Faculty Bibliography

The auditory system must constantly decompose the complex mixture of sound arriving at the ear into perceptually independent streams constituting accurate representations of individual sources in the acoustic environment. How the brain accomplishes this task is not well understood. The present study combined a classic behavioral paradigm with direct cortical recordings from neurosurgical patients with epilepsy in order to further describe the neural correlates of auditory streaming. Participants listened to sequences of pure tones alternating in frequency and indicated whether they heard one or two 'streams.' The intracranial EEG was simultaneously recorded from sub-dural electrodes placed over temporal, frontal, and parietal cortex. Like healthy subjects, patients heard one stream when the frequency separation between tones was small and two when it was large. Robust evoked-potential correlates of frequency separation were observed over widespread brain areas. Waveform morphology was highly variable across individual electrode sites both within and across gross brain regions. Surprisingly, few evoked-potential correlates of perceptual organization were observed after controlling for physical stimulus differences. The results indicate that the cortical areas engaged during the streaming task are more complex and widespread than has been demonstrated by previous work, and that, by-and-large, correlates of bistability during streaming are probably located on a spatial scale not assessed - or in a brain area not examined - by the present study

Rationale: Magnetic resonance imaging has revolutionized the detection of small structural abnormalities in patients with epilepsy. However, many focal abnormalities remain undetected in routine visual inspection. Here we used morphometric MRI to quantify imaging features related to epileptogenic cortical malformations to detect abnormal cortical thickness and blurred gray-white matter boundaries that went undetected by routine clinical visual inspection. Methods: Using MRI morphometry at 3T with surface-based spherical averaging techniques that precisely align anatomical structures between individual brains, we compared single patients with known lesions to a large normal control group to detect clusters of abnormal cortical thickness and gray-white matter contrast (GWC). To assess the effects of threshold and smoothing on detection sensitivity and specificity, we systematically varied these parameters with different thresholds and smoothing levels. To establish the effectiveness of the technique, we compared the detected structural abnormalities to resection margins, seizure onset zones based on intracranial EEG and pathological features using post-resection histology. Results: We report optimal parameters by which cortical thickness and GWC features detected previously occult lesions. We present sensitivity and specificity measures for each threshold and smoothing level to allow for selection of parameters based on clinical need. Conclusions: This automated approach may be a valuable additional clinical tool to improve the detection of subtle or previously occult malformations and therefore may improve identification of patients with intractable focal epilepsy who may benefit from surgery

Repetition priming is a core feature of memory processing whose anatomical correlates remain poorly understood. In this study, we use advanced multimodal imaging (functional magnetic resonance imaging (fMRI) and magnetoencephalography; MEG) to investigate the spatiotemporal profile of repetition priming. We use intracranial electroencephalography (iEEG) to validate our fMRI/MEG measurements. Twelve controls completed a semantic judgment task with fMRI and MEG that included words presented once (new, 'N') and words that repeated (old, 'O'). Six patients with epilepsy completed the same task during iEEG recordings. Blood-oxygen level dependent (BOLD) responses for N vs. O words were examined across the cortical surface and within regions of interest. MEG waveforms for N vs. O words were estimated using a noise-normalized minimum norm solution, and used to interpret the timecourse of fMRI. Spatial concordance was observed between fMRI and MEG repetition effects from 350 to 450 ms within bilateral occipitotemporal and medial temporal, left prefrontal, and left posterior temporal cortex. Additionally, MEG revealed widespread sources within left temporoparietal regions, whereas fMRI revealed bilateral reductions in occipitotemporal and left superior frontal, and increases in inferior parietal, precuneus, and dorsolateral prefrontal activity. BOLD suppression in left posterior temporal, left inferior prefrontal, and right occipitotemporal cortex correlated with MEG repetition-related reductions. IEEG responses from all three regions supported the timecourse of MEG and localization of fMRI. Furthermore, iEEG decreases to repeated words were associated with decreased gamma power in several regions, providing evidence that gamma oscillations are tightly coupled to cognitive phenomena and reflect regional activations seen in the BOLD signal

Accurate pronunciation of phonetically irregular words (exception words) requires prior exposure to unique relationships between orthographic and phonemic features. Whether such word knowledge is accompanied by structural variation in areas associated with orthographic-to-phonemic transformations has not been investigated. We used high-resolution MRI to determine whether performance on a visual word-reading test composed of phonetically irregular words, the Wechsler Test of Adult Reading (WTAR), is associated with regional variations in cortical structure. A sample of 60 right-handed, neurologically intact individuals were administered the WTAR and underwent 3T volumetric MRI. Using quantitative, surface-based image analysis, cortical thickness was estimated at each vertex on the cortical mantle and correlated with WTAR scores while controlling for age. Higher scores on the WTAR were associated with thicker cortex in bilateral anterior superior temporal gyrus, bilateral angular gyrus/posterior superior temporal gyrus, and left hemisphere intraparietal sulcus. Higher scores were also associated with thinner cortex in left hemisphere posterior fusiform gyrus and central sulcus, bilateral inferior frontal gyrus, and right hemisphere lingual gyrus and supramarginal gyrus. These results suggest that the ability to correctly pronounce phonetically irregular words is associated with structural variations in cortical areas that are commonly activated in functional neuroimaging studies of word reading, including areas associated with grapheme-to-phonemic conversion

Epileptic cortex is characterized by paroxysmal electrical discharges. Analysis of these interictal discharges typically manifests as spike-wave complexes on electroencephalography, and plays a critical role in diagnosing and treating epilepsy. Despite their fundamental importance, little is known about the neurophysiological mechanisms generating these events in human focal epilepsy. Using three different systems of microelectrodes, we recorded local field potentials and single-unit action potentials during interictal discharges in patients with medically intractable focal epilepsy undergoing diagnostic workup for localization of seizure foci. We studied 336 single units in 20 patients. Ten different cortical areas and the hippocampus, including regions both inside and outside the seizure focus, were sampled. In three of these patients, high density microelectrode arrays simultaneously recorded between 43 and 166 single units from a small (4 mm x 4 mm) patch of cortex. We examined how the firing rates of individual neurons changed during interictal discharges by determining whether the firing rate during the event was the same, above or below a median baseline firing rate estimated from interictal discharge-free periods (Kruskal-Wallis one-way analysis, P<0.05). Only 48% of the recorded units showed such a modulation in firing rate within 500 ms of the discharge. Units modulated during the discharge exhibited significantly higher baseline firing and bursting rates than unmodulated units. As expected, many units (27% of the modulated population) showed an increase in firing rate during the fast segment of the discharge (+ or - 35 ms from the peak of the discharge), while 50% showed a decrease during the slow wave. Notably, in direct contrast to predictions based on models of a pure paroxysmal depolarizing shift, 7.7% of modulated units recorded in or near the seizure focus showed a decrease in activity well ahead (0-300 ms) of the discharge onset, while 12.2% of units increased in activity in this period. No such pre-discharge changes were seen in regions well outside the seizure focus. In many recordings there was also a decrease in broadband field potential activity during this same pre-discharge period. The different patterns of interictal discharge-modulated firing were classified into more than 15 different categories. This heterogeneity in single unit activity was present within small cortical regions as well as inside and outside the seizure onset zone, suggesting that interictal epileptiform activity in patients with epilepsy is not a simple paroxysm of hypersynchronous excitatory activity, but rather represents an interplay of multiple distinct neuronal types within complex neuronal networks

OBJECTIVE: To report 4 cases of hyperfamiliarity for faces (HFF) and review 5 previously reported cases. METHODS: We identified cases of HFF from PubMed search and references in prior reports. RESULTS: Three of our 4 cases had pathologic findings that were most extensive in the left temporal lobe. HFF occurred after a tonic-clonic seizure (cases 1 and 3), during simple partial seizures (case 2), and in the setting of an increase in simple partial seizure frequency but not during seizures (case 4). All 9 cases were adults with 1 or more seizures; symptoms first occurred after seizures in 5 cases and during seizures in 1 case. Ictal symptoms lasted from seconds to minutes and from 2 days to more than 7 years in the other 6 cases. The duration of HFF was not associated with the presence or extent of a structural lesion. While in several cases HFF appears to result from a postictal Todd paralysis, the mechanism underlying persistent cases is uncertain. CONCLUSIONS: This modality (visual)-specific and stimulus (face)-specific syndrome is associated with diverse structural, functional imaging, and neurophysiologic findings. Lesions are more often left-sided and involve the temporal lobe. Epilepsy and seizures were present in all 9 cases, suggesting a pathophysiologic relationship, which likely varies among cases. Although only reported in 9 patients, HFF is probably much more common than it is diagnosed