Difficulties with visual-spatial learning are frequently observed and often considered to be the hallmark of neurocognitive impairment in neurofibromatosis type 1. The computerized Arena Maze is a virtual environment task that has been developed as a human paradigm to the Morris Water Maze, which is used to evaluate spatial learning in animal models. The authors evaluated this task as a measure of spatial learning in children with neurofibromatosis type 1 compared with their unaffected siblings. Affected children were able to learn the task and navigate the virtual environment; however, they performed more poorly on standard measures of spatial learning and spatial working memory than their siblings. The group with neurofibromatosis type 1 demonstrated decreased proficiency in earlier target trials and had more difficulty in remembering target location. This study demonstrates the potential utility of a novel virtual task to assess spatial learning deficits in children with neurofibromatosis type 1.
National Institutes of Health Consensus Development Conference Statement: neurofibromatosis. Bethesda, Md., USA, July 13-15, 1987. Neurofibromatosis. 1988;1:172-178.
2.
Listernick R. , Charrow J.Neurofibromatosis type 1 in childhood. J Pediatr. 1990;116:845-853.
3.
Cutting LE, Koth CW, Denckla MBHow children with neurofibromatosis type 1 differ from ‘‘typical’’ learning disabled clinic attenders: nonverbal learning disabilities revisited . Dev Neuropsychol. 2000;17:29-47.
4.
Hyman SL, Shores A., North KNThe nature and frequency of cognitive deficits in children with neurofibromatosis type 1. Neurology. 2005;65:1037-1044.
5.
Hofman KJ, Harris EL, Bryan RN, Denckla MBNeurofibromatosis type 1: the cognitive phenotype. J Pediatr . 1994;124:S1-S8.
6.
Coude FX, Mignot C., Lyonnet S., Munnich A.Academic impairment is the most frequent complication of neurofibromatosis type-1 (NF1) in children. Behav Genet. 2006 ;11:1-5.
7.
Schrimsher GW , Billingsley RL, Slopis JM, Moore BD III.Visual-spatial performance deficits in children with neurofibromatosis type-1. Am J Med Genet A. 2003;120:326-330.
8.
Li C., Cheng Y., Gutmann DA, Mangoura D.Differential localization of the neurofibromatosis 1 (NF1) gene product, neurofibromin, with the F-actin or microtubule cytoskeleton during differentiation of telencephalic neurons. Brain Res Dev Brain Res. 2001;130:231-248.
9.
Shen MH, Harper PS, Upadhyaya M.Molecular genetics of neurofibromatosis type 1 (NF1). J Med Genet. 1996;33:2-17.
10.
Weiss B., Bollag G., Shannon K.Hyperactive Ras as a therapeutic target in neurofibromatosis type 1. Am J Med Genet. 1999;89: 14-22.
11.
Costa RM, Silva AJMolecular and cellular mechanisms underlying the cognitive deficits associated with neurofibromatosis 1. J Child Neurol. 2002;17:622-626; discussion 627-629, 646-651.
12.
Costa RM, Federov NB, Kogan JH, et al. Mechanism for the learning deficits in a mouse model of neurofibromatosis type 1. Nature. 2002;415:526-530.
13.
Li W., Cui Y., Kushner SA, et al. The HMG-CoA reductase inhibitor lovastatin reverses the learning and attention deficits in a mouse model of neurofibromatosis type 1. Curr Biol. 2005;15: 1961-1967.
14.
Kallai J., Makany T., Karadi K., Jacobs WJSpatial orientation strategies in Morris-type virtual water task for humans . Behav Brain Res. 2005;159:187-196.
15.
Thomas KG, Hsu M., Laurance HE, Nadel L., Jacobs WJPlace learning in virtual space: III. Investigation of spatial navigation training procedures and their application to fMRI and clinical neuropsychology . Behav Res Methods Instrum Comput. 2001; 33:21-37.
16.
Astur RS, Taylor LB, Mamelak AN, Philpott L., Sutherland RJHumans with hippocampus damage display severe spatial memory impairments in a virtual Morris water task. Behav Brain Res. 2002;132:77-84.
17.
Skelton RW, Bukach CM, Laurance HE, Thomas KG, Jacobs JWHumans with traumatic brain injuries show place-learning deficits in computer-generated virtual space. J Clin Exp Neuropsychol. 2000 ;22:157-175.
18.
Laurance HE , Learmonth AE, Nadel L., Jacobs WJMaturation of spatial navigation: convergent findings from computerized spatial environments and self-report. J Cogn Dev. 2003;4:211-238.
19.
Paquier PF, van Mourik M., Van Dongen HR, Catsman-Berrevoets CE, Creten WL, Stronks DLClinical utility of the judgment of line orientation test and facial recognition test in children with acquired unilateral cerebral lesions. J Child Neurol. 1999;14:243-248.
20.
Woodard JL, Benedict RH, Salthouse TA, Toth JP, Zgaljardic DJ, Hancock HENormative data for equivalent, parallel forms of the Judgment of Line Orientation Test. J Clin Exp Neuropsychol. 1998;20:457-462.
21.
De Luca CR, Wood SJ, Anderson V., et al. Normative data from the CANTAB. I: development of executive function over the lifespan. J Clin Exp Neuropsychol. 2003;25:242-254.
22.
Clark CR, Paul RH, Williams LM, et al. Standardized assessment of cognitive functioning during development and aging using an automated touchscreen battery. Arch Clin Neuropsychol. 2006; 21:449-467.
23.
Mayes SD, Calhoun SLWISC-IV and WISC-III profiles in children with ADHD. J Atten Disord. 2006;9:486-493.
24.
Needelman H. , Schnoes CJ, Ellis CRThe New WISC-IV. J Dev Behav Pediatr. 2006;27:127-128.
25.
Beebe DW, Ris MD, Dietrich KNThe relationship between CVLT-C process scores and measures of executive functioning: lack of support among community-dwelling adolescents. J Clin Exp Neuropsychol. 2000;22:779-792.
26.
McCandless S., O’Laughlin L.The clinical utility of the Behavior Rating Inventory of Executive Function (BRIEF) in the diagnosis of ADHD. J Atten Disord. 2007;10:381-389.
27.
Gioia GA, Isquith PKEcological assessment of executive function in traumatic brain injury. Dev Neuropsychol. 2004;25:135-158.
28.
Cohen ML, Kelly PC, Atkinson AWParent, teacher, child: a trilateral approach to attention deficit disorder . Am J Dis Child. 1989;143:1229-1233.
29.
Wechsler D.Wechsler Intelligence Scale for Children. 4th ed. San Antonio, TX: Harcourt Brace Jovanovich ; 2003.
30.
North K., Joy P., Yuille D., Cocks N., Hutchins P.Cognitive function and academic performance in children with neurofibromatosis type 1. Dev Med Child Neurol. 1995;37:427-436.
31.
Hyman SL, Arthur Shores E., North KNLearning disabilities in children with neurofibromatosis type 1: subtypes, cognitive profile, and attention-deficit-hyperactivity disorder. Dev Med Child Neurol. 2006;48:973-977.
32.
Koth CW, Cutting LE, Denckla MBThe association of neurofibromatosis type 1 and attention deficit hyperactivity disorder. Child Neuropsychol. 2000;6:185-194.
33.
Moore BD III , Ater JL , Needle MN, Slopis J., Copeland DRNeuropsychological profile of children with neurofibromatosis, brain tumor, or both. J Child Neurol. 1994;9:368-377.
34.
North K.Neurofibromatosis type 1: review of the first 200 patients in anAustralian clinic. J Child Neurol. 1993;8:395-402.
35.
North K., Joy P., Yuille D., et al. Specific learning disability in children with neurofibromatosis type 1: significance of MRI abnormalities. Neurology. 1994;44:878-883.
36.
Eliason MJNeurofibromatosis: implications for learning and behavior. J Dev Behav Pediatr. 1986;7:175-179.
37.
Joy P., Roberts C., North K., de Silva M.Neuropsychological function and MRI abnormalities in neurofibromatosis type 1. Dev Med Child Neurol. 1995;37:906-914.
38.
Rizzo AA, Cohen I., Weiss PL, et al. Design and development of virtual reality based perceptual-motor rehabilitation scenarios. Conf Proc IEEE Eng Med Biol Soc . 2004;7: 4852-4855.
