Faculty Bibliography

Direct recordings from the human brain have historically involved epilepsy patients undergoing invasive electroencephalography (iEEG) for surgery. However, these measurements are temporally limited and affected by clinical variables. The RNS System (NeuroPace, Inc.) is a chronic, closed-loop electrographic seizure detection and stimulation system. When adapted by investigators for research, it facilitates cognitive testing in a controlled ambulatory setting, with measurements collected over months to years. We utilized an associative learning paradigm in 5 patients with traditional iEEG and 3 patients with chronic iEEG, and found increased hippocampal gamma (60-100 Hz) sustained at 1.3-1.5 seconds during encoding in successful versus failed trials in surgical patients, with similar results in our RNS System patients (1.4-1.6 seconds). Our findings replicate other studies demonstrating that sustained hippocampal gamma supports encoding. Importantly, we have validated the RNS System to make sensitive measurements of hippocampal dynamics during cognitive tasks in a chronic ambulatory research setting.

Broca's area has long been considered central for speech production. Recently, several intracranial studies have challenged this view by elucidating the temporal and causal dynamics of cortical networks including Broca's area. Here we review intracranial perturbation and recording studies leading up to recent advances and remaining questions in the field.

Electrophysiology and neuroimaging provide conflicting evidence for the neural contributions to target detection. Scalp electroencephalography (EEG) studies localize the P3b event-related potential component mainly to parietal cortex, whereas neuroimaging studies report activations in both frontal and parietal cortices. We addressed this discrepancy by examining the sources that generate the target-detection process using electrocorticography (ECoG). We recorded ECoG activity from cortex in 14 patients undergoing epilepsy monitoring, as they performed an auditory or visual target-detection task. We examined target-related responses in 2 domains: high frequency band (HFB) activity and the P3b. Across tasks, we observed a greater proportion of electrodes that showed target-specific HFB power relative to P3b over frontal cortex, but their proportions over parietal cortex were comparable. Notably, there was minimal overlap in the electrodes that showed target-specific HFB and P3b activity. These results revealed that the target-detection process is characterized by at least 2 different neural markers with distinct cortical distributions. Our findings suggest that separate neural mechanisms are driving the differential patterns of activity observed in scalp EEG and neuroimaging studies, with the P3b reflecting EEG findings and HFB activity reflecting neuroimaging findings, highlighting the notion that target detection is not a unitary phenomenon.

In this issue of Neuron, Long et al. (2016) employ a novel technique of intraoperative cortical cooling in humans during speech production. They demonstrate that cooling Broca's area interferes with speech timing but not speech quality.

OBJECTIVE: To investigate the feasibility and clinical utility of using passive electrocorticography (ECoG) for online spatial-temporal functional mapping (STFM) of language cortex in patients being monitored for epilepsy surgery. METHODS: We developed and tested an online system that exploits ECoG's temporal resolution to display the evolution of statistically significant high gamma (70-110 Hz) responses across all recording sites activated by a discrete cognitive task. We illustrate how this spatial-temporal evolution can be used to study the function of individual recording sites engaged during different language tasks, and how this approach can be particularly useful for mapping eloquent cortex. RESULTS: Using electrocortical stimulation mapping (ESM) as the clinical gold standard for localizing language cortex, the average sensitivity and specificity of online STFM across 7 patients were 69.9% and 83.5%, respectively. Moreover, relative to regions of interest where discrete cortical lesions have most reliably caused language impairments in the literature, the sensitivity of STFM was significantly greater than that of ESM, while its specificity was also greater than that of ESM, though not significantly so. CONCLUSIONS: This study supports the feasibility and clinical utility of online STFM for mapping human language function, particularly under clinical circumstances in which time is limited and comprehensive ESM is impractical.

For over a century neuroscientists have debated the dynamics by which human cortical language networks allow words to be spoken. Although it is widely accepted that Broca's area in the left inferior frontal gyrus plays an important role in this process, it was not possible, until recently, to detail the timing of its recruitment relative to other language areas, nor how it interacts with these areas during word production. Using direct cortical surface recordings in neurosurgical patients, we studied the evolution of activity in cortical neuronal populations, as well as the Granger causal interactions between them. We found that, during the cued production of words, a temporal cascade of neural activity proceeds from sensory representations of words in temporal cortex to their corresponding articulatory gestures in motor cortex. Broca's area mediates this cascade through reciprocal interactions with temporal and frontal motor regions. Contrary to classic notions of the role of Broca's area in speech, while motor cortex is activated during spoken responses, Broca's area is surprisingly silent. Moreover, when novel strings of articulatory gestures must be produced in response to nonword stimuli, neural activity is enhanced in Broca's area, but not in motor cortex. These unique data provide evidence that Broca's area coordinates the transformation of information across large-scale cortical networks involved in spoken word production. In this role, Broca's area formulates an appropriate articulatory code to be implemented by motor cortex.