UCSF

The brain is a living organ with distinct metabolic constraints. However, these constraints are typically considered as secondary or supportive of information processing which is primarily performed by neurons. The default operational definition of neural information processing is that (1) it is ultimately encoded as a change in individual neuronal firing rate as this correlates with the presentation of a peripheral stimulus, motor action or cognitive task. Two additional assumptions are associated with this default interpretation: (2) that the incessant background firing activity against which changes in activity are measured plays no role in assigning significance to the extrinsically evoked change in neural firing, and (3) that the metabolic energy that sustains this background activity and which correlates with differences in neuronal firing rate is merely a response to an evoked change in neuronal activity. These assumptions underlie the design, implementation, and interpretation of neuroimaging studies, particularly fMRI, which relies on changes in blood oxygen as an indirect measure of neural activity. In this article we reconsider all three of these assumptions in light of recent evidence. We suggest that by combining EEG with fMRI, new experimental work can reconcile emerging controversies in neurovascular coupling and the significance of ongoing, background activity during resting-state paradigms. A new conceptual framework for neuroimaging paradigms is developed to investigate how ongoing neural activity is "entangled" with metabolism. That is, in addition to being recruited to support locally evoked neuronal activity (the traditional hemodynamic response), changes in metabolic support may be independently "invoked" by non-local brain regions, yielding flexible neurovascular coupling dynamics that inform the cognitive context. This framework demonstrates how multimodal neuroimaging is necessary to probe the neurometabolic foundations of cognition, with implications for the study of neuropsychiatric disorders.