Linking brain functional trajectories in neurodevelopmental disorders to underlying neurotransmitter systems

• Applicants: Professor Dr. Jürgen Dukart; Professor Dr. Georg von Polier
• Subject Area: Developmental Neurobiology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 549186835

Maturation of different neurotransmitter systems is an important component of normal brain development in childhood and adolescence. Accordingly, alterations in these neurotransmitter systems are likely to be involved in most neurodevelopmental disorders. However, due to methodological and ethical problems (e.g., use of radioactive isotopes), it is almost impossible to use established methods to study in detail the normal and pathological development of neurotransmitter systems at this critical developmental stages. Recently, we established a new spatial correlation approach to investigate the possible contribution of different neurotransmitters to functional brain activity using MRI-based measures of brain function.Thereby, we estimate neurotransmitter development using the co-localization strength of functional MRI measures with neurotransmitter expression derived from adult populations. Using this approach, in the proposed project we will use MRI data from several large developmental cohorts to determine developmental trajectories of normal functional brain development. We will adopt a normative modeling approach to model neurotransmitter development for all major neurotransmitter systems through childhood and adolescence into early adulthood. Based on results of this modeling, we will then also use large available MRI databases to examine how two of the most common neurodevelopmental disorders – autism spectrum and attention and hyperactivity disorders - deviate from healthy developmental trajectories in terms of maturation of individual neurotransmitter systems and how sensitive and specific these deviations are for the respective disorders. Furthermore, using the co-localization approach on the example of attention and hyperactivity disorders, we will investigate how established pharmacological therapies interact with the affected neurotransmitter systems to achieve an individual therapeutic effect. The results of this project have the potential to substantially improve the study of developmental disorders in terms of their neurobiological correlates. The outcomes of the project will allow us to gain a much better understanding of the respective disorders with the potential of identifying novel therapeutic targets.

• DFG Programme: Research Grants
• Co-Investigators: Professor Dr. Simon Eickhoff; Dr. Leon Lotter