Faculty Bibliography

Audiovisual (AV) interaction has been shown in many studies of auditory cortex. However, the underlying processes and circuits are unclear because few studies have used methods that delineate the timing and laminar distribution of net excitatory and inhibitory processes within areas, much less across cortical levels. This study examined laminar profiles of neuronal activity in auditory core (AC) and parabelt (PB) cortices recorded from macaques during active discrimination of conspecific faces and vocalizations. We found modulation of multi-unit activity (MUA) in response to isolated visual stimulation, characterized by a brief deep MUA spike, putatively in white matter, followed by mid-layer MUA suppression in core auditory cortex; the later suppressive event had clear current source density concomitants, while the earlier MUA spike did not. We observed a similar facilitation-suppression sequence in the PB, with later onset latency. In combined AV stimulation, there was moderate reduction of responses to sound during the visual-evoked MUA suppression interval in both AC and PB. These data suggest a common sequence of afferent spikes, followed by synaptic inhibition; however, differences in timing and laminar location may reflect distinct visual projections to AC and PB.

Audiovisual (AV) interaction has been shown in many studies of auditory cortex. However, the underlying processes and circuits are unclear because few studies have used methods that delineate the timing and laminar distribution of net excitatory and inhibitory processes within areas, much less across cortical levels. This study examined laminar profiles of neuronal activity in auditory core (AC) and parabelt (PB) cortices recorded from macaques during active discrimination of conspecific faces and vocalizations. We found modulation of multi-unit activity (MUA) in response to isolated visual stimulation, characterized by a brief deep MUA spike, putatively in white matter, followed by mid-layer MUA suppression in core auditory cortex; the later suppressive event had clear current source density concomitants, while the earlier MUA spike did not. We observed a similar facilitation-suppression sequence in the PB, with later onset latency. In combined AV stimulation, there was moderate reduction of responses to sound during the visual-evoked MUA suppression interval in both AC and PB. These data suggest a common sequence of afferent spikes, followed by synaptic inhibition; however, differences in timing and laminar location may reflect distinct visual projections to AC and PB.

Audiovisual (AV) interaction has been shown in many studies of auditory cortex. However, the underlying processes and circuits are unclear because few studies have used methods that delineate the timing and laminar distribution of net excitatory and inhibitory processes within areas, much less across cortical levels. This study examined laminar profiles of neuronal activity in auditory core (AC) and parabelt (PB) cortices recorded from macaques during active discrimination of conspecific faces and vocalizations. We found modulation of multi-unit activity (MUA) in response to isolated visual stimulation, characterized by a brief deep MUA spike, putatively in white matter, followed by mid-layer MUA suppression in core auditory cortex; the later suppressive event had clear current source density concomitants, while the earlier MUA spike did not. We observed a similar facilitation-suppression sequence in the PB, with later onset latency. In combined AV stimulation, there was moderate reduction of responses to sound during the visual-evoked MUA suppression interval in both AC and PB. These data suggest a common sequence of afferent spikes, followed by synaptic inhibition; however, differences in timing and laminar location may reflect distinct visual projections to AC and PB.

Audiovisual (AV) interaction has been shown in many studies of auditory cortex. However, the underlying processes and circuits are unclear because few studies have used methods that delineate the timing and laminar distribution of net excitatory and inhibitory processes within areas, much less across cortical levels. This study examined laminar profiles of neuronal activity in auditory core (AC) and parabelt (PB) cortices recorded from macaques during active discrimination of conspecific faces and vocalizations. We found modulation of multi-unit activity (MUA) in response to isolated visual stimulation, characterized by a brief deep MUA spike, putatively in white matter, followed by mid-layer MUA suppression in core auditory cortex; the later suppressive event had clear current source density concomitants, while the earlier MUA spike did not. We observed a similar facilitation-suppression sequence in the PB, with later onset latency. In combined AV stimulation, there was moderate reduction of responses to sound during the visual-evoked MUA suppression interval in both AC and PB. These data suggest a common sequence of afferent spikes, followed by synaptic inhibition; however, differences in timing and laminar location may reflect distinct visual projections to AC and PB.

High-frequency (>60 Hz) neuroelectric signals likely have functional roles distinct from low-frequency (<30 Hz) signals. While high-gamma activity (>60 Hz) does not simply equate to neuronal spiking, they are highly correlated, having similar information encoding. High-gamma activity is typically considered broadband and poorly phase-locked to sensory stimuli and thus is typically analyzed after transformations into absolute amplitude or spectral power. However, those analyses discard signal polarity, compromising the interpretation of neuroelectric events that are essentially dipolar. In the spectrotemporal profiles of field potentials in auditory cortex, we show high-frequency spectral peaks not phase-locked to sound onset, which follow the broadband peak of phase-locked onset responses. Isolating the signal components comprising the high-frequency peaks reveals narrow-band high-frequency oscillatory events, whose instantaneous frequency changes rapidly from >150 to 60 Hz, which may underlie broadband high-frequency spectral peaks in previous reports. The laminar amplitude distributions of the isolated activity had two peak positions, while the laminar phase patterns showed a counterphase relationship between those peaks, indicating the formation of dipoles. Our findings suggest that nonphase-locked HGA arises in part from oscillatory or recurring activity of supragranular-layer neuronal ensembles in auditory cortex.

Animal models of neuropsychiatric disorders with appropriate biomarkers can greatly inform the neurobiological basis of disorder-related deficits of cognitive and/or sensory processes. Given the genetic, physiologic, and behavioral similarities between humans and nonhuman primates (NHPs), NHP studies are monumentally important for preclinical translational research. Capitalizing on the NHP's similarities with human systems provides one of the best opportunities to gain detailed insight into the mechanisms underlying disorder-related symptoms and to accumulate a foundation of information for the development of therapeutic interventions. Here, we discuss how results from NHP studies have provided insight into the generation and modulation of select auditory biomarkers of schizophrenia including auditory steady-state responses and mismatch negativity. Since neuro-oscillatory activity has been shown to be relatively preserved across species, we highlight how incorporating the analysis of local and network-level oscillations from multiple nodes across different pathways involved in auditory processing has been used to further the precision of translational comparisons across species.

We developed a detailed model of macaque auditory thalamocortical circuits, including primary auditory cortex (A1), medial geniculate body (MGB), and thalamic reticular nucleus, utilizing the NEURON simulator and NetPyNE tool. The A1 model simulates a cortical column with over 12,000 neurons and 25 million synapses, incorporating data on cell-type-specific neuron densities, morphology, and connectivity across six cortical layers. It is reciprocally connected to the MGB thalamus, which includes interneurons and core and matrix-layer-specific projections to A1. The model simulates multiscale measures, including physiological firing rates, local field potentials (LFPs), current source densities (CSDs), and electroencephalography (EEG) signals. Laminar CSD patterns, during spontaneous activity and in response to broadband noise stimulus trains, mirror experimental findings. Physiological oscillations emerge spontaneously across frequency bands comparable to those recorded in vivo. We elucidate population-specific contributions to observed oscillation events and relate them to firing and presynaptic input patterns. The model offers a quantitative theoretical framework to integrate and interpret experimental data and predict its underlying cellular and circuit mechanisms.

Through the process of saccadic inhibition, visual events briefly suppress eye movements including microsaccades. In humans, saccadic inhibition has been shown to occur in response to the presentation of parafoveal or peripheral visual distractors during fixation and target-directed saccades and to physical changes of behaviorally relevant visual objects. In monkeys performing tasks that controlled eye movements, saccadic inhibition of microsaccades and target-directed saccades has been shown. Using eye data from three previously published studies, we investigated how saccade rate changed while monkeys were presented with visual stimuli under conditions with loose or no viewing demands. In two conditions, animals passively sat while an LED lamp flashed or screen-wide images appeared in front of them. In the third condition, images were repeated semiperiodically while animals had to maintain their gaze within a wide rectangular area and detect oddballs. Despite animals not being required to maintain fixation or make saccades to particular targets, the onset of visual events led to a temporary reduction of saccade rate across all conditions. Interestingly, saccadic inhibition was found at image offsets as well. These results show that saccadic inhibition occurs in monkeys during free viewing.NEW & NOTEWORTHY We investigated the time courses of saccade rate following visual stimuli during three conditions of free viewing in macaque monkeys. Under all conditions, saccade rate decreased transiently after the onset of visual stimuli. These results suggest that saccadic inhibition occurs during free viewing.

Electrophysiological oscillations in the brain have been shown to occur as multi-cycle events, with onset and offset dependent on behavioral and cognitive state. To provide a baseline for state-related and task-related events, we quantified oscillation features in resting-state recordings. We developed an open-source wavelet-based tool to detect and characterize such oscillation events (OEvents) and exemplify the use of this tool in both simulations and two invasively-recorded electrophysiology datasets: one from human, and one from non-human primate auditory system. After removing incidentally occurring event related potentials, we used OEvents to quantify oscillation features. We identified about 2 million oscillation events, classified within traditional frequency bands: delta, theta, alpha, beta, low gamma, gamma, and high gamma. Oscillation events of 1-44 cycles could be identified in at least one frequency band 90% of the time in human and non-human primate recordings. Individual oscillation events were characterized by non-constant frequency and amplitude. This result necessarily contrasts with prior studies which assumed frequency constancy, but is consistent with evidence from event-associated oscillations. We measured oscillation event duration, frequency span, and waveform shape. Oscillations tended to exhibit multiple cycles per event, verifiable by comparing filtered to unfiltered waveforms. In addition to the clear intra-event rhythmicity, there was also evidence of inter-event rhythmicity within bands, demonstrated by finding that coefficient of variation of interval distributions and Fano Factor measures differed significantly from a Poisson distribution assumption. Overall, our study provides an easy-to-use tool to study oscillation events at the single-trial level or in ongoing recordings, and demonstrates that rhythmic, multi-cycle oscillation events dominate auditory cortical dynamics.Significance StatementTo provide a baseline for auditory system cortical dynamics, we quantified neuronal oscillation event features in resting-state recordings of the auditory system. We found that even at rest, event-like oscillations are the dominant operational mode of the auditory cortex in both humans and non-human primates. Our results highlight the importance of the auditory system's rhythmic neuronal fluctuations in setting the context on top of which auditory processing necessary for behavior and cognition occurs. In addition, we demonstrate the importance of studying basic features of oscillation events in ongoing and single-trial recordings to understand their role in cognition and the mechanisms generating them.

Previous studies indicate that motor sampling patterns modulate neuronal excitability in sensory brain regions by entraining brain rhythms, a process termed motor-initiated entrainment. In addition, rhythms of the external environment are also capable of entraining brain rhythms. Our first goal was to investigate the properties of motor-initiated entrainment in the auditory system using a prominent visual motor sampling pattern in primates, saccades. Second, we wanted to determine whether/how motor-initiated entrainment interacts with visual environmental entrainment. We examined laminar profiles of neuronal ensemble activity in primary auditory cortex and found that whereas motor-initiated entrainment has a suppressive effect, visual environmental entrainment has an enhancive effect. We also found that these processes are temporally coupled, and their temporal relationship ensures that their effect on excitability is complementary rather than interfering. Altogether, our results demonstrate that motor and sensory systems continuously interact in orchestrating the brain's context for the optimal sampling of our multisensory environment.