Envelope reconstruction of speech and music highlights stronger tracking of speech at low frequencies.

The human brain tracks amplitude fluctuations of both speech and music, which reflects acoustic processing in addition to the encoding of higher-order features and one's cognitive state. Comparing neural tracking of speech and music envelopes can elucidate stimulus-general mechanisms, but direct comparisons are confounded by differences in their envelope spectra. Here, we use a novel method of frequency-constrained reconstruction of stimulus envelopes using EEG recorded during passive listening. We expected to see music reconstruction match speech in a narrow range of frequencies, but instead we found that speech was reconstructed better than music for all frequencies we examined. Additionally, models trained on all stimulus types performed as well or better than the stimulus-specific models at higher modulation frequencies, suggesting a common neural mechanism for tracking speech and music. However, speech envelope tracking at low frequencies, below 1 Hz, was associated with increased weighting over parietal channels, which was not present for the other stimuli. Our results highlight the importance of low-frequency speech tracking and suggest an origin from speech-specific processing in the brain.

Personalized Biofeedback on Inhaler Adherence and Technique by Community Pharmacists: A Cluster Randomized Clinical Trial.

BACKGROUND: Guidelines recommend that patients treated with inhalers receive adherence counseling and device training. Digital technologies that assess both inhaler adherence and technique have been developed. Using these technologies community pharmacists, who have regular contact with patients, are well placed to deliver personalized inhaler education. OBJECTIVE: To determine the impact of a pharmacist intervention, informed by digital technology, on inhaler technique and adherence of patients with asthma in the community. METHODS: A cluster randomized, parallel-group, multisite pharmacy study was conducted over 6 months. All study groups had an electronic device (inhaler compliance assessment device) attached to their maintenance inhaler. A biofeedback group received personalized inhaler training informed by data recorded by the device. The demonstration group received inhaler training, by physical demonstration with a placebo inhaler. The control group received usual care. The primary outcome was inhaler adherence, which was classified as "actual adherence" and expressed as the proportion of expected drug accumulation if adherence and technique had been perfect. Secondary outcomes were quality-of-life scores as measured by the St George's Respiratory Questionnaire, symptoms, and exacerbations. RESULTS: A total of 152 participants (n = 74 biofeedback, n = 56 demonstration, and n = 22 control) were recruited. Asthma was the predominant condition among participants (n = 83), with chronic obstructive pulmonary disease (n = 55) and asthma/chronic obstructive pulmonary disease overlap also reported (n = 8). In intention-to-treat analysis, adherence in the biofeedback group during month 2 was 62%, 18% higher (95% CI, 6 to 30) than that in the demonstration group (P = .004) and 24% higher (95% CI, 9 to 40) than that in the control group (P = .003). During month 6, adherence was 14% higher (95% CI, -1 to 30; P = .07) in the biofeedback group than in the demonstration group and 31% higher (95% CI, 13 to 48; P = .001) than in the control group. At the end of the study, the biofeedback group had a sustained fall in St George's Respiratory Questionnaire from baseline, -6.1 (95% CI, -9 to -0.4; P = .04) and had significantly improved daily respiratory symptoms. CONCLUSIONS: Community pharmacist-delivered inhaler training informed by a digital technology improved adherence and health status.

A Study of the Midbrain Network for Covert Attentional Orienting in Cervical Dystonia Patients using Dynamic Causal Modelling.

Understanding the neuronal network dynamics underlying the third most common movement disorder, cervical dystonia, can be achieved using dynamic causal modelling. Current literature establishes structures of the midbrain network for covert attentional orienting as dysfunctional in patients with cervical dystonia. One of these structures is the superior colliculus, for which it is hypothesised that deficient GABAergic activity therein causes cervical dystonia. To understand the role that this node plays in cervical dystonia, various connectivity models of the midbrain network were compared under the influence of a loom-recede visual stimulus fMRI paradigm. These models included the thalamus and striatum, crucial nodes in the direct/indirect pathways for motor movement and inhibition. The parametric empirical Bayes approach was used to quantify the difference in connection strengths across the winning models between patients and controls. Our findings demonstrated greater modulation by a looming stimulus event on the strength of connection from the striatum to the superior colliculus in patients. These results offer new means to understanding the pathophysiology of cervical dystonia.

A randomised clinical trial of feedback on inhaler adherence and technique in patients with severe uncontrolled asthma.

In severe asthma, poor control could reflect issues of medication adherence or inhaler technique, or that the condition is refractory. This study aimed to determine if an intervention with (bio)feedback on the features of inhaler use would identify refractory asthma and enhance inhaler technique and adherence.Patients with severe uncontrolled asthma were subjected to a stratified-by-site random block design. The intensive education group received repeated training in inhaler use, adherence and disease management. The intervention group received the same intervention, enhanced by (bio)feedback-guided training. The primary outcome was rate of actual inhaler adherence. Secondary outcomes included a pre-defined assessment of clinical outcome. Outcome assessors were blinded to group allocation. Data were analysed on an intention-to-treat and per-protocol basis.The mean rate of adherence during the third month in the (bio)feedback group (n=111) was higher than that in the enhanced education group (intention-to-treat, n=107; 73% versus 63%; 95% CI 2.8%-17.6%; p=0.02). By the end of the study, asthma was either stable or improved in 54 patients (38%); uncontrolled, but poorly adherent in 52 (35%); and uncontrolled, but adherent in 40 (27%).Repeated feedback significantly improved inhaler adherence. After a programme of adherence and inhaler technique assessment, only 40 patients (27%) were refractory and adherent, and might therefore need add-on therapy.

Depth matters - Towards finding an objective neurophysiological measure of behavioral amplitude modulation detection based on neural threshold determination.

With increasing numbers undergoing intervention for hearing impairment at a young age, the clinical need for objective assessment tools of auditory discrimination abilities is growing. Amplitude modulation (AM) sensitivity has been known to be an important factor for speech recognition particularly among cochlear implant (CI) users. It therefore would be useful to develop objective measures of AM detection for future clinical assessment of CI users; this study aimed to verify the feasibility of a neurophysiological approach studying a cohort of normal-hearing participants. The mismatch waveform (MMW) was evaluated as a potential objective measure of AM detection for a low modulation rate (8 Hz). This study also explored the relationship between behavioral AM detection and speech-in-noise recognition. The following measures were obtained for 15 young adults with no known hearing impairment: (1) psychoacoustic sinusoidal AM detection ability for a modulation rate of 8 Hz; (2) neural AM detection thresholds estimated from morphology weighted cortical auditory evoked potentials elicited to various AM depths; and (3) AzBio sentence scores for speech-in-noise recognition. No significant correlations were found between speech recognition and behavioral AM detection measures. Individual neural thresholds were obtained from MMW data and showed significant positive correlations with behavioral AM detection thresholds. Neural thresholds estimated from morphology weighted MMWs provide a novel, objective approach for assessing low-rate AM detection. The findings of this study encourage the continued investigation of the MMW as a neural correlate of low-rate AM detection in larger normal-hearing cohorts and subsequently in clinical cohorts such as cochlear implant users.

Signal Propagation in the Human Visual Pathways: An Effective Connectivity Analysis.

Although the visual system has been extensively investigated, an integrated account of the spatiotemporal dynamics of long-range signal propagation along the human visual pathways is not completely known or validated. In this work, we used dynamic causal modeling approach to provide insights into the underlying neural circuit dynamics of pattern reversal visual-evoked potentials extracted from concurrent EEG-fMRI data. A recurrent forward-backward connectivity model, consisting of multiple interacting brain regions identified by EEG source localization aided by fMRI spatial priors, best accounted for the data dynamics. Sources were first identified in the thalamic area, primary visual cortex, as well as higher cortical areas along the ventral and dorsal visual processing streams. Consistent with hierarchical early visual processing, the model disclosed and quantified the neural temporal dynamics across the identified activity sources. This signal propagation is dominated by a feedforward process, but we also found weaker effective feedback connectivity. Using effective connectivity analysis, the optimal dynamic causal modeling revealed enhanced connectivity along the dorsal pathway but slightly suppressed connectivity along the ventral pathway. A bias was also found in favor of the right hemisphere consistent with functional attentional asymmetry. This study validates, for the first time, the long-range signal propagation timing in the human visual pathways. A similar modeling approach can potentially be used to understand other cognitive processes and dysfunctions in signal propagation in neurological and neuropsychiatric disorders. Significance statement: An integrated account of long-range visual signal propagation in the human brain is currently incomplete. Using computational neural modeling on our acquired concurrent EEG-fMRI data under a visual evoked task, we found not only a substantial forward propagation toward "higher-order" brain regions but also a weaker backward propagation. Asymmetry in our model's long-range connectivity accounted for the various observed activity biases. Importantly, the model disclosed the timing of signal propagation across these connectivity pathways and validates, for the first time, long-range signal propagation in the human visual system. A similar modeling approach could be used to identify neural pathways for other cognitive processes and their dysfunctions in brain disorders.

The irregular firing properties of thalamic head direction cells mediate turn-specific modulation of the directional tuning curve.

Head direction cells encode an animal's heading in the horizontal plane. However, it is not clear why the directionality of a cell's mean firing rate differs for clockwise, compared with counterclockwise, head turns (this difference is known as the "separation angle") in anterior thalamus. Here we investigated in freely behaving rats whether intrinsic neuronal firing properties are linked to this phenomenon. We found a positive correlation between the separation angle and the spiking variability of thalamic head direction cells. To test whether this link is driven by hyperpolarization-inducing currents, we investigated the effect of thalamic reticular inhibition during high-voltage spindles on directional spiking. While the selective directional firing of thalamic neurons was preserved, we found no evidence for entrainment of thalamic head direction cells by high-voltage spindle oscillations. We then examined the role of depolarization-inducing currents in the formation of separation angle. Using a single-compartment Hodgkin-Huxley model, we show that modeled neurons fire with higher frequencies during the ascending phase of sinusoidal current injection (mimicking the head direction tuning curve) when simulated with higher high-threshold calcium channel conductance. These findings demonstrate that the turn-specific encoding of directional signal strongly depends on the ability of thalamic neurons to fire irregularly in response to sinusoidal excitatory activation. Another crucial factor for inducing phase lead to sinusoidal current injection was the presence of spike-frequency adaptation current in the modeled neurons. Our data support a model in which intrinsic biophysical properties of thalamic neurons mediate the physiological encoding of directional information.

Objective assessment of spectral ripple discrimination in cochlear implant listeners using cortical evoked responses to an oddball paradigm.

Cochlear implants (CIs) can partially restore functional hearing in deaf individuals. However, multiple factors affect CI listener's speech perception, resulting in large performance differences. Non-speech based tests, such as spectral ripple discrimination, measure acoustic processing capabilities that are highly correlated with speech perception. Currently spectral ripple discrimination is measured using standard psychoacoustic methods, which require attentive listening and active response that can be difficult or even impossible in special patient populations. Here, a completely objective cortical evoked potential based method is developed and validated to assess spectral ripple discrimination in CI listeners. In 19 CI listeners, using an oddball paradigm, cortical evoked potential responses to standard and inverted spectrally rippled stimuli were measured. In the same subjects, psychoacoustic spectral ripple discrimination thresholds were also measured. A neural discrimination threshold was determined by systematically increasing the number of ripples per octave and determining the point at which there was no longer a significant difference between the evoked potential response to the standard and inverted stimuli. A correlation was found between the neural and the psychoacoustic discrimination thresholds (R2=0.60, p<0.01). This method can objectively assess CI spectral resolution performance, providing a potential tool for the evaluation and follow-up of CI listeners who have difficulty performing psychoacoustic tests, such as pediatric or new users.

Endogenous auditory frequency-based attention modulates electroencephalogram-based measures of obligatory sensory activity in humans.

Auditory selective attention is the ability to enhance the processing of a single sound source, while simultaneously suppressing the processing of other competing sound sources. Recent research has addressed a long-running debate by showing that endogenous attention produces effects on obligatory sensory responses to continuous and competing auditory stimuli. However, until now, this result has only been shown under conditions where the competing stimuli differed in both their frequency characteristics and, importantly, their spatial location. Thus, it is unknown whether endogenous selective attention based only on nonspatial features modulates obligatory sensory processing. Here, we investigate this issue using a diotic paradigm, such that competing auditory stimuli differ in frequency, but had no separation in space. We find a significant effect of attention on electroencephalogram-based measures of obligatory sensory processing at several poststimulus latencies. We discuss these results in terms of previous research on feature-based attention and by comparing our findings with the previous work using stimuli that differed both in terms of spatial and frequency-based characteristics.

Auditory mismatch negativity in cochlear implant users: a window to spectral discrimination.

A cochlear implant (CI) can partially restore hearing in patients with severe to profound sensorineural hearing loss. However, the large outcome variability in CI users prompts the need for more objective measures of speech perception performance. Electrophysiological metrics of CI performance may be an important tool for audiologists in the assessment of hearing rehabilitation. Utilizing electroencephalography (EEG), it may be possible to evaluate speech perception correlates such as spectral discrimination. The mismatch negativity (MMN) of 10 CI subjects was recorded for stimuli containing different spectral densities. The neural spectral discrimination threshold, estimated by the MMN responses, showed a significant correlation with the behavioral spectral discrimination threshold measured in each subject. Results suggest that the MMN can be potentially used to obtain an objective estimate of spectral discrimination abilities in CI users.

Cochlear implant artifact attenuation in late auditory evoked potentials: a single channel approach.

Recent evidence suggests that late auditory evoked potentials (LAEP) provide a useful objective metric of performance in cochlear implant (CI) subjects. However, the CI produces a large electrical artifact that contaminates LAEP recordings and confounds their interpretation. Independent component analysis (ICA) has been used in combination with multi-channel recordings to effectively remove the artifact. The applicability of the ICA approach is limited when only single channel data are needed or available, as is often the case in both clinical and research settings. Here we developed a single-channel, high sample rate (125 kHz), and high bandwidth (0-100 kHz) acquisition system to reduce the CI stimulation artifact. We identified two different artifacts in the recording: 1) a high frequency artifact reflecting the stimulation pulse rate, and 2) a direct current (DC, or pedestal) artifact that showed a non-linear time varying relationship to pulse amplitude. This relationship was well described by a bivariate polynomial. The high frequency artifact was completely attenuated by a 35 Hz low-pass filter for all subjects (n = 22). The DC artifact could be caused by an impedance mismatch. For 27% of subjects tested, no DC artifact was observed when electrode impedances were balanced to within 1 kΩ. For the remaining 73% of subjects, the pulse amplitude was used to estimate and then attenuate the DC artifact. Where measurements of pulse amplitude were not available (as with standard low sample rate systems), the DC artifact could be estimated from the stimulus envelope. The present artifact removal approach allows accurate measurement of LAEPs from CI subjects from single channel recordings, increasing their feasibility and utility as an accessible objective measure of CI function.

Rate and onset cues can improve cochlear implant synthetic vowel recognition in noise.

Understanding speech-in-noise is difficult for most cochlear implant (CI) users. Speech-in-noise segregation cues are well understood for acoustic hearing but not for electric hearing. This study investigated the effects of stimulation rate and onset delay on synthetic vowel-in-noise recognition in CI subjects. In experiment I, synthetic vowels were presented at 50, 145, or 795 pulse/s and noise at the same three rates, yielding nine combinations. Recognition improved significantly if the noise had a lower rate than the vowel, suggesting that listeners can use temporal gaps in the noise to detect a synthetic vowel. This hypothesis is supported by accurate prediction of synthetic vowel recognition using a temporal integration window model. Using lower rates a similar trend was observed in normal hearing subjects. Experiment II found that for CI subjects, a vowel onset delay improved performance if the noise had a lower or higher rate than the synthetic vowel. These results show that differing rates or onset times can improve synthetic vowel-in-noise recognition, indicating a need to develop speech processing strategies that encode or emphasize these cues.

At what time is the cocktail party? A late locus of selective attention to natural speech.

Distinguishing between speakers and focusing attention on one speaker in multi-speaker environments is extremely important in everyday life. Exactly how the brain accomplishes this feat and, in particular, the precise temporal dynamics of this attentional deployment are as yet unknown. A long history of behavioral research using dichotic listening paradigms has debated whether selective attention to speech operates at an early stage of processing based on the physical characteristics of the stimulus or at a later stage during semantic processing. With its poor temporal resolution fMRI has contributed little to the debate, while EEG-ERP paradigms have been hampered by the need to average the EEG in response to discrete stimuli which are superimposed onto ongoing speech. This presents a number of problems, foremost among which is that early attention effects in the form of endogenously generated potentials can be so temporally broad as to mask later attention effects based on the higher level processing of the speech stream. Here we overcome this issue by utilizing the AESPA (auditory evoked spread spectrum analysis) method which allows us to extract temporally detailed responses to two concurrently presented speech streams in natural cocktail-party-like attentional conditions without the need for superimposed probes. We show attentional effects on exogenous stimulus processing in the 200-220 ms range in the left hemisphere. We discuss these effects within the context of research on auditory scene analysis and in terms of a flexible locus of attention that can be deployed at a particular processing stage depending on the task.

Theta-modulated head direction cells in the rat anterior thalamus.

A major tool in understanding how the brain processes information is the analysis of neuronal output at each hierarchical level along the pathway of signal propagation. Theta rhythm and head directionality are the two main signals found across all levels of Papez's circuit, which supports episodic memory formation. Here, we provide evidence that the functional interaction between both signals occurs at a subcortical level. We show that there is population of head direction cells (39%) in rat anteroventral thalamic nucleus that exhibit rhythmic spiking in the theta range. This class of units, termed HD-by-theta (head direction-by-theta) cells, discharged predominantly in spike trains at theta frequency (6-12 Hz). The highest degree of theta rhythmicity was evident when the animal was heading/facing in the preferred direction, expressed by the Gaussian peak of the directional tuning curve. The theta-rhythmic mode of spiking was closely related to the firing activity of local theta-bursting cells. We also found that 32% of anteroventral theta-bursting cells displayed a head-directional modulation of their spiking. This crossover between theta and head-directional signals indicates that anterior thalamus integrates information related to heading and movement, and may therefore actively modulate hippocampo-dencephalic information processing.

Audiovisual temporal discrimination is less efficient with aging: an event-related potential study.

We investigated the crossmodal temporal discrimination deficit characterizing older adults and its event-related potential (electroencephalogram) correlates using an audiovisual temporal order judgment task. Audiovisual stimuli were presented at stimulus onset asynchronies (SOA) of 70 or 270 ms. Older were less accurate than younger adults with an SOA of 270 ms but not 70 ms. With an SOA of 270 ms only, older adults had smaller posterior P1 and frontocentral N1 amplitudes for visual stimuli in auditory-visual trials and auditory stimuli in visual-auditory trials, respectively. These results suggest a deficit in cross-sensory processing with aging reflected at the behavioural and neural level, and suggest an impairment in switching between modalities even when the inputs are separated by long temporal intervals.

Endogenous auditory spatial attention modulates obligatory sensory activity in auditory cortex.

Endogenous attention is the self-directed focus of attention to a region or feature of the environment. In this study, we assess the effects of endogenous attention on temporally detailed responses to continuous and competing auditory stimuli obtained using the novel auditory evoked spread spectrum analysis (AESPA) method. There is some debate as to whether an enhancement of sensory processing is involved in endogenous attention. It has been suggested that attentional effects are not due to increased sensory activity but are due to engagement of separate temporally overlapping nonsensory attention-related activity. There are also issues with the fact that the influence of exogenous attention grabbing mechanisms may hamper studies of endogenous attention. Due to the nature of the AESPA method, the obtained responses represent activity directly related to the stimulus envelope and thus predominantly correspond to obligatory sensory processing. In addition, the continuous nature of the stimuli minimizes exogenous attentional influence. We found attentional modulations at ~136 ms (during the Nc component of the AESPA response) and localized this to auditory cortex. Although the involvement of separate nonsensory attentional centers cannot be ruled out, these findings clearly demonstrate that endogenous attention does modulate obligatory sensory activity in auditory cortex.

Resolving precise temporal processing properties of the auditory system using continuous stimuli.

In natural environments complex and continuous auditory stimulation is virtually ubiquitous. The human auditory system has evolved to efficiently process an infinity of everyday sounds, which range from short, simple bursts of noise to signals with a much higher order of information such as speech. Investigation of temporal processing in this system using the event-related potential (ERP) technique has led to great advances in our knowledge. However, this method is restricted by the need to present simple, discrete, repeated stimuli to obtain a useful response. Alternatively the continuous auditory steady-state response is used, although this method reduces the evoked response to its fundamental frequency component at the expense of useful information on the timing of response transmission through the auditory system. In this report, we describe a method for eliciting a novel ERP, which circumvents these limitations, known as the AESPA (auditory-evoked spread spectrum analysis). This method uses rapid amplitude modulation of audio carrier signals to estimate the impulse response of the auditory system. We show AESPA responses with high signal-to-noise ratios obtained using two types of carrier wave: a 1-kHz tone and broadband noise. To characterize these responses, they are compared with auditory-evoked potentials elicited using standard techniques. A number of similarities and differences between the responses are noted and these are discussed in light of the differing stimulation and analysis methods used. Data are presented that demonstrate the generalizability of the AESPA method and a number of applications are proposed.

Neural mass model of human multisensory integration.

A neural mass model of interacting macro-columns is stimulated to reproduce unisensory, auditory and visually evoked potentials and multisensory (concurrent audiovisual) evoked potentials. These were elicited from patients conducting a reaction response task and recorded from intracranial electrodes placed on the parietal lobe. Important features of this model include inhibitory and excitatory feedback connections to pyramidal cells and extrinsic input to the stellate cell pool, with provision for hierarchical positioning depending on extrinsic connections. Both auditory and visually evoked potentials were best fit using a top-down paradigm. The multisensory response reconstructed from its constituent models was then compared to the actual multisensory EP. Fitting of the multisensory response from constituent models to the actual response required no significant changes to the architecture but did require a decrease in top-down feedback delay. This suggests that multisensory integration, and its related improvement in reaction behavior is not an automatic process but instead controlled by a central executive functioning.