Faculty Bibliography

Historically, the study of speech processing has emphasized a strong link between auditory perceptual input and motor production output. A kind of 'parity' is essential, as both perception- and production-based representations must form a unified interface to facilitate access to higher-order language processes such as syntax and semantics, believed to be computed in the dominant, typically left hemisphere. Although various theories have been proposed to unite perception and production, the underlying neural mechanisms are unclear. Early models of speech and language processing proposed that perceptual processing occurred in the left posterior superior temporal gyrus (Wernicke's area) and motor production processes occurred in the left inferior frontal gyrus (Broca's area). Sensory activity was proposed to link to production activity through connecting fibre tracts, forming the left lateralized speech sensory-motor system. Although recent evidence indicates that speech perception occurs bilaterally, prevailing models maintain that the speech sensory-motor system is left lateralized and facilitates the transformation from sensory-based auditory representations to motor-based production representations. However, evidence for the lateralized computation of sensory-motor speech transformations is indirect and primarily comes from stroke patients that have speech repetition deficits (conduction aphasia) and studies using covert speech and haemodynamic functional imaging. Whether the speech sensory-motor system is lateralized, like higher-order language processes, or bilateral, like speech perception, is controversial. Here we use direct neural recordings in subjects performing sensory-motor tasks involving overt speech production to show that sensory-motor transformations occur bilaterally. We demonstrate that electrodes over bilateral inferior frontal, inferior parietal, superior temporal, premotor and somatosensory cortices exhibit robust sensory-motor neural responses during both perception and production in an overt word-repetition task. Using a non-word transformation task, we show that bilateral sensory-motor responses can perform transformations between speech-perception- and speech-production-based representations. These results establish a bilateral sublexical speech sensory-motor system.

Advances in MRI have transformed the in vivo detection of brain abnormalities in neurological disease. However, many subtle structural abnormalities remain undetected, especially in individual patients, where clinical relevance is highest. We present a quantitative, multifeature morphometry approach combined with machine learning algorithms for detecting structural cortical abnormalities in epilepsy patients with focal cortical dysplasia (FCD). FCD is a malformation of cortical development and is the most common etiology in pediatric epilepsy and the second most common etiology in adults with treatment resistant epilepsy. Lesions may occur anywhere in cortex. Seizure freedom after surgery is reported at 66% with a detected lesion, but only 29% in MRI-negative patients. Yet, 70% to 80% of histologically confirmed FCD cases go undetected by visual inspection of the MRI. Sixty-one controls and 23 MRI-negative patients in whom no focal lesion was detected during routine visual radiological analysis and 7 MRI-positive patients were scanned before surgery at 3 T using a T1-weighted MRI sequence. All patients subsequently underwent intracranial EEG monitoring and resection of the epileptic focus and pathology confirmed FCD. Morphometric routines with surface-based spherical averaging techniques were used to align anatomical structures between individual brains and to calculate 6 features at each vertex, including cortical thickness, gray-white contrast, local gyrification, sulcal depth, Jacobian distance, and curvature. A logistic regression classifier was trained on normal control data and the data from the FCD region of MRI-positive patients to classify, in MRI-negative patients, vertices into lesional and nonlesional. The logistic regression approach correctly classified lesions within the resection zone in 14 out of the 24 (58%) MRInegative patients. The overall false positive rate (by vertex) was never greater than 1.05%. Quantitative MRI can aid in the presurgical detection of FCD lesions, even !

OBJECTIVE: To measure the volume of basal forebrain septal nuclei in patients with temporal lobe epilepsy (TLE) as compared to patients with extratemporal epilepsy and controls. In animal models of TLE, septal lesions facilitate epileptogenesis, while septal stimulation is antiepileptic. METHOD: Subjects were recruited from 2 sites and consisted of patients with pharmacoresistant focal epilepsy (20 with TLE and mesial temporal sclerosis [MTS], 24 with TLE without MTS, 23 with extratemporal epilepsy) and 114 controls. Septal volume was measured using high-resolution MRI in association with newly developed probabilistic septal nuclei maps. Septal volume was compared between subject groups while controlling for relevant factors. RESULTS: Patients with TLE without MTS had significantly larger septal nuclei than patients with extratemporal epilepsy and controls. This was not true for patients with MTS. These results are interpreted with reference to prior studies demonstrating expansion of the septo-hippocampal cholinergic system in animal models of TLE and human TLE surgical specimens. CONCLUSION: Septal nuclei are enlarged in patients with TLE without MTS. Further investigation of septal nuclei and antiepileptic septo-hippocampal neurocircuitry could be relevant to development of new therapeutic interventions such as septal stimulation for refractory TLE.

Hemispheric asymmetry represents a cardinal feature of cerebral organization, but the nature of structural and functional differences between the hemispheres is far from fully understood. Using Magnetic Resonance Imaging morphometry, we identified several volumetric differences between the two hemispheres of the human brain. Heteromodal inferoparietal and lateral prefrontal cortices are more extensive in the right than left hemisphere, as is visual cortex. Heteromodal mesial and orbital prefrontal and cingulate cortices are more extensive in the left than right hemisphere, as are somatosensory, parts of motor, and auditory cortices. Thus, heteromodal association cortices are more extensively represented on the lateral aspect of the right than in the left hemisphere, and modality-specific cortices are more extensively represented on the lateral aspect of the left than in the right hemisphere. On the mesial aspect heteromodal association cortices are more extensively represented in the left than right hemisphere

Despite decades of cognitive, neuropsychological and neuroimaging studies, it is unclear if letters are identified before word-form encoding during reading, or if letters and their combinations are encoded simultaneously and interactively. Here using functional magnetic resonance imaging, we show that a 'letter-form' area (responding more to consonant strings than false fonts) can be distinguished from an immediately anterior 'visual word-form area' in ventral occipito-temporal cortex (responding more to words than consonant strings). Letter-selective magnetoencephalographic responses begin in the letter-form area approximately 60 ms earlier than word-selective responses in the word-form area. Local field potentials confirm the latency and location of letter-selective responses. This area shows increased high-gamma power for approximately 400 ms, and strong phase-locking with more anterior areas supporting lexico-semantic processing. These findings suggest that during reading, visual stimuli are first encoded as letters before their combinations are encoded as words. Activity then rapidly spreads anteriorly, and the entire network is engaged in sustained integrative processing.

Making sense of the world requires us to process information over multiple timescales. We sought to identify brain regions that accumulate information over short and long timescales and to characterize the distinguishing features of their dynamics. We recorded electrocorticographic (ECoG) signals from individuals watching intact and scrambled movies. Within sensory regions, fluctuations of high-frequency (64-200 Hz) power reliably tracked instantaneous low-level properties of the intact and scrambled movies. Within higher order regions, the power fluctuations were more reliable for the intact movie than the scrambled movie, indicating that these regions accumulate information over relatively long time periods (several seconds or longer). Slow (<0.1 Hz) fluctuations of high-frequency power with time courses locked to the movies were observed throughout the cortex. Slow fluctuations were relatively larger in regions that accumulated information over longer time periods, suggesting a connection between slow neuronal population dynamics and temporally extended information processing.

Intracranial electrode arrays are routinely used in the pre-surgical evaluation of patients with medically refractory epilepsy, and recordings from these electrodes have been increasingly employed in human cognitive neurophysiology due to their high spatial and temporal resolution. For both researchers and clinicians, it is critical to localize electrode positions relative to the subject-specific neuroanatomy. In many centers, a post-implantation MRI is utilized for electrode detection because of its higher sensitivity for surgical complications and the absence of radiation. However, magnetic susceptibility artifacts surrounding each electrode prohibit unambiguous detection of individual electrodes, especially those that are embedded within dense grid arrays. Here, we present an efficient method to accurately localize intracranial electrode arrays based on pre- and post-implantation MR images that incorporates array geometry and the individual's cortical surface. Electrodes are directly visualized relative to the underlying gyral anatomy of the reconstructed cortical surface of individual patients. Validation of this approach shows high spatial accuracy of the localized electrode positions (mean of 0.96mm+/-0.81mm for 271 electrodes across 8 patients). Minimal user input, short processing time, and utilization of radiation-free imaging are strong incentives to incorporate quantitatively accurate localization of intracranial electrode arrays with MRI for research and clinical purposes. Co-registration to a standard brain atlas further allows inter-subject comparisons and relation of intracranial EEG findings to the larger body of neuroimaging literature.