Publications using TDT

Sensory environments change over a wide dynamic range and sensory processing can change rapidly to facilitate stable perception. While rapid changes may occur throughout the sensory processing pathway, cortical changes are believed to profoundly influence perception. Prior stimulation studies showed that orbitofrontal cortex (OFC) can modify receptive fields and sensory coding in A1, but the engagement of OFC during listening and the pathways mediating OFC influences on A1 are unknown. We show in mice that OFC neurons respond to sounds consistent with a role of OFC in audition. We then show in vitro that OFC axons are present in A1 and excite pyramidal and GABAergic cells in all layers of A1 via glutamatergic synapses. Optogenetic stimulation of OFC terminals in A1 in vivo evokes short-latency neural activity in A1 and pairing activation of OFC projections in A1 with sounds alters sound-evoked A1 responses. Together, our results identify a direct connection from OFC to A1 that can excite A1 neurons at the earliest stage of cortical processing, and thereby sculpt A1 receptive fields. These results are consistent with a role for OFC in adjusting to changing behavioral relevance of sensory inputs and modulating A1 receptive fields to enhance sound processing.

Onsets of acoustic stimuli are salient transients and are relevant in humans for the perception of music and speech. Previous studies of onset-duration discrimination and matching focused on whether onsets are perceived categorically. In this study, we address two issues. First, we revisit onset-duration matching and measure, for 79 conditions, how accurately and precisely human listeners can adjust the onset duration of a comparison stimulus to subjectively match that of a standard stimulus. Second, we explore measures for quantifying performance in this and other matching tasks. The conventional measures of accuracy and precision are defined by arithmetic descriptive statistics and the Euclidean distance function on the real numbers. We propose novel measures based on geometric descriptive statistics and the log-ratio distance function, the Euclidean distance function on the positive-real numbers. Only these properly account for the fact that the magnitude of onset durations, like the magnitudes of most physical quantities, can attain only positive real values. The conventional (arithmetic) measures possess a convexity bias that yields errors that grow with the width of the distribution of matches. This convexity bias leads to misrepresentations of the constant error and could even imply the existence of perceptual illusions where none exist. This is not so for the proposed (geometric) measures. We collected up to 68 matches from a given listener for each condition (about 34,000 matches in total) and examined inter-listener variability and the effects of onset duration, plateau duration, sound level, carrier, and restriction of the range of adjustable comparison stimuli on measures of accuracy and precision. Results obtained with the conventional measures generally agree with those reported in the literature. The variance across listeners is highly heterogeneous for the conventional measures but is homogeneous for the proposed measures. Furthermore, the proposed measures show that listeners tend to under- rather than to overestimate the onset duration of the comparison stimuli. They further reveal effects of the stimulus carrier on accuracy and precision which are missed by the conventional measures. Our results have broad implications for psychophysical studies that use arithmetic measures to quantify performance when geometric measures should instead be used.

Anesthesia is known to affect the auditory brainstem response (ABR) in mice, rats, birds and lizards. The present study investigated how the level of anesthesia affects ABR recordings in an amphibian species, Babina daunchina. To do this, we compared ABRs evoked by tone pip stimuli recorded from 35 frogs when Tricaine methane sulphonate (MS-222) anesthetic immersion times varied from 0, 5 and 10 minutes after anesthesia induction at sound frequencies between 0.5 and 6 kHz. ABR thresholds increased significantly with immersion time across the 0.5 kHz to 2.5 kHz frequency range, which is the most sensitive frequency range for hearing and the main frequency range of male calls. There were no significant differences for anesthetic levels across the 3 kHz to 6 kHz range. ABR latency was significantly longer in the 10 min group than in the 0 and 5 min groups at frequencies of 0.5, 1.0, 1.5, 2.5 kHz, while ABR latency did not differ across the 3 kHz to 4 kHz range and at 2.0 kHz. Taken together, these results show that the level of anesthesia affects the amplitude, threshold and latency of ABRs in frogs.

Neuronal activity in early visual cortex depends on attention shifts but the contribution to working memory has remained unclear. Here, we examine neuronal activity in the different layers of the primary visual cortex (V1) in an attention-demanding and a working memory task. A current-source density analysis reveales top-down inputs in the superficial layers and layer 5, and an increase in neuronal firing rates most pronounced in the superficial and deep layers and weaker in input layer 4. This increased activity is strongest in the attention task but it is also highly reliable during working memory delays. A visual mask erases the V1 memory activity, but it reappeares at a later point in time. These results provide new insights in the laminar circuits involved in the top-down modulation of activity in early visual cortex in the presence and absence of visual stimuli.

When hearing knocking on a door, a listener typically identifies both the action (forceful and repeated impacts) and the object (a thick wooden board) causing the sound. The current work studied the neural bases of sound source identification by switching listeners' attention toward these different aspects of a set of simple sounds during functional magnetic resonance imaging scanning: participants either discriminated the action or the material that caused the sounds, or they simply discriminated meaningless scrambled versions of them. Overall, discriminating action and material elicited neural activity in a left-lateralized frontoparietal network found in other studies of sound identification, wherein the inferior frontal sulcus and the ventral premotor cortex were under the control of selective attention and sensitive to task demand. More strikingly, discriminating materials elicited increased activity in cortical regions connecting auditory inputs to semantic, motor, and even visual representations, whereas discriminating actions did not increase activity in any regions. These results indicate that discriminating and identifying material requires deeper processing of the stimuli than discriminating actions. These results are consistent with previous studies suggesting that auditory perception is better suited to comprehend the actions than the objects producing sounds in the listeners' environment.

Cortical entrainment of the auditory cortex to the broadband temporal envelope of a speech signal is crucial for speech comprehension. Entrainment results in phases of high and low neural excitability, which structure and decode the incoming speech signal. Entrainment to speech is strongest in the theta frequency range (4–8 Hz), the average frequency of the speech envelope. If a speech signal is degraded, entrainment to the speech envelope is weaker and speech intelligibility declines. Besides perceptually evoked cortical entrainment, transcranial alternating current stimulation (tACS) entrains neural oscillations by applying an electric signal to the brain. Accordingly, tACS-induced entrainment in auditory cortex has been shown to improve auditory perception. The aim of the current study was to modulate speech intelligibility externally by means of tACS such that the electric current corresponds to the envelope of the presented speech stream (i.e., envelope-tACS). Participants performed the Oldenburg sentence test with sentences presented in noise in combination with envelope-tACS. Critically, tACS was induced at time lags of 0 to 250 ms in 50-ms steps relative to sentence onset (auditory stimuli were simultaneous to or preceded tACS). We performed single-subject sinusoidal, linear, and quadratic fits to the sentence comprehension performance across the time lags. We could show that the sinusoidal fit described the modulation of sentence comprehension best. Importantly, the average frequency of the sinusoidal fit was 5.12 Hz, corresponding to the peaks of the amplitude spectrum of the stimulated envelopes. This finding was supported by a significant 5-Hz peak in the average power spectrum of individual performance time series. Altogether, envelope tACS modulates intelligibility of speech in noise, presumably by enhancing and disrupting (time lag with in-or out-of-phase stimulation, respectively) cortical entrainment to the speech envelope in auditory cortex.

Recent evidence suggests that specific neuronal populations in the ventral temporal cortex show larger electrophysiological responses to visual numerals compared with morphologically similar stimuli. This study investigates how these responses change from simple reading of numerals to the active use of numerals in an arithmetic context. We recorded high-frequency broadband (HFB) signals, a reliable measure for local neuronal population activity, while 10 epilepsy patients implanted with subdural electrodes performed separate numeral reading and calculation tasks. We found that calculation increased activity in the posterior inferior temporal gyrus (ITG) with a factor of approximately 1.5 over the first 500 ms of calculation, whereas no such increase was noted for reading numerals without calculation or reading and judging memory statements. In a second experiment conducted in 2 of the same subjects, we show that HFB responses increase in a systematic manner when the single numerals were presented successively in a calculation context: The HFB response in the ITG, to the second and third numerals (i.e., b and c in a + b = c), was approximately 1.5 times larger than the responses to the first numeral (a). These results provide electrophysiological evidence for modulation of local neuronal population responses to visual stimuli based on increasing task demands.

Amplitude modulation (AM) detection was measured with a short (50 ms), high-frequency carrier as a function of carrier level (Experiment I) and modulation frequency (Experiment II) for conditions with or without a notched-noise precursor. A longer carrier (500 ms) was also included in Experiment I. When the carrier was preceded by silence (no precursor condition) AM detection thresholds worsened for moderate-level carriers compared to lower- or higher-level carriers, resulting in a “mid-level hump.” AM detection thresholds with a precursor were better than those without a precursor, primarily for moderate-to-high level carriers, thus eliminating the mid-level hump in AM detection. When the carrier was 500 ms, AM thresholds improved by a constant (across all levels) relative to AM thresholds with a precursor, consistent with the longer carrier providing more “looks” to detect the AM signal. Experiment II revealed that improved AM detection with compared to without a precursor is limited to low-modulation frequencies (<60 Hz). These results are consistent with (1) a reduction in cochlear gain over the course of the precursor perhaps via the medial olivocochlear reflex or (2) a form of perceptual enhancement which may be mediated by adaptation of inhibition.

In many situations, listeners with sensorineural hearing loss demonstrate reduced spatial release from masking compared to listeners with normal hearing. This deficit is particularly evident in the “symmetric masker” paradigm in which competing talkers are located to either side of a central target talker. However, there is some evidence that reduced target audibility (rather than a spatial deficit per se) under conditions of spatial separation may contribute to the observed deficit. In this study a simple “glimpsing” model (applied separately to each ear) was used to isolate the target information that is potentially available in binaural speech mixtures. Intelligibility of these glimpsed stimuli was then measured directly. Differences between normally hearing and hearing-impaired listeners observed in the natural binaural condition persisted for the glimpsed condition, despite the fact that the task no longer required segregation or spatial processing. This result is consistent with the idea that the performance of listeners with hearing loss in the spatialized mixture was limited by their ability to identify the target speech based on sparse glimpses, possibly as a result of some of those glimpses being inaudible.

In contrast to static sounds, spatially dynamic sounds have received little attention in psychoacoustic research so far. This holds true especially for acoustically complex (reverberant, multisource) conditions and impaired hearing. The current study therefore investigated the influence of reverberation and the number of concurrent sound sources on source movement detection in young normal-hearing (YNH) and elderly hearing-impaired (EHI) listeners. A listening environment based on natural environmental sounds was simulated using virtual acoustics and rendered over headphones. Both near-far (‘radial’) and left-right (‘angular’) movements of a frontal target source were considered. The acoustic complexity was varied by adding static lateral distractor sound sources as well as reverberation. Acoustic analyses confirmed the expected changes in stimulus features that are thought to underlie radial and angular source movements under anechoic conditions and suggested a special role of monaural spectral changes under reverberant conditions. Analyses of the detection thresholds showed that, with the exception of the single-source scenarios, the EHI group was less sensitive to source movements than the YNH group, despite adequate stimulus audibility. Adding static sound sources clearly impaired the detectability of angular source movements for the EHI (but not the YNH) group. Reverberation, on the other hand, clearly impaired radial source movement detection for the EHI (but not the YNH) listeners. These results illustrate the feasibility of studying factors related to auditory movement perception with the help of the developed test setup.

The purpose of this study was to test the hypothesis that listeners with frequent exposure to loud music exhibit deficits in suprathreshold auditory performance consistent with cochlear synaptopathy. Young adults with normal audiograms were recruited who either did ( n = 31) or did not ( n = 30) have a history of frequent attendance at loud music venues where the typical sound levels could be expected to result in temporary threshold shifts. A test battery was administered that comprised three sets of procedures: (a) electrophysiological tests including distortion product otoacoustic emissions, auditory brainstem responses, envelope following responses, and the acoustic change complex evoked by an interaural phase inversion; (b) psychoacoustic tests including temporal modulation detection, spectral modulation detection, and sensitivity to interaural phase; and (c) speech tests including filtered phoneme recognition and speech-in-noise recognition. The results demonstrated that a history of loud music exposure can lead to a profile of peripheral auditory function that is consistent with an interpretation of cochlear synaptopathy in humans, namely, modestly abnormal auditory brainstem response Wave I/Wave V ratios in the presence of normal distortion product otoacoustic emissions and normal audiometric thresholds. However, there were no other electrophysiological, psychophysical, or speech perception effects. The absence of any behavioral effects in suprathreshold sound processing indicated that, even if cochlear synaptopathy is a valid pathophysiological condition in humans, its perceptual sequelae are either too diffuse or too inconsequential to permit a simple differential diagnosis of hidden hearing loss.

Objective: There is currently no accepted method of mapping bilateral cochlear-implant (BiCI) users to maximize binaural performance, but the current approach of mapping one ear at a time could produce spatial perceptions that are not consistent with a sound’s physical location in space. The goal of this study was to investigate the perceived intracranial lateralization of bilaterally synchronized electrical stimulation with a range of interaural level differences (ILDs) and to determine a method to produce relatively more centered auditory images when provided multielectrode stimulation. Design: Using direct stimulation, lateralization curves were measured in nine BiCI listeners using 1000-pulses per second (pps), 500-msec constant-amplitude pulse trains with ILDs that ranged from −20 to +20 clinical current units (CUs). The stimuli were presented bilaterally at 70 to 80% of the dynamic range on single or multiple electrode pairs. For the multielectrode pairs, the ILD was applied consistently across all the pairs. The lateralization response range and the bias magnitude at 0 CU ILD (i.e., the number of CUs needed to produce a centered auditory image) were computed. Then the levels that elicit a centered auditory image with single-electrode stimulation were used with multielectrode stimulation to determine if this produced fewer significant biases at 0 CU ILD. Lastly, a multichannel ILD processing model was used to predict lateralization for the multielectrode stimulation from the single-electrode stimulation. Results: BiCI listeners often perceived both single- and multielectrode stimulation at 0-CU ILD as not intracranially centered. For single-electrode stimulation, 44% of the lateralization curves had relatively large (≥5 CU) bias magnitudes. For the multielectrode stimulation, 25% of the lateralization curves had large bias magnitudes. After centering the single-electrode pairs, the percentage of multielectrode combinations that produced large biases significantly decreased to only 4% ( p < 0.001, McNemar’s test). The lateralization with multielectrode stimulation was well predicted by a model that used unweighted or weighted average single-electrode lateralization percepts across electrode pairs (87 or 90%, respectively). Conclusion: Current BiCI mapping procedures can produce an inconsistent association between a physical ILD and the perceived location across electrodes for both single- and multielectrode stimulation. Explicit centering of single-electrode pairs using the perceived centered intracranial location almost entirely corrects this problem and such an approach is supported by our understanding and model of across-frequency ILD processing. Such adjustments might be achieved by clinicians using single-electrode binaural comparisons. Binaural abilities, like sound localization and understanding speech in noise, may be improved if these across-electrode perceptual inconsistencies are removed.

Sensory stimulation drives complex interactions across neural circuits as information is encoded and then transmitted from one brain region to the next. In the highly interconnected thalamocortical circuit, these complex interactions elicit repeatable neural dynamics in response to temporal patterns of stimuli that provide insight into the circuit properties that generated them. Here, using a combination of in vivo voltage-sensitive dye (VSD) imaging of cortex, single-unit recording in thalamus, and optogenetics to manipulate thalamic state in the rodent vibrissa pathway, we probed the thalamocortical circuit with simple temporal patterns of stimuli delivered either to the whiskers on the face (sensory stimulation) or to the thalamus directly via electrical or optogenetic inputs (artificial stimulation). VSD imaging of cortex in response to whisker stimulation revealed classical suppressive dynamics, while artificial stimulation of thalamus produced an additional facilitation dynamic in cortex not observed with sensory stimulation. Thalamic neurons showed enhanced bursting activity in response to artificial stimulation, suggesting that bursting dynamics may underlie the facilitation mechanism we observed in cortex. To test this experimentally, we directly depolarized the thalamus, using optogenetic modulation of the firing activity to shift from a burst to a tonic mode. In the optogenetically depolarized thalamic state, the cortical facilitation dynamic was completely abolished. Together, the results obtained here from simple probes suggest that thalamic state, and ultimately thalamic bursting, may play a key role in shaping more complex stimulus-evoked dynamics in the thalamocortical pathway. NEW & NOTEWORTHY For the first time, we have been able to utilize optogenetic modulation of thalamic firing modes combined with optical imaging of cortex in the rat vibrissa system to directly test the role of thalamic state in shaping cortical response properties.

OBJECTIVE Contemporary theories of the pathophysiology of movement disorders emphasize abnormal oscillatory activity in basal ganglia-thalamocortical loops, but these have been studied in humans mainly using depth recordings. Recording from the surface of the cortex using electrocorticography (ECoG) provides a much higher amplitude signal than depth recordings, is less susceptible to deep brain stimulation (DBS) artifacts, and yields a surrogate measure of population spiking via “broadband gamma” (50–200 Hz) activity. Therefore, a technical approach to movement disorders surgery was developed that employs intraoperative ECoG as a research tool. METHODS One hundred eighty-eight patients undergoing DBS for the treatment of movement disorders were studied under an institutional review board–approved protocol. Through the standard bur hole exposure that is clinically indicated for DBS lead insertion, a strip electrode (6 or 28 contacts) was inserted to cover the primary motor or prefrontal cortical areas. Localization was confirmed by the reversal of the somatosensory evoked potential and intraoperative CT or 2D fluoroscopy. The ECoG potentials were recorded at rest and during a variety of tasks and analyzed offline in the frequency domain, focusing on activity between 3 and 200 Hz. Strips were removed prior to closure. Postoperative MRI was inspected for edema, signal change, or hematoma that could be related to the placement of the ECoG strip. RESULTS One hundred ninety-eight (99%) strips were successfully placed. Two ECoG placements were aborted due to resistance during the attempted passage of the electrode. Perioperative surgical complications occurred in 8 patients, including 5 hardware infections, 1 delayed chronic subdural hematoma requiring evacuation, 1 intraparenchymal hematoma, and 1 venous infarction distant from the site of the recording. None of these appeared to be directly related to the use of ECoG. CONCLUSIONS Intraoperative ECoG has long been used in neurosurgery for functional mapping and localization of seizure foci. As applied during DBS surgery, it has become an important research tool for understanding the brain networks in movement disorders and the mechanisms of therapeutic stimulation. In experienced hands, the technique appears to add minimal risk to surgery.