Faculty Bibliography

While the function of the pulvinar remains one of the least explored among the thalamic nuclei despite occupying the most thalamic volume in primates, it has long been suspected to play a crucial role in attentive stimulus processing. In this issue of Neuron, Zhou et al. (2016) use simultaneous pulvinar-visual cortex recordings and pulvinar inactivation to provide evidence that the pulvinar is essential for intact stimulus processing, maintenance of neuronal oscillatory dynamics, and mediating the effects of attention.

Earlier studies demonstrate that when the frequency of rhythmic tone sequences or streams is task relevant, ongoing excitability fluctuations (oscillations) of neuronal ensembles in primary auditory cortex (A1) entrain to stimulation in a frequency dependent way that sharpens frequency tuning. The phase distribution across A1 neuronal ensembles at time points when attended stimuli are predicted to occur reflects the focus of attention along the spectral attribute of auditory stimuli. This study examined how neuronal activity is modulated if only the temporal features of rhythmic stimulus streams are relevant. We presented macaques with auditory clicks arranged in 33 Hz (gamma timescale) quintets, repeated at a 1.6 Hz (delta timescale) rate. Such multi-scale, hierarchically organized temporal structure is characteristic of vocalizations and other natural stimuli. Monkeys were required to detect and respond to deviations in the temporal pattern of gamma quintets. As expected, engagement in the auditory task resulted in the multi-scale entrainment of delta- and gamma-band neuronal oscillations across all of A1. Surprisingly, however, the phase-alignment, and thus, the physiological impact of entrainment differed across the tonotopic map in A1. In the region of 11-16 kHz representation, entrainment most often aligned high excitability oscillatory phases with task-relevant events in the input stream and thus resulted in response enhancement. In the remainder of the A1 sites, entrainment generally resulted in response suppression. Our data indicate that the suppressive effects were due to low excitability phase delta oscillatory entrainment and the phase amplitude coupling of delta and gamma oscillations. Regardless of the phase or frequency, entrainment appeared stronger in left A1, indicative of the hemispheric lateralization of auditory function.

Recent electrophysiological and neuroimaging studies provide converging evidence that attending to sounds increases the response selectivity of neuronal ensembles even at the first cortical stage of auditory stimulus processing in primary auditory cortex (A1). This is achieved by enhancement of responses in the regions that process attended frequency content, and by suppression of responses in the surrounding regions. The goals of our study were to define the extent to which A1 neuronal ensembles are involved in this process, determine its effect on the frequency tuning of A1 neuronal ensembles, and examine the involvement of the different cortical layers. To accomplish these, we analyzed laminar profiles of synaptic activity and action potentials recorded in A1 of macaques performing a rhythmic intermodal selective attention task. We found that the frequency tuning of neuronal ensembles was sharpened due to both increased gain at the preferentially processed or best frequency and increased response suppression at all other frequencies when auditory stimuli were attended. Our results suggest that these effects are due to a frequency-specific counterphase entrainment of ongoing delta oscillations, which predictively orchestrates opposite sign excitability changes across all of A1. This results in a net suppressive effect due to the large proportion of neuronal ensembles that do not specifically process the attended frequency content. Furthermore, analysis of laminar activation profiles revealed that although attention-related suppressive effects predominate the responses of supragranular neuronal ensembles, response enhancement is dominant in the granular and infragranular layers, providing evidence for layer-specific cortical operations in attentive stimulus processing.

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.

Previous studies indicate that primary somatosensory cortical area 3b in macaques contains a somatotopic map of the hand, encompassing representations of each digit. However, numerous observations including recent findings in anesthetized New World monkeys indicate that that the digit representations within the map are not discrete. We assessed the generality and spatial extent of these effects in awake macaques. We show that, within a given digit representation, (1) there is response to stimulation of all other digits tested, extending across most or all of the digit map, and (2) response to stimulation of the locally preferred digit is modulated by concurrent stimulation of each of the other digits. Control experiments rule out effects of attention and mechanical spread of stimulation. We thus confirm that, even at the first level of somatosensory cortical processing, inputs from potentially all of the digits frame the context within which the input to a single digit is represented.

Attending to a stimulus enhances its neuronal representation, even at the level of primary sensory cortex. Cross-modal modulation can similarly enhance a neuronal representation, and this process can also operate at the primary cortical level. Phase reset of ongoing neuronal oscillatory activity has been shown to be an important element of the underlying modulation of local cortical excitability in both cases. We investigated the influence of attention on oscillatory phase reset in primary auditory and visual cortices of macaques performing an intermodal selective attention task. In addition to responses 'driven' by preferred modality stimuli, we noted that both preferred and nonpreferred modality stimuli could 'modulate' local cortical excitability by phase reset of ongoing oscillatory activity, and that this effect was linked to their being attended. These findings outline a supramodal mechanism by which attention can control neurophysiological context, thus determining the representation of specific sensory content in primary sensory cortex

Recent anatomical, physiological, and neuroimaging findings indicate multisensory convergence at early, putatively unisensory stages of cortical processing. The objective of this study was to confirm somatosensory-auditory interaction in A1 and to define both its physiological mechanisms and its consequences for auditory information processing. Laminar current source density and multiunit activity sampled during multielectrode penetrations of primary auditory area A1 in awake macaques revealed clear somatosensory-auditory interactions, with a novel mechanism: somatosensory inputs appear to reset the phase of ongoing neuronal oscillations, so that accompanying auditory inputs arrive during an ideal, high-excitability phase, and produce amplified neuronal responses. In contrast, responses to auditory inputs arriving during the opposing low-excitability phase tend to be suppressed. Our findings underscore the instrumental role of neuronal oscillations in cortical operations. The timing and laminar profile of the multisensory interactions in A1 indicate that nonspecific thalamic systems may play a key role in the effect.

We examined effects of eye position on auditory cortical responses in macaques. Laminar current-source density (CSD) and multiunit activity (MUA) profiles were sampled with linear array multielectrodes. Eye position significantly modulated auditory-evoked CSD amplitude in 24/29 penetrations (83%), across A1 and belt regions; 4/24 cases also showed significant MUA AM. Eye-position effects occurred mainly in the supragranular laminae and lagged the co-located auditory response by, on average, 38 ms. Effects in A1 and belt regions were indistinguishable in amplitude, laminar profile, and latency. The timing and laminar profile of the eye-position effects suggest that they are not combined with auditory signals at a subcortical stage of the lemniscal auditory pathways and simply "fed-forward" into cortex. Rather, these effects may be conveyed to auditory cortex by feedback projections from parietal or frontal cortices, or alternatively, they may be conveyed by nonclassical feedforward projections through auditory koniocellular (calbindin positive) neurons.

Recent findings in both monkeys and humans indicate that multisensory convergence occurs in low-level cortical structures generally believed to be unisensory in function. In an in-depth treatment of this theme, this paper reviews anatomical and physiological findings relating to the convergence of visual, somatosensory and auditory signals at early stages of auditory cortical processing. We discuss the potential anatomical sources of the input, and the types of known projections, and attempt to integrate this information with the current hierarchical model of auditory processing. Finally, we consider the functional implications of multisensory integration in early sensory processing.