Faculty Bibliography

The electroencephalogram (EEG) is a mainstay of clinical neurology and is tightly correlated with brain function, but the specific currents generating human EEG elements remain poorly specified because of a lack of microphysiological recordings. The largest event in healthy human EEGs is the K-complex (KC), which occurs in slow-wave sleep. Here, we show that KCs are generated in widespread cortical areas by outward dendritic currents in the middle and upper cortical layers, accompanied by decreased broadband EEG power and decreased neuronal firing, which demonstrate a steep decline in network activity. Thus, KCs are isolated 'down-states,' a fundamental cortico-thalamic processing mode already characterized in animals. This correspondence is compatible with proposed contributions of the KC to sleep preservation and memory consolidation

Measurement of the blood-oxygen-level dependent (BOLD) response with fMRI has revolutionized cognitive neuroscience and is increasingly important in clinical care. The BOLD response reflects changes in deoxy-hemoglobin concentration, blood volume, and blood flow. These hemodynamic changes ultimately result from neuronal firing and synaptic activity, but the linkage between these domains is complex, poorly understood, and may differ across species, cortical areas, diseases, and cognitive states. We describe here a technique that can measure neural and hemodynamic changes simultaneously from cortical microdomains in waking humans. We utilize a 'laminar optode,' a linear array of microelectrodes for electrophysiological measures paired with a micro-optical device for hemodynamic measurements. Optical measurements include laser Doppler to estimate cerebral blood flow as well as point spectroscopy to estimate oxy- and deoxy-hemoglobin concentrations. The microelectrode array records local field potential gradients (PG) and multi-unit activity (MUA) at 24 locations spanning the cortical depth, permitting estimation of population trans-membrane current flows (Current Source Density, CSD) and population cell firing in each cortical lamina. Comparison of the laminar CSD/MUA profile with the origins and terminations of cortical circuits allows activity in specific neuronal circuits to be inferred and then directly compared to hemodynamics. Access is obtained in epileptic patients during diagnostic evaluation for surgical therapy. Validation tests with relatively well-understood manipulations (EKG, breath-holding, cortical electrical stimulation) demonstrate the expected responses. This device can provide a new and robust means for obtaining detailed, quantitative data for defining neurovascular coupling in awake humans