Hostname: page-component-586b7cd67f-r5fsc Total loading time: 0 Render date: 2024-11-22T06:39:57.813Z Has data issue: false hasContentIssue false
  • English
  • Français

Association between microstructural integrity of frontostriatal tracts and school functioning: ADHD symptoms and executive function as mediators

Published online by Cambridge University Press:  28 July 2014

S. S. Gau ,
W.-L. Tseng ,
W.-Y. I. Tseng ,
Y.-H. Wu  and
Y.-C. Lo
S. S. Gau*
Affiliation:
Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, Taiwan Department of Psychology, School of Occupational Therapy, Graduate Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan
W.-L. Tseng
Affiliation:
Institute of Child Development, University of Minnesota, Twin Cities, Minnesota, MN, USA
W.-Y. I. Tseng
Affiliation:
Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, Taiwan Center for Optoelectronic Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
Y.-H. Wu
Affiliation:
School of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
Y.-C. Lo
Affiliation:
Center for Optoelectronic Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
*
*Address for correspondence: S. S. Gau, M.D., Ph.D., Department of Psychiatry, National Taiwan University Hospital and College of Medicine, No. 7, Chung-Shan South Road, Taipei 10002, Taiwan. (Email: [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Deficits in executive function (EF), impaired school functioning and altered white matter integrity in frontostriatal networks have been associated with attention-deficit/hyperactivity disorder (ADHD). However, relationships between impairments in these areas are unclear. Using a sample of youths with and without ADHD, this study examined the association between microstructural integrity of frontostriatal tracts and school dysfunction and the mediating roles of EF and ADHD symptoms in this association.

Method

The sample included 32 Taiwanese youths with ADHD and 32 age-, sex-, handedness- and IQ-matched typically-developing (TD) youths. Participants were assessed using psychiatric interviews, parent reports on ADHD symptoms and school functioning, and EF measures from the Cambridge Neuropsychological Test Automated Battery (CANTAB). The frontostriatal tracts were reconstructed by diffusion spectrum imaging (DSI) tractography and were subdivided into four functionally distinct segments: caudate–dorsolateral, caudate–medial prefrontal, caudate–orbitofrontal and caudate–ventrolateral tracts.

Results

Youths with ADHD, relative to TD youths, showed altered white matter integrity in all four bilateral pairs of frontostriatal tracts (decreased general fractional anisotropy, GFA), had poor attention, vigilance and response inhibition, and showed impaired school functioning. Altered microstructural integrity in frontostriatal tracts was significantly associated with school dysfunction, which was mediated by EF measures of attention/vigilance and response inhibition in addition to inattention and hyperactivity symptoms.

Conclusions

Our findings demonstrate an association between white matter integrity in the frontostriatal networks and school functioning and suggest that EF deficits and ADHD symptoms may be the mediating mechanisms for this association. Future research is needed to test the directionality and specificity of this finding.

Keywords

Attention-deficit/hyperactivity disorderdiffusion spectrum imaging tractographyexecutive functionfrontostriatal tractsmediatorsschool function
Type
Original Articles
Information
Psychological Medicine , Volume 45 , Issue 3 , February 2015 , pp. 529 - 543
Copyright
Copyright © Cambridge University Press 2014 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Afifi, AK, Bergman, RA (1998). Functional Neuroanatomy: Text and Atlas. McGraw-Hill, Health Professions Division: New York.Google Scholar
Ashtari, M, Kumra, S, Bhaskar, SL, Clarke, T, Thaden, E, Cervellione, KL, Rhinewine, J, Kane, JM, Adesman, A, Milanaik, R, Maytal, J, Diamond, A, Szeszko, P, Ardekani, BA (2005). Attention-deficit/hyperactivity disorder: a preliminary diffusion tensor imaging study. Biological Psychiatry 57, 448–455.Google Scholar
Barkley, RA (1997). Behavioral inhibition, sustained attention, and executive functions: constructing a unifying theory of ADHD. Psychological Bulletin 121, 65–94.Google Scholar
Biederman, J, Faraone, SV, Chen, WJ (1993). Social adjustment inventory for children and adolescents: concurrent validity in ADHD children. Journal of the American Academy of Child and Adolescent Psychiatry 32, 1059–1064.Google Scholar
Biederman, J, Monuteaux, MC, Doyle, AE, Seidman, LJ, Wilens, TE, Ferrero, F, Morgan, CL, Faraone, SV (2004). Impact of executive function deficits and attention-deficit/hyperactivity disorder (ADHD) on academic outcomes in children. Journal of Consulting and Clinical Psychology 72, 757–766.Google Scholar
Bush, G, Valera, EM, Seidman, LJ (2005). Functional neuroimaging of attention-deficit/hyperactivity disorder: a review and suggested future directions. Biological Psychiatry 57, 1273–1284.Google Scholar
Callaghan, P (1991). Principles of Nuclear Magnetic Resonance Microscopy. Clarendon Press: Oxford.Google Scholar
Casey, BJ, Castellanos, FX, Giedd, JN, Marsh, WL, Hamburger, SD, Schubert, AB, Vauss, YC, Vaituzis, AC, Dickstein, DP, Sarfatti, SE, Rapoport, JL (1997). Implication of right frontostriatal circuitry in response inhibition and attention-deficit/hyperactivity disorder. Journal of the American Academy of Child and Adolescent Psychiatry 36, 374–383.Google Scholar
Casey, BJ, Epstein, JN, Buhle, J, Liston, C, Davidson, MC, Tonev, ST, Spicer, J, Nioqi, S, Millner, AJ, Reiss, A, Garrett, A, Hinshaw, SP, Greenhill, LL, Shafritz, KM, Vitolo, A, Kotler, LA, Jarrett, MA, Glover, G (2007). Frontostriatal connectivity and its role in cognitive control in parent-child dyads with ADHD. American Journal of Psychiatry 164, 1729–1736.Google Scholar
Chamberlain, SR, Robbins, TW, Winder-Rhodes, S, Müller, U, Sahakian, BJ, Blackwell, AD, Barnett, JH (2011). Translational approaches to frontostriatal dysfunction in attention-deficit/hyperactivity disorder using a computerized neuropsychological battery. Biological Psychiatry 69, 1192–1203.Google Scholar
Conturo, TE, Lori, NF, Cull, TS, Akbudak, E, Snyder, AZ, Shimony, JS, McKinstry, RC, Burton, H, Raichle, ME (1999). Tracking neuronal fiber pathways in the living human brain. Proceedings of the National Academy of Sciences USA 96, 10422–10427.CrossRefGoogle ScholarPubMed
Cubillo, A, Halari, R, Smith, A, Taylor, E, Rubia, K (2012). A review of fronto-striatal and fronto-cortical brain abnormalities in children and adults with attention deficit hyperactivity disorder (ADHD) and new evidence for dysfunction in adults with ADHD during motivation and attention. Cortex 48, 194–215.Google Scholar
Davenport, ND, Karatekin, C, White, T, Lim, KO (2010). Differential fractional anisotropy abnormalities in adolescents with ADHD or schizophrenia. Psychiatry Research 181, 193–198.Google Scholar
de Zeeuw, P, Mandl, RCW, Hulshoff Pol, HE, Van Engeland, H, Durston, S (2012). Decreased frontostriatal microstructural organization in attention deficit/hyperactivity disorder. Human Brain Mapping 33, 1941–1951.Google Scholar
Gau, SS (2007). Parental and family factors for attention-deficit hyperactivity disorder in Taiwanese children. Australian and New Zealand Journal of Psychiatry 41, 688–696.Google Scholar
Gau, SS, Chong, MY, Chen, TH, Cheng, AT (2005). A 3-year panel study of mental disorders among adolescents in Taiwan. American Journal of Psychiatry 162, 1344–1350.Google Scholar
Gau, SS, Shang, CY (2010). Executive functions as endophenotypes in ADHD: evidence from the Cambridge Neuropsychological Test Battery (CANTAB). Journal of Child Psychology and Psychiatry 51, 838–849.Google Scholar
Gau, SS, Shang, CY, Liu, SK, Lin, CH, Swanson, JM, Liu, Y, Tu, CL (2008). Psychometric properties of the Chinese version of the Swanson, Nolan, and Pelham, version IV scale – parent form. International Journal of Methods in Psychiatric Research 17, 35–44.Google Scholar
Gau, SS, Shen, HY, Chou, MC, Tang, CS, Chiu, YN, Gau, CS (2006 a). Determinants of adherence to methylphenidate and the impact of poor adherence on maternal and family measures. Journal of Child and Adolescent Psychopharmacology 16, 286–297.CrossRefGoogle ScholarPubMed
Gau, SS, Shen, HY, Soong, WT, Gau, CS (2006 b). An open-label, randomized, active-controlled equivalent trial of osmotic release oral system methylphenidate in children with attention-deficit/hyperactivity disorder in Taiwan. Journal of Child and Adolescent Psychopharmacology 16, 441–455.Google Scholar
Griswold, DE, Barnhill, GP, Myles, BS, Hagiwara, T, Simpson, RL (2002). Asperger syndrome and academic achievement. Focus on Autism and Other Developmental Disabilities 17, 94–102.Google Scholar
Hamilton, LS, Levitt, JG, Neill, JO, Alger, JR, Luders, E, Phillips, OR, Caplan, R, Toga, AW, McCracken, J, Narr, KL (2008). Reduced white matter integrity in attention-deficit hyperactivity disorder. Neuroreport 19, 1705–1708.Google Scholar
Hess, CP, Mukherjee, P, Han, ET, Xu, D, Vigneron, DB (2006). Q-ball reconstruction of multimodal fiber orientations using the spherical harmonic basis. Magnetic Resonance Medicine 56, 104–117.Google Scholar
Hinshaw, SP (1992). Externalizing behavior problems and academic underachievement in childhood and adolescence: causal relationships and underlying mechanisms. Psychological Bulletin 111, 127–155.Google Scholar
Holzapfel, M, Barnea-Goraly, N, Eckert, MA, Kesler, SR, Reiss, AL (2006). Selective alterations of white matter associated with visuospatial and sensorimotor dysfunction in Turner syndrome. Journal of Neuroscience 26, 7007–7013.CrossRefGoogle ScholarPubMed
Humphrey, N, Symes, W (2010). Responses to bullying and use of social support among pupils with autism spectrum disorders (ASDs) in mainstream schools: a qualitative study. Journal of Research in Special Educational Needs 10, 82–90.Google Scholar
Jarvis, HL, Gathercole, SE (2003). Verbal and non-verbal working memory and achievements on National Curriculum tests at 11 and 14 years of age. Educational and Child Psychology 20, 123–140.Google Scholar
John, K, Gammon, GD, Prusoff, BA, Warner, V (1987). The Social Adjustment Inventory for Children and Adolescents (SAICA). Testing of a new semistructured interview. Journal of the American Academy of Child and Adolescent Psychiatry 26, 898–911.Google Scholar
Kain, W, Perner, J (2003). Do children with ADHD not need their frontal lobes for theory of mind? A review of brain imaging and neuropsychological studies. In The Social Brain: Evolution and Pathology (ed. Brune, M., Ribbert, H. and Schiefenhovel, W.), pp. 197–230. John Wiley & Sons: Chichester, UK.Google Scholar
Kawabata, Y, Tseng, WL, Gau, SS (2012). Symptoms of attention-deficit/hyperactivity disorder and social and school adjustment: the moderating roles of age and parenting. Journal of Abnormal Child Psychology 40, 177–188.Google Scholar
Klarborg, B, Skak Madsen, K, Vestergaard, M, Skimminge, A, Jernigan, TL, Baaré, WFC (2013). Sustained attention is associated with right superior longitudinal fasciculus and superior parietal white matter microstructure in children. Human Brain Mapping 34, 3216–3232.Google Scholar
Kobel, M, Bechtel, N, Specht, K, Klarhöfer, M, Weber, P, Scheffler, K, Opwis, K, Penner, IK (2010). Structural and functional imaging approaches in attention deficit/hyperactivity disorder: does the temporal lobe play a key role? Psychiatry Research 183, 230–236.Google Scholar
Koechlin, E, Ody, C, Kouneiher, F (2003). The architecture of cognitive control in the human prefrontal cortex. Science 302, 1181–1185.Google Scholar
Konrad, A, Dielentheis, TF, El Masri, D, Bayerl, M, Fehr, C, Gesierich, T, Vucurevic, G, Stoeter, P, Winterer, G (2010). Disturbed structural connectivity is related to inattention and impulsivity in adult attention deficit hyperactivity disorder. European Journal of Neuroscience 31, 912–919.Google Scholar
Konrad, K, Eickhoff, SB (2010). Is the ADHD brain wired differently? A review on structural and functional connectivity in attention deficit hyperactivity disorder. Human Brain Mapping 31, 904–916.Google Scholar
Li, Q, Sun, J, Guo, L, Zang, Y, Feng, Z, Huang, X, Yang, H, Lv, Y, Huang, M, Gong, Q (2010). Increased fractional anisotropy in white matter of the right frontal region in children with attention-deficit/hyperactivity disorder: a diffusion tensor imaging study. Neuroendocrinology Letters 31, 747–753.Google Scholar
Liston, C, Cohen, MM, Teslovich, T, Levenson, D, Casey, BJ (2011). Atypical prefrontal connectivity in attention-deficit/hyperactivity disorder: pathway to disease or pathological end point? Biological Psychiatry 69, 1168–1177.Google Scholar
Liston, C, Watts, R, Tottenham, N, Davidson, MC, Niogi, S, Ulug, AM, Casey, BJ (2006). Frontostriatal microstructure modulates efficient recruitment of cognitive control. Cerebral Cortex 16, 553–560.Google Scholar
Lo, YC, Soong, WT, Gau, SS, Wu, YY, Lai, MC, Yeh, FC, Chiang, WY, Kuo, LW, Jaw, FS, Tseng, WY (2011). The loss of asymmetry and reduced interhemispheric connectivity in adolescents with autism: a study using diffusion spectrum imaging tractography. Psychiatry Research 192, 60–66.CrossRefGoogle ScholarPubMed
Loe, IM, Feldman, HM (2007). Academic and educational outcomes of children with ADHD. Journal of Pediatric Psychology 32, 643–654.Google Scholar
Mabbott, DJ, Noseworthy, M, Bouffet, E, Laughlin, S, Rockel, C (2006). White matter growth as a mechanism of cognitive development in children. NeuroImage 33, 936–946.Google Scholar
MacKinnon, DP, Fairchild, AJ, Fritz, MS (2007). Mediation analysis. Annual Review of Psychology 58, 593–614.Google Scholar
Mori, S, Zhang, J (2006). Principles of diffusion tensor imaging and its applications to basic neuroscience research. Neuron 51, 527–539.Google Scholar
Nagel, BJ, Bathula, D, Herting, M, Schmitt, C, Kroenke, CD, Fair, D, Nigg, JT (2011). Altered white matter microstructure in children with attention-deficit/hyperactivity disorder. Journal of the American Academy of Child and Adolescent Psychiatry 50, 283–292.Google Scholar
Nakagawa, S (2004). A farewell to Bonferroni: the problems of low statistical power and publication bias. Behavioral Ecology 15, 1044–1045.Google Scholar
Oldfield, RC (1971). The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9, 97–113.Google Scholar
Pennington, BF, Ozonoff, S (1996). Executive functions and developmental psychopathology. Journal of Child Psychology and Psychiatry 37, 51–87.Google Scholar
Perneger, TV (1998). What's wrong with Bonferroni adjustments. British Medical Journal 316, 1236–1238.Google Scholar
Peterson, DJ, Ryan, M, Rimrodt, SL, Cutting, LE, Denckla, MB, Kaufmann, WE, Mahone, EM (2011). Increased regional fractional anisotropy in highly screened attention-deficit hyperactivity disorder (ADHD). Journal of Child Neurology 26, 1296–1302.Google Scholar
Petrides, M, Milner, B (1982). Deficits on subject-ordered tasks after frontal- and temporal-lobe lesions in man. Neuropsychologia 20, 249–262.Google Scholar
Preacher, KJ, Hayes, AF (2008). Asymptotic and resampling strategies for assessing and comparing indirect effects in multiple mediator models. Behavior Research Methods 40, 879–891.Google Scholar
Rapport, MD, Scanlan, SW, Denney, CB (1999). Attention-deficit/hyperactivity disorder and scholastic achievement: a model of dual developmental pathways. Journal of Child Psychology and Psychiatry 40, 1169–1183.Google Scholar
Reese, TG, Heid, O, Weisskoff, RM, Wedeen, VJ (2003). Reduction of eddy-current-induced distortion in diffusion MRI using a twice-refocused spin echo. Magnetic Resonance Medicine 49, 177–182.Google Scholar
Rubia, K, Cubillo, A, Smith, AB, Woolley, J, Heyman, I, Brammer, MJ (2010). Disorder-specific dysfunction in right inferior prefrontal cortex during two inhibition tasks in boys with attention-deficit hyperactivity disorder compared to boys with obsessive-compulsive disorder. Human Brain Mapping 31, 287–299.CrossRefGoogle ScholarPubMed
Rubia, K, Halari, R, Cubillo, A, Mohammad, A-M, Brammer, M, Taylor, E (2009). Methylphenidate normalises activation and functional connectivity deficits in attention and motivation networks in medication-naïve children with ADHD during a rewarded continuous performance task. Neuropharmacology 57, 640–652.Google Scholar
Sahakian, B, Jones, G, Levy, R, Gray, J, Warburton, D (1989). The effects of nicotine on attention, information processing, and short-term memory in patients with dementia of the Alzheimer type. British Journal of Psychiatry 154, 797–800.Google Scholar
Shang, CY, Wu, YH, Gau, SS, Tseng, WY (2013). Disturbed microstructural integrity of the frontostriatal fiber pathways and executive dysfunction in children with attention deficit hyperactivity disorder. Psychological Medicine 43, 1093–1107.Google Scholar
Silk, TJ, Vance, A, Rinehart, N, Bradshaw, JL, Cunnington, R (2009). White-matter abnormalities in attention deficit hyperactivity disorder: a diffusion tensor imaging study. Human Brain Mapping 30, 2757–2765.Google Scholar
Sonuga-Barke, EJ (2003). The dual pathway model of AD/HD: an elaboration of neuro-developmental characteristics. Neuroscience and Biobehavioral Reviews 27, 593–604.CrossRefGoogle ScholarPubMed
Swanson, JM, Kraemer, HC, Hinshaw, SP, Arnold, LE, Conners, CK, Abikoff, HB, Clevenger, W, Davies, M, Elliott, GR, Greenhill, LL, Hechtman, L, Hoza, B, Jensen, PS, March, JS, Newcorn, JH, Owens, EB, Pelham, WE, Schiller, E, Severe, JB, Simpson, S, Vitiello, B, Wells, K, Wigal, T, Wu, M (2001). Clinical relevance of the primary findings of the MTA: success rates based on severity of ADHD and ODD symptoms at the end of treatment. Journal of the American Academy of Child and Adolescent Psychiatry 40, 168–179.Google Scholar
Tamm, L, Barnea-Goraly, N, Reiss, AL (2012). Diffusion tensor imaging reveals white matter abnormalities in attention-deficit/hyperactivity disorder. Psychiatry Research 202, 150–154.Google Scholar
Tournier, J-D, Calamante, F, Gadian, DG, Connelly, A (2004). Direct estimation of the fiber orientation density function from diffusion-weighted MRI data using spherical deconvolution. NeuroImage 23, 1176–1185.Google Scholar
Tseng, WL, Kawabata, Y, Gau, SS (2011). Social adjustment among Taiwanese children with symptoms of ADHD, ODD, and ADHD comorbid with ODD. Child Psychiatry and Human Development 42, 134–151.Google Scholar
Tuch, DS (2004). Q-ball imaging. Magnetic Resonance Medicine 52, 1358–1372.Google Scholar
Tuch, DS, Salat, DH, Wisco, JJ, Zaleta, AK, Hevelone, ND, Rosas, HD (2005). Choice reaction time performance correlates with diffusion anisotropy in white matter pathways supporting visuospatial attention. Proceedings of the National Academy of Sciences USA 102, 12212–12217.Google Scholar
Uekermann, J, Kraemer, M, Abdel-Hamid, M, Schimmelmann, BG, Hebebrand, J, Daum, I, Wiltfang, J, Kis, B (2010). Social cognition in attention-deficit hyperactivity disorder (ADHD). Neuroscience and Biobehavioral Reviews 34, 734–743.Google Scholar
van Ewijk, H, Heslenfeld, DJ, Zwiers, MP, Buitelaar, JK, Oosterlaan, J (2012). Diffusion tensor imaging in attention deficit/hyperactivity disorder: a systematic review and meta-analysis. Neuroscience and Biobehavioral Reviews 36, 1093–1106.Google Scholar
van Ewijk, H, Heslenfeld, DJ, Zwiers, MP, Faraone, SV, Luman, M, Hartman, CA, Hoekstra, PJ, Franke, B, Buitelaar, JK, Oosterlaan, J (2014). Different mechanisms of white matter abnormalities in attention-deficit/hyperactivity disorder: a diffusion tensor imaging study. Journal of the American Academy of Child and Adolescent Psychiatry 53, 790–799.e3.Google Scholar
Vestergaard, M, Madsen, KS, Baaré, WFC, Skimminge, A, Ejersbo, LR, Ramsøy, TZ, Gerlach, C, Akeson, P, Paulson, OB, Jernigan, TL (2011). White matter microstructure in superior longitudinal fasciculus associated with spatial working memory performance in children. Journal of Cognitive Neuroscience 23, 2135–2146.Google Scholar
Wedeen, VJ, Hagmann, P, Tseng, WY, Reese, TG, Weisskoff, RM (2005). Mapping complex tissue architecture with diffusion spectrum magnetic resonance imaging. Magnetic Resonance Medicine 54, 1377–1386.Google Scholar
Wedeen, VJ, Wang, RP, Schmahmann, JD, Benner, T, Tseng, WY, Dai, G, Pandya, DN, Hagmann, P, D'Arceuil, H, de Crespigny, AJ (2008). Diffusion spectrum magnetic resonance imaging (DSI) tractography of crossing fibers. NeuroImage 41, 1267–1277.Google Scholar
Willcutt, EG, Doyle, AE, Nigg, JT, Faraone, SV, Pennington, BF (2005). Validity of the executive function theory of attention-deficit/hyperactivity disorder: a meta-analytic review. Biological Psychiatry 57, 1336–1346.Google Scholar
Wolf, RC, Plichta, MM, Sambataro, F, Fallgatter, AJ, Jacob, C, Lesch, KP, Herrmann, MJ, Schönfeldt-Lecuona, C, Connemann, BJ, Grön, G, Vasic, N (2009). Regional brain activation changes and abnormal functional connectivity of the ventrolateral prefrontal cortex during working memory processing in adults with attention-deficit/hyperactivity disorder. Human Brain Mapping 30, 2252–2266.Google Scholar
Wu, SY, Gau, SS (2013). Correlates for academic performance and school functioning among youths with and without persistent attention-deficit/hyperactivity disorder. Research in Developmental Disabilities 34, 505–515.Google Scholar
Wu, YH, Gau, SS, Lo, YC, Tseng, WY (2014). White matter tract integrity of frontostriatal circuit in attention deficit hyperactivity disorder: association with attention performance and symptoms. Human Brain Mapping 35, 199–212.Google Scholar
Yeterian, EH, Pandya, DN (1991). Prefrontostriatal connections in relation to cortical architectonic organization in rhesus monkeys. Journal of Comparative Neurology 312, 43–67.Google Scholar
Zelazo, PD, Carlson, SM (2012). Hot and cool executive function in childhood and adolescence: development and plasticity. Child Development Perspectives 6, 354–360.Google Scholar
Supplementary material: File

Gau Supplementary Material

Supplementary Information

Download Gau Supplementary Material(File)
File 624.1 KB