Attention to odor modulates thalamocortical connectivity in the human brain

It is widely assumed that the thalamus is functionally irrelevant for the sense of smell. Although animal studies suggest that the mediodorsal (MD) thalamus links primary olfactory (piriform) cortex to olfactory neocortical projection sites in orbitofrontal cortex (OFC), this transthalamic route is regarded to be inconsequential, particularly compared with a direct monosynaptic pathway linking piriform cortex and OFC. In this study, we combined functional magnetic resonance imaging with novel effective connectivity techniques to measure attention-dependent network coherence within direct (nonthalamic) and indirect (transthalamic) olfactory pathways. Human subjects were presented with (or without) an odor and with (or without) a tone, while selectively attending to either modality. Attention to odor significantly modulated neural coupling within the indirect pathway, strengthening MD thalamus-OFC connectivity. Critically, these effects were modality specific (odor > tone attention), directionally sensitive (forward > backward connections), and selective to route (indirect > direct pathway). Our findings support the idea that the human transthalamic pathway is an active modulatory target of olfactory attention. The results imply that olfaction, like all other sensory modalities, requires a thalamic relay, if only to consciously analyze a smell.