Faculty Bibliography

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

We describe the anesthetic management of a morbidly obese patient with obstructive sleep apnea who underwent awake craniotomy. The patient's personal continuous positive airway pressure (CPAP) machine was used to support ventilation intraoperatively. Dexmedetomidine was used as the primary sedative. During cortical mapping, the CPAP was discontinued. The patient was comfortable and able to cooperate with language testing

This preliminary study sought to localize epileptogenic regions in patients with partial epilepsy by analysis of interictal EEG activity utilizing variable resolution electromagnetic tomography (VARETA), a three-dimensional quantitative electroencephalographic (QEEG) frequency-domain distributed source modeling technique. The very narrow band (VNB) spectra spanned the frequency range 0.39 Hz to 19.1 Hz, in 0.39 Hz steps. These VNB spectra were compared to normative data and transformed to provide Z-scores for every scalp derivation, and the spatial distributions of the probable EEG generators of the most abnormal values were displayed on slices from a probabilistic MRI atlas. Each voxel was color-coded to represent the significance of the deviation relative to age appropriate normative values. We compared the resulting three-dimensional images to the localization of epileptogenic regions based on invasive intracranial EEG recordings of seizure onsets. The VARETA image indicated abnormal interictal spectral power values in regions of seizure onset identified by invasive monitoring, mainly in delta and theta range (1.5 to 8.0 Hz). The VARETA localization of the most abnormal voxel was congruent with the epileptogenic regions identified by intracranial recordings with regard to hemisphere in all 6 cases, and with regard to lobe in 5 cases. In contrast, abnormal findings with routine EEG agreed with invasive monitoring with regard to hemisphere in 3 cases and with regard to lobe in 2 cases. These results suggest that analysis of background interictal EEG utilizing distributed source models should be investigated further in clinical epilepsy

Antiepileptic drug (AED) delivery directly into the neocortex has recently been shown to be able to both prevent and terminate focal seizures in rats. The present clinical experiment aimed to test the local effects of lidocaine delivered onto the pia mater adjacent to epileptogenic zones in human patients. Administration of lidocaine resulted in a marked diminishment of spike counts on all patients, with a decremental effect of lidocaine on the faster frequency elements of individual spikes and overall testing epochs. The direct cortical application of lidocaine appears to affect local epileptogenic activity in human patients with intractable focal epilepsy

OBJECTIVE: To evaluate the safety, efficacy, and utility of a novel surgical strategy consisting of multiple (more than two) operative stages performed during the same hospital admission with subdural grid and strip electrodes in selected pediatric extratemporal epilepsy. METHODS: Subdural grid and strip electrodes were used for multistage chronic electroencephalographic monitoring in 15 pediatric patients (age, <19 yr) with refractory localization-related epilepsy and poor surgical prognostic factors. Initial resective surgery and/or multiple subpial transections were performed, followed by further monitoring and additional resection and/or multiple subpial transections. RESULTS: Mean patient age was 9.7 years. Mean duration of total invasive monitoring was 10.5 days (range, 8-14 d). The first monitoring period averaged 6.5 days, and the second averaged 3.9 days. Additional surgery was performed in 13 of 15 patients. Two patients who did not undergo additional surgery had a Class I outcome. Rationales for reinvestigation included incomplete localization, multifocality, and proximity to eloquent cortex. Complications were minimal, including two transfusions. There were no cases of wound infection, cerebral edema, hemorrhage, or major permanent neurological deficit. Minimum duration of follow-up was 31 months. Outcomes were 60% Engel Class I (9 of 15 patients), 27% Class III (4 of 15 patients), and 13% Class IV (2 of 15 patients). CONCLUSION: In a very select group of pediatric patients with poor surgical prognostic factors, the multistage approach can be beneficial. After failed epilepsy surgery, subsequent reoperation with additional intracranial investigation traditionally is used when a single residual focus is suspected. Our results, however, support the contention that multistage epilepsy surgery is safe, effective, and useful in a challenging and select pediatric population with extratemporal medically refractory epilepsy