Tonotopic Organization Research Articles

Purinergic Modulation of Activity in the Developing Auditory Pathway.

Purinergic P2 receptors, activated by endogenous ATP, are prominently expressed on neuronal and non-neuronal cells during development of the auditory periphery and central auditory neurons. In the mature cochlea, extracellular ATP contributes to ion homeostasis, and has a protective function against noise exposure. Here, we focus on the modulation of activity by extracellular ATP during early postnatal development of the lower auditory pathway. In mammals, spontaneous patterned activity is conveyed along afferent auditory pathways before the onset of acoustically evoked signal processing. During this critical developmental period, inner hair cells fire bursts of action potentials that are believed to provide a developmental code for synaptic maturation and refinement of auditory circuits, thereby establishing a precise tonotopic organization. Endogenous ATP-release triggers such patterned activity by raising the extracellular K+ concentration and contributes to firing by increasing the excitability of auditory nerve fibers, spiral ganglion neurons, and specific neuron types within the auditory brainstem, through the activation of diverse P2 receptors. We review recent studies that provide new models on the contribution of purinergic signaling to early development of the afferent auditory pathway. Further, we discuss potential future directions of purinergic research in the auditory system.

An optically transparent multi-electrode array for combined electrophysiology and optophysiology at the mesoscopic scale

Objective. A number of tissue penetrating opto-electrodes to simultaneously record and optogenetically influence brain activity have been developed. For experiments at the surface of the brain, such as electrocorticogram (ECoG) recordings and surface optogenetics, fewer devices have been described and no device has found widespread adoption for neuroscientific experiments. One issue slowing adoption is the complexity and fragility of existing devices, typically based on transparent electrode materials like graphene and indium-tin oxide (ITO). We focused here on improving existing processes based on metal traces and polyimide (PI), which produce more robust and cost-effective devices, to develop a multi-electrode array for optophysiology. Approach. The most widely used substrate material for surface electrodes, PI, has seen little use for optophysiologicalμECoG/ECoG arrays. This is due to its lack of transparency at optogenetically relevant short wavelengths. Here we use very thin layers of PI in combination with chrome-gold-platinum electrodes to achieve the necessary substrate transparency and high mechanical flexibility in a device that still rejects light artifacts well. Main results. The manufactured surface arrays have a thickness of only 6.5 µm, resulting in 80% transparency for blue light. We demonstrate immunity against opto-electric artifacts, long term stability and biocompatibility as well as suitability for optical voltage imaging. The biocompatible arrays are capable of recording stable ECoGs over months without any measurable degradation and can be used to map the tonotopic organization of the curved rodent auditory cortex. Significance. Our novel probes combine proven materials and processing steps to create optically near-transparent electrode arrays with superior longevity. In contrast to previous opto-electrodes, our probes are simple to manufacture, robust, offer long-term stability, and are a practical engineering solution for optophysiological experiments not requiring transparency of the electrode sites themselves.

Correction to: The Developing Concept of Tonotopic Organization of the Inner Ear.

The email address for Robert J. Ruben should be rruben@montefiore.org.

The Developing Concept of Tonotopic Organization of the Inner Ear.

This study aims to document the historical conceptualization of the inner ear as the anatomical location for the appreciation of sound at a continuum of frequencies and to examine the evolution of concepts of tonotopic organization to our current understanding. Primary sources used are from the sixth century BCE through the twentieth century CE. Each work/reference was analyzed from two points of view: to understand the conception of hearing and the role of the inner ear and to define the main evidential method. The dependence on theory alone in the ancient world led to inaccurate conceptualization of the mechanism of hearing. In the sixteenth century, Galileo described the physical and mathematical basis of resonance. The first theory of tonotopic organization, advanced in the seventeenth century, was that high-frequency sound is mediated at the apex of the cochlea and low-frequency at the base of the cochlea. In the eighteenth and nineteenth centuries, more accurate anatomical information was developed which led to what we now know is the accurate view of tonotopic organization: the high-frequency sound is mediated at the base and low-frequency sound at the apex. The electrical responses of the ear discovered in 1930 allowed for physiological studies that were consistent with the concept of a high to low tone sensitivity continuum from base to apex. In the mid-twentieth century, physical observations of models and anatomical specimens confirmed the findings of greater sensitivity to high tones at the base and low tones at the apex and, further, demonstrated that for high-intensity sound, there was a spread of effect through the entire cochlea, more so for low-frequency tones than for high tones. Animal and human behavioral studies provided empirical proof that sound is mediated at a continuum of frequencies from high tones at the base through low tones at the apex of the cochlea. Current understanding of the tonotopic organization of the inner ear with regard to pure tones is the result of the acquisition over time of knowledge of acoustics and the anatomy, physical properties, and physiology of the inner ear, with the ultimate verification being behavioral studies. Examination of this complex evolution leads to understanding of the way each approach and evidential method through time draws upon previously developed knowledge, with behavioral studies providing empirical verification.

Is chirp more effective than click and tone-burst during oVEMP test?

Aim: We aimed to show the effectivity of chirp stimulus and to compare with tone-burst and click stimulus during ocular VEMP (oVEMP) and also to exhibit same stimulation response pattern in utricle as seen in cochlea. Material and Methods: A total of 85 healthy volunteers without any vestibular and otologic disease history were enrolled in this study. Three different types of air conduction stimuli (tone-burst, click and chirp) were used for the oVEMP test. N1, P1 latencies, N1P1 amplitudes and asymmetry ratios were investigated for each stimulus type according to age subgroups and sex.Results: The ratio of presence of oVEMP response was found to be 94.1%, 82.1% and 98.8% with tone-burst, click and chirp stimuli respectively. The latencies were significantly shorter in chirp stimulus with respect to others in both ears. The amplitudes were also significantly larger in chirp stimulus with respect to other in both ears. According to analysis of N1P1 asymmetry ratios, N1 and P1 latency asymmetry, there were no statistically significant difference in these values within each stimulus types.Conclusion: oVEMP is more practical, easier, faster and less invasive method. oVEMP results with chirp stimulus have shorter latency and higher amplitude and more clear waveform morphology with higher ratio of response when compared to click and tone-burst stimulus. As a result, chirp is a reliable and suitable stimulus type for oVEMP analysis. In the light of these unique results with chirp stimulus, utricular hair cells may have similar frequency specific tonotopic organization as seen in cochlea.

Tonotopic and non-auditory organization of the mouse dorsal inferior colliculus revealed by two-photon imaging.

The dorsal (DCIC) and lateral cortices (LCIC) of the inferior colliculus are major targets of the auditory and non-auditory cortical areas, suggesting a role in complex multimodal information processing. However, relatively little is known about their functional organization. We utilized in vivo two-photon Ca2+ imaging in awake mice expressing GCaMP6s in GABAergic or non-GABAergic neurons in the IC to investigate their spatial organization. We found different classes of temporal responses, which we confirmed with simultaneous juxtacellular electrophysiology. Both GABAergic and non-GABAergic neurons showed spatial microheterogeneity in their temporal responses. In contrast, a robust, double rostromedial-caudolateral gradient of frequency tuning was conserved between the two groups, and even among the subclasses. This, together with the existence of a subset of neurons sensitive to spontaneous movements, provides functional evidence for redefining the border between DCIC and LCIC.

Abnormal auditory tonotopy in patients with schizophrenia

Auditory hallucinations are among the most prevalent and most distressing symptoms of schizophrenia. Despite significant progress, it is still unclear whether auditory hallucinations arise from abnormalities in primary sensory processing or whether they represent failures of higher-order functions. To address this knowledge gap, we capitalized on the increased spatial resolution afforded by ultra-high field imaging at 7 Tesla to investigate the tonotopic organization of the auditory cortex in patients with schizophrenia with a history of recurrent hallucinations. Tonotopy is a fundamental feature of the functional organization of the auditory cortex that is established very early in development and predates the onset of symptoms by decades. Compared to healthy participants, patients showed abnormally increased activation and altered tonotopic organization of the auditory cortex during a purely perceptual task, which involved passive listening to tones across a range of frequencies (88–8000 Hz). These findings suggest that the predisposition to auditory hallucinations is likely to be predicated on abnormalities in the functional organization of the auditory cortex and which may serve as a biomarker for the early identification of vulnerable individuals.

Pitch perception conveyed by cochlear implant and tactile stimulation

The healthy auditory system encodes acoustic frequency as a tonotopic and synchronous neural response. Cochlear implants (CIs) excite tonotopic organization through place of stimulation and excite a synchronous neural response through stimulation timing, but typically limited to amplitude modulations less than 300 Hz. The results from two experiments will be presented. The first experiment uses CI stimulation to examine the contributions of place and rate of stimulation to pitch perception. Frequency discrimination thresholds were measured in adult CI users for fundamental frequencies ranging from 100 to 1600 Hz. Stimulation was controlled to probe pitch sensitivity as conveyed by place, rate, and covaried place and rate of stimulation. Subjects received a significant low-frequency benefit from combined stimulation, which diminished above 400 Hz as stimulation rate no longer provided a salient sense of pitch. The second experiment considers how well tactile stimulation can be used to augment pitch perception in CIs. Tactile discrimination thresholds were measured for 55 and 110 Hz. Preliminary results will be presented for the second experiment designed to test how well CI users can combine pitch cues provided by stimulation rate and by tactile stimulation.

Polyphonic pitch perception in cochlear implant users

Cochlear implant (CI) devices take advantage of the tonotopic organization of the auditory nerve to provide moderate speech recognition. While commercial place-pitch strategies are sufficient for speech comprehension in quiet conditions, CI users struggle to detect multiple, simultaneous sources of pitch. In a polyphonic pitch-trajectory task, two streams (low and high pitch) are presented simultaneously. Participants perform a 1-interval-4-alternative forced-choice procedure to identify which stream changed in pitch and whether it went higher or lower in pitch (low-lower/low-higher/high-lower/high-higher). The low and high streams are high-rate pulsetrains modulated at 110 Hz and 220 Hz, respectively. The stimulus is 1 s in duration and the target stream contains an ascending or descending modulation-frequency sweep over the last 200 ms. The low stream will be presented to the most apical electrode and the high stream presented to electrode separations of 0, 2, 4, and 8. Preliminary results indicate that CI users perform better on the electrode psychophysical tasks than on acoustic variations. Additionally, performance is improved with sharper temporal envelopes. These results suggest that CI users are able to perceive polyphonic pitch and that resolution is limited by how temporal information is conveyed by clinical devices.

Frizzled3 and Frizzled6 Cooperate with Vangl2 to Direct Cochlear Innervation by Type II Spiral Ganglion Neurons.

Type II spiral ganglion neurons provide afferent innervation to outer hair cells of the cochlea and are proposed to have nociceptive functions important for auditory function and homeostasis. These neurons are anatomically distinct from other classes of spiral ganglion neurons because they extend a peripheral axon beyond the inner hair cells that subsequently makes a distinct 90 degree turn toward the cochlear base. As a result, patterns of outer hair cell innervation are coordinated with the tonotopic organization of the cochlea. Previously, it was shown that peripheral axon turning is directed by a nonautonomous function of the core planar cell polarity (PCP) protein VANGL2. We demonstrate using mice of either sex that Fzd3 and Fzd6 similarly regulate axon turning, are functionally redundant with each other, and that Fzd3 genetically interacts with Vangl2 to guide this process. FZD3 and FZD6 proteins are asymmetrically distributed along the basolateral wall of cochlear-supporting cells, and are required to promote or maintain the asymmetric distribution of VANGL2 and CELSR1. These data indicate that intact PCP complexes formed between cochlear-supporting cells are required for the nonautonomous regulation of axon pathfinding. Consistent with this, in the absence of PCP signaling, peripheral axons turn randomly and often project toward the cochlear apex. Additional analyses of Porcn mutants in which WNT secretion is reduced suggest that noncanonical WNT signaling establishes or maintains PCP signaling in this context. A deeper understanding of these mechanisms is necessary for repairing auditory circuits following acoustic trauma or promoting cochlear reinnervation during regeneration-based deafness therapies.SIGNIFICANCE STATEMENT Planar cell polarity (PCP) signaling has emerged as a complementary mechanism to classical axon guidance in regulating axon track formation, axon outgrowth, and neuronal polarization. The core PCP proteins are also required for auditory circuit assembly, and coordinate hair cell innervation with the tonotopic organization of the cochlea. This is a non-cell-autonomous mechanism that requires the formation of PCP protein complexes between cochlear-supporting cells located along the trajectory of growth cone navigation. These findings are significant because they demonstrate how the fidelity of auditory circuit formation is ensured during development, and provide a mechanism by which PCP proteins may regulate axon outgrowth and guidance in the CNS.

Effects of developmental noise exposure on inhibitory cell densities and perineuronal nets in A1 and AAF of mice

Within the auditory cortex, there are two primary-like regions considered to be ‘core’ cortical fields, the primary auditory cortex (A1) and the anterior auditory field (AAF). Both fields have sharp frequency tuning, tonotopic organization, and inputs from the ventral division of the medial geniculate body of the thalamus. AAF seems to be more specialized for faster spectrotemporal processing than A1, but the underlying mechanisms are unclear. A1 has been studied extensively in developmental plasticity, but how AAF changes with developmental experience is less clear. To address potential cellular correlates of processing differences between the two fields, we used immunohistochemistry to quantify the density of GABA, parvalbumin (PV), and somatostatin (SOM) cells in A1 and AAF of mice. We also compared the density of perineuronal nets (PNN) between A1 and AAF. PNNs are a specialized assembly of extracellular matrix involved in network maturation and plasticity. Finally, we compared the effects of developmental noise exposure on inhibitory and PNN cell density in these two core regions. In adult mice, there were more PV cells and PNNs surrounding cell bodies in AAF than in A1. Moderate level noise exposure during early development leads to 1) increased GABA and SOM cell density in both A1 and AAF, and 2) decreased PNN cell density in A1, but not AAF. Inhibitory cells without PNN appear to be more susceptible to changes following developmental noise exposure in both fields. Deep layers (5/6) are more susceptible to change in PNN density compared to superficial layers (1–4) of A1. Results are consistent with altered cortical gain control models and impaired maturation of cortex in response to noisy environments, and suggest that PNNs may be more prone to modification in A1 than AAF.

Auditory brainstem stimulation with a conformable microfabricated array elicits responses with tonotopically organized components

Auditory brainstem implants (ABIs) restore hearing to deaf individuals not eligible for cochlear implants. Speech comprehension in ABI users is generally poor compared to that of cochlear implant users, and side effects are common. The poor performance may result from activating broad areas and multiple neuronal populations of the cochlear nucleus, however detailed studies of the responses to surface stimulation of the cochlear nucleus are lacking. A conformable electrode array was microfabricated to fit on the rat's dorsal cochlear nucleus (DCN). It hosts 20 small electrodes (each 100 μm diam.). The array was tested by recording evoked potentials and neural activity along the tonotopic axis of the inferior colliculus (IC). Almost all bipolar electrode pairs elicited responses, in some cases with an even, or relatively constant, pattern of thresholds and supra-threshold measures along the long axis of the array. This pattern suggests that conformable arrays can provide relatively constant excitation along the surface of the DCN and thus might decrease the ABI side effects caused by spread of high current to adjacent structures. We also examined tonotopic patterns of the IC responses. Compared to sound-evoked responses, electrically-evoked response mappings had less tonotopic organization and were broader in width. They became more tonotopic when the evoked activity common to all electrodes and the late phase of response were subtracted out, perhaps because the remaining activity is from tonotopically organized principal cells of the DCN. Responses became less tonotopic when inter-electrode distance was increased from 400 μm to 800 μm but were relatively unaffected by changing to monopolar stimulation. The results illustrate the challenges of using a surface array to present tonotopic cues and improve speech comprehension in humans who use the ABI.

Local homogeneity of tonotopic organization in the primary auditory cortex of marmosets

Marmoset has emerged as a useful nonhuman primate species for studying brain structure and function. Previous studies on the mouse primary auditory cortex (A1) showed that neurons with preferential frequency-tuning responses are mixed within local cortical regions, despite a large-scale tonotopic organization. Here we found that frequency-tuning properties of marmoset A1 neurons are highly uniform within local cortical regions. We first defined the tonotopic map of A1 using intrinsic optical imaging and then used in vivo two-photon calcium imaging of large neuronal populations to examine the tonotopic preference at the single-cell level. We found that tuning preferences of layer 2/3 neurons were highly homogeneous over hundreds of micrometers in both horizontal and vertical directions. Thus, marmoset A1 neurons are distributed in a tonotopic manner at both macro- and microscopic levels. Such organization is likely to be important for the organization of auditory circuits in the primate brain.

Neurod1 Is Essential for the Primary Tonotopic Organization and Related Auditory Information Processing in the Midbrain.

Hearing depends on extracting frequency, intensity, and temporal properties from sound to generate an auditory map for acoustical signal processing. How physiology intersects with molecular specification to fine tune the developing properties of the auditory system that enable these aspects remains unclear. We made a novel conditional deletion model that eliminates the transcription factor NEUROD1 exclusively in the ear. These mice (both sexes) develop a truncated frequency range with no neuroanatomically recognizable mapping of spiral ganglion neurons onto distinct locations in the cochlea nor a cochleotopic map presenting topographically discrete projections to the cochlear nuclei. The disorganized primary cochleotopic map alters tuning properties of the inferior colliculus units, which display abnormal frequency, intensity, and temporal sound coding. At the behavioral level, animals show alterations in the acoustic startle response, consistent with altered neuroanatomical and physiological properties. We demonstrate that absence of the primary afferent topology during embryonic development leads to dysfunctional tonotopy of the auditory system. Such effects have never been investigated in other sensory systems because of the lack of comparable single gene mutation models.SIGNIFICANCE STATEMENT All sensory systems form a topographical map of neuronal projections from peripheral sensory organs to the brain. Neuronal projections in the auditory pathway are cochleotopically organized, providing a tonotopic map of sound frequencies. Primary sensory maps typically arise by molecular cues, requiring physiological refinements. Past work has demonstrated physiologic plasticity in many senses without ever molecularly undoing the specific mapping of an entire primary sensory projection. We genetically manipulated primary auditory neurons to generate a scrambled cochleotopic projection. Eliminating tonotopic representation to auditory nuclei demonstrates the inability of physiological processes to restore a tonotopic presentation of sound in the midbrain. Our data provide the first insights into the limits of physiology-mediated brainstem plasticity during the development of the auditory system.

Anisotropic Panglial Coupling Reflects Tonotopic Organization in the Inferior Colliculus.

Astrocytes and oligodendrocytes in different brain regions form panglial networks and the topography of such networks can correlate with neuronal topography and function. Astrocyte-oligodendrocyte networks in the lateral superior olive (LSO)—an auditory brainstem nucleus—were found to be anisotropic with a preferred orientation orthogonally to the tonotopic axis. We hypothesized that such a specialization might be present in other tonotopically organized brainstem nuclei, too. Thus, we analyzed gap junctional coupling in the center of the inferior colliculus (IC)—another nucleus of the auditory brainstem that exhibits tonotopic organization. In acute brainstem slices obtained from mice, IC networks were traced employing whole-cell patch-clamp recordings of single sulforhodamine (SR) 101-identified astrocytes and concomitant intracellular loading of the gap junction-permeable tracer neurobiotin. The majority of dye-coupled networks exhibited an oval topography, which was preferentially oriented orthogonal to the tonotopic axis. Astrocyte processes showed preferentially the same orientation indicating a correlation between astrocyte and network topography. In addition to SR101-positive astrocytes, IC networks contained oligodendrocytes. Using Na+ imaging, we analyzed the capability of IC networks to redistribute small ions. Na+ bi-directionally diffused between SR101-positive astrocytes and SR101-negative cells—presumably oligodendrocytes—showing the functionality of IC networks. Taken together, our results demonstrate that IC astrocytes and IC oligodendrocytes form functional anisotropic panglial networks that are preferentially oriented orthogonal to the tonotopic axis. Thus, our data indicate that the topographic specialization of glial networks seen in IC and LSO might be a general feature of tonotopically organized auditory brainstem nuclei.

Spiking Pattern of the Mouse Developing Inner Hair Cells Is Mostly Invariant Along the Tonotopic Axis.

During development, the sensory cells of the cochlea, the inner hair cells (IHCs), fire spontaneous calcium action potentials. This activity at the pre-hearing stage allows the IHCs to autonomously excite the auditory nerve fibers and hence, represents an efficient mechanism to shape the tonotopic organization along the ascending auditory pathway. Using calcium imaging, we show that the activity in the developing cochlea consists of calcium waves that propagate across the supporting and sensory cells. Both basal and apical IHCs were characterized by similar spontaneous calcium transients interspaced with silent periods, consistent with bursts of action potentials recorded in patch-clamp. In addition, adjacent auditory hair cells tend to have a synchronized [Ca2+]i activity, irrespective of their location along the base-to-apex gradient of the cochlea. Finally, we show that the mechanical ablation of the inner phalangeal cells (IPCs), a class of supporting cells, reduces the synchronized [Ca2+]i activity between neighboring sensory cells. These findings support the hypothesis that the tonotopic map refinement in higher auditory centers would depend on the synchronization of a discrete number of auditory sensory cells.

Perceptual Encoding in Auditory Brainstem Responses: Effects of Stimulus Frequency.

A central question about auditory perception concerns how acoustic information is represented at different stages of processing. The auditory brainstem response (ABR) provides a potentially useful index of the earliest stages of this process. However, it is unclear how basic acoustic characteristics (e.g., differences in tones spanning a wide range of frequencies) are indexed by ABR components. This study addresses this by investigating how ABR amplitude and latency track stimulus frequency for tones ranging from 250 to 8000 Hz. In a repeated-measures experimental design, listeners were presented with brief tones (250, 500, 1000, 2000, 4000, and 8000 Hz) in random order while electroencephalography was recorded. ABR latencies and amplitudes for Wave V (6-9 ms) and in the time window following the Wave V peak (labeled as Wave VI; 9-12 ms) were measured. Wave V latency decreased with increasing frequency, replicating previous work. In addition, Waves V and VI amplitudes tracked differences in tone frequency, with a nonlinear response from 250 to 8000 Hz and a clear log-linear response to tones from 500 to 8000 Hz. Results demonstrate that the ABR provides a useful measure of early perceptual encoding for stimuli varying in frequency and that the tonotopic organization of the auditory system is preserved at this stage of processing for stimuli from 500 to 8000 Hz. Such a measure may serve as a useful clinical tool for evaluating a listener's ability to encode specific frequencies in sounds. https://doi.org/10.23641/asha.6987422.

Organizational principles of multidimensional predictions in human auditory attention

Anticipating the future rests upon our ability to exploit contextual cues and to formulate valid internal models or predictions. It is currently unknown how multiple predictions combine to bias perceptual information processing, and in particular whether this is determined by physiological constraints, behavioral relevance (task demands), or past knowledge (perceptual expertise). In a series of behavioral auditory experiments involving musical experts and non-musicians, we investigated the respective and combined contribution of temporal and spectral predictions in multiple detection tasks. We show that temporal and spectral predictions alone systematically increase perceptual sensitivity, independently of task demands or expertise. When combined, however, spectral predictions benefit more to non-musicians and dominate over temporal ones, and the extent of the spectrotemporal synergistic interaction depends on task demands. This suggests that the hierarchy of dominance primarily reflects the tonotopic organization of the auditory system and that expertise or attention only have a secondary modulatory influence.

Analyzing transient-evoked otoacoustic emissions by concentration of frequency and time

The linear part of transient evoked otoacoustic emission (TEOAE) is thought to be generated via coherent reflection near the characteristic place of constituent wave components. Because of the tonotopic organization of the cochlea, high frequency emissions return earlier than low frequencies; however, due to the random nature of coherent reflection, the instantaneous frequency (IF) and amplitude envelope of TEOAEs both fluctuate. Multiple reflection components and synchronized spontaneous emissions can further make it difficult to extract the IF by linear transforms. This paper proposes to model TEOAEs as a sum of intrinsic mode-type functions and analyze it by a nonlinear-type time-frequency (T-F) analysis technique called concentration of frequency and time (ConceFT). When tested with synthetic otoacoustic emission signals with possibly multiple oscillatory components, the present method is able to produce clearly visualized traces of individual components on the T-F plane. Further, when the signal is noisy, the proposed method is compared with existing linear and bilinear methods in its accuracy for estimating the fluctuating IF. Results suggest that ConceFT outperforms the best of these methods in terms of optimal transport distance, reducing the error by 10% to 21% when the signal to noise ratio is 10 dB or below.

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BackgroundDespite rapid developments in fMRI, there is still ongoing debate on the optimal paradigm for evaluating the level of auditory cortex activation.Material and MethodsA number of modern neuroimaging methods can be used to assess brain responses to acoustic stimulation, but new paradigms are still needed. Here the sparse fMRI approach is used to examine frequency-specific activation in auditory cortex in 12 normal hearing individuals.ResultsThe size of activation expanded with increasing sound intensity and decreasing sound frequency. At the same time, the main site of frequency-specific activation remained the same across intensities, indicating fixed tonotopic organization. The findings of the study are explained in terms of basilar membrane phenomena such as the travelling wave pattern and spread of activation.ConclusionsStimulation levels of at least 60 dB are necessary in order to obtain robust maps of group activation in auditory cortex.