Cerebellar Circuitry in Development, Learning, and Clinical Conditions

Principal Investigator: Heidi Feldman, MD, PhD 

Research Coordinator: Lisa Bruckert, PhD / Email: bruckert@stanford.edu / Phone: (650) 498-7690

OUR RESEARCH

The cerebellum is a division of the human brain, situated below the cerebral hemispheres in the posterior fossa (Figure 1). Its distinctive anatomical structure is comprised of a continuous, tightly folded cortical sheet, creating the appearance of thin parallel grooves. The role of the cerebellum in motor functioning is well known. However, the cerebellum seems to play an important role in non-motor functions, including language and reading. Study of the cerebellum in children is particularly important because many disease processes injure the cerebellum during childhood.  Posterior fossa brain tumors are the most prevalent solid tumor in children. When these tumors are removed by surgery, approximately, 10-25% of children experience mutism, the total inability to speak, as a complication. Abnormal cerebellar development is a complication of extreme prematurity and has been associated with poor developmental outcomes. Cerebellar injury or dysmaturity has been implicated in developmental disabilities, including autism. The cerebellar cognitive affective syndrome is a serious condition with deficits in cognitive skills and emotional regulation. It affects children and adults and is caused by lesions within the cerebellum.

Beneath the cerebellar cortex is the cerebellar white matter. White matter contains bundles of myelinated axons that, like electrical wiring, connect local and distant gray matter regions of the cerebellum and cerebrum. Three major white matter pathways link the cerebellum to the cerebral hemispheres and spinal column—the superior, middle, and inferior cerebellar peduncles (Figure 2). The structure and functional properties of the cerebellar peduncles has not been well characterized in children at different ages. While many recent studies document the importance of cerebral white matter circuitry in human development and learning, it remains unclear how circuits that connect cerebellum to the rest of the brain change with age, experience, and disease.

This transdisciplinary project integrates the disciplines of pediatrics, neurology, radiology, psychology, neuroscience, human development, and education with the long-term goal of understanding the white matter circuitry of the human cerebellum in normal development and in relation to healthy and disordered cognitive functioning. The main tool for assessing the properties of white matter in vivo we use is diffusion magnetic resonance imaging (dMRI), which takes advantage of different diffusion properties of water within cerebrospinal fluid, gray matter, and white matter to generate measures of white matter cohesion and connectivity.

To date, we have analyzed clinically-acquired dMRI scans on over 100 children from age 4 days to 17 years to describe age-dependent characteristics of the cerebellar peduncles. We have documented significant associations between diffusion properties of the peduncles and individual differences in reading (Figure 3).  We have further found that diffusion properties of the inferior cerebellar peduncle at age 6 years predict their reading skills at age 8, even after consideration of demographic variables and individual variation in pre-reading prerequisite skills. Finally, we have been able to segment and tract the cerebellar peduncles in children who have undergone resection of cerebellar tumors.

We seek students who would like to gain knowledge and experience in neuroimaging to join our team to analyze new data sets regarding cerebellar circuitry.

Figure 1. Diffusion-weighted images of the cerebellum from a post-mortem specimen of a macaque, provided to Wandell from a colleague at the NIH. Left panel, axial view, and right panel, sagittal view show the intricate orientation of the tracts of the cerebellum: red = left-right orientation, green = anterior-posterior and blue = inferior-superior.  These images will be used in validation of diffusion images obtained in living children. 

 

Figure 2. Tractography of cerebellar peduncles. Two-dimensional rendering of inferior (yellow), middle (red) and superior (blue) cerebellar tracts. Left sagittal views (A-B) and coronal views (C-D). ICP=inferior cerebellar peduncle; MCP=middle cerebellar peduncle; SCP=superior cerebellar peduncle. L=left; R=right

Figure 3. FA of the left SCP, MCP and left ICP is associated with decoding skills. Strength of correlations between decoding standard scores and FA at 30 equidistant nodes are displayed on a colored cylinder surrounding tract renderings for the left SCP (a), MCP (c) and left ICP (e). Negative associations are observed between decoding skills and FA of the left SCP (a) and left ICP (e) as indicated in blue. Positive associations are observed between decoding skills and FA of the MCP (c) as indicated in red. Brown arrows (a,c,e) indicate cluster location where significant associations between Scatter plots represent the association between decoding standard scores and significant cluster mean FA for the left SCP (b), MCP (d) and left ICP (f). Color bar represents Spearman correlation coefficients. (FA = fractional anisotropy; SCP = superior cerebellar peduncle; MCP = middle cerebellar peduncle; ICP = inferior cerebellar peduncle; L = left; R = right; FT = full term; PT = preterm; rs = Spearman correlation coefficient).