Neuromodulatory Effects of Monoaminergic Brainstem Nuclei on Large Scale Brain Networks

Summary

Preclinical work has revealed that projections from brainstem nuclei to the cortex are involved in awareness and wakefulness. Despite this, there are no precise accounts of the modulatory relationships between these nuclei and cortical/subcortical networks relevant for consciousness and associated disorders.

Our findings so far support an important role for the dopaminergic system in consciousness. Specifically, we have shown that the functional relationship between the ventral tegmental area (VTA - the origin of the dopaminergic cell bodies of the mesocorticolimbic dopamine system) and posterior Default Mode Network is disrupted both under anaesthesia and in disorders of consciousness. Importantly, this connectivity re-emerges after recovery from anaesthesia and is upregulated by methylphenidate, a dopaminergic (and noradrenergic) agonist (Spindler et al., 2021).

Project aims

Next, we will focus on modulatory influences of cortical networks from other monoaminergic nuclei (e.g. locus coeruleus). The proposed work will develop high spatial/temporal resolution, ultra-high field 7T MRI protocols to overcome limitations in existing 3T MRI imaging of the human brainstem.

This work provides an in vivo translational bridge between preclinical and clinical research and can potentially aid the identification of specific neurotransmitter systems as viable therapeutic targets for pharmacological or electro-stimulatory interventions. Experience in neuroimaging, in particular MRI analysis, is required for these projects. Skills in scientific computing and programming (e.g., Linux, Matlab, Python) are essential. 

Contact details

Emmanuel A Stamatakis (eas46@cam.ac.uk) Anaesthesia

Opportunities

This project is open to applicants who want to do a:

• PhD
• MPhil