Conrad Rockel

Diffusion tensor imaging of white matter after cranial radiation in children for medulloblastoma: Correlation with IQ

Treatment of children with cranial-spinal radiation (CSR) for brain tumors is associated with adverse intellectual outcome and white matter damage. However, the correlation between IQ and measures of white matter integrity has received little attention. We examined apparent diffusion coefficient (ADC), fractional anisotropy (FA), and intelligence in pediatric patients treated with CSR for medulloblastoma relative to control subjects. ADC and FA measures were obtained for eight patients and eight control children and evaluated in multiple regions of interest in the cerebral hemispheres. Mean ADC and mean FA for each region were calculated, group differences were evaluated, and the relationship between these measures and intelligence were examined. In our study group, decreased IQ was associated with increased ADC and decreased FA (P < 0.01). Mean IQ for the CSR group was lower than that for the control group, but the difference was not significant when controlling for overall mean FA or ADC (P > 0.10). Overall mean FA was lower and ADC was higher in the CSR group relative to controls (P < 0.01). Specifically, FA was lower in the genu of the corpus callosum, the anterior and posterior limbs of the internal capsule, inferior frontal white matter, and high frontal white matter, and ADC was higher in all regions in patients relative to controls (P < 0.01). Compromised white matter integrity was observed for multiple regions within the cerebral hemispheres following CSR. A novel finding was that microscopic damage in normal-appearing white matter, as indexed by higher ADC and lower FA, was related to poor intellectual outcome relative to age-matched controls.

White matter growth as a mechanism of cognitive development in children

We examined the functional role of white matter growth in cognitive development. Specifically, we used hierarchical regression analyses to test the unique contributions of age versus white matter integrity in accounting for the development of information processing speed. Diffusion tensor imaging was acquired for 17 children and adolescents (age range 6-17 years), with apparent diffusion coefficient (ADC) and fractional anisotropy (FA) calculated for 10 anatomically defined fiber pathways and 12 regions of hemispheric white matter. Measures of speeded visual-spatial searching, rapid picture naming, reaction time in a sustained attention task, and intelligence were administered. Age-related increases were evident across tasks, as well as for white matter integrity in hemispheric white matter. ADC was related to few measures. FA within multiple hemispheric compartments predicted rapid picture naming and standard error of reaction time in sustained attention, though it did not contribute significantly to the models after controlling for age. Independent of intelligence, visual-spatial searching was related to FA in a number of hemispheric regions. A novel finding was that only right frontal-parietal regions contributed uniquely beyond the effect of age in accounting for performance: age did not contribute to visual-spatial searching when FA within these regions was first included in the models. Considering we found that both FA in right frontal-parietal regions and speed of visual-spatial searching increased with age, our findings are consistent with the growth of regional white matter organization as playing an important role in increased speed of visual searching with age.

A comparison of contour and interval processing in musicians and nonmusicians using event-related potentials

Musicians and nonmusicians detected infrequent changes to the last note of five-note melodies that either altered the contour (up/down pattern) or the intervals (pitch distance between notes). Robust frontal P3as, reflecting automatic capture of attention, as well as P3bs, reflecting analytic stimulus evaluation, were generated in both contour and interval tasks. These components did not differ across groups for contour, but were smaller and delayed in nonmusicians compared to musicians for interval. However, the topologies were similar for P3a (frontal midline focus) and P3b (parietal midline focus) across groups and tasks, The amplitude of the P3b in musicians was negatively correlated with the age of onset of music lessons. Taken together these findings suggest that (a) contour processing is more basic, (b) interval processing may be more affected than contour by experience, and (c) similar brain networks are involved in generating the P3a and P3b in musicians and nonmusicians.

The relations between white matter and declarative memory in older children and adolescents.

Neural communication between the temporal and frontal cortex underlies mature declarative memory skills. The integrity of white matter pathways connecting these regions is likely critical in supporting this communication. Little is known about the relationship between white matter and declarative memory in older children and adolescents, an age period when advanced function in this domain is established. We acquired diffusion tensor imaging (DTI) data for 22 participants (9-15 years). Multiple DTI indices were calculated for the uncinate fasciculus - the major white matter tract connecting temporal and prefrontal regions. Indices were also calculated for compartments of lobar and posterior fossa white matter. Measures of visual-perceptual and auditory-verbal memory were administered. Correlation analyses were used to examine the relations between age, DTI indices, and memory. Voxel-wise analyses were also conducted. Age-related increases in FA were evident for frontal, parietal, and temporal hemispheric white matter. Proficiency in auditory-verbal memory was related to white matter integrity in the left uncinate fasciculus as well as parietal and cerebellar white matter. Proficiency in recall of a complex design was related to integrity within parietal and temporal regions. Our findings support the role of white matter in facilitating connectivity between cerebral regions important for declarative memory.

Cerebello-thalamo-cerebral connections in pediatric brain tumor patients: impact on working memory.

Brain tumors are the leading cause of death and disability from childhood disease in developed countries. Pediatric posterior fossa tumors are often effectively controlled with a combination of surgery, radiation, and chemotherapy, depending on tumor type. White matter injury following resection of tumor and radiation treatment is associated with cognitive declines, including working memory deficits. We investigated how brain injury following treatment for posterior fossa tumors results in deficits in working memory. We used diffusion tensor imaging and probabilistic tractography to examine the structural integrity of cerebello-thalamo-cerebral tracts in patients and healthy children. We also compared working memory outcome in patients versus controls, and related this function to integrity of cerebello-thalamo-cerebral tracts. Bilateral cerebello-thalamo-cerebral tracts were delineated in all participants. Patients treated with a combination of surgery and radiation had lower mean anisotropy and higher mean radial diffusivity within the cerebellar regions of the cerebello-thalamo-cerebral tract compared to patients treated with surgery only and healthy controls. Poorer working memory scores were observed for the cranial radiation group relative to controls. Reduced anisotropy and higher radial diffusivity within the entire cerebello-thalamo-cerebral pathway predicted lower working memory. Our finding that working memory function is related to the integrity of cerebello-thalamo-cerebral connections is a novel contribution to the understanding of cerebral-cerebellar communication. Identifying differences in the structural integrity of white matter for specific pathways is an essential step in attempting to localize the effects of posterior fossa tumors and their treatment methods.

White matter integrity and core cognitive function in children diagnosed with sickle cell disease.

Children diagnosed with sickle cell disease (SCD) have an increased risk of stroke, often associated with white matter damage and neurocognitive morbidity. Growing evidence suggests that subtle changes in white matter integrity, which do not pass the threshold to be visible on a clinical magnetic resonance image and classified as stroke, may contribute to decreased cognitive performance. We used archived diffusion-weighted imaging and neurocognitive assessment data to identify associations between microstructural changes in normal-appearing white matter and cognitive performance in children with SCD. Study participants included 10 healthy children and 15 pediatric SCD patients (5 with identified lesions and 10 without lesion). After excluding lesioned tissue from analyses, we detected significant increases in apparent diffusion coefficient across the brains of patients in comparison with control children, suggesting compromise to the structure of normal-appearing white matter. Deficits in working memory and processing speed were also apparent in patients. Increased apparent diffusion coefficient and deficiencies in processing speed were again detected in a subanalysis including only the patients without lesion. Correlation analyses evidenced associations between the microstructure of the right frontal lobe and cerebellum, and processing speed. This outcome suggests a relationship between tissue integrity and cognitive morbidity in SCD patients.

White matter maturation in visual and motor areas predicts the latency of visual activation in children

In humans, white matter maturation is important for the improvement of cognitive function and performance with age. Across studies the variables of white matter maturity and age are highly correlated; however, the unique contributions of white matter to information processing speed remain relatively unknown. We investigated the relations between the speed of the visually‐evoked P100m response and the biophysical properties of white matter in 11 healthy children performing a simple, visually‐cued finger movement. We found that: (1) the latency of the early, visually‐evoked response was related to the integrity of white matter in both visual and motor association areas and (2) white matter maturation in these areas accounted for the variations in visual processing speed, independent of age. Our study is a novel investigation of spatial‐temporal dynamics in the developing brain and provides evidence that white matter maturation accounts for age‐related decreases in the speed of visual response. Developmental models of cortical specialization should incorporate the unique role of white matter maturation in mediating changes in performance during tasks involving visual processing. Hum Brain Mapp, 2012.

Relations between white matter maturation and reaction time in childhood.

White matter matures with age and is important for the efficient transmission of neuronal signals. Consequently, white matter growth may underlie the development of cognitive processes important for learning, including the speed of information processing. To dissect the relationship between white matter structure and information processing speed, we administered a reaction time task (finger abduction in response to visual cue) to 27 typically developing, right-handed children aged 4 to 13. Magnetoencephalography and Diffusion Tensor Imaging were used to delineate white matter connections implicated in visual-motor information processing. Fractional anisotropy (FA) and radial diffusivity (RD) of the optic radiation in the left hemisphere, and FA and mean diffusivity (MD) of the optic radiation in the right hemisphere changed significantly with age. MD and RD decreased with age in the right inferior fronto-occipital fasciculus, and bilaterally in the cortico-spinal tracts. No age-related changes were evident in the inferior longitudinal fasciculus. FA of the cortico-spinal tract in the left hemisphere and MD of the inferior fronto-occipital fasciculus of the right hemisphere contributed uniquely beyond the effect of age in accounting for reaction time performance of the right hand. Our findings support the role of white matter maturation in the development of information processing speed.

Mapping of the cortical spinal tracts using magnetoencephalography and diffusion tensor tractography in pediatric brain tumor patients.

Prior to resection of a cerebral brain tumor, mapping of the functional and structural anatomy of the adjacent tissue is essential to reduce the risk of damage to descending and ascending pathways. We investigated the effectiveness of concurrent magnetoencephalography (MEG) and diffusion tensor imaging (DTI) tractography to delineate the motor cortex and associated corticospinal tract (CST) in a case series of children with brain tumors seen for pre-surgical evaluation. Using activation points generated from MEG to launch tractography, we delineated the CST of four patients and eight control subjects. Displacement of the CST was considerably larger in children with tumors located in the center of the hemisphere than in children whose tumors were more posteriorly located. Our findings suggest that the use of concurrent MEG and DTI may be an effective tool in the pre-surgical evaluation of eloquent cortex and associated white matter tracts in pediatric brain tumor patients.

Functional reorganization of the corticospinal tract in a pediatric patient with an arteriovenous malformation.

Presurgical mapping in a pediatric patient diagnosed with arteriovenous malformation in the left hemisphere revealed a case of apparent functional reorganization of a white matter tract. Magnetoencephalography (MEG) was used to identify the motor fields following hand movement. As expected, motor field activity for the left hand was detected in the right hemisphere. Surprisingly, MEG activity was also detected in the right hemisphere following movement of the right hand. MEG activations served as seeds from which to launch diffusion tensor imaging tractography to delineate the corticospinal tracts (CSTs). Using the MEG activation for movement of the right hand, we delineated a tract in the right hemisphere. A tract corresponding to motor function for the left hand was also delineated in the right hemisphere. For comparison, the CSTs of the patient were launched from anatomical landmarks at the precentral gyrus, and were successfully delineated in each hemisphere. Our findings suggest that the functional delineation of white matter pathways may be more sensitive than anatomical delineation for identifying reorganization of the developing brain in response to a lesion. This study is, to our knowledge, the first description of a functional reorganization of an existing tract to serve as a CST in children.