Publications using TDT

The basic circuitry of auditory, visual, somatosensory and other cortical areas is highly stereotyped (Douglas and Martin, 2004). However, it remains unclear whether this anatomical stereotypy implies functional homogeneity, or whether instead different cortical areas are specialized to process the diverse sensory inputs they receive. Here we have used a two alternative forced choice task to assess modality-specific differences in the ability of rats to exploit precise neuronal timing. We delivered pairs of electrical pulses directly to different areas of cortex to determine the minimum timing differences subjects could detect. By stimulating the cortex directly, we isolated differences due to cortical circuitry rather than to sensory transduction and subcortical processing. Surprisingly, the minimum detectable timing differences varied over more than an order of magnitude, ranging from 1 ms in barrel cortex to 15 ms in visual cortex. Furthermore, these modality-specific differences depended upon sensory experience: although animals subjected to whisker clipping initially showed an impaired ability to exploit fine timing in barrel cortical stimulation, behavioral training partially rescued this deficit. Our results suggest that different cortical areas are adapted to the specific structure of the input signals they process, and that precise spike timing may play a more important role for some cortical areas than for others.

Sensory systems across the brain are specialized for their input, yet some principles of neural organization are conserved across modalities. The pattern of anatomical connections from the primate auditory cortex to the temporal, parietal, and prefrontal lobes suggests a possible division into dorsal and ventral auditory processing streams, with the dorsal stream originating from more caudal areas of the auditory cortex, and the ventral stream originating from more rostral areas. These streams are hypothesized to be analogous to the well-established dorsal and ventral streams of visual processing. In the visual system, the dorsal processing stream shows substantially faster neural response latencies than does the ventral stream. However, the relative timing of putative dorsal and ventral stream processing has yet to be explored in other sensory modalities. Here, we compare distributions of neural response latencies from 10 different areas of macaque auditory cortex, confirmed by individual anatomical reconstructions, to determine whether a similar timing advantage is found for the hypothesized dorsal auditory stream. Across three varieties of auditory stimuli (clicks, noise, and pure tones), we find that latencies increase with hierarchical level, as predicted by anatomical connectivity. Critically, we also find a pronounced timing differential along the caudal-to-rostral axis within the same hierarchical level, with caudal (dorsal stream) latencies being faster than rostral (ventral stream) latencies. This observed timing differential mirrors that found for the dorsal stream of the visual system, suggestive of a common timing advantage for the dorsal stream across sensory modalities.

Background: Transplantations of human stem cell derivatives have been widely investigated in rodent models for the potential restoration of function of neural pathways after spinal cord injury (SCI). Studies have already demonstrated cells survival following transplantation in SCI. We sought to evaluate survival and potential therapeutic effects of transplanted human embryonic stem (hES) cell-derived oligodendrocyte progenitor cells (OPCs) in a contusive injury in rats. Bioluminescence imaging was utilized to verify survivability of cells up to 4 weeks, and somatosensory evoked potential (SSEPs) were recorded at the cortex to monitor function of sensory pathways throughout the 6-week recovery period. Principal findings: hES cells were transduced with the firefly luciferase gene and differentiated into OPCs. OPCs were transplanted into the lesion epicenter of rat spinal cords 2 hours after inducing a moderate contusive SCI. The hES-treatment group showed improved SSEPs, including increased amplitude and decreased latencies, compared to the control group. The bioluminescence of transplanted OPCs decreased by 97% in the injured spinal cord compared to only 80% when injected into an uninjured spinal cord. Bioluminescence increased in both experimental groups such that by week 3, no statistical difference was detected, signifying that the cells survived and proliferated independent of injury. Post-mortem histology of the spinal cords showed integration of human cells expressing mature oligodendrocyte markers and myelin basic protein without the expression of markers for astrocytes (GFAP) or pluripotent cells (OCT4). Conclusions: hES-derived OPCs transplanted 2 hours after contusive SCI survive and differentiate into OLs that produce MBP. Treated rats demonstrated functional improvements in SSEP amplitudes and latencies compared to controls as early as 1 week post-injury. Finally, the hostile injury microenvironment at 2 hours post-injury initially caused increased cell death but did not affect the long-term cell proliferation or survival, indicating that cells can be transplanted sooner than conventionally accepted.

We aimed to investigate the pathophysiology of diabetes-associated hearing impairment in type 1 diabetes using mice with streptozotocin-induced diabetes (C57BL/6J; male). Hearing function was evaluated 1, 3, and 5 months after induction of diabetes (five diabetic and five control animals per time point) using auditory-evoked brain stem responses (ABRs). Mice (four diabetic and four control) were exposed to loud noise (105 dB) 5 months after induction of diabetes. ABRs were measured before and after noise exposure. Cochlear blood flows were measured by laser-Doppler flowmeter. Spiral ganglion cells (SGCs) were counted. Vessel endothelial cells were observed by CD31 immunostaining. Chronologic changes in the ABR threshold shift were not significantly different between the diabetic and control groups. However, vessel walls in the modiolus of the cochleae were significantly thicker in the diabetic group than the control group. Additionally, recovery from noise-induced injury was significantly impaired in diabetic mice. Reduced cochlea blood flows and SGC loss were observed in diabetic mice cochleae after noise exposure. Our data suggest that diabetic cochleae are more susceptible than controls to loud noise exposure, and decreased cochlear blood flow due to sclerosis of the vessels and consequent loss of SGCs are possible mechanisms of hearing impairment in diabetic patients.

To study the role of harmonic structure in pitch perception, normal-hearing listeners were tested using noise-vocoded harmonic tone complexes. When tested in a magnitude judgment procedure using vocoded versions generated with 2–128 channels, judgments of pitch strength increased systematically as the number of channels increased and reflected acoustic cues based on harmonic peak-to-valley ratio, but not cues based on periodicity strength. When tested in a fundamental frequency discrimination task, listeners correctly recognized the direction of pitch change with as few as eight noise-vocoded channels. The results suggest that spectral processing contributes substantially to pitch perception in normal-hearing listeners.

Listeners are good at attending to one auditory stream in a crowded environment. However, is there an upper limit of streams present in an auditory scene at which this selective attention breaks down? Here, participants were asked to attend one stream of spoken letters amidst other letter streams. In half of the trials, an initial primer was played, cueing subjects to the sound configuration. Results indicate that performance increases with token repetitions. Priming provided a performance benefit, suggesting that stream selection, not formation, is the bottleneck associated with attention in an overcrowded scene. Results' implications for brain-computer interfaces are discussed.

Sodium salicylate (NaSal), an aspirin metabolite, can cause tinnitus in animals and human subjects. To explore neural mechanisms underlying salicylate-induced tinnitus, we examined effects of NaSal on neural activities of the medial geniculate body (MGB), an auditory thalamic nucleus that provides the primary and immediate inputs to the auditory cortex, by using the whole-cell patch-clamp recording technique in MGB slices. Rats treated with NaSal (350 mg/kg) showed tinnitus-like behavior as revealed by the gap prepulse inhibition of acoustic startle (GPIAS) paradigm. NaSal (1.4 mM) decreased the membrane input resistance, hyperpolarized the resting membrane potential, suppressed current-evoked firing, changed the action potential, and depressed rebound depolarization in MGB neurons. NaSal also reduced the excitatory and inhibitory postsynaptic response in the MGB evoked by stimulating the brachium of the inferior colliculus. Our results demonstrate that NaSal alters neuronal intrinsic properties and reduces the synaptic transmission of the MGB, which may cause abnormal thalamic outputs to the auditory cortex and contribute to NaSal-induced tinnitus.

Oscillatory neural activity within the gamma band (25–90 Hz) is generally thought to be able to provide a timing signal for harmonizing neural computations across different brain regions. Using time–frequency analyses of the dynamics of gamma-band activity in the local field potentials recorded from monkey primary visual cortex, we found identical temporal characteristics of gamma activity in both awake and anesthetized brain states, including large variability of peak frequency, brief oscillatory epochs (<100 ms on average), and stochastic statistics of the incidence and duration of oscillatory events. These findings indicate that gamma-band activity is temporally unstructured and is inherently a stochastic signal generated by neural networks. This idea was corroborated further by our neural-network simulations. Our results suggest that gamma-band activity is too random to serve as a clock signal for synchronizing neuronal responses in awake as in anesthetized monkeys. Instead, gamma-band activity is more likely to be filtered neuronal network noise. Its mean frequency changes with global state and is reduced under anesthesia.

The present study used an optical imaging paradigm to investigate plastic changes in the auditory cortex induced by fear conditioning, in which a sound (conditioned stimulus, CS) was paired with an electric foot-shock (unconditioned stimulus, US). We report that, after conditioning, auditory information could be retrieved on the basis of an electric foot-shock alone. Before conditioning, the auditory cortex showed no response to a foot-shock presented in the absence of sound. In contrast, after conditioning, the mere presentation of a foot-shock without any sound succeeded in eliciting activity in the auditory cortex. Additionally, the magnitude of the optical response in the auditory cortex correlated with variation in the electrocardiogram (correlation coefficient: -0.68). The area activated in the auditory cortex, in response to the electric foot-shock, statistically significantly had a larger cross-correlation value for tone response to the CS sound (12 kHz) compared to the non-CS sounds in normal conditioning group. These results suggest that integration of different sensory modalities in the auditory cortex was established by fear conditioning.

There is increasing evidence that alterations in the focus of attention result in changes in neural responding at the most peripheral levels of the auditory system. To date, however, those studies have not ruled out differences in task demands or overall arousal in explaining differences in responding across intermodal attentional conditions. The present study sought to compare changes in the response of cochlear outer hair cells, employing distortion product otoacoustic emissions (DPOAEs), under different, balanced conditions of intermodal attention. DPOAEs were measured while the participants counted infrequent, brief exemplars of the DPOAE primary tones (auditory attending), and while counting visual targets, which were instances of Gabor gradient phase shifts (visual attending). Corroborating an earlier study from our laboratory, the results show that DPOAEs recorded in the auditory-ignoring condition were significantly higher in overall amplitude, compared with DPOAEs recorded while participants attended to the eliciting primaries; a finding in apparent contradiction with more central measures of intermodal attention. Also consistent with our previous findings, DPOAE rapid adaptation, believed to be mediated by the medial olivocochlear efferents (MOC), was unaffected by changes in intermodal attention. The present findings indicate that manipulations in the conditions of attention, through the corticofugal pathway, and its last relay to cochlear outer hair cells (OHCs), the MOC, alter cochlear sensitivity to sound. These data also suggest that the MOC influence on OHC sensitivity is composed of two independent processes, one of which is under attentional control.

This paper presents a new actuation scheme for in-plane bidirectional translation of polysilicon microelectrodes. The new Chevron-peg actuation scheme uses microelectromechanical systems (MEMS) based electrothermal microactuators to move microelectrodes for brain implant applications. The design changes were motivated by specific needs identified by the in vivo testing of an earlier generation of MEMS microelectrodes that were actuated by the Chevron-latch type of mechanism. The microelectrodes actuated by the Chevron-peg mechanism discussed here show improved performance in the following key areas: higher force generation capability (111 μN per heat strip compared to 50 μN), reduced power consumption (91 mW compared to 360 mW), and reliable performance with consistent forward and backward movements of microelectrodes. Failure analysis of the Chevron-latch and the Chevron-peg type of actuation schemes showed that the latter is more robust to wear over four million cycles of operation. The parameters for the activation waveforms for Chevron-peg actuators were optimized using statistical analysis. Waveforms with a 1-ms time period and a 1-Hz frequency of operation showed minimal error between the expected and the actual movement of the microelectrodes. The new generation of Chevron-peg actuators and microelectrodes are therefore expected to enhance the longevity and performance of implanted microelectrodes in the brain. [2011-0341].

Anatomical and pharmacological studies have shown that the lateral superior olive (LSO) receives inputs from a number of sources and that LSO cells can alter the balance of their own excitatory and inhibitory drive. It is thus likely that the ongoing sound-evoked responses of LSO cells reflect a complex interplay of excitatory and inhibitory events, which may be affected by anesthesia. The goal of this study was to characterize the temporal discharge patterns of single units in the LSO of unanesthetized, decerebrate cats in response to long-duration ipsilateral best-frequency tone bursts. A decision tree is presented to partition LSO units on the basis of poststimulus time histogram shape, adaptation of instantaneous firing rate as a function of time, and sustained discharge rate. The results suggest that LSO discharge patterns form a continuum with four archetypes: sustained choppers that show two or more peaks of activity at stimulus onset and little adaptation of rate throughout the response, transient choppers that undergo a decrease in rate that eventually stabilizes with time, primary-like units that display an initial peak of activity followed by a monotonic decline in rate to a steady-state value, and onset-sustained units that exhibit an initial peak of activity at stimulus onset followed by a low sustained activity. Compared with the chopper units, the nonchopper units tend to show longer first-spike latencies, lower peak firing rates, and more irregular sustained discharge patterns. Modeling studies show that the full range of LSO response types can be obtained from an underlying sustained chopper by varying the strength and latency of a sound-driven ipsilateral inhibition relative to that of excitation. Together, these results suggest that inhibition plays a major role in shaping the temporal discharge patterns of units in unanesthetized preparations.

Purpose Perceptual estimates of voice quality obtained using rating scales are subject to contextual biases that influence how individuals assign numbers to estimate the magnitude of vocal quality. Because rating scales are commonly used in clinical settings, assessments of voice quality are also subject to the limitations of these scales. Instead, a matching task can be used to obtain objective measures of voice quality, thereby facilitating model development and tools for clinical use. Method Twenty-seven individuals participated in a rating task or at least 1 of 3 matching tests (named after their modulation functions: SINE, SQUARE, POWER) to quantify the degree of roughness in dysphonic voice stimuli. Participants evaluated the roughness of 34 voice samples using an amplitude-modulated complex carrier. Results The matching thresholds were highly correlated with the ratings estimates. Reliability of thresholds did not significantly differ across tasks, but linear regressions showed that the POWER test resulted in larger perceptual distances. Conclusions A matching task can be used to obtain reliable estimates of roughness in dysphonic voices. The POWER comparison is recommended because the variability in matching thresholds across the range of roughness was evenly distributed, and the perceptual distances between stimuli were maximized.

Frequency selectivity was evaluated under two conditions designed to assess the influence of a “precursor” stimulus on auditory filter bandwidths. The standard condition consisted of a short masker, immediately followed by a short signal. The precursor condition was identical except a 100-ms sinusoid at the signal frequency (i.e., the precursor) was presented before the masker. The standard and precursor conditions were compared for measurements of psychophysical tuning curves (PTCs), and notched noise tuning characteristics. Estimates of frequency selectivity were significantly broader in the precursor condition. In the second experiment, PTCs in the standard and precursor conditions were simulated to evaluate the influence of the precursor on PTC bandwidth. The model was designed to account for the influence of additivity of masking between the masker and precursor. Model simulations were able to qualitatively account for the perceptual data when outer hair cell gain of the model was reduced in the precursor condition. These findings suggest that the precursor may have reduced cochlear gain, in addition to producing additivity of masking. This reduction in gain may be mediated by the medial olivocochlear reflex.

The physiology of the medial olivocochlear reflex suggests that a sufficiently long stimulus (>100 ms) may reduce cochlear gain and result in broadened frequency selectivity. The current study attempted to avoid gain reduction by using short maskers (20 ms) to measure psychophysical tuning curves (PTCs) and notched-noise tuning characteristics, with a 4-kHz signal. The influence of off-frequency listening on PTCs was evaluated using two types of background noise. Iso-level curves were derived using an estimate of the cochlear input/output (I/O) function, which was obtained using an off-frequency masker as a linear reference. The influence of masker duration on PTCs was assessed using a model that assumed long maskers (>20 ms) evoked gain reduction. The results suggested that the off-frequency masker was a valid linear reference when deriving I/O functions and that off-frequency listening may have occurred in auditory filters apical to the signal place. The iso-level curves from this growth-of-masking study were consistent with those from a temporal-masking-curve study by Eustaquio-Martin and Lopez-Poveda [J. Assoc. Res. Otolaryngol. 12, 281–299. (2011)], suggesting that either approach may be used to derive iso-level curves. Finally, model simulations suggested that masker duration may not influence estimates of frequency selectivity.

Connexin26 (Cx26, GJB2) mutations can induce congenital deafness and are responsible for ∼50% of nonsyndromic hearing loss in children. Mouse models show that Cx26 deficiency induces cochlear development disorder, hair cell loss, and spiral ganglion (SG) neuron degeneration. Hair cell loss and cell degeneration have been considered as a primary causer responsible for Cx26 deficiency associated hearing loss. In this study, by coincidental examination of cochlear postnatal development with recording of auditory brainstem response (ABR) and hair cell function, we found that occurrence of hearing loss in Cx26 knockout (KO) mice was ahead of hair cell loss and cochlear cell degeneration. ABR was absent at the whole-frequency range (8-40 kHz) after birth. However, cochlear cells including SG neurons had no significant degeneration throughout postnatal development. Severe cochlear hair cell loss and SG neuron degeneration were only visible in middle and basal turns, i.e., in middle and high frequency regions, in the adult Cx26 KO mouse cochlea. Functional tests show that hair cells in Cx26 KO mice functioned normally; outer hair cells retained electromotility. These data suggest that cell degeneration is not a primary causer of Cx26 deficiency associated hearing loss. Some mechanisms other than cell degeneration, such as cochlear development disorders, may play an essential role in this common hereditary deafness.

To separate sounds from different sound sources, common properties of natural sounds are used by the auditory system, such as coherent temporal envelope fluctuations and correlated changes of frequency in different frequency regions. The present study investigates how the auditory system processes a combination of these cues using a generalized comodulation masking release (CMR) paradigm. CMR is the effect of a better signal detectability in the presence of comodulated maskers than in the presence of maskers with uncorrelated envelope fluctuations across frequencies. Using a flanking-band paradigm, the results of the first experiment of the present study show that CMR is still observed for the masker and the signal coherently sweeping up or down in frequency over time, up to a sweep rate of six octaves per second. Motivated by the successful modeling of CMR using filters sensitive to temporal modulations and recent physiological evidence of spectro-temporal modulation filters, the second experiment investigates whether CMR is also observed for spectro-temporal masker modulations generated using time-shifted versions of the masker envelope for each component. The thresholds increase as soon as the temporally coherent masker modulation is changed to a spectro-temporal masker modulation, indicating that spectro-temporal modulation filters are presumably not required in CMR models.

Recent studies in humans and monkeys have reported that acoustic stimulation influences visual responses in the primary visual cortex (V1). Such influences can be generated in V1, either by direct auditory projections or by feedback projections from extrastriate cortices. To test these hypotheses, cortical activities were recorded using optical imaging at a high spatiotemporal resolution from multiple areas of the guinea pig visual cortex, to visual and/or acoustic stimulations. Visuo-auditory interactions were evaluated according to differences between responses evoked by combined auditory and visual stimulation, and the sum of responses evoked by separate visual and auditory stimulations. Simultaneous presentation of visual and acoustic stimulations resulted in significant interactions in V1, which occurred earlier than in other visual areas. When acoustic stimulation preceded visual stimulation, significant visuo-auditory interactions were detected only in V1. These results suggest that V1 is a cortical origin of visuo-auditory interaction.

While functional imaging is widely used in studies of the brain, how well the hemodynamic signal represents the underlying neural activity is still unclear. And there is a debate on whether hemodynamic signal is more tightly related to synaptic activity or action potentials. This study intends to address these questions by examining neurovascular coupling driven by pyramidal cells in the motor cortex of rats. Pyramidal cells in the motor cortex of rats were selectively transduced with the light sensitive cation channel channelrhodopsin-2 (ChR2). Electrophysiological recordings and optical intrinsic signal imaging were performed simultaneously and synchronously to capture the neural activity and hemodynamics induced by optical stimulation of ChR2-expressing pyramidal cells. Our results indicate that both synaptic activity (local field potential, LFP) and action potentials (multi-unit activity, MUA) are tightly related to hemodynamic signals. While LFPs in γ band are better in predicting hemodynamic signals elicited by short stimuli, MUA has better predictions to hemodynamic signals elicited by long stimuli. Our results also indicate that strong nonlinearity exists in neurovascular coupling.

Objectives: This study aimed to (1) investigate the relationship between the acoustic change complex (ACC) and perceptual measures of frequency and intensity discrimination, and gap detection; and (2) examine the effects of acoustic change on the amplitudes and latencies of the ACC. Design: Psychophysical thresholds for frequency and intensity discrimination and gap detection, as well as ACCs elicited by stimuli containing increments in frequency, or intensity or gaps, were recorded from the same group of subjects. The magnitude of the acoustic change was systematically varied for the ACC recording. Study sample: Twenty-six adults with normal hearing, ranging in age between 19 and 39 years. Results: Electrophysiological and psychophysical measures for frequency and intensity discrimination were significantly correlated. Electrophysiological thresholds were comparable to psychophysical thresholds for intensity discrimination but were higher than psychophysical thresholds for gap detection and frequency discrimination. Increasing the magnitude of acoustic change increased the ACC amplitude but did not show consistent effects across acoustic dimensions for ACC latency. Conclusions: The ACC can be used as an objective index of auditory discrimination in frequency and intensity. The ACC amplitude is a better indicator for auditory processing than the ACC latency.