Saccadic inhibition during free viewing in macaque monkeys.

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.

Magnifying Traveling Waves on the Scalp.

Traveling waves appear in various signals that measure neuronal activity. Some signals measured in animals have singles-cell resolution and directly point to neuronal activity. In those cases, activation of distributed neurons forms a wave front, and the front propagates across the cortical surface. Other signals are variants of neuroelectric potentials, i.e. electroencephalography, electrocorticography and field potentials. Instead of having fine spatial resolution, these signals reflect the activity of neuronal populations via volume conduction (VC). Sources of traveling waves in neuroelectric potentials have not been well addressed so far. As animal studies show propagating activation of neurons that spread in measured areas, it is often considered that neuronal activations during scalp waves have similar trajectories of activation, spreading like scalp waves. However, traveling waves on the scalp differ from those found directly on the cortical surface in several dimensions: traveling velocity, traveling distance and areal size occupied by single polarity. We describe that the simplest sources can produce scalp waves with perceived spatial dimensions which are actually a magnification of neuronal activity emanating from local sources due to VC. This viewpoint is not a rigorous proof of our magnification concept. However, we suggest the possibility that the actual dimensions of neuronal activity producing traveling waves is not as large as the dimension of the traveling waves.

Cross Laminar Traveling Components of Field Potentials due to Volume Conduction of Non-Traveling Neuronal Activity in Macaque Sensory Cortices.

Field potentials (FPs) reflect neuronal activities in the brain, and often exhibit traveling peaks across recording sites. While traveling FPs are interpreted as propagation of neuronal activity, not all studies directly reveal such propagating patterns of neuronal activation. Neuronal activity is associated with transmembrane currents that form dipoles and produce negative and positive fields. Thereby, FP components reverse polarity between those fields and have minimal amplitudes at the center of dipoles. Although their amplitudes could be smaller, FPs are never flat even around these reversals. What occurs around the reversal has not been addressed explicitly, although those are rationally in the middle of active neurons. We show that sensory FPs around the reversal appeared with peaks traveling across cortical laminae in macaque sensory cortices. Interestingly, analyses of current source density did not depict traveling patterns but lamina-delimited current sinks and sources. We simulated FPs produced by volume conduction of a simplified 2 dipoles' model mimicking sensory cortical laminar current source density components. While FPs generated by single dipoles followed the temporal patterns of the dipole moments without traveling peaks, FPs generated by concurrently active dipole moments appeared with traveling components in the vicinity of dipoles by superimposition of individually non-traveling FPs generated by single dipoles. These results indicate that not all traveling FP are generated by traveling neuronal activity, and that recording positions need to be taken into account to describe FP peak components around active neuronal populations.SIGNIFICANCE STATEMENT Field potentials (FPs) generated by neuronal activity in the brain occur with fields of opposite polarity. Likewise, in the cerebral cortices, they have mirror-imaged waveforms in upper and lower layers. We show that FPs appear like traveling across the cortical layers. Interestingly, the traveling FPs occur without traveling components of current source density, which represents transmembrane currents associated with neuronal activity. These seemingly odd findings are explained using current source density models of multiple dipoles. Concurrently active, non-traveling dipoles produce FPs as mixtures of FPs produced by individual dipoles, and result in traveling FP waveforms as the mixing ratio depends on the distances from those dipoles. The results suggest that not all traveling FP components are associated with propagating neuronal activity.

Comparison of Scalp ERP to Faces in Macaques and Humans.

Face recognition is an essential activity of social living, common to many primate species. Underlying processes in the brain have been investigated using various techniques and compared between species. Functional imaging studies have shown face-selective cortical regions and their degree of correspondence across species. However, the temporal dynamics of face processing, particularly processing speed, are likely different between them. Across sensory modalities activation of primary sensory cortices in macaque monkeys occurs at about 3/5 the latency of corresponding activation in humans, though this human simian difference may diminish or disappear in higher cortical regions. We recorded scalp event-related potentials (ERPs) to presentation of faces in macaques and estimated the peak latency of ERP components. Comparisons of latencies between macaques (112 ms) and humans (192 ms) suggested that the 3:5 ratio could be preserved in higher cognitive regions of face processing between those species.

Dissociation of broadband high-frequency activity and neuronal firing in the neocortex.

Broadband high-frequency activity (BHA; 70 to 150 Hz), also known as "high gamma," a key analytic signal in human intracranial (electrocorticographic) recordings, is often assumed to reflect local neural firing [multiunit activity (MUA)]. As the precise physiological substrates of BHA are unknown, this assumption remains controversial. Our analysis of laminar multielectrode data from V1 and A1 in monkeys outlines two components of stimulus-evoked BHA distributed across the cortical layers: an "early-deep" and "late-superficial" response. Early-deep BHA has a clear spatial and temporal overlap with MUA. Late-superficial BHA was more prominent and accounted for more of the BHA signal measured near the cortical pial surface. However, its association with local MUA is weak and often undetectable, consistent with the view that it reflects dendritic processes separable from local neuronal firing.

Primary Generators of Visually Evoked Field Potentials Recorded in the Macaque Auditory Cortex.

Prior studies have reported "local" field potential (LFP) responses to faces in the macaque auditory cortex and have suggested that such face-LFPs may be substrates of audiovisual integration. However, although field potentials (FPs) may reflect the synaptic currents of neurons near the recording electrode, due to the use of a distant reference electrode, they often reflect those of synaptic activity occurring in distant sites as well. Thus, FP recordings within a given brain region (e.g., auditory cortex) may be "contaminated" by activity generated elsewhere in the brain. To determine whether face responses are indeed generated within macaque auditory cortex, we recorded FPs and concomitant multiunit activity with linear array multielectrodes across auditory cortex in three macaques (one female), and applied current source density (CSD) analysis to the laminar FP profile. CSD analysis revealed no appreciable local generator contribution to the visual FP in auditory cortex, although we did note an increase in the amplitude of visual FP with cortical depth, suggesting that their generators are located below auditory cortex. In the underlying inferotemporal cortex, we found polarity inversions of the main visual FP components accompanied by robust CSD responses and large-amplitude multiunit activity. These results indicate that face-evoked FP responses in auditory cortex are not generated locally but are volume-conducted from other face-responsive regions. In broader terms, our results underscore the caution that, unless far-field contamination is removed, LFPs in general may reflect such "far-field" activity, in addition to, or in absence of, local synaptic responses.SIGNIFICANCE STATEMENT Field potentials (FPs) can index neuronal population activity that is not evident in action potentials. However, due to volume conduction, FPs may reflect activity in distant neurons superimposed upon that of neurons close to the recording electrode. This is problematic as the default assumption is that FPs originate from local activity, and thus are termed "local" (LFP). We examine this general problem in the context of previously reported face-evoked FPs in macaque auditory cortex. Our findings suggest that face-FPs are indeed generated in the underlying inferotemporal cortex and volume-conducted to the auditory cortex. The note of caution raised by these findings is of particular importance for studies that seek to assign FP/LFP recordings to specific cortical layers.

Chronic recordings reveal tactile stimuli can suppress spontaneous activity of neurons in somatosensory cortex of awake and anesthetized primates.

In somatosensory cortex, tactile stimulation within the neuronal receptive field (RF) typically evokes a transient excitatory response with or without postexcitatory inhibition. Here, we describe neuronal responses in which stimulation on the hand is followed by suppression of the ongoing discharge. With the use of 16-channel microelectrode arrays implanted in the hand representation of primary somatosensory cortex of New World monkeys and prosimian galagos, we recorded neuronal responses from single units and neuron clusters. In 66% of our sample, neuron activity tended to display suppression of firing when regions of skin outside of the excitatory RF were stimulated. In a small proportion of neurons, single-site indentations suppressed firing without initial increases in response to any of the tested sites on the hand. Latencies of suppressive responses to skin indentation (usually 12-34 ms) were similar to excitatory response latencies. The duration of inhibition varied across neurons. Although most observations were from anesthetized animals, we also found similar neuron response properties in one awake galago. Notably, suppression of ongoing neuronal activity did not require conditioning stimuli or multi-site stimulation. The suppressive effects were generally seen following single-site skin indentations outside of the neuron's minimal RF and typically on different digits and palm pads, which have not often been studied in this context. Overall, the characteristics of widespread suppressive or inhibitory response properties with and without initial facilitative or excitatory responses add to the growing evidence that neurons in primary somatosensory cortex provide essential processing for integrating sensory stimulation from across the hand.

Auditory properties in the parabelt regions of the superior temporal gyrus in the awake macaque monkey: an initial survey.

The superior temporal gyrus (STG) is on the inferior-lateral brain surface near the external ear. In macaques, 2/3 of the STG is occupied by an auditory cortical region, the "parabelt," which is part of a network of inferior temporal areas subserving communication and social cognition as well as object recognition and other functions. However, due to its location beneath the squamous temporal bone and temporalis muscle, the STG, like other inferior temporal regions, has been a challenging target for physiological studies in awake-behaving macaques. We designed a new procedure for implanting recording chambers to provide direct access to the STG, allowing us to evaluate neuronal properties and their topography across the full extent of the STG in awake-behaving macaques. Initial surveys of the STG have yielded several new findings. Unexpectedly, STG sites in monkeys that were listening passively responded to tones with magnitudes comparable to those of responses to 1/3 octave band-pass noise. Mapping results showed longer response latencies in more rostral sites and possible tonotopic patterns parallel to core and belt areas, suggesting the reversal of gradients between caudal and rostral parabelt areas. These results will help further exploration of parabelt areas.

Predictive motor control of sensory dynamics in auditory active sensing.

Neuronal oscillations present potential physiological substrates for brain operations that require temporal prediction. We review this idea in the context of auditory perception. Using speech as an exemplar, we illustrate how hierarchically organized oscillations can be used to parse and encode complex input streams. We then consider the motor system as a major source of rhythms (temporal priors) in auditory processing, that act in concert with attention to sharpen sensory representations and link them across areas. We discuss the circuits that could mediate this audio-motor interaction, notably the potential role of the somatosensory system. Finally, we reposition temporal predictions in the context of internal models, discussing how they interact with feature-based or spatial predictions. We argue that complementary predictions interact synergistically according to the organizational principles of each sensory system, forming multidimensional filters crucial to perception.

Generation of field potentials and modulation of their dynamics through volume integration of cortical activity.

Field potentials (FPs) recorded within the brain, often called "local field potentials" (LFPs), are useful measures of net synaptic activity in a neuronal ensemble. However, due to volume conduction, FPs spread beyond regions of underlying synaptic activity, and thus an "LFP" signal may not accurately reflect the temporal patterns of synaptic activity in the immediately surrounding neuron population. To better understand the physiological processes reflected in FPs, we explored the relationship between the FP and its membrane current generators using current source density (CSD) analysis in conjunction with a volume conductor model. The model provides a quantitative description of the spatiotemporal summation of immediate local and more distant membrane currents to produce the FP. By applying the model to FPs in the macaque auditory cortex, we have investigated a critical issue that has broad implications for FP research. We have shown that FP responses in particular cortical layers are differentially susceptible to activity in other layers. Activity in the supragranular layers has the strongest contribution to FPs in other cortical layers, and infragranular FPs are most susceptible to contributions from other layers. To define the physiological processes generating FPs recorded in loci of relatively weak synaptic activity, strong effects produced by synaptic events in the vicinity have to be taken into account. While outlining limitations and caveats inherent to FP measurements, our results also suggest specific peak and frequency band components of FPs can be related to activity in specific cortical layers. These results may help improving the interpretability of FPs.

Feedforward and feedback projections of caudal belt and parabelt areas of auditory cortex: refining the hierarchical model.

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.

Thalamic connections of auditory cortex in marmoset monkeys: lateral belt and parabelt regions.

The primate auditory cortex is comprised of a core region of three primary areas, surrounded by a belt region of secondary areas and a parabelt region lateral to the belt. The main sources of thalamocortical inputs to the auditory cortex are the medial geniculate complex (MGC), medial pulvinar (PM), and several adjoining nuclei in the posterior thalamus. The distribution of inputs varies topographically by cortical area and thalamic nucleus, but in a manner that has not been fully characterized in primates. In this study, the thalamocortical connections of the lateral belt and parabelt were determined by placing retrograde tracer injections into various areas of these regions in the marmoset monkey. Both regions received projections from the medial (MGm) and posterodorsal (MGpd) divisions of the medial geniculate complex (MGC); however, labeled cells in the anterodorsal (MGad) division were present only from injections into the caudal belt. Thalamic inputs to the lateral belt appeared to come mainly from the MGC, whereas the parabelt also received a strong projection from the PM, consistent with its position as a later stage of auditory cortical processing. The results of this study also indicate that the organization of the marmoset auditory cortex is similar to other primates.

Cortical connections of auditory cortex in marmoset monkeys: lateral belt and parabelt regions.

The current working model of primate auditory cortex is constructed from a number of studies of both new and old world monkeys. It includes three levels of processing. A primary level, the core region, is surrounded both medially and laterally by a secondary belt region. A third level of processing, the parabelt region, is located lateral to the belt. The marmoset monkey (Callithrix jacchus jacchus) has become an important model system to study auditory processing, but its anatomical organization has not been fully established. In previous studies, we focused on the architecture and connections of the core and medial belt areas (de la Mothe et al., 2006a, J Comp Neurol 496:27-71; de la Mothe et al., 2006b, J Comp Neurol 496:72-96). In this study, the corticocortical connections of the lateral belt and parabelt were examined in the marmoset. Tracers were injected into both rostral and caudal portions of the lateral belt and parabelt. Both regions revealed topographic connections along the rostrocaudal axis, where caudal areas of injection had stronger connections with caudal areas, and rostral areas of injection with rostral areas. The lateral belt had strong connections with the core, belt, and parabelt, whereas the parabelt had strong connections with the belt but not the core. Label in the core from injections in the parabelt was significantly reduced or absent, consistent with the idea that the parabelt relies mainly on the belt for its cortical input. In addition, the present and previous studies indicate hierarchical principles of anatomical organization in the marmoset that are consistent with those observed in other primates.

How local is the local field potential?

Local field potentials (LFPs) are of growing importance in neurophysiological investigations. LFPs supplement action potential recordings by indexing activity relevant to EEG, magnetoencephalographic, and hemodynamic (fMRI) signals. Recent reports suggest that LFPs reflect activity within very small domains of several hundred micrometers. We examined this conclusion by comparing LFP, current source density (CSD), and multiunit activity (MUA) signals in macaque auditory cortex. Estimated by frequency tuning bandwidths, these signals' "listening areas" differ systematically with an order of MUA < CSD < LFP. Computational analyses confirm that observed LFPs receive local contributions. Direct measurements indicate passive spread of LFPs to sites more than a centimeter from their origins. These findings appear to be independent of the frequency content of the LFP. Our results challenge the idea that LFP recordings typically integrate over extremely circumscribed local domains. Rather, LFPs appear as a mixture of local potentials with "volume conducted" potentials from distant sites.

Auditory cortical tuning to band-pass noise in primate A1 and CM: a comparison to pure tones.

We examined multiunit responses to tones and to 1/3 and 2/3 octave band-pass noise (BPN) in the marmoset primary auditory cortex (A1) and the caudomedial belt (CM). In both areas, BPN was more effective than tones, evoking multiunit responses at lower intensity and across a wider frequency range. Typically, the best responses to BPN remained at the characteristic frequency. Additionally, in both areas responses to BPN tended to be of greater magnitude and shorter latency than responses to tones. These effects are consistent with the integration of more excitatory inputs driven by BPN than by tones. While it is generally thought that single units in A1 prefer narrow band sounds such as tones, we found that best responses for multi units in both A1 and CM were obtained with noises of narrow spectral bandwidths.

Coding of FM sweep trains and twitter calls in area CM of marmoset auditory cortex.

The primate auditory cortex contains three interconnected regions (core, belt, parabelt), which are further subdivided into discrete areas. The caudomedial area (CM) is one of about seven areas in the belt region that has been the subject of recent anatomical and physiological studies conducted to define the functional organization of auditory cortex. The main goal of the present study was to examine temporal coding in area CM of marmoset monkeys using two related classes of acoustic stimuli: (1) marmoset twitter calls; and (2) frequency-modulated (FM) sweep trains modeled after the twitter call. The FM sweep trains were presented at repetition rates between 1 and 24 Hz, overlapping the natural phrase frequency of the twitter call (6-8 Hz). Multiunit recordings in CM revealed robust phase-locked responses to twitter calls and FM sweep trains. For the latter, phase-locking quantified by vector strength (VS) was best at repetition rates between 2 and 8 Hz, with a mean of about 5 Hz. Temporal response patterns were not strictly phase-locked, but exhibited dynamic features that varied with the repetition rate. To examine these properties, classification of the repetition rate from the temporal response pattern evoked by twitter calls and FM sweep trains was examined by Fisher's linear discrimination analysis (LDA). Response classification by LDA revealed that information was encoded not only by phase-locking, but also other components of the temporal response pattern. For FM sweep trains, classification was best for repetition rates from 2 to 8 Hz. Thus, the majority of neurons in CM can accurately encode the envelopes of temporally complex stimuli over the behaviorally-relevant range of the twitter call. This suggests that CM could be engaged in processing that requires relatively precise temporal envelope discrimination, and supports the hypothesis that CM is positioned at an early stage of processing in the auditory cortex of primates.

Neuronal oscillations and visual amplification of speech.

It is widely recognized that viewing a speaker's face enhances vocal communication, although the neural substrates of this phenomenon remain unknown. We propose that the enhancement effect uses the ongoing oscillatory activity of local neuronal ensembles in the primary auditory cortex. Neuronal oscillations reflect rhythmic shifting of neuronal ensembles between high and low excitability states. Our hypothesis holds that oscillations are 'predictively' modulated by visual input, so that related auditory input arrives during a high excitability phase and is thus amplified. We discuss the anatomical substrates and key timing parameters that enable and constrain this effect. Our hypothesis makes testable predictions for future studies and emphasizes the idea that 'background' oscillatory activity is instrumental to cortical sensory processing.

Cortical connections of the auditory cortex in marmoset monkeys: core and medial belt regions.

The auditory cortex of primates contains a core region of three primary areas surrounded by a belt region of secondary areas. Recent neurophysiological studies suggest that the belt areas medial to the core have unique functional roles, including multisensory properties, but little is known about their connections. In this study and its companion, the cortical and subcortical connections of the core and medial belt regions of marmoset monkeys were compared to account for functional differences between areas and refine our working model of the primate auditory cortex. Anatomical tracer injections targeted two core areas (A1 and R) and two medial belt areas (rostromedial [RM] and caudomedial [CM]). RM and CM had topographically weighted connections with all other areas of the auditory cortex ipsilaterally, but these were less widespread contralaterally. CM was densely connected with caudal auditory fields, the retroinsular (Ri) area of the somatosensory cortex, the superior temporal sulcus (STS), and the posterior parietal and entorhinal cortex. The connections of RM favored rostral auditory areas, with no clear somatosensory inputs. RM also projected to the lateral nucleus of the amygdala and tail of the caudate nucleus. A1 and R had topographically weighted connections with medial and lateral belt regions, infragranular inputs from the parabelt, and weak connections with fields outside the auditory cortex. The results indicated that RM and CM are distinct areas of the medial belt region with direct inputs from the core. CM also has somatosensory input and may correspond to an area on the posteromedial transverse gyrus of humans and the anterior auditory field of other mammals.

Thalamic connections of the auditory cortex in marmoset monkeys: core and medial belt regions.

In this study and its companion, the cortical and subcortical connections of the medial belt region of the marmoset monkey auditory cortex were compared with the core region. The main objective was to document anatomical features that account for functional differences observed between areas. Injections of retrograde and bi-directional anatomical tracers targeted two core areas (A1 and R), and two medial belt areas (rostromedial [RM] and caudomedial [CM]). Topographically distinct patterns of connections were revealed among subdivisions of the medial geniculate complex (MGC) and multisensory thalamic nuclei, including the suprageniculate (Sg), limitans (Lim), medial pulvinar (PM), and posterior nucleus (Po). The dominant thalamic projection to the CM was the anterior dorsal division (MGad) of the MGC, whereas the posterior dorsal division (MGpd) targeted RM. CM also had substantial input from multisensory nuclei, especially the magnocellular division (MGm) of the MGC. RM had weak multisensory connections. Corticotectal projections of both RM and CM targeted the dorsomedial quadrant of the inferior colliculus, whereas the CM projection also included a pericentral extension around the ventromedial and lateral portion of the central nucleus. Areas A1 and R were characterized by focal topographic connections within the ventral division (MGv) of the MGC, reflecting the tonotopic organization of both core areas. The results indicate that parallel subcortical pathways target the core and medial belt regions and that RM and CM represent functionally distinct areas within the medial belt auditory cortex.

Entropy analysis of neuronal spike train synchrony.

Although vector strength (VS) and the Rayleigh tests are widely used to quantify neuronal firing synchrony to cyclic events, their use is valid only for singly peaked, unimodal distributions. In this report, we propose a new method to quantify synchrony, applicable to both unimodal and multimodal distributions. We also propose a statistical test to examine temporal structure under a null hypothesis of no synchrony.