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.     

Spectral and temporal processing in rat posterior auditory cortex

The rat auditory cortex is divided anatomically into several areas, but little is known about the functional differences in information processing between these areas. To determine the filter properties of rat posterior auditory field (PAF) neurons, we compared neurophysiological responses to simple tones, frequency modulated (FM) sweeps, and amplitude modulated noise and tones with responses of primary auditory cortex (A1) neurons. PAF neurons have excitatory receptive fields that are on average 65% broader than A1 neurons. The broader receptive fields of PAF neurons result in responses to narrow and broadband inputs that are stronger than A1. In contrast to A1, we found little evidence for an orderly topographic gradient in PAF based on frequency. These neurons exhibit latencies that are twice as long as A1. In response to modulated tones and noise, PAF neurons adapt to repeated stimuli at significantly slower rates. Unlike A1, neurons in PAF rarely exhibit facilitation to rapidly repeated sounds. Neurons in PAF do not exhibit strong selectivity for rate or direction of narrowband one octave FM sweeps. These results indicate that PAF, like nonprimary visual fields, processes sensory information on larger spectral and longer temporal scales than primary cortex.     

Visual modulation of neurons in auditory cortex

Our brain integrates the information provided by the different sensory modalities into a coherent percept, and recent studies suggest that this process is not restricted to higher association areas. Here we evaluate the hypothesis that auditory cortical fields are involved in cross-modal processing by probing individual neurons for audiovisual interactions. We find that visual stimuli modulate auditory processing both at the level of field potentials and single-unit activity and already in primary and secondary auditory fields. These interactions strongly depend on a stimulus' efficacy in driving the neurons but occur independently of stimulus category and for naturalistic as well as artificial stimuli. In addition, interactions are sensitive to the relative timing of audiovisual stimuli and are strongest when visual stimuli lead by 20-80 msec. Exploring the underlying mechanisms, we find that enhancement correlates with the resetting of slow (approximately 10 Hz) oscillations to a phase angle of optimal excitability. These results demonstrate that visual stimuli can modulate the firing of neurons in auditory cortex in a manner that depends on stimulus efficacy and timing. These neurons thus meet the criteria for sensory integration and provide the auditory modality with multisensory contextual information about co-occurring environmental events.     

Propofol attenuates responses of the auditory cortex to acoustic stimulation in a dose-dependent manner: a FMRI study

BACKGROUND: Functional magnetic resonance imaging (fMRI) using blood-oxygen-level-dependent (BOLD) contrasts is a common method for studying sensory or cognitive brain functions. The aim of the present study was to assess the effect of the intravenous anaesthetic propofol on auditory-induced brain activation using BOLD contrast fMRI. METHODS: In eight neurosurgical patients, musical stimuli were presented binaurally in a block design. Imaging was performed under five conditions: no propofol (or wakefulness) and propofol plasma target concentrations of 0.5, 1.0, 1.5, and 2.0 microg ml(-1). RESULTS: During wakefulness we found activations in the superior temporal gyrus (STG) corresponding to the primary and secondary auditory cortex as well as in regions of higher functions of auditory information processing. The BOLD response decreased with increasing concentrations of propofol but remained partially preserved in areas of basic auditory processing in the STG during propofol 2.0 microg ml(-1). CONCLUSIONS: Our results suggest a dose-dependent impairment of central processing of auditory information after propofol administration. These results are consistent with electrophysiological findings measuring neuronal activity directly, thus suggesting a dose-dependent impairment of central processing of auditory information after propofol administration. However, propofol did not totally blunt primary cortical responses to acoustic stimulation, indicating that patients may process auditory information under general anaesthesia.     

A comparison of visual and auditory motion processing in human cerebral cortex

Visual and auditory motion information can be used together to provide complementary information about the movement of objects. To investigate the neural substrates of such cross-modal integration, functional magnetic resonance imaging was used to assess brain activation while subjects performed separate visual and auditory motion discrimination tasks. Areas of unimodal activation included the primary and/or early sensory cortex for each modality plus additional sites extending toward parietal cortex. Areas conjointly activated by both tasks included lateral parietal cortex, lateral frontal cortex, anterior midline and anterior insular cortex. The parietal site encompassed distinct, but partially overlapping, zones of activation in or near the intraparietal sulcus (IPS). A subsequent task requiring an explicit cross-modal speed comparison revealed several foci of enhanced activity relative to the unimodal tasks. These included the IPS, anterior midline, and anterior insula but not frontal cortex. During the unimodal auditory motion task, portions of the dorsal visual motion system showed signals depressed below resting baseline. Thus, interactions between the two systems involved either enhancement or suppression depending on the stimuli present and the nature of the perceptual task. Together, these results identify human cortical regions involved in polysensory integration and the attentional selection of cross-modal motion information.     

Posterior cingulate cortex: sensory and oculomotor properties of single neurons in behaving cat.

The posterior cingulate cortex of the cat is strongly linked to cortical areas with sensory and oculomotor functions. We have now recorded from feline posterior cingulate neurons in order to determine whether they are active in conjunction with sensory events and eye movements. The results described here are based on monitoring the electrical activity of 195 single neurons in the posterior cingulate cortex of three cats equipped with surgically implanted scleral search coils and trained to fixate visual targets. Posterior cingulate neurons carry tonic orbital position signals and are phasically active in conjunction with saccadic eye movements. Activity related to eye movements and gaze is attenuated but not abolished by the elimination of visual feedback. Posterior cingulate neurons also are responsive to visual, auditory, and somatosensory stimulation. Systematic testing with visual stimuli revealed that responses are sharply reduced due to refractoriness at rates of stimulation greater than a few per second. These results conform to the theory that posterior cingulate cortex is involved in processes underlying visuospatial cognition.     

Repeatedly pairing vagus nerve stimulation with a movement reorganizes primary motor cortex

Although sensory and motor systems support different functions, both systems exhibit experience-dependent cortical plasticity under similar conditions. If mechanisms regulating cortical plasticity are common to sensory and motor cortices, then methods generating plasticity in sensory cortex should be effective in motor cortex. Repeatedly pairing a tone with a brief period of vagus nerve stimulation (VNS) increases the proportion of primary auditory cortex responding to the paired tone (Engineer ND, Riley JR, Seale JD, Vrana WA, Shetake J, Sudanagunta SP, Borland MS, Kilgard MP. 2011. Reversing pathological neural activity using targeted plasticity. Nature. 470:101-104). In this study, we predicted that repeatedly pairing VNS with a specific movement would result in an increased representation of that movement in primary motor cortex. To test this hypothesis, we paired VNS with movements of the distal or proximal forelimb in 2 groups of rats. After 5 days of VNS movement pairing, intracranial microstimulation was used to quantify the organization of primary motor cortex. Larger cortical areas were associated with movements paired with VNS. Rats receiving identical motor training without VNS pairing did not exhibit motor cortex map plasticity. These results suggest that pairing VNS with specific events may act as a general method for increasing cortical representations of those events. VNS movement pairing could provide a new approach for treating disorders associated with abnormal movement representations.     

Spatiotemporal properties of layer V neurons of the rat primary somatosensory cortex.

Animals in their natural environments actively process spatiotemporally complex sensory signals in order to guide adaptive behavior. It therefore seems likely that the properties of both single neurons and neural ensembles should reflect the dynamic nature of such interactions. During exploratory behaviors, rats move their whiskers to actively discriminate between different tactile features. We investigated whether this dynamic sensory processing was reflected in the spatial and temporal properties of neurons in layer V of the 'whisker area' in the rat primary somatosensory cortex. We found that the majority of layer V neurons had large (8.5+/-4.9 whiskers) spatiotemporal receptive fields (i.e. individual cells responded best to different whiskers as a function of post-stimulus time), and that the excitatory responses of surround whiskers formed a spatial gradient of excitation that seemed to reflect the greater use of the ventral and caudal whiskers during natural behaviors. Analyses of ensembles of layer V neurons revealed that single-whisker stimuli activated a portion of layer V that extends well beyond a single cortical column (average of 5.6 barrel cortical columns). Based on these results, we conclude that the rat primary somatosensory cortex does not appear to operate as a static decoder of tactile information. On the contrary, our data suggest that tactile processing in rats is likely to involve the on-going interactions between populations of broadly tuned neurons in the thalamocortical pathway.     

Motor and sensory cortex in humans: topography studied with chronic subdural stimulation.

Classic neurosurgical teaching holds that once the Rolandic fissure (Rf) has been located, there are distinct differentiated primary motor and sensory functional units confined within a narrow cortical strip: Brodmann's Areas 4 and 6 for primary motor units in front of the Rf and 3, 1, and 2 for sensory units behind the Rf. To test this assumption, we examined in detail the records of cortical mapping done by electrical stimulation of the cerebral cortex via implanted subdural electrode grids in 35 patients with seizure disorders. Of 1381 stimulations of the electrode sites, 346 (25.1%) produced primary motor or motor-arrest and sensory responses in contralateral body parts: 56.8% were primary motor responses; 16.2% were motor-arrest; 22.5% were sensory; and the remaining 4.5% were mixed motor and sensory responses. Two-thirds (65.9%) of the primary motor responses were located within 10 mm of the Rf, and the remaining one-third (34.1%) were more than 10 mm anterior to the Rf or were posterior to the Rf. Furthermore, in the patient group with brain lesions, fewer than one-third (28.1%) of the responses were within the 10-mm narrow anterior strip. Our study reconfirmed that a significant number--at least one-third--of motor responses are distributed outside the classic narrow cortical strip. In patients with brain lesions, the motor representation is further displaced outside the narrow strip. This finding indicates that primary motor cortex may extend beyond the gyrus immediately anterior to the Rf.     

Concurrent performance of two working memory tasks: potential mechanisms of interference

When two tasks are performed simultaneously, performance often deteriorates, with concomitant increases in reaction time and error rate. Three potential neurophysiological mechanisms behind this deterioration in performance have been considered here: (i) dual-task performance requires additional cognitive operations and activation of cortical areas in addition to those active during single-task performance; (ii) two tasks interfere if they require activation of the same part of cortex; and (iii) cross-modal inhibition causes interference between two tasks involving stimuli from different sensory modalities. Positron emission tomography was used to measure regional cerebral blood flow (rCBF) during performance of an auditory working memory (WM) task, a visual WM task, both WM tasks (dual task) and a control condition. Compared to the control condition, the auditory and visual WM tasks activated sensory-specific areas in the superior temporal gyrus and occipital pole respectively. Both WM tasks also activated overlapping parts of cortex in the dorsolateral prefrontal, inferior parietal and cingulate cortex. There was no separate cortical area which was activated only in the dual task, and thus no area which could be associated with any dual task specific cognitive process such as task-coordination or divided attention. Decrease in rCBF in one WM task did not overlap with the areas of rCBF increase in the other WM task. However, an inhibitory mechanism could not be ruled out, since the rCBF increase in sensory specific areas was smaller in the dual- task condition than in the single-task conditions. The cortical activity underlying WM was to a large extent organized in a non-sensory specific, or non-parallel, way, and the results are consistent with the hypothesis that concurrent tasks interfere with each other if they demand activation of the same part of cortex.      

Topography of cortical activation differs for fundamental and harmonic frequencies of the steady-state visual-evoked responses. An EEG and PET H215O study

In humans, visual flicker stimuli of graded frequency (2-90 Hz) elicit an electroencephalographic (EEG) steady-state visual-evoked response (SSVER) with the same fundamental frequency as the stimulus and, in addition, a series of harmonic responses. The fundamental component of the SSVER is generated by increased synaptic activity in primary visual cortex (V1). We set out to determine the cortical origin of the harmonic responses in humans. For this purpose, we recorded the SSVERs at 5 different frequencies (5, 10, 15, 25, and 40 Hz) and measured regional cerebral blood flow (rCBF) with positron emission tomography-H(2)(15)O at rest and during visual stimulation at the same frequencies. The rCBF contrast weighted by the amplitude of the SSVERs first harmonics showed activation of a swath of cortex perpendicular to V1, including mostly the inferior half of the parieto-occipital sulcus. This area overlapped minimally with the primary visual cortex activated by the fundamental frequency. A different method, estimating EEG cortical source current density with low-resolution brain electromagnetic tomography, gave the same results. Our finding suggests that the inferior portion of the banks of the parieto-occipital sulci contains association visual cortex involved in the processing of stimuli that can be as simple as a flickering light source.     

A neural model of binocular integration and rivalry based on the coordination of action-potential timing in primary visual cortex

In normal vision, the inputs from the two eyes are integrated into a single percept. When dissimilar images are presented to the two eyes, however, they compete for perceptual dominance, so that one eye's view suppresses that of the other. Recent evidence suggests that this phenomenon, known as binocular rivalry, arises through competition between alternative stimulus interpretations in extrastriate cortex. Because eye-specific information appears to be lost at this stage, it remains unclear how the stimulus conditions that yield binocular rivalry are distinguished from those that produce stable single vision. Using a neural network that models the mammalian early visual system, I investigate here the hypothesis that congruent and conflicting stimuli are distinguished by their different effects on the relative timing of action potentials in primary visual cortex (V1), where monocular inputs are first combined. In the model, congruent stimulation of both eyes results in synchronization of discharges among binocular neurons in V1. By contrast, conflicting stimulation of the two eyes results in neuronal asynchrony in this area. This asynchrony then produces rivalrous response suppression at later stages in the visual pathway. Synchronization of firing in V1, however, prevents such competition, thereby ensuring non-rivalrous responses. These novel effects of spike timing on competition emerge naturally from the network dynamics. The results suggest that input-related differences in relative spike timing at an early stage of visual processing may play an important part in the phenomena both of binocular integration and rivalry; furthermore, they indicate that the temporal patterning of cortical activity may be a fundamental mechanism of selection among competing stimulus representations.      

Disruption of layer 4 development alters laminar processing in ferret somatosensory cortex

Treatment with the anti-mitotic agent methylazoxymethanol (MAM) on embryonic day 33 (E33) in ferrets changes features of somatosensory cortex. These include dramatic reduction of cells in layer 4, and altered distributions of thalamocortical afferent terminations and GABA(A) receptors. To determine the effect of the relative absence of layer 4 on processing of sensory stimuli we used current source-density profiles to assess laminar activity patterns. Nearly synchronous activation occurs across all layers in treated animals, which contrasts with the normal cortical activation pattern of initial sinks in layer 4. This change after MAM treatment is consistent with the absence of layer 4 cells and widespread termination of thalamocortical afferents. Using periodic stimulation at 'flutter' frequency, layer 4 neurons in normal somatosensory cortex fire reproducibly to the stimulus rate; the capacity for entrainment is best for layer 4 and weaker in the extragranular layers. The capacity to encode periodic sensory stimuli is disrupted in MAM-treated somatosensory cortex; after an initial response to the onset of periodic stimuli, neurons in all cortical layers show weak entrainment. Neural responses to sensory drive in E33 MAM-treated cortex are also embedded in levels of neural activity substantially above those in normal somatosensory cortex. Sustained stimulation additionally reveals different capacities in each layer for improved signal-to-noise ratios, with layer 4 neurons in normal animals exhibiting the most improved signaling over time. We conclude that normal thalamic terminations, an intact layer 4 and subsequent intracortical processing are integral to proper encoding of stimulus features.     

Binaural interactions in primary auditory cortex of the awake macaque

The functional organization of primary auditory cortex in non-primates is generally modeled as a tonotopic gradient with an orthogonal representation of independently mapped binaural interaction columns along the isofrequency contours. Little information is available regarding the validity of this model in the primate brain, despite the importance of binaural cues for sound localization and auditory scene analysis. Binaural and monaural responses of A1 to pure tone stimulation were studied using auditory evoked potentials, current source density and multiunit activity. Key findings include: (i) differential distribution of binaural responses with respect to best frequency, such that 74% of the sites exhibiting binaural summation had best frequencies below 2000 Hz; (ii) the pattern of binaural responses was variable with respect to cortical depth, with binaural summation often observed in the supragranular laminae of sites showing binaural suppression in thalamorecipient laminae; and (iii) dissociation of binaural responses between the initial and sustained action potential firing of neuronal ensembles in A1. These data support earlier findings regarding the temporal and spatial complexity of responses in A1 in the awake state, and are inconsistent with a simple orthogonal arrangement of binaural interaction columns and best frequency in A1 of the awake primate.     

Working memory specific activity in auditory cortex: potential correlates of sequential processing and maintenance

Working memory (WM) tasks involve several interrelated processes during which past information must be transiently maintained, recalled, and compared with test items according to previously instructed rules. It is not clear whether the rule-specific comparisons of perceptual with memorized items are only performed in previously identified frontal and parietal WM areas or whether these areas orchestrate such comparisons by feedback to sensory cortex. We tested the latter hypothesis by focusing on auditory cortex (AC) areas with low-noise functional magnetic resonance imaging in a 2-back WM task involving frequency-modulated (FM) tones. The control condition was a 0-back task on the same stimuli. Analysis of the group data identified an area on right planum temporale equally activated by both tasks and an area on the left planum temporale specifically involved in the 2-back task. A region of interest analysis in each individual revealed that activation on the left planum temporale in the 2-back task positively correlated with the task performance of the subjects. This strongly suggests a prominent role of the AC in 2-back WM tasks. In conjunction with previous findings on FM processing, the left lateralized effect presumably reflects the complex sequential processing demand of the 2-back matching to sample task.     

Activation of the human occipital and parietal cortex by pattern and luminance stimuli: neuromagnetic measurements

We compared cortical reactivity to pattern and luminance stimuli by recording evoked responses and spontaneous brain rhythms from 10 subjects with a whole-scalp neuromagnetometer. Hemifield patterns (black-and-white checkerboards) elicited strong contralateral transient activation of the occipital V1/V2 cortex, maximum at 65-75 ms, followed by sustained activation during the 2 s stimulus. Responses to hemifield luminance stimuli also had an occipital component, but they were dominated by activation of the medial parieto-occipital sulcus (POS) 60- 70 ms later. The POS region was equally well activated by foveal and extrafoveal stimuli. The occipital responses to hemifield luminance stimuli differed from those to pattern stimuli in two main aspects: the sustained activation was significantly weaker, and the responses were almost symmetrical, indicating a surprisingly bilateral occipital activation. These effects were similar with foveal and extrafoveal stimuli. The spontaneous 10 Hz alpha rhythm, originating predominantly in the POS region, was suppressed after both stimulus onsets and offsets, more strongly for luminance than pattern stimuli. Activation of the occipital cortex dominated after pattern stimuli, whereas the effect of luminance stimulation was stronger in the parieto-occipital region. The distinct signal distributions in the occipital and POS regions suggest that the two types of stimuli activate the magno- and parvocellular pathways to a varying degree. These findings are also in line with a stronger attention-catching value of the luminance than pattern stimuli.      

Representation of surface luminance and contrast in primary visual cortex

In visual perception, object identification requires both the ability to define regions of uniform luminance and zones of luminance contrast. Neural processes underlying contrast detection have been well studied, while those defining luminance remain poorly understood and controversial. Partially because stimuli comprised of uniform luminance are relatively ineffective in driving responses of cortical neurons, little effort has been made to systematically compare responses of individual neurons to both uniform luminance and contrast. Using large static uniform luminance and contrast stimuli, modulated temporally in luminance or contrast, we found a continuum of responses ranging from a few cells modulated only by luminance (luminance-only), to many cells modulated by both luminance and contrast (luminance-contrast), and to many others modulated only by contrast (contrast-only) in primary visual cortex. Moreover, luminance-contrast cells had broader orientation tuning, larger receptive field (RF) and lower spatial frequency Preference, on average, than contrast-only cells. Contrast-only cells had contrast responses more linearly correlated to the spatial structure of their RFs than luminance-contrast cells. Taken together these results suggest that luminance and contrast are represented, to some degree, by independent mechanisms that may be shaped by different classes of subcortical and/or cortical inputs.     

Principles governing auditory cortex connections

Topographic maps are common constituents of the primary auditory, visual, and somatic sensory cortex. However, in most cortical areas, no such maps have yet been identified, posing a conceptual problem for theories of cortical function centered on topography. What principle guides the organization of these other areas? We investigated this issue in cat auditory cortex. The connectional topography of five tonotopic areas and eight non-tonotopic areas was assessed using retrograde tract tracing and quantified by three metrics: clustering, dispersion, and separation. Clustering measures the spatial density of labeled neurons, dispersion provides an index of their spread, and separation serves as a scaling metric. These parameters each show that all auditory cortical regions receive precise and equally topographic connections from thalamic, corticocortical, and commissural sources. This isotropic principle suggests a common substrate for coordinating communication across the cortex and may reflect common mechanisms related to the developmental patterning of connections. This unifying principle extends to auditory and prefrontal cortex, and perhaps to other neocortical areas.     

Evidence of functional connectivity between auditory cortical areas revealed by amplitude modulation sound processing

The human auditory cortex includes several interconnected areas. A better understanding of the mechanisms involved in auditory cortical functions requires a detailed knowledge of neuronal connectivity between functional cortical regions. In human, it is difficult to track in vivo neuronal connectivity. We investigated the interarea connection in vivo in the auditory cortex using a method of directed coherence (DCOH) applied to depth auditory evoked potentials (AEPs). This paper presents simultaneous AEPs recordings from insular gyrus (IG), primary and secondary cortices (Heschl's gyrus and planum temporale), and associative areas (Brodmann area [BA] 22) with multilead intracerebral electrodes in response to sinusoidal modulated white noises in 4 epileptic patients who underwent invasive monitoring with depth electrodes for epilepsy surgery. DCOH allowed estimation of the causality between 2 signals recorded from different cortical sites. The results showed 1) a predominant auditory stream within the primary auditory cortex from the most medial region to the most lateral one whatever the modulation frequency, 2) unidirectional functional connection from the primary to secondary auditory cortex, 3) a major auditory propagation from the posterior areas to the anterior ones, particularly at 8, 16, and 32 Hz, and 4) a particular role of Heschl's sulcus dispatching information to the different auditory areas. These findings suggest that cortical processing of auditory information is performed in serial and parallel streams. Our data showed that the auditory propagation could not be associated to a unidirectional traveling wave but to a constant interaction between these areas that could reflect the large adaptive and plastic capacities of auditory cortex. The role of the IG is discussed.     

Seeing touch is correlated with content-specific activity in primary somatosensory cortex

There is increasing evidence to suggest that primary sensory cortices can become active in the absence of external stimulation in their respective modalities. This occurs, for example, when stimuli processed via one sensory modality imply features characteristic of a different modality; for instance, visual stimuli that imply touch have been observed to activate the primary somatosensory cortex (SI). In the present study, we addressed the question of whether such cross-modal activations are content specific. To this end, we investigated neural activity in the primary somatosensory cortex of subjects who observed human hands engaged in the haptic exploration of different everyday objects. Using multivariate pattern analysis of functional magnetic resonance imaging data, we were able to predict, based exclusively on the activity pattern in SI, which of several objects a subject saw being explored. Along with previous studies that found similar evidence for other modalities, our results suggest that primary sensory cortices represent information relevant for their modality even when this information enters the brain via a different sensory system.