsley, R. L., Jackson, E. F., Slopis, J. M., Swank, P. R., Mahankali, S., & Moore, B. D. (2003). Functional magnetic resonance imaging of phonologic processing in neurofibromatosis 1. Journal of Child Neurology, 18, 731–740.

    Article  PubMed  Google Scholar 

  • Billingsley, R. L., Jackson, E. F., Slopis, J. M., Swank, P. R., Mahankali, S., & Moore, B. D. (2004). Functional MRI of visual-spatial processing in neurofibromatosis, type I. Neuropsychologia, 42(3), 395–404.

    Article  PubMed  Google Scholar 

  • Bressler, S. L., & Menon, V. (2010). Large-scale brain networks in cognition: Emerging methods and principles. Trends in Cognitive Science, 14, 277–290.

    Article  Google Scholar 

  • Brown, J. A., Xu, J., Diggs-Andrews, K. A., Wozniak, D. F., Mach, R. H., & Gutmann, D. H. (2011). PET imaging for attention deficit preclinical drug testing in neurofibromatosis- 1 mice. Experimental Neurology, 232, 333–338.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bush, G., Luu, P., Posner, M. I. (2000). Cognitive and emotional influences in anterior cingulate cortex. Trends in Cognitive Sciences, 4(6), 215–222.

  • Chabernaud, C., Mennes, C., Kardel, P. G., Gaillard, W. D., Kalbfleisch, M. L., VanMeter, J. W., et al. (2012). Lovastatin regulates brain spontaneous low-frequency brain activity in Neurofibromatosis type 1. Neuroscience Letters, 515(28–33).

  • Conners, C. K. (2008). Conners 3rd Edition parent assessment long form. Toronto, Ontario: Multi-Health Systems Inc..

    Google Scholar 

  • Corbetta, M., Patel, G., & Shulman, G. L. (2008). The reorienting system of the human brain: From environment to theory of mind. Neuron, 58(3), 306–324.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Corbetta, M., & Shulman, G. L. (2002). Control of goal-directed and stimulus driven attention in the brain. Nature Reviews Neuroscience, 3, 201–215.

    Article  CAS  PubMed  Google Scholar 

  • Cortese, S., Kelly, C., Chabernaud, C., Proal, E., Di Martino, A., Milham, M. P., et al. (2012). Toward systems neuroscience of ADHD: A meta-analysis of 55 fMRI studies. American Journal of Psychiatry, 169, 1038–1055.

    Article  PubMed  Google Scholar 

  • Crottaz-Herbette, S., & Menon, V. (2006). Where and when the anterior cingulate cortex modulates attentional response: Combined fMRI and ERP evidence. Journal of Cognitive Neuroscience, 18(5), 766–780.

    Article  CAS  PubMed  Google Scholar 

  • Debener, S., Kranczioch, C., Herrmann, C. S., & Engel, A. K. (2002). Auditory oddball allows reliable distinction of top-down and bottom-up processes of attention. International Journal of Psychophysiology, 46, 77–84.

    Article  CAS  PubMed  Google Scholar 

  • Dichter, G. S., Felder, J. N., & Bodwish, J. W. (2009). Autism is charactersied by dorsal anterior cingulate hyperactivation during social target detection. Scan, 4, 215–226.

    PubMed  PubMed Central  Google Scholar 

  • Diggs-Andrews, K. A., & Gutmann, D. H. (2013). Modeling cognitive dysfunction in neurofibromatosis-1. Trends in Neuroscience, 36(4), 237–247.

    Article  CAS  Google Scholar 

  • Evans, A. C., & Group., B. D. C. (2006). The NIH MRI study of normal brain development. NeuroImage, 30(1), 184–202.

    Article  Google Scholar 

  • Evans, G., Howard, E., Giblin, C., Clancy, T., Spencer, H., Huson, S. M., et al. (2010). Birth incidence and prevalence of tumour-prone syndromes: Estimates from a UK family register service. American Journal of Medical Genetics Part A, 152A, 327–332.

    Article  CAS  PubMed  Google Scholar 

  • Ferner, R. E., Hughes, R. A., & Weinman, J. (1996). Intellectual impairment in neurofibromatosis 1. Journal of the Neurological Sciences, 138(1–2), 125–133.

    Article  CAS  PubMed  Google Scholar 

  • Fox, M. D., Snyder, A. Z., Vincent, J. L., Corbetta, M., Van Essen, D., & Raichle, M. (2005). The human brain is intrinsically organised into dynamic anticorrelated functional networks. Proceedings of the National Academy of Sciences, 102, 9673–9678.

    Article  CAS  Google Scholar 

  • Garg, S., Green, J., Leadbitter, K., Emsley, R., Lehtonen, A., Evans, D. G., et al. (2013a). Neurofibromatosis type 1 and autism spectrum disorder. Paediatrics, 132(6). doi:10.1542/peds.2013-1868.

  • Garg, S., Lehtonen, A., Huson, S. M., Emsley, R., Trump, D., Evans, D. G., et al. (2013b). Autism and other psychiatric comorbidity in neurofibromatosis type 1: Evidence from a population-based study. Developmental Medicine & Child Neurology, 55(2), 139–145.

    Article  Google Scholar 

  • Gomot, M., Bernard, F. A., Davis, M. H., Belmonte, M. K., Ashwin, C., Bullmore, E. T., et al. (2005). Change detection in children with autism: An auditory event-related fMRI study. NeuroImage, 29, 475–484.

    Article  PubMed  Google Scholar 

  • Helenius, P., Laasonen, M., Hokkanen, L., Paetau, R., & Niemivirta, M. (2011). Impaired engagement of the ventral attentional pathway in ADHD. Neuropsychologia, 49, 1889–1896.

    Article  PubMed  Google Scholar 

  • Hofman, K. J., Harris, E. L., Bryan, R. N., & Denckla, M. B. (1994). Neurofibromatosis type 1: The cognitive phenotype. The Journal of Pediatrics, 124(4), S1–S8.

    Article  CAS  PubMed  Google Scholar 

  • Huijbregts, S., Jahja, R., De Sonneville, L., de Breij, S., Swaab-Barneveld, H. (2010). Social information processing in children and adolescents with neurofibromatosis type 1. Developmental Medicine & Child Neurology, 52(7), 620–625

  • Hyman, S. L., Shores, A., & North, K. (2005). The nature and frequency of cognitive deficits in children with neurofibromatosis type 1. Neurology, 65(7), 1037–1044.

    Article  PubMed  Google Scholar 

  • IBM Corp. Released 2012. IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp.

  • Joy, P., Roberts, C., North, K., & de Silva, M. (1995). Neuropsychological function and MRI abnormalities in neurofibromatosis type 1. Developmental Medicine and Child Neurology, 37(10), 906–914.

    Article  CAS  PubMed  Google Scholar 

  • Karlsgodt, K. H., Rosser, T., Lutkenhoff, E. S., Cannon, T. D., Silva, A. J., & Bearden, C. E. (2012). Alterations in white matter microstructure in neurofibromatosis-1. PloS One, 7(10).

  • Keehn, B., Nair, A., Lincoln, A. J., Townsend, J., & Muller, R. A. (2016). Under-reactive but easily distracted: An fMRI investigation of attentional capture in autism spectrum disorder. Developmental Cognitive Neuroscience, 17, 46–56.

    Article  PubMed  Google Scholar 

  • Kim, H. (2014). Involvement of the dorsal and ventral attention networks in oddball stimulus processing: A meta-analysis. Human Brain Mapping, 35, 2265–2284.

    Article  PubMed  Google Scholar 

  • Koini, M., Rombouts, S. A. R. B., Veer, I. M., Van Buchem, M. A., & Huijbregts, S. C. J. (2016). White matter microstrucutre of patients with neurofibromatosis type 1 and its relation to inhibitory control. Brain Imaging and Behavior, 1–10. doi:10.1007/s11682-016-9641-3.

  • Korgaonkar, M. S., Grieve, S. M., Etkin, A., Koslow, S. H., & Williams, L. M. (2013). Using standardised fMRI protocols to identify patterns of prefrontal circuit dysregulation that are common and specific to cognitive and emotional tasks in major depressive disorder: First wave results from the iSPOT-D study. Neuropsychopharmacology, 38(5), 863–871.

    Article  PubMed  PubMed Central  Google Scholar 

  • Laird, A. R., Robinson, J. L., McMillian, K. M., Tordesillas-Gutierrez, D., Moran, S. T., Gonzales, S. M., et al. (2010). Comparison of the disparity between Talairach and MNI coordinates in functional neuroimaging data: Validation of the Lancaster transform. NeuroImage, 51, 677–683.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lehtonen, A., Howie, E., Trump, D., & Huson, S. M. (2013). Behaviour in children with neurofibromatosis type 1: Cognition, executive function, attention, emotion, and social competence. Developmental Medicine & Child Neurology, 55(2), 111–125.

    Article  Google Scholar 

  • Li, W., Cui, Y., Kushner, S. A., Brown, R. A., Jentsch, J. D., Frankland, P. W., et al. (2005). The HMG-CoA reductase inhibitor lovastatin reverses the learning and attention deficits in a mouse model of neurofibromatosis type 1. Current Biology, 15(21), 1961–1967.

    Article  CAS  PubMed  Google Scholar 

  • Manly, T., Robertson, I. H., Anderson, V., & Nimmo-Smith, I. (1999). The test of Everyday attention for children. London, England: Battley Brothers.

    Google Scholar 

  • Mascaluso, E. (2010). Orienting of spatial attention and the interplay between the senses. Cortex, 46, 282–297.

    Article  Google Scholar 

  • Mautner, V. F., Kluwe, L., Thakker, S. D., & Leark, R. A. (2002). Treatment of ADHD in neurofibromatosis type 1. Developmental Medicine and Child Neurology, 44(164–170).

  • Mazzocco, M. M. M., Turner, J. E., Denckla, M. B., Hofman, K. J., Scanlon, D. C., & Vellutino, F. R. (1995). Language and reading deficits associated with Neurofibromatosis type 1: Evidence for a not-so-nonverbal learning disability. Developmental Neuropsychology, 11(4), 503–522.

    Article  Google Scholar 

  • NIH. (1988). Neurofibromatosis conference statement. National Institutes of Health consensus development conference. Archives of Neurology, 45(5), 575–578.

    Article  Google Scholar 

  • Payne, J. M., Hyman, S. L., Shores, E. A., & North, K. (2011). Assessment of executive function and attention in children with neurofibromatosis type 1: Relationships between cognitive measures and real-world behavior. Child Neuropsychology, 17(4), 313–329.

    Article  PubMed  Google Scholar 

  • Pride, N. A., Korgaonkar, M. S., Barton, B., Payne, J. M., & North, K. N. (2013). The genetic and neuroanatomical basis of social dysfunction: Lessons from neurofibromatosis type 1. Human Brain Mapping, 35(5), 2372–2382.

    Article  PubMed  Google Scholar 

  • Pride, N. A., Payne, J. M., & North, K. N. (2012). The impact of ADHD on the cognitive and academic functioning of children with NF1. Developmental Neuropsychology, 37(7), 590–600.

    Article  PubMed  Google Scholar 

  • Rowbotham, I., Pit-ten Cate, I. M., Sonuga-Barke, E. J. S., & Huijbregts, S. C. J. (2009). Cognitive control in adolescents with neurofibromatosis type 1. Neuropsychology, 23(1), 50–60.

    Article  CAS  PubMed  Google Scholar 

  • Sangster, J., Shores, E. A., Watt, S., & North, K. (2011). The cognitive profile of preschool-aged children with neurofibromatosis type 1. Child Neuropsychology, 17(1), 1–16.

    Article  PubMed  Google Scholar 

  • Sestieri, C., Shulman, G. L., & Corbetta, M. (2012). Orienting to the environment: Separate contributions of dorsal and ventral fronto-parietal attention networks. In G. R. Mangun (Ed.), The neuroscience of attention: Attentional control and selection (pp. 100–130). New York: Oxford University Press.

    Chapter  Google Scholar 

  • Sheehan, D. V., Sheehan, K. H., Shytle, R. D., Janavs, J., Bannon, Y., Rogers, J. E., et al. (2010). Reliability and validity of the Mini international neuropsychiatric interview for children and adolescents (MINI-KID). Journal of Clinical Psychiatry, 71(3), 313–326.

    Article  PubMed  Google Scholar 

  • Shilyansky, C., Karlsgodt, K. H., Cummings, D. M., Sidiropoulou, K., Hardt, M., James, A. S., et al. (2010). Neurofibromin regulates corticostriatal inhibitory networks during working memory performance. Proceedings of the National Academy of Sciences, 107(29), 13141–13146.

    Article  CAS  Google Scholar 

  • Stevens, M. C., Pearlson, G. D., & Kiehl, K. A. (2007). An FMRI auditory oddball study of combined-subtype attention deficit hyperactivity disorder. American Journal of Psychiatry, 164(11), 1737–1749.

    Article  PubMed  Google Scholar 

  • Tomson, S. N., Schreiner, M. J., Narayan, M., Rosser, T., Enrique, N., Silva, A. J., et al. (2015). Resting state functional MRI reveals abnormal network connectivity in neurofibromatosis 1. Human Brain Mapp, 36, 4566–4581.

    Article  Google Scholar 

  • Violante, I. R., Ribeiro, M. J., Edden, A. E., Guimaraes, P., Bernardino, I., Rebola, J., et al. (2013). GABA deficit in the visual cortex of patients with neurofibromatosis type 1: Genotype-phenotype correlations and functional impact. Brain, 136, 918–925.

    Article  PubMed  Google Scholar 

  • Vossel, S., Geng, J. J., & Fink, G. R. (2014). Dorsal and ventral attention systems. The Neuroscientist, 20(2), 150–159.

    Article  PubMed  PubMed Central  Google Scholar 

  • Walsh, K., Valez, J., Kardel, P., Imas, D., Muenke, M., Packer, R., et al. (2013). Autism spectrum disorder (ASD) symptomatology in a neurofibromatosis type 1 (NF1) population. Developmental Medicine and Child Neurology, 55(2), 131–138.

    Article  PubMed  Google Scholar 

  • Wilke, M., Holland, S. K., Altaye, M., & Gaser, C. (2008). Template-O-Matic: A toolbox for creating customised paedaitric templates. NeuroImage, 41, 903–913.

    Article  PubMed  Google Scholar 

  • Wu, Q., Chang, C. F., Xi, S., Huan, W., Liu, Z., Juan, C. H., et al. (2015). A critical role of temporoparietal junction in the integration of top-down and bottom-up attentional control. Human Brain Mapping, 36(11), 4317–4333.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zoller, M. E., Rembeck, B., & Backman, L. (1997). Neuropsychological deficits in adults with neurofibromatosis type 1. Acta Neurologica Scandinavica, 95(4), 225–232.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Natalie A. Pride.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Electronic supplementary material

ESM 1

(PDF 220 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pride, N.A., Korgaonkar, M.S., North, K.N. et al. Impaired engagement of the ventral attention system in neurofibromatosis type 1. Brain Imaging and Behavior 12, 499–508 (2018). https://doi.org/10.1007/s11682-017-9717-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11682-017-9717-8

Keywords

Navigation