Restricted accessResearch articleFirst published online 2023-2
Fronto-Cerebellar Neurometabolite Alterations After Methylphenidate in Children and Adolescents With ADHD: A Proton Magnetic Resonance Spectroscopy Study
The fronto-cerebellar circuit is involved in ADHD pathophysiology. Methylphenidate, as a first-line medication for ADHD, affects different brain regions, however, its effect on the fronto-cerebellar circuit is not investigated sufficiently. We aimed to investigate the effect of 8-week treatment with methylphenidate on neurometabolite ratios in the fronto-cerebellar circuit in ADHD participants using magnetic resonance spectroscopy (MRS).
Methods:
Fifteen drug-naïve ADHD children and adolescents were enrolled in the present study. Two single-voxel MR spectra were acquired from the right dorsolateral prefrontal cortex (DLPFC) and left Crus 1, before and after the medication. Also, neuropsychological and behavioral assessments were administered.
Results:
After medication, the glutamate/creatine in the DLPFC and the choline/creatine in the Crus 1 decreased in the ADHD participants.
Conclusion:
These findings propose that methylphenidate-induced metabolite changes in the fronto-cerebellar circuit could be associated with improvement in cognitive/behavioral characteristics in ADHD. Also, results highlighted cerebellar engagement in ADHD pathophysiology.
AltabellaL.ZorattoF.AdrianiW.CaneseR. (2014). MR imaging-detectable metabolic alterations in attention deficit/hyperactivity disorder: From preclinical to clinical studies. American Journal of Neuroradiology, 35(6 suppl), S55–S63.
2.
ArdilaA. (2008). On the evolutionary origins of executive functions. Brain and Cognition, 68(1), 92–99.
3.
ArnoldL. E.HodgkinsP.KahleJ.MadhooM.KewleyG. (2015). Long-term outcomes of ADHD: Academic achievement and performance. Journal of Attention Disorders, 24(1), 73–85. https://doi.org/10.1177/1087054714566076
4.
BarkleyR. A. (1997). Behavioral inhibition, sustained attention, and executive functions: Constructing a unifying theory of ADHD. Psychological Bulletin, 121(1), 65–94.
5.
BenamorL. (2014). (1)H-magnetic resonance spectroscopy study of stimulant medication effect on brain metabolites in French Canadian children with attention deficit hyperactivity disorder. Neuropsychiatric Disease and Treatment, 10, 47–54. https://doi.org/10.2147/NDT.S52338
6.
BerginströmN.JohanssonJ.NordströmP.NordströmA. (2015). Attention in older adults: A normative study of the integrated visual and auditory continuous performance test for persons aged 70 years. Clinical Neuropsychologist, 29(5), 595–610. https://doi.org/10.1080/13854046.2015.1063695
7.
BidwellL. C.McClernonF. J.KollinsS. H. (2011). Cognitive enhancers for the treatment of ADHD. Pharmacology Biochemistry and Behavior, 99(2), 262–274. https://doi.org/10.1016/j.pbb.2011.05.002
8.
BikicA.LeckmanJ. F.ChristensenT. Ø.BilenbergN.DalsgaardS. (2018). Attention and executive functions computer training for attention-deficit/hyperactivity disorder (ADHD): Results from a randomized, controlled trial. European Child & Adolescent Psychiatry, 27(12), 1563–1574. https://doi.org/10.1007/s00787-018-1151-y
9.
BlumN. J.MaukJ. E.McComasJ. J.MaceF. C. (1996). Separate and combined effects of methylphenidate and a behavioral intervention on disruptive behavior in children with mental retardation. Journal of Applied Behavior Analysis, 29(3), 305–319.
10.
Bogner-StraussJ. G. (2017). N-acetylaspartate metabolism outside the brain: Lipogenesis, histone acetylation, and cancer. Frontiers in Endocrinology, 8, 240.
11.
BostanA. C.DumR. P.StrickP. L. (2013). Cerebellar networks with the cerebral cortex and basal ganglia. Trends in Cognitive Sciences, 17(5), 241–254.
12.
BucknerR. L.KrienenF. M.CastellanosA.DiazJ. C.YeoB. T. (2011). The organization of the human cerebellum estimated by intrinsic functional connectivity. Journal of Neurophysiology, 106(5), 2322–2345.
13.
BushG.SpencerT. J.HolmesJ.ShinL. M.ValeraE. M.SeidmanL. J.MakrisN.SurmanC.AleardiM.MickE.BiedermanJ. (2008). Functional magnetic resonance imaging of methylphenidate and placebo in attention-deficit/hyperactivity disorder during the multi-source interference task. Archives of General Psychiatry, 65(1), 102–114. https://doi.org/10.1001/archgenpsychiatry.2007.16
14.
CarmonaS.VilarroyaO.BielsaA.TrèmolsV.SolivaJ. C.RoviraM.TomàsJ.RahebC.GispertJ. D.BatlleS.BulbenaA. (2005). Global and regional gray matter reductions in ADHD: A voxel-based morphometric study. Neuroscience Letters, 389(2), 88–93.
15.
CarreyN. J.MacMasterF. P.GaudetL.SchmidtM. H. (2007). Striatal creatine and glutamate/glutamine in attention-deficit/hyperactivity disorder. Journal of Child and Adolescent Psychopharmacology, 17(1), 11–17.
16.
CarreyN.MacMasterF. P.FogelJ.SparkesS.WaschbuschD.SullivanS.SchmidtM. (2003). Metabolite changes resulting from treatment in children with ADHD: A 1H-MRS study. Clinical Neuropharmacology, 26(4), 218–221.
17.
CarreyN.MacMasterF. P.SparkesS. J.KhanS. C.KusumakarV. (2002). Glutamatergic changes with treatment in attention deficit hyperactivity disorder: A preliminary case series. Journal of Child and Adolescent Psychopharmacology, 12(4), 331–336.
18.
CastellanoG.DiasC. S.FoersterB.LiL. M.CovolanR. J. (2012). NAA and NAAG variation in neuronal activation during visual stimulation. Brazilian Journal of Medical and Biological Research, 45, 1031–1036.
19.
CastellanosF. X.GieddJ. N.MarshW. L.HamburgerS. D.VaituzisA. C.DicksteinD. P.SarfattiS. E.VaussY. C.SnellJ. W.LangeN.KaysenD.KrainA. L.RitchieG. F.RajapakseJ. C.RapoportJ. L. (1996). Quantitative brain magnetic resonance imaging in attention-deficit hyperactivity disorder. Archives of General Psychiatry, 53(7), 607–616.
20.
CastellanosF. X.LeeP. P.SharpW.JeffriesN. O.GreensteinD. K.ClasenL. S.BlumenthalJ. D.JamesR. S.EbensC. L.WalterJ. M.ZijdenbosA.EvansA. C.GieddJ. N.RapoportJ. L. (2002). Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorder. The Journal of the American Medical Association, 288(14), 1740–1748.
21.
ChildressA. C.BerryS. A. (2012). Pharmacotherapy of attention-deficit hyperactivity disorder in adolescents. Drugs, 72(3), 309–325.
22.
CloakC. C.ChangL.ErnstT. (2004). Increased frontal white matter diffusion is associated with glial metabolites and psychomotor slowing in HIV. Journal of Neuroimmunology, 157(1-2), 147–152.
23.
CoghillD. R.RhodesS. M.MatthewsK. (2007). The neuropsychological effects of chronic methylphenidate on drug-naive boys with attention-deficit/hyperactivity disorder. Biological Psychiatry, 62(9), 954–962.
24.
CoghillD. R.SethS.PedrosoS.UsalaT.CurrieJ.GaglianoA. (2014). Effects of methylphenidate on cognitive functions in children and adolescents with attention-deficit/hyperactivity disorder: Evidence from a systematic review and a meta-analysis. Biological Psychiatry, 76(8), 603–615. https://doi.org/10.1016/j.biopsych.2013.10.005
25.
ColletteF.Van der LindenM.LaureysS.DelfioreG.DegueldreC.LuxenA.SalmonE. (2005). Exploring the unity and diversity of the neural substrates of executive functioning. Human Brain Mapping, 25(4), 409–423.
26.
CorteseS.KellyC.ChabernaudC.ProalE.Di MartinoA.MilhamM. P.CastellanosF. X. (2012). Toward systems neuroscience of ADHD: A meta-analysis of 55 fMRI studies. American Journal of Psychiatry, 169(10), 1038–1055.
27.
CourvoisieH.HooperS. R.FineC.KwockL.CastilloM. (2004). Neurometabolic functioning and neuropsychological correlates in children with ADHD-H: Preliminary findings. The Journal of Neuropsychiatry and Clinical Neurosciences, 16(1), 63–69.
28.
CurrieS.HadjivassiliouM.CravenI. J.WilkinsonI. D.GriffithsP. D.HoggardN. (2013). Magnetic resonance spectroscopy of the brain. Postgraduate Medical Journal, 89(1048), 94–106.
29.
CzerniakS. M.SikogluE. M.KingJ. A.KennedyD. N.MickE.FrazierJ.MooreC. M. (2013). Areas of the brain modulated by single-dose methylphenidate treatment in youth with ADHD during task-based fMRI: A systematic review. Harvard Review of Psychiatry, 21(3), 151–162.
30.
DanboltN. C. (2001). Glutamate uptake. Progress in Neurobiology, 65(1), 1–105.
31.
DebS.DhaliwalA. J.RoyM. (2008). The usefulness of Conners’ rating scales-revised in screening for attention deficit hyperactivity disorder in children with intellectual disabilities and borderline intelligence. Journal of Intellectual Disability Research, 52(11), 950–965. https://doi.org/10.1111/j.1365-2788.2007.01035.x
32.
DoughertyD. D.BonabA. A.SpencerT. J.RauchS. L.MadrasB. K.FischmanA. J. (1999). Dopamine transporter density in patients with attention deficit hyperactivity disorder. Lancet, 354(9196), 2132–2133.
33.
DoyonJ.PenhuneV.UngerleiderL. G. (2003). Distinct contribution of the cortico-striatal and cortico-cerebellar systems to motor skill learning. Neuropsychologia, 41(3), 252–262.
34.
ErchingerV. J.ErslandL.AuklandS. M.AbbottC. C.OltedalL. (2021). Magnetic resonance spectroscopy in depressed subjects treated with electroconvulsive therapy-A systematic review of literature. Frontiers in Psychiatry, 12, 608857. https://doi.org/10.3389/fpsyt.2021.608857
35.
EvartsE. V.ThachW. T. (1969). Motor mechanisms of the CNS: Cerebrocerebellar interrelations. Annual Review of Physiology, 31(1), 451–498.
36.
ExnerC.WenigerG.IrleE. (2004). Cerebellar lesions in the PICA but not SCA territory impair cognition. Neurology, 63(11), 2132–2135.
37.
FaraoneS. V.BanaschewskiT.CoghillD.ZhengY.BiedermanJ.BellgroveM. A.NewcornJ. H.GignacM.Al SaudN. M.ManorI.RohdeL. A.YangL.CorteseS.AlmagorD.SteinM. A.AlbattiT. H.AljoudiH. F.AlqahtaniM. M. J.AshersonP.. . . WangY. (2021). The world federation of ADHD international consensus statement: 208 evidence-based conclusions about the disorder. Neuroscience and Biobehavioral Reviews, 128, 789–818. https://doi.org/10.1016/j.neubiorev.2021.01.022
38.
FilipekP. A.Semrud-ClikemanM.SteingardR. J.RenshawP. F.KennedyD. N.BiedermanJ. (1997). Volumetric MRI analysis comparing subjects having attention-deficit hyperactivity disorder with normal controls. Neurology, 48(3), 589–601.
39.
FrayP. J.RobbinsT. W.SahakianB. J. (1996). Neuorpsychiatyric applications of CANTAB. International Journal of Geriatric Psychiatry, 11, 329–336.
40.
GaoW.-J.Goldman-RakicP. S. (2003). Selective modulation of excitatory and inhibitory microcircuits by dopamine. Proceedings of the National Academy of Sciences, 100(5), 2836–2841.
41.
GauS. S.ShangC. Y. (2010). Executive functions as endophenotypes in ADHD: Evidence from the Cambridge neuropsychological test battery (CANTAB). Journal of Child Psychology and Psychiatry, 51(7), 838–849.
42.
Goldman-RakicP. S.LeranthC.WilliamsS. M.MonsN.GeffardM. (1989). Dopamine synaptic complex with pyramidal neurons in primate cerebral cortex. Proceedings of the National Academy of Sciences, 86(22), 9015–9019.
43.
GrahamS. (2017). Attention-deficit/hyperactivity disorder (ADHD), learning disabilities (LD), and executive functioning: Recommendations for future research. Contemporary Educational Psychology, 50, 97–101.
44.
HabasC.KamdarN.NguyenD.PraterK.BeckmannC. F.MenonV.GreiciusM. D. (2009). Distinct cerebellar contributions to intrinsic connectivity networks. Neuroscience Journal, 29(26), 8586–8594.
45.
HammernessP.BiedermanJ.PettyC.HeninA.MooreC. M. (2012). Brain biochemical effects of methylphenidate treatment using proton magnetic spectroscopy in youth with attention-deficit hyperactivity disorder: A controlled pilot study. CNS Neuroscience & Therapeutics, 18(1), 34–40.
46.
HartH.ChantilukeK.CubilloA. I.SmithA. B.SimmonsA.BrammerM. J.MarquandA. F.RubiaK. (2014). Pattern classification of response inhibition in ADHD: Toward the development of neurobiological markers for ADHD. Human Brain Mapping, 35(7), 3083–3094.
47.
HartH.RaduaJ.NakaoT.Mataix-ColsD.RubiaK. (2013). Meta-analysis of functional magnetic resonance imaging studies of inhibition and attention in attention-deficit/hyperactivity disorder: exploring task-specific, stimulant medication, and age effects. JAMA Psychiatry, 70(2), 185–198.
48.
HusarovaV.BittsanskyM.OndrejkaI.DobrotaD. (2014). Prefrontal grey and white matter neurometabolite changes after atomoxetine and methylphenidate in children with attention deficit/hyperactivity disorder: A 1H magnetic resonance spectroscopy study. Psychiatry Research Neuroimaging, 222(1-2), 75–83.
49.
ItoM. (2000). Mechanisms of motor learning in the cerebellum. Brain Research, 886(1-2), 237–245.
50.
IvanovI.MurroughJ. W.BansalR.HaoX.PetersonB. S. (2014). Cerebellar morphology and the effects of stimulant medications in youths with attention deficit-hyperactivity disorder. Neuropsychopharmacology, 39(3), 718–726.
51.
KasparekT.TheinerP.FilovaA. (2015). Neurobiology of ADHD from childhood to adulthood: Findings of imaging methods. Journal of Attention Disorders, 19(11), 931–943.
52.
KenarA. I.UnalG.KirogluY.HerkenH. (2017). Effects of methylphenidate treatment on the cerebellum in adult attention-deficit hyperactivity disorder: A magnetic resonance spectroscopy study. European Review for Medical and Pharmacological Sciences, 21, 383–388.
53.
KimJ.LeeY.HanD.MinK.KimD.LeeC. (2015). The utility of quantitative electroencephalography and integrated visual and auditory continuous performance test as auxiliary tools for the attention deficit hyperactivity disorder diagnosis. Clinical Neurophysiology, 126(3), 532–540.
54.
KleinR. G.AbikoffH. (1997). Behavior therapy and methylphenidate in the treatment of children with ADHD. Journal of Attention Disorders, 2(2), 89–114.
55.
KoflerM. J.SarverD. E.HarmonS. L.MoltisantiA.AduenP. A.SotoE. F.FerrettiN. (2018). Working memory and organizational skills problems in ADHD. Journal of Child Psychology and Psychiatry, 59(1), 57–67.
56.
KreisR.ErnstT.RossB. D. (1993). Development of the human brain: in vivo quantification of metabolite and water content with proton magnetic resonance spectroscopy. Magnetic Resonance in Medicine, 30(4), 424–437.
57.
KreisR.RossB. D.FarrowN. A.AckermanZ. (1992). Metabolic disorders of the brain in chronic hepatic encephalopathy detected with H-1 MR spectroscopy. Radiology, 182(1), 19–27.
58.
KronenbergG.EndeG.AlmB.DeuschleM.HeuserI.CollaM. (2008). Increased NAA and reduced choline levels in the anterior cingulum following chronic methylphenidate. A spectroscopic test-retest study in adult ADHD. European Archives of Psychiatry and Clinical Neuroscience, 258(7), 446–450.
59.
LeschK. P.MerkerS.ReifA.NovakM. (2013). Dances with black widow spiders: Dysregulation of glutamate signalling enters centre stage in ADHD. European Neuropsychopharmacology, 23(6), 479–491.
60.
LienY. H.ShapiroJ. I.ChanL. (1990). Effects of hypernatremia on organic brain osmoles. Journal of Clinical Investigation, 85(5), 1427–1435.
MakrisN.BiedermanJ.ValeraE. M.BushG.KaiserJ.KennedyD. N.CavinessV. S.FaraoneS. V.SeidmanL. J. (2007). Cortical thinning of the attention and executive function networks in adults with attention-deficit/hyperactivity disorder. Cerebral Cortex, 17(6), 1364–1375.
63.
MasonG. F.KrystalJ. H. (2006). MR spectroscopy: Its potential role for drug development for the treatment of psychiatric diseases. NMR in Biomedicine, 19(6), 690–701.
64.
MatsuuraN.IshitobiM.AraiS.KawamuraK.AsanoM.InoharaK.FujiokaT.NarimotoT.WadaY.HirataniM.KosakaH. (2014). Effects of methylphenidate in children with attention deficit hyperactivity disorder: A near-infrared spectroscopy study with CANTAB®. Child and Adolescent Psychiatry and Mental Health, 8(1), 273–273. https://doi.org/10.1186/s13034-014-0032-5
65.
MattinglyG. W.WilsonJ.RostainA. L. (2017). A clinician’s guide to ADHD treatment options. Postgraduate Medicine, 129(7), 657–666.
66.
MeijerW. M.FaberA.Den BanE.TobiH. (2009). Current issues around the pharmacotherapy of ADHD in children and adults. Pharmacy World & Science, 31(5), 509–516.
67.
MillerB. L. (1991). A review of chemical issues in 1H NMR spectroscopy: N-acetyl-l-aspartate, creatine and choline. NMR in Biomedicine, 4(2), 47–52. L
68.
MooreC. M.BiedermanJ.WozniakJ.MickE.AleardiM.WardropM.DoughertyM.HarpoldT.HammernessP.RandallE.RenshawP. F. (2006). Differences in brain chemistry in children and adolescents with attention deficit hyperactivity disorder with and without comorbid bipolar disorder: A proton magnetic resonance spectroscopy study. American Journal of Psychiatry, 163(2), 316–318.
69.
Naeeni DavaraniM.Arian DarestaniA.Hassani-AbharianP.VaseghiS.ZarrindastM.-R.NasehiM. (2022). RehaCom rehabilitation training improves a wide-range of cognitive functions in multiple sclerosis patients. Applied Neuropsychology. Adult, 29, 262–272.
70.
NarayanaP. A. (2005). Magnetic resonance spectroscopy in the monitoring of multiple sclerosis. Journal of Neuroimaging, 15(4 Suppl), 46S–57S.
71.
NiederA. (2009). Prefrontal cortex and the evolution of symbolic reference. Current Opinion in Neurobiology, 19(1), 99–108.
72.
PenningtonB. F.OzonoffS. (1996). Executive functions and developmental psychopathology. Journal of Child Psychology and Psychiatry, 37(1), 51–87.
73.
PerlovE.PhilipsenA.MatthiesS.DrielingT.MaierS.BublE.HesslingerB.BuechertM.HenningJ.EbertD.Tebartz Van ElstL. (2009). Spectroscopic findings in attention-deficit/hyperactivity disorder: Review and meta-analysis. The World Journal of Biological Psychiatry, 10(4 Pt 2), 355–365.
74.
PerlovE.Tebarzt van ElstL.BuechertM.MaierS.MatthiesS.EbertD.HesslingerB.PhilipsenA. (2010). H¹-MR-spectroscopy of cerebellum in adult attention deficit/hyperactivity disorder. Journal of Psychiatric Research, 44(14), 938–943.
75.
RajkowskaG.Goldman-RakicP. S. (1995). Cytoarchitectonic definition of prefrontal areas in the normal human cortex: II. Variability in locations of areas 9 and 46 and relationship to the Talairach coordinate system. Cerebral Cortex, 5(4), 323–337.
76.
RamnaniN. (2012). Frontal lobe and posterior parietal contributions to the cortico-cerebellar system. Cerebellum, 11(2), 366–383.
77.
ReynoldsG.WilsonM.PeetA.ArvanitisT. N. (2006). An algorithm for the automated quantitation of metabolites in in vitro NMR signals. Magnetic Resonance in Medicine, 56(6), 1211–1219.
78.
RosenY.LenkinskiR. E. (2007). Recent advances in magnetic resonance neurospectroscopy. Neurotherapeutics, 4(3), 330–345.
79.
RossB.KreisR.ErnstT. (1992). Clinical tools for the 90s: magnetic resonance spectroscopy and metabolite imaging. European Journal of Radiology, 14(2), 128–140.
80.
RussellV. A. (2003). Dopamine hypofunction possibly results from a defect in glutamate-stimulated release of dopamine in the nucleus accumbens shell of a rat model for attention deficit hyperactivity disorder—the spontaneously hypertensive rat. Neuroscience and Biobehavioral Reviews, 27(7), 671–682.
81.
SahakianB.JonesG.LevyR.GrayJ.WarburtonD. (1989). The effects of nicotine on attention, information processing, and short-term memory in patients with dementia of the Alzheimer type. The British Journal of Psychiatry, 154(6), 797–800.
82.
ScheauC.PredaE. M.PopaG. A.GhergusA. E.CapsaR. A.LupescuI. G. (2012). Magnetic resonance spectroscopy–a non-invasive method in evaluating focal and diffuse central nervous system disease. Journal of Medicine and Life, 5(4), 423–427.
83.
SchmahmannJ. D.MacmoreJ.VangelM. (2009). Cerebellar stroke without motor deficit: Clinical evidence for motor and non-motor domains within the human cerebellum. Neuroscience, 162(3), 852–861.
84.
SchmahmannJ. D.ShermanJ. C. (1998). The cerebellar cognitive affective syndrome. Brain, 121(4), 561–579.
85.
SchochB.DimitrovaA.GizewskiE. R.TimmannD. (2006). Functional localization in the human cerebellum based on voxelwise statistical analysis: Aa study of 90 patients. NeuroImage, 30(1), 36–51.
86.
SeidmanL. J. (2006). Neuropsychological functioning in people with ADHD across the lifespan. Clinical Psychology Review, 26(4), 466–485.
87.
ShahrivarZ.KoushaM.MoallemiS.Tehrani-DoostM.Alaghband RadJ. (2010). The reliability and validity of kiddie-schedule for affective disorders and schizophrenia - present and life-time version - Persian version. Child and Adolescent Mental Health, 15, 97–102. https://doi.org/10.1111/j.1475-3588.2008.00518.x
88.
ShawM.HodgkinsP.CaciH.YoungS.KahleJ.WoodsA. G.ArnoldL. E. (2012). A systematic review and analysis of long-term outcomes in attention deficit hyperactivity disorder: Effects of treatment and non-treatment. BMC Medicine, 10(1), 1–15.
89.
ShortE. J.FairchildL.FindlingR. L.ManosM. J. (2007). Developmental and subtype differences in behavioral assets and problems in children diagnosed with ADHD. Journal of Attention Disorders, 11(1), 28–36.
90.
StoodleyC. J.SchmahmannJ. D. (2009). Functional topography in the human cerebellum: AA meta-analysis of neuroimaging studies. NeuroImage, 44(2), 489–501.
91.
StoodleyC. J.ValeraE. M.SchmahmannJ. D. (2012). Functional topography of the cerebellum for motor and cognitive tasks: An fMRI study. NeuroImage, 59(2), 1560–1570.
92.
StorebøO. J.KroghH. B.RamstadE.Moreira-MaiaC. R.HolmskovM.SkoogM.NilausenT. D.MagnussonF. L.ZwiM.GilliesD.RosendalS.GrothC.RasmussenK. B.GauciD.KirubakaranR.ForsbølB.SimonsenE.GluudC. (2015). Methylphenidate for attention-deficit/hyperactivity disorder in children and adolescents: Cochrane systematic review with meta-analyses and trial sequential analyses of randomised clinical trials. BMJ, 351, h5203. https://doi.org/10.1136/bmj.h5203
93.
StrickP. L.DumR. P.FiezJ. A. (2009). Cerebellum and nonmotor function. Annual Review of Neuroscience, 32(1), 413–434.
94.
TafazoliS.O’NeillJ.BejjaniA.LyR.SalamonN.McCrackenJ. T.AlgerJ. R.LevittJ. G. (2013). 1H MRSI of middle frontal gyrus in pediatric ADHD. Journal of Psychiatric Research, 47(4), 505–512.
95.
TannockR.IckowiczA.SchacharR. (1995). Differential effects of methylphenidate on working memory in ADHD children with and without comorbid anxiety. Journal of the American Academy of Child and Adolescent Psychiatry, 34(7), 886–896. https://doi.org/10.1097/00004583-199507000-00012
UnalG. A.KenarA. N.HerkenH.KirogluY. (2015). Association of adult attention deficit hyperactivity disorder subtypes and response to methylphenidate HCL treatment: Aa magnetic resonance spectroscopy study. Neuroscience Letters, 604, 188–192.
98.
ValeraE. M.FaraoneS. V.MurrayK. E.SeidmanL. J. (2007). Meta-analysis of structural imaging findings in attention-deficit/hyperactivity disorder. Biological Psychiatry, 61(12), 1361–1369.
99.
Van der OordS.PrinsP. J.OosterlaanJ.EmmelkampP. M. (2008). Efficacy of methylphenidate, psychosocial treatments and their combination in school-aged children with ADHD: AA meta-analysis.undefined. Clinical Psychology Review, 28(5), 783–800.
100.
Veisi-PirkoohiS.Hassani-AbharianP.KazemiR.VaseghiS.ZarrindastM. R.NasehiM. (2020). Efficacy of RehaCom cognitive rehabilitation software in activities of daily living, attention and response control in chronic stroke patients. Journal of Clinical Neuroscience, 71, 101–107.
101.
VideenJ. S.MichaelisT.PintoP.RossB. D. (1995). Human cerebral osmolytes during chronic hyponatremia. A proton magnetic resonance spectroscopy study. Journal of Clinical Investigation, 95(2), 788–793.
102.
VillarroelM.CiudinA.HernándezC.SimóR. (2010). Neurodegeneration: An early event of diabetic retinopathy. World Journal of Diabetes, 1(2), 57–64. https://doi.org/10.4239/wjd.v1.i2.57
103.
VlesJ. S.FeronF. J.HendriksenJ. G.JollesJ.van KroonenburghM. J.WeberW. E. (2003). Methylphenidate down-regulates the dopamine receptor and transporter system in children with attention deficit hyperkinetic disorder (ADHD). Neuropediatrics, 34(2), 77–80.
104.
VolkowN. D.WangG.-J.FowlerJ. S.LoganJ.AngristB.HitzemannR.LiebermanJ.PappasN. (1997). Effects of methylphenidate on regional brain glucose metabolism in humans: Relationship to dopamine D2 receptors. American Journal of Psychiatry, 154(1), 50–55.
105.
VolkowN. D.WangG. J.FowlerJ. S.LoganJ.GerasimovM.MaynardL.DingY. S.GatleyS. J.GiffordA.FranceschiD. (2001). Therapeutic doses of oral methylphenidate significantly increase extracellular dopamine in the human brain. The Journal of Neuroscience, 21(2), Rc121.
106.
WartonF. L.HowellsF. M.RussellV. A. (2009). Increased glutamate-stimulated release of dopamine in substantia nigra of a rat model for attention-deficit/hyperactivity disorder–lack of effect of methylphenidate. Metabolic Brain Disease, 24(4), 599–613. https://doi.org/10.1007/s11011-009-9166-1
107.
WigunaT.GuerreroA. P.WibisonoS.SastroasmoroS. (2012). Effect of 12-week administration of 20-mg long-acting methylphenidate on Glu/Cr, NAA/Cr, Cho/Cr, and mI/Cr ratios in the prefrontal cortices of school-age children in Indonesia: A study using 1H magnetic resonance spectroscopy (MRS). Clinical Neuropharmacology, 35(2), 81–85.
108.
WolosinS. M.RichardsonM. E.HennesseyJ. G.DencklaM. B.MostofskyS. H. (2009). Abnormal cerebral cortex structure in children with ADHD. Human Brain Mapping, 30(1), 175–184.
109.
YeoR. A.HillD. E.CampbellR. A.VigilJ.PetropoulosH.HartB.ZamoraL.BrooksW. M. (2003). Proton magnetic resonance spectroscopy investigation of the right frontal lobe in children with attention-deficit/hyperactivity disorder. Journal of the American Academy of Child and Adolescent Psychiatry, 42(3), 303–310.
110.
ZarrabiM.ShahrivarZ.Tehrani DoostM.KhademiM.Zargari NejadG. (2015). Concurrent validity of the behavior rating inventory of executive function in children with attention deficit hyperactivity disorder. Iranian Journal of Psychiatry and Behavioral Sciences, 9(1), e213–e213. https://doi.org/10.17795/ijpbs213
