scholarly journals Deconstructing the Cortical Sources of Frequency Following Responses to Speech: A Cross-species Approach

2021 ◽  
Author(s):  
G. Nike Gnanteja ◽  
Kyle Rupp ◽  
Fernando Llanos ◽  
Madison Remick ◽  
Marianny Pernia ◽  
...  
Keyword(s):  
Animal Models ◽  
Auditory Cortex ◽  
Human Subjects ◽  
Auditory Pathway ◽  
Time Varying ◽  
Volume Conduction ◽  
Cortical Sources ◽  
Neural Ensembles ◽  
Processing Of Speech Signals ◽  
Time Varying Pitch

Time-varying pitch is a vital cue in the processing of speech signals. Neural processing of time-varying pitch cues in speech has been extensively assayed using scalp-recorded frequency-following responses (FFRs), which are thought to reflect integrated phase-locked activity from neural ensembles exclusively along the subcortical auditory pathway. Emerging evidence however suggests that the auditory cortex contributes to the FFRs as well. However, the response properties and the relative cortical contribution to the scalp-recorded FFR are only beginning to be explored. Here we used direct intracortical recordings from human subjects and animal models (macaque, guinea pig) to deconstruct the cortical sources of FFRs and leveraged representational similarity analysis as a translational bridge to characterize similarities between the human and animal models. We found robust FFRs in the auditory cortex that emerged from the thalamorecepient layers of the auditory cortex and contributed to the scalp-recorded FFRs via volume conduction.

Neural Mechanisms of Music and Language

2019 ◽  
pp. 906-952
Author(s):  
Mattson Ogg ◽  
L. Robert Slevc
Keyword(s):  
Auditory Cortex ◽  
Language Processing ◽  
Auditory Processing ◽  
Cortical Plasticity ◽  
Speaker Identification ◽  
Auditory Pathway ◽  
Cognitive Mechanisms ◽  
Cross Domain ◽  
Music And Language ◽  
Cortical Regions

Music and language are uniquely human forms of communication. What neural structures facilitate these abilities? This chapter conducts a review of music and language processing that follows these acoustic signals as they ascend the auditory pathway from the brainstem to auditory cortex and on to more specialized cortical regions. Acoustic, neural, and cognitive mechanisms are identified where processing demands from both domains might overlap, with an eye to examples of experience-dependent cortical plasticity, which are taken as strong evidence for common neural substrates. Following an introduction describing how understanding musical processing informs linguistic or auditory processing more generally, findings regarding the major components (and parallels) of music and language research are reviewed: pitch perception, syntax and harmonic structural processing, semantics, timbre and speaker identification, attending in auditory scenes, and rhythm. Overall, the strongest evidence that currently exists for neural overlap (and cross-domain, experience-dependent plasticity) is in the brainstem, followed by auditory cortex, with evidence and the potential for overlap becoming less apparent as the mechanisms involved in music and speech perception become more specialized and distinct at higher levels of processing.

scholarly journals Nutritional programming of gastrointestinal tract development. Is the pig a good model for man?

2010 ◽  
Vol 23 (1) ◽  
pp. 4-22 ◽  
Author(s):  
Paul Guilloteau ◽  
Romuald Zabielski ◽  
Harald M. Hammon ◽  
Cornelia C. Metges
Keyword(s):  
Gastrointestinal Tract ◽  
Animal Models ◽  
Animal Studies ◽  
Reference Model ◽  
Human Subjects ◽  
Mammalian Species ◽  
Epidemiological Studies ◽  
Long Term Effects ◽  
Nutritional Programming ◽  
The Impact

The consequences of early-life nutritional programming in man and other mammalian species have been studied chiefly at the metabolic level. Very few studies, if any, have been performed in the gastrointestinal tract (GIT) as the target organ, but extensive GIT studies are needed since the GIT plays a key role in nutrient supply and has an impact on functions of the entire organism. The possible deleterious effects of nutritional programming at the metabolic level were discovered following epidemiological studies in human subjects, and confirmed in animal models. Investigating the impact of programming on GIT structure and function would need appropriate animal models due to ethical restrictions in the use of human subjects. The aim of the present review is to discuss the use of pigs as an animal model as a compromise between ethically acceptable animal studies and the requirement of data which can be interpolated to the human situation. In nutritional programming studies, rodents are the most frequently used model for man, but GIT development and digestive function in rodents are considerably different from those in man. In that aspect, the pig GIT is much closer to the human than that of rodents. The swine species is closely comparable with man in many nutritional and digestive aspects, and thus provides ample opportunity to be used in investigations on the consequences of nutritional programming for the GIT. In particular, the ‘sow–piglets’ dyad could be a useful tool to simulate the ‘human mother–infant’ dyad in studies which examine short-, middle- and long-term effects and is suggested as the reference model.

scholarly journals Spatial Sensitivity in Field PAF of Cat Auditory Cortex

2003 ◽  
Vol 89 (6) ◽  
pp. 2889-2903 ◽  
Author(s):  
G. Christopher Stecker ◽  
Brian J. Mickey ◽  
Ewan A. Macpherson ◽  
John C. Middlebrooks
Keyword(s):  
Auditory Cortex ◽  
Primary Auditory Cortex ◽  
Median Plane ◽  
Stimulus Location ◽  
Population Coding ◽  
Broadband Noise ◽  
Spatial Sensitivity ◽  
Neural Ensembles ◽  
Artificial Neural Network Ann ◽  
Spike Patterns

We compared the spatial tuning properties of neurons in two fields [primary auditory cortex (A1) and posterior auditory field (PAF)] of cat auditory cortex. Broadband noise bursts of 80-ms duration were presented from loudspeakers throughout 360° in the horizontal plane (azimuth) or 260° in the vertical median plane (elevation). Sound levels varied from 20 to 40 dB above units' thresholds. We recorded neural spike activity simultaneously from 16 sites in field PAF and/or A1 of α-chloralose-anesthetized cats. We assessed spatial sensitivity by examining the dependence of spike count and response latency on stimulus location. In addition, we used an artificial neural network (ANN) to assess the information about stimulus location carried by spike patterns of single units and of ensembles of 2–32 units. The results indicate increased spatial sensitivity, more uniform distributions of preferred locations, and greater tolerance to changes in stimulus intensity among PAF units relative to A1 units. Compared to A1 units, PAF units responded at significantly longer latencies, and latencies varied more strongly with stimulus location. ANN analysis revealed significantly greater information transmission by spike patterns of PAF than A1 units, primarily reflecting the information transmitted by latency variation in PAF. Finally, information rates grew more rapidly with the number of units included in neural ensembles for PAF than A1. The latter finding suggests more accurate population coding of space in PAF, made possible by a more diverse population of neural response types.

Temporal and rate representations of time-varying signals in the auditory cortex of awake primates

10.1038/nn737 ◽  
2001 ◽  
Vol 4 (11) ◽  
pp. 1131-1138 ◽  
Author(s):  
Thomas Lu ◽  
Li Liang ◽  
Xiaoqin Wang
Keyword(s):  
Auditory Cortex ◽  
Time Varying

scholarly journals Cortical Representations of Speech in a Multi-talker Auditory Scene

2017 ◽  
Author(s):  
Krishna C. Puvvada ◽  
Jonathan Z. Simon
Keyword(s):  
Auditory Cortex ◽  
Human Subjects ◽  
Higher Order ◽  
Neural Representation ◽  
Cortical Areas ◽  
Auditory Scene ◽  
Global Representation ◽  
Stimulus Reconstruction ◽  
Background Object ◽  
Cortical Representations

AbstractThe ability to parse a complex auditory scene into perceptual objects is facilitated by a hierarchical auditory system. Successive stages in the hierarchy transform an auditory scene of multiple overlapping sources, from peripheral tonotopically-based representations in the auditory nerve, into perceptually distinct auditory-objects based representation in auditory cortex. Here, using magnetoencephalography (MEG) recordings from human subjects, both men and women, we investigate how a complex acoustic scene consisting of multiple speech sources is represented in distinct hierarchical stages of auditory cortex. Using systems-theoretic methods of stimulus reconstruction, we show that the primary-like areas in auditory cortex contain dominantly spectro-temporal based representations of the entire auditory scene. Here, both attended and ignored speech streams are represented with almost equal fidelity, and a global representation of the full auditory scene with all its streams is a better candidate neural representation than that of individual streams being represented separately. In contrast, we also show that higher order auditory cortical areas represent the attended stream separately, and with significantly higher fidelity, than unattended streams. Furthermore, the unattended background streams are more faithfully represented as a single unsegregated background object rather than as separated objects. Taken together, these findings demonstrate the progression of the representations and processing of a complex acoustic scene up through the hierarchy of human auditory cortex.Significance StatementUsing magnetoencephalography (MEG) recordings from human listeners in a simulated cocktail party environment, we investigate how a complex acoustic scene consisting of multiple speech sources is represented in separate hierarchical stages of auditory cortex. We show that the primary-like areas in auditory cortex use a dominantly spectro-temporal based representation of the entire auditory scene, with both attended and ignored speech streams represented with almost equal fidelity. In contrast, we show that higher order auditory cortical areas represent an attended speech stream separately from, and with significantly higher fidelity than, unattended speech streams. Furthermore, the unattended background streams are represented as a single undivided background object rather than as distinct background objects.

scholarly journals Wireless, battery-free optoelectronic systems as subdermal implants for local tissue oximetry

2019 ◽  
Vol 5 (3) ◽  
pp. eaaw0873 ◽  
Author(s):  
Hao Zhang ◽  
Philipp Gutruf ◽  
Kathleen Meacham ◽  
Michael C. Montana ◽  
Xingyue Zhao ◽  
...  
Keyword(s):  
Animal Models ◽  
Tissue Oxygenation ◽  
Human Subjects ◽  
Brain Regions ◽  
Disease States ◽  
Data Output ◽  
Subdermal Implants ◽  
Underlying Mechanisms ◽  
Tissue Oximetry

Monitoring regional tissue oxygenation in animal models and potentially in human subjects can yield insights into the underlying mechanisms of local O2-mediated physiological processes and provide diagnostic and therapeutic guidance for relevant disease states. Existing technologies for tissue oxygenation assessments involve some combination of disadvantages in requirements for physical tethers, anesthetics, and special apparatus, often with confounding effects on the natural behaviors of test subjects. This work introduces an entirely wireless and fully implantable platform incorporating (i) microscale optoelectronics for continuous sensing of local hemoglobin dynamics and (ii) advanced designs in continuous, wireless power delivery and data output for tether-free operation. These features support in vivo, highly localized tissue oximetry at sites of interest, including deep brain regions of mice, on untethered, awake animal models. The results create many opportunities for studying various O2-mediated processes in naturally behaving subjects, with implications in biomedical research and clinical practice.

scholarly journals Translational Development Strategies for TAK-063, a Phosphodiesterase 10A Inhibitor

2020 ◽  
Vol 23 (8) ◽  
pp. 524-532
Author(s):  
Thomas A Macek ◽  
Kazunori Suzuki ◽  
Karen Asin ◽  
Haruhide Kimura
Keyword(s):  
Animal Models ◽  
Healthy Subjects ◽  
Human Subjects ◽  
Phase 1 ◽  
Clinical Manifestations ◽  
Receptor Activation ◽  
Guanosine Monophosphate ◽  
Antipsychotic Activity ◽  
Dose Study ◽  
Phosphodiesterase 10A

Abstract Background TAK-063 is an inhibitor of phosphodiesterase 10A (PDE10A), an enzyme highly expressed in medium spiny neurons of the striatum. PDE10A hydrolyzes both cyclic adenosine monophosphate and cyclic guanosine monophosphate and modulates dopamine signaling downstream of receptor activation in both direct and indirect pathways of the striatum. TAK-063 exhibited antipsychotic-like effects in animal models; however, the translatability of these models to the clinical manifestations of schizophrenia and the meaningfulness for new targets such as PDE10A has not been established. Methods The TAK-063 phase 1 program included a comprehensive translational development strategy with the main objective of determining whether the antipsychotic-like pharmacodynamic effects seen in nonclinical models would translate to human subjects. To evaluate this objective, we conducted a single-rising dose study (84 healthy subjects), a positron emission tomography (PET) study (12 healthy subjects), a functional magnetic resonance imaging blood oxygen level-dependent (BOLD) study (27 healthy subjects), and a multiple-rising dose study that included people with schizophrenia (30 healthy Japanese subjects and 47 subjects with stable schizophrenia). In addition, assessments of cognition and electroencephalography (27 healthy subjects and 47 subjects with stable schizophrenia) were included. Results PDE10A engagement by TAK-063 was verified with a novel PET radiotracer for use in primates and humans. TAK-063 showed favorable pharmacokinetic and safety profiles in humans, and TAK-063 reduced ketamine-induced changes in electroencephalography and BOLD signaling in animal models and healthy human subjects. In addition, analogous effects on cognition were observed in animal models and human subjects. Conclusions Overall, the phase 1 results showed some consistent evidence of antipsychotic activity. This translational strategy may be valuable for the future development of novel therapeutic approaches, even when relevant nonclinical models are not available.

Relative Bioavailabilities of Natural and Synthetic Vitamin E Formulations Containing Mixed Tocopherols in Human Subjects

1999 ◽  
Vol 69 (2) ◽  
pp. 92-95 ◽  
Author(s):  
Chopra ◽  
Bhagavan
Keyword(s):  
Vitamin E ◽  
Animal Models ◽  
Human Subjects ◽  
Alpha Tocopherol ◽  
Tocopheryl Acetate ◽  
Normal Male ◽  
Gamma Tocopherol ◽  
Synthetic Vitamin ◽  
Male Subjects ◽  
Natural And Synthetic

There are several reports in the literature on the relative bioavailabilities of RRR (natural) vs. all-rac (synthetic) forms of vitamin E in humans and animal models but none on the bioavailability of alpha-tocopherol in mixed vitamin E formulations. In the present study we examined the bioavailability of alpha-tocopherol in a typical commercially available product containing mixed tocopherols. We also tested a formulation containing all-rac-alpha-tocopherol with mixed tocopherols for purposes of comparison along with straight RRR-and all-rac-alpha-tocopheryl acetate as reference products. Normal male subjects were given one of the four formulations of vitamin E (800 IU per day in softgel capsule form for 10 days): 1. All-rac-alpha-tocopheryl acetate, 2. RRR-alpha-tocopheryl acetate, 3. RRR-alpha-tocopherol with mixed tocopherols, and 4. all-rac-alpha-tocopherol with mixed tocopherols. Both serum alpha- and gamma-tocopherols were determined by HPLC at baseline, and at days 2, 4, 7 and 10. The values for alpha- at baseline and 10 days were 0.80, 0.80, 0.80 & 0.79 mg/dl and 1.67, 1.72, 1.76 & 1.62 mg/dl. The values for gamma- were 0.28, 0.29, 0.30 & 0.29 mg/dl and 0.11, 0.08, 0.10 & 0.10 mg/dl. Thus the data show that a) the bioavailability of RRR-and all-rac-alpha-tocopherols is not affected by other tocopherols, and b) both RRR-and all-rac-alpha-tocopherol (free or esterified) significantly suppress the serum gamma tocopherol to the same extent. Furthermore, since there was no difference in the serum values of alpha-tocopherol between RRR-and all-rac-vitamin E given the same dose as IUs, the data also support the currently accepted ratio of 1.36 for the biopotency of RRR- vs. all-rac-alpha-tocopheryl acetate.

scholarly journals Coding of Amplitude Modulation in Primary Auditory Cortex

2011 ◽  
Vol 105 (2) ◽  
pp. 582-600 ◽  
Author(s):  
Pingbo Yin ◽  
Jeffrey S. Johnson ◽  
Kevin N. O'Connor ◽  
Mitchell L. Sutter
Keyword(s):  
Auditory Cortex ◽  
Mixed Mode ◽  
Modulation Frequency ◽  
Primary Auditory Cortex ◽  
Auditory Pathway ◽  
Temporal Modulation ◽  
Temporal Synchrony ◽  
Trial Analysis ◽  
A1 Neurons ◽  
Vector Strength

Conflicting results have led to different views about how temporal modulation is encoded in primary auditory cortex (A1). Some studies find a substantial population of neurons that change firing rate without synchronizing to temporal modulation, whereas other studies fail to see these nonsynchronized neurons. As a result, the role and scope of synchronized temporal and nonsynchronized rate codes in AM processing in A1 remains unresolved. We recorded A1 neurons' responses in awake macaques to sinusoidal AM noise. We find most (37–78%) neurons synchronize to at least one modulation frequency (MF) without exhibiting nonsynchronized responses. However, we find both exclusively nonsynchronized neurons (7–29%) and “mixed-mode” neurons (13–40%) that synchronize to at least one MF and fire nonsynchronously to at least one other. We introduce new measures for modulation encoding and temporal synchrony that can improve the analysis of how neurons encode temporal modulation. These include comparing AM responses to the responses to unmodulated sounds, and a vector strength measure that is suitable for single-trial analysis. Our data support a transformation from a temporally based population code of AM to a rate-based code as information ascends the auditory pathway. The number of mixed-mode neurons found in A1 indicates this transformation is not yet complete, and A1 neurons may carry multiplexed temporal and rate codes.

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