Decreased Callosal Thickness in Attention-Deficit/Hyperactivity Disorder

doi:10.1016/j.biopsych.2008.08.027

Biological Psychiatry

Volume 65, Issue 1, 1 January 2009, Pages 84-88

https://doi.org/10.1016/j.biopsych.2008.08.027 Get rights and content

Background

Neuroimaging studies of attention-deficit/hyperactivity disorder (ADHD) have revealed structural abnormalities in the brains of affected individuals. One of the most replicated alterations is a significantly smaller corpus callosum (CC), for which conflicting reports exist with respect to the affected callosal segments.

Methods

We applied novel surface-based geometrical modeling methods to establish the presence, direction, and exact location of callosal alterations in ADHD at high spatial resolution. For this purpose, we calculated the thickness of the CC at 100 equidistant midsagittal points in an age-matched male sample of 19 individuals with ADHD and 19 typically developing control subjects.

Results

In close agreement with many prior observations, the CC was shown to be significantly thinner in ADHD subjects in anterior and, particularly, posterior callosal sections. Covarying for intelligence did not significantly alter the observed ADHD effects. However, group differences were no longer present in anterior sections when covarying for brain volume and after excluding ADHD subjects comorbid for oppositional defiant disorder.

Conclusions

Decreased callosal thickness may be associated with fewer fibers or a decrease in the myelination of fibers connecting the parietal and prefrontal cortices. This might affect interhemispheric communication channels that are necessary to sustain attention or motor control, thus contributing to symptoms of hyperactivity and impulsivity, or inattention, observed in ADHD. Future studies are necessary to determine whether callosal abnormalities reflect maturational delays or persist into adulthood.

Section snippets

Subjects

We analyzed a sample of 19 children and adolescents with ADHD (mean age ± SD: 11.8 ± 2.7 years) and 19 age-matched normally developing control subjects (mean age ± SD: 11.7 ± 2.6 years), ranging from 7.2 to 16.2 years. The maximum allowed age difference within a matched pair was 6 months (for further demographic and clinical details, see Supplements 1 and 2). Only male subjects were studied because of the greater prevalence of ADHD among boys (18), as well as to minimize variance due to

ADHD Effects

Recruitment procedures attempted to match control to ADHD participants for overall intelligence, but ADHD individuals still had significantly lower IQ scores than normally developing age-matched control subjects (mean IQ ± SD: ADHD group = 92.11 ± 13.75; control group = 104.37 ± 9.95; p ≤ .03). In addition, ADHD individuals had significantly smaller total brain volumes than normally developing age-matched control subjects (mean TBV ± SD: ADHD group = 1430 cm³ ± .01; control group = 1530 cm³ ±

Discussion

In this study, we applied novel computational surface-based methods to calculate and compare callosal thickness at high spatial resolution in an age-matched sample of male ADHD and normally developing control subjects. We revealed significant ADHD effects in both anterior (genu/rostral body) and posterior sections (isthmus/anterior splenium). These findings are in agreement with previous studies that revealed a reduced callosal size in the callosal rostral body (6, 8), the genu (9), the isthmus

References (45)

E.M. Valera et al.
Meta-analysis of structural imaging findings in attention-deficit/hyperactivity disorder
Biol Psychiatry
(2007)
L.J. Seidman et al.
Structural brain imaging of attention-deficit/hyperactivity disorder
Biol Psychiatry
(2005)
A.L. Krain et al.
Brain development and ADHD
Clin Psychol Rev
(2006)
S. Hofer et al.
Topography of the human corpus callosum revisited—comprehensive fiber tractography using diffusion tensor magnetic resonance imaging
Neuroimage
(2006)
K.M. Bishop et al.
Sex differences in the human corpus callosum: Myth or reality?
Neurosci Biobehav Rev
(1997)
D. Shaffer et al.
NIMH Diagnostic Interview Schedule for Children Version IV (NIMH DISC-IV): description, differences from previous versions, and reliability of some common diagnoses
J Am Acad Child Adolesc Psychiatry
(2000)
J.C. Mazziotta et al.
A probabilistic atlas of the human brain: Theory and rationale for its developmentThe International Consortium for Brain Mapping (ICBM)
Neuroimage
(1995)
D.W. Shattuck et al.
Magnetic resonance image tissue classification using a partial volume model
Neuroimage
(2001)
M. Semrud-Clikeman et al.
Attention-deficit hyperactivity disorder: Magnetic resonance imaging morphometric analysis of the corpus callosum
J Am Acad Child Adolesc Psychiatry
(1994)
J. Liu et al.
Features of functional MRI in children with oppositional defiant disorder
Zhong Nan Da Xue Xue Bao Yi Xue Ban
(2008)

G.M. McAlonan et al.

Mapping brain structure in attention deficit-hyperactivity disorder: A voxel-based MRI study of regional grey and white matter volume

Psychiatry Res

(2007)

C.W. Wong

Corpus callosum and cerebral laterality in a modular brain model

Med Hypotheses

(2000)

J. Buchmann et al.

Disturbed transcallosally mediated motor inhibition in children with attention deficit hyperactivity disorder (ADHD)

Clin Neurophysiol

(2003)

J. Buchmann et al.

Modulation of transcallosally mediated motor inhibition in children with attention deficit hyperactivity disorder (ADHD) by medication with methylphenidate (MPH)

Neurosci Lett

(2006)

Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR)

(2000)

S. Durston

A review of the biological bases of ADHD: What have we learned from imaging studies?

Ment Retard Dev Disabil Res Rev

(2003)

J.N. Giedd et al.

Quantitative morphology of the corpus callosum in attention deficit hyperactivity disorder

Am J Psychiatry

(1994)

F.X. Castellanos et al.

Quantitative brain magnetic resonance imaging in attention-deficit hyperactivity disorder

Arch Gen Psychiatry

(1996)

T.L. Baumgardner et al.

Corpus callosum morphology in children with Tourette syndrome and attention deficit hyperactivity disorder

Neurology

(1996)

G.W. Hynd et al.

Corpus callosum morphology in attention deficit-hyperactivity disorder: Morphometric analysis of MRI

J Learn Disabil

(1991)

I.K. Lyoo et al.

The corpus callosum and lateral ventricles in children with attention-deficit hyperactivity disorder: A brain magnetic resonance imaging study

Biol Psychiatry

(1996)

D.E. Hill et al.

Magnetic resonance imaging correlates of attention-deficit/hyperactivity disorder in children

Neuropsychology

(2003)

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The corpus callosum (CC) is known to be altered in patients with schizophrenia. However, its morphologic characteristics are less well studied in treatment-naive first-episode schizophrenia patients, as is the effect of antipsychotic treatment on this structure.
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Compared with HCs, AN-FES patients showed a significant reduction of thickness in the posterior midbody of the CC. This deficit was correlated with severity of negative symptoms. After one year of antipsychotic treatment, there was no significant change in CC morphological measurements in schizophrenia patients, nor was there a significant difference of CC morphological measurements between good-outcome and poor-outcome subgroups at baseline or at 1-year follow-up.
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Citation Excerpt :
Given that the isthmus projects to primary motor and primary somatosensory cortices, this finding suggests that poor performance on a Go/No-Go task in girls with ADHD could be due to structural abnormalities in these regions. Luders et al. found that male adolescents with ADHD showed thinner CCs than their TD peers in anterior regions and, particularly, in posterior regions, whose fibers project to the parietal cortex, where the post-central gyrus is located (Luders et al., 2009). In a sample of male adults, Luders et al. observed a negative relationship between callosal thickness and ADHD symptomology, such that thinner callosal thickness was associated with greater inattention and hyperactivity (Luders et al., 2016).
Mirror overflow is a developmental phenomenon defined as unintentional movements that mimic the execution of intentional movements in homologous muscles on the opposite side of the body. In children with attention-deficit/hyperactivity disorder (ADHD), mirror overflow is commonly excessive, abnormally persistent, and correlated with ADHD symptom severity. As such, it represents a promising clinical biomarker for disinhibited behavior associated with ADHD. Yet, the neural underpinnings of mirror overflow in ADHD remain unclear. Our objective was to test whether intrinsic interhemispheric functional connectivity between homologous regions of the somatomotor network (SMN) is associated with mirror overflow in school age children with and without ADHD using resting state functional magnetic resonance imaging. To this end, we quantified mirror overflow in 119 children (8–12 years old, 62 ADHD) during a finger sequencing task using finger twitch transducers affixed to the index and ring fingers. Group ICA was used to identify right- and left-lateralized SMNs and subject-specific back reconstructed timecourses were correlated to obtain a measure of SMN interhemispheric connectivity. We found that children with ADHD showed increased mirror overflow (p < 0.001; d = 0.671) and interhemispheric SMN functional connectivity (p = 0.023; d = 0.521) as compared to typically developing children. In children with ADHD, but not the typically developing children, there was a significant relationship between interhemispheric SMN functional connectivity and mirror overflow (t = 2.116; p = 0.039). Our findings of stronger interhemispheric functional connectivity between homologous somatomotor regions in children with ADHD is consistent with previous transcranial magnetic stimulation and diffusion-tractography imaging studies suggesting that interhemispheric cortical inhibitory mechanisms may be compromised in children with ADHD. The observed brain-behavior correlation further suggests that abnormally strong interhemispheric SMN connectivity in children with ADHD may diminish their ability to suppress overflow movements.
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Speech sound disorder (SSD) is common, yet its neurobiology is poorly understood. Recent studies indicate atypical structural and functional anomalies either in one hemisphere or both hemispheres, which might be accompanied by alterations in inter-hemispheric connectivity. Indeed, abnormalities of the corpus callosum – the main fiber tract connecting the two hemispheres – have been linked to speech and language deficits in associated disorders, such as stuttering, dyslexia, aphasia, etc. However, there is a dearth of studies examining the corpus callosum in SSD. Here, we investigated whether a sample of 18 children with SSD differed in callosal morphology from 18 typically developing children carefully matched for age. Significantly reduced dimensions of the corpus callosum, particularly in the callosal anterior third, were observed in children with SSD. These findings indicating pronounced callosal aberrations in SSD make an important contribution to an understudied field of research and may suggest that SSD is accompanied by atypical lateralization of speech and language function.
Structural Integrity in the Genu of Corpus Callosum Predicts Conflict-induced Functional Connectivity Between Medial Frontal Cortex and Right Posterior Parietal Cortex
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Studies using the flanker task have reported that response conflict is detected by the medial frontal cortex (MFC). As a conflict alert system, the MFC shows enhanced functional communication with task-related regions. Previous studies have revealed individual differences in functional connectivity during cognitive task performance. However, the mechanisms underlying these individual differences remain unclear. In the current study, electroencephalography (EEG) was recorded while 30 subjects performed a flanker task that was modified to exclude feature integration and contingency learning. The diffusion tensor imaging (DTI) data were collected the day before the EEG session. FCz-P3/4 theta phase synchronization was used to measure functional connectivity between the MFC and posterior parietal cortex (PPC). Hierarchical regression analyses were used to assess the relationship between MFC-PPC conflict-induced theta phase synchronization and white matter integrity in significant regions derived from tract-based spatial statistics (TBSS) analysis. As expected, MFC-PPC theta phase synchronization was significantly enhanced during conflict, suggesting a conflict-induced functional connectivity. However, these findings were only found in the right hemisphere, which may be related to the asymmetrical role of the bilateral PPC in response conflict processing. Furthermore, hierarchical regression analyses revealed that 44% of individual variability in FCz-P4 conflict-induced theta phase synchronization could be explained by variations in axial diffusivity (AD) in the genu of the corpus callosum (gCC). These results demonstrated that structural integrity in the gCC predicts conflict-induced functional connectivity between the MFC and right PPC.
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Archival ReportDecreased Callosal Thickness in Attention-Deficit/Hyperactivity Disorder

Background

Methods

Results

Conclusions

Section snippets

Subjects

ADHD Effects

Discussion

Biol Psychiatry

Biol Psychiatry

Clin Psychol Rev

Neuroimage

Neurosci Biobehav Rev

J Am Acad Child Adolesc Psychiatry

Neuroimage

Neuroimage

J Am Acad Child Adolesc Psychiatry

Zhong Nan Da Xue Xue Bao Yi Xue Ban

Psychiatry Res

Med Hypotheses

Clin Neurophysiol

Neurosci Lett

Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR)

A review of the biological bases of ADHD: What have we learned from imaging studies?

Ment Retard Dev Disabil Res Rev

Quantitative morphology of the corpus callosum in attention deficit hyperactivity disorder

Am J Psychiatry

Quantitative brain magnetic resonance imaging in attention-deficit hyperactivity disorder

Arch Gen Psychiatry

Corpus callosum morphology in children with Tourette syndrome and attention deficit hyperactivity disorder

Neurology

Corpus callosum morphology in attention deficit-hyperactivity disorder: Morphometric analysis of MRI

J Learn Disabil

The corpus callosum and lateral ventricles in children with attention-deficit hyperactivity disorder: A brain magnetic resonance imaging study

Biol Psychiatry

Magnetic resonance imaging correlates of attention-deficit/hyperactivity disorder in children

Neuropsychology

Archival Report
Decreased Callosal Thickness in Attention-Deficit/Hyperactivity Disorder