Samina Asad Taherbhoy Abstract - ETD Index Page

Samina Asad Taherbhoy
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Doctoral Dissertation
Samina Asad Taherbhoy
samina.taherbhoy@gmail.com
Neural Systems for Reading in Childhood
Medulloblastoma Survivors – An fMRI Study
Doctor of Philosophy
Biomedical Sciences
Integrated Program in Biomedical Sciences
Neuroscience
Robert J. Ogg, Ph.D.
robert.ogg@stjude.org
Detlef Heck, Ph.D.
Chia-Ho Hua, Ph.D.
Graduation Date: May 2013
Richard J. Smeyne, Ph.D.
Stephen White, DPhil
DCM, fMRI, Implicit reading,
Medulloblastoma, Orthographic, Phonologic
Embargoed for 12 months
Abstract
Medulloblastoma is the most common malignant brain tumor in children that occurs in
the cerebellum. Survival rates exceeding 75% are achieved with current treatment protocols,
which involve maximum surgical resection, craniospinal irradiation with or without
chemotherapy. Unfortunately, the majority of these survivors face life-long learning problems
and diminished IQ levels. A body of evidence suggests that disturbances in brain function,
including reading, may be related to a radiation insult to otherwise healthy nervous tissue.
Processing orthographic information takes place in the ventral visual system, which includes
brain areas exposed to high radiation dose due to close proximity to the tumor location.
Therefore, we hypothesized that radiation therapy causes disruption in the maturation of the

ain networks involved in reading. In order to compare how the brain networks of these cancer
survivors differ from the normal healthy controls, we studied these participants at varied time
points – right from start of therapy to end of therapy and 1 year follow-up in the patients as well
as baseline and 1 year after baseline for the controls. We used functional magnetic resonance
imaging (fMRI), a non-invasive technique, to explore which brain regions respond to
orthographic-phonologic processing and implicit reading. We evaluated the hemispheric
lateralization of the function and used dynamic causal modeling (DCM) to determine the
effective connectivity between regions of the ventral visual pathway. There was a decline in
overall brain activation in medulloblastoma patients after therapy and a shift from left
hemisphere dominance to a more bilateral pattern of activation. The effective connectivity
between regions involved in the reading process changed after therapy, with evidence of
increased dorsal visual pathway involvement to compensate for disrupted connectivity from
ventral visual areas to inferior frontal language areas. The functional imaging results support our
hypothesis of treatment-induced disruption of neural systems for reading. This research has
advanced understanding of the adverse effects of cancer therapy on brain function in children.
Functional neuroimaging will help identify potential targets for pharmacological and behavioral
interventions to improve cognitive function in cancer survivors who have already been treated,
and discover opportunities to reduce the negative effects of cancer therapy on patients treated in
the future.
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Revised 20 May 2013