Whereas gamma-band neuronal oscillations clearly appear integral to visual attention, the role of lower-frequency oscillations is still being debated. Mounting evidence indicates that a key functional property of these oscillations is the rhythmic shifting of excitability in local neuronal ensembles. Here, we show that when attended stimuli are in a rhythmic stream, delta-band oscillations in the primary visual cortex entrain to the rhythm of the stream, resulting in increased response gain for task-relevant events and decreased reaction times. Because of hierarchical cross-frequency coupling, delta phase also determines momentary power in higher-frequency activity. These instrumental functions of low-frequency oscillations support a conceptual framework that integrates numerous earlier findings.

Summary The ability to focus on and understand one talker in a noisy social environment is a critical social-cognitive capacity, whose underlying neuronal mechanisms are unclear. We investigated the manner in which speech streams are represented in brain activity and the way that selective attention governs the brain’s representation of speech using a ‘Cocktail Party’ Paradigm, coupled with direct recordings from the cortical surface in surgical epilepsy patients. We find that brain activity dynamically tracks speech streams using both low frequency phase and high frequency amplitude fluctuations, and that optimal encoding likely combines the two. In and near low level auditory cortices, attention ‘modulates’ the representation by enhancing cortical tracking of attended speech streams, but ignored speech remains represented. In higher order regions, the representation appears to become more ‘selective,’ in that there is no detectable tracking of ignored speech. This selectivity itself seems to sharpen as a sentence unfolds.

Rheumatoid arthritis (RA) is a heterogeneous, prevalent, chronic autoimmune disease characterized by painful swollen joints and significant disabilities. Symptomatic relief can be achieved in up to 50% of patients using biological agents that inhibit tumor necrosis factor (TNF) or other mechanisms of action, but there are no universally effective therapies. Recent advances in basic and preclinical science reveal that reflex neural circuits inhibit the production of cytokines and inflammation in animal models. One well-characterized cytokine-inhibiting mechanism, termed the “inflammatory reflex,” is dependent upon vagus nerve signals that inhibit cytokine production and attenuate experimental arthritis severity in mice and rats. It previously was unknown whether directly stimulating the inflammatory reflex in humans inhibits TNF production. Here we show that an implantable vagus nerve-stimulating device in epilepsy patients inhibits peripheral blood production of TNF, IL-1β, and IL-6. Vagus nerve stimulation (up to four times daily) in RA patients significantly inhibited TNF production for up to 84 d. Moreover, RA disease severity, as measured by standardized clinical composite scores, improved significantly. Together, these results establish that vagus nerve stimulation targeting the inflammatory reflex modulates TNF production and reduces inflammation in humans. These findings suggest that it is possible to use mechanism-based neuromodulating devices in the experimental therapy of RA and possibly other autoimmune and autoinflammatory diseases.