White Matter and Connectivity Abnormalities in Learning Disabilities: Evaluation by Diffusion Tensor Imaging

Walter E. Kaufmann, M.D.

Kennedy Krieger Institute, Baltimore, MD

Grant Program:

David Mahoney Neuroimaging Program

Funded in:

September 2000, for 4 years

Funding Amount:

$100,000

Investigator Biographies

Walter E. Kaufmann, M.D.

Professor of Neurology, Pediatrics, Psychiatry and Radiology, Kennedy Krieger Institute

Hypothesis

Hypothesis:
Cognitive deficits in some learning disability associated syndromes are the consequence of abnormalities in specific neural pathways. In velocardiofacial syndrome (VCFS), several major pathways in the posterior cortical regions seem to be affected, whereas reading disability (RD, dyslexia) specific deficits are related to a more selective involvement of pathways in the left perisylvian region.

Goals:
To characterize patterns of white matter abnormality in children with velocardiofacial syndrome and reading disabilities, with and without attention deficit hyperactivity disorder (ADHD), through evaluations of white matter architecture as well as fiber bundle integrity by DTI-based fiber bundle direction (color-coded) maps and fiber tracking. To assess the neurobehavioral predictive value of DTI parameters in these children by correlating DTI findings with cognitive variables.

Methods:
A MRI protocol will consist of either a high (zero-filled to 1x1x3mm) or low (zero-filled to 1x1x5mm) resolution diffusion-weighted multishot EPI sequence and a T1- weighted anatomical scan. Post-processing (Stieltjes et al. 2001) will include steps to calculate apparent diffusion coefficients (ADC), coherence index, and fractional anisotropy (FA). DTI measures will be quantified for defined areas and tracking results, and will be correlated with behavioral data.

Findings:
Our preliminary studies in dyslexia indicate that disruptions of white matter integrity and fiber bundle organization in the perisylvian region may underlie reading disability. Specifically, we observed decreased FA in the left superior longitudinal fasciculus (SLF), a major pathway connecting language-relevant areas of the cortex, as well as changes in the SLF’s orientation in the right hemisphere. Both parameters were directly related to reading ability, with greater tract abnormality being associated with poorer reading performance.

Selected Publications

Kanaan R.A., Kim J.S., Kaufmann W.E., Pearlson G.D., and McGuire P.K. Diffusion tensor imaging in schizophrenia: promise and reality. Biol Psychiatry. 2005 Dec 15;58(12):921-9.

Mori S., Kaufmann W.E., Davatzikos C., Stieltjes B., Amodei L., Fredericksen K., Pearlson G.D., Melhem E.R., Solaiyappan M., Raymond G.V., Moser H.W., and van Zijl P.C. Imaging cortical association tracts in the human brain using diffusion-tensor-based axonal tracking. Magn Reson Med. 2002 Feb;47(2):215-23.

Kates W.R., Frederikse M., Mostofsky S.H., Folley B.S., Cooper K., Mazur-Hopkins P., Kofman O., Singer H.S., Denckla M.B., Pearlson G.D., and Kaufmann W.E. MRI parcellation of the frontal lobe in boys with attention deficit hyperactivity disorder or Tourette syndrome. Psychiatry Res. 2002 Nov 30;116(1-2):63-81.

Stieltjes B., Kaufmann W.E., van Zijl P.C., Fredericksen K., Pearlson G.D., Solaiyappan M., and Mori S. Diffusion tensor imaging and axonal tracking in the human brainstem. Neuroimage. 2001 Sep;14(3):723-35.

Kates W.R., Burnette C.P., Jabs E.W., Rutberg J., Murphy A.M., Grados M., Geraghty M., Kaufmann W.E., and Pearlson G.D. Regional cortical white matter reductions in velocardiofacial syndrome: A volumetric MRI analysis. Biol Psychiatry. 2001 Apr 15;49(8):677-84.

Naidu S., Kaufmann W.E., Abrams M.T., Pearlson G.D., Lanham D.C., Fredericksen K.A., Barker P.B., Horska A., Golay X., Mori S., Wong D.F., Yablonski M., Moser H.W., and Johnston M.V. Neuroimaging studies in Rett syndrome. Brain Dev. 2001 Dec;23 Suppl 1:S62-71.