Fernando R. Nodal

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]), ~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.

The descending corticocollicular pathway mediates learning-induced auditory plasticity

Descending projections from sensory areas of the cerebral cortex are among the largest pathways in the brain, suggesting that they are important for subcortical processing. Although corticofugal inputs have been shown to modulate neuronal responses in the thalamus and midbrain, the behavioral importance of these changes remains unknown. In the auditory system, one of the major descending pathways is from cortical layer V pyramidal cells to the inferior colliculus in the midbrain. We examined the role of these neurons in experience-dependent recalibration of sound localization in adult ferrets by selectively killing the neurons using chromophore-targeted laser photolysis. When provided with appropriate training, animals normally relearn to localize sound accurately after altering the spatial cues available by reversibly occluding one ear. However, this ability was lost after eliminating corticocollicular neurons, whereas normal sound-localization accuracy was unaffected. The integrity of this descending pathway is therefore critical for learning-induced localization plasticity.

Training-induced plasticity of auditory localization in adult mammals

Accurate auditory localization relies on neural computations based on spatial cues present in the sound waves at each ear. The values of these cues depend on the size, shape, and separation of the two ears and can therefore vary from one individual to another. As with other perceptual skills, the neural circuits involved in spatial hearing are shaped by experience during development and retain some capacity for plasticity in later life. However, the factors that enable and promote plasticity of auditory localization in the adult brain are unknown. Here we show that mature ferrets can rapidly relearn to localize sounds after having their spatial cues altered by reversibly occluding one ear, but only if they are trained to use these cues in a behaviorally relevant task, with greater and more rapid improvement occurring with more frequent training. We also found that auditory adaptation is possible in the absence of vision or error feedback. Finally, we show that this process involves a shift in sensitivity away from the abnormal auditory spatial cues to other cues that are less affected by the earplug. The mature auditory system is therefore capable of adapting to abnormal spatial information by reweighting different localization cues. These results suggest that training should facilitate acclimatization to hearing aids in the hearing impaired.

Physiological and behavioral studies of spatial coding in the auditory cortex.

Despite extensive subcortical processing, the auditory cortex is believed to be essential for normal sound localization. However, we still have a poor understanding of how auditory spatial information is encoded in the cortex and of the relative contribution of different cortical areas to spatial hearing. We investigated the behavioral consequences of inactivating ferret primary auditory cortex (A1) on auditory localization by implanting a sustained release polymer containing the GABA(A) agonist muscimol bilaterally over A1. Silencing A1 led to a reversible deficit in the localization of brief noise bursts in both the horizontal and vertical planes. In other ferrets, large bilateral lesions of the auditory cortex, which extended beyond A1, produced more severe and persistent localization deficits. To investigate the processing of spatial information by high-frequency A1 neurons, we measured their binaural-level functions and used individualized virtual acoustic space stimuli to record their spatial receptive fields (SRFs) in anesthetized ferrets. We observed the existence of a continuum of response properties, with most neurons preferring contralateral sound locations. In many cases, the SRFs could be explained by a simple linear interaction between the acoustical properties of the head and external ears and the binaural frequency tuning of the neurons. Azimuth response profiles recorded in awake ferrets were very similar and further analysis suggested that the slopes of these functions and location-dependent variations in spike timing are the main information-bearing parameters. Studies of sensory plasticity can also provide valuable insights into the role of different brain areas and the way in which information is represented within them. For example, stimulus-specific training allows accurate auditory localization by adult ferrets to be relearned after manipulating binaural cues by occluding one ear. Reversible inactivation of A1 resulted in slower and less complete adaptation than in normal controls, whereas selective lesions of the descending cortico collicular pathway prevented any improvement in performance. These results reveal a role for auditory cortex in training-induced plasticity of auditory localization, which could be mediated by descending cortical pathways.

Auditory Cortex Represents Both Pitch Judgments and the Corresponding Acoustic Cues

Summary The neural processing of sensory stimuli involves a transformation of physical stimulus parameters into perceptual features, and elucidating where and how this transformation occurs is one of the ultimate aims of sensory neurophysiology. Recent studies have shown that the firing of neurons in early sensory cortex can be modulated by multisensory interactions [1–5], motor behavior [1, 3, 6, 7], and reward feedback [1, 8, 9], but it remains unclear whether neural activity is more closely tied to perception, as indicated by behavioral choice, or to the physical properties of the stimulus. We investigated which of these properties are predominantly represented in auditory cortex by recording local field potentials (LFPs) and multiunit spiking activity in ferrets while they discriminated the pitch of artificial vowels. We found that auditory cortical activity is informative both about the fundamental frequency (F0) of a target sound and also about the pitch that the animals appear to perceive given their behavioral responses. Surprisingly, although the stimulus F0 was well represented at the onset of the target sound, neural activity throughout auditory cortex frequently predicted the reported pitch better than the target F0.

Responses of Auditory Cortex to Complex Stimuli: Functional Organization Revealed Using Intrinsic Optical Signals

We used optical imaging of intrinsic signals to study the large-scale organization of ferret auditory cortex in response to complex sounds. Cortical responses were collected during continuous stimulation by sequences of sounds with varying frequency, period, or interaural level differences. We used a set of stimuli that differ in spectral structure, but have the same periodicity and therefore evoke the same pitch percept (click trains, sinusoidally amplitude modulated tones, and iterated ripple noise). These stimuli failed to reveal a consistent periodotopic map across the auditory fields imaged. Rather, gradients of period sensitivity differed for the different types of periodic stimuli. Binaural interactions were studied both with single contralateral, ipsilateral, and diotic broadband noise bursts and with sequences of broadband noise bursts with varying level presented contralaterally, ipsilaterally, or in opposite phase to both ears. Contralateral responses were generally largest and ipsilateral responses were smallest when using single noise bursts, but the extent of the activated area was large and comparable in all three aural configurations. Modulating the amplitude in counter phase to the two ears generally produced weaker modulation of the optical signals than the modulation produced by the monaural stimuli. These results suggest that binaural interactions seen in cortex are most likely predominantly due to subcortical processing. Thus our optical imaging data do not support the theory that the primary or nonprimary cortical fields imaged are topographically organized to form consistent maps of systematically varying sensitivity either to stimulus pitch or to simple binaural properties of the acoustic stimuli.

Lesions of the auditory cortex impair azimuthal sound localization and its recalibration in ferrets.

The role of auditory cortex in sound localization and its recalibration by experience was explored by measuring the accuracy with which ferrets turned toward and approached the source of broadband sounds in the horizontal plane. In one group, large bilateral lesions were made of the middle ectosylvian gyrus, where the primary auditory cortical fields are located, and part of the anterior and/or posterior ectosylvian gyrus, which contain higher-level fields. In the second group, the lesions were intended to be confined to primary auditory cortex (A1). The ability of the animals to localize noise bursts of different duration and level was measured before and after the lesions were made. A1 lesions produced a modest disruption of approach-to-target responses to short-duration stimuli (<500 ms) on both sides of space, whereas head orienting accuracy was unaffected. More extensive lesions produced much greater auditory localization deficits, again primarily for shorter sounds. In these ferrets, the accuracy of both the approach-to-target behavior and the orienting responses was impaired, and they could do little more than correctly lateralize the stimuli. Although both groups of ferrets were still able to localize long-duration sounds accurately, they were, in contrast to ferrets with an intact auditory cortex, unable to relearn to localize these stimuli after altering the spatial cues available by reversibly plugging one ear. These results indicate that both primary and nonprimary cortical areas are necessary for normal sound localization, although only higher auditory areas seem to contribute to accurate head orienting behavior. They also show that the auditory cortex, and A1 in particular, plays an essential role in training-induced plasticity in adult ferrets, and that this is the case for both head orienting responses and approach-to-target behavior.

Sound localization behavior in ferrets : comparison of acoustic orientation and approach-to-target responses

Auditory localization experiments typically either require subjects to judge the location of a sound source from a discrete set of response alternatives or involve measurements of the accuracy of orienting responses made toward the source location. To compare the results obtained by both methods, we trained ferrets by positive conditioning to stand on a platform at the center of a circular arena prior to stimulus presentation and then approach the source of a broadband noise burst delivered from 1 of 12 loudspeakers arranged at 30 degrees intervals in the horizontal plane. Animals were rewarded for making a correct choice. We also obtained a non-categorized measure of localization accuracy by recording head-orienting movements made during the first second following stimulus onset. The accuracy of the approach-to-target responses declined as the stimulus duration was reduced, particularly for lateral and posterior locations, although responses to sounds presented in the frontal region of space and directly behind the animal remained quite accurate. Head movements had a latency of approximately 200 ms and varied systematically in amplitude with stimulus direction. However, the final head bearing progressively undershot the target with increasing eccentricity and rarely exceeded 60 degrees to each side of the midline. In contrast to the approach-to-target responses, the accuracy of the head orienting responses did not change much with stimulus duration, suggesting that the improvement in percent correct scores with longer stimuli was due, at least in part, to re-sampling of the acoustical stimulus after the initial head turn had been made. Nevertheless, for incorrect trials, head orienting responses were more closely correlated with the direction approached by the animals than with the actual target direction, implying that at least part of the neural circuitry for translating sensory spatial signals into motor commands is shared by these two behaviors.

Topographic organization of the dorsal nucleus of the lateral lemniscus in the cat

The dorsal nucleus of the lateral lemniscus (DNLL) is an auditory structure of the brainstem. It plays an important role in binaural processing and sound localization and it provides the inferior colliculus with an inhibitory projection. The DNLL is a highly conserved auditory structure across mammals, but differences among species in its detailed organization have been reported.

Direct Input from Cochlear Root Neurons to Pontine Reticulospinal Neurons in Albino Rat

The cochlear root neurons (CRNs) are thought to mediate the auditory startle reflex (ASR) in the rat, which is widely used as a behavioral model for the investigation of the sensorimotor integration. CRNs project, among other targets, to the nucleus reticularis pontis caudalis (PnC), a major component of the ASR circuit, but little is known about the organization of this projection. Thus, we injected biotinylated dextran amine (BDA) in CRNs to study their projections with light and electron microscopy. Also, we performed double‐labeling experiments, injecting BDA in the CRNs and subunit B of the cholera toxin or Fluorogold in the spinal cord to verify that CRNs project onto reticulospinal neurons. Electron microscopy of the labeled CRNs axons and terminals showed that even their most central and thinnest processes are myelinated. Most of the terminals are axodendritic, with multiple asymmetric synapses, and contain round vesicles (50 nm diameter). Double‐labeling experiments demonstrated that CRN terminals are apposed to retrogradely labeled reticulospinal neurons in the contralateral nucleus reticularis PnC and bilaterally in the lateral paragigantocellular nucleus. Analyses of serial sections revealed that multiple CRNs synapse on single reticulospinal neurons in PnC, suggesting a convergence of auditory information. The morphometric features of these neurons classify them as giant neurons. This study confirms that CRNs project directly onto reticulospinal neurons and presents other anatomical features of the CRNs that contribute to a better understanding of the circuitry of the ASR in the rat. J. Comp. Neurol. 460:80–93, 2003.