Structural white matter connectometry of reading and dyslexia.

Current views on the neural network subserving reading and its deficits in dyslexia rely largely on evidence derived from functional neuroimaging studies. However, understanding the structural organization of reading and its aberrations in dyslexia requires a hodological approach, studies of which have not provided consistent findings. Here, we adopted a whole brain hodological approach and investigated relationships between structural white matter connectivity and reading skills and phonological processing in a cross-sectional study of 44 adults using individual local connectome matrix from diffusion MRI data. Moreover, we performed quantitative anisotropy aided differential tractography to uncover structural white matter anomalies in dyslexia (23 dyslexics and 21 matched controls) and their correlation to reading-related skills. The connectometry analyses indicated that reading skills and phonological processing were both associated with corpus callosum (tapetum), forceps major and minor, as well as cerebellum bilaterally. Furthermore, the left dorsal and right thalamic pathways were associated with phonological processing. Differential tractography analyses revealed structural white matter anomalies in dyslexics in the left ventral route and bilaterally in the dorsal route compared to the controls. Connectivity deficits were also observed in the corpus callosum, forceps major, vertical occipital fasciculus and corticostriatal and thalamic pathways. Altered structural connectivity in the observed differential tractography results correlated with poor reading skills and phonological processing. Using a hodological approach, the current study provides novel evidence for the extent of the reading-related connectome and its aberrations in dyslexia. The results conform current functional neuroanatomical models of reading and developmental dyslexia but provide novel network-level and tract-level evidence on structural connectivity anomalies in dyslexia, including the vertical occipital fasciculus.

TMS uncovers details about sub-regional language-specific processing networks in early bilinguals.

Despite numerous functional neuroimaging and intraoperative electrical cortical mapping studies aimed at investigating the cortical organisation of native (L1) and second (L2) language processing, the neural underpinnings of bilingualism remain elusive. We investigated whether the neural network engaged in speech production over the bilateral posterior inferior frontal gyrus (pIFG) is the same (i.e., shared) or different (i.e., language-specific) for the two languages of bilingual speakers. Navigated transcranial magnetic stimulation (TMS) was applied over the left and right posterior inferior gyrus (pIFG), while early simultaneous bilinguals performed a picture naming task with their native languages. An ex-Gaussian distribution was fitted to the naming latencies and the resulting parameters were compared between languages and across stimulation conditions. The results showed that although the naming performance in general was highly comparable between the languages, TMS produced a language-specific effect when the pulses were delivered to the left pIFG at 200 ms poststimulus. We argue that this result causally demonstrates, for the first time, that even within common language-processing areas, there are distinct language-specific neural populations for the different languages in early simultaneous bilinguals.

Sluggish cognitive tempo in children and adolescents with higher functioning autism spectrum disorders: Social impairments and internalizing symptoms.

Sluggish cognitive tempo (SCT) was introduced in 1980s in the field of attention deficit hyperactivity disorder (ADHD). Studies indicate that symptoms of SCT are separate from symptoms of ADHD and independently associated with multiple domains of functioning in clinical groups and in typical development. We assessed whether similar pattern would apply to higher functioning autism spectrum disorders (ASD). Children with higher functioning ASD (N = 55; 5-15 years) were divided into the ASD+High SCT (n = 17), the ASD+Medium SCT (n = 18) and the ASD+Low SCT (n = 20) groups based on parent-rated daydreaming and slowness on the Five to Fifteen questionnaire (FTF). The groups were compared on SCT-related impairments found in previous studies: social skills, academic functioning, psychiatric symptoms, and processing speed. Assessment methods were the FTF, the Development and Well-Being Assessment, and the Coding subtest of the WISC-III. The ADHD symptoms were statistically controlled due to the overlap between SCT and ADHD. The ASD+High SCT and ASD+Medium SCT groups were significantly more likely to have the most pronounced social impairments, and the ASD+High SCT group had significantly higher rate of internalizing disorders compared to the ASD+Low SCT group. Our results suggest that children with higher functioning ASD and high or medium levels of SCT symptoms could be at higher risk for psychosocial impairments than children with higher functioning ASD with low levels of SCT symptoms. Co-occurring ADHD symptoms do not explain the finding. Recognizing SCT symptoms in higher functioning ASD would be important to targeting preventive support.

Cortical speech and non-speech discrimination in relation to cognitive measures in preschool children.

Effective speech sound discrimination at preschool age is known to be a prerequisite for the development of language skills and later literacy acquisition. However, the speech specificity of cortical discrimination skills in small children is currently not known, as previous research has either studied speech functions without comparison with non-speech sounds, or used much simpler sounds such as harmonic or sinusoidal tones as control stimuli. We investigated the cortical discrimination of five syllable features (consonant, vowel, vowel duration, fundamental frequency, and intensity), covering both segmental and prosodic phonetic changes, and their acoustically matched non-speech counterparts in 63 6-year-old typically developed children, by using a multi-feature mismatch negativity (MMN) paradigm. Each of the five investigated features elicited a unique pattern of differentiating negativities: an early differentiating negativity, MMN, and a late differentiating negativity. All five studied features showed speech-related enhancement of at least one of these responses, suggesting experience-related neural commitment in both phonetic and prosodic speech processing. In addition, the cognitive performance and language skills of the children were tested extensively. The speech-related neural enhancement was positively associated with the level of performance in several neurocognitive tasks, indicating a relationship between successful establishment of cortical memory traces for speech and enhanced cognitive functioning. The results contribute to the understanding of typical developmental trajectories of linguistic vs. non-linguistic auditory skills, and provide a reference for future studies investigating deficits in language-related disorders at preschool age.

Long-term influence of recurrent acute otitis media on neural involuntary attention switching in 2-year-old children.

BACKGROUND: A large group of young children are exposed to repetitive middle ear infections but the effects of the fluctuating hearing sensations on immature central auditory system are not fully understood. The present study investigated the consequences of early childhood recurrent acute otitis media (RAOM) on involuntary auditory attention switching. METHODS: By utilizing auditory event-related potentials, neural mechanisms of involuntary attention were studied in 22-26 month-old children (N = 18) who had had an early childhood RAOM and healthy controls (N = 19). The earlier and later phase of the P3a (eP3a and lP3a) and the late negativity (LN) were measured for embedded novel sounds in the passive multi-feature paradigm with repeating standard and deviant syllable stimuli. The children with RAOM had tympanostomy tubes inserted and all the children in both study groups had to have clinically healthy ears at the time of the measurement assessed by an otolaryngologist. RESULTS: The results showed that lP3a amplitude diminished less from frontal to central and parietal areas in the children with RAOM than the controls. This might reflect an immature control of involuntary attention switch. Furthermore, the LN latency was longer in children with RAOM than in the controls, which suggests delayed reorientation of attention in RAOM. CONCLUSIONS: The lP3a and LN responses are affected in toddlers who have had a RAOM even when their ears are healthy. This suggests detrimental long-term effects of RAOM on the neural mechanisms of involuntary attention.

Learning-induced neural plasticity of speech processing before birth.

Learning, the foundation of adaptive and intelligent behavior, is based on plastic changes in neural assemblies, reflected by the modulation of electric brain responses. In infancy, auditory learning implicates the formation and strengthening of neural long-term memory traces, improving discrimination skills, in particular those forming the prerequisites for speech perception and understanding. Although previous behavioral observations show that newborns react differentially to unfamiliar sounds vs. familiar sound material that they were exposed to as fetuses, the neural basis of fetal learning has not thus far been investigated. Here we demonstrate direct neural correlates of human fetal learning of speech-like auditory stimuli. We presented variants of words to fetuses; unlike infants with no exposure to these stimuli, the exposed fetuses showed enhanced brain activity (mismatch responses) in response to pitch changes for the trained variants after birth. Furthermore, a significant correlation existed between the amount of prenatal exposure and brain activity, with greater activity being associated with a higher amount of prenatal speech exposure. Moreover, the learning effect was generalized to other types of similar speech sounds not included in the training material. Consequently, our results indicate neural commitment specifically tuned to the speech features heard before birth and their memory representations.

Rapid and automatic speech-specific learning mechanism in human neocortex.

A unique feature of human communication system is our ability to rapidly acquire new words and build large vocabularies. However, its neurobiological foundations remain largely unknown. In an electrophysiological study optimally designed to probe this rapid formation of new word memory circuits, we employed acoustically controlled novel word-forms incorporating native and non-native speech sounds, while manipulating the subjects' attention on the input. We found a robust index of neurolexical memory-trace formation: a rapid enhancement of the brain's activation elicited by novel words during a short (~30min) perceptual exposure, underpinned by fronto-temporal cortical networks, and, importantly, correlated with behavioural learning outcomes. Crucially, this neural memory trace build-up took place regardless of focused attention on the input or any pre-existing or learnt semantics. Furthermore, it was found only for stimuli with native-language phonology, but not for acoustically closely matching non-native words. These findings demonstrate a specialised cortical mechanism for rapid, automatic and phonology-dependent formation of neural word memory circuits.

Background Noise Degrades Central Auditory Processing in Toddlers.

OBJECTIVES: Noise, as an unwanted sound, has become one of modern society's environmental conundrums, and many children are exposed to higher noise levels than previously assumed. However, the effects of background noise on central auditory processing of toddlers, who are still acquiring language skills, have so far not been determined. The authors evaluated the effects of background noise on toddlers' speech-sound processing by recording event-related brain potentials. The hypothesis was that background noise modulates neural speech-sound encoding and degrades speech-sound discrimination. DESIGN: Obligatory P1 and N2 responses for standard syllables and the mismatch negativity (MMN) response for five different syllable deviants presented in a linguistic multifeature paradigm were recorded in silent and background noise conditions. The participants were 18 typically developing 22- to 26-month-old monolingual children with healthy ears. RESULTS: The results showed that the P1 amplitude was smaller and the N2 amplitude larger in the noisy conditions compared with the silent conditions. In the noisy condition, the MMN was absent for the intensity and vowel changes and diminished for the consonant, frequency, and vowel duration changes embedded in speech syllables. Furthermore, the frontal MMN component was attenuated in the noisy condition. However, noise had no effect on P1, N2, or MMN latencies. CONCLUSIONS: The results from this study suggest multiple effects of background noise on the central auditory processing of toddlers. It modulates the early stages of sound encoding and dampens neural discrimination vital for accurate speech perception. These results imply that speech processing of toddlers, who may spend long periods of daytime in noisy conditions, is vulnerable to background noise. In noisy conditions, toddlers' neural representations of some speech sounds might be weakened. Thus, special attention should be paid to acoustic conditions and background noise levels in children's daily environments, like day-care centers, to ensure a propitious setting for linguistic development. In addition, the evaluation and improvement of daily listening conditions should be an ordinary part of clinical intervention of children with linguistic problems.

Effects of recurrent acute otitis media on cortical speech-sound processing in 2-year old children.

OBJECTIVES: To investigate at the age of 2 years the effects of childhood recurrent acute otitis media (RAOM) on central auditory processing by using cortical event-related potentials elicited by syllable stimuli. DESIGN: During a 1-year period, 22- to 26-month-old children fulfilling the criteria for tympanostomy tube insertion in Oulu University Hospital, Oulu, Finland, were recruited to the RAOM group (N = 20). The control group (N = 19) was matched by age, sex, and mother's educational level. In both groups, children were typically developing and had no family history of language disorder or developmental language problems. Finnish syllables /ke:/ and /pi:/ as standards and their variants with changes in frequency, intensity, vowel, consonant, and vowel duration as deviants were used to record P1, N2, and mismatch negativity (MMN) responses in the multifeature paradigm. The clinically healthy ears at the time of registration were a prerequisite for the participation. RESULTS: Children with RAOM and their controls showed the age-typical P1 and N2 responses with no differences in the amplitudes or latencies between the groups, which suggests unaffected basic encoding of sound features and sound representation formation. However, the groups showed different auditory discrimination profiles. In children with RAOM, frequency and vowel MMN amplitudes were increased. Furthermore, the MMN latency for the frequency change was shorter and the frequency MMN amplitude lateralized to the left hemisphere in the RAOM group instead of an adult-like right-hemispheric lateralization observed in the controls. The children with RAOM had a more anterior MMN amplitude scalp distribution for the intensity change than control children. In addition, the MMN amplitude elicited by consonant change was evenly distributed unlike in controls, who had a left-side preponderant lateralization. Taken together, these results suggest an elevated responsiveness for frequency, vowel, and intensity changes, and an immature pattern of discriminating small speech sound contrasts in children with RAOM. CONCLUSIONS: The results suggest that childhood RAOM does not affect the central auditory pathway integrity or sound encoding. However, RAOM may lead to aberrant preattentive discrimination of sound features even when the peripheral auditory input is normal. These results are clinically significant because even transient problems with auditory processing may delay language development.

Infant neural speech encoding is associated with pre-reading skill development.

OBJECTIVE: We longitudinally investigated whether infant P1 and N2 ERPs recorded in newborns and at 28 months could predict pre-reading skills at 28 months and 4-5 years. METHODS: We recorded ERPs to a pseudoword in newborns and at 28 months in a sample over-represented by infants with familial dyslexia risk. Using multiple linear regression models, we examined P1 and N2 associations with pre-reading skills at 28 months and 4-5 years. RESULTS: Shorter latencies of the newborn P1 predicted faster serial naming at 28 months. Larger amplitudes and shorter latencies of P1 at 28 months predicted better serial naming abilities and auditory working memory across the pre-reading stage. Right-lateralized P1 and N2 were related to poorer pre-reading skills. CONCLUSIONS: Infant ERPs, particularly P1, providing information about neural speech encoding abilities, are associated with pre-reading skill development. SIGNIFICANCE: Infant and early childhood neural speech encoding abilities may work as early predictive markers of reading development and impairment. This study may help to plan early interventions targeting phonological processing to prevent or ameliorate learning deficits.

Establishing neural representations for new word forms in 12-month-old infants.

During the first year of life, infants start to learn the lexicon of their native language. Word learning includes the establishment of longer-term representations for the phonological form and the meaning of the word in the brain, as well as the link between them. However, it is not known how the brain processes word forms immediately after they have been learned. We familiarized 12-month-old infants (N = 52) with two pseudowords and studied their neural signatures. Specifically, we determined whether a newly learned word form elicits neural signatures similar to those observed when a known word is recognized (i.e., when a well-established word representation is activated, eliciting enhanced mismatch responses) or whether the processing of a newly learned word form shows the suppression of the neural response along with the principles of predictive coding of a learned rule (i.e., the order of the syllables of the new word form). The pattern of results obtained in the current study suggests that recognized word forms elicit a mismatch response of negative polarity, similar to newly learned and previously known words with an established representation in long-term memory. In contrast, prediction errors caused by acoustic novelty or deviation from the expected order in a sequence of (pseudo)words elicit responses of positive polarity. This suggests that electric brain activity is not fully explained by the predictive coding framework.

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.

Prerequisites of language acquisition in the newborn brain.

Learning to decode and produce speech is one of the most demanding tasks faced by infants. Nevertheless, infants typically utter their first words within a year, and phrases soon follow. Here we review cognitive abilities of newborn infants that promote language acquisition, focusing primarily on studies tapping neural activity. The results of these studies indicate that infants possess core adult auditory abilities already at birth, including statistical learning and rule extraction from variable speech input. Thus, the neonatal brain is ready to categorize sounds, detect word boundaries, learn words, and separate speech streams: in short, to acquire language quickly and efficiently from everyday linguistic input.

Development of associations between elementary school students' mindsets and attentional neural processing of feedback in an arithmetic task.

The aim of this study was to examine the development of the associations between elementary school students' mindsets and the attentional neural processing of positive and negative feedback in math. For this, we analyzed data collected twice from 100 Finnish elementary school students. During the autumn semesters of their 3rd and 4th grade, the participants' general intelligence mindset and math ability mindset were measured with a questionnaire, and their brain responses elicited by performance-relevant feedback were recorded during an arithmetic task. We found that students' fixed mindsets about general intelligence and math ability were associated with greater attention allocated to positive feedback as indicated by a larger P300. These associations were driven by the effects of mindsets on attention allocation to positive feedback in grade 4. Additionally, 4th graders' more fixed general intelligence mindset was marginally associated with greater attention allocated to negative feedback. In addition, the effects of both mindsets on attention allocation to feedback were marginally stronger when the children were older. The present results, although marginal in the case of negative feedback and mainly driven by effects in grade 4, are possibly a reflection of the greater self-relevance of feedback stimuli for students with a more fixed mindset. It is also possible that these findings reflect the fact that, in evaluative situations, mindset could influence stimulus processing in general. The marginal increase in the effects of mindsets as children mature may reflect the development of coherent mindset meaning systems during elementary school years.

The mismatch negativity: an index of cognitive decline in neuropsychiatric and neurological diseases and in ageing.

Cognitive impairment is a core element shared by a large number of different neurological and neuropsychiatric diseases. Irrespective of their different aetiologies and symptomatologies, most appear to converge at the functional deficiency of the auditory-frontal cortex network of auditory discrimination, which indexes cognitive impairment shared by these abnormalities. This auditory-frontal cortical deficiency, and hence cognitive decline, can now be objectively measured with the mismatch negativity and its magnetic equivalent. The auditory-frontal cortical network involved seems, therefore, to play a pivotal, unifying role in the different abnormalities. It is, however, more likely that the dysfunction that can be detected with the mismatch negativity and its magnetoencephalographic equivalent manifests a more widespread brain disorder, namely, a deficient N-methyl-D-aspartate receptor function, shared by these abnormalities and accounting for most of the cognitive decline.

More efficient formation of longer-term representations for word forms at birth can be linked to better language skills at 2 years.

Infants are able to extract words from speech early in life. Here we show that the quality of forming longer-term representations for word forms at birth predicts expressive language ability at the age of two years. Seventy-five neonates were familiarized with two spoken disyllabic pseudowords. We then tested whether the neonate brain predicts the second syllable from the first one by presenting a familiarized pseudoword frequently, and occasionally violating the learned syllable combination by different rare pseudowords. Distinct brain responses were elicited by predicted and unpredicted word endings, suggesting that the neonates had learned the familiarized pseudowords. The difference between responses to predicted and unpredicted pseudowords indexing the quality of word-form learning during familiarization significantly correlated with expressive language scores (the mean length of utterance) at 24 months in the same infant. These findings suggest that 1) neonates can memorize disyllabic words so that a learned first syllable generates predictions for the word ending, and 2) early individual differences in the quality of word-form learning correlate with language skills. This relationship helps early identification of infants at risk for language impairment.

Association of lifetime major depressive disorder with enhanced attentional sensitivity measured with P3 response in young adult twins.

Major depression is associated with alterations in the auditory P3 event-related potential (ERP). However, the persistence of these abnormalities after recovery from depressive episodes, especially in young adults, is not well known. Furthermore, the potential influence of substance use on this association is poorly understood. Young adult twin pairs (N = 177) from the longitudinal FinnTwin16 study were studied with a psychiatric interview, and P3a and P3b ERPs elicited by task-irrelevant novel sounds and targets, respectively. Dyadic linear mixed-effect models were used to distinguish the effects of lifetime major depressive disorder from familial factors and effects of alcohol problem drinking and tobacco smoking. P3a amplitude was significantly increased and P3b latency decreased, in individuals with a history of lifetime major depression, when controlling the fixed effects of alcohol abuse, tobacco, gender, twins' birth order, and zygosity. These results suggest that past lifetime major depressive disorder may be associated with enhanced attentional sensitivity.

Event-related potentials reflecting the frequency of unattended spoken words: a neuronal index of connection strength in lexical memory circuits?

How are words represented in the human brain and can these representations be qualitatively assessed with respect to their structure and properties? Recent research demonstrates that neurophysiological signatures of individual words can be measured when subjects do not focus their attention on speech input. These automatic activations, which take the form of negative deflections of event-related potentials, can appear surprisingly early (within ~200 ms) and are based on robust connections within neuronal memory circuits encoding individual words that ignite even when attentional resources are scarce. A new and critical prediction of this framework is that words with high frequency of occurrence have especially strong connections of their underlying memory circuits and should thus yield more negative ERPs compared with rarer words. We tested this prediction by presenting our subjects, in passive non-attend conditions, with acoustically matched high- and low-frequency words along with pseudo-words. Using factorial and correlation analyses, we found that already at ~120 ms after the spoken stimulus information was available, amplitude of brain responses was modulated by the words' lexical frequency. Topographic mapping and source analysis suggested that this early automatic frequency effect originates from the left inferior-frontal cortices. While, at this early latency, lexical differences between words and pseudo-words (more negative-going potential for meaningful words) could be seen only for the most frequent word stimuli, later-on (~270 ms), a more global lexicality effect with bilateral perisylvian sources was found for all stimuli, suggesting faster access to more frequent lexical entries. Our results support the account of word memory traces as interconnected neuronal circuits, and suggest that speed and magnitude of their activation are determined by their internal connection strength, which, in turn, is determined by the everyday language use.

A longitudinal twin study of effects of adolescent alcohol abuse on the neurophysiology of attention and orienting.

BACKGROUND: Long-term functional brain effects of adolescent alcohol abuse remain uncertain, partially because of difficulties in distinguishing inherited deficits from neuronal effects of ethanol and by confounds associated with alcohol abuse, especially nicotine exposure. We conducted a longitudinal twin study to determine neurocognitive effects of adolescent alcohol abuse, as measured with the auditory event-related potential (ERP) component P3, a putative marker of genetic vulnerability to alcoholism. METHODS: Twin pairs (N=177; 150 selected for intrapair concordance/discordance for alcohol-related problems at age 18½) were recruited from ongoing studies of twins born 1975-1979 in Finland. Alcohol and tobacco use were assessed with questionnaires at ages 16, 17, 18½, and ~25, and by a structured psychiatric interview concurrent with the ERP testing at mean age 25.8. During ERP recordings, subjects were instructed to detect target tones within a train of frequent "standards" and to ignore occasional "novel" sounds. To distinguish familial factors from ethanol effects, ERP and self-reported alcohol use measures were incorporated into hierarchical multiple regression (HMR) analysis, and intrapair differences in ERP were associated with intra-pair differences in alcohol variables. RESULTS: Novel-sound P3 amplitude correlated negatively with self-reported alcohol use in both between- and within-family analyses. No similar effect was observed for target-tone P3. HMR results suggest that twins' similarity for novel-sound P3 amplitude is modulated by their alcohol use, and this effect of alcohol use is influenced by genetic factors. CONCLUSIONS: Our results, from a large sample of twins selected from a population-based registry for pairwise concordance/discordance for alcohol problems at 18½, demonstrate that adolescent alcohol abuse is associated with subtle neurophysiological changes in attention and orienting. The changes are reflected in decreased novel-sound P3 amplitude and may be modified by genetic factors.