Faculty Bibliography

Brain operation is profoundly rhythmic. Oscillations of neural excitability shape sensory, motor, and cognitive processes. Intrinsic oscillations also entrain to external rhythms, allowing the brain to optimize the processing of predictable events such as speech. Moreover, selective attention to a particular rhythm in a complex environment entails entrainment of neural oscillations to its temporal structure. Entrainment appears to form one of the core mechanisms of selective attention, which is likely to be relevant to certain psychiatric disorders. Deficient entrainment has been found in schizophrenia and dyslexia and mounting evidence also suggests that it may be abnormal in attention-deficit/hyperactivity disorder (ADHD). Accordingly, we suggest that studying entrainment in selective-attention paradigms is likely to reveal mechanisms underlying deficits across multiple disorders.

Our working model of the primate auditory cortex recognizes three major regions (core, belt, parabelt), subdivided into thirteen areas. The connections between areas are topographically ordered in a manner consistent with information flow along two major anatomical axes: core-belt-parabelt and caudal-rostral. Remarkably, most of the connections supporting this model were revealed using retrograde tracing techniques. Little is known about laminar circuitry, as anterograde tracing of axon terminations has rarely been used. The purpose of the present study was to examine the laminar projections of three areas of auditory cortex, pursuant to analysis of all areas. The selected areas were: middle lateral belt (ML); caudomedial belt (CM); and caudal parabelt (CPB). Injections of anterograde tracers yielded data consistent with major features of our model, and also new findings that compel modifications. Results supporting the model were: (1) feedforward projection from ML and CM terminated in CPB; (2) feedforward projections from ML and CPB terminated in rostral areas of the belt and parabelt; and (3) feedback projections typified inputs to the core region from belt and parabelt. At odds with the model was the convergence of feedforward inputs into rostral medial belt from ML and CPB. This was unexpected since CPB is at a higher stage of the processing hierarchy, with mainly feedback projections to all other belt areas. Lastly, extending the model, feedforward projections from CM, ML, and CPB overlapped in the temporal parietal occipital area (TPO) in the superior temporal sulcus, indicating significant auditory influence on sensory processing in this region. The combined results refine our working model and highlight the need to complete studies of the laminar inputs to all areas of auditory cortex. Their documentation is essential for developing informed hypotheses about the neurophysiological influences of inputs to each layer and area.

Recent neuroscience advances suggest that when interacting with our environment, along with previous experience, we use contextual cues and regularities to form predictions that guide our perceptions and actions. The goal of such active "predictive sensing" is to selectively enhance the processing and representation of behaviorally relevant information in an efficient manner. Since a hallmark of schizophrenia is impaired information selection, we tested whether this deficiency stems from dysfunctional predictive sensing by measuring the degree to which neuronal activity predicts relevant events. In healthy subjects, we established that these mechanisms are engaged in an effort-dependent manner and that, based on a correspondence between human scalp and intracranial nonhuman primate recordings, their main role is a predictive suppression of excitability in task-irrelevant regions. In contrast, schizophrenia patients displayed a reduced alignment of neuronal activity to attended stimuli, which correlated with their behavioral performance deficits and clinical symptoms. These results support the relevance of predictive sensing for normal and aberrant brain function, and highlight the importance of neuronal mechanisms that mold internal ongoing neuronal activity to model key features of the external environment.

The ability to focus on and understand one talker in a noisy social environment is a critical social-cognitive capacity, whose underlying neuronal mechanisms are unclear. We investigated the manner in which speech streams are represented in brain activity and the way that selective attention governs the brain's representation of speech using a "Cocktail Party" paradigm, coupled with direct recordings from the cortical surface in surgical epilepsy patients. We find that brain activity dynamically tracks speech streams using both low-frequency phase and high-frequency amplitude fluctuations and that optimal encoding likely combines the two. In and near low-level auditory cortices, attention "modulates" the representation by enhancing cortical tracking of attended speech streams, but ignored speech remains represented. In higher-order regions, the representation appears to become more "selective," in that there is no detectable tracking of ignored speech. This selectivity itself seems to sharpen as a sentence unfolds.

Although we have convincing evidence that attention to auditory stimuli modulates neuronal responses at or before the level of primary auditory cortex (A1), the underlying physiological mechanisms are unknown. We found that attending to rhythmic auditory streams resulted in the entrainment of ongoing oscillatory activity reflecting rhythmic excitability fluctuations in A1. Strikingly, although the rhythm of the entrained oscillations in A1 neuronal ensembles reflected the temporal structure of the attended stream, the phase depended on the attended frequency content. Counter-phase entrainment across differently tuned A1 regions resulted in both the amplification and sharpening of responses at attended time points, in essence acting as a spectrotemporal filter mechanism. Our data suggest that selective attention generates a dynamically evolving model of attended auditory stimulus streams in the form of modulatory subthreshold oscillations across tonotopically organized neuronal ensembles in A1 that enhances the representation of attended stimuli.

How does auditory cortex respond to silence? In this issue of Neuron, show that activity in macaque auditory cortex is highly structured even in the absence of sensory stimuli. These data reveal a close link between spontaneous neural activity and the functional organization of auditory cortex.

Previous studies raise the hypothesis that attentional bias in the phase of neocortical excitability fluctuations (oscillations) represents a fundamental mechanism for tuning the brain to the temporal dynamics of task-relevant event patterns. To evaluate this hypothesis, we recorded intracranial electrocortical activity in human epilepsy patients while they performed an audiovisual stream selection task. Consistent with our hypothesis, (1) attentional modulation of oscillatory entrainment operates in a distinct network of areas including auditory, visual, posterior parietal, inferior motor, inferior frontal and superior midline frontal cortex, (2) the degree of oscillatory entrainment depends on the predictability of the stimulus stream, and (3) the attentional phase shift of entrained oscillation cooccurs with classical attentional effects observed on phase-locked evoked activity in sensory-specific areas but seems to operate on entrained low-frequency oscillations that cannot be explained by sensory activity evoked at the rate of stimulation. Thus, attentional entrainment appears to tune a network of brain areas to the temporal dynamics of behaviorally relevant event streams, contributing to its perceptual and behavioral selection

Inhibition plays an essential role in shaping and refining the brain's representation of sensory stimulus attributes. In primary auditory cortex (A1), so-called "sideband" inhibition helps to sharpen the tuning of local neuronal responses. Several distinct types of anatomical circuitry could underlie sideband inhibition, including direct thalamocortical (TC) afferents, as well as indirect intracortical mechanisms. The goal of the present study was to characterize sideband inhibition in A1 and to determine its mechanism by analyzing laminar profiles of neuronal ensemble activity. Our results indicate that both lemniscal and nonlemniscal TC afferents play a role in inhibitory responses via feedforward inhibition and oscillatory phase reset, respectively. We propose that the dynamic modulation of excitability in A1 due to the phase reset of ongoing oscillations may alter the tuning of local neuronal ensembles and can be regarded as a flexible overlay on the more obligatory system of lemniscal feedforward type responses.