Spectrotemporal analysis of evoked and induced electroencephalographic responses in primary auditory cortex (A1) of the awake monkey

Electroencephalography is increasingly being used to probe the functional organization of auditory cortex. Modulation of the electroencephalographic (EEG) signal by tones was examined in primary auditory cortex (A1) of awake monkeys. EEG data were measured at 4 laminar depths defined by current source density profiles evoked by best frequency (BF) tones. Midlaminar multiunit activity was used to define the tuning characteristics of A1 sites. Presentation of BF tones increased EEG power across the range of frequencies examined (4-290 Hz), with maximal effects evident within the first 100 ms after stimulus onset. The largest relative increases in EEG power generally occurred at very high gamma frequency bands (130-210 Hz). Increases in EEG power for frequencies less than 70 Hz primarily represented changes in phase-locked activity, whereas increases at higher frequencies primarily represented changes in non-phase-locked activity. Power increases in higher gamma bands were better correlated with the A1 tonotopic organization than power increases in lower frequency bands. Results were similar across the 4 laminar depths examined. These findings highlight the value of examining high-frequency EEG components in exploring the functional organization of auditory cortex and may enhance interpretation of related studies in humans.     

Interaction of excitatory and inhibitory frequency-receptive fields in determining fundamental frequency sensitivity of primary auditory cortex neurons in awake cats

Harmonic complex tones produce pitch-height perception corresponding to the fundamental frequency (F0). This study investigates how the spectral cue of F0 is processed in neurons of the primary auditory cortex (A1) with sustained-response properties. We found F0-sensitive and -insensitive cells: the former discriminated between harmonics and noise, while the latter did not. F0-sensitive cells preferred F0s corresponding to the best frequency (BF) and 0.5 x BF. The F0-sensitivity to F0=0.5 x BF was preserved for missing F0, but abolished by eliminating both F0 and the second harmonic. The inhibitory subfield of the frequency-receptive field was restricted to the spectral region between the preferred harmonics in F0-sensitive cells, while it was frequency unspecific in F0-insensitive cells. We conclude that (i) A1 is well organized for discrimination between harmonics and noise; (ii) pitch-height is represented along with the tonotopic axis; (iii) all aspects of the sustained neural responses to harmonic and noise stimuli are consequences of spectral filtering; and (iv) although the observed cell behavior explains some psychophysical pitch perception behaviors, such as pitch-chroma (helical pitch perception with frequency elevation), pitch-level tolerance and adaptive behavior, F0-encoding in A1 remains at the incomplete perceptual level (dominance of the third to fifth harmonics for pitch strength is unexplainable by the cell behavior).     

Organization of horizontal axons in the inferior temporal cortex and primary visual cortex of the macaque monkey

We investigated the organization of horizontal connections at two distinct hierarchical levels in the ventral visual cortical pathway of the monkey, the inferior temporal (TE) and primary visual (V1) cortices. After injections of anterograde tracers into layers 2 and 3, clusters of terminals ('patches') of labeled horizontal collaterals in TE appeared at various distances up to 8 mm from the injection site, while in V1 clear patches were distributed only within 2 mm. The size and spacing of these patches in TE were larger and more irregular than those observed in V1. The labeling intensity of patches in V1 declined sharply with distance from the injection site. This tendency was less obvious in TE; a number of densely labeled patches existed at distant sites beyond weakly labeled patches. While injections into both areas resulted in an elongated pattern of patches, the anisotropy was greater in TE than in V1 for injections of a similar size. Dual tracer injections and larger-sized injections further revealed that the adjacent sites in TE had spatially distinct horizontal projections, compared to those in V1. These area-specific characteristics of the horizontal connections may contribute to the differences in visual information processing of TE and V1.     

Sequence sensitivity of neurons in cat primary auditory cortex

Properties of sequence-sensitive neurons in primary auditory cortex of cats were explored in detail. Stimuli were sequences of two tones, in which the frequency and intensity of the first tone and the temporal separation between the first and second, or probe, tone were parametrically varied. After presentation of the first tone, the responses of 32 single units and 48 multiunits to the probe tone were found to be enhanced up to 140-5270% (median 340%) above the response obtained in the single-tone condition. Probe tone enhancement was induced from a considerable number of sequence conditions and depended on the frequency and intensity of the first tone and on the temporal separation between the onsets of the first and the probe tone. On average, the maximally enhanced response occurred when the first tone was 1 octave below or above the probe tone and its intensity was 14 dB louder than the probe tone. The most effective temporal separation of the tones for an enhancement effect was approximately 100 ms. The range of enhancing tones was largely outside the excitatory tuning curve of a neuron. Results extend previous findings of properties of sequence-sensitive neurons in the auditory cortex of echolocating bats and non-echolocating mammals, and suggest that sequence-sensitive neurons are quite common and involved in the cortical representation of spectrotemporal patterns of acoustic signals.     

The intrinsic shape of human and macaque primary visual cortex

Previous studies have reported considerable variability in primary visual cortex (V1) shape in both humans and macaques. Here, we demonstrate that much of this variability is due to the pattern of cortical folds particular to an individual and that V1 shape is similar among individual humans and macaques as well as between these 2 species. Human V1 was imaged ex vivo using high-resolution (200 microm) magnetic resonance imaging at 7 T. Macaque V1 was identified in published histological serial section data. Manual tracings of the stria of Gennari were used to construct a V1 surface, which was computationally flattened with minimal metric distortion of the cortical surface. Accurate flattening allowed investigation of intrinsic geometric features of cortex, which are largely independent of the highly variable cortical folds. The intrinsic shape of V1 was found to be similar across human subjects using both nonparametric boundary matching and a simple elliptical shape model fit to the data and is very close to that of the macaque monkey. This result agrees with predictions derived from current models of V1 topography. In addition, V1 shape similarity suggests that similar developmental mechanisms are responsible for establishing V1 shape in these 2 species.     

Anatomical substrates for functional columns in macaque monkey primary visual cortex

In this review we re-examine the concept of a cortical column in macaque primary visual cortex, and consider to what extent a functionally defined column reflects any sort of anatomical entity that subdivides cortical territory. Functional studies have shown that columns relating to different response properties are mapped in cortex at different spatial scales. We suggest that these properties first emerge in mid-layer 4C through a combination of thalamic afferent inputs and local intracortical circuitry, and are then transferred to other layers in a columnar fashion, via interlaminar relays, where additional processing occurs. However, several properties are not strictly columnar since they do not appear in all cortical layers. In contrast to the functional column, an anatomically based cortical column is defined most clearly in terms of the reciprocal connections it makes, both via intra-areal lateral connections and inter-areal feedback/feedforward pathways. The column boundaries are reinforced by interplay between lateral inhibition spreading beyond the column boundary and disinhibition within the column. The anatomical column acts as a functionally tuned unit and point of information collation from laterally offset regions and feedback pathways. Thalamic inputs provide the high-contrast receptive field sizes of the column's neurons, intra-areal lateral connections provide their low contrast summation field sizes, and feedback pathways provide surround modulation of receptive fields responses.     

Physiological and anatomical evidence for multisensory interactions in auditory cortex

Recent studies, conducted almost exclusively in primates, have shown that several cortical areas usually associated with modality-specific sensory processing are subject to influences from other senses. Here we demonstrate using single-unit recordings and estimates of mutual information that visual stimuli can influence the activity of units in the auditory cortex of anesthetized ferrets. In many cases, these units were also acoustically responsive and frequently transmitted more information in their spike discharge patterns in response to paired visual-auditory stimulation than when either modality was presented by itself. For each stimulus, this information was conveyed by a combination of spike count and spike timing. Even in primary auditory areas (primary auditory cortex [A1] and anterior auditory field [AAF]), approximately 15% of recorded units were found to have nonauditory input. This proportion increased in the higher level fields that lie ventral to A1/AAF and was highest in the anterior ventral field, where nearly 50% of the units were found to be responsive to visual stimuli only and a further quarter to both visual and auditory stimuli. Within each field, the pure-tone response properties of neurons sensitive to visual stimuli did not differ in any systematic way from those of visually unresponsive neurons. Neural tracer injections revealed direct inputs from visual cortex into auditory cortex, indicating a potential source of origin for the visual responses. Primary visual cortex projects sparsely to A1, whereas higher visual areas innervate auditory areas in a field-specific manner. These data indicate that multisensory convergence and integration are features common to all auditory cortical areas but are especially prevalent in higher areas.     

Descending projections from extrastriate visual cortex modulate responses of cells in primary auditory cortex

Primary sensory cortical responses are modulated by the presence or expectation of related sensory information in other modalities, but the sources of multimodal information and the cellular locus of this integration are unclear. We investigated the modulation of neural responses in the murine primary auditory cortical area Au1 by extrastriate visual cortex (V2). Projections from V2 to Au1 terminated in a classical descending/modulatory pattern, with highest density in layers 1, 2, 5, and 6. In brain slices, whole-cell recordings revealed long latency responses to stimulation in V2L that could modulate responses to subsequent white matter (WM) stimuli at latencies of 5-20 ms. Calcium responses imaged in Au1 cell populations showed that preceding WM with V2L stimulation modulated WM responses, with both summation and suppression observed. Modulation of WM responses was most evident for near-threshold WM stimuli. These data indicate that corticocortical projections from V2 contribute to multimodal integration in primary auditory cortex.     

Strabismic suppression is mediated by inhibitory interactions in the primary visual cortex

Most strabismic observers do not suffer from double vision because of suppression from conscious perception of 1 of the 2 eyes' conflicting views. Direct evidence for the site and neural substrate of strabismic suppression has not been available so far, although psychophysical data suggest a cortical origin. On the other hand, cross-orientation suppression among conflicting stimuli presented monocularly has recently been shown to have a strong thalamic component. Here we present evidence, using both visual stimulation and pharmacological techniques, that strabismic suppression occurs in the primary visual cortex and involves gamma-amino butyric acid (GABA)-mediated inhibition. We show that its dependency on the drift rate of the suppressing stimulus is consistent with a cortical origin; unlike monocular cross-orientation suppression, it cannot be evoked by very fast-moving stimuli. Furthermore, strabismic suppression is greatly reduced when GABAergic inhibition is locally blocked by the GABA(A) antagonist bicuculline.     

Spectrotemporal receptive fields in anesthetized cat primary auditory cortex are context dependent

In order to investigate how the auditory scene is analyzed and perceived, auditory spectrotemporal receptive fields (STRFs) are generally used as a convenient way to describe how frequency and temporal sound information is encoded. However, using broadband sounds to estimate STRFs imperfectly reflects the way neurons process complex stimuli like conspecific vocalizations insofar as natural sounds often show limited bandwidth. Using recordings in the primary auditory cortex of anesthetized cats, we show that presentation of narrowband stimuli not including the best frequency of neurons provokes the appearance of residual peaks and increased firing rate at some specific spectral edges of stimuli compared with classical STRFs obtained from broadband stimuli. This result is the same for STRFs obtained from both spikes and local field potentials. Potential mechanisms likely involve release from inhibition. We thus emphasize some aspects of context dependency of STRFs, that is, how the balance of inhibitory and excitatory inputs is able to shape the neural response from the spectral content of stimuli.     

Laminar patterns of local excitatory input to layer 5 neurons in macaque primary visual cortex

Layer 5 neurons in primary visual cortex make putative reciprocal feedback connections to the superficial layers. To test this hypothesis, we employed scanning laser photostimulation combined with intracellular dye injection to examine local functional excitatory inputs to and axonal projections from individual layer 5 neurons in brain slices from monkey V1. In contrast with previous studies of other V1 neurons, layer 5 neurons received significant input from nearly all of the cortical layers, suggesting individual layer 5 cells integrate information from a broad range of input sources. Nevertheless relative strengths of laminar inputs varied across neurons. Cluster analysis of relative strength of laminar inputs to individual layer 5 neurons revealed four discrete clusters representing recurring input patterns; each cluster included both excitatory and inhibitory neurons. Twenty-five of 40 layer 5 neurons fell into two clusters, both characterized by very strong input from superficial layers. These input patterns are consistent with layer 5 neurons providing feedback to superficial layers. The remaining 15 neurons received stronger input from deep layers. Differences in input from layer 4Calpha versus 4Cbeta also suggest specific associations of the magnocellular and parvocellular visual pathways, with populations receiving stronger input from deep versus superficial cortical layers.     

A study of pyramidal cell structure in the cingulate cortex of the macaque monkey with comparative notes on inferotemporal and primary visual cortex

Recent studies have revealed a marked degree of variation in the pyramidal cell phenotype in visual, somatosensory, motor and prefrontal cortical areas in the brain of different primates, which are believed to subserve specialized cortical function. In the present study we carried out comparisons of dendritic structure of layer III pyramidal cells in the anterior and posterior cingulate cortex and compared their structure with those sampled from inferotemporal cortex (IT) and the primary visual area (V1) in macaque monkeys. Cells were injected with Lucifer Yellow in flat-mounted cortical slices, and processed for a light-stable DAB reaction product. Size, branching pattern, and spine density of basal dendritic arbors was determined, and somal areas measured. We found that pyramidal cells in anterior cingulate cortex were more branched and more spinous than those in posterior cingulate cortex, and cells in both anterior and posterior cingulate were considerably larger, more branched, and more spinous than those in area V1. These data show that pyramidal cell structure differs between posterior dysgranular and anterior granular cingulate cortex, and that pyramidal neurons in cingulate cortex have different structure to those in many other cortical areas. These results provide further evidence for a parallel between structural and functional specialization in cortex.     

Characteristics of intracellularly injected infragranular pyramidal neurons in cat primary auditory cortex.

Pyramidal neurons in layers V and VI of cat primary auditory cortex (AI) were intracellularly injected with biocytin after functional characterization according to a position relative to an anteroposterior sequence of best-frequency responses. A sample of 19 completely filled neurons was analyzed, and a preliminary classification was made on the basis of dendritic morphology and axon collateral distribution. Layer V cells could be divided into two types. Cells in the upper part of layer V and projecting toward the diencephalon had a large cell body and an apical dendrite with extensive branches in layer I. These cells had few recurrent axon collaterals, and no terminal axonal bushes were formed in the vicinity of the dendritic field. Long horizontal collaterals with many boutons, however, extended in various directions parallel to the cortical surface. By contrast, cells in the lower part of layer V and sending an axon into the putamen, or without an obvious subcortical axon, had a medium soma and an apical dendrite with few branches in layer I. These cells had a dense bush of recurrent collaterals extending into layers II and III and surrounding the dendritic field, but few or no horizontal collaterals. Layer VI injected neurons were more heterogeneous. All had a thin ascending dendrite with oblique branches both ending in layer III. Axon collateral distributions varied from cell to cell. Relatively small cells with an apical dendrite that branched frequently in layers III and IV had a dense network of recurrent collaterals in the dendritic field, but virtually no horizontal collaterals. This type projected toward the diencephalon. Cells with relatively long horizontal collaterals and a weak recurrent system confined to layers V and VI had a unique arborization pattern of basal dendrites. This type may have projected to the claustrum or other cortical areas. One cell with dendritic branches restricted to layer VI had horizontal collaterals predominantly in layer VI. This cell projected into the corpus callosum. The apparent close correlation between extrinsic projections of infragranular neurons and their dendritic morphology and intracortical collateral distributions suggests that differentially projecting cells may engage different elements of intracortical circuitry in AI.     

Perceptual learning on an auditory frequency discrimination task by cats: association with changes in primary auditory cortex

The aim of this study was to determine whether auditory perceptual learning is associated with changes in the frequency organization and/or neuronal response properties of primary auditory cortex (AI). Five out of six cats trained on an 8 kHz frequency discrimination task showed improvements in performance that reflected changes in discriminative capacity. Quantitative measures of the response characteristics and frequency organization of AI revealed that the frequency organization of AI in trained cats did not differ from that in controls, but there was a tendency for neurons with a CF immediately above 8 kHz to have slightly broader tuning in the trained cats than in controls, and neurons in one of these bands had significantly shorter latency. These results are in accord with recent reports that cortical topography in primary visual cortex is unchanged in animals trained on visual discrimination tasks, but are at variance with an earlier report of enlarged representations of training frequencies in AI of monkeys trained on a frequency discrimination task. It is concluded that substantial changes in perceptual discriminative capacity can occur without change in primary cortical topography and with only small changes in neuronal response characteristics.     

Effects of continuous noise maskers on tone-evoked potentials in cat primary auditory cortex.

In nine barbiturate-anesthetized cats, cortical evoked potentials for tones presented to the contralateral ear were studied for the effects of continuous wideband noise masking. In five animals, input-output functions for tones were obtained in the presence of continuous noise masking at the same ear. Tone thresholds were raised by the presence of the masker, and they closely tracked the level of the masker, such that increments in masker level brought about tone threshold elevations of the same magnitude. In four animals, we compared the effect on responses to contralateral tones of continuous maskers presented to the same ear as the tone, to the opposite ear, and to both ears simultaneously. The presence of the masker at the ear opposite the tone had a small and variable effect on the response to the stimulus at the ear with the tone, whether or not noise was also present at that ear. Consideration of extant single-neuron evidence provides an interpretation of these findings. Whereas maskers at the ear with the tone are known to reduce signal sensitivity for almost all cortical neurons, the effects of masking at the ear opposite the tone (ipsilateral to the cortex) are likely to be very heterogeneous. It is likely that the perceptual salience of signals that have different binaural configurations to concurrent maskers resides in which neuronal elements are activated, rather than in the total number of cells excited, and it is perhaps for this reason that the evoked potentials show only modest effects of this masking parameter.     

Separate processing dynamics for texture elements, boundaries and surfaces in primary visual cortex of the macaque monkey.

A visual scene is rapidly segmented into the regions that are occupied by different objects and background. Segmentation may be initiated from the detection of boundaries, followed by the filling-in of the surfaces between these boundaries to render them visible. Alternatively, segmentation may be based on grouping of surface elements that are similar, so that boundaries are (implicitly) identified as the borders between elements that are grouped into objects. Here, we present recordings from awake monkey primary visual cortex that show that in late (>80 ms) components of the neural responses a correlate of boundary formation is expressed, followed by a filling-in (also called colouring) between the edges. These data favour a model of segmentation where boundary formation initiates surface filling-in.     

Intracellular characterization of suppressive responses in supragranular pyramidal neurons of cat primary auditory cortex in vivo

Several suppressive processes shape the response properties of auditory neurons, namely lateral inhibition, non-monotonic rate level function and excitation/inhibition binaural interaction. By combining intracellular recording from and staining of layers 2 and 3 pyramidal neurons (PNs) in cat primary auditory cortex, we demonstrate the temporal aspects of depolarization and hyperpolarization underlying these suppressions using pure tone stimulation. Two populations can be distinguished by the occurrence of hyperpolarization following onset depolarization (O-DEP). In layer 2 PNs there is an absence of hyperpolarization following O-DEP, while in layer 3 PNs hyperpolarization follows O-DEP. The latency of O-DEP is shortest at the neuron's best frequency. The latency shortens as sound intensity increases. In non-monotonic PNs, hyperpolarization onset becomes shorter as sound intensity increases. This earlier onset of hyperpolarization shortens the duration of the preceding O-DEP, resulting in a decreased O-DEP amplitude. Diverse patterns in the temporal interaction of depolarization and hyperpolarization underlie the binaural suppression interaction. These results demonstrate that diverse suppressive responses result from differences in the temporal timing of excitation and inhibition. The present results also suggest the possibility of distinct connections between PNs responding in a similar manner.     

Perception-related modulations of local field potential power and coherence in primary visual cortex of awake monkey during binocular rivalry

Cortical synchronization at gamma-frequencies (35-90 Hz) has been proposed to define the connectedness among the local parts of a perceived visual object. This hypothesis is still under debate. We tested it under conditions of binocular rivalry (BR), where a monkey perceived alternations among conflicting gratings presented singly to each eye at orthogonal orientations. We made multi-channel microelectrode recordings of multi-unit activity (MUA) and local field potentials (LFP) from striate cortex (V1) during BR while the monkey indicated his perception by pushing a lever. We analyzed spectral power and coherence of MUA and LFP over 4-90 Hz. As in previous work, coherence of gamma-signals in most pairs of recording locations strongly depended on grating orientation when stimuli were presented congruently in both eyes. With incongruent (rivalrous) stimulation LFP power was often consistently modulated in consonance with the perceptual state. This was not visible in MUA. These perception-related modulations of LFP occurred at low and medium frequencies (< 30 Hz), but not at gamma-frequencies. Perception-related modulations of LFP coherence were also restricted to the low-medium range. In conclusion, our results do not support the expectation that gamma-synchronization in V1 is related to the perceptual state during BR, but instead suggest a perception-related role of synchrony at low and medium frequencies.     

Isofrequency band-like zones of activation revealed by optical imaging of intrinsic signals in the cat primary auditory cortex

Neurons of similar frequency preference are arranged in isofrequency bands (IFBs) across the primary auditory cortex (AI) of many mammals. Across the AI of the cat, one of the most frequently studied species for auditory anatomy and function, we demonstrate IFB-like responses using optical imaging of intrinsic signals (OIS). Optically defined activations were extensively elongated along the dorsoventral axis of AI (the ratio of the major and minor axes was approximately 2:1), and systematically shifted as a function of stimulus frequency. The elongation of this IFB-like zone was more conspicuous at higher frequencies. In the ventral sector of the imaged field, the IFB-like zones of activation evoked at different pure tone frequencies tended to overlap extensively. Electrophysiological recording from loci within the optically defined zones of activation revealed matched responses to the frequencies used for optical imaging at 65% of these loci. The dorsoventral orientation of these zones of activation was also closely matched with the orientation of tangentially spreading intrinsic axon terminals, as revealed anatomically. The visualization of IFB-like architecture and tonotopic organization by OIS provides a basic framework for investigating the relationships of different spectral channels and between multiple acoustic parameters at a neuronal population level.     

Development of inhibitory timescales in auditory cortex

The time course of inhibition plays an important role in cortical sensitivity, tuning, and temporal response properties. We investigated the development of L2/3 inhibitory circuitry between fast-spiking (FS) interneurons and pyramidal cells (PCs) in auditory thalamocortical slices from mice between postnatal day 10 (P10) and P29. We found that the maturation of the intrinsic and synaptic properties of both FS cells and their connected PCs influence the timescales of inhibition. FS cell firing rates increased with age owing to decreased membrane time constants, shorter afterhyperpolarizations, and narrower action potentials. Between FS-PC pairs, excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs) changed with age. The latencies, rise, and peak times of the IPSPs, as well as the decay constants of both EPSPs and IPSPs decreased between P10 and P29. In addition, decreases in short-term depression at excitatory PC-FS synapses resulted in more sustained synaptic responses during repetitive stimulation. Finally, we show that during early development, the temporal properties that influence the recruitment of inhibition lag those of excitation. Taken together, our results suggest that the changes in the timescales of inhibitory recruitment coincide with the development of the tuning and temporal response properties of auditory cortical networks.