Language and sensory characteristics are reflected in voice-evoked responses in low birth weight children.

BACKGROUND: Children born with very low birth weight (VLBW) are at higher risk for cognitive impairment, including language deficits and sensorimotor difficulties. Voice-evoked response (P1m), which has been suggested as a language development biomarker in young children, remains unexplored for its efficacy in VLBW children. Furthermore, the relation between P1m and sensory difficulties in VLBW children remains unclear. METHODS: 40 children with VLBW were recruited at 5-to-6 years old (26 male, 14 female, mean age of months ± SD, 80.0 ± 4.9). We measured their voice-evoked brain response using child-customized magnetoencephalography (MEG) and examined the relation between P1m and language conceptual inference ability and sensory characteristics. RESULTS: The final sample comprised 36 children (23 boys, 13 girls; ages 61-86 months; gestational ages 24-36 weeks). As a result of multiple regression analysis, voice-evoked P1m in the left hemisphere was correlated significantly with language ability (ß = 0.414 P = 0.015) and sensory hypersensitivity (ß = 0.471 P = 0.005). CONCLUSION: Our findings indicate that the relation between P1m and language conceptual inference ability observed in term children in earlier studies is replicated in VLBW children, and suggests P1m intensity as a biomarker of sensory sensitivity characteristics. IMPACT: We investigated brain functions related to language development and sensory problems in very low birth-weight children. In very low birth weight children at early school age, brain responses to human voices are associated with language conceptual inference ability and sensory hypersensitivity. These findings promote a physiological understanding of both language development and sensory characteristics in very low birth weight children.

Rats did not show evidence of prospective information-seeking: a pilot study.

Information-seeking behavior often features in research on metacognition in non-human animals; some species seek more information when they do not know the location of a food reward. Rats are known to do this in situations of uncertainty, but it is still unclear if they seek information prospectively for solving a later problem. In this study, we investigated rats' information-seeking responses in two areas that presented different cognitive challenges (N = 4). In one area, a memory task was presented in which rats could access a cue for a food reward during the information-seeking phase of a trial, but the cue was removed before the subsequent test phase. In the other area, a discrimination task presented a cue that was available in both the information-seeking and the test phases, so that it was not necessary to seek information prospectively. The memory and discrimination test trials were given in quasi-random order (Experiment 1). Rats explored in the memory task area no more than in the discrimination task area during the information-seeking phase, even after extensive training. When they were exposed exclusively to the memory task over multiple sessions (Experiment 2), they developed a strategy of exploring the available object cues. In Experiment 3, rats were found to stay longer in an area, which had an object than in other, less potentially informative areas; they were sensitive to the presence of information. Although these results did not support the existence of prospective information-seeking in rats, they do not necessarily imply that rats lack related abilities. This consideration is due to the constraints of the small sample size and the limited scope of the testing environment. Accumulating not only positive but also negative evidence would further understanding of the factors influencing metacognitive responses in non-human animals.

Detection of the 40 Hz auditory steady-state response with optically pumped magnetometers.

Magnetoencephalography (MEG) is a functional neuroimaging technique that noninvasively detects the brain magnetic field from neuronal activations. Conventional MEG measures brain signals using superconducting quantum interference devices (SQUIDs). SQUID-MEG requires a cryogenic environment involving a bulky non-magnetic Dewar flask and the consumption of liquid helium, which restricts the variability of the sensor array and the gap between the cortical sources and sensors. Recently, miniature optically pumped magnetometers (OPMs) have been developed and commercialized. OPMs do not require cryogenic cooling and can be placed within millimeters from the scalp. In the present study, we arranged six OPM sensors on the temporal area to detect auditory-related brain responses in a two-layer magnetically shielded room. We presented the auditory stimuli of 1 kHz pure-tone bursts with 200 ms duration and obtained the M50 and M100 components of auditory-evoked fields. We delivered the periodic stimuli with a 40 Hz repetition rate and observed the gamma-band power changes and inter-trial phase coherence of auditory steady-state responses at 40 Hz. We found that the OPM sensors have a performance comparable to that of conventional SQUID-MEG sensors, and our results suggest the feasibility of using OPM sensors for functional neuroimaging and brain-computer interface applications.

Alterations in brain networks in children with sub-threshold autism spectrum disorder: A magnetoencephalography study.

Individuals with sub-threshold autism spectrum disorder (ASD) are those who have social communication difficulties but do not meet the full ASD diagnostic criteria. ASD is associated with an atypical brain network; however, no studies have focused on sub-threshold ASD. Here, we used the graph approach to investigate alterations in the brain networks of children with sub-threshold ASD, independent of a clinical diagnosis. Graph theory is an effective approach for characterizing the properties of complex networks on a large scale. Forty-six children with ASD and 31 typically developing children were divided into three groups (i.e., ASD-Unlikely, ASD-Possible, and ASD-Probable groups) according to their Social Responsiveness Scale scores. We quantified magnetoencephalographic signals using a graph-theoretic index, the phase lag index, for every frequency band. Resultantly, the ASD-Probable group had significantly lower small-worldness (SW) in the delta, theta, and beta bands than the ASD-Unlikely group. Notably, the ASD-Possible group exhibited significantly higher SW than the ASD-Probable group and significantly lower SW than the ASD-Unlikely group in the delta band only. To our knowledge, this was the first report of the atypical brain network associated with sub-threshold ASD. Our findings indicate that magnetoencephalographic signals using graph theory may be useful in detecting sub-threshold ASD.

Effect of CNTNAP2 polymorphism on receptive language in children with autism spectrum disorder without language developmental delay.

AIM: The receptive language ability of individuals with autism spectrum disorder (ASD) seems to lag behind expressive language ability. Several autism-related genes may influence this developmental delay. Polymorphism of one such gene, namely, the contactin-associated protein-like 2 gene (CNTNAP2), affects receptive language in individuals with language delay. However, the association between CNTNAP2 polymorphism and receptive language in individuals with no language delay remains unclear. METHODS: We included 59 children with ASD and 57 children with typical development in this study and investigated this association using coarse-grained exact matching. RESULTS: We present the first evidence of an association between CNTNAP2 rs2710102 (A-allele carrier) and reduced receptive language ability in children with ASD whose language development was not delayed. Similarly, among children with typical development, A-allele carriers had lower receptive language ability, but the difference was non-significant. CONCLUSIONS: It is possible that the effect of rs2710102 on receptive language ability is larger in the presence of autism-related genes. Consequently, we speculate that the effect of rs2710102 on receptive language ability would be exerted in combination with other genes. These findings provide new insights into the genetic interactions between mutations associated with common language disorders and ASD and identify molecular mechanisms and risk alleles that contribute to receptive vocabulary. These findings also provide practical guidance in terms of providing candidate genetic markers that may provide opportunities for targeted early intervention to stratify risk and improve prognosis for poor receptive language development in children with ASD.

Altered sensory integration from body and language development in children with autism spectrum disorder.

Aim: Although atypical sensory motor processing has been investigated in children with autism spectrum disorder (ASD), whether or not atypical sensory motor processing is related to altered language function in children with ASD remains unclear. Methods: This study examined the relationship between sensory motor processing and language conceptual inference ability in 3-10-year-old children with (n = 61) and without (n = 114) ASD. Language performance was assessed using the language conceptual inference task of the Kaufman Assessment Battery for Children (K-ABC). Sensory processing was assessed using the Caregiver Sensory Profile. Results: In children with ASD, altered processing of the fine motor/perceptual factor scored by sensory profile was found to be significantly related to language conceptual inference ability in the K-ABC, representing the integrated abilities of language comprehension and language expression, which reflect language semantic concept formation. Conclusions: For children with ASD, the results suggest a relationship between difficulties of integrating sensory information perceived from the body adjusting fine movement and deficiencies of language semantic conceptual formation.

A common variant of CNTNAP2 is associated with sub-threshold autistic traits and intellectual disability.

Sub-threshold autistic traits are common in the general population. Children with sub-threshold autistic traits have difficulties with social adaptation. Contactin-associated protein-like 2 (CNTNAP2) is associated with the development of Autism spectrum disorder (ASD) and the single-nucleotide polymorphism rs2710102 (G/A) of CNTNAP2 is suggested to contribute to sub-threshold social impairments and intellectual disabilities. We recruited 67 children with Autistic disorder (AD) (49 boys, 18 girls, aged 38-98 months) and 57 typically developing (TD) children (34 boys, 23 girls, aged 53-90 months). We assessed the participants' intelligence and social reciprocity using the Kaufman Assessment Battery for Children (K-ABC) and the Social Responsiveness Scale (SRS), respectively. Genomic DNA was extracted from the buccal mucosa and genotyped for rs2710102. A chi-square test revealed a significant association between genotype and group [χ2(2) = 6.56, p = 0.038]. When a co-dominant model was assumed, the results from linear regression models demonstrated that TD children with A-carriers (AA + AG) presented higher SRS T-scores [t(55) = 2.11, p = 0.039] and lower simultaneous processing scale scores of K-ABC [t(55) = -2.19, p = 0.032] than those with GG homozygotes. These associations were not significant in children with ASD. TD children with the rs2710102 A-allele may have more sub-threshold autistic traits than those with GG homozygotes, reflected in higher SRS scores and lower simultaneous processing scale scores. These results support the use of genetic evidence to detect sub-threshold autistic traits.

Atypical Resting State Functional Neural Network in Children With Autism Spectrum Disorder: Graph Theory Approach.

Measuring whole brain networks is a promising approach to extract features of autism spectrum disorder (ASD), a brain disorder of widespread regions. Objectives of this study were to evaluate properties of resting-state functional brain networks in children with and without ASD and to evaluate their relation with social impairment severity. Magnetoencephalographic (MEG) data were recorded for 21 children with ASD (7 girls, 60-89 months old) and for 25 typically developing (TD) control children (10 girls, 60-91 months old) in a resting state while gazing at a fixation cross. After signal sources were localized onto the Desikan-Killiany brain atlas, statistical relations between localized activities were found and evaluated in terms of the phase lag index. After brain networks were constructed and after matching with intelligence using a coarsened exact matching algorithm, ASD and TD graph theoretical measures were compared. We measured autism symptoms severity using the Social Responsiveness Scale and investigated its relation with altered small-worldness using linear regression models. Children with ASD were found to have significantly lower small-worldness in the beta band (p = 0.007) than TD children had. Lower small-worldness in the beta band of children with ASD was associated with higher Social Responsiveness Scale total t-scores (p = 0.047). Significant relations were also inferred for the Social Awareness (p = 0.008) and Social Cognition (p = 0.015) sub-scales. Results obtained using graph theory demonstrate a difference between children with and without ASD in MEG-derived resting-state functional brain networks, and the relation of that difference with social impairment. Combining graph theory and MEG might be a promising approach to establish a biological marker for ASD.

Epileptiform discharges relate to altered functional brain networks in autism spectrum disorders.

Many individuals with autism spectrum disorders have comorbid epilepsy. Even in the absence of observable seizures, interictal epileptiform discharges are common in individuals with autism spectrum disorders. However, how these interictal epileptiform discharges are related to autistic symptomatology remains unclear. This study used magnetoencephalography to investigate the relation between interictal epileptiform discharges and altered functional brain networks in children with autism spectrum disorders. Instead of particularly addressing individual brain regions, we specifically examine network properties. For this case-control study, we analysed 70 children with autism spectrum disorders (52 boys, 18 girls, 38-92 months old) and 19 typically developing children (16 boys, 3 girls, 48-88 months old). After assessing the participants' social reciprocity using the Social Responsiveness Scale, we constructed graphs of functional brain networks from frequency band separated task-free magnetoencephalography recordings. Nodes corresponded to Desikan-Killiany atlas-based 68 brain regions. Edges corresponded to phase lag index values between pairs of brain regions. To elucidate the effects of the existence of interictal epileptiform discharges on graph metrics, we matched each of three pairs from three groups (typically developing children, children with autism spectrum disorders who had interictal epileptiform discharges and those who did not) in terms of age and sex. We used a coarsened exact matching algorithm and applied adjusted regression analysis. We also investigated the relation between social reciprocity and the graph metric. Results show that, in children with autism spectrum disorders, the average clustering coefficient in the theta band was significantly higher in children who had interictal epileptiform discharges. Moreover, children with autism spectrum disorders who had no interictal epileptiform discharges had a significantly lower average clustering coefficient in the theta band than typically developing children had. However, the difference between typically developing children and children with autism spectrum disorder who had interictal epileptiform discharges was not significant. Furthermore, the higher average clustering coefficient in the theta band corresponded to severe autistic symptoms in children with autism spectrum disorder who had interictal epileptiform discharges. However, the association was not significant in children with autism spectrum disorders who had no interictal epileptiform discharge. In conclusion, results demonstrate that alteration of functional brain networks in children with autism spectrum disorders depends on the existence of interictal epileptiform discharges. Interictal epileptiform discharges might 'normalize' the deviation of altered brain networks in autism spectrum disorders, increasing the clustering coefficient. However, when the effect exceeds tolerance, it actually exacerbates autistic symptoms.

Shorter P1m Response in Children with Autism Spectrum Disorder without Intellectual Disabilities.

(1) Background: Atypical auditory perception has been reported in individuals with autism spectrum disorder (ASD). Altered auditory evoked brain responses are also associated with childhood ASD. They are likely to be associated with atypical brain maturation. (2) Methods: This study examined children aged 5-8 years old: 29 with ASD but no intellectual disability and 46 age-matched typically developed (TD) control participants. Using magnetoencephalography (MEG) data obtained while participants listened passively to sinusoidal pure tones, bilateral auditory cortical response (P1m) was examined. (3) Results: Significantly shorter P1m latency in the left hemisphere was found for children with ASD without intellectual disabilities than for children with TD. Significant correlation between P1m latency and language conceptual ability was found in children with ASD, but not in children with TD. (4) Conclusions: These findings demonstrated atypical brain maturation in the auditory processing area in children with ASD without intellectual disability. Findings also suggest that ASD has a common neural basis for pure-tone sound processing and language development. Development of brain networks involved in language concepts in early childhood ASD might differ from that in children with TD.

Aberrant brain oscillatory coupling from the primary motor cortex in children with autism spectrum disorders.

Autism spectrum disorder (ASD) often involves dysfunction in general motor control and motor coordination, in addition to core symptoms. However, the neural mechanisms underlying motor dysfunction in ASD are poorly understood. To elucidate this issue, we focused on brain oscillations and their coupling in the primary motor cortex (M1). We recorded magnetoencephalography in 18 children with ASD, aged 5 to 7 years, and 19 age- and IQ-matched typically-developing children while they pressed a button during a video-game-like motor task. The motor-related gamma (70 to 90 Hz) and pre-movement beta oscillations (15 to 25 Hz) were analyzed in the primary motor cortex using an inverse method. To determine the coupling between beta and gamma oscillations, we applied phase-amplitude coupling to calculate the statistical dependence between the amplitude of fast oscillations and the phase of slow oscillations. We observed a motor-related gamma increase and a pre-movement beta decrease in both groups. The ASD group exhibited a reduced motor-related gamma increase and enhanced pre-movement beta decrease in the ipsilateral primary motor cortex. We found phase-amplitude coupling, in which high-gamma activity was modulated by the beta rhythm in the primary motor cortex. Phase-amplitude coupling in the ipsilateral primary motor cortex was reduced in the ASD group compared with the control group. Using oscillatory changes and their couplings, linear discriminant analysis classified the ASD and control groups with high accuracy (area under the receiver operating characteristic curve: 97.1%). The current findings revealed alterations in oscillations and oscillatory coupling, reflecting the dysregulation of motor gating mechanisms in ASD. These results may be helpful for elucidating the neural mechanisms underlying motor dysfunction in ASD, suggesting the possibility of developing a biomarker for ASD diagnosis.

Capuchin monkeys (Sapajus apella) failed to seek information for their potential forgetting in a computerized task.

Memory is always vulnerable to loss because it fades over time. To avoid the potential loss of a particular memory, individuals who can anticipate this loss might seek an opportunity to re-encode the information at the later point. Evidence shows that animals engage in online memory monitoring, but few studies have addressed whether they seek information prospectively to guard against potential forgetting. In the present study, to address this issue three capuchin monkeys were tested using a delayed matching-to-sample task with a cue signaling delay length (short or long). In the tests, subjects could choose at the onset of the delay whether or not to seek a re-presentation of a sample after the delay. Results showed that two monkeys sought re-presentation in the long delay more frequently than in the short delay, suggesting knowledge of the necessity of re-presentation based on knowing the length of the delay. However, further tests provided no evidence that this response was based on metacognitive cues. Whether capuchin monkeys are capable of prospective information-seeking for own potential forgetting remains to be established.

Prospective information-seeking in human children (Homo sapiens): When to seek and what to seek.

Human adults often envisage future events and prepare items or information in advance. Studies have shown that young children can also prepare items for upcoming events, but little is known about their ability to prepare information for such events. Here, we used nonverbal measures, which are widely used in comparative cognitive research, to ask whether children seek information for their future knowledge states or events. In Experiment 1, 4- and 5-year-olds had to find a sticker located under an opaque or transparent cup. The children could observe by peeking while an experimenter placed the sticker for the trial. We found that 5-year-olds peeked for longer in the opaque than the transparent condition but 4-year-olds did not. In Experiment 2, 5- and 6-year-olds had to find stickers in 2 rooms; in 1 room, an actor hid a sticker under 1 of 5 opaque cups, whereas in the other room, another actor placed a sticker under 1 of 5 transparent cups. Children could observe what the actors were doing via a monitor and then choose a room in which to search. Children of both age-groups watched events in the opaque-cup room longer than the transparent-cup room in the first trial. These results suggest that at least 5-year-olds can collect appropriate information for a future task. Our procedure should be easily adaptable for a range of nonhuman species. Studies using this procedure might reveal the phylogenetic distribution of this metacognitive ability. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Do capuchins (Sapajus apella) know how well they will remember? Analysis of delay length-dependency with memory strategies.

[Correction Notice: An Erratum for this article was reported online in Journal of Comparative Psychology on May 9 2019 (see record 2019-35064-001). Reports several errors in errors in the article: the descriptions of conditions in the Discussion section were incorrect, the number of decimal places for some statistical values was greater, the participants' names were swapped in Tables 1, 2, 3, and 4, and the labels indicating trial types in Figures 3 and 4 were swapped and so did not correctly match the data. All versions of this article have been corrected.] Flexibly changing information processing based on required cognitive resources allows adaptation in terms of cognitive parsimony. Several species have been shown to use temporal durations between memory acquisition and retrieval as a cue for memory-controlling and to engage selectively in active memorization in situations involving lower cognitive cost. However, few studies have addressed whether signaling delay length at different stages of memory affects memorization differently. In the present study with tufted capuchin monkeys (Sapajus apella), we added visual cues signaling upcoming delay length to a delayed matching-to-sample task, so that the monkeys were informed about how long information should be maintained at different points during with-sample or after-sample conditions. We investigated whether the monkeys changed their information processing depending on their expectation of the upcoming delay length and on whether encoding was controllable (4 s vs. 16 s, Experiment 1). The results indicate that two monkeys showed different patterns depending on whether encoding was controllable, whereas the third monkey never changed her strategy. The following experiment using shorter delays showed that one monkey showed a similar pattern across experiments, providing robust evidence for cognitive flexibility in accordance with relative task difficulty (1 s vs. 8 s, Experiment 2). Overall, our results suggest that capuchins adopt two kinds of strategies depending on the experimental context, that is, expending fewer resources on relatively difficult trials and/or maintaining their processing style irrespective of delays. Their strategies aiming at saving cognitive costs may reflect a psychological function to control memory formation either prospectively or retrospectively. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Thrombotic microangiopathy with intraglomerular IgM pseudothrombi in Waldenström macroglobulinemia and IgM monoclonal gammopathy.

IgM secreting myelomas or lymphomas, including Waldenström macroglobulinemia, are associated with a varied spectrum of renal pathology, including intracapillary hyaline deposits, cryoglobulin, membranoproliferative glomerulonephritis, amyloid, monoclonal immunoglobulin deposition disease, cast nephropathy, and lymphoma infiltration. We report our single institution experience, and describe five cases with distinctive glomerular pathology: intracapillary IgM pseudothrombi and thrombotic microangiopathic change, with glomerular intracellular crystals in two biopsies. Two patients were hypocomplementemic at presentation. This series adds to the recent literature on paraprotein associated thrombotic microangiopathy.

Pigeons (Columba livia) know when they will need hints: prospective metacognition for reference memory?

Despite their impressive cognitive abilities, avian species have shown less evidence for metacognition than mammals. We suspect that commonly used tasks such as matching to sample might be too demanding to allow metacognitive processing within birds' working memory. Here, we examined whether pigeons could control their behavior as a function of knowledge levels on a three-item sequence learning task, a reference memory task supposedly requiring fewer working memory resources. The experiment used two types of lists differing in familiarity. One was familiar to the pigeons through repeated exposure, whereas the other was novel in every new session. In test sessions, pigeons could choose between a trial with a hint specifying the next item to peck and one with no hint. However, successful responses in trials with a hint resulted in lowered rates of primary reinforcement: .60 in the first test and .75 in the second. Results showed that two of four pigeons chose the trial with a hint significantly more often before receiving a novel list than the familiar list in the four sessions of the first test, and three did so in the second test. Impressively, one bird showed robust evidence in the very first sessions in both tests. These results suggest that pigeons may monitor their long-term knowledge states and thereby control their environment before starting to solve a task.

Do pigeons (Columba livia) seek information when they have insufficient knowledge?

Seeking information in uncertain situations has been interpreted as evidence of metacognitive abilities. We examined whether pigeons could monitor their own knowledge states and seek new information when in need. In Experiment 1, we required the pigeons to learn novel sequences of responses for various trios of illustrations. On half of the trials, subjects were given the opportunity to ask for "hints" as to the next correct response in a sequence. If the subjects completed a trial correctly without any hints, they were rewarded with food and light. If the subjects sought one or more hints during the course of completing a trial correctly, they were rewarded either with food and light, or with light only. Incorrect responses resulted in a time-out. We analyzed when the pigeons sought hints. Two of four pigeons sought hints in early sessions more often than in the final sessions of learning novel sequences, and the frequency of hint-seeking was inversely correlated with accuracy on those trials in which hints were unavailable. In Experiment 2, however, the pigeons failed to generalize their "hint-seeking" behavior in a novel situation involving visual search as the primary task. In sum, the results suggest that this species might have an ability to differentiate between their own cognitive states of knowing and not knowing, although the evidence is inconclusive.