Beyond haemodynamics: functional MRS as a complementary window into neural activity

Understanding brain function requires going beyond what the BOLD signal alone can tell us. Functional MRI has transformed human neuroscience, but its haemodynamic basis means it captures neural activity only indirectly and cannot disambiguate the neurochemical processes that drive it. Functional MRS (fMRS) measures dynamic changes in neurometabolite concentrations — most notably glutamate, GABA, and lactate — in vivo, offering a more direct readout of the excitation-inhibition balance underlying brain responses. In this talk, I will present a series of 7T studies that explore the complementary natureof fMRS and fMRI, and ask what fMRS adds that fMRI cannot provide on its own.

Across paradigms ranging from sensory and motor tasks to pharmacological challenges, we show that neurometabolic and haemodynamic responses are related but dissociable, carrying partially non-overlapping information about neural processes. Extending fMRS to simultaneous multi-voxel acquisitions further reveals distributed neurochemical dynamics that spatially constrained designs would miss, while integrating fMRS with fMRI connectivity analyses allows drug-induced neurometabolic changes to be linked to network-level reorganisation across neurotransmitter systems. Together, these findings make a case for fMRS as an essential complement to fMRI for interpreting haemodynamic observations in their neurochemical context— with implications for how we design and interpret studies of both healthy brain function and psychotropic drug action.