Abnormal Brain Activation in Neurofibromatosis Type 1: A Link between Visual Processing and the Default Mode Network

Visual Neuroscience Laboratory, Institute of Biomedical Research in Light and Image, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
PLoS ONE (Impact Factor: 3.53). 06/2012; 7(6):e38785. DOI: 10.1371/journal.pone.0038785
Source: PubMed

ABSTRACT Neurofibromatosis type 1 (NF1) is one of the most common single gene disorders affecting the human nervous system with a high incidence of cognitive deficits, particularly visuospatial. Nevertheless, neurophysiological alterations in low-level visual processing that could be relevant to explain the cognitive phenotype are poorly understood. Here we used functional magnetic resonance imaging (fMRI) to study early cortical visual pathways in children and adults with NF1. We employed two distinct stimulus types differing in contrast and spatial and temporal frequencies to evoke relatively different activation of the magnocellular (M) and parvocellular (P) pathways. Hemodynamic responses were investigated in retinotopically-defined regions V1, V2 and V3 and then over the acquired cortical volume. Relative to matched control subjects, patients with NF1 showed deficient activation of the low-level visual cortex to both stimulus types. Importantly, this finding was observed for children and adults with NF1, indicating that low-level visual processing deficits do not ameliorate with age. Moreover, only during M-biased stimulation patients with NF1 failed to deactivate or even activated anterior and posterior midline regions of the default mode network. The observation that the magnocellular visual pathway is impaired in NF1 in early visual processing and is specifically associated with a deficient deactivation of the default mode network may provide a neural explanation for high-order cognitive deficits present in NF1, particularly visuospatial and attentional. A link between magnocellular and default mode network processing may generalize to neuropsychiatric disorders where such deficits have been separately identified.

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Available from: Ines Bernardino, Aug 21, 2015
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    • "This is the only in vivo tool capable of non-invasively measuring brain metabolites. Magnetic resonance spectroscopy measurements were performed in early visual cortex, an area where the role of inhibition has been widely studied and where we previously found evidence for functional alterations (Ribeiro et al., 2012; Violante et al., 2012). Moreover, it has recently been shown that GABA concentration in the human visual cortex is significantly related to performance levels in visual perceptual tasks assessing orientation-specific surround suppression (Yoon et al., 2010) and orientation discrimination performance (Edden et al., 2009). "
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    ABSTRACT: Alterations in the balance between excitatory and inhibitory neurotransmission have been implicated in several neurodevelopmental disorders. Neurofibromatosis type 1 is one of the most common monogenic disorders causing cognitive deficits for which studies on a mouse model (Nfl(+/-)) proposed increased γ-aminobutyric acid-mediated inhibitory neurotransmission as the neural mechanism underlying these deficits. To test whether a similar mechanism translates to the human disorder, we used magnetic resonance spectroscopy to measure γ-aminobutyric acid levels in the visual cortex of children and adolescents with neurofibromatosis type 1 (n = 20) and matched control subjects (n = 26). We found that patients with neurofibromatosis type 1 have significantly lower γ-aminobutyric acid levels than control subjects, and that neurofibromatosis type 1 mutation type significantly predicted cortical γ-aminobutyric acid. Moreover, functional imaging of the visual cortex indicated that blood oxygen level-dependent signal was correlated with γ-aminobutyric acid levels both in patients and control subjects. Our results provide in vivo evidence of γ-aminobutyric acidergic dysfunction in neurofibromatosis type 1 by showing a reduction in γ-aminobutyric acid levels in human patients. This finding is relevant to understand the physiological profile of the disorder and has implications for the identification of targets for therapeutic strategies.
    Brain 03/2013; 136(Pt 3):918-25. DOI:10.1093/brain/aws368 · 10.23 Impact Factor
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    Journal of Neurodevelopmental Disorders 02/2013; 5(1):3. DOI:10.1186/1866-1955-5-3 · 3.71 Impact Factor
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