Objective: To compare children with Neurofibromatosis type 1 and associated ADHD symptomatology (NF1 + ADHD) with children having received a diagnosis of ADHD without NF1. The idea was that performance differences in tasks of attention between these two groups would be attributable not to the ADHD symptomatology, but to NF1 alone. Method: One group of children with NF1 + ADHD (N = 32), one group of children with ADHD (N = 31), and one group of healthy controls (N = 40) participated in a set of computerized tasks assessing intensive, selective, and executive aspects of attention. Results: Differences were found between the two groups of patients in respect of several aspects of attention. Children with NF1 + ADHD did not always perform worse than children with ADHD. Several double dissociations can be established between the two groups of patients. Conclusion: ADHD symptomatology in NF1 does not contribute to all attention deficits, and ADHD cannot account for all attention impairments in NF1.
AcostaM. T.GioiaG. A.SilvaA. J. (2006). Neurofibromatosis type 1: New insights into neurocognitive issues. Current Neurology & Neuroscience Reports, 6, 136-143.
2.
American Psychiatric Association. (1996). DSM-IV. Manuel diagnostique et statistique des troubles mentaux [Diagnostic and statistical manual of mental disorders: DSM-IV]. Paris, France: Masson.
3.
ArciaE.ConnersC. K. (1998). Gender differences in ADHD?Journal of Developmental & Behavioral Pediatrics, 19, 77-83.
4.
AronA. R. (2007). The neural basis of inhibition in cognitive control. Neuroscientist, 13, 214-228.
5.
AronA. R.PoldrackR. A. (2005). The cognitive neuroscience of response inhibition: Relevance for genetic research in attention-deficit/hyperactivity disorder. Biological Psychology, 57, 1285-1292.
6.
BarbeyA. K.ColomR.GrafmanJ. (2013). Architecture of cognitive flexibility revealed by lesion mapping. NeuroImage, 82, 547-554.
7.
BarkleyR. A. (1997). Behavioral inhibition, sustained attention, and executive functions: Constructing a unifying theory of ADHD. Psychological Bulletin, 121, 65-94.
8.
BartolomeoP.SiéroffE.ChokronS.DecaixC. (2001). Variability of response times as a marker of diverted attention. Neuropsychologia, 39, 358-363
9.
BartonBNorthK. (2004). Social kills of children with neurofibromatosis type 1. Developmental Medicine & Child Neurology, 46, 553-563.
10.
BokorG.AndersonP. D. (2014). Attention-deficit/hyperactivity disorder. Journal of Pharmacy Practice, 27, 336-349.
11.
BrownJ. A.EmnettR. J.WhiteC. R.YuedeC. M.ConyersS. B.O’MalleyK. L.. . . GutmannD. H. (2010). Reduced striatal dopamine underlies the attention system dysfunction in neurofibromatosis-1 mutant mice. Human Molecular Genetics, 19, 4515-4528.
12.
BushG. (2010). Attention-deficit/hyperactivity disorder and attention networks. Neuropsychopharmacology, 35, 278-300.
13.
BushG. (2011). Cingulate, frontal, and parietal cortical dysfunction in Attention-Deficit/Hyperactivity Disorder. Biological Psychiatry, 69, 1160-1167.
14.
CaoQ.ZangY.ZhuC.CaoX.SunL.ZhouX.WangY. (2008). Alerting deficits in children with attention deficit/hyperactivity disorder: Event-related fMRI evidence. Brain Research, 1219, 159-168.
15.
CastellanosF. X.ProalE. (2012). Large-scale brain systems in ADHD: Beyond the prefrontal-striatal model. Trends in Cognitive Sciences, 16, 17-26.
16.
ChambersC. D.GaravanH.BellgroveM. A. (2009). Insights into the neural basis of response inhibition from cognitive and clinical neuroscience. Neuroscience & Behavioral Reviews, 33, 631-646.
17.
ConnersC. K. (2001). Development of the CRS-R. In ConnersC. K. (Ed.), Conners’ Rating Scales-Revised (pp. 83-98). North Tonawanda, NY: Multi-Health Systems.
18.
ConnersC. K. (2002). Forty years of methylphenidate treatment in attention-deficit⁄hyperactivity disorder. Journal of Attention Disorders, 6, S17-S30.
19.
CorbettaM.ShulmanG. (2002). Control of goal-directed and stimulus-driven attention in the brain. Nature Reviews Neuroscience, 3, 201-215.
20.
CostaR. M.SilvaA. J. (2002). Molecular and cellular mechanisms underlying the cognitive deficits associated with neurofibromatosis 1. Journal of Child Neurology, 17, 622-626.
21.
CoudéF. X.MignotC.LyonnetS.MunnichA. (2006). Academic impairment is the most frequent complication of neurofibromatosis type-1 (NF1) in children. Behavioral Genetics, 36, 660-664.
22.
CoudéF. X.MignotC.LyonnetS.MunnichA. (2007). Early grade repetition and inattention associated with neurofibromatosis type 1. Journal of Attention Disorders, 11, 101-105.
23.
CuttingL. E.LevineT. M. (2010). Cognitive profile of children with neurofibromatosis and reading disabilities. Child Neuropsychology, 16, 417-432.
24.
del CampoN.FryerT. D.HongY. T.SmithR.BrichardL.Acosta-CabroneroJ.. . . MüllerU. (2013). A positron emission tomography study of nigro-striatal dopaminergic mechanisms underlying attention: Implications for ADHD and its treatment. Brain, 136, 3252-3270.
25.
DescheemaekerM. J.GhesquiereP.SymonsH.FrynsJ. P.LegiusE. (2005). Behavioural, academic and neuropsychological profile of normally gifted neurofibromatosis Type 1 children. Journal of Intellectual Disability Research, 49, 33-46.
26.
Diggs-AndrewsK. A.BrownJ. A.GianinoS. M.RubinJ. B.WozniakD. F.GutmannD. H. (2014). Sex is a major determinant of neuronal dysfunction in neurofibromatosis type 1. Annals of Neurology, 75, 309-316
27.
Diggs-AndrewsK. A.GutmannD. H. (2013). Modeling cognitive dysfunction in neurofibromatosis-1. Trends in Neuroscience, 36, 237-247.
28.
Diggs-AndrewsK. A.TokudaK.IzumiY.ZorumskiC. F.WozniakD. F.GutmannD. H. (2013). Dopamine deficiency underlies learning deficits in neurofibromatosis-1 mice. Annals of Neurology, 73, 309-315.
29.
FarrantB. M.FletcherJ.MayberyM. T. (2014). Cognitive flexibility, theory of mind, and Hyperactivity/Inattention. Child Development Research, 2014, Article ID 741543.
30.
FernerR. E.HughesR. A. C.WeinmanJ. (1996). Intellectual impairment in neurofibromatosis 1. Journal of the Neurological Sciences, 138, 125-133.
31.
FrankeB.NealeB. M.FaraoneS. V. (2009). Genome-wide association studies in ADHD. Human Genetics, 126, 13-50.
32.
GalassoC.Lo-CastroA.Di CarloL.PitziantiM. B.D’AgatiE.CuratoloP.PasiniA. (2014). Planning deficit in children with neurofibromatosis type 1: A neurocognitive trait independent from attention-deficit hyperactivity disorder (ADHD)?Journal of Child Neurology, 29, 1320-1326.
33.
GaymardB.LynchJ.PlonerC. J.CondyC.Rivaud-PéchouxS. (2003). The parieto-collicular pathway: Anatomical location and contribution to saccade generation. European Journal of Neuroscience, 17, 1518-1526.
34.
GaymardB.PlonerC. J.RivaudS.VermerschA. I.Pierrot-DeseillignyC. (1998). Cortical control of saccades. Experimental Brain Research, 123, 159-163.
35.
GershonJ. (2002). A meta-analytic review of gender differences in ADHD. Journal of Attention Disorders, 5, 143-154.
36.
GilboaY.RosenblumS.Fattal-ValevskiAToledano-AlhadefH.RizzoA.JosmanN. (2011). Using a virtual classroom environment to describe the attention deficits profile of children with neurofibromatosis type 1. Research in Developmental Disabilities, 32, 2608-2613.
37.
GreenD. M.SwetsJ. A. (1966). Signal detection theory and psychophysics. New York, NY: Wiley.
38.
GreenhillL. L.FindlingR. L.SwansonJ. M. (2002). A double-blind, placebo-controlled study of modified-release methylphenidate in children with attention-deficit/hyperactivity disorder. Pediatrics, 109, E39.
39.
GutmannD. H.AylsworthA.CareyJ. C.KorfB. R.MarksJ.PyeritzR. E.. . .ViskochilD. (1997). The diagnostic evaluation and multidisciplinary management of NF 1 and NF 2. Journal of the American Medical Association, 278, 51-57.
40.
GutmannD. H.ParadaL. F.SilvaA. J.RatnerN. (2012). Neurofibromatosis type 1: Modeling CNS dysfunction. The Journal of Neuroscience, 32, 14087-14093.
41.
HuijbregtsS. (2012). Cognitive-behavioral phenotype or comorbid disorder? The case of attention-deficit-hyperactivity disorder in neurofibromatosis type 1. Developmental Medicine & Child Neurology, 54, 873-874.
42.
HuijbregtsS. C.de SonnevilleL. M. (2011). Does cognitive impairment explain behavioral and social problems of children with neurofibromatosis type 1?Behavioral Genetics, 41, 430-436.
43.
HuijbregtsS.SwaabH.de SonnevilleL. (2010). Cognitive and motor control in neurofibromatosis type I: Influence of maturation and hyperactivity-inattention. Developmental Neuropsychology, 35, 737-751.
44.
HymanS.ArthurE.NorthK. N. (2006). Learning disabilities in children with neurofibromatosis Type 1: Subtypes, cognitive profile, and attention-deficit-hyperactivity disorder. Developmental Medicine & Child Neurology, 48, 973-977.
45.
HymanS. L.GillD.ShoresA.SteinbergA.NorthK. N. (2007). T2 hyperintensities in chilmdren with neurofibromatosis type 1 and their relationship to cognitive functioning. Journal of Neurology, Neurosurgery & Psychiatry, 78, 1088-1091.
46.
HymanS. L.ShoresA.NorthK. N. (2005). The nature and frequency of cognitive deficits in children with neurofibromatosis Type 1. Neurology, 65, 1037-1044.
47.
IsenbergJ.TemplerA.GaoF.TitusJ.GutmannD. (2013). Attention skills in children with Neurofibromatosis Type I. Journal of Child Neurology, 28, 45-49.
48.
KaufmannL.ZierenN.ZotterS.KarallD.Scholl-BürgiS.HaberlandtE.FimmB. (2010). Predictive validity of attentional functions in differentiating children with and without ADHD: A componential analysis. Developmental Medicine & Child Neurology, 52, 371-378.
49.
KirkebyB. S.RobinsonM. D. (2005). Impulsive behavior and stimulus–response variability in choice reaction time. Journal of Research in Personality, 39, 263-277.
50.
LaskerA. G.DencklaM. B.ZeeD. S. (2003). Ocular motor behavior of children with neurofibromatosis 1. Journal of Child Neurology, 18, 348-355.
51.
LehtonenA.HowieE.TrumpD.HusonS. M. (2012). Behaviour in children with neurofibromatosis type 1: Cognition, executive function, attention, emotion, and social competence. Developmental Medicine & Child Neurology, 55, 111-125.
52.
LidzbaK.GranstroemS.LearkR. A.Kraegeloh-MannI.MautnerV. F. (2014). Pharmacotherapy of attention deficit in neurofibromatosis type 1: Effects on cognition. Neuropediatrics, 45, 240-246.
53.
LidzbaK.GranströmS.LindenauJ.MautnerV.-F. (2012). The adverse influence of attention-deficit disorder with or without hyperactivity on cognition in neurofibromatosis type 1. Developmental Medicine & Child Neurology, 54, 892-897.
54.
Lion-FrançoisL.GueyffierF.MercierC.GérardD.HerbillonV.KemlinI.. . . KassaïB. (2014). The effect of methylphenidate on neurofibromatosis type 1: A randomised, double-blind, placebo-controlled, crossover trial. Orphanet Journal of Rare Diseases, 9, 142.
55.
MarroccoR. T.DavidsonM. C. (1998) Neurochemistry of attention. In ParasuramanR. (Ed.), The attentive brain (pp. 35-50). Cambridge, MA: MIT Press.
56.
MasonD. J.HumphreysG. W.KentL. S. (2003). Exploring selective attention in ADHD: Visual search through space and time. Journal of Child Psychology and Psychiatry, 44, 1158-1176.
57.
MasonD. J.HumphreysG. W.KentL. S. (2005). Insights into the control of attentional set in ADHD using the attentional blink paradigm. Journal of Child Psychology and Psychiatry, 46, 1345-1353.
58.
MautnerV. F.KluweL.ThakkerS. D.LearkR. A. (2002). Treatment of ADHD in neurofibromatosis type 1. Developmental Medicine & Child Neurology, 44, 164-170.
59.
MazzoccoM. M. M.TurnerJ. E.DencklaM. B.HofmanK. J.ScanlonD. C.VellutinoF. R. (1995). Language and reading deficits associated with neurofibromatosis Type 1: Evidence for a not-so-nonverbal learning disability. Developmental Neuropsychology, 11, 503-522
60.
MesulamM. M. (1999). Spatial attention and neglect: Parietal, frontal and cingulate contributions to the mental representation and attentional targeting of salient extrapersonal events. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 354, 1325-1346.
61.
MichaelG. A.GarciaS.BussyG.François-LionL.GuibaudL. (2009). Reactivity to visual signals and the cerebellar vermis: Evidence from a rare case with Rhombencephalosynapsis. Behavioral Neuroscience, 123, 86-96.
62.
MichaelG. A.GarciaS.FernandezD.SellalF.BoucartM. (2006). The ventral premotor cortex (vPM) and resistance to interference. Behavioral Neuroscience, 120, 442-467.
63.
MichaelG. A.GarciaS.HerbillonV.Lion-FrançoisL. (2014). Reactivity to visual signals in neurofibromatosis type 1: Is everything OK?Neuropsychology, 28, 423-428.
64.
MichaelG. A.MizziR.CouffeC.Gálvez-GarcíaG. (2014). Dissociable yet tied inhibitory processes: The structure of inhibitory control. Cognitive, Affective & Behavioral Neuroscience, 14, 1026-1040.
65.
MiyakeA.FriedmanN. P.EmersonM. J.WitzkiA. H.HowerterA.WagerT. D. (2000). The unity and diversity of executive functions and their contributions to complex “frontal lobe” tasks: A latent variable analysis. Cognitive Psychology, 41, 49-100.
66.
MooreB. D.SlopisJ. M.SchomerD.JacksonE. F.LevyB. M. (1996). Neuropsychological significance of areas of high signal intensity on brain MRIs of children with neurofibromatosis. Neurology, 46, 1660-1668.
67.
Morein-ZamirS.RobbinsT. W. (2015). Fronto-striatal circuits in response-inhibition: Relevance to addiction. Brain Research, 1628, 117-129. doi:10.1016/j.brainres.2014.09.012
68.
NakaoT.RaduaJ.RubiaK.Mataix-ColsD. (2011). Gray matter volume abnormalities in ADHD: Voxel-based meta-analysis exploring the effects of age and stimulant medication. American Journal of Psychiatry, 168, 1154-1163.
69.
National Institutes of Health Consensus Development Conference Statement. (1988). Neurofibromatosis. Archives of Neurology, 45, 575-578.
70.
NorthK. (2000). Neurofibromatosis type 1. American Journal of Medical Genetics, 97, 119-127.
71.
NorthK.HymanS. L.BartonB. (2002). Cognitive deficits in neurofibromatosis 1. Journal of Child Neurology, 17, 605-612.
72.
OzonoffS. (1999). Cognitive impairment in neurofibromatosis type 1. American Journal of Medical Genetics, 89, 45-52.
73.
PackerR. J. (2006). Neurocognitive deficits in children with neurofibromatosis type 1. Current Neurology & Neuroscience Reports, 6, 119-120.
74.
PayneJ. M.ArnoldS. S.PrideN. A.NorthK. N. (2012). Does attention-deficit-hyperactivity disorder exacerbate executive dysfunction in children with neurofibromatosis type 1?Developmental Medicine & Child Neurology, 54, 898-904.
75.
PayneJ. M.HymanS. L.ShoresE. A.NorthK. N. (2011). Assessment of executive function and attention in children with neurofibromatosis type 1: Relationships between cognitive measures and real-world behavior. Child Neuropsychology, 17, 313-329.
76.
PayneJ. M.MoharirM. D.WebsterR.NorthK. N. (2010). Brain structure and function in neurofibromatosis type1: Current concepts and future directions. Journal of Neurology, Neurosurgery & Psychiatry, 81, 304-309.
77.
PetersenS. E.PosnerM. I. (2012). The attention system of the human brain: 20 years after. Annual Review of Neuroscience, 35, 73-89.
78.
PosnerM. I.PetersenS. E. (1990). The attention system of the human brain. Annual Review of Neuroscience, 13, 25-42.
79.
ReaderM. J.HarrisE. L.SchuerholzL. J.DencklaM. B. (1994). Attention deficit hyperactivity disorder and executive dysfunction. Developmental Neuropsychology, 10, 493-512.
80.
RosenbergM. D.ZhangS.HsuW. T.ScheinostD.FinnE. S.ShenX.. . . NeurosciJ. (2016). Methylphenidate modulates functional network connectivity to enhance attention. Journal of Neuroscience, 36, 9547-9557. Article I. doi:10.1523/JNEUROSCI.1746-16.2016
81.
RosserT. L.PackerR. J. (2003). Neurocognitive dysfunction in children with neurofibromatosis type 1. Current Neurology & Neuroscience Reports, 3, 129-136.
82.
RowbothamI.Pit-ten CateI. M.Sonuga-BarkeE. J. S.HuijbregtsS. C. J. (2009). Cognitive control in adolescents with neurofibromatosis type 1. Neuropsychology, 23, 50-60.
83.
RoyA.BarbarotS.RoulinJ. L.CharbonnierV.FasottiL.StalderJ. F.Le GallD. (2012). Is executive function specifically impaired in children with neurofibromatosis type 1? A neuropsychological investigation of cognitive flexibility. Applied Neuropsychology: Child, 3, 94-102.
84.
RuffH. A.LawsonK. R. (1990). Development of sustained, focused attention in young children during free play. Developmental Psychology, 26, 85-93.
85.
SergeantJ.GeurtsH.HuijbregtsS.ScheresA.OosterlaanJ. (2003). The top and the bottom of ADHD: A neuropsychological perspective. Neuroscience & Biobehavioral Reviews, 27, 583-592.
86.
SolantoM. V.AbikoffH.Sonuga-BarkeE.SchacharR.LoganG. D.WigalT.. . . TurkelE. (2001). The ecological validity of delay aversion and response inhibition as measures of impulsivity in ADHD: A supplement to the NIMH multimodal treatment study of ADHD. Journal of Abnormal Child Psychology, 29, 215-228.
87.
Sonuga-BarkeE. J. S. (2002). Psychological heterogeneity in ADHD—A dual pathway model of behaviour and cognition. Behavioural Brain Research, 130, 29-36.
88.
SturmW.LongoniF.WeisS.SpechtK.HerzogH.VohnR.. . . WillmesK. (2004). Functional reorganisation in patients with right hemisphere stroke after training of alertness: A longitudinal PET and fMRI study in eight cases. Neuropsychologia, 42, 434-450.
89.
SturmW.WillmesK. (2001). On the functional neuroanatomy of intrinsic and phasic alertness. NeuroImage, 14, 76-84.
90.
SturmW.WillmesK.OrgassB.HartjeW. (1997). Do specific attention deficits need specific training?Neuropsychological Rehabilitation, 7, 81-103.
91.
TemplerA.TitusJ.GutmannD. (2013). A neuropsychological perspective on attention problems in neurofibromatosis type 1. Journal of Attention Disorders, 17, 489-496.
92.
TreismanA.GeladeG. (1980). A feature-integration theory of attention. CognitivePsychology, 12, 97-136.
93.
Van der StigchelS.RommelseN. N.DeijenJ. B.GeldofC. J.WitloxJ.OosterlaanJ.. . . TheeuwesJ. (2007). Oculomotor capture in ADHD. Cognitive Neuropsychology, 24, 535-549.
94.
Van ZomerenA. H.BrouwerW. H. (1994). Clinical neuropsychology of attention. New York, NY: Oxford University Press.
95.
WechslerD. (1991). The Wechsler Intelligence Scale For Children—Third edition. San Antonio, TX: The Psychological Corporation.
96.
WechslerD. (2004). The Wechsler Intelligence Scale For Children—Fourth edition. London, England: Pearson Assessment.
97.
WillcuttE. G.DoyleA. E.NiggJ. T.FaraoneS. V.PenningtonB. F. (2005). Validity of the executive function theory of attention-deficit/hyperactivity disorder: A meta-analytic review. Biological Psychiatry, 57, 1336-1346.
98.
ZihlJ. (1999). Oculomotor scanning performance in subjects with homonymous visual field disorders. Visual Impairment Research, 1, 23-31.
99.
ZöllerM. E.RembeckB.BackmanL. (1997). Neuropsychological deficits in adults with neurofibromatosis type 1. Acta Neurologica Scandinavica, 95, 225-232.
