Martin Pienkowski

Long-term, partially-reversible reorganization of frequency tuning in mature cat primary auditory cortex can be induced by passive exposure to moderate-level sounds

We recently reported that passive exposure for at least 4 months of adult cats to a two-octave-wide tone pip ensemble at 80 dB SPL, decreased the responsiveness of primary auditory cortex (AI) to sound frequencies in the exposure band, and increased the responsiveness to frequencies at the outer edges of the band. Here we expand on this by demonstrating qualitatively similar plasticity for a 6-week exposure level of 68 dB SPL. Though no peripheral hearing loss is induced by the exposure, the resulting reorganization of the AI tonotopic map resembles that following a restricted lesion of the sensory epithelium. Most exposure-induced effects were likely present in the thalamus, as deduced from changes in local field potentials, but were further modified in AI. We then examined the potential for the reversal of these changes, given recovery in a quiet laboratory environment for up to 12 weeks after the cessation of exposure. While frequency tuning returned to near-normal, other neuronal response properties, as well as tonotopic map organization, remained abnormal at the end of our 12-week window. This could have implications for persistently noisy work/recreation/living environments, even at levels considerably below those presently considered unacceptable.

Measurement of cerebral blood volume in mouse brain regions using micro-computed tomography

Micro-computed tomography (micro-CT) is an X-ray imaging technique that can produce detailed 3D images of cerebral vasculature. This paper describes the development of a novel method for using micro-CT to measure cerebral blood volume (CBV) in the mouse brain. As an application of the methodology, we test the hypotheses that differences in CBV exist over anatomical brain regions and that high energy demanding primary sensory regions of the cortex have locally elevated CBV, which may reflect a vascular specialization. CBV was measured as the percentage of tissue space occupied by a radio-opaque silicon rubber that fills the vasculature. To ensure accuracy of the CBV measurements, several innovative refinements were made to standard micro-CT specimen preparation and analysis procedures. Key features of the described method are vascular perfusion under controlled pressure, registration of the micro-CT images to an MRI anatomical brain atlas and re-scaling of micro-CT intensities to CBV units with selectable exclusion of major vessels. Histological validation of the vascular perfusion showed that the average percentage of vessels filled was 93+/-3%. Comparison of thirteen brain regions in nine mice revealed significant differences in CBV between regions (p<0.0001) while cortical maps showed that primary visual and auditory areas have higher CBV than primary somatosensory areas.

Cortical tonotopic map plasticity and behavior

Central topographic representations of sensory epithelia have a genetic basis, but are refined by patterns of afferent input and by behavioral demands. Here we review such experience-driven map development and plasticity, focusing on the auditory system, and giving particular consideration to its adaptive value and to the putative mechanisms involved. Recent data have challenged the widely held notion that only the developing auditory brain can be influenced by changes to the prevailing acoustic environment, unless those changes convey information of behavioral relevance. Specifically, it has been shown that persistent exposure of adult animals to random, bandlimited, moderately loud sounds can lead to a reorganization of auditory cortex not unlike that following restricted hearing loss. The mature auditory brain is thus more plastic than previously supposed, with potentially troubling consequences for those working or living in noisy environments, even at exposure levels considerably below those presently considered just-acceptable.

Increasing Spectrotemporal Sound Density Reveals an Octave-Based Organization in Cat Primary Auditory Cortex

Auditory neurons are likely adapted to process complex stimuli, such as vocalizations, which contain spectrotemporal modulations. However, basic properties of auditory neurons are often derived from tone pips presented in isolation, which lack spectrotemporal modulations. In this context, it is unclear how to deduce the functional role of auditory neurons from their tone pip-derived tuning properties. In this study, spectrotemporal receptive fields (STRFs) were obtained from responses to multi-tone stimulus ensembles differing in their average spectrotemporal density (i.e., number of tone pips per second). STRFs for different stimulus densities were derived from multiple single-unit activity (MUA) and local field potentials (LFPs), simultaneously recorded in primary auditory cortex of cats. Consistent with earlier studies, we found that the spectral bandwidth was narrower for MUA compared with LFPs. Both neural firing rate and LFP amplitude were reduced when the density of the stimulus ensemble increased. Surprisingly, we found that increasing the spectrotemporal sound density revealed with increasing clarity an over-representation of response peaks at frequencies of ∼3, 5, 10, and 20 kHz, in both MUA- and LFP-derived STRFs. Although the decrease in spectral bandwidth and neural activity with increasing stimulus density can likely be accounted for by forward suppression, the mechanisms underlying the over-representation of the octave-spaced response peaks are unclear. Plausibly, the over-representation may be a functional correlate of the periodic pattern of corticocortical connections observed along the tonotopic axis of cat auditory cortex.

A Review of Hyperacusis and Future Directions: Part I. Definitions and Manifestations

PURPOSE Hyperacusis can be extremely debilitating, and at present, there is no cure. We provide an overview of the field, and possible related areas, in the hope of facilitating future research. METHOD We review and reference literature on hyperacusis and related areas. We have divided the review into 2 articles. In Part I, we discuss definitions, epidemiology, different etiologies and subgroups, and how hyperacusis affects people. In Part II, we review measurements, models, mechanisms, and treatments, and we finish with some suggestions for further research. RESULTS Hyperacusis encompasses a wide range of reactions to sound, which can be grouped into the categories of excessive loudness, annoyance, fear, and pain. Many different causes have been proposed, and it will be important to appreciate and quantify different subgroups. Reasonable approaches to assessing the different forms of hyperacusis are emerging, including psychoacoustical measures, questionnaires, and brain imaging. CONCLUSIONS Hyperacusis can make life difficult for many, forcing sufferers to dramatically alter their work and social habits. We believe this is an opportune time to explore approaches to better understand and treat hyperacusis.

Reversible long-term changes in auditory processing in mature auditory cortex in the absence of hearing loss induced by passive, moderate-level sound exposure.

It has become increasingly clear that even occasional exposure to loud sounds in occupational or recreational settings can cause irreversible damage to the hair cells of the cochlea and the auditory nerve fibers, even if the resulting partial loss of hearing sensitivity, usually accompanied by tinnitus, disappears within hours or days of the exposure. Such exposure may explain at least some cases of poor speech intelligibility in noise in the face of a normal or near-normal audiogram. Recent findings from our laboratory suggest that long-term changes to auditory brain function—potentially leading to problems with speech intelligibility—can be effected by persistent, passive exposure to more moderate levels of noise (in the 70 dB SPL range) in the apparent absence of damage to the auditory periphery (as reflected in normal distortion product otoacoustic emissions and auditory brainstem responses). Specifically, passive exposure of adult cats to moderate levels of band-pass-filtered noise, or to band-limited ensembles of dense, random tone pips, can lead to a profound decrease of neural activity in the auditory cortex roughly in the exposure frequency range, and to an increase of activity outside that range. This can progress to an apparent reorganization of the cortical tonotopic map, which is reminiscent of the reorganization resulting from hearing loss restricted to a part of the hearing frequency range, although again, no hearing loss was apparent after our moderate-level sound exposure. Here, we review this work focusing specifically on the potential hearing problems that may arise despite a normally functioning auditory periphery.

Comparison of LFP-based and spike-based spectro-temporal receptive fields and cross-correlation in cat primary auditory cortex.

Multi-electrode array recordings of spike and local field potential (LFP) activity were made from primary auditory cortex of 12 normal hearing, ketamine-anesthetized cats. We evaluated 259 spectro-temporal receptive fields (STRFs) and 492 frequency-tuning curves (FTCs) based on LFPs and spikes simultaneously recorded on the same electrode. We compared their characteristic frequency (CF) gradients and their cross-correlation distances. The CF gradient for spike-based FTCs was about twice that for 2–40 Hz-filtered LFP-based FTCs, indicating greatly reduced frequency selectivity for LFPs. We also present comparisons for LFPs band-pass filtered between 4–8 Hz, 8–16 Hz and 16–40 Hz, with spike-based STRFs, on the basis of their marginal frequency distributions. We find on average a significantly larger correlation between the spike based marginal frequency distributions and those based on the 16–40 Hz filtered LFP, compared to those based on the 4–8 Hz, 8–16 Hz and 2–40 Hz filtered LFP. This suggests greater frequency specificity for the 16–40 Hz LFPs compared to those of lower frequency content. For spontaneous LFP and spike activity we evaluated 1373 pair correlations for pairs with >200 spikes in 900 s per electrode. Peak correlation-coefficient space constants were similar for the 2–40 Hz filtered LFP (5.5 mm) and the 16–40 Hz LFP (7.4 mm), whereas for spike-pair correlations it was about half that, at 3.2 mm. Comparing spike-pairs with 2–40 Hz (and 16–40 Hz) LFP-pair correlations showed that about 16% (9%) of the variance in the spike-pair correlations could be explained from LFP-pair correlations recorded on the same electrodes within the same electrode array. This larger correlation distance combined with the reduced CF gradient and much broader frequency selectivity suggests that LFPs are not a substitute for spike activity in primary auditory cortex.

Intermittent exposure with moderate-level sound impairs central auditory function of mature animals without concomitant hearing loss

Long-term, passive, continuous exposure of mature animals to moderate-level, band-limited sounds can profoundly decrease neural activity in primary auditory cortex (AI) to sounds in the exposure frequency range, and increase activity to sounds outside the exposure range. The resulting reorganization of the AI tonotopic map resembles that following a restricted lesion of the cochlear epithelium. Here we show qualitatively similar effects of passive exposure when it is limited to 12 h/day, simulating a noisy-work/quiet-living environment, albeit at substantially lower intensity levels (68 dB SPL) than are considered harmful to hearing. Compared to continuous exposure at the same SPL and over a similar duration (6-12 weeks), this intermittent exposure produced a smaller decrease in AI spike and LFP (local field potential) activity in response to sound frequencies in the exposure range, and an increase in activity only for frequencies above the exposure range. As expected at these exposure levels, cortical changes occurred in the absence of concomitant hearing loss (i.e., absolute threshold shifts). Our results have implications for occupational noise exposure standards, which presently may not prevent changes in central auditory function that cannot be detected on the standard behavioral audiogram.

Passive exposure of adult cats to moderate-level tone pip ensembles differentially decreases AI and AII responsiveness in the exposure frequency range.

Passive exposure of adult animals to a random ensemble of tone pips band limited between 4 and 20 kHz has been shown to suppress neural activity in primary auditory cortex (AI) to sounds in the exposure frequency range. In the long-term (>3 months), the suppressed neurons can be reactivated by frequencies above and below the exposure range, i.e., tonotopic map reorganization occurs. The suppression can be at least partially reversed after a long period of quiet recovery, as the moderate-level exposure does not impair peripheral hearing. Here we exposed adult cats, for 7-13 weeks without interruption, to two different moderate-level tone pip ensembles, in separate experiments. One exposure stimulus consisted of an octave-wide 2-4 kHz band, which overlaps substantially with the cat vocalization range; the other consisted of a pair of third-octave bands centered at 4 and 16 kHz. We again report a decrease in AI responsiveness in the exposure frequency range, irrespective of the exposure stimulus bandwidth or center frequency, and a slow, partial recovery over a 12-week post-exposure window. In contrast to our previous studies, the suppression in both of the present experiments extended well beyond the exposure frequency range. In particular, following the 4 and 16 kHz experimental acoustic environment, AI activity was strongly suppressed not only in response to frequencies close to the two exposure bands, but also in response to frequencies between the bands, i.e., the results resembled those to a single broadband stimulus spanning the 3-18 kHz range. On the other hand, responses in secondary auditory cortex (AII) were suppressed predominantly around 4 and 16 kHz, with little or no suppression in between.

The endocochlear potential alters cochlear micromechanics.

Acoustic stimulation gates mechanically sensitive ion channels in cochlear sensory hair cells. Even in the absence of sound, a fraction of these channels remains open, forming a conductance between hair cells and the adjacent fluid space, scala media. Restoring the lost endogenous polarization of scala media in an in vitro preparation of the whole cochlea depolarizes the hair cell soma. Using both digital laser interferometry and time-resolved confocal imaging, we show that this causes a structural refinement within the organ of Corti that is dependent on the somatic electromotility of the outer hair cells (OHCs). Specifically, the inner part of the reticular lamina up to the second row of OHCs is pulled toward the basilar membrane, whereas the outer part (third row of OHCs and the Hensens cells) unexpectedly moves in the opposite direction. A similar differentiated response pattern is observed for sound-evoked vibrations: restoration of the endogenous polarization decreases vibrations of the inner part of the reticular lamina and results in up to a 10-fold increase of vibrations of the outer part. We conclude that the endogenous polarization of scala media affects the function of the hearing organ by altering its geometry, mechanical and electrical properties.