Normal and pathological brain connectivity
Abnormal connectivity in Autism Spectrum Disorder
The most salient and unique feature of Autism Spectrum Disorder (ASD) is the deficit in social interaction. Deficits in social interaction and a lack of motivation to engage in social activities appear to be unique to this disorder, and some have suggested that social interaction deficits are ‘superordinate’, in that they may explain some of the other features of ASD. Previous studies have focused on investigating the neural correlates of social deficits in ASD, however, these studies have repeatedly failed to generate cogent neuropathological models or successful intervention strategies. We believe that by analyzing interactions between brain regions either at rest (Balsters et al. In Prep; Di Martino et al. 2013) or during task execution (Alaerts et al. 2014; Balsters et al. 2015; Delmonte et al. 2013) and by applying computational approaches we can significantly improve our understanding and the future treatment of ASD.
Moreover, progress in understanding the pathophysiology of brain disorders greatly benefits from the use of suitable animal models. In our lab we study animal models for ASD that express molecular and social behavioral deficits similar to humans with ASD. Our primary goal is to provide a crucial methodological link between genetic variations causing molecular/synaptic alterations and dysfunctional connectivity, which is related to ASD-like behavioral traits (ETH fellowship granted to Valerio Zerbi).
Stratification of therapy in cerebral palsy based on connectivity biomarkers
Cerebral palsy (CP) is the leading cause of childhood disability and is caused by a non-progressive lesion of the developing fetal or infant brain. CP causes lifelong impairments that can be highly disabling if untreated. Moreover, the heterogeneous nature of CP requires individually adjusted treatment planning to increase the chance of success. To date, structural MR images of the brain have been used to derive neural biomarkers, such as lesion location and extent, which serve as a general classification scheme of gross motor function and upper limb abilities. However, neural biomarkers that predict upper limb functional outcomes at the level of the individual child are still lacking. In the context of the Marie Curie Project of Dr. E Jaspers, we are focusing on the development of new methods for quantifying the functional connectivity of the sensorimotor system by combining behavioral tests, transcranial magnetic stimulation, EEG and advanced MR imaging (resting state and diffusion weighted imaging).
Stratified medicine refers to matching patients with pharmacological or non-pharmacological therapies based on clinical biomarkers, which can entail any diagnostic test or clinical observation. The strategic and economic significance of such marker-based identification of subgroups or strata of patients has been clearly demonstrated in e.g. cancer research. However, neurological diseases and particularly those occurring during early development like cerebral palsy (CP) can cause highly divergent symptoms, which requires individually adjusted treatment planning to increase the chance of success. With our research we aim to lay the foundation for a stratified therapy approach in CP by developing biomarkers reflecting an individual’s status at the level of the brain.