Publications using TDT

In this study, we acutely identified a target branch of the vagus nerve known as the pancreatic branch of the vagus nerve, which exclusively innervates the pancreas by applying electrical stimulus to the known cervical vagus nerve and observing compound neural action potentials at the target nerve. In a set of chronically implanted rats, the target nerve was again cuffed using an electrode and also implanted with a continuous glucose monitor. A model of type 1 diabetes (T1D) was chemically induced and hyperglycemic state confirmed. After induction, stimulation was applied to the pancreatic branch of the vagus nerve and heart rate variability measured to assess the targeted nature of the stimulation. Pancreatic vagus nerve stimulation in a diabetic model was not found to influence heart rate demonstrating the ability of targeted stimulation to be used as for organ-specific neuromodulation while minimizing side effects.

The dorsomedial striatum (DMS) is critically involved in motor control and reward processing, but the specific neural circuit mediators are poorly understood. Recent evidence highlights the extensive connectivity of low-threshold spiking interneurons (LTSIs) within local striatal circuitry; however, the in vivo function of LTSIs remains largely unexplored. We employed fiber photometry to assess LTSI calcium activity in a range of DMS-mediated behaviors, uncovering specific reward-related activity that is down-modulated during goal-directed learning. Using two mechanistically distinct manipulations, we demonstrated that this down-modulation of LTSI activity is critical for acquisition of novel contingencies, but not for their modification. In contrast, continued LTSI activation slowed instrumental learning. Similar manipulations of fast-spiking interneurons did not reproduce these effects, implying a specific function of LTSIs. Finally, we revealed a role for the γ-aminobutyric acid (GABA)ergic functions of LTSIs in learning. Together, our data provide new insights into this striatal interneuron subclass as important gatekeepers of goal-directed learning.

Craving for cocaine progressively increases in cocaine users during drug-free periods, contributing to relapse. The projection from the infralimbic cortex to the nucleus accumbens shell (IL-NAc) is thought to inhibit cocaine seeking. However, it is not known whether and how IL-NAc neurons contribute to the increased motivation associated with a drug-free period. We first performed cellular resolution imaging of IL-NAc neurons in rats during a drug-seeking test. This revealed neurons with spatial selectivity within the cocaine-associated context, a decrease in activity around the time of cocaine seeking, and an inverse relationship between cocaine-seeking activity and subsequent cocaine motivation. All these properties were reduced by a drug-free period. Next, we transiently activated this projection, which resulted in reduced drug seeking, regardless of the drug-free period. Taken together, this suggests that altered IL-NAc activity after a drug-free period may enhance cocaine motivation without fundamentally altering the projection's ability to inhibit drug seeking.

Distortion product otoacoustic emissions (DPOAEs) evoked by two pure tones carry information about the mechanisms that generate and shape them. Thus, DPOAEs hold promise for providing powerful noninvasive diagnostic details of cochlear operations, middle ear (ME) transmission, and impairments. DPOAEs are sensitive to ME function because they are influenced by ME transmission twice, i.e., by the inward-going primary tones in the forward direction and the outward traveling DPOAEs in the reverse direction. However, the effects of ME injuries on DPOAEs have not been systematically characterized. The current study focused on exploring the utility of DPOAEs for examining ME function by methodically characterizing DPOAEs and ME transmission under pathological ME conditions, specifically under conditions of tympanic-membrane (TM) perforation and spontaneous healing. Results indicated that DPOAEs were measurable with TM perforations up to ∼50%, and DPOAE reductions increased with increasing size of the TM perforation. DPOAE reductions were approximately flat across test frequencies when the TM was perforated about 10% (<1/8 of pars tensa) or less. However, with perforations greater than 10%, DPOAEs decreased further with a low-pass filter shape, with ∼30 dB loss at frequencies below 10 kHz and a quick downward sloping pattern at higher frequencies. The reduction pattern of DPOAEs across frequencies was similar to but much greater than, the directly measured ME pressure gain in the forward direction, which suggested that reduction in the DPOAE was a summation of losses of ME ear transmission in both the forward and reverse directions. Following 50% TM perforations, DPOAEs recovered over a 4-week spontaneously healing interval, and these recoveries were confirmed by improvements in auditory brainstem response (ABR) thresholds. However, up to 4-week post-perforation, DPOAEs never fully recovered to the levels obtained with normal intact TM, consistent with the incomplete recovery of ABR thresholds and ME transmission, especially at high-frequency regions, which could be explained by an irregularly dense and thickened healed TM. Since TM perforations in patients are commonly caused by either trauma or infection, the present results contribute towards providing insight into understanding ME transmission under pathological conditions as well as promoting the application of DPOAEs in the evaluation and diagnosis of deficits in the ME-transmission system.

Background: As an alternative pathway to air conduction, bone conduction is a multipathway process that transmits sound energy to the inner ear through the skull in general. Based on this mechanism, bone conduction devices (BCDs) have been used widely in the rehabilitation of hearing loss. Although great efforts have been devoted to improving BCDs, drawbacks still exist in most categories of BCDs due to the complicated process of bone conduction. We hypothesized that if a bone conduction transducer was placed on the cochlea to stimulate it directly, the attenuation would be minimized, and the frequency dependency would be different from that of the vibratory response induced by traditional BCDs. This study aimed to explore the feasibility of direct promontory stimulation and to investigate its frequency-response characteristics. Methods: Measurements were conducted in twelve cat ears. To stimulate the promontory directly, the floating mass transducer (FMT) of the Vibrant Soundbridge© (VSB) implant was glued to the promontory coupled with an oval window (OW) coupler. Auditory brainstem response (ABR) and laser Doppler vibrometry (LDV) measurements were used to evaluate the auditory response induced by the FMT. In both measurements, the FMT was driven by direct voltage stimuli. Results: ABR waves could be induced under direct promontory stimulation by the FMT. In the frequency range of 1-12 kHz, the variation in the voltage threshold level were limited to 16 dB SPL with a maximum of 0.2 V at 1 kHz and a minimum of 0.04 V at 10 kHz. In the LDV measurements and the relative motion of the round window membrane (RWM) and the promontory were used to evaluate the cochlear response. The LDV results indicated a weak frequency dependency from 1 to 12 kHz. Conclusion: Different from traditional stimulation via transcranial bone conduction, direct promontory stimulation is a new method in which a small bone conduction transducer stimulates the cochlear shell directly. The current experimental data demonstrate that it is feasible to generate sensations through bone conduction by stimulating the cochlea directly. Furthermore, the cochlear response induced by this type of stimulus in cats was weakly frequency dependent at frequencies ranging from 1 to 12 kHz. This study may provide a basis for the design of new transducers that can perform well over a wide range of frequencies.

Nociceptin and its receptor are widely distributed throughout the brain in regions associated with reward behavior, yet how and when they act is unknown. Here, we dissected the role of a nociceptin peptide circuit in reward seeking. We generated a prepronociceptin (Pnoc)-Cre mouse line that revealed a unique subpopulation of paranigral ventral tegmental area (pnVTA) neurons enriched in prepronociceptin. Fiber photometry recordings during progressive ratio operant behavior revealed pnVTAPnoc neurons become most active when mice stop seeking natural rewards. Selective pnVTAPnoc neuron ablation, inhibition, and conditional VTA nociceptin receptor (NOPR) deletion increased operant responding, revealing that the pnVTAPnoc nucleus and VTA NOPR signaling are necessary for regulating reward motivation. Additionally, optogenetic and chemogenetic activation of this pnVTAPnoc nucleus caused avoidance and decreased motivation for rewards. These findings provide insight into neuromodulatory circuits that regulate motivated behaviors through identification of a previously unknown neuropeptide-containing pnVTA nucleus that limits motivation for rewards.

When two voices compete, listeners can segregate and identify concurrent speech sounds using pitch (fundamental frequency, F0) and timbre (harmonic) cues. Speech perception is also hindered by the signal-to-noise ratio (SNR). How clear and degraded concurrent speech sounds are represented at early, pre-attentive stages of the auditory system is not well understood. To this end, we measured scalp-recorded frequency-following responses (FFR) from the EEG while human listeners heard two concurrently presented, steady-state (time-invariant) vowels whose F0 differed by zero or four semitones (ST) presented diotically in either clean (no noise) or noise-degraded (+5dB SNR) conditions. Listeners also performed a speeded double vowel identification task in which they were required to identify both vowels correctly. Behavioral results showed that speech identification accuracy increased with F0 differences between vowels, and this perceptual F0 benefit was larger for clean compared to noise degraded (+5dB SNR) stimuli. Neurophysiological data demonstrated more robust FFR F0 amplitudes for single compared to double vowels and considerably weaker responses in noise. F0 amplitudes showed speech-on-speech masking effects, along with a non-linear constructive interference at 0ST, and suppression effects at 4ST. Correlations showed that FFR F0 amplitudes failed to predict listeners' identification accuracy. In contrast, FFR F1 amplitudes were associated with faster reaction times, although this correlation was limited to noise conditions. The limited number of brain-behavior associations suggests subcortical activity mainly reflects exogenous processing rather than perceptual correlates of concurrent speech perception. Collectively, our results demonstrate that FFRs reflect pre-attentive coding of concurrent auditory stimuli that only weakly predict the success of identifying concurrent speech.

Since most dominant human mutations are single nucleotide substitutions1,2, we explored gene editing strategies to disrupt dominant mutations efficiently and selectively without affecting wild-type alleles. However, single nucleotide discrimination can be difficult to achieve3 because commonly used endonucleases, such as Streptococcus pyogenes Cas9 (SpCas9), can tolerate up to seven mismatches between guide RNA (gRNA) and target DNA. Furthermore, the protospacer-adjacent motif (PAM) in some Cas9 enzymes can tolerate mismatches with the target DNA3,4. To circumvent these limitations, we screened 14 Cas9/gRNA combinations for specific and efficient disruption of a nucleotide substitution that causes the dominant progressive hearing loss, DFNA36. As a model for DFNA36, we used Beethoven mice5, which harbor a point mutation in Tmc1, a gene required for hearing that encodes a pore-forming subunit of mechanosensory transduction channels in inner-ear hair cells6. We identified a PAM variant of Staphylococcus aureus Cas9 (SaCas9-KKH) that selectively and efficiently disrupted the mutant allele, but not the wild-type Tmc1/TMC1 allele, in Beethoven mice and in a DFNA36 human cell line. Adeno-associated virus (AAV)-mediated SaCas9-KKH delivery prevented deafness in Beethoven mice up to one year post injection. Analysis of current ClinVar entries revealed that ~21% of dominant human mutations could be targeted using a similar approach.

Glibenclamide (GBC) improves cerebral outcome after cardiac arrest (CA) in rats. We aim to investigate the effect of GBC on electrophysiological recovery and to explore the mechanism of neuroprotective effects of GBC on the acute stage of brain injury after the return of spontaneous circulation (ROSC) in a rodent model of CA. 16 anesthetized male Wistar rats subjected to 8-min asphyxia-CA were randomly assigned to the GBC or control group (N=8 each group). GBC was administered with a loading dose of 10ug/kg i. p. injection 10 min after ROSC and followed with a maintaining dose of 1.6ug/kg per 8 hours throughout the first 24 hours. Quantitative measures of EEG-information quantity (qEEG-IQ) and neurological deficit score (NDS) were used to predict and evaluate the functional outcome. There was a significant improvement of NDS in rats treated with GBC compared with the control group (p <; 0.01). Compared to the control group, the rats treated with GBC showed qEEG-IQ scores that indicated better recovery (p <; 0.001). Meanwhile, early QEEG-IQ was significantly correlated with 72-hr NDS as early as 45min after ROSC. Furthermore, on the molecular basis, the NLRP3 inflammasome was strongly activated in the hippocampal CA1 area 3 days after CA in control rats, which was suppressed with GBC treatment. Taken together, GBC treatment markedly improved electrophysiological and neurologic outcomes of the acute brain injury after CA. These neuroprotective effects may be associated with the attenuation of inflammatory response via down-regulation of NLRP3 inflammasome signal.

Cardiac arrest (CA) is a serious disease with high rates of mortality and disability worldwide. Currently, neither pharmacological intervention nor therapeutic hypothermia can reverse the neural injury caused by CA. Neural stem cell therapy is a promising treatment for brain injury. We investigated the effects of the intracerebroventricular (ICV) administration of human neural stem cells (hNSCs) on global brain ischemia injury after CA. Twelve Long-Evans rats (4 Male and 8 female) subjected to 8-min asphyxia-CA were randomly assigned to hNSC treatment (n=7) or control group (n=5). The hNSCs were slowly infused into the left lateral ventricular 3 hours after resuscitation. An additional two rats subjected to 8-min asphyxia-CA were euthanized at 4 weeks after resuscitation to confirm the survival and function of transplanted PKH26 pre-labeled hNSCs by brain slides and whole cell patch clamp. Electrophysiological monitoring, quantitative EEG value (qEEG-IQ) and neurological deficit score (NDS) were used to evaluate the functional outcome. Immunofluorescence staining was used to investigate the survival of neurons and track migration of hNSCs. There was a significant improvement on the behavior tests evaluated as a subgroup of NDS (p <; 0.05) in the NSCs group than the control group. Immunofluorescent co-staining of PKH26 and NeuN verified the neuronal differentiation from transplanted PKH26+ hNSCs in the hippocampus CA1 and cortex 4 weeks after CA. The whole-cell patch clamp technique confirmed the spontaneous firing activity that was recorded in cell-attached mode from the functional mature neurons derived from transplanted cells. Transplanted hNSCs via ICV administration markedly improved neurologic outcomes after CA. Further studies are needed to elucidate the neuroprotective mechanism.

Stimulation of the cortex can modulate the connectivity between brain regions. Although targeted neuroplasticity has been demonstrated in-vitro, in-vivo models have been inconsistent in their response to stimulation. In this paper, we tested various stimulation protocols to characterize the effect of stimulation on coherence in the non-human primate cortex in-vivo. We found that the stimulation latency, the state of the cortex during stimulation, and the stimulation site all affected the modulation of cortical coherence. We further investigated features of a resting-state network that could predict how a connection is likely to change with stimulation.

Hypothesis: Use of micro-mechanical control during cochlear implant (CI) electrode insertion will result in reduced number and magnitude of pressure transients when compared with standard insertion by hand. Introduction: With increasing focus on hearing preservation during CI surgery, atraumatic electrode insertion is of the utmost importance. It has been established that large intracochlear pressure spikes can be generated during the insertion of implant electrodes. Here, we examine the effect of using a micro-mechanical insertion control tool on pressure trauma exposures during implantation. Methods: Human cadaveric heads were surgically prepared with an extended facial recess. Electrodes from three manufacturers were placed both by using a micro-mechanical control tool and by hand. Insertions were performed at three different rates: 0.2 mm/s, 1.2 mm/s, and 2 mm/s (n = 20 each). Fiber-optic sensors measured pressures in scala vestibuli and tympani. Results: Electrode insertion produced pressure transients up to 174 dB SPL. ANOVA revealed that pressures were significantly lower when using the micro-mechanical control device compared with insertion by hand ( p << 0.001). No difference was noted across electrode type or speed. Chi-square analysis showed a significantly lower proportion of insertions contained pressure spikes when the control system was used ( p << 0.001). Conclusion: Results confirm previous data that suggest CI electrode insertion can cause pressure transients with intensities similar to those elicited by high-level sounds. Results suggest that the use of a micro-mechanical insertion control system may mitigate trauma from pressure events, both by reducing the amplitude and the number of pressure spikes resulting from CI electrode insertion.

Local field potential (LFP) oscillations are primarily shaped by the superposition of postsynaptic currents. Hippocampal LFP oscillations in the 25- to 50-Hz range (“slow γ”) are proposed to support memory retrieval independent of other frequencies. However, θ harmonics extend up to 48 Hz, necessitating a study to determine whether these oscillations are fundamentally the same. We compared the spectral analysis methods of wavelet, ensemble empirical-mode decomposition (EEMD), and Fourier transform. EEMD, as previously applied, failed to account for the θ harmonics. Depending on analytical parameters selected, wavelet may convolve over high-order θ harmonics due to the variable time-frequency atoms, creating the appearance of a broad 25- to 50-Hz rhythm. As an illustration of this issue, wavelet and EEMD depicted slow γ in a synthetic dataset that only contained θ and its harmonics. Oscillatory transience cannot explain the difference in approaches as Fourier decomposition identifies ripples triggered to epochs of high-power, 120- to 250-Hz events. When Fourier is applied to high power, 25- to 50-Hz events, only θ harmonics are resolved. This analysis challenges the identification of the slow γ rhythm as a unique fundamental hippocampal oscillation. While there may be instances in which slow γ is present in the rat hippocampus, the analysis presented here shows that unless care is exerted in the application of EEMD and wavelet techniques, the results may be misleading, in this case misrepresenting θ harmonics. Moreover, it is necessary to reconsider the characteristics that define a fundamental hippocampal oscillation as well as theories based on multiple independent γ bands.

Many forms of behavior require selective amplification of neuronal representations of relevant environmental signals. Emotional learning enhances sensory responses in the sensory cortex, yet the underlying circuits remain poorly understood. We identify a pathway between the basolateral amygdala (BLA), an emotional learning center in the mouse brain, and the inhibitory reticular nucleus of the thalamus (TRN). Optogenetic activation of BLA suppressed spontaneous, but not tone-evoked, activity in the auditory cortex (AC), amplifying tone-evoked responses. Viral tracing identified BLA projections terminating at TRN. Optogenetic activation of amygdala-TRN projections further amplified tone-evoked responses in the auditory thalamus and cortex. The results are explained by a computational model of the thalamocortical circuitry, in which activation of TRN by BLA primes thalamocortical neurons to relay relevant sensory input. This circuit mechanism shines a neural spotlight on behaviorally relevant signals and provides a potential target for the treatment of neuropsychological disorders.

Background: Middle ear (intratympanic, IT) administration is a promising therapeutic method as it offers the possibility of achieving high inner ear drug concentrations with low systemic levels, thus minimizing the risk of systemic side effects and drug-drug interactions. Premature elimination through the Eustachian tube may be reduced by stabilizing drug solutions with a hydrogel, but this raises the secondary issue of conductive hearing loss. Aim: This study aimed to investigate the properties of a chitosan-based particulate hydrogel formulation when used as a drug carrier for IT administration in an in vivo model of ototoxicity. Materials and methods: Two particulate chitosan-based IT delivery systems, Thio-25 and Thio-40, were investigated in albino guinea pigs (n = 94). Both contained the hearing protecting drug candidate sodium thiosulfate with different concentrations of chitosan gel particles (25% vs. 40%). The safety of the two systems was explored in vivo. The most promising system was then tested in guinea pigs subjected to a single intravenous injection with the anticancer drug cisplatin (8 mg/kg b.w.), which has ototoxic side effects. Hearing status was evaluated with acoustically evoked frequency-specific auditory brainstem response (ABR) and hair cell counting. Finally, in vivo magnetic resonance imaging was used to study the distribution and elimination of the chitosan-based system from the middle ear cavity in comparison to a hyaluronan-based system. Results: Both chitosan-based IT delivery systems caused ABR threshold elevations (p < 0.05) that remained after 10 days (p < 0.05) without evidence of hair cell loss, although the elevation induced by Thio-25 was significantly lower than for Thio-40 (p < 0.05). Thio-25 significantly reduced cisplatin-induced ABR threshold elevations (p < 0.05) and outer hair cell loss (p < 0.05). IT injection of the chitosan- and hyaluronan-based systems filled up most of the middle ear space. There were no significant differences between the systems in terms of distribution and elimination. Conclusion: Particulate chitosan is a promising drug carrier for IT administration. Future studies should assess whether the physical properties of this technique allow for a smaller injection volume that would reduce conductive hearing loss.

The left hemisphere’s dominance in processing social communication has been known for over a century, but the mechanisms underlying this lateralized cortical function are poorly understood. Here, we compare the structure, function, and development of each auditory cortex (ACx) in the mouse to look for specializations that may underlie lateralization. Using Fos brain volume imaging, we found greater activation in the left ACx in response to vocalizations, while the right ACx responded more to frequency sweeps. In vivo recordings identified hemispheric differences in spectrotemporal selectivity, reinforcing their functional differences. We then compared the synaptic connectivity within each hemisphere and discovered lateralized circuit-motifs that are hearing experience-dependent. Our results suggest a specialist role for the left ACx, focused on facilitating the detection of specific vocalization features, while the right ACx is a generalist with the ability to integrate spectrotemporal features more broadly.

Gentamicin, one of the most widely used aminoglycoside antibiotics, is known to have toxic effects on the inner ear. Taken up by cochlear hair cells and spiral ganglion neurons (SGNs), gentamicin induces the accumulation of reactive oxygen species (ROS) and initiates apoptosis or programmed cell death, resulting in a permanent and irreversible hearing loss. Since the survival of SGNs is specially required for cochlear implant, new procedures that prevent SGN cell loss are crucial to the success of cochlear implantation. ROS modulates the activity of the mammalian target of rapamycin (mTOR) signaling pathway, which mediates apoptosis or autophagy in cells of different organs. However, whether mTOR signaling plays an essential role in the inner ear and whether it is involved in the ototoxic side effects of gentamicin remain unclear. In the present study, we found that gentamicin induced apoptosis and cell loss of SGNs in vivo and significantly decreased the density of SGN and outgrowth of neurites in cultured SGN explants. The phosphorylation levels of ribosomal S6 kinase and elongation factor 4E binding protein 1, two critical kinases in the mTOR complex 1 (mTORC1) signaling pathway, were modulated by gentamicin application in the cochlea. Meanwhile, rapamycin, a specific inhibitor of mTORC1, was co-applied with gentamicin to verify the role of mTOR signaling. We observed that the density of SGN and outgrowth of neurites were significantly increased by rapamycin treatment. Our finding suggests that mTORC1 is hyperactivated in the gentamicin-induced degeneration of SGNs, and rapamycin promoted SGN survival and outgrowth of neurites.

This study describes sound localization and speech-recognition-in-noise abilities of a cochlear-implant user with electro-acoustic stimulation (EAS) in one ear, and a hearing aid in the contralateral ear. This listener had low-frequency, up to 250 Hz, residual hearing within the normal range in both ears. The objective was to determine how hearing devices affect spatial hearing for an individual with substantial unaided low-frequency residual hearing. Sound-localization performance was assessed for three sounds with different bandpass characteristics: low center frequency (100-400 Hz), mid center frequency (500-1,500 Hz) and high frequency broad-band (500-20,000 Hz) noise. Speech recognition was assessed with the Dutch Matrix sentence test presented in noise. Tests were performed while the listener used several on-off combinations of the devices. The listener localized low-center frequency sounds well in all hearing conditions, but mid-center frequency and high frequency broadband sounds were localized well almost exclusively in the completely unaided condition (mid-center frequency sounds were also localized well with the EAS device alone). Speech recognition was best in the fully aided condition with speech presented in the front and noise presented at either side. Furthermore, there was no significant improvement in speech recognition with all devices on, compared to when the listener used her cochlear implant only. Hearing aids and cochlear implant impair high frequency spatial hearing due to improper weighing of interaural time and level difference cues. The results reinforce the notion that hearing symmetry is important for sound localization. The symmetry is perturbed by the hearing devices for higher frequencies. Speech recognition depends mainly on hearing through the cochlear implant and is not significantly improved with the added information from hearing aids. A contralateral hearing aid provides benefit when the noise is spatially separated from the speech. However, this benefit is explained by the head shadow in that ear, rather than by an ability to spatially segregate noise from speech, as sound localization was perturbed with all devices in use.

TRIOBP remodels the cytoskeleton by forming unusually dense F-actin bundles and is implicated in human cancer, schizophrenia, and deafness. Mutations ablating human and mouse TRIOBP-4 and TRIOBP-5 isoforms are associated with profound deafness, as inner ear mechanosensory hair cells degenerate after stereocilia rootlets fail to develop. However, the mechanisms regulating formation of stereocilia rootlets by each TRIOBP isoform remain unknown. Using 3 new Triobp mouse models, we report that TRIOBP-5 is essential for thickening bundles of F-actin in rootlets, establishing their mature dimensions and for stiffening supporting cells of the auditory sensory epithelium. The coiled-coil domains of this isoform are required for reinforcement and maintenance of stereocilia rootlets. A loss of TRIOBP-5 in mouse results in dysmorphic rootlets that are abnormally thin in the cuticular plate but have increased widths and lengths within stereocilia cores, and causes progressive deafness recapitulating the human phenotype. Our study extends the current understanding of TRIOBP isoform–specific functions necessary for life-long hearing, with implications for insight into other TRIOBPopathies.

Purpose Growing evidence supports the inclusion of perceptual tests that quantify the processing of temporal fine structure (TFS) in clinical hearing assessment. Many tasks have been used to evaluate TFS in the laboratory that vary greatly in the stimuli used and whether the judgments require monaural or binaural comparisons of TFS. The purpose of this study was to compare laboratory measures of TFS for inclusion in a battery of suprathreshold auditory tests. A subset of available TFS tasks were selected on the basis of potential clinical utility and were evaluated using metrics that focus on characteristics important for clinical use. Method TFS measures were implemented in replication of studies that demonstrated clinical utility. Monaural, diotic, and dichotic measures were evaluated in 11 young listeners with normal hearing. Measures included frequency modulation (FM) tasks, harmonic frequency shift detection, interaural phase difference (TFS–low frequency), interaural time difference (ITD), monaural gap duration discrimination, and tone detection in noise with and without a difference in interaural phase (N 0 S 0 , N 0 S π ). Data were compared with published results and evaluated with metrics of consistency and efficiency. Results Thresholds obtained were consistent with published data. There was no evidence of predictive relationships among the measures consistent with a homogenous group. The most stable tasks across repeated testing were TFS–low frequency, diotic and dichotic FM, and N 0 S π . Monaural and diotic FM had the lowest normalized variance and were the most efficient accounting for differences in total test duration, followed by ITD. Conclusions Despite a long stimulus duration, FM tasks dominated comparisons of consistency and efficiency. Small differences separated the dichotic tasks FM, ITD, and N 0 S π . Future comparisons following procedural optimization of the tasks will evaluate clinical efficiency in populations with impairment.