Infant mismatch responses to speech-sound changes predict language development in preschoolers at risk for dyslexia.

OBJECTIVE: We investigated how infant mismatch responses (MMRs), which have the potential for providing information on auditory discrimination abilities, could predict subsequent development of pre-reading skills and the risk for familial dyslexia. METHODS: We recorded MMRs to vowel, duration, and frequency deviants in pseudo-words at birth and 28 months in a sample over-represented by infants with dyslexia risk. We examined MMRs' associations with pre-reading skills at 28 months and 4-5 years and compared the results in subgroups with vs. without dyslexia risk. RESULTS: Larger positive MMR (P-MMR) at birth was found to be associated with better serial naming. In addition, increased mismatch negativity (MMN) and late discriminative negativity (LDN), and decreased P-MMR at 28 months overall, were shown to be related to better pre-reading skills. The associations were influenced by dyslexia risk, which was also linked to poor pre-reading skills. CONCLUSIONS: Infant MMRs, providing information about the maturity of the auditory system, are associated with the development of pre-reading skills. Speech-processing deficits may contribute to deficits in language acquisition observed in dyslexia. SIGNIFICANCE: Infant MMRs could work as predictive markers of atypical linguistic development during early childhood. Results may help in planning preventive and rehabilitation interventions in children at risk of learning impairments.

Infancy and early childhood maturation of neural auditory change detection and its associations to familial dyslexia risk.

OBJECTIVE: We investigated early maturation of the infant mismatch response MMR, including mismatch negativity (MMN), positive MMR (P-MMR), and late discriminative negativity (LDN), indexing auditory discrimination abilities, and the influence of familial developmental dyslexia risk. METHODS: We recorded MMRs to vowel, duration, and frequency deviants in pseudo-words at 0, 6, and 28 months and compared MMRs in subgroups with vs. without dyslexia risk, in a sample over-represented by risk infants. RESULTS: Neonatal MMN to the duration deviant became larger and earlier by 28 months; MMN was elicited by more deviants only at 28 months. The P-MMR was predominant in infancy; its amplitude increased by 6 and decreased by 28 months; latency decreased with increasing age. An LDN emerged by 6 months and became larger and later by 28 months. Dyslexia risk affected MMRs and their maturation. CONCLUSIONS: MMRs demonstrate an expected maturational pattern with 2-3 peaks by 28 months. The effects of dyslexia risk are prominent but not always as expected. SIGNIFICANCE: This large-scale longitudinal study shows MMR maturation with three age groups and three deviants. Results illuminate MMR's relation to the adult responses, and hence their cognitive underpinnings, and help in identifying typical/atypical auditory development in early childhood.

Case report: The MSI-L/p-MMR metastatic rectal cancer patient who failed systemic therapy responds to anti-PD-1 immunotherapy after stereotactic body radiation-therapy.

Background: Traditionally, patients with microsatellite stability (MSS)/microsatellite instability-Low (MSI-L)/proficient mismatch repair (p-MMR) metastatic colorectal cancer (mCRC) have had poor benefit from immunotherapy. Therefore, how to enhance the response of immunotherapy is still a challenge for MSS/MSI-L/p-MMR CRC patient. Case presentation: We report a special case of a rectal cancer patient with programmed death-ligand 1 (PD-L1) negative expression, MSI-L/p-MMR, tumor mutational burden-low (TMB-L) and liver metastases, who partial response (PR) to immunotherapy after systemic therapy failure including chemotherapy, anti-angiogenesis therapy and stereotactic body radiation-therapy (SBRT). The computed tomography (CT) results showed that among three liver metastases had been reduction or disappearance after Tislelizumab treatment for three times. Besides, the carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA199) decrease and maintained at a low level for 3 months. The progression-free survival (PFS) of patient has exceeded 3 months. Conclusions: This case indicates that the patient with MSI-L/p-MMR mCRC can respond to anti-PD-1 immunotherapy after systemic therapy. And the SBRT (targeting liver metastases) may a method for increase-sensitivity of immunotherapy in CRC patients with MSI-L/p-MMR.

Non-speech and speech pitch perception among Cantonese-speaking children with autism spectrum disorder: An ERP study.

The present study compared how Cantonese-speaking children with Autism Spectrum Disorder (ASD) and their typically developing counterparts perceived speech pitch and non-speech pitch information using ERP measurements. Sixteen children with ASD (mean age = 10.42 years, SD = 2.12 years) and sixteen normal controls (mean age = 9.48 years, SD =.86 years) participated in two experiments, in which Cantonese lexical tone contrasts and non-speech pitch variations were presented to children following an oddball paradigm when they watched a silent movie. The results showed that: 1) When processing speech pitch contour, the two groups did not differ in the amplitude of mismatch response (p-MMR), while typically developing controls showed larger mismatch negativity (MMN) responses than children with ASD. In the processing of speech pitch height, more positive p-MMR was observed among children with ASD than among normal controls and stronger MMN was found for typically developing children than for children with ASD. 2) For the processing of non-speech pitch, MMN rather than p-MMR was observed and the two groups did not differ significantly with each other in the amplitudes of MMN. These results indicated that Cantonese-speaking children with ASD manifested impaired ability when processing speech pitch information (i.e., lexical tone), which was in line with previous research. However, they did not show the advantage in processing non-speech or auditory pitch information, which was not in agreement with the previous studies. Results were discussed from the perspective of how language background (i.e., Cantonese) might shape the perceptive abilities of children.

The Development of Mismatch Responses to Mandarin Lexical Tone in 12- to 24-Month-Old Infants.

This study explores the development of mismatch responses (MMRs) to Mandarin lexical tone changes in infants at 12, 18, and 24 months of age using the multi-deviant oddball paradigm with the low dipping Tone 3 (T3) as the standard, the high level Tone 1 (T1) as the large, and the high rising Tone 2 (T2) as the small deviant. The results show that the large acoustic change between T1/T3 elicited mismatch negativity (MMN) in all three age groups. The small acoustic change between T2/T3 elicited a positive mismatch response (P-MMR) at 12 and 18 months of age, but no MMR was found to the T2/T3 change at 24 months. The coexistence of MMN and P-MMR in the same age group implies that different mechanisms were used for discriminating large and small deviants. Infants were able to detect the T1/T3 change automatically and showed adult-like MMN as early as 6 months of age. However, the detection of the T2/T3 change remains effortful in infants under 24 months of age. These findings support the notion that MMN and P-MMR may be used to index the maturation of speech perception.

Feature-specific transition from positive mismatch response to mismatch negativity in early infancy: mismatch responses to vowels and initial consonants.

This study investigated how phonological saliency, deviance size, and maturation affect mismatch responses (MMRs) in early infancy. MMRs to Mandarin vowels and initial consonants were measured using a multi-deviant oddball paradigm in adults, newborns, and 6-month-olds. The vowel condition consisted of Mandarin syllable da as the standard, du as the large deviant and di as small deviant. As for initial consonant condition, we took syllable ba as standard, ga as large deviant, and ba as small deviant. While adults showed typical mismatch negativities (MMNs), newborns demonstrated broad positive MMRs (P-MMRs) to both initial consonants and vowels. For 6-month-olds, deviance size affected the polarity of MMRs to vowels. The large deviant du/da contrast elicited an adult-like MMN, while the small deviant di/da contrast elicited a P-MMR. Initial consonant changes elicited only P-MMRs, regardless of deviance size. In summary, MMRs to vowels switched from P-MMR at birth to MMN at 6 months. However, the polarity transition was not found for MMRs to initial consonants. The developmental trajectories of MMRs to vowels and initial consonants further support the phonological saliency hypothesis.

Segmental and suprasegmental features in speech perception in Cantonese-speaking second graders: an ERP study.

Using a multiple-deviant oddball paradigm, this study examined second graders' brain responses to Cantonese speech. We aimed to address the question of whether a change in a consonant or lexical tone could be automatically detected by children. We measured auditory mismatch responses to place of articulation and voice onset time (VOT), reflecting segmental perception, as well as Cantonese lexical tones including level tone and contour tone, reflecting suprasegmental perception. The data showed that robust mismatch negativities (MMNs) were elicited by all deviants in the time window of 300-500 ms in second graders. Moreover, relative to the standard stimuli, the VOT deviant elicited a robust positive mismatch response, and the level tone deviant elicited a significant MMN in the time window of 150-300 ms. The findings suggest that Hong Kong second graders were sensitive to neural discriminations of speech sounds both at the segmental and suprasegmental levels.

The impact of spectral resolution on the mismatch response to Mandarin Chinese tones: an ERP study of cochlear implant simulations.

OBJECTIVE: This study examined the impact of spectral resolution on the processing of lexical tones and the number of frequency channels required for a cochlear implant (CI) to transmit Chinese tonal information to the brain. METHODS: ERPs were recorded in an auditory oddball task. Normal-hearing participants listened to speech sounds of two tones and their CI simulations in 1, 4, 8, or 32 channels. The mismatch response elicited by speech sounds and CI simulations in different numbers of channels were compared. RESULTS: The mismatch negativity (MMN) was observed for speech sounds. For the 1-channel CI simulations, deviants elicited a more positive waveform than standard stimuli. No MMN response was observed with the 4-channel simulations. A reliable MMN response was observed for the 8- and 32-channel simulations. The MMN responses elicited by the 8- and 32-channel simulations were equivalent in magnitudes and smaller than that elicited by speech sounds. CONCLUSIONS: More than eight frequency channels are required for a CI to transmit Chinese tonal information. The presence of both positive and negative mismatch responses suggests multiple mechanisms underlying auditory mismatch responses. SIGNIFICANCE: The current findings of spectral resolution constraints on the transmission of tonal information should be taken into account in the design of the CI devices.

Neural correlates of acoustic cues of English lexical stress in Cantonese-speaking children.

The present study investigated the temporal course of neural discriminations of acoustic cues of English lexical stress (i.e., pitch, intensity and duration) in Cantonese-speaking children. We used an event-related potential (ERP) measure with a multiple-deviant oddball paradigm to record auditory mismatch responses to four deviants, namely, a change in pitch, intensity, or duration, or a change in all three acoustic dimensions, of English lexical stress in familiar words. In the time window of 170-270 ms, we found that the pitch deviant elicited significant positive mismatch responses (p-MMRs) and that the duration deviant elicited a mismatch negativity (MMN) response as compared with the standard. In the time window of 270-400 ms, the intensity deviant elicited a significant p-MMR, whereas both the duration and the three-dimension changed deviants elicited significant MMNs. These results suggest that Cantonese-speaking children are sensitive to either single or convergent acoustic cues of English words, and that the relative weighting of pitch, intensity and duration in stress processing may correlate with different ERP components at different time windows in Cantonese second graders.