Autism Spectrum Disorders (ASD) encompass a wide array of debilitating symptoms, including severe sensory deficits and abnormal language development. Sensory deficits early in development may lead to broader symptomatology in adolescents and adults. The mechanistic links between ASD risk genes, sensory processing and language impairment are unclear. There is also a sex bias in ASD diagnosis and symptomatology. The current study aims to identify the developmental trajectory and genotype- and sex-dependent differences in auditory sensitivity and temporal processing in a Pten-deletion (phosphatase and tensin homolog missing on chromosome 10) mouse model of ASD. Auditory temporal processing is crucial for speech recognition and language development and deficits will cause language impairments. However, very little is known about the development of temporal processing in ASD animal models, and if there are sex differences. To address this major gap, we recorded epidural electroencephalography (EEG) signals from the frontal (FC) and auditory (AC) cortex in developing and adult Nse-cre PTEN mice, in which Pten is deleted in specific cortical layers (layers III-V) (PTEN conditional knock-out (cKO). We quantified resting EEG spectral power distribution, auditory event related potentials (ERP) and temporal processing from awake and freely moving male and female mice. Temporal processing is measured using a gap-in-noise-ASSR (auditory steady state response) stimulus paradigm. The experimental manipulation of gap duration and modulation depth allows us to measure cortical entrainment to rapid gaps in sounds. Temporal processing was quantified using inter-trial phase clustering (ITPC) values that account for phase consistency across trials. The results show genotype differences in resting power distribution in PTEN cKO mice throughout development. Male and female cKO mice have significantly increased beta power but decreased high frequency oscillations in the AC and FC. Both male and female PTEN cKO mice show diminished ITPC in their gap-ASSR responses in the AC and FC compared to control mice. Overall, deficits become more prominent in adult (p60) mice, with cKO mice having significantly increased sound evoked power and decreased ITPC compared to controls. While both male and female cKO mice demonstrated severe temporal processing deficits across development, female cKO mice showed increased hypersensitivity compared to males, reflected as increased N1 and P2 amplitudes. These data identify a number of novel sensory processing deficits in a PTEN-ASD mouse model that are present from an early age. Abnormal temporal processing and hypersensitive responses may contribute to abnormal development of language function in ASD.

This work demonstrates a physical reservoir using a back-end-of-line compatible thin-film transistor (TFT) with tin monoxide (SnO) as the channel material for neuromorphic computing. The electron trapping and time-dependent detrapping at the channel interface induce the SnO·TFT to exhibit fading memory and nonlinearity characteristics, the critical assets for physical reservoir computing. The three-terminal configuration of the TFT allows the generation of higher-dimensional reservoir states by simultaneously adjusting the bias conditions of the gate and drain terminals, surpassing the performances of typical two-terminal-based reservoirs such as memristors. The high-dimensional SnO TFT reservoir performs exceptionally in two benchmark tests, achieving a 94.1% accuracy in Modified National Institute of Standards and Technology handwritten number recognition and a normalized root-mean-square error of 0.089 in Mackey-Glass time-series prediction. Furthermore, it is suitable for vertical integration because its fabrication temperature is <250 °C, providing the benefit of achieving a high integration density.

Auditory temporal processing is a vital component of auditory stream segregation, or the process in which complex sounds are separated and organized into perceptually meaningful objects. Temporal processing can degrade prior to hearing loss, and is suggested to be a contributing factor to difficulties with speech-in-noise perception in normal-hearing listeners. The current study tested this hypothesis in middle-aged adults-an under-investigated cohort, despite being the age group where speech-in-noise difficulties are first reported. In 76 participants, three mechanisms of temporal processing were measured: peripheral auditory nerve function using electrocochleography, subcortical encoding of periodic speech cues (i.e., fundamental frequency; F0) using the frequency following response, and binaural sensitivity to temporal fine structure (TFS) using a dichotic frequency modulation detection task. Two measures of speech-in-noise perception were administered to explore how contributions of temporal processing may be mediated by different sensory demands present in the speech perception task. This study supported the hypothesis that temporal coding deficits contribute to speech-in-noise difficulties in middle-aged listeners. Poorer speech-in-noise perception was associated with weaker subcortical F0 encoding and binaural TFS sensitivity, but in different contexts, highlighting that diverse aspects of temporal processing are differentially utilized based on speech-in-noise task characteristics.

The human brain is a constructive organ. It generates predictions to modulate its functioning and continuously adapts to a dynamic environment. Increasingly, the temporal dimension of motor and non-motor behaviour is recognised as a key component of this predictive bias. Nevertheless, the intricate interplay of the neural mechanisms that encode, decode and evaluate temporal information to give rise to a sense of time and control over sensorimotor timing remains largely elusive. Among several brain systems, the basal ganglia have been consistently linked to interval- and beat-based timing operations. Considering the tight embedding of the basal ganglia into multiple complex neurofunctional networks, it is clear that they have to interact with other proximate and distal brain systems. While the primary target of basal ganglia output is the thalamus, many regions connect to the striatum of the basal ganglia, their main input relay. This establishes widespread connectivity, forming the basis for first- and second-order interactions with other systems implicated in timing such as the cerebellum and supplementary motor areas. However, next to this structural interconnectivity, additional functions need to be considered to better understand their contribution to temporally predictive adaptation. To this end, we develop the concept of interval-based patterning, conceived as a temporally explicit hierarchical sequencing operation that underlies motor and non-motor behaviour as a common interpretation of basal ganglia function.

Converging experimental and computational evidence indicate that on the scale of seconds the brain encodes time through changing patterns of neural activity. Experimentally, two general forms of neural dynamic regimes that can encode time have been observed: neural population clocks and ramping activity. Neural population clocks provide a high-dimensional code to generate complex spatiotemporal output patterns, in which each neuron exhibits a nonlinear temporal profile. A prototypical example of neural population clocks are neural sequences, which have been observed across species, brain areas, and behavioral paradigms. Additionally, neural sequences emerge in artificial neural networks trained to solve time-dependent tasks. Here, we examine the role of neural sequences in the encoding of time, and how they may emerge in a biologically plausible manner. We conclude that neural sequences may represent a canonical computational regime to perform temporal computations.

Anterior cingulate cortex (ACC) activity is important for operations that require the ability to integrate multiple experiences over time, such as rule learning, cognitive flexibility, working memory, and long-term memory recall. To shed light on this, we analyzed neuronal activity while rats repeated the same behaviors during hour-long sessions to investigate how activity changed over time. We recorded neuronal ensembles as rats performed a decision-free operant task with varying reward likelihoods at three different response ports (n = 5). Neuronal state space analysis revealed that each repetition of a behavior was distinct, with more recent behaviors more similar than those further apart in time. ACC activity was dominated by a slow, gradual change in low-dimensional representations of neural state space aligning with the pace of behavior. Temporal progression, or drift, was apparent on the top principal component for every session and was driven by the accumulation of experiences and not an internal clock. Notably, these signals were consistent across subjects, allowing us to accurately predict trial numbers based on a model trained on data from a different animal. We observed that non-continuous ramping firing rates over extended durations (tens of minutes) drove the low-dimensional ensemble representations. 40% of ACC neurons\' firing ramped over a range of trial lengths and combinations of shorter duration ramping neurons created ensembles that tracked longer durations. These findings provide valuable insights into how the ACC, at an ensemble level, conveys temporal information by reflecting the accumulation of experiences over extended periods.

Older listeners have difficulty processing temporal cues that are important for word discrimination, and deficient processing may limit their ability to benefit from these cues. Here, we investigated aging effects on perception and neural representation of the consonant transition and the factors that contribute to successful perception. To further understand the neural mechanisms underlying the changes in processing from brainstem to cortex, we also examined the factors that contribute to exaggerated amplitudes in cortex. We enrolled 30 younger normal-hearing and 30 older normal-hearing participants who met the criteria of clinically normal hearing. Perceptual identification functions were obtained for the words BEAT and WHEAT on a 7-step continuum of consonant-transition duration. Auditory brainstem responses (ABRs) were recorded to click stimuli and frequency-following responses (FFRs) and cortical auditory-evoked potentials were recorded to the endpoints of the BEAT-WHEAT continuum. Perceptual performance for identification of BEAT vs. WHEAT did not differ between younger and older listeners. However, both subcortical and cortical measures of neural representation showed age group differences, such that FFR phase locking was lower but cortical amplitudes (P1 and N1) were higher in older compared to younger listeners. ABR Wave I amplitude and FFR phase locking, but not audiometric thresholds, predicted early cortical amplitudes. Phase locking to the transition region and early cortical peak amplitudes (P1) predicted performance on the perceptual identification function. Overall, results suggest that the neural representation of transition durations and cortical overcompensation may contribute to the ability to perceive transition duration contrasts. Cortical overcompensation appears to be a maladaptive response to decreased neural firing/synchrony.

BACKGROUND: Autism spectrum disorder (ASD) is currently diagnosed in approximately 1 in 44 children in the United States, based on a wide array of symptoms, including sensory dysfunction and abnormal language development. Boys are diagnosed ~ 3.8 times more frequently than girls. Auditory temporal processing is crucial for speech recognition and language development. Abnormal development of temporal processing may account for ASD language impairments. Sex differences in the development of temporal processing may underlie the differences in language outcomes in male and female children with ASD. To understand mechanisms of potential sex differences in temporal processing requires a preclinical model. However, there are no studies that have addressed sex differences in temporal processing across development in any animal model of ASD.
METHODS: To fill this major gap, we compared the development of auditory temporal processing in male and female wildtype (WT) and Fmr1 knock-out (KO) mice, a model of Fragile X Syndrome (FXS), a leading genetic cause of ASD-associated behaviors. Using epidural screw electrodes, we recorded auditory event related potentials (ERP) and auditory temporal processing with a gap-in-noise auditory steady state response (ASSR) paradigm at young (postnatal (p)21 and p30) and adult (p60) ages from both auditory and frontal cortices of awake, freely moving mice.
RESULTS: The results show that ERP amplitudes were enhanced in both sexes of Fmr1 KO mice across development compared to WT counterparts, with greater enhancement in adult female than adult male KO mice. Gap-ASSR deficits were seen in the frontal, but not auditory, cortex in early development (p21) in female KO mice. Unlike male KO mice, female KO mice show WT-like temporal processing at p30. There were no temporal processing deficits in the adult mice of both sexes.
CONCLUSIONS: These results show a sex difference in the developmental trajectories of temporal processing and hypersensitive responses in Fmr1 KO mice. Male KO mice show slower maturation of temporal processing than females. Female KO mice show stronger hypersensitive responses than males later in development. The differences in maturation rates of temporal processing and hypersensitive responses during various critical periods of development may lead to sex differences in language function, arousal and anxiety in FXS.

An existing theoretical framework proposes that aberrant temporal processing and a fast internal clock, denoted by overestimation and under-reproduction of time, increases the likelihood of engagement in risky behaviors (ERB). The primary aim of this project was to improve our understanding of the relationship between temporal processing and ERB in college students. The present study used the Wittmann and Paulus (2008) theoretical framework to examine the associations between temporal processing and ERB in college students. College student participants (N = 215) completed self-report measures of ERB, delay aversion, inhibitory control, ADHD symptoms and objective cognitive time estimation and time reproduction tasks. Time estimation accuracy was significantly associated with lower engagement in sexual risk behaviors (OR = .988; 95% CI: .979, .996; p = .006) and aggressive behaviors (OR = .989; 95% CI: .980, .998; p = .018). Time reproduction was not significantly associated with ERB. The present study established preliminary support for the associations between aberrant temporal processing, namely aberrant time estimation, and ERB among college students.

BACKGROUND: Rehabilitation of hearing and listening difficulties through neuroplasticity of the auditory nervous system is a promising technique. Evidence of enhanced auditory processing in adult musicians is often not based on clinical auditory processing tests and is lacking in children with musical education.
OBJECTIVE: The aim of this study is to investigate the temporal resolution and frequency discrimination elements of auditory processing both in adults and children with musical education and to compare them with those without any musical education.
METHODS: Participants consisted of ten children without musical training and ten children with musical training with mean age 11.3 years and range 8-15 years as well as ten adults without musical education and ten adults with musical education with mean age 38.1 years and range 30-45 years. All participants were tested with two temporal resolution tests (GIN:Gaps-In-Noise and RGDT:Random Gap Detection Test), a temporal ordering frequency test (FPT:Frequency Pattern Test), and a frequency discrimination test (DLF: Different Limen for Frequency).
RESULTS: All test results revealed better performance in both children and adults with musical training for both ears.
CONCLUSIONS: A positive effect of formal music education for specific auditory processing elements in both children and adults is documented. Larger samples, longitudinal studies, as well as groups with impaired hearing and/or auditory processing are needed to further substantiate the effect shown.