Interrupted mosaic speech revisited: Gain and loss in intelligibility by stretchinga).

Our previous investigation on the effect of stretching spectrotemporally degraded and temporally interrupted speech stimuli showed remarkable intelligibility gains [Udea, Takeichi, and Wakamiya (2022). J. Acoust. Soc. Am. 152(2), 970-980]. In this previous study, however, gap durations and temporal resolution were confounded. In the current investigation, we therefore observed the intelligibility of so-called mosaic speech while dissociating the effects of interruption and temporal resolution. The intelligibility of mosaic speech (20 frequency bands and 20 ms segment duration) declined from 95% to 78% and 33% by interrupting it with 20 and 80 ms gaps. Intelligibility improved, however, to 92% and 54% (14% and 21% gains for 20 and 80 ms gaps, respectively) by stretching mosaic segments to fill silent gaps (n = 21). By contrast, the intelligibility was impoverished to a minimum of 9% (7% loss) when stretching stimuli interrupted with 160 ms gaps. Explanations based on auditory grouping, modulation unmasking, or phonemic restoration may account for the intelligibility improvement by stretching, but not for the loss. The probability summation model accounted for "U"-shaped intelligibility curves and the gain and loss of intelligibility, suggesting that perceptual unit length and speech rate may affect the intelligibility of spectrotemporally degraded speech stimuli.

Checkerboard and interrupted speech: Intelligibility contrasts related to factor-analysis-based frequency bandsa).

It has been shown that the intelligibility of checkerboard speech stimuli, in which speech signals were periodically interrupted in time and frequency, drastically varied according to the combination of the number of frequency bands (2-20) and segment duration (20-320 ms). However, the effects of the number of frequency bands between 4 and 20 and the frequency division parameters on intelligibility have been largely unknown. Here, we show that speech intelligibility was lowest in four-band checkerboard speech stimuli, except for the 320-ms segment duration. Then, temporally interrupted speech stimuli and eight-band checkerboard speech stimuli came in this order (N = 19 and 20). At the same time, U-shaped intelligibility curves were observed for four-band and possibly eight-band checkerboard speech stimuli. Furthermore, different parameters of frequency division resulted in small but significant intelligibility differences at the 160- and 320-ms segment duration in four-band checkerboard speech stimuli. These results suggest that factor-analysis-based four frequency bands, representing groups of critical bands correlating with each other in speech power fluctuations, work as speech cue channels essential for speech perception. Moreover, a probability summation model for perceptual units, consisting of a sub-unit process and a supra-unit process that receives outputs of the speech cue channels, may account for the U-shaped intelligibility curves.

Auditory grouping is necessary to understand interrupted mosaic speech stimuli.

The intelligibility of interrupted speech stimuli has been known to be almost perfect when segment duration is shorter than 80 ms, which means that the interrupted segments are perceptually organized into a coherent stream under this condition. However, why listeners can successfully group the interrupted segments into a coherent stream has been largely unknown. Here, we show that the intelligibility for mosaic speech in which original speech was segmented in frequency and time and noise-vocoded with the average power in each unit was largely reduced by periodical interruption. At the same time, the intelligibility could be recovered by promoting auditory grouping of the interrupted segments by stretching the segments up to 40 ms and reducing the gaps, provided that the number of frequency bands was enough ( ≥ 4) and the original segment duration was equal to or less than 40 ms. The interruption was devastating for mosaic speech stimuli, very likely because the deprivation of periodicity and temporal fine structure with mosaicking prevented successful auditory grouping for the interrupted segments.

Recent updates of eye movement abnormalities in patients with schizophrenia: A scoping review.

AIM: Although eye-tracking technology expands beyond capturing eye data just for the sole purpose of ensuring participants maintain their gaze at the presented fixation cross, gaze technology remains of less importance in clinical research. Recently, impairments in visual information encoding processes indexed by novel gaze metrics have been frequently reported in patients with schizophrenia. This work undertakes a scoping review of research on saccadic dysfunctions and exploratory eye movement deficits among patients with schizophrenia. It gathers promising pieces of evidence of eye movement abnormalities in attention-demanding tasks on the schizophrenia spectrum that have mounted in recent years and their outcomes as potential biological markers. METHODS: The protocol was drafted based on PRISMA for scoping review guidelines. Electronic databases were systematically searched to identify articles published between 2010 and 2020 that examined visual processing in patients with schizophrenia and reported eye movement characteristics as potential biomarkers for this mental illness. RESULTS: The use of modern eye-tracking instrumentation has been reported by numerous neuroscientific studies to successfully and non-invasively improve the detection of visual information processing impairments among the screened population at risk of and identified with schizophrenia. CONCLUSIONS: Eye-tracking technology has the potential to contribute to the process of early intervention and more apparent separation of the diagnostic entities, being put together by the syndrome-based approach to the diagnosis of schizophrenia. However, context-processing paradigms should be conducted and reported in equally accessible publications to build comprehensive models.

Intelligibility of chimeric locally time-reversed speech.

The intelligibility of chimeric locally time-reversed speech was investigated. Both (1) the boundary frequency between the temporally degraded band and the non-degraded band and (2) the segment duration were varied. Japanese mora accuracy decreased if the width of the degraded band or the segment duration increased. Nevertheless, the chimeric stimuli were more intelligible than the locally time-reversed controls. The results imply that the auditory system can use both temporally degraded speech information and undamaged speech information over different frequency regions in the processing of the speech signal, if the amplitude envelope in the frequency range of 840-1600 Hz was preserved.

Irrelevant speech effects with locally time-reversed speech: Native vs non-native language.

Irrelevant speech is known to interfere with short-term memory of visually presented items. Here, this irrelevant speech effect was studied with a factorial combination of three variables: the participants' native language, the language the irrelevant speech was derived from, and the playback direction of the irrelevant speech. We used locally time-reversed speech as well to disentangle the contributions of local and global integrity. German and Japanese speech was presented to German (n = 79) and Japanese (n = 81) participants while participants were performing a serial-recall task. In both groups, any kind of irrelevant speech impaired recall accuracy as compared to a pink-noise control condition. When the participants' native language was presented, normal speech and locally time-reversed speech with short segment duration, preserving intelligibility, was the most disruptive. Locally time-reversed speech with longer segment durations and normal or locally time-reversed speech played entirely backward, both lacking intelligibility, was less disruptive. When the unfamiliar, incomprehensible signal was presented as irrelevant speech, no significant difference was found between locally time-reversed speech and its globally inverted version, suggesting that the effect of global inversion depends on the familiarity of the language.

Memory disruption by irrelevant noise-vocoded speech: Effects of native language and the number of frequency bands.

To investigate the mechanisms by which unattended speech impairs short-term memory performance, speech samples were systematically degraded by means of a noise vocoder. For experiment 1, recordings of German and Japanese sentences were passed through a filter bank dividing the spectrum between 50 and 7000 Hz into 20 critical-band channels or combinations of those, yielding 20, 4, 2, or just 1 channel(s) of noise-vocoded speech. Listening tests conducted with native speakers of both languages showed a monotonic decrease in speech intelligibility as the number of frequency channels was reduced. For experiment 2, 40 native German and 40 native Japanese participants were exposed to speech processed in the same manner while trying to memorize visually presented sequences of digits in the correct order. Half of each sample received the German, the other half received the Japanese speech samples. The results show large irrelevant-speech effects increasing in magnitude with the number of frequency channels. The effects are slightly larger when subjects are exposed to their own native language. The results are neither predicted very well by the speech transmission index, nor by psychoacoustical fluctuation strength, most likely, since both metrics fail to disentangle amplitude and frequency modulations in the signals.

Electric dipolar Kondo effect emerging from a vibrating magnetic ion.

When a magnetic ion vibrates in a metal, it inevitably introduces a new channel of hybridization with conduction electrons, and in general, the vibrating ion induces an electric dipole moment. In such a situation, we find that magnetic and nonmagnetic Kondo effects alternatively occur due to the screening of the spin moment and electric dipole moment of the vibrating ion. In particular, the electric dipolar two-channel Kondo effect is found to occur for a weak Coulomb interaction. We also show that a magnetically robust heavy-electron state appears near the fixed point of the electric dipolar two-channel Kondo effect. We believe that the vibrating magnetic ion opens a new door in Kondo physics.

The common limitations in auditory temporal processing for Mandarin Chinese and Japanese.

The present investigation focused on how temporal degradation affected intelligibility in two types of languages, i.e., a tonal language (Mandarin Chinese) and a non-tonal language (Japanese). The temporal resolution of common daily-life sentences spoken by native speakers was systematically degraded with mosaicking (mosaicising), in which the power of original speech in each of regularly spaced time-frequency unit was averaged and temporal fine structure was removed. The results showed very similar patterns of variations in intelligibility for these two languages over a wide range of temporal resolution, implying that temporal degradation crucially affected speech cues other than tonal cues in degraded speech without temporal fine structure. Specifically, the intelligibility of both languages maintained a ceiling up to about the 40-ms segment duration, then the performance gradually declined with increasing segment duration, and reached a floor at about the 150-ms segment duration or longer. The same limitations for the ceiling performance up to 40 ms appeared for the other method of degradation, i.e., local time-reversal, implying that a common temporal processing mechanism was related to the limitations. The general tendency fitted to a dual time-window model of speech processing, in which a short (~ 20-30 ms) and a long (~ 200 ms) time-window run in parallel.

Syntrophin mutation associated with long QT syndrome through activation of the nNOS-SCN5A macromolecular complex.

Mutations in 11 genes that encode ion channels or their associated proteins cause inherited long QT syndrome (LQTS) and account for approximately 75-80% of cases (LQT1-11). Direct sequencing of SNTA1, the gene encoding alpha1-syntrophin, was performed in a cohort of LQTS patients that were negative for mutations in the 11 known LQTS-susceptibility genes. A missense mutation (A390V-SNTA1) was found in a patient with recurrent syncope and markedly prolonged QT interval (QTc, 530 ms). SNTA1 links neuronal nitric oxide synthase (nNOS) to the nNOS inhibitor plasma membrane Ca-ATPase subtype 4b (PMCA4b); SNTA1 also is known to associate with the cardiac sodium channel SCN5A. By using a GST-fusion protein of the C terminus of SCN5A, we showed that WT-SNTA1 interacted with SCN5A, nNOS, and PMCA4b. In contrast, A390V-SNTA1 selectively disrupted association of PMCA4b with this complex and increased direct nitrosylation of SCN5A. A390V-SNTA1 expressed with SCN5A, nNOS, and PMCA4b in heterologous cells increased peak and late sodium current compared with WT-SNTA1, and the increase was partially inhibited by NOS blockers. Expression of A390V-SNTA1 in cardiac myocytes also increased late sodium current. We conclude that the A390V mutation disrupted binding with PMCA4b, released inhibition of nNOS, caused S-nitrosylation of SCN5A, and was associated with increased late sodium current, which is the characteristic biophysical dysfunction for sodium-channel-mediated LQTS (LQT3). These results establish an SNTA1-based nNOS complex attached to SCN5A as a key regulator of sodium current and suggest that SNTA1 be considered a rare LQTS-susceptibility gene.

Intelligibility of chimeric locally time-reversed speech: Relative contribution of four frequency bands.

Intelligibility of four-band speech stimuli was investigated (n = 18), such that only one of the frequency bands was preserved, whereas other bands were locally time-reversed (segment duration: 75-300 ms), or vice versa. Intelligibility was best retained (82% at 75 ms) when the second lowest band (540-1700 Hz) was preserved. When the same band was degraded, the largest drop (10% at 300 ms) occurred. The lowest and second highest bands contributed similarly less strongly to intelligibility. The highest frequency band contributed least. A close connection between the second lowest frequency band and sonority was suggested.

Phonemic restoration of interrupted locally time-reversed speech : Effects of segment duration and noise levels.

Intelligibility of temporally degraded speech was investigated with locally time-reversed speech (LTR) and its interrupted version (ILTR). Control stimuli comprising interrupted speech (I) were also included. Speech stimuli consisted of 200 Japanese meaningful sentences. In interrupted stimuli, speech segments were alternated with either silent gaps or pink noise bursts. The noise bursts had a level of - 10, 0 or + 10 dB relative to the speech level. Segment duration varied from 20 to 160 ms for ILTR sentences, but was fixed at 160 ms for I sentences. At segment durations between 40 and 80 ms, severe reductions in intelligibility were observed for ILTR sentences, compared with LTR sentences. A substantial improvement in intelligibility (30-33%) was observed when 40-ms silent gaps in ILTR were replaced with 0- and + 10-dB noise. Noise with a level of - 10 dB had no effect on the intelligibility. These findings show that the combined effects of interruptions and temporal reversal of speech segments on intelligibility are greater than the sum of each individual effect. The results also support the idea that illusory continuity induced by high-level noise bursts improves the intelligibility of ILTR and I sentences.

Contribution of Eye-Tracking to Study Cognitive Impairments Among Clinical Populations.

In the field of psychology, the merge of decision-theory and neuroscientific methods produces an array of scientifically recognized paradigms. For example, by exploring consumer's eye-movement behavior, researchers aim to deepen the understanding of how patterns of retinal activation are being meaningfully transformed into visual experiences and connected with specific reactions (e.g., purchase). Notably, eye-movements provide knowledge of one's homeostatic balance and gatekeep information that shape decisions. Hence, vision science investigates the quality of observed environments determined under various experimental conditions. Moreover, it answers questions on how human process visual stimuli and use gained information for a successful strategy to achieve certain goals. While capturing cognitive states with the support of the eye-trackers progresses at a relatively fast pace in decision-making research, measuring the visual performance of real-life tasks, which require complex cognitive skills, is tentatively translated into clinical experiments. Nevertheless, the potential of the human eye as a highly valuable source of biomarkers has been underlined. In this article, we aim to draw readers attention to decision-making experimental paradigms supported with eye-tracking technology among clinical populations. Such interdisciplinary approach may become an important component that will (i) help in objectively illustrating patient's models of beliefs and values, (ii) support clinical interventions, and (iii) contribute to health services. It is possible that shortly, eye-movement data from decision-making experiments will grant the scientific community a greater understanding of mechanisms underlining mental states and consumption practices that medical professionals consider as obsessions, disorders or addiction.

Checkerboard speech vs interrupted speech: Effects of spectrotemporal segmentation on intelligibility.

The intelligibility of interrupted speech (interrupted over time) and checkerboard speech (interrupted over time-by-frequency), both of which retained a half of the original speech, was examined. The intelligibility of interrupted speech stimuli decreased as segment duration increased. 20-band checkerboard speech stimuli brought nearly 100% intelligibility irrespective of segment duration, whereas, with 2 and 4 frequency bands, a trough of 35%-40% appeared at the 160-ms segment duration. Mosaic speech stimuli (power was averaged over a time-frequency unit) yielded generally poor intelligibility ( ⩽10%). The results revealed the limitations of underlying auditory organization for speech cues scattered in a time-frequency domain.

Long-term safety and efficacy of agalsidase beta in Japanese patients with Fabry disease: aggregate data from two post-authorization safety studies.

BACKGROUND: Enzyme replacement therapy in Fabry disease has been available in Japan since 2004. Two post-authorization safety studies were conducted to evaluate agalsidase beta in Japanese patients with Fabry disease in real-world practice. RESEARCH DESIGN AND METHODS: The Special Drug Use Investigation monitored the long-term safety and efficacy of agalsidase beta, and the Drug Use Investigation monitored safety in patients not participating in the Special Drug Use Investigation. Safety and efficacy evaluations included adverse drug reactions (ADRs), infusion-associated reactions and hypersensitivity reactions, and change in blood GL-3 level over time. RESULTS: Of 396 patients in the aggregated data set, safety and efficacy analysis sets comprised 307 and 196 patients, respectively. ADRs occurred in 93 (30.3%) patients and serious ADRs occurred in 25 (8.1%) patients, with general disorders and administration site conditions (n=55, 17.9%), nervous system disorders (n=30, 9.8%) and skin and subcutaneous tissue disorders (n=23, 7.5%) the most common. Reductions in blood GL-3 levels occurred over the study, irrespective of age or disease phenotype. CONCLUSIONS: Agalsidase beta demonstrated acceptable safety and tolerability, with sustained reductions in blood GL-3 levelsin Japanese patients with Fabry disease in real-world clinical practice. CLINICAL TRIAL REGISTRATION: NCT00233870/AGAL03004 (Special Drug Use Investigation of Agalsidase beta).

Safety and efficacy of idursulfase in the treatment of mucopolysaccharidosis II (Hunter syndrome): a post-marketing study in Japan.

OBJECTIVES: Enzyme replacement therapy with idursulfase has been shown to improve somatic signs and symptoms of mucopolysaccharidosis type II (MPS II). Idursulfase is available in Japan (since 2007), based on the outcome of clinical trials conducted in the United States, but data from Japanese patients are limited. METHODS: This was a postmarketing study of Japanese MPS II patients treated with 0.5 mg/kg intravenous idursulfase weekly, conducted over a period of 8 years after initial administration. Assessments included the safety profile, survival rate, degree of clinical improvement, change in urinary uronic acid (UA) concentration, and 6-minute walk test (6MWT). RESULTS: The safety and efficacy analysis populations included 145 and 143 patients, respectively. The incidence of serious adverse events was 42.8% and the incidence of adverse drug reactions was 48.3%. The 7-year survival rate was 82.7%. Improvements in the clinical features of hepatosplenomegaly, skin, joint, and respiratory disorders were reported (per investigator's assessment). The mean change in urinary UA concentration was -128.39 mg/g creatinine, and that of 6MWT walking distance was +31.8 m. CONCLUSION: Long-term idursulfase treatment was well tolerated, and effective in improving clinical features, reducing urinary UA, and slowing disease progression in Japanese MPS II patients.

Perceived Congruency in Audiovisual Stimuli Consisting of Gabor Patches and AM and FM Tones.

Experiments that focus on how humans perceive temporal, spatial or synaesthetic congruency in audiovisual sensory information have often employed stimuli consisting of a Gabor patch and an amplitude (AM) or frequency (FM)-modulated sound. Introducing similarity between the static and dynamic features of the Gabor patch and the (carrier) frequency or modulation frequency of the sound is often assumed to be effective enough to induce congruency. However, comparative empirical data on perceived congruency of various stimulus parameters are not readily available, and in particular with respect to sound modulation, it is still not clear which type (AM or FM) induces perceived congruency best in tandem with various patch parameters. In two experiments, we examined Gabor patches of various spatial frequencies with flickering (2, 3 and 4 flickers/s) or drifting (0.5, 1.0 and 1.5 degrees/s) gratings in combinations with AM or FM tones of 2-, 3- and 4-Hz modulation and 500-, 1000- and 2000-Hz carrier frequencies. Perceived congruency ratings were obtained by asking participants to rate stimulus (in)congruency from 1 (incongruent) to 7 (congruent). The data showed that varying the spatial frequency of the Gabor patch and the carrier frequency of the modulated tone had comparatively little impact on perceived congruency. Similar to previous findings, similarity between the temporal frequency of the Gabor patch and the modulated tone effectively promoted perceived congruency. Furthermore, direct comparisons convincingly showed that AM tones in combination with flickering Gabor patches received significantly higher audiovisual congruency ratings compared to FM tones.

GPD1L links redox state to cardiac excitability by PKC-dependent phosphorylation of the sodium channel SCN5A.

The SCN5A-encoded cardiac sodium channel underlies excitability in the heart, and dysfunction of sodium current (I(Na)) can cause fatal ventricular arrhythmia in maladies such as long QT syndrome, Brugada syndrome (BrS), and sudden infant death syndrome (SIDS). The gene GPD1L encodes the glycerol phosphate dehydrogenase 1-like protein with homology to glycerol phosphate dehydrogenase (GPD1), but the function for this enzyme is unknown. Mutations in GPD1L have been associated with BrS and SIDS and decrease I(Na) through an unknown mechanism. Using a heterologous expression system, we show that GPD1L associated with SCN5A and that the BrS- and SIDS-related mutations in GPD1L caused a loss of enzymatic function resulting in glycerol-3-phosphate PKC-dependent phosphorylation of SCN5A at serine 1503 (S1503) through a GPD1L-dependent pathway. The direct phosphorylation of S1503 markedly decreased I(Na). These results show a function for GPD1L in cell physiology and a mechanism linking mutations in GPD1L to sudden cardiac arrest. Because the enzymatic step catalyzed by GPD1L depends upon nicotinamide adenine dinucleotide, this GPD1L pathway links the metabolic state of the cell to I(Na) and excitability and may be important more generally in cardiac ischemia and heart failure.

Role of HCN4 channel in preventing ventricular arrhythmia.

Bradycardia is a trigger of ventricular arrhythmias in patients with arrhythmia including Brugada syndrome and long QT syndrome. The HCN4 channel controls the heart rate, and its mutations predispose to inherited sick sinus syndrome and long QT syndrome associated with bradycardia. We found a 4 base-insertion at the splice donor site of the HCN4 gene in a patient with idiopathic ventricular tachycardia, which was supposed to generate a truncated channel. To investigate the role of the HCN4 channel in ventricular arrhythmia, we introduced a ventricular action potential of I(f) channel produced by HCN4 in a computer simulation model and found that the I(f) channel generated a leaky outward current during the plateau phase of ventricular action potential. Currents through the I(f) channel were suggested to contribute to the shortening of the action potential duration and the prevention of early after-depolarization in bradycardia. These observations suggested that the HCN4 channel played a preventive role in triggering bradycardia-induced ventricular arrhythmias.