Infant ERPs separate children at risk of dyslexia who become good readers from those who become poor readers.

Dyslexia is heritable and associated with phonological processing deficits that can be reflected in the event-related potentials (ERPs). Here, we recorded ERPs from 2-month-old infants at risk of dyslexia and from a control group to investigate whether their auditory system processes /bAk/ and /dAk/ changes differently. The speech sounds were presented in an oddball paradigm. The children were followed longitudinally and performed a word reading fluency test in second grade. The infant ERPs were subsequently analyzed according to high or low reading fluency in order to find a neurophysiological precursor of poor reading fluency. The results show that the fluent reading children (from both the at-risk and the control group) processed the speech sound changes differentially in infancy as indicated by a mismatch response (MMR). In the control group the MMR was frontally positive and in the fluent at-risk group the MMR was parietally positive. The non-fluent at-risk group did not show an MMR. We conclude that at-risk children who became fluent readers were better at speech processing in infancy than those who became non-fluent readers. This indicates a very early speech processing deficit in the group of later non-fluent readers.

STXBP1 Syndrome Is Characterized by Inhibition-Dominated Dynamics of Resting-State EEG.

STXBP1 syndrome is a rare neurodevelopmental disorder caused by heterozygous variants in the STXBP1 gene and is characterized by psychomotor delay, early-onset developmental delay, and epileptic encephalopathy. Pathogenic STXBP1 variants are thought to alter excitation-inhibition (E/I) balance at the synaptic level, which could impact neuronal network dynamics; however, this has not been investigated yet. Here, we present the first EEG study of patients with STXBP1 syndrome to quantify the impact of the synaptic E/I dysregulation on ongoing brain activity. We used high-frequency-resolution analyses of classical and recently developed methods known to be sensitive to E/I balance. EEG was recorded during eyes-open rest in children with STXBP1 syndrome (n = 14) and age-matched typically developing children (n = 50). Brain-wide abnormalities were observed in each of the four resting-state measures assessed here: (i) slowing of activity and increased low-frequency power in the range 1.75-4.63 Hz, (ii) increased long-range temporal correlations in the 11-18 Hz range, (iii) a decrease of our recently introduced measure of functional E/I ratio in a similar frequency range (12-24 Hz), and (iv) a larger exponent of the 1/f-like aperiodic component of the power spectrum. Overall, these findings indicate that large-scale brain activity in STXBP1 syndrome exhibits inhibition-dominated dynamics, which may be compensatory to counteract local circuitry imbalances expected to shift E/I balance toward excitation, as observed in preclinical models. We argue that quantitative EEG investigations in STXBP1 and other neurodevelopmental disorders are a crucial step to understand large-scale functional consequences of synaptic E/I perturbations.

The Role of Categorical Speech Perception and Phonological Processing in Familial Risk Children With and Without Dyslexia.

Purpose: This study assessed whether a categorical speech perception (CP) deficit is associated with dyslexia or familial risk for dyslexia, by exploring a possible cascading relation from speech perception to phonology to reading and by identifying whether speech perception distinguishes familial risk (FR) children with dyslexia (FRD) from those without dyslexia (FRND). Method: Data were collected from 9-year-old FRD (n = 37) and FRND (n = 41) children and age-matched controls (n = 49) on CP identification and discrimination and on the phonological processing measures rapid automatized naming, phoneme awareness, and nonword repetition. Results: The FRD group performed more poorly on CP than the FRND and control groups. Findings on phonological processing align with the literature in that (a) phonological processing related to reading and (b) the FRD group showed the lowest phonological processing outcomes. Furthermore, CP correlated weakly with reading, but this relationship was fully mediated by rapid automatized naming. Conclusion: Although CP phonological skills are related to dyslexia, there was no strong evidence for a cascade from CP to phonology to reading. Deficits in CP at the behavioral level are not directly associated with dyslexia.

Auditory organization of sound sequences by a temporal or numerical regularity--a mismatch negativity study comparing musicians and non-musicians.

The human auditory system can encode regularities in the acoustic environment without the requirement of attention. We investigated whether the auditory system of musicians is more sensitive than that of non-musicians in encoding complex regularities. We presented tone sequences containing either a temporal or a numerical regularity. The sequence with the temporal regularity could be divided into segments of a constant duration while the segments contained a varying number of tones. The sequence with the numerical regularity, on the other hand, could be divided into segments containing a constant number of tones while the segments varied in duration. Auditory encoding of the regularity was determined by measuring whether an occasional segment lengthening, either in time or by number elicited the mismatch negativity (MMN). In both musicians and non-musicians, an MMN was elicited when the temporal regularity was violated. In contrast, only in musicians an MMN was elicited to violations of the numerical regularity. The results show that temporal processing is of general importance in audition since at an involuntary auditory processing stage a complex temporal regularity can be encoded irrespective of musical expertise. Furthermore, the auditory system of professional musicians can encode a numerical regularity without attention being required reflecting the functional importance of beat tracking in the perceptual organization of music.

Basic auditory processing is related to familial risk, not to reading fluency: an ERP study.

Less proficient basic auditory processing has been previously connected to dyslexia. However, it is unclear whether a low proficiency level is a correlate of having a familial risk for reading problems, or whether it causes dyslexia. In this study, children's processing of amplitude rise time (ART), intensity and frequency differences was measured with event-related potentials (ERPs). ERP components of interest are components reflective of auditory change detection; the mismatch negativity (MMN) and late discriminative negativity (LDN). All groups had an MMN to changes in ART and frequency, but not to intensity. Our results indicate that fluent readers at risk for dyslexia, poor readers at risk for dyslexia and fluent reading controls have an LDN to changes in ART and frequency, though the scalp activation of frequency processing was different for familial risk children. On intensity, only controls showed an LDN. Contrary to previous findings, our results suggest that neither ART nor frequency processing is related to reading fluency. Furthermore, our results imply that diminished sensitivity to changes in intensity and differential lateralization of frequency processing should be regarded as correlates of being at familial risk for dyslexia, that do not directly relate to reading fluency.

Linguistic processing in visual and modality-nonspecific brain areas: PET recordings during selective attention.

Positron emission tomography (PET) was used to investigate the neural basis of selective processing of linguistic material during concurrent presentation of multiple stimulus streams ("cocktail-party effect"). Fifteen healthy right-handed adult males were to attend to one of three simultaneously presented messages: one presented visually, one to the left ear, and one to the right ear. During the control condition, subjects attended to visually presented consonant letter strings and ignored auditory messages. This paper reports the modality-nonspecific language processing and visual word-form processing, whereas the auditory attention effects have been reported elsewhere [Cogn. Brain Res. 17 (2003) 201]. The left-hemisphere areas activated by both the selective processing of text and speech were as follows: the inferior prefrontal (Brodmann's area, BA 45, 47), anterior temporal (BA 38), posterior insular (BA 13), inferior (BA 20) and middle temporal (BA 21), occipital (BA 18/30) cortices, the caudate nucleus, and the amygdala. In addition, bilateral activations were observed in the medial occipito-temporal cortex and the cerebellum. Decreases of activation during both text and speech processing were found in the parietal (BA 7, 40), frontal (BA 6, 8, 44) and occipito-temporal (BA 37) regions of the right hemisphere. Furthermore, the present data suggest that the left occipito-temporal cortex (BA 18, 20, 37, 21) can be subdivided into three functionally distinct regions in the posterior-anterior direction on the basis of their activation during attentive processing of sublexical orthography, visual word form, and supramodal higher-level aspects of language.

Distributional vowel training is less effective for adults than for infants. A study using the mismatch response.

Distributional learning of speech sounds (i.e., learning from simple exposure to frequency distributions of speech sounds in the environment) has been observed in the lab repeatedly in both infants and adults. The current study is the first attempt to examine whether the capacity for using the mechanism is different in adults than in infants. To this end, a previous event-related potential study that had shown distributional learning of the English vowel contrast /æ/∼/ε/ in 2-to-3-month old Dutch infants was repeated with Dutch adults. Specifically, the adults were exposed to either a bimodal distribution that suggested the existence of the two vowels (as appropriate in English), or to a unimodal distribution that did not (as appropriate in Dutch). After exposure the participants were tested on their discrimination of a representative [æ] and a representative [ε], in an oddball paradigm for measuring mismatch responses (MMRs). Bimodally trained adults did not have a significantly larger MMR amplitude, and hence did not show significantly better neural discrimination of the test vowels, than unimodally trained adults. A direct comparison between the normalized MMR amplitudes of the adults with those of the previously tested infants showed that within a reasonable range of normalization parameters, the bimodal advantage is reliably smaller in adults than in infants, indicating that distributional learning is a weaker mechanism for learning speech sounds in adults (if it exists in that group at all) than in infants.

Fast phonetic learning occurs already in 2-to-3-month old infants: an ERP study.

An important mechanism for learning speech sounds in the first year of life is "distributional learning," i.e., learning by simply listening to the frequency distributions of the speech sounds in the environment. In the lab, fast distributional learning has been reported for infants in the second half of the first year; the present study examined whether it can also be demonstrated at a much younger age, long before the onset of language-specific speech perception (which roughly emerges between 6 and 12 months). To investigate this, Dutch infants aged 2 to 3 months were presented with either a unimodal or a bimodal vowel distribution based on the English /æ/~/ε/ contrast, for only 12 minutes. Subsequently, mismatch responses (MMRs) were measured in an oddball paradigm, where one half of the infants in each group heard a representative [æ] as the standard and a representative [ε] as the deviant, and the other half heard the same reversed. The results (from the combined MMRs during wakefulness and active sleep) disclosed a larger MMR, implying better discrimination of [æ] and [ε], for bimodally than unimodally trained infants, thus extending an effect of distributional training found in previous behavioral research to a much younger age when speech perception is still universal rather than language-specific, and to a new method (using event-related potentials). Moreover, the analysis revealed a robust interaction between the distribution (unimodal vs. bimodal) and the identity of the standard stimulus ([æ] vs. [ε]), which provides evidence for an interplay between a perceptual asymmetry and distributional learning. The outcomes show that distributional learning can affect vowel perception already in the first months of life.

Beat processing is pre-attentive for metrically simple rhythms with clear accents: an ERP study.

The perception of a regular beat is fundamental to music processing. Here we examine whether the detection of a regular beat is pre-attentive for metrically simple, acoustically varying stimuli using the mismatch negativity (MMN), an ERP response elicited by violations of acoustic regularity irrespective of whether subjects are attending to the stimuli. Both musicians and non-musicians were presented with a varying rhythm with a clear accent structure in which occasionally a sound was omitted. We compared the MMN response to the omission of identical sounds in different metrical positions. Most importantly, we found that omissions in strong metrical positions, on the beat, elicited higher amplitude MMN responses than omissions in weak metrical positions, not on the beat. This suggests that the detection of a beat is pre-attentive when highly beat inducing stimuli are used. No effects of musical expertise were found. Our results suggest that for metrically simple rhythms with clear accents beat processing does not require attention or musical expertise. In addition, we discuss how the use of acoustically varying stimuli may influence ERP results when studying beat processing.

Preliteracy signatures of poor-reading abilities in resting-state EEG.

The hereditary character of dyslexia suggests the presence of putative underlying neural anomalies already in preliterate age. Here, we investigated whether early neurophysiological correlates of future reading difficulties-a hallmark of dyslexia-could be identified in the resting-state EEG of preliterate children. The children in this study were recruited at birth and classified on the basis of parents' performance on reading tests to be at-risk of becoming poor readers (n = 48) or not (n = 14). Eyes-open rest EEG was measured at the age of 3 years, and the at-risk children were divided into fluent readers (n = 24) and non-fluent readers (n = 24) after reading assessment at their third grade of school. We found that fluent readers and non-fluent readers differed in normalized spectral amplitude. Non-fluent readers were characterized by lower amplitude in the delta-1 frequency band (0.5-2 Hz) and higher amplitude in the alpha-1 band (6-8 Hz) in multiple scalp regions compared to control and at-risk fluent readers. Interestingly, across groups these EEG biomarkers correlated with several behavioral test scores measured in the third grade. Specifically, the performance on reading fluency, phonological and orthographic tasks and rapid automatized naming task correlated positively with delta-1 and negatively with alpha-1. Together, our results suggest that combining family-risk status, neurophysiological testing and behavioral test scores in a longitudinal setting may help uncover physiological mechanisms implicated with neurodevelopmental disorders such as the predisposition to reading disabilities.

Temporal auditory processing at 17 months of age is associated with preliterate language comprehension and later word reading fluency: an ERP study.

Dyslexia is heritable and associated with auditory processing deficits. We investigate whether temporal auditory processing is compromised in young children at-risk for dyslexia and whether it is associated with later language and reading skills. We recorded EEG from 17 months-old children with or without familial risk for dyslexia to investigate whether their auditory system was able to detect a temporal change in a tone pattern. The children were followed longitudinally and performed an intelligence- and language development test at ages 4 and 4.5 years. Literacy related skills were measured at the beginning of second grade, and word- and pseudo-word reading fluency were measured at the end of second grade. The EEG responses showed that control children could detect the temporal change as indicated by a mismatch response (MMR). The MMR was not observed in at-risk children. Furthermore, the fronto-central MMR amplitude correlated with preliterate language comprehension and with later word reading fluency, but not with phonological awareness. We conclude that temporal auditory processing differentiates young children at risk for dyslexia from controls and is a precursor of preliterate language comprehension and reading fluency.

Change detection in newborns using a multiple deviant paradigm: a study using magnetoencephalography.

OBJECTIVE: Mismatch responses are elicited to changes in sound streams in healthy newborns. In the ideal case, these responses can predict cognitive problems later in life. We employed a multiple deviant paradigm for a fast assessment of the ability of the newborn brain to respond to various types of acoustic changes. METHODS: In 12 healthy newborns, we recorded an electroencephalogram (EEG) and magnetoencephalogram while presenting auditory stimuli. Between repeated stimuli, four types of acoustic changes (frequency, intensity, duration, and a gap) were presented, varying in deviance magnitude. RESULTS: One major response was present in the neonatal evoked potentials and fields at 250-260 ms. Magnetic mismatch responses were elicited to all change types except for the duration deviant and they were positive in polarity. The frequency deviant elicited more positive EEG amplitudes than the standard, whereas the response to the duration deviant was more negative. CONCLUSIONS: These results show that newborns can detect changes to at least four types of deviances within a sound stream. Furthermore, the use of magneto- and electroencephalography is complementary in newborns, since the methods may reveal different outcomes. SIGNIFICANCE: Further studies are warranted to determine whether the present study design can play a role in testing auditory function in clinical infant populations.

Object representation in the human auditory system.

One important principle of object processing is exclusive allocation. Any part of the sensory input, including the border between two objects, can only belong to one object at a time. We tested whether tones forming a spectro-temporal border between two sound patterns can belong to both patterns at the same time. Sequences were composed of low-, intermediate- and high-pitched tones. Tones were delivered with short onset-to-onset intervals causing the high and low tones to automatically form separate low and high sound streams. The intermediate-pitch tones could be perceived as part of either one or the other stream, but not both streams at the same time. Thus these tones formed a pitch 'border' between the two streams. The tones were presented in a fixed, cyclically repeating order. Linking the intermediate-pitch tones with the high or the low tones resulted in the perception of two different repeating tonal patterns. Participants were instructed to maintain perception of one of the two tone patterns throughout the stimulus sequences. Occasional changes violated either the selected or the alternative tone pattern, but not both at the same time. We found that only violations of the selected pattern elicited the mismatch negativity event-related potential, indicating that only this pattern was represented in the auditory system. This result suggests that individual sounds are processed as part of only one auditory pattern at a time. Thus tones forming a spectro-temporal border are exclusively assigned to one sound object at any given time, as are spatio-temporal borders in vision.

Implicit, intuitive, and explicit knowledge of abstract regularities in a sound sequence: an event-related brain potential study.

Implicit knowledge has been proposed to be the substrate of intuition because intuitive judgments resemble implicit processes. We investigated whether the automatically elicited mismatch negativity (MMN) component of the auditory event-related potentials (ERPs) can reflect implicit knowledge and whether this knowledge can be utilized for intuitive sound discrimination. We also determined the sensitivity of the attention-and task-dependent P3 component to intuitive versus explicit knowledge. We recorded the ERPs elicited in an "abstract" oddball paradigm. Tone pairs roving over different frequencies but with a constant ascending inter-pair interval, were presented as frequent standard events. The standards were occasionally replaced by deviating, descending tone pairs. The ERPs were recorded under both ignore and attend conditions. Subjects were interviewed and classified on the basis of whether or not they could datect the deviants. The deviants elicited an MMN even in subjects who subsequent to the MMN recording did not express awareness of the deviants. This suggests that these subjects possessed implicit knowledge of the sound-sequence structure. Some of these subjects learned, in an associative training session, to detect the deviants intuitively, that is, they could detect the deviants but did not give a correct description of how the deviants differed from the standards. Intuitive deviant detection was not accompanied by P3 elicitation whereas subjects who developed explicit knowledge of the sound sequence during the training did show a P3 to the detected deviants.

To musicians, the message is in the meter pre-attentive neuronal responses to incongruent rhythm are left-lateralized in musicians.

Musicians exchange non-verbal cues as messages when they play together. This is particularly true in music with a sketchy outline. Jazz musicians receive and interpret the cues when performance parts from a regular pattern of rhythm, suggesting that they enjoy a highly developed sensitivity to subtle deviations of rhythm. We demonstrate that pre-attentive brain responses recorded with magnetoencephalography to rhythmic incongruence are left-lateralized in expert jazz musicians and right-lateralized in musically inept non-musicians. The left-lateralization of the pre-attentive responses suggests functional adaptation of the brain to a task of communication, which is much like that of language.

Grouping of sequential sounds--an event-related potential study comparing musicians and nonmusicians.

It is believed that auditory processes governing grouping and segmentation of sounds are automatic and represent universal aspects of music perception (e.g., they are independent of the listener's musical skill). The present study challenges this view by showing that musicians and nonmusicians differ in their ability to preattentively group consecutive sounds. We measured event-related potentials (ERPs) from professional musicians and nonmusicians who were presented with isochronous tone sequences that they ignored. Four consecutive tones in a sequence could be grouped according to either pitch similarity or good continuation of pitch. Occasionally, the tone-group length was violated by a deviant tone. The mismatch negativity (MMN) was elicited to the deviants in both subject groups when the sounds could be grouped based on pitch similarity. In contrast, MMN was only elicited in musicians when the sounds could be grouped according to good continuation of pitch. These results suggest that some forms of auditory grouping depend on musical skill and that not all aspects of auditory grouping are universal.