Objective: Recent theoretical and empirical work suggests that while unmedicated, children with ADHD have a deficit in subcortical processing that leads to greater and more varied prefrontal cortical (PFC) activation, compared to (a) age-matched control participants and (b) their own brain activity while on stimulant medication. This pattern has been described elsewhere as inefficient. Method: Functional magnetic resonance imaging (fMRI) and functional connectivity analyses were used during a working memory task for five female adolescents with ADHD, aged 11 to 17 years, both on and off their usual dose of stimulant medication. Results: On medication, adolescents with ADHD demonstrated less PFC activation and less functional connectivity between frontal and subcortical regions compared to off medication. Conclusions: Because of the small sample size, results are presented as preliminary findings which await replication in a larger sample. However, these findings lend support to the idea that remediation of inefficiencies in PFC function for individuals with ADHD by stimulant medication may be related, in part, to frontal-subcortical connectivity. (J. of Att. Dis. 2010; 14(1) 69-78)
Aron, A., & Poldrack, R. ( 2005). The cognitve neuroscience of response inhibition: Relevance for genetic research in ADHD. Biological Psychiatry, 57, 1285-1292.
2.
Buchsbaum, B.R., Olsen, R.K., Koch, P., Berman, K.F. ( 2005). Human dorsal ventral auditory streams subserve rehearsal-based and echoic processes during verbal working memory. Neuron , 48(4), 687-97.
3.
Bush, G., Frzier, J., Rauch, S., Seidman, L., Whalen, P., Jenike, M., et al. (1999). Anterior cingulate cortex dysfunction in attention-deficit/hyperactivity disorder revealed by fMRI and the counting stroop. Biological Psychiatry, 45, 1542-1552.
4.
Casey, B.J., & Durston, S. ( 2006). From behavior to cognition to the brain and back: What have we learned from functional imaging studies of attention deficit hyperactivity disorder? American Journal of Psychiatry, 163, 957-960.
5.
Casey, B.J., Epstein, J.N., Buhle, J., Liston, C., Davidson, M.C., Tonev, S.T., et al. (2007). Frontostriatal connectivity and its role in cognitive control in parent-child dyads with ADHD American Journal of Psychiatry, 164, 1729-1736.
6.
Castellanos, X. ( 1999). The psychobiology of attention-deficit/ hyperactivity disorder. In Q. Hogan (Ed.), Handbook of disruptive behavior disorders(pp. 179-198). New York: Kluwer Academic/ Plenum Publishers.
7.
Castellanos, X., & Tannock, R. ( 2002). Neuroscience of attention-deficit/hyperactivity disorder: The search for endophenotypes. Nature Reviews Neuroscience , 3, 617-628.
8.
Denney, C.B., & Rapport, M.D. ( 1999). Predicting methylphenidate response in children with ADHD: Theoretical, empirical, and conceptual models. Journal of the American Academy of Child & Adolescent Psychiatry, 38, 393-401.
9.
D’Esposito, M., & Postle, B. ( 2002). The organization of working memory function in lateral prefrontal cortex: Evidence from event-related functional MRI. In D. K. Stuss, R. T. Knight (Ed.), Principles of frontal lobe function (pp. 168-187). New York: Oxford University Press.
10.
Dougherty, D.D., Bonab, A.A., Spencer, T.J., Rauch, S.L., Madras, B.K., & Fischman, A.J. (1999). Dopamine transporter density in patients with attention deficit hyperactivity disorder. Lancet, 354, 2132-2133.
11.
Dunlap, W.P., Cortina, J.M., Vaslow, J.B., & Burke, M.J. ( 1996). Meta-analysis of experiments with matched groups or repeated measures designs. Psychological Methods, 1, 170-177.
12.
Durston, S. ( 2003). A review of the biological bases of ADHD: What have we learned from imaging studies? Mental Retardation and Developmental Disabilities Research Reviews, 9, 184-195.
13.
Durston, S., Tottenham, N., Thomas, K., Davidson, M., Eigsti, I., & Yang, Y. ( 2003). Differential patterns of striatal activation in young children with and without ADHD. Biological Psychiatry, 53, 871-878.
14.
Fischer, M., Barkley, R.A., Smallish, L., & Fletcher, K. ( 2007). Hyperactive children as young adults: Driving abilities, safe driving behavior, and adverse driving outcomes. Accident Analysis & Prevention, 39, 94-105.
15.
Friston, K.J., Frith, C.D., Frackowiak, R.S.J., & Turner, R. ( 1995). Characterizing dynamic brain responses with fMRI: A multivariate approach. NeuroImage, 2, 166-172.
16.
Friston, K.J., Frith, C.D., Liddle, P.F., & Frackowiak, R.S. (1991). Comparing functional (PET) images: The assessment of significant change. Journal of Cerebral Blood Flow, 11, 690-699.
17.
Gazzaley A., Rissman, J., D’Esposito, M. ( 2004). Functional connectivity during working memory maintenance . Cognitive Affective and Behavioral Neuroscience. 4(4), 580-99.
18.
Giedd, J., Blumenthal, J., Molloy, E., & Castellanos, X. (2001). Brain imaging of attention deficit/hyperactivity disorder. In J. W. Wasserstein , L. E. Wolf, & F. Frank LeFever (Ed.), Brain mechanisms and life outcome (Vol. 931, pp. 33-49). New York: New York Academy of Sciences.
19.
Grace, A. ( 1995). The tonic/phasic model of dopamine system regulation: Its relevance for understanding how stimulant abuse can alter basal ganglia function. Drug and Alcohol Dependence, 37, 111-129.
20.
Greenhill, L., Beyer, D., Finkleson, J., Shaffer, D., Biederman, J., Conners, C., et al. (2002). Guidelines and algorithms for the use of methylphenidate in children with attention-deficit/ hyperactivity disorder . Journal of Attention Disorders, 6, s89-100.
21.
Halperin, J., & Schulz, K. ( 2006). Revisiting the role of the prefrontal cortex in the pathophysiology of attention-deficit/hyperactivity disorder. Psychological Bulletin, 132, 560-581.
22.
Hinshaw, S.P. ( 2002). Preadolescent girls with attention-deficit/ hyperactivity disorder: I. Background characteristics, comorbidity, cognitive and social functioning, and parenting practices. Journal of Consulting and Clinical Psychology, 70, 1086-1098.
23.
Liston, C., Watts, R., Tottenham, N., Davidson, M.C., Niogi, S., Ulug, A.M., et al. (2006). Frontostriatal microstructure modulates efficient recruitment of cognitive control. Cerebral Cortex , 16, 553-560.
24.
Mehta, M., Owen, A., Sahakian, B., Mavaddat, N., Pickard, J., & Robbins, T. ( 2000). Methylphenidate enhances working memory by modulating discrete frontal and parietal lobe regions in the human brain. Journal of Neuroscience, 20, 1-6.
25.
Nigg, J.T., Blaskey, L.G., Stawicki, J.A., & Sachek, J. ( 2004). Evaluating the endophenotype model of ADHD neuropsychological deficit: Results for parents and siblings of children with ADHD combined and inattentive subtypes. Journal of Abnormal Psychology, 113, 614-625.
26.
Nigg, J.T., & Casey, B.J. ( 2005). An integrative theory of attention-deficit/hyperactivity disorder based on the cognitive and affective neurosciences. Developmental Psychopathology, 17, 785-806.
27.
Rissman, J., Gazzaley, A., & D’Esposito, M. (2004). Measuring functional connectivity during distinct stages of a cognitive task. NeuroImage, 23, 752-763.
28.
Rubia, K., Smith, A.B., Brammer, M.J., & Taylor, E. ( 2007). Temporal lobe dysfunction in medication-naive boys with attention-deficit/ hyperactivity disorder during attention allocation and its relation to response variability. Biological Psychiatry , 62, 999-1006.
29.
Schulz, K.P., Fan, J., Tang, C., Newcorn, J., Buchsbaum, M., & Cheung, A. ( 2004). Response inhibition in adolescents diagnosed with attention deficit hyperactivity disorder during childhood: An event-related fMRI study . American Journal of Psychiatry, 161, 1650-1656.
30.
Schulz, K.P., Tang, C.Y., Fan, J., Marks, D.J., Newcorn, J.H., Cheung, A.M., et al. (2005). Differential prefrontal cortex activation during inhibitory control in adolescents with and without childhood attention-deficit/hyperactivity disorder. Neuropsychology, 19, 390-402.
31.
Schweitzer, J., Lee, D., Hanford, R., Tagamets, M., Hoffman, J., Grafton, S., et al. (2003). A positron emission tomography study of methylphenidate in adults with ADHD: Alterations in resting blood flow and predicting treatment response. Neuropsychopharmacology, 28, 967-973.
32.
Schweitzer, J.B., Faber, T.L., Grafton, S.T., Tune, L.E., Hoffman, J.M., Kilts, C.D. ( 2000). Alterations in the functional anatomy of working memory in adult attention deficit hyperactivity disorder. American Journal of Psychiatry, 157(2), 278-280.
33.
Schweitzer, J.B., Lee, D.O., Hanford, R.B., Zink, C.F., Ely, T.D., Tagaments, M.A., et al. (2004). Effect of methylphenidate on executive functioning in adults with attention-deficit/hyperactivity disorder: normalization of behavior but not related brain activity. Biological Psychiatry . 56(8): 597-606.
34.
Shaffer, D., Fisher, P., Lucas, C.P., Dulcan, M.K.,Schwab-Stone,M.E. ( 2000) NIMH Diagnostic Interview Schedule for Children Version IV (NIMH-DISC-IV): description, differences from previous versions, and reliability of some common diagnoses. Journal of the American Academy of Child and Adolescent Psychiatry. 39(1), 28-38.
35.
Sheridan, M.A., Hinshaw, S.P., & D’Esposito, M. (2007). Efficiency of the prefrontal cortex during working memory in attention-deficit/ hyperactivity disorder . Journal of the American Academy of Child and Adolescent Psychiatry, 46, 1357-1366.
36.
Sternberg, S. ( 1966). High-speed scanning in human memory. Science, 153, 652-654.
37.
Tamm, L., Menon, V., & Reiss, A.L. ( 2006). Parietal attentional system aberrations during target detection in adolescents with attention deficit hyperactivity disorder: Event-related fMRI evidence. American Journal of Psychiatry, 163, 1033-1043.
38.
Tzourio-Mazoyer, N., Landeau, B., Papathanassiou, D., Crivello, F., Etard, O., Delcroix, N., et al. (2002). Automated anatomical labeling of activations in SPM using macroscopic anatomical parcellation of the MNI MRI single-subject brain. Neuroimage, 15(1), 273-89.
39.
Volkow, N.D., & Swanson, J. ( 2003). Variables that affect the use and abuse of methylphenidate in the treatment of ADHD. American Journal of Psychiatry, 160, 1909-1918.
40.
Volkow, N.D., Wang, G.-J., Fowler, J.S., & Ding, Y.-S. ( 2005). Imaging the effects of methylphenidate on brain dopamine: New model on its therapeutic actions for attention-deficit/hyperactivity disorder . Biological Psychiatry, 57, 1410-1415.
41.
Volkow, N.D., Wang, G.-J., Fowler, J.-S., Telang, F., Maynard, L., Logan, J., et al. (2004). Evidence that methylphenidate enhances the saliency of a mathematical task by increasing dopamine in the human brain . American Journal of Psychiatry, 161, 1173-1180.
42.
Volkow, N.D., Wang, G.-J., Newcorn, J., Telang, F., Solanto, M.V., Fowler, J.S., et al. (2007). Depressed dopamine activity in caudate and preliminary evidence of limbic involvement in adults with attention-deficit/hyperactivity disorder. Archives of General Psychiatry, 64, 932-940.
43.
Wechsler, D. ( 1991). Manual for the Wechsler Intelligence Scale for Children-III (WISC-III). New York: Psychological Corporation.
