Faculty Bibliography

Purpose: To examine distributed patterns of language processing in healthy controls and patients with epilepsy using magnetoencephalography (MEG), and to evaluate the concordance between laterality of distributed MEG sources and language laterality as determined by the intracarotid amobarbital procedure (IAP). Methods: MEG was performed in 10 healthy controls using an anatomically constrained, noise-normalized distributed source solution (dynamic statistical parametric map, dSPM). Distributed source modeling of language was then applied to eight patients with intractable epilepsy. Average source strengths within temporoparietal and frontal lobe regions of interest (ROIs) were calculated, and the laterality of activity within ROIs during discrete time windows was compared to results from the IAP. Results: In healthy controls, dSPM revealed activity in visual cortex bilaterally from approximately 80 to 120 ms in response to novel words and sensory control stimuli (i.e., false fonts). Activity then spread to fusiform cortex approximately 160-200 ms, and was dominated by left hemisphere activity in response to novel words. From approximately 240 to 450 ms, novel words produced activity that was left-lateralized in frontal and temporal lobe regions, including anterior and inferior temporal, temporal pole, and pars opercularis, as well as bilaterally in posterior superior temporal cortex. Analysis of patient data with dSPM demonstrated that from 350 to 450 ms, laterality of temporoparietal sources agreed with the IAP 75% of the time, whereas laterality of frontal MEG sources agreed with the IAP in all eight patients. Discussion: Our results reveal that dSPM can unveil the timing and spatial extent of language processes in patients with epilepsy and may enhance knowledge of language lateralization and localization for use in preoperative planning

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

In natural face-to-face communication, speech perception utilizes both auditory and visual information. We described previously an acoustically responsive area on the posterior lateral surface of the superior temporal gyrus (field PLST) that is distinguishable on physiological grounds from other auditory fields located within the superior temporal plane. Considering the empirical findings in humans and non-human primates of cortical locations responsive to heard sounds and/or seen sound-sources, we reasoned that area PLST would also contain neural signals reflecting audiovisual speech interactions. To test this hypothesis, event related potentials (ERPs) were recorded from area PLST using chronically implanted multi-contact subdural surface-recording electrodes in patient-subjects undergoing diagnosis and treatment of medically intractable epilepsy, and cortical ERP maps were acquired during five contrasting auditory, visual and bimodal speech conditions. Stimulus conditions included consonant-vowel (CV) syllable sounds alone, silent seen speech or CV sounds paired with a female face articulating matched or mismatched syllables. Data were analyzed using a MANOVA framework, with the results from planned comparisons used to construct cortical significance maps. Our findings indicate that evoked responses recorded from area PLST to auditory speech stimuli are influenced significantly by the addition of visual images of the moving lower face and lips, either articulating the audible syllable or carrying out a meaningless (gurning) motion. The area of cortex exhibiting this audiovisual influence was demonstrably greater in the speech-dominant hemisphere