Small brain, Big Consequences: EMC Synergy CDCM

Background

Understanding how the brain develops and how deviations from typical neurodevelopment are linked to health and disease remains a top priority in clinical neuroscience. Research to date has disproportionately focused on the development of the cerebrum, thereby omitting the so-called ‘small brain’, the cerebellum. While the cerebellum’s involvement in motor control is well-documented, recent studies have made clear that it also plays a crucial role in higher cognitive function.

Small brain, big consequences

Recent work suggests that disrupted cerebellar development distorts cortical maturation. However, little is known about mechanisms underlying this relationship, and whether this complex cerebellar-cortical interplay during development can serve as a biomarker remains an open question. Indeed, multiple studies have shown that perinatal damage to the cerebellum dramatically increases the risk for neurodevelopmental disorders, particularly for autism spectrum disorder (ASD).

Project overview

Here we will address this knowledge gap by studying the influence of cerebellar development on cortical maturation within an interdisciplinary framework combining data from large-scale, longitudinal, human neuroimaging data (N ~ 8,500)  with pre-clinical ultra-high resolution imaging (7T)  and lesion studies. This will allow us to identify reciprocal  cerebello-cortical maturation patterns in humans, to establish causality of cerebellar impact on cortical maturation, and to combine this information to develop a prediction model for Autism Spectrum Disorder.

Impact

Together, the results of our collaborative study will establish mechanisms of cerebello-cortical maturation and provide clinicians with a biomarker predictive of neurodevelopmental deficits.

Aim 1 

The Synergy CDCM project aims to utilize cutting-edge causal inference methods in epidemiological samples to understand how the cerebellum is related to cortical function. Here we leverage repeated-measures data from large, population-based cohorts to model how cerebellar features influence cortical maturation.

Aim 2

Using preclinical models, we investigate the impact of early life cerebellar growth on cortical maturation using high-resolution 7Tesla neuroimaging.

Aim 3

Consolidating information from Aims 1 & 2, we build a prediction model to understand how various early-life factors, including cerebellar development, confer risk for the emergence and stability of autistic symptoms from childhood to adolescence.

Internal collaborations

• Department of Child and Adolescent Psychiatry/Psychology
• Department of Neuroscience
• Department of Epidemiology
• Department of Neurology
• AIME Core Facility

• Carolin Gaiser
• Ryan Muetzel
• Aleksandra Badura
• Jeremy Labrecque
• Maarten Frens
• Rick van der Vliet
• Monique Bernsen