Publications using TDT

A crucial function of the brain is to be able to distinguish whether or not changes in the environment are caused by one's own actions. Even the smallest brains appear to be capable of making this distinction, as has been shown by closed-loop behavioral experiments in flies controlling visual stimuli in virtual reality paradigms. We questioned whether activity in the fruit fly brain is different during such closed-loop behavior, compared with passive viewing of a stimulus. To address this question, we used a procedure to record local field potential (LFP) activity across the fly brain while flies were controlling a virtual object through their movement on an air-supported ball. The virtual object was flickered at a precise frequency (7 Hz), creating a frequency tag that allowed us to track brain responses to the object while animals were behaving. Following experiments under closed-loop control, we replayed the same stimulus to the fly in open loop, such that it could no longer control the stimulus. We found identical receptive fields and similar strength of frequency tags across the brain for the virtual object under closed loop and replay. However, when comparing central versus peripheral brain regions, we found that brain responses were differentially modulated depending on whether flies were in control or not. Additionally, coherence of LFP activity in the brain increased when flies were in control, compared with replay, even if motor behavior was similar. This suggests that processes associated with closed-loop control promote temporal coordination in the insect brain. Significance statement: We show that closed-loop control of a visual stimulus promotes temporal coordination across the Drosophila brain, compared with open-loop replay of the same visual sequences. This is significant because it suggests that, to understand goal-directed behavior or visual attention in flies, it may be most informative to sample neural activity from multiple regions across the brain simultaneously, and to examine temporal relationships (e.g., coherence) between these regions.

In this study, we investigated the effects of varying intensity levels of repeated moderate noise exposures on hearing. The aim was to define an appropriate intensity level that could be repeated several times without giving rise to a permanent hearing loss, and thus establish a model for early adulthood moderate noise exposure in rats. Female Sprague-Dawley rats were exposed to broadband noise for 90 min, with a 50 % duty cycle at levels of 101, 104, 107, or 110 dB sound pressure level (SPL), and compared to a control group of non-exposed animals. Exposure was repeated every 6 weeks for a maximum of six repetitions or until a permanent hearing loss was observed. Hearing was assessed by the auditory brainstem response (ABR). Rats exposed to the higher intensities of 107 and 110 dB SPL showed permanent threshold shifts following the first exposure, while rats exposed to 101 and 104 dB SPL could be exposed at least six times without a sustained change in hearing thresholds. ABR amplitudes decreased over time for all groups, including the non-exposed control group, while the latencies were unaffected. A possible change in noise susceptibility following the repeated moderate noise exposures was tested by subjecting the animals to high-intensity noise exposure of 110 dB for 4 h. Rats previously exposed repeatedly to 104 dB SPL were slightly more resistant to high-intensity noise exposure than non-exposed rats or rats exposed to 101 dB SPL. Repeated moderate exposure to 104 dB SPL broadband noise is a viable model for early adulthood noise exposure in rats and may be useful for the study of noise exposure on age-related hearing loss.

There is little biological data available for diving birds because many live in hard-to-study, remote habitats. Only one species of diving bird, the black-footed penguin (Spheniscus demersus), has been studied in respect to auditory capabilities (Wever et al., Proc Natl Acad Sci USA 63:676-680, 1969). We, therefore, measured in-air auditory threshold in ten species of diving birds, using the auditory brainstem response (ABR). The average audiogram obtained for each species followed the U-shape typical of birds and many other animals. All species tested shared a common region of the greatest sensitivity, from 1000 to 3000 Hz, although audiograms differed significantly across species. Thresholds of all duck species tested were more similar to each other than to the two non-duck species tested. The red-throated loon (Gavia stellata) and northern gannet (Morus bassanus) exhibited the highest thresholds while the lowest thresholds belonged to the duck species, specifically the lesser scaup (Aythya affinis) and ruddy duck (Oxyura jamaicensis). Vocalization parameters were also measured for each species, and showed that with the exception of the common eider (Somateria mollisima), the peak frequency, i.e., frequency at the greatest intensity, of all species' vocalizations measured here fell between 1000 and 3000 Hz, matching the bandwidth of the most sensitive hearing range.

How neuronal ensembles compute information is actively studied in early visual cortex. Much less is known about how local ensembles function in inferior temporal (IT) cortex, the last stage of the ventral visual pathway that supports visual recognition. Previous reports suggested that nearby neurons carry information mostly independently, supporting efficient processing (Barlow, 1961). However, others postulate that noise covariation effects may depend on network anisotropy/homogeneity and on how the covariation relates to representation. Do slow trial-by-trial noise covariations increase or decrease IT's object coding capability, how does encoding capability relate to correlational structure (i.e., the spatial pattern of signal and noise redundancy/homogeneity across neurons), and does knowledge of correlational structure matter for decoding? We recorded simultaneously from ∼80 spiking neurons in ∼1 mm(3) of macaque IT under light neurolept anesthesia. Noise correlations were stronger for neurons with correlated tuning, and noise covariations reduced object encoding capability, including generalization across object pose and illumination. Knowledge of noise covariations did not lead to better decoding performance. However, knowledge of anisotropy/homogeneity improved encoding and decoding efficiency by reducing the number of neurons needed to reach a given performance level. Such correlated neurons were found mostly in supragranular and infragranular layers, supporting theories that link recurrent circuitry to manifold representation. These results suggest that redundancy benefits manifold learning of complex high-dimensional information and that subsets of neurons may be more immune to noise covariation than others. Significance statement: How noise affects neuronal population coding is poorly understood. By sampling densely from local populations supporting visual object recognition, we show that recurrent circuitry supports useful representations and that subsets of neurons may be more immune to noise covariation than others.

Traveling waves in the inner ear exhibit an amplitude peak that shifts with frequency. The peaking is commonly believed to rely on motile processes that amplify the wave by inserting energy. We recorded the vibrations at adjacent positions on the basilar membrane in sensitive gerbil cochleae and tested the putative power amplification in two ways. First, we determined the energy flux of the traveling wave at its peak and compared it to the acoustic power entering the ear, thereby obtaining the net cochlear power gain. For soft sounds, the energy flux at the peak was 1 ± 0.6 dB less than the middle ear input power. For more intense sounds, increasingly smaller fractions of the acoustic power actually reached the peak region. Thus, we found no net power amplification of soft sounds and a strong net attenuation of intense sounds. Second, we analyzed local wave propagation on the basilar membrane. We found that the waves slowed down abruptly when approaching their peak, causing an energy densification that quantitatively matched the amplitude peaking, similar to the growth of sea waves approaching the beach. Thus, we found no local power amplification of soft sounds and strong local attenuation of intense sounds. The most parsimonious interpretation of these findings is that cochlear sensitivity is not realized by amplifying acoustic energy, but by spatially focusing it, and that dynamic compression is realized by adjusting the amount of dissipation to sound intensity.

Defects in the rat sarcoma viral oncogene homolog (Ras)/extracellular-signal-regulated kinase and the phosphatidylinositol 3-kinase-mammalian target of rapamycin (mTOR) signaling pathways are responsible for several neurodevelopmental disorders. These disorders are an important cause for intellectual disability; additional manifestations include autism spectrum disorder, seizures, and brain malformations. Changes in synaptic function are thought to underlie the neurological conditions associated with these syndromes. We therefore studied morphology and in vivo synaptic transmission of the calyx of Held synapse, a relay synapse in the medial nucleus of the trapezoid body (MNTB) of the auditory brainstem, in mouse models of tuberous sclerosis complex (TSC), Fragile X syndrome (FXS), Neurofibromatosis type 1 (NF1), and Costello syndrome. Calyces from both Tsc1(+/-) and from Fmr1 knock-out (KO) mice showed increased volume and surface area compared to wild-type (WT) controls. In addition, in Fmr1 KO animals a larger fraction of calyces showed complex morphology. In MNTB principal neurons of Nf1 (+/) (-) mice the average delay between EPSPs and APs was slightly smaller compared to WT controls, which could indicate an increased excitability. Otherwise, no obvious changes in synaptic transmission, or short-term plasticity were observed during juxtacellular recordings in any of the four lines. Our results in these four mutants thus indicate that abnormalities of mTOR or Ras signaling do not necessarily result in changes in in vivo synaptic transmission.

Optogenetic techniques enable precise excitation and inhibition of firing in specified neuronal populations and artifact-free recording of firing activity. Several studies have suggested that optical stimulation provides the precision and dynamic range requisite for closed-loop neuronal control, but no approach yet permits feedback control of neuronal firing. Here we present the ‘optoclamp’, a feedback control technology that provides continuous, real-time adjustments of bidirectional optical stimulation in order to lock spiking activity at specified targets over timescales ranging from seconds to days. We demonstrate how this system can be used to decouple neuronal firing levels from ongoing changes in network excitability due to multi-hour periods of glutamatergic or GABAergic neurotransmission blockade in vitro as well as impinging vibrissal sensory drive in vivo. This technology enables continuous, precise optical control of firing in neuronal populations in order to disentangle causally related variables of circuit activation in a physiologically and ethologically relevant manner.

It is well known that, although psychophysical scaling produces good qualitative agreement between experiments, precise quantitative agreement between experimental results, such as that routinely achieved in physics or biology, is rarely or never attained. A particularly galling example of this is the fact that power function exponents for the same psychological continuum, measured in different laboratories but ostensibly using the same scaling method, magnitude estimation, can vary by a factor of three. Constrained scaling (CS), in which observers first learn a standardized meaning for a set of numerical responses relative to a standard sensory continuum and then make magnitude judgments of other sensations using the learned response scale, has produced excellent quantitative agreement between individual observers' psychophysical functions. Theoretically it could do the same for across-laboratory comparisons, although this needs to be tested directly. We compared nine different experiments from four different laboratories as an example of the level of across experiment and across-laboratory agreement achievable using CS. In general, we found across experiment and across-laboratory agreement using CS to be significantly superior to that typically obtained with conventional magnitude estimation techniques, although some of its potential remains to be realized.

Decisions are often made based on which option will result in the largest reward. When given a choice between a smaller but immediate reward and a larger delayed reward, however, humans and animals often choose the smaller, an effect known as temporal discounting. Dopamine (DA) neurotransmission is central to reward processing and encodes delayed reward value. Impulsivity, the tendency to act without forethought, is associated with excessive discounting of rewards, which has been documented in patients with attention deficit hyperactivity disorder (ADHD). Both impulsivity and temporal discounting are linked to the dopaminergic system. Methylphenidate (MPH), which blocks the DA transporter and increases extracellular levels of DA in the basal ganglia and prefrontal cortex, is a primary treatment for ADHD and, at low doses, ameliorates impulsivity in both humans and animals. This study tested the hypothesis that low doses of MPH would decrease the discounting rate of rhesus monkeys performing an intertemporal choice task, suggesting a reduction in impulsivity. The results support this hypothesis and provide further evidence for the role of DA in temporal discounting and impulsive behavior.

Deep brain stimulation (DBS) of the subgenual cingulate gyrus (SCG) has been used to treat patients with treatment-resistant depression. As in humans, DBS applied to the ventromedial prefrontal cortex of rats induces antidepressant-like responses. Physiological interactions between structures that play a role in depression and antidepressant treatment are still unknown. The present study examined the effect of DBS on inter-region communication by measuring the coherence of local field potentials in the rat infralimbic cortex (IL; homologue of the SCG) and one of its major afferents, the ventral hippocampus (VH). Rats received daily IL DBS treatment (100 μA, 90 μs, 130 Hz; 8h/day). Recordings were conducted in unrestrained, behaving animals on the day before treatment, after 1 and 10 days of treatment, and 10 days stimulation offset. VH-IL coherence in the 2-4 Hz range was reduced in DBS-treated animals compared with shams after 10 days, but not after only 1 day of treatment. No effect of DBS was observed in the 6-10 Hz (theta) range, where coherence was generally high and could be further evoked with a loud auditory stimulus. Finally, coherence was not affected by fluoxetine (10mg/kg), suggesting that the effects of DBS were not likely mediated by increased serotonin levels. While these data support the hypothesis that DBS disrupts communication between regions important for expectation-based control of emotion, they also suggest that lasting physiological effects require many days of treatment and, furthermore, may be specific to lower-frequency patterns, the nature and scope of which await further investigation.

Ischemic brain stroke is a leading cause of disability and includes hearing loss. Clinical reports have also suggested that there is hearing loss in stroke patients but the mechanism was not determined. Therefore, we hypothesized that hearing loss after cerebral ischemia may be associated with changes to the synapse, gap junction, and sodium channel (NaC) proteins. Ischemia–reperfusion injury was induced in wild-type mice (I/R group). The lesion volume was determined by 2,3,5-triphenyltetrazolium chloride (TTC) staining of the brain sections. BBB disruption was confirmed by Evans blue staining and leakage of bovine serum albumin labeled with fluorescein isothiocyanate (BSA-FITC). We found that brain edema, infarct size, and permeability were increased in ischemic mice as compared with the sham-operated group. Caspase-3, caspase-9, and TUNEL-positive cells were increased in I/R mice, indicating neuronal apoptosis. Moreover, there were increased expressions of matrix metalloprotease’s (MMP-2, -3, -9, and -13), interleukin (IL)-6, and decreased expressions of tight junction proteins (TJP) in the I/R group, as compared with the sham group, which signifies inflammation and BBB disruption. We also observed decreased levels of post-synaptic density protein-95 (PSD-95), synapse-associated protein 97 (SAP-97), connexin-43, NaC-α, and NaC-β, and increased expression of connexin-45, whereas no substantial change was observed in connexin-26 expression in the I/R group. Interestingly, auditory response was reduced in the I/R mice, indicating hearing loss. These data suggest that hearing loss in ischemic mice was primarily due to alterations in connexin, synapses, and NaC channels.

Current models for neural coding of vowels are typically based on linear descriptions of the auditory periphery, and fail at high sound levels and in background noise. These models rely on either auditory nerve discharge rates or phase locking to temporal fine structure. However, both discharge rates and phase locking saturate at moderate to high sound levels, and phase locking is degraded in the CNS at middle to high frequencies. The fact that speech intelligibility is robust over a wide range of sound levels is problematic for codes that deteriorate as the sound level increases. Additionally, a successful neural code must function for speech in background noise at levels that are tolerated by listeners. The model presented here resolves these problems, and incorporates several key response properties of the nonlinear auditory periphery, including saturation, synchrony capture, and phase locking to both fine structure and envelope temporal features. The model also includes the properties of the auditory midbrain, where discharge rates are tuned to amplitude fluctuation rates. The nonlinear peripheral response features create contrasts in the amplitudes of low-frequency neural rate fluctuations across the population. These patterns of fluctuations result in a response profile in the midbrain that encodes vowel formants over a wide range of levels and in background noise. The hypothesized code is supported by electrophysiological recordings from the inferior colliculus of awake rabbits. This model provides information for understanding the structure of cross-linguistic vowel spaces, and suggests strategies for automatic formant detection and speech enhancement for listeners with hearing loss.

A recent study from our laboratory assessed vowel identification in cochlear implant (CI) users, using full /dVd/ syllables and partial (center- and edges-only) syllables with duration cues neutralized [Donaldson, Rogers, Cardenas, Russell, and Hanna (2013). J. Acoust. Soc. Am. 134, 3021–3028]. CI users' poorer performance for partial syllables as compared to full syllables, and for edges-only syllables as compared to center-only syllables, led to the hypotheses (1) that CI users may rely strongly on vowel duration cues; and (2) that CI users have more limited access to dynamic spectral cues than steady-state spectral cues. The present study tested those hypotheses. Ten CI users and ten young normal hearing (YNH) listeners heard full /dVd/ syllables and modified (center- and edges-only) syllables in which vowel duration cues were either preserved or eliminated. The presence of duration cues significantly improved vowel identification scores in four CI users, suggesting a strong reliance on duration cues. Duration effects were absent for the other CI users and the YNH listeners. On average, CI users and YNH listeners demonstrated similar performance for center-only stimuli and edges-only stimuli having the same total duration of vowel information. However, three CI users demonstrated significantly poorer performance for the edges-only stimuli, indicating apparent deficits of dynamic spectral processing.

The ability to segregate simultaneous sound sources based on their spatial locations is an important aspect of auditory scene analysis. While the role of sound azimuth in segregation is well studied, the contribution of sound elevation remains unknown. Although previous studies in humans suggest that elevation cues alone are not sufficient to segregate simultaneous broadband sources, the current study demonstrates they can suffice. Listeners segregating a temporally modulated noise target from a simultaneous unmodulated noise distracter differing in elevation fall into two statistically distinct groups: one that identifies target direction accurately across a wide range of modulation frequencies (MF) and one that cannot identify target direction accurately and, on average, reports the opposite direction of the target for low MF. A non-spiking model of inferior colliculus neurons that process single-source elevation cues suggests that the performance of both listener groups at the population level can be accounted for by the balance of excitatory and inhibitory inputs in the model. These results establish the potential for broadband elevation cues to contribute to the computations underlying sound source segregation and suggest a potential mechanism underlying this contribution.

Whether crossing a busy intersection or attending a large dinner party, listeners sometimes need to attend to multiple spatially distributed sound sources or streams concurrently. How they achieve this is not clear—some studies suggest that listeners cannot truly simultaneously attend to separate streams, but instead combine attention switching with short-term memory to achieve something resembling divided attention. This paper presents two oddball detection experiments designed to investigate whether directing attention to phonetic versus semantic properties of the attended speech impacts listeners' ability to divide their auditory attention across spatial locations. Each experiment uses four spatially distinct streams of monosyllabic words, variation in cue type (providing phonetic or semantic information), and requiring attention to one or two locations. A rapid button-press response paradigm is employed to minimize the role of short-term memory in performing the task. Results show that differences in the spatial configuration of attended and unattended streams interact with linguistic properties of the speech streams to impact performance. Additionally, listeners may leverage phonetic information to make oddball detection judgments even when oddballs are semantically defined. Both of these effects appear to be mediated by the overall complexity of the acoustic scene.

Sensory systems must represent stimuli in manners dependent upon a wealth of factors, including stimulus intensity and duration. One way the brain might handle these complex functions is to assign the tasks throughout distributed nodes, each contributing to information processing. We sought to explore this important aspect of sensory network function in the mammalian olfactory system, wherein the intensity and duration of odor exposure are critical contributors to odor perception. This is a quintessential model for exploring processing schemes given the distribution of odor information by olfactory bulb mitral and tufted cells into several anatomically distinct secondary processing stages, including the piriform cortex (PCX) and olfactory tubercle (OT), whose unique contributions to odor coding are unresolved. We explored the coding of PCX and OT neuron responses to odor intensity and duration. We found that both structures similarly partake in representing descending intensities of odors by reduced recruitment and modulation of neurons. Additionally, while neurons in the OT adapt to odor exposure, they display reduced capacity to adapt to either repeated presentations of odor or a single prolonged odor presentation compared with neurons in the PCX. These results provide insights into manners whereby secondary olfactory structures may, at least in some cases, uniquely represent stimulus features.

Gap junctions play a critical role in hearing. Connexin gap junction gene mutations can induce a high incidence of hearing loss. Pannexin (Panx) gene also encodes gap junction proteins in vertebrates. Panx1 is a predominant pannexin isoform and has extensive expression in the cochlea. Here, we report that deletion of Panx1 in the cochlea could produce a progressive hearing loss. The auditory brainstem response (ABR) recording showed that hearing loss was moderate to severe and severe at high-frequencies. Distortion product otoacoustic emission (DPOAE), which reflects the activity of active cochlear mechanics that can amply acoustic stimulation to enhance hearing sensitivity and frequency selectivity, was also reduced. We further found that Panx1 deficiency could activate Caspase-3 cell apoptotic pathway in the cochlea to cause hair cells and other types of cells degeneration. These data indicate that like connexins Panx1 deficiency can also induce hearing loss. These data also suggest that pannexins play important rather than redundant roles in the cochlea and hearing.

The century-old duplex theory of sound localization posits that low- and high-frequency sounds are localized with two different acoustical cues, interaural time and level differences (ITDs and ILDs), respectively. While behavioral studies in humans and behavioral and neurophysiological studies in a variety of animal models have largely supported the duplex theory, behavioral sensitivity to ILD is curiously invariant across the audible spectrum. Here we demonstrate that auditory midbrain neurons in the chinchilla ( Chinchilla lanigera) also encode ILDs in a frequency-invariant manner, efficiently representing the full range of acoustical ILDs experienced as a joint function of sound source frequency, azimuth, and distance. We further show, using Fisher information, that nominal “low-frequency” and “high-frequency” ILD-sensitive neural populations can discriminate ILD with similar acuity, yielding neural ILD discrimination thresholds for near-midline sources comparable to behavioral discrimination thresholds estimated for chinchillas. These findings thus suggest a revision to the duplex theory and reinforce ecological and efficiency principles that hold that neural systems have evolved to encode the spectrum of biologically relevant sensory signals to which they are naturally exposed.

The benefit provided to listeners with sensorineural hearing loss (SNHL) by an acoustic beamforming microphone array was determined in a speech-on-speech masking experiment. Normal-hearing controls were tested as well. For the SNHL listeners, prescription-determined gain was applied to the stimuli, and performance using the beamformer was compared with that obtained using bilateral amplification. The listener identified speech from a target talker located straight ahead (0° azimuth) in the presence of four competing talkers that were either colocated with, or spatially separated from, the target. The stimuli were spatialized using measured impulse responses and presented via earphones. In the spatially separated masker conditions, the four maskers were arranged symmetrically around the target at ±15° and ±30° or at ±45° and ±90°. Results revealed that masked speech reception thresholds for spatially separated maskers were higher (poorer) on average for the SNHL than for the normal-hearing listeners. For most SNHL listeners in the wider masker separation condition, lower thresholds were obtained through the microphone array than through bilateral amplification. Large intersubject differences were found in both listener groups. The best masked speech reception thresholds overall were found for a hybrid condition that combined natural and beamforming listening in order to preserve localization for broadband sources.

Are musicians better able to understand speech in noise than non-musicians? Recent findings have produced contradictory results. Here we addressed this question by asking musicians and non-musicians to understand target sentences masked by other sentences presented from different spatial locations, the classical ‘cocktail party problem’ in speech science. We found that musicians obtained a substantial benefit in this situation, with thresholds ~6 dB better than non-musicians. Large individual differences in performance were noted particularly for the non-musically trained group. Furthermore, in different conditions we manipulated the spatial location and intelligibility of the masking sentences, thus changing the amount of ‘informational masking’ (IM) while keeping the amount of ‘energetic masking’ (EM) relatively constant. When the maskers were unintelligible and spatially separated from the target (low in IM), musicians and non-musicians performed comparably. These results suggest that the characteristics of speech maskers and the amount of IM can influence the magnitude of the differences found between musicians and non-musicians in multiple-talker “cocktail party” environments. Furthermore, considering the task in terms of the EM-IM distinction provides a conceptual framework for future behavioral and neuroscientific studies which explore the underlying sensory and cognitive mechanisms contributing to enhanced “speech-in-noise” perception by musicians.