Spatial processing in the auditory cortex of the macaque monkey

The patterns of cortico-cortical and cortico-thalamic connections of auditory cortical areas in the rhesus monkey have led to the hypothesis that acoustic information is processed in series and in parallel in the primate auditory cortex. Recent physiological experiments in the behaving monkey indicate that the response properties of neurons in different cortical areas are both functionally distinct from each other, which is indicative of parallel processing, and functionally similar to each other, which is indicative of serial processing. Thus, auditory cortical processing may be similar to the serial and parallel “what” and “where” processing by the primate visual cortex. If “where” information is serially processed in the primate auditory cortex, neurons in cortical areas along this pathway should have progressively better spatial tuning properties. This prediction is supported by recent experiments that have shown that neurons in the caudomedial field have better spatial tuning properties than neurons in the primary auditory cortex. Neurons in the caudomedial field are also better than primary auditory cortex neurons at predicting the sound localization ability across different stimulus frequencies and bandwidths in both azimuth and elevation. These data support the hypothesis that the primate auditory cortex processes acoustic information in a serial and parallel manner and suggest that this may be a general cortical mechanism for sensory perception.

Modular organization of intrinsic connections associated with spectral tuning in cat auditory cortex

Many response properties in primary auditory cortex (AI) are segregated spatially and organized topographically as those in primary visual cortex. Intensive study has not revealed an intrinsic, anatomical organizing principle related to an AI functional topography. We used retrograde anatomic tracing and topographic physiologic mapping of acoustic response properties to reveal long-range (≥1.5 mm) convergent intrinsic horizontal connections between AI subregions with similar bandwidth and characteristic frequency selectivity. This suggests a modular organization for processing spectral bandwidth in AI.

Subdivisions of auditory cortex and processing streams in primates

The auditory system of monkeys includes a large number of interconnected subcortical nuclei and cortical areas. At subcortical levels, the structural components of the auditory system of monkeys resemble those of nonprimates, but the organization at cortical levels is different. In monkeys, the ventral nucleus of the medial geniculate complex projects in parallel to a core of three primary-like auditory areas, AI, R, and RT, constituting the first stage of cortical processing. These areas interconnect and project to the homotopic and other locations in the opposite cerebral hemisphere and to a surrounding array of eight proposed belt areas as a second stage of cortical processing. The belt areas in turn project in overlapping patterns to a lateral parabelt region with at least rostral and caudal subdivisions as a third stage of cortical processing. The divisions of the parabelt distribute to adjoining auditory and multimodal regions of the temporal lobe and to four functionally distinct regions of the frontal lobe. Histochemically, chimpanzees and humans have an auditory core that closely resembles that of monkeys. The challenge for future researchers is to understand how this complex system in monkeys analyzes and utilizes auditory information.

Activation of human primary motor cortex during action observation: A neuromagnetic study

The monkey premotor cortex contains neurons that discharge during action execution and during observation of actions made by others. Transcranial magnetic stimulation experiments suggest that a similar observation/execution matching system also is present in humans. We recorded neuromagnetic oscillatory activity of the human precentral cortex from 10 healthy volunteers while (i) they had no task to perform, (ii) they were manipulating a small object, and (iii) they were observing another individual performing the same task. The left and right median nerves were stimulated alternately (interstimulus interval, 1.5 s) at intensities exceeding motor threshold, and the poststimulus rebound of the rolandic 15- to 25-Hz activity was quantified. In agreement with previous studies, the rebound was strongly suppressed bilaterally during object manipulation. Most interestingly, the rebound also was significantly diminished during action observation (31–46% of the suppression during object manipulation). Control experiments, in which subjects were instructed to observe stationary or moving stimuli, confirmed the specificity of the suppression effect. Because the recorded 15- to 25-Hz activity is known to originate mainly in the precentral motor cortex, we concluded that the human primary motor cortex is activated during observation as well as execution of motor tasks. These findings have implications for a better understanding of the machinery underlying action recognition in humans.

Optical images of visible and invisible percepts in the primary visual cortex of primates

We optically imaged a visual masking illusion in primary visual cortex (area V-1) of rhesus monkeys to ask whether activity in the early visual system more closely reflects the physical stimulus or the generated percept. Visual illusions can be a powerful way to address this question because they have the benefit of dissociating the stimulus from perception. We used an illusion in which a flickering target (a bar oriented in visual space) is rendered invisible by two counter-phase flickering bars, called masks, which flank and abut the target. The target and masks, when shown separately, each generated correlated activity on the surface of the cortex. During the illusory condition, however, optical signals generated in the cortex by the target disappeared although the image of the masks persisted. The optical image thus was correlated with perception but not with the physical stimulus.

Coinciding early activation of the human primary visual cortex and anteromedial cuneus

Proper understanding of processes underlying visual perception requires information on the activation order of distinct brain areas. We measured dynamics of cortical signals with magnetoencephalography while human subjects viewed stimuli at four visual quadrants. The signals were analyzed with minimum current estimates at the individual and group level. Activation emerged 55–70 ms after stimulus onset both in the primary posterior visual areas and in the anteromedial part of the cuneus. Other cortical areas were active after this initial dual activation. Comparison of data between species suggests that the anteromedial cuneus either comprises a homologue of the monkey area V6 or is an area unique to humans. Our results show that visual stimuli activate two cortical areas right from the beginning of the cortical response. The anteromedial cuneus has the temporal position needed to interact with the primary visual cortex V1 and thereby to modify information transferred via V1 to extrastriate cortices.

Plasticity of the cochleotopic (frequency) map in specialized and nonspecialized auditory cortices

Auditory conditioning (associative learning) causes reorganization of the cochleotopic (frequency) maps of the primary auditory cortex (AI) and the inferior colliculus. Focal electric stimulation of the AI also evokes basically the same cortical and collicular reorganization as that caused by conditioning. Therefore, part of the neural mechanism for the plasticity of the central auditory system caused by conditioning can be explored by focal electric stimulation of the AI. The reorganization is due to shifts in best frequencies (BFs) together with shifts in frequency-tuning curves of single neurons. In the AI of the Mongolian gerbil (Meriones unguiculatus) and the posterior division of the AI of the mustached bat (Pteronotus parnellii), focal electric stimulation evokes BF shifts of cortical auditory neurons located within a 0.7-mm distance along the frequency axis. The amount and direction of BF shift differ depending on the relationship in BF between stimulated and recorded neurons, and between the gerbil and mustached bat. Comparison in BF shift between different mammalian species and between different cortical areas of a single species indicates that BF shift toward the BF of electrically stimulated cortical neurons (centripetal BF shift) is common in the AI, whereas BF shift away from the BF of electrically stimulated cortical neurons (centrifugal BF shift) is special. Therefore, we propose a hypothesis that reorganization, and accordingly organization, of cortical auditory areas caused by associative learning can be quite different between specialized and nonspecialized (ordinary) areas of the auditory cortex.

Pain perception: Is there a role for primary somatosensory cortex?

Anatomical, physiological, and lesion data implicate multiple cortical regions in the complex experience of pain. These regions include primary and secondary somatosensory cortices, anterior cingulate cortex, insular cortex, and regions of the frontal cortex. Nevertheless, the role of different cortical areas in pain processing is controversial, particularly that of primary somatosensory cortex (S1). Human brain-imaging studies do not consistently reveal pain-related activation of S1, and older studies of cortical lesions and cortical stimulation in humans did not uncover a clear role of S1 in the pain experience. Whereas studies from a number of laboratories show that S1 is activated during the presentation of noxious stimuli as well as in association with some pathological pain states, others do not report such activation. Several factors may contribute to the different results among studies. First, we have evidence demonstrating that S1 activation is highly modulated by cognitive factors that alter pain perception, including attention and previous experience. Second, the precise somatotopic organization of S1 may lead to small focal activations, which are degraded by sulcal anatomical variability when averaging data across subjects. Third, the probable mixed excitatory and inhibitory effects of nociceptive input to S1 could be disparately represented in different experimental paradigms. Finally, statistical considerations are important in interpreting negative findings in S1. We conclude that, when these factors are taken into account, the bulk of the evidence now strongly supports a prominent and highly modulated role for S1 cortex in the sensory aspects of pain, including localization and discrimination of pain intensity.

Functional analysis of primary visual cortex (V1) in humans

Human area V1 offers an excellent opportunity to study, using functional MRI, a range of properties in a specific cortical visual area, whose borders are defined objectively and convergently by retinotopic criteria. The retinotopy in V1 (also known as primary visual cortex, striate cortex, or Brodmann’s area 17) was defined in each subject by using both stationary and phase-encoded polar coordinate stimuli. Data from V1 and neighboring retinotopic areas were displayed on flattened cortical maps. In additional tests we revealed the paired cortical representations of the monocular “blind spot.” We also activated area V1 preferentially (relative to other extrastriate areas) by presenting radial gratings alternating between 6% and 100% contrast. Finally, we showed evidence for orientation selectivity in V1 by measuring transient functional MRI increases produced at the change in response to gratings of differing orientations. By systematically varying the orientations presented, we were able to measure the bandwidth of the orientation “transients” (45°).

The acquisition of skilled motor performance: Fast and slow experience-driven changes in primary motor cortex

Behavioral and neurophysiological studies suggest that skill learning can be mediated by discrete, experience-driven changes within specific neural representations subserving the performance of the trained task. We have shown that a few minutes of daily practice on a sequential finger opposition task induced large, incremental performance gains over a few weeks of training. These gains did not generalize to the contralateral hand nor to a matched sequence of identical component movements, suggesting that a lateralized representation of the learned sequence of movements evolved through practice. This interpretation was supported by functional MRI data showing that a more extensive representation of the trained sequence emerged in primary motor cortex after 3 weeks of training. The imaging data, however, also indicated important changes occurring in primary motor cortex during the initial scanning sessions, which we proposed may reflect the setting up of a task-specific motor processing routine. Here we provide behavioral and functional MRI data on experience-dependent changes induced by a limited amount of repetitions within the first imaging session. We show that this limited training experience can be sufficient to trigger performance gains that require time to become evident. We propose that skilled motor performance is acquired in several stages: “fast” learning, an initial, within-session improvement phase, followed by a period of consolidation of several hours duration, and then “slow” learning, consisting of delayed, incremental gains in performance emerging after continued practice. This time course may reflect basic mechanisms of neuronal plasticity in the adult brain that subserve the acquisition and retention of many different skills.

Rapidly induced auditory plasticity: The ventriloquism aftereffect

Cortical representational plasticity has been well documented after peripheral and central injuries or improvements in perceptual and motor abilities. This has led to inferences that the changes in cortical representations parallel and account for the improvement in performance during the period of skill acquisition. There have also been several examples of rapidly induced changes in cortical neuronal response properties, for example, by intracortical microstimulation or by classical conditioning paradigms. This report describes similar rapidly induced changes in a cortically mediated perception in human subjects, the ventriloquism aftereffect, which presumably reflects a corresponding change in the cortical representation of acoustic space. The ventriloquism aftereffect describes an enduring shift in the perception of the spatial location of acoustic stimuli after a period of exposure of spatially disparate and simultaneously presented acoustic and visual stimuli. Exposure of a mismatch of 8° for 20–30 min is sufficient to shift the perception of acoustic space by approximately the same amount across subjects and acoustic frequencies. Given that the cerebral cortex is necessary for the perception of acoustic space, it is likely that the ventriloquism aftereffect reflects a change in the cortical representation of acoustic space. Comparisons between the responses of single cortical neurons in the behaving macaque monkey and the stimulus parameters that give rise to the ventriloquism aftereffect suggest that the changes in the cortical representation of acoustic space may begin as early as the primary auditory cortex.

Mechanisms and streams for processing of “what” and “where” in auditory cortex

The functional specialization and hierarchical organization of multiple areas in rhesus monkey auditory cortex were examined with various types of complex sounds. Neurons in the lateral belt areas of the superior temporal gyrus were tuned to the best center frequency and bandwidth of band-passed noise bursts. They were also selective for the rate and direction of linear frequency modulated sweeps. Many neurons showed a preference for a limited number of species-specific vocalizations (“monkey calls”). These response selectivities can be explained by nonlinear spectral and temporal integration mechanisms. In a separate series of experiments, monkey calls were presented at different spatial locations, and the tuning of lateral belt neurons to monkey calls and spatial location was determined. Of the three belt areas the anterolateral area shows the highest degree of specificity for monkey calls, whereas neurons in the caudolateral area display the greatest spatial selectivity. We conclude that the cortical auditory system of primates is divided into at least two processing streams, a spatial stream that originates in the caudal part of the superior temporal gyrus and projects to the parietal cortex, and a pattern or object stream originating in the more anterior portions of the lateral belt. A similar division of labor can be seen in human auditory cortex by using functional neuroimaging.

Lightness constancy in primary visual cortex

When the illumination of a visual scene changes, the quantity of light reflected from objects is altered. Despite this, the perceived lightness of the objects generally remains constant. This perceptual lightness constancy is thought to be important behaviorally for object recognition. Here we show that interactions from outside the classical receptive fields of neurons in primary visual cortex modulate neural responses in a way that makes them immune to changes in illumination, as is perception. This finding is consistent with the hypothesis that the responses of neurons in primary visual cortex carry information about surface lightness in addition to information about form. It also suggests that lightness constancy, which is sometimes thought to involve “higher-level” processes, is manifest at the first stage of visual cortical processing.

Role of cortical N-methyl-D-aspartate receptors in auditory sensory memory and mismatch negativity generation: implications for schizophrenia.

Working memory refers to the ability of the brain to store and manipulate information over brief time periods, ranging from seconds to minutes. As opposed to long-term memory, which is critically dependent upon hippocampal processing, critical substrates for working memory are distributed in a modality-specific fashion throughout cortex. N-methyl-D-aspartate (NMDA) receptors play a crucial role in the initiation of long-term memory. Neurochemical mechanisms underlying the transient memory storage required for working memory, however, remain obscure. Auditory sensory memory, which refers to the ability of the brain to retain transient representations of the physical features (e.g., pitch) of simple auditory stimuli for periods of up to approximately 30 sec, represents one of the simplest components of the brain working memory system. Functioning of the auditory sensory memory system is indexed by the generation of a well-defined event-related potential, termed mismatch negativity (MMN). MMN can thus be used as an objective index of auditory sensory memory functioning and a probe for investigating underlying neurochemical mechanisms. Monkeys generate cortical activity in response to deviant stimuli that closely resembles human MMN. This study uses a combination of intracortical recording and pharmacological micromanipulations in awake monkeys to demonstrate that both competitive and noncompetitive NMDA antagonists block the generation of MMN without affecting prior obligatory activity in primary auditory cortex. These findings suggest that, on a neurophysiological level, MMN represents selective current flow through open, unblocked NMDA channels. Furthermore, they suggest a crucial role of cortical NMDA receptors in the assessment of stimulus familiarity/unfamiliarity, which is a key process underlying working memory performance.