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Brain & Development 27 (2005) 279285


Original article
Regional cerebral blood flow in children with ADHD: changes with age
Ozgur Onera,*, Pnar Onerb, Ayla Aysevc, Ozlem Kucukd, Erkan Ibisd
Advanced Research Fellow, NIMH Fogarty International Mental Health and Developmental Disabilities Program, Istanbul, Turkey
Mersin University School of Medicine Psychiatry Department, Turkey
Department of Child Psychiatry, University of Ankara Medical School, Ankara, Turkey
Department of Nuclear Medicine, University of Ankara Medical School, Ankara, Turkey
Received 4 June 2003; received in revised form 12 July 2004; accepted 22 July 2004

The aim of this study was to investigate the changes in regional cerebral blood flow (rCBF) with age in patients with attention deficit
hyperactivity disorder (ADHD). Twenty-nine drug-naive ADHD subjects (24 boys, 5 girls; age 713; meanGSDZage 9.2G2.1) and 12
subjects with epilepsy (all diagnosed as having complex partial seizure, 6 boys, 6 girls; age 714; meanGSDZ8.5G2.1) were included in
the study. All cases of ADHD were diagnosed according to DSM-IV criteria. Cerebral blood flow was evaluated with Tc-99m-
hexamethylpropyleneamine oxime (Tc99m HMPAO) brain single photon emission tomography (SPECT) during standard resting condition
in all of the cases. Asymmetry indices for each region of interest were calculated. Absolute rCBF values were normalized as the absolute
rCBF values divided by the whole brain absolute value. The prefrontal lobe asymmetry indices were significantly negatively correlated with
age in ADHD cases (rZK0.408, PZ0.025), which indicated the increased prefrontal rCBF lateralization from the right to the left side with
age. When ADHD cases older than 7 years of age were compared with those with epilepsy, the ADHD cases had lower right prefrontal and
frontal rCBF and higher left parietal rCBF. The epilepsy group showed no significant correlations between age and asymmetry indices and
showed a different developmental trajectory for prefrontal asymmetry and right prefrontal rCBF values. The results indicated that the left
hemisphere dominance in the prefrontal cortex significantly increases with age in ADHD cases.
q 2004 Elsevier B.V. All rights reserved.

Keywords: Attention deficit hyperactivity disorder; SPECT; Prefrontal cortex

1. Introduction cortex, and the caudate nucleus [816]. Thus, right-sided

abnormalities of the prefrontal cortex-basal ganglia circuit
Attention Deficit Hyperactivity Disorder (ADHD) is a have been implicated in pathophysiology of ADHD [17].
common disorder that affects many children, significantly There have been a number of MRI studies evaluating
impacting their potential for development [1]. There is an structural changes of the brain in normal subjects including
increasing convergence of results demonstrating both children. The findings of those studies are summarized as
structural and functional characteristics of the brains of follows: cerebral volume does not change significantly after
patients with ADHD. Structural MRI studies have shown 5 years of age [1820]; the cortical gray matter volume
abnormalities of the whole brain, the frontal lobes, the basal decreases significantly with age [21]; and the cerebral white
ganglia, the corpus callosum, the parietal lobes, and the matter volume increases throughout childhood [2022]:
cerebellar vermis [27]. The results of functional studies, these changes appear to be region specific [23].
mostly comprised of SPECT and PET, have not been PET studies involving children with neurological con-
entirely consistent, but indicated reduced brain activity in cerns (e.g. seizures, epilepsy, SturgeWeber syndrome)
the prefrontal and the parietal cortices, the anterior cingulate indicate that cerebral glucose metabolic rates follow a
triphasic evolution characterized by rapid increase after
* Corresponding author. Address: Gazi Ethem Pasa Sokak, Atala Apt.
birth, persistent high levels during childhood, possibly a
6/1, Senesenevler, 34742 Istanbul, Turkey. Fax: C90 312 3620809. result of increased energy demand resulting from transient
E-mail address: ozz_oner@yahoo.com (O. Oner). synaptic exuberance, and a subsequent decline to reach
0387-7604/$ - see front matter q 2004 Elsevier B.V. All rights reserved.
280 O. Oner et al. / Brain & Development 27 (2005) 279285

the adult levels by the end of adolescence [24,25]. Results of were mentally retarded as judged from their academic and
SPECT studies indicated that the activities of the frontal, social functioning. MRI images of those cases were not
parietal, left temporal and cingulate cortices were signifi- available. The SPECT scans of those subjects with epilepsy
cantly higher in children than in adults [26]. were collected from Ankara University Nuclear Medicine
The aim of the present study was to investigate the age- Department archives and analyzed quantitatively later for
specific changes in regional cerebral blood flow (rCBF) and this research. All of them were judged as unremarkable at
the degree of asymmetry in rCBF in ADHD subjects. There the level of visual inspection. We adopted those subjects as
have been few previous SPECT studies involving ADHD controls in this study because, as in the previous studies
children and none have evaluated the changes in rCBF conducted with children, it was impossible to obtain SPECT
with age. images of children with no neurological problems.

2.2. Image acquisition

2. Method
All children and their parents were informed of the
2.1. Subjects procedure for SPECT. The subjects were asked to lie calmly
at supine with one of his/her parents accompanying them
Subjects were 29 patients with ADHD (24 boys, 5 girls; without talking to him/her, with eyes closed with minimal
age 713; meanGSDZ9.19G2.01). None of the cases were sensory stimulation for 5 min and then received Tc99m
left handed per Pediatric Assessment of Neurological Soft HMPAO intravenously under resting conditions with
Signs [27] handedness items. All of the cases were minimal sensory stimulation (eyes covered in a quiet,
Caucasian. All subjects were recruited from the general dimly lit room). The dose of Tc99m HMPAO was calculated
outpatient clinic at the Child Psychiatry Department, who as [(ageC1)/(ageC7)]!standard adult dose (15 mCi).
fulfilled the inclusion criteria. The same group of patients Patients were asked to lie calmly for an additional period
has been the subjects of the two previous studies by the of 5 min after the injection. The SPECT image acquisition
same investigators: the one on the effects of methylpheni- started 15 min after the injection. The researchers were
date on the rCBF [28] and the other one on the rCBF in present during the scanning in order to control the
juvenile obsessive-compulsive disorders and ADHD [29]. conditions for compliance with the procedure.
Informed consent was obtained from the parents before The radiochemical purity was assessed by instant thin-
enrollment with local ethics committee approval for layer chromatography and was always above 90%. Scans
inclusion in both of the studies. Diagnosis was based on were performed with a SPECT system (GE 4000I) using a
DSM-IV criteria and was established by a consensus of at high resolution collimator and were acquired over 3 min as
least two psychiatrists. ADHD symptom severity was 128 projections into 64!64 matrices (each pixel 4!4 mm).
evaluated in 17 cases using Conners Teacher Rating These data were processed using Meltz filter and were
Scale [31]: inattentiveness score was 11.2G4.9 (meanG reconstructed by filtered back-projection with a Ramp filter.
SD); hyperactivity 13.2G0.4; conduct problems 9.0G0.8; Attenuation correction was applied to the data using the
total score 39.0G10.6. Sorenson method. Oblique reorientation was performed to
All ADHD cases had unremarkable medical history other yield 2-pixel-thick (8 mm) transaxial images parallel to the
than ADHD and were clinically screened for psychosis, orbitomeatal line.
eating disorders, substance use disorders, pervasive devel- Regions of interest (ROIs) were generated manually over
opmental disorders, and mental retardation. In all of the the right cerebral hemisphere in the prefrontal, frontal,
ADHD cases, diagnoses were of combined subtype [30]. All temporal, and parietal cortices. Occipital cortex, basal
patients were diagnosed for the first time and had never been ganglia, and cerebellum could not be evaluated due to data
evaluated for psychiatric disorders or treated with psycho- loss by a computer error for these regions in a substantial
pharmacological medicine. SPECT study was performed proportion of the subjects of the epilepsy group. Analysis
relatively shortly (within 2 weeks) after the diagnosis was was performed by one of the authors who were unaware of
made. the subjects diagnosis. To increase the objectivity of the
The subjects with epilepsy (age range 714 years; findings, a Bayesian approach to interpretation was used,
meanGSDZ8.5G2.11; 6 boys and 6 girls) included with the reading rendered initially without, and then with,
children who were referred for SPECT investigation for the knowledge of the clinical parameters [32]. Double-
epilepsy work-up, as the diagnosis of complex partial reading of scans with third-party adjudication for disputed
seizure (legion related epilepsy) was suspected: the most findings was used to ensure quality control.
common clinical manifestations included altered level of Transaxial slices were selected with a neuroanatomical
consciousness (i.e. aura followed by confusional state, etc.), reference method [33] used as a reference guide, in order to
which were suggestive of complex partial seizures. These encompass the different ROIs. Semiquantitative evaluation
children had been diagnosed as epilepsy for the first time was performed by drawing irregular ROIs in five standar-
and never been on antiepileptic drugs. None of the patients dized 8-mm-thick oblique slices corresponding to
O. Oner et al. / Brain & Development 27 (2005) 279285 281

anatomical levels that define the boundaries of anatomical 3.3. Correlations with the teacher ratings
structures. No attempt was made to compare counts in ROIs
directly. Uptakes of the radioligand in these regions were Right prefrontal and left temporal rCBF were significantly
calculated and expressed as within-subject ratios to the correlated with the inattentiveness score (rZ0.547, PZ0.02;
cortical blood flow (the sum of the rCBF values for the rZK0.528, PZ0.03, respectively). There were no other
bilateral prefrontal, frontal, parietal, and temporal cortices) significant correlations between the teacher ratings and the
to normalize the scans. Right and left hemisphere rCBF SPECT variables (K0.34!r!0.44; 0.08!P!0.99).
asymmetry indices were calculated by the formula (right Regarding the asymmetry indices, the most significant
rCBFKleft rCBF)/(right rCBFCleft rCBF). correlation was between the Total Problems score and the
prefrontal asymmetry values (rZ0.44, PZ0.08). Age of the
2.3. Data analysis patients was not significantly correlated with the teacher
ratings (K0.162!r!0.385; 0.127!P!0.535).
In order to detect rCBF changes with age, we calculated
the correlations of relative perfusions in the right and left
cerebral areas and asymmetry indices with age by using the 4. Discussion
Pearsons correlation coefficient. The gender distribution in
the ADHD group and epilepsy group were different, but Our results indicate that the prefrontal cortex rCBF
did not reach statistically significant levels (x2Z4.64, during resting conditions in ADHD cases shows increased
PZ0.052, Fishers Exact Test). The age distribution in the lateralization from the right to the left with age and that
ADHD cases and epilepsy group were not statistically ADHD cases have lower right prefrontal and frontal and
different (FZ0.91; dfZ1,39; PZ0.34). MannWhitney-U higher parietal relative rCBF values compared with those
test and analysis of variance (ANOVA) were performed in patients with epilepsies. The differences between the groups
order to compare the rCBF between ADHD cases and are more prominent when subjects older than 7 years of age
epilepsy cases. Two-tailed significance tests (P!0.05) are were compared. The decreased right prefrontal and frontal
reported throughout. SPSS 10.0 statistical package (SPSS, rCBF is consistent with previous studies that reported
Inc.) was used for the analysis. greater dysfunction in the right hemisphere [1734]. A loss
of normal asymmetry in the volume of the caudate nucleus
and in the volume of the right striatal and anterior frontal
areas in subjects with ADHD has been demonstrated, which
3. Results is suggestive of a deviation from normal development of
right frontal-subcortical circuits [2,3]. Functional imaging
and electroencephalographic studies have shown a failure of
3.1. Correlations with age right prefrontal activation during response inhibition
paradigms in ADHD [15,35,36]. Normally, there is a
Age was not significantly correlated with any of the coupling of cerebral blood flow and functional activity
relative rCBF values (K0.340!r!0.193; 0.07!P!0.91) [10], and of glucose utilization and the number of neurons
in the ADHD group. However, with increasing age and synapses in a region [25]. The lower prefrontal cortex
prefrontal asymmetry indices decreased significantly volumes reported previously might be related with lower
(rZK0.407, P!0.028) in the ADHD group. In the epilepsy prefrontal rCBF values in ADHD cases. The parietal cortex
group, there were no significant correlations of rCBF was also reported to be effected in ADHD [3]. Overall, our
or asymmetry indices with age (K0.100!r!0.430; results were consistent with these studies, particularly for
0.15!P!0.84). Changes with age in the rCBF values cases older than 7 years of age.
(Fig. 1) and asymmetry indices (Fig. 2) in the prefrontal and Our results have shown a trend as increasing age for
frontal cortices in the two groups were evaluated. lower right and higher left prefrontal and frontal rCBF
values in the ADHD group (Figs. 1 and 2). The correlation
3.2. rCBF in ADHD and epilepsy subjects coefficients become significant when the asymmetry values,
that is the difference between right and left rCBF, are taken
ADHD cases had significantly lower right prefrontal and into account. The epilepsy subjects showed a different
frontal rCBF values (FZ4.99, dfZ1,39, PZ0.03; FZ5.05, developmental trajectory for prefrontal asymmetry and right
dfZ1,39, PZ0.03) and higher left parietal rCBF values prefrontal rCBF values. An intriguing finding of the present
(FZ5.03, dfZ1,39, PZ0.03, ANOVA) compared with study was that the rCBF differences between the ADHD and
epilepsy subjects (Table 1). These differences were more epilepsy groups (lower right prefrontal and frontal rCBF
significant when cases older than 7 years of age (nZ20 for values and higher left parietal rCBF values in ADHD) were
ADHD, nZ7 for epilepsy) were compared (right prefrontal: more prominent in cases older than 7 years of age. From the
zZK2.76, PZ0.004; right frontal: zZK2.21, PZ0.027; regression lines in Fig. 2 (indicating decreasing right
left parietal: zZK2.82, PZ0.003; MannWhitney-U test). relative to left prefrontal and frontal rCBF values with age
282 O. Oner et al. / Brain & Development 27 (2005) 279285

Fig. 1. Right and left prefrontal and frontal rCBF values in ADHD subjects (nZ29) (left side) and those with epilepsy (nZ12) (right side). Regression lines
with 95% confidence intervals. Abscissa: age in years. Ordinate: CBF in percent of total rCBF (the sum of rCBF values for the bilateral prefrontal, frontal,
parietal, and temporal cortices) to the prefrontal and frontal regions.

in ADHD group), we infer that the decrease of relative right Frontal lobes are among the last cortical regions to
prefrontal rCBF with age in ADHD group might account for mature anatomically and functionally and the frontalisation
the more prominent rCBF differences in older subjects. process may not be over until the mid-twenties [25,3739].
However, with the 95% confidence intervals for older Previous studies conducted with normal pediatric popu-
subjects being quite large in the epilepsy group, these results lations have indicated that the rates of glucose metabolism
must be interpreted with caution. in the cerebrum exceed those of adults by 34 years of age,
O. Oner et al. / Brain & Development 27 (2005) 279285 283

Fig. 2. Prefrontal and frontal asymmetry values of ADHD (nZ29) (left side) and epilepsy (nZ12) (right side) groups. Regression lines with 95% confidence

maintained until approximately 9 years of age when they fluorodopa ([F18]FDOPA) PET in adult ADHD cases,
begin to decline [25]. A former SPECT study conducted and the variability of F18 ratios may be higher in regions
with 23 normal children indicated that both left and right with low dopaminergic activity like prefrontal cortex, which
cortical rCBF values decreased with age [26]. The decrease makes interpretation of results more difficult. Another
of the relative right prefrontal rCBF with age in the ADHD important point is the ages of the sample. As the authors
group observed in the present study was somehow suggested, due to maturation and aging processes, there
unexpected. It may be accounted for as follows; the might be clinical and biological differences between adult
ADHD cases in our study were diagnosed for the first and child ADHD cases [40].
time and had never been treated for ADHD. Those data The present study has several limitations. Our study
taken together, it may be inferred that the longer period had a methodological disadvantage as compared to PET
before the diagnosis is made might be related with the lower Table 1
prefrontal brain volumes and hence with the lower rCBF rCBF in percent of total CBF (the sum of the CBF values for bilateral
values. However, more data are required to support this prefrontal, frontal, parietal, and temporal cortices)
hypothesis. Region Epilepsy (CPS) ADHD
The symptom severity assessed by teacher reports was
Mean SD Mean SD
correlated positively with right prefrontal rCBF in ADHD
cases. Some of the former studies reported a negative Right prefrontal 12.7 0.81 12.2 0.69
Right frontal 12.7 0.55 12.3 0.45
correlation between symptom severity and prefrontal Right parietal 12.1 0.78 12.5 0.75
dopamine metabolism [40], while others reported that Right temporal 12.7 0.64 13.0 0.98
higher symptom severity was related with higher right Left prefrontal 12.4 0.73 12.2 0.72
perfusion relative to left [41]. These differences might be Left frontal 12.6 0.54 12.4 0.48
Left parietal 11.9 0.72 12.4 0.52
related with the neuroimaging methods and sample
Left temporal 12.7 0.88 13.0 0.98
characteristics. The former study utilized [fluorine-18]
284 O. Oner et al. / Brain & Development 27 (2005) 279285

and fMRI studies due to the thicker slices and lower [6] Castellanos FX, Lee PP, Sharp W, Jeffries NO, Greenstein DK,
resolution, which do not allow us to discriminate between Clasen LS, et al. Developmental trajectories of brain volume
abnormalities in children and adolescents with attention-deficit
specific subregions, especially in subcortical structures. We
hyperactivity disorder. J Am Med Assoc 2002;288:17408.
did not have MRI or EEG evaluations, which could have [7] Mostofsky SH, Reiss AL, Lockhart P, Denckla MB. Evaluation of
detected an asymmetry. The group of epilepsy (complex cerebellar size in attention-deficit hyperactivity disorder. J Child
partial seizure, legion related epilepsy) could not be Neurol 1998;13:4349.
considered as healthy control and was not screened for [8] Zametkin AJ, Nordahl TE, Gross ME, King AC, Semple WE,
psychiatric disorders. Further, we did not have rCBF values Rumsey J, et al. Cerebral glucose metabolism in adults with
hyperactivity of childhood onset. N Engl J Med 1990;323:13616.
for some of the cortical and subcortical regions and for the [9] Zametkin AJ, Liebenauer LL, Fitzgerald GA, King AC,
cerebellum, which were all reported to be important in the Minkunas DV, Herscovitch P, et al. Brain metabolism in teenagers
pathophysiology of ADHD. For this reason it was with attention-deficit hyperactivity disorder. Arch Gen Psychiatry
impossible to investigate the basal ganglia-prefrontal 1993;50:33340.
circuit. Because there were only two subjects with epilepsy [10] Lou H, Edvinsson L, MacKenzie ET. The concept of coupling blood
flow to brain function: revision required? Ann Neurol 1987;22:
that were older than 9 years old, it was not fully justifiable to
compare rCBF values between epilepsy and ADHD cases in [11] Lou H, Henriksen L, Bruhn P. Focal cerebral dysfunction in
this age group. developmental learning disabilities. Lancet 1990;335:811.
Nevertheless, though preliminary, this is one of few [12] Sieg KG, Gaffney GR, Preston DF, Hellings JA. SPECT brain
studies concerned with age-specific changes of rCBF in imaging abnormalities in attention deficit hyperactivity disorder. Clin
ADHD subjects. Our results indicated that, with increasing Nucl Med 1995;20:5560.
[13] Brandeis D, van Leeuwen TH, Rubia K, Vitacco D, Steger J, Pascual-
age, left hemisphere dominance in the prefrontal cortex Marqui RD, et al. Neuroelectric mapping reveals precursor of stop
significantly increased in ADHD cases as compared to failures in children with attention deficits. Behav Brain Res 1998;94:
epileptic patients. Knowledge about functional changes of 11125.
the brain in children with ADHD is critical in understanding [14] Bush G, Frazier JA, Rauch SL, Seidman LJ, Whalen PJ, Jenike MA,
the pathophysiology of the disorder. et al. Anterior cingulate cortex dysfunction in attention-deficit/-
hyperactivity disorder revealed by fMRI and the Counting Stroop.
Biol Psychiatry 1999;45:154252.
[15] Rubia K, Overmeyer S, Taylor E, Brammer M, Williams SC,
Simmons A, et al. Hypofrontality in attention deficit hyperactivity
disorder during higher-order motor control: a study with functional
MRI. Am J Psychiatry 1999;156:8916.
Part of this study was supported by the Ankara [16] Vaidya CJ, Austin G, Kirkorian G, Ridlehuber HW, Desmond JE,
University, project number: 201-08-09-045. We would Glover GH, et al. Selective effects of methylphenidate in attention
also like to thank Kerim M. Munir, the Principle deficit hyperactivity disorder: a functional magnetic resonance study.
Investigator of the NIMH Fogarty International Mental Proc Natl Acad Sci 1998;144949.
[17] Castellanos FX. Toward a pathophysiology of attention deficit
Health and Developmental Disabilities Research Training hyperactvity disorder. Clin Pediatr 1997;36:38193.
Program (D43TW05807) at Childrens Hospital Boston, [18] Giedd JN, Snell JW, Lange N, Rajapakse JC, Casey BJ, Kozuch PL,
and Verda Tunaligil for their contributions to this article. et al. Quantitative magnetic resonance imaging of human brain
development: ages, 418. Cereb Cortex 1996;6:55160.
[19] Giedd JN, Vaituzis AC, Hamburger SD, Lange N, Rajapakse JC,
Kaysen D, et al. Quantitative MRI of the temporal lobe, amygdala,
References and hippocampus in normal human development: ages 418 years.
J Comp Neurol 1996;366:22330.
[1] Seidman LJ, Biederman J, Faraone SV, Weber W, Ouellette C. [20] Reiss AL, Abrams MT, Singer HS, Ross JL, Denckla MB. Brain
Toward defining a neuropsychology of attention deficit-hyperactivity development, gender and IQ in children. A volumetric imaging study.
disorder: performance of children and adolescents from a large Brain 1996;119:176374.
clinically referred sample. J Consult Clin Psychol 1997;65:15060. [21] Giedd JN, Blumenthal J, Jeffries NO, Castellanos FX, Liu H,
[2] Castellanos FX, Giedd JN, Marsh WL, Hamburger SD, Vaituzis AC, Zijdenbos A, et al. Brain development during childhood and
Dickstein DP, et al. Quantitative brain magnetic resonance imaging in adolescence: a longitudinal MRI study. Nat Neurosci 1999;2:8613.
attention-deficit hyperactivity disorder. Arch Gen Psychiatry 1996;53: [22] Frazier JA, Giedd JN, Hamburger SD, Albus KE, Kaysen D,
60716. Vaituzis AC, et al. Brain anatomic magnetic resonance imaging in
[3] Filipek PA, Semrud-Clikeman M, Steingard RJ, Renshaw PF, childhood-onset schizophrenia. Arch Gen Psychiatry 1996;53:
Kennedy DN, Biederman J. Volumetric MRI analysis comparing 61724.
subjects having attention-deficit hyperactivity disorder with normal [23] Casey BJ, Giedd JN, Thomas KM. Structural and functional brain
controls. Neurology 1997;48:589601. development and its relation to cognitive development. Biol Psychol
[4] Casey BJ, Castellanos FX, Giedd JN, Marsh WL, Hamburger SD, 2000;54:24157.
Schubert AB, et al. Implication of right frontostriatal circuitry in [24] Bentourkia M, Michel C, Ferriere G, Bol A, Coppens A, Sibomana M,
response inhibition and attention-deficit/hyperactivity disorder. J Am et al. Evolution of brain glucose metabolism with age in epileptic
Acad Child Adolesc Psychiatry 1997;36:37483. infants, children and adolescents. Brain Dev 1998;20:5249.
[5] Berquin PC, Giedd JN, Jacobsen LK, Hamburger SD, Krain AL, [25] Chugani HT, Phelps ME, Mazziotta JC. Positron emission tomogra-
Rapoport JL, et al. Cerebellum in attention-deficit hyperactivity phy study of human brain functional development. Ann Neurol 1987;
disorder: a morphometric MRI study. Neurology 1998;50:108793. 22:48797.
O. Oner et al. / Brain & Development 27 (2005) 279285 285

[26] Barthel H, Wiener M, Dannenberg C, Bettin S, Sattler B, Knapp WH. [34] Reid HM, Norvilitis JM. Evidence for anomalous lateralization across
Age specific cerebral perfusion in 4 to 15 year old children: a high- domain in ADHD children as well as adults identified with the
resolution brain SPET study using 99mTc-ECD. Eur J Nucl Med 1997; Wender Utah Rating scale. J Psychiatr Res 2000;34:3116.
24:124552. [35] Langleben DD, Austin G, Krikorian G, Ridlehuber HW, Goris ML,
[27] Denckla MB. Revised neurological examination and subtle signs. Strauss HW. Interhemispheric asymmetry of regional cerebral blood
Psychopharmacol Bull 1985;21:7739. flow in prepubescent boys with attention deficit hyperactivity
[28] Aysev A, Oner , Ibis E, Kucuk O. SPECT imaging of ADHD children disorder. Nucl Med Commun 2001;22:133340.
before and after methylphenidate treatment. Presentation in 11th [36] Oades RD. Frontal, temporal and lateralized brain function in children
international congress of European society of child and adolescent with attention-deficit hyperactivity disorder: a psychophysiological
psychiatry, abstract in congress book 1999 p. 223. and neuropsychological viewpoint on development. Behav Brain Res
[29] Oner P, Aysev A, Oner , Kucuk , Ibis E. Exploration of cerebral blood 1998;94:8395.
flow of children with obsessive compulsive disorder and attention [37] Weinberger DR. Implications of normal brain development for the
pathogenesis of schizophrenia. Arch Gen Psychiatry 1987;44:6609.
deficit hyperactivity disorder: a comparative SPECT study. 2002
[38] Huttenlocher PR. Morphometric study of human cerebral cortex
ICCAPAP abstract book 2002 p. 49.
development. Neuropsychologia 1990;28:51727.
[30] American Psychiatric Association. Diagnostic and statistical manual
[39] Sowell ER, Thompson PM, Tessner KD, Toga AW. Mapping
of mental disorders, 4th ed. Washington, DC: APA; 1994.
continued brain growth and gray matter density reduction in dorsal
[31] Goyette CH, Conners CK, Ulrich RF. Normative data on revised
frontal cortex: inverse relationships during postadolescent brain
Conners parent and teacher rating scales. J Abnorm Child Psychol
maturation. J Neurosci 2001;21:881929.
1978;6:22136. [40] Ernst M, Zametkin AJ, Matochik JA, Jons PH, Cohen RM. DOPA
[32] OTuama LA, Dickstein DP, Neeper R, Gascon GG. Functional brain decarboxylase activity in attention deficit hyperactivity disorder
imaging in neuropsychiatric disorders of childhood. J Child Neurol adults. A [Fluorine-18]Fluorodopa positron emission tomographic
1999;14:20721. study. J Neurosci 1998;18:59017.
[33] Mountz JM, Zhang B, Liu BH, Inampudi C. A reference method for [41] Spalletta G, Pasini A, Pau F, Guido G, Menghini L, Caltagirone C.
correlation of anatomic and functional brain images: validation and Prefrontal blood flow dysregulation in drug naive ADHD children
clinical application. Semin Nucl Med 1994;24:25671. without structural abnormalities. J Neural Transm 2001;108:120316.