Faculty Bibliography

Cognitive functions, for example speech processing, are distributed asymmetrically in the two hemispheres that mostly have homologous anatomical structures. Dichotic listening is a well-established paradigm to investigate hemispherical lateralization of speech. However, the mixed results of dichotic listening, especially when using tonal languages as stimuli, complicates the investigation of functional lateralization. We hypothesized that the inconsistent results in dichotic listening are due to an interaction in processing a mixture of acoustic and linguistic attributes that are differentially processed over the two hemispheres. In this study, a within-subject dichotic listening paradigm was designed, in which different levels of speech and linguistic information was incrementally included in different conditions that required the same tone identification task. A left ear advantage (LEA), in contrast with the commonly found right ear advantage (REA) in dichotic listening, was observed in the hummed tones condition, where only the slow frequency modulation of tones was included. However, when phonemic and lexical information was added in simple vowel tone conditions, the LEA became unstable. Furthermore, ear preference became balanced when phonological and lexical-semantic attributes were included in the consonant-vowel (CV), pseudo-word, and word conditions. Compared with the existing REA results that use complex vowel word tones, a complete pattern emerged gradually shifting from LEA to REA. These results support the hypothesis that an acoustic analysis of suprasegmental information of tones is preferably processed in the right hemisphere, but is influenced by phonological and lexical semantic processes residing in the left hemisphere. The ear preference in dichotic listening depends on the levels of speech and linguistic analysis and preferentially lateralizes across the different hemispheres. That is, the manifestation of functional lateralization depends on the integration of information across the two hemispheres.

Dynamic interactions between remote but functionally specialized brain regions enable complex information processing. This intercortical communication is disrupted in the neural networks of patients with focal epilepsy, and epileptic activity can exert widespread effects within the brain. Using large-scale human intracranial electroencephalography recordings, we show that interictal epileptiform discharges (IEDs) are significantly coupled with spindles in discrete, individualized brain regions outside of the epileptic network. We found that a substantial proportion of these localized spindles travel across the cortical surface. Brain regions that participate in this IED-driven oscillatory coupling express spindles that have a broader spatial extent and higher tendency to propagate than spindles occurring in uncoupled regions. These altered spatiotemporal oscillatory properties identify areas that are shaped by epileptic activity independent of IED or seizure detection. Our findings suggest that IED-spindle coupling may be an important mechanism of interictal global network dysfunction that could be targeted to prevent disruption of normal neural activity.

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.

Slow-oscillations and spindle activity during non-REM sleep have been implicated in memory consolidation. Closed-loop acoustic stimulation has previously been shown to enhance slow oscillations and spindle activity during sleep and improve verbal associative memory. We assessed the effect of closed-loop acoustic stimulation during a daytime nap on a virtual reality spatial navigation task in 12 healthy human subjects in a randomized within-subject crossover design. We show robust enhancement of slow-spindle activity during sleep. However, no effects on behavioral performance were observed when comparing real versus sham stimulation. To explore whether memory enhancement effects were task-specific and dependent on nocturnal sleep, in a second experiment with 19 healthy subjects, we aimed to replicate a previous study which used closed-loop acoustic stimulation to enhance memory for word pairs. Methods were as close as possible to the original study, except we used a double-blind protocol, in which both subject and experimenter were unaware of the test condition. Again, we successfully enhanced slow-spindle power, but again did not strengthen associative memory performance with stimulation. We conclude that enhancement of slow-spindle oscillations may be insufficient to enhance memory performance in spatial navigation or verbal association tasks, and provide possible explanations for lack of behavioral replication.SIGNIFICANCE STATEMENT Prior studies have demonstrated that a closed-loop acoustic pulse paradigm during sleep can enhance verbal memory performance. This technique has widespread scientific and clinical appeal due to its non-invasive nature and ease of application. We tested with a rigorous double-blind design whether this technique could enhance key sleep rhythms associated sleep-dependent memory performance. We discovered that we could reliably enhance slow and spindle rhythms, but did not improve memory performance in the stimulation condition compared to sham condition. Our findings suggest that enhancing slow-spindle rhythms is insufficient to enhance sleep-dependent learning.

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.