Developmental course of the repetition effect and change detection responses from infancy through childhood: a longitudinal study.

Neuronal repetition effect (repetition suppression and repetition enhancement) and change detection responses are fundamental brain responses that have implications in learning and cognitive development in infants and children. Studies have shown altered neuronal repetition and change detection responses in various clinical populations. However, the developmental course of these neuronal responses from infancy through childhood is still unknown. Using an electroencephalography oddball task, we investigate the developmental peculiarities of repetition effect and change detection responses in 43 children that we followed longitudinally from 3 months to 4 years of age. Analyses were conducted on theta (3-5 Hz), alpha (5-10 Hz), and beta (10-30 Hz) time-frequency windows. Results indicated that in the theta time-frequency window, in frontocentral and frontal regions of the brain, repetition and change detection responses followed a U-shaped pattern from 3 months to 4 years of age. Moreover, the change detection response was stronger in young infants compared to older children in frontocentral regions, regardless of the time-frequency window. Our findings add to the evidence of top-down modulation of perceptual systems in infants and children.

Genome-wide analysis of gene dosage in 24,092 individuals estimates that 10,000 genes modulate cognitive ability.

Genomic copy number variants (CNVs) are routinely identified and reported back to patients with neuropsychiatric disorders, but their quantitative effects on essential traits such as cognitive ability are poorly documented. We have recently shown that the effect size of deletions on cognitive ability can be statistically predicted using measures of intolerance to haploinsufficiency. However, the effect sizes of duplications remain unknown. It is also unknown if the effect of multigenic CNVs are driven by a few genes intolerant to haploinsufficiency or distributed across tolerant genes as well. Here, we identified all CNVs > 50 kilobases in 24,092 individuals from unselected and autism cohorts with assessments of general intelligence. Statistical models used measures of intolerance to haploinsufficiency of genes included in CNVs to predict their effect size on intelligence. Intolerant genes decrease general intelligence by 0.8 and 2.6 points of intelligence quotient when duplicated or deleted, respectively. Effect sizes showed no heterogeneity across cohorts. Validation analyses demonstrated that models could predict CNV effect sizes with 78% accuracy. Data on the inheritance of 27,766 CNVs showed that deletions and duplications with the same effect size on intelligence occur de novo at the same frequency. We estimated that around 10,000 intolerant and tolerant genes negatively affect intelligence when deleted, and less than 2% have large effect sizes. Genes encompassed in CNVs were not enriched in any GOterms but gene regulation and brain expression were GOterms overrepresented in the intolerant subgroup. Such pervasive effects on cognition may be related to emergent properties of the genome not restricted to a limited number of biological pathways.

Febrile seizures and increased stress sensitivity in children: How it relates to seizure characteristics.

BACKGROUND: Studies suggest that the relationship between seizures and stress starts early in life. However, evidence of long-term altered stress reactivity following early-life seizures is lacking. Our objectives were to assess alterations in stress hormone reactivity in children with past febrile seizures (FS) and investigate how these alterations relate to clinical characteristics. METHOD: This case-control study compared a convenience sample of children with simple FS (n = 24), complex FS (n = 18), and matched healthy controls (n = 42). Stress was induced by electrode placement for an electroencephalography (EEG) exam. Salivary cortisol to stress, using three samples collected before and after the stressor, was compared between groups and sex. The relationship between stress reactivity and clinical characteristics (i.e., FS duration, age at first FS, time since the last FS) was investigated. RESULTS: Cortisol reactivity to stress was significantly different depending on study groups, F(1, 78) = 6.415, p = 0.003, η2p = 0.141, but not sex nor was there a significant interaction between group and sex (p ≥ 0.581). Participants with simple FS showed higher cortisol reactivity to stress (M = 14.936, Standard deviation (SD) = 26.852) compared with those with complex FS (M = -4.663, SD = 18.649, p = 0.015) and controls (M = -3.817, SD = 18.907, p = 0.003). There was no significant difference between participants with complex FS and controls (p > 0.999). Stress reactivity was not linked to clinical characteristics. CONCLUSIONS: Children with past simple FS showed greater changes in salivary cortisol following stress, suggesting enhanced stress sensitivity. As similar results were not found in a population with complex FS, our study shows that stress alterations are not caused by seizure severity. Future studies are needed to investigate whether stress sensitivity may be premorbid to simple FS and may contribute to simple FS incidence.

EEG repetition and change detection responses in infancy predict adaptive functioning in preschool age: a longitudinal study.

Neurodevelopmental disorders (NDDs) are mostly diagnosed around the age of 4-5 years, which is too late considering that the brain is most susceptive to interventions during the first two years of life. Currently, diagnosis of NDDs is based on observed behaviors and symptoms, but identification of objective biomarkers would allow for earlier screening. In this longitudinal study, we investigated the relationship between repetition and change detection responses measured using an EEG oddball task during the first year of life and at two years of age, and cognitive abilities and adaptive functioning during preschool years (4 years old). Identification of early biomarkers is challenging given that there is a lot of variability in developmental courses among young infants. Therefore, the second aim of this study is to assess whether brain growth is a factor of interindividual variability that influences repetition and change detection responses. To obtain variability in brain growth beyond the normative range, infants with macrocephaly were included in our sample. Thus, 43 normocephalic children and 20 macrocephalic children were tested. Cognitive abilities at preschool age were assessed with the WPPSI-IV and adaptive functioning was measured with the ABAS-II. Time-frequency analyses were conducted on the EEG data. Results indicated that repetition and change detection responses in the first year of life predict adaptive functioning at 4 years of age, independently of head circumference. Moreover, our findings suggested that brain growth explains variability in neural responses mostly in the first years of life, so that macrocephalic children did not display repetition suppression responses, while normocephalic children did. This longitudinal study demonstrates that the first year of life is an important period for the early screening of children at risk of developing NDDs.

Time-frequency analyses of repetition suppression and change detection in children with neurofibromatosis type 1.

Children with neurofibromatosis type 1 (NF1) are at increased risk of developing cognitive problems, including attention deficits and learning difficulties. Alterations in brain response to repetition and change have been evidenced in other genetic conditions associated with cognitive dysfunctions. Whether the integrity of these fundamental neural responses is compromised in school-aged children with NF1 is still unknown. In this study, we examined the repetition suppression (RS) and change detection responses in children with NF1 (n = 36) and neurotypical controls (n = 41) aged from 4 to 13 years old, using a simple sequence of vowels. We performed time-frequency analyses to compare spectral power and phase synchronization between groups, in the theta, alpha and beta frequency bands. Correlational analyses were performed between the neural responses and the level of intellectual functioning, as well as with behavioral symptoms of comorbid neurodevelopmental disorders measured through parental questionnaires. Children with NF1 showed preserved RS, but increased spectral power in the change detection response. Correlational analyses performed with measures of change detection revealed a negative association between the alpha-band spectral power and symptoms of inattention and hyperactivity. These findings suggest atypical neural response to change in children with NF1. Further studies should be conducted to clarify the interaction with comorbid neurodevelopmental disorders and the possible role of altered inhibitory mechanisms in this enhanced neural response.

Nighttime in dreams.

Based on the continuity hypothesis of dreaming, a study was designed to examine whether time of day within the dream was related to dream emotions. A sample of 1,612 dreams reported by 444 participants was analyzed. As predicted, dream scenarios set at nighttime were associated with less positive and more negative emotions compared to dream scenarios set at other times of the day. In order to pursue this line of research, it would be fruitful to study the dreams of persons with specific nighttime fears.

Steady-state visual evoked potentials in children with neurofibromatosis type 1: associations with behavioral rating scales and impact of psychostimulant medication.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a genetic disorder often associated with cognitive dysfunctions, including a high occurrence of deficits in visuoperceptual skills. The neural underpinnings of these visuoperceptual deficits are not fully understood. We used steady-state visual evoked potentials (SSVEPs) to investigate possible alterations in the synchronization of neural activity in the occipital cortex of children with NF1. METHODS: SSVEPs were measured using electroencephalography and compared between children with NF1 (n = 28) and neurotypical controls (n = 28) aged between 4 and 13 years old. SSVEPs were recorded during visual stimulation with coloured icons flickering at three different frequencies (6 Hz, 10 Hz, and 15 Hz) and analyzed in terms of signal-to-noise ratios. A mixed design ANCOVA was performed to compare SSVEP responses between groups at the three stimulation frequencies. Pearson's correlations with levels of intellectual functioning as well as with symptoms of ADHD, ASD and emotional/behavioral problems were performed. The impact of psychostimulant medication on the SSVEP responses was analyzed in a subset of the NF1 group (n = 8) with paired t-tests. RESULTS: We observed reduced signal-to-noise ratios of the SSVEP responses in children with NF1. The SSVEP responses were negatively correlated with symptoms of inattention and with symptoms of emotional/behavioral problems in the NF1 group. The SSVEP response generated by the lowest stimulation frequency (i.e., 6 Hz) was rescued with the intake of psychostimulant medication. CONCLUSIONS: Impaired processing of rhythmic visual stimulation was evidenced in children with NF1 through measures of SSVEP responses. Those responses seem to be more reduced in children with NF1 who exhibit more symptoms of inattention and emotional/behavioral problems in their daily life. SSVEPs are potentially sensitive electrophysiological markers that could be included in future studies investigating the impact of medication on brain activity and cognitive functioning in children with NF1.

Corrigendum: EEG Signal Complexity Is Reduced During Resting-State in Fragile X Syndrome.

[This corrects the article DOI: 10.3389/fpsyt.2021.716707.].

Cognitive and behavioural development in children presenting with complex febrile seizures: at onset and school age.

OBJECTIVE: Our goal was to assess development, cognition and behaviour following an initial complex febrile seizure (FS), at onset and school age, in the context of known risk factors for cognitive development. METHODS: Two cohorts were recruited. Thirty-five infants with an initial complex FS were assessed within the first year post-seizure and compared to 30 controls (simple FS) based on measures of cognitive, motor and language development, behaviour and emotions. Additionally, 19 school-age children with previous complex FS (11 multiple, eight prolonged) were assessed and compared to 19 controls (simple FS) based on measures of intelligence, learning/memory, executive functioning, behaviour and emotions. RESULTS: Within the first year post-onset, infants with complex FS did not significantly differ from controls based on developmental measures. Seizure duration and age at seizure onset did not impact developmental outcome. School-age children with complex FS showed unaltered global intelligence, but lower executive functioning, compared to controls. Children with prolonged FS also showed evidence of a lower level of learning and memory abilities. Neuropsychological scores correlated with seizure duration. Children with complex FS showed more attentional problems and anxious/depressed symptomatology at onset and school age, and more hyperactivity at school age. SIGNIFICANCE: Infants with complex FS seemed to show normal development within the first year post-seizure onset. However, challenges in executive functioning, learning and memory at school age were found in children with a history of FS. Hence, at school age, cognitive challenges cannot be excluded based on undifferentiated early cognitive development, and may occur even in the absence of the most severe form of FS (i.e., FSE). Beyond the limits of this study (i.e., small sample size, use of parental questionnaires for emotional/behavioural outcome, absence of focal cases in the school-age cohort), our results suggest that a follow-up is necessary beyond the early preschool years in order to understand the long-term outcome.

EEG Signal Complexity Is Reduced During Resting-State in Fragile X Syndrome.

Introduction: Fragile X syndrome (FXS) is a genetic disorder caused by a mutation of the fragile X mental retardation 1 gene (FMR1). FXS is associated with neurophysiological abnormalities, including cortical hyperexcitability. Alterations in electroencephalogram (EEG) resting-state power spectral density (PSD) are well-defined in FXS and were found to be linked to neurodevelopmental delays. Whether non-linear dynamics of the brain signal are also altered remains to be studied. Methods: In this study, resting-state EEG power, including alpha peak frequency (APF) and theta/beta ratio (TBR), as well as signal complexity using multi-scale entropy (MSE) were compared between 26 FXS participants (ages 5-28 years), and 7 neurotypical (NT) controls with a similar age distribution. Subsequently a replication study was carried out, comparing our cohort to 19 FXS participants independently recorded at a different site. Results: PSD results confirmed the increased gamma, decreased alpha power and APF in FXS participants compared to NT controls. No alterations in TBR were found. Importantly, results revealed reduced signal complexity in FXS participants, specifically in higher scales, suggesting that altered signal complexity is sensitive to brain alterations in this population. The replication study mostly confirmed these results and suggested critical points of stagnation in the neurodevelopmental curve of FXS. Conclusion: Signal complexity is a powerful feature that can be added to the electrophysiological biomarkers of brain maturation in FXS.

Learning abilities.

Learning abilities are present in infancy, as they are critical for adaptation. From simple habituation and novelty responses to stimuli, learning capacities evolve throughout the lifespan. During development, learning abilities become more flexible and integrated across sensory modalities, allowing the encoding of more complex information, and in larger amounts. In turn, an increasing knowledge base leads to adaptive changes in behavior, making responses and actions more precise and effective. The objective of this chapter is to review the main behavioral manifestations of human learning abilities in early development and their biologic underpinnings, ranging from the cellular level to neurocognitive systems and mechanisms. We first focus on the ability to learn from repetitions of stimuli and how years of research in this field have recently contributed to theories of fundamental brain mechanisms whose implications for cognitive development are under study. The ability to memorize associations between different items and events is addressed next as we review the variety of contexts in which this associative memory and its neurologic bases come into play. Together, repetition-based learning and associative memory provide powerful means of understanding the surrounding environment, not only through the gathering and consolidation of specific types of information, but also by continually testing and adjusting stored information to better adapt to changing conditions.

Increased EEG alpha peak frequency in adolescents with idiopathic scoliosis during balance control in normal upright standing.

Adolescent idiopathic scoliosis (AIS) is a multifactorial disorder characterized by a tridimensional deformation of the spine. AIS pathophysiology is still unclear and its aetiology is unknown. Results from several studies revealed balance control alterations in adolescents with AIS suggesting cortical sensorimotor processing impairments. Studies assessing cortical activity involved in balance control revealed an increase in alpha peak frequency (APF), which is a neurophysiological marker of thalamo-cortical transmission, related to a more challenging balance task. The objective of this study is to assess APF of adolescents with AIS during balance control in upright standing posture using electroencephalography (EEG). EEG was recorded in 16 girls with AIS and 15 control girls in normal standing posture on a force platform. The participants stood upright for 2 min with eyes open and 2 min with eyes closed. Fast Fourier transformations of EEG data were calculated to obtain APF. Balance performances were assessed through the area of an ellipse covering the center of pressure (COP) displacement and the root mean square value of the COP velocity. Compared to the control group, APF was higher in the AIS group at central, frontal, parietal and occipital regions. Further, COP analyses did not reveal any difference between AIS and control groups. A higher APF may indicate the need for increased cortical processing to maintain balance control in normal upright standing in adolescents with AIS compared to healthy controls. We suggest that this may be a compensatory strategy to overcome balance control challenges.

Prolonged and unprolonged complex febrile seizures differently affect frontal theta brain activity.

OBJECTIVE: Studies have identified mild but persistent cognitive and functional deficits, which could be linked to each other, in children with complex febrile seizures (FS). Our aim was to investigate differences in brain activity in children with a history of complex FS, through a study paradigm notably associated with the development of learning capacities and using electroencephalographic (EEG) signal. To further increase our understanding of these differences, complex FS were studied separately depending on their type. METHOD: EEG was recorded in 43 children with past FS. Brain activity associated with auditory learning was investigated using a habituation paradigm, in which repetition suppression (RS) is typically found following stimulus repetition. Auditory stimuli were repeated three times, and each presentation were analysed separately in the time-frequency (TF) domain. A mixed-analysis of variance was used to assess differences in spectral power between stimulus repetition and FS type (simple vs complex prolonged; CP vs complex unprolonged; CUP). RESULTS: Repetition effects were found in the 3-6 Hz during 150-600 ms time window after stimulus onset at frontal sites (F(2, 40) = 5.645, p = 0.007, η2p = 0.220). Moreover, an interaction effect between stimulus repetition and FS type (F(4, 80) = 2.607, p = 0.042, η2p = 0.115) was found. Children with CP FS showed greater increase in spectral power in response to the first stimulus presentation, while children with CUP FS failed to show a RS pattern. SIGNIFICANCE: Our results show distinct abnormalities in brain activity to a habituation paradigm. We argue that these changes suggest children with CP FS may be hyperexcitable, while children with CUP FS show impaired habituation processes. Still, these differences may be associated with other clinical features linked to complex FS as well. Hence, the role of these differences in complex FS incidence and prognosis should be the subject of future studies.

Cortical dynamics of sensorimotor information processing associated with balance control in adolescents with and without idiopathic scoliosis.

OBJECTIVE: This study aims at examining the cortical dynamics of sensorimotor information processing related to balance control in participants with adolescent idiopathic scoliosis (AIS) and in age-matched controls (CTL). METHODS: Cortical dynamics during standing balance control were assessed in 13 girls with AIS and 13 age-matched controls using electroencephalography. Time-frequency analysis were used to determine frequency power during ankle proprioception alteration (ankle tendons co-vibration interval) or reintegration of ankle proprioception (post-vibration interval) with or without vision. RESULTS: Balance control did not differ between groups. In the co-vibration interval, a significant suppression in alpha (8-12 Hz) and beta (13-30 Hz) band power and a significant increase in theta (4-7 Hz) band power were found respectively in the vision and non-vision condition in the AIS group compared to the CTL group. In the post-vibration interval, significant suppressions in beta (13-30 Hz) and gamma (30-50 Hz) band power were observed in the AIS group in the non-vision condition. CONCLUSION: Participants with AIS showed brain oscillations differences compared to CTL in the sensorimotor cortex while controlling their balance in various sensory conditions. SIGNIFICANCE: Future study using evaluation of cortical dynamics could serve documenting whether rehabilitation programs have an effect on sensorimotor function in AIS.

The relationship between acute stress and EEG repetition suppression in infants.

Over activation of the hypothalamo-pituitary-adrenal (HPA) axis in stress situations is known to influence learning and memory. In adults, an inverted-U shape relationship between acute stress, and learning and memory has been demonstrated. Whether this model fits learning performances in infants is unknown. In this study, we used EEG repetition suppression as physiological measure of learning and salivary cortisol in response to a stressor to investigate the relationship between acute stress and learning in infants. We hypothesized that EEG repetition suppression would be modulated by acute stress following an inverted-U shape relationship. Saliva samples were collected during an EEG experiment before, during and after EEG net installation in 37 healthy infants (18 males) aged between 6 and 26 months. The effect of variation in stress hormones on repetition suppression were modeled using a linear mixed model, with cortisol, age and sex as predictors. Results indicated that in healthy infants, elevations in stress hormones within the normal range are associated with a higher repetition suppression response and an increased response to the first presentation of the stimulus. The later increase could be related to vigilance. Considering that early childhood is a critical period of development, future studies should keep investigating the influence of stress on learning processes in infants.

Association between fat-soluble nutrient status and auditory and visual related potentials in newly diagnosed non-screened infants with cystic fibrosis: A case-control study.

Nutritional deficiencies often precede the diagnosis of cystic fibrosis (CF) in infants, and occur at a stage where the rapidly developing brain is more vulnerable to insult. We aim to compare fat-soluble nutrient status of newly diagnosed non-screened infants with CF to that of healthy infants, and explore the association with neurodevelopment evaluated by electroencephalography (EEG). Our results show that CF infants had lower levels of all fat-soluble vitamins and docosahexaenoic acid (DHA) compared to controls. The auditory evoked potential responses were higher in CF compared to controls whereas the visual components did not differ between groups. DHA levels were correlated with auditory evoked potential responses. Although resting state frequency power was similar between groups, we observed a negative correlation between DHA levels and low frequencies. This study emphasizes the need for long-term neurodevelopmental follow-up of CF infants and pursuing intervention strategies in the future.

Computer-aided lateral ventricular and brain volume measurements in 3D ultrasound for assessing growth trajectories in newborns and neonates.

For newborns and neonates, ultrasound (US) is the most common imaging modality used for examinations due to its accessibility and ease of use. However, precise volume measurements remain limited in 2D, while MRI in newborns is typically avoided because of immobilization issues which may require sedation. The objective of this study is to assess and validate the lateral ventricular and total brain volumes obtained with an automatic segmentation method using cerebral trans-fontanelle 3D US. Infants aged between 2 and 8.5 months old were recruited, with both MRI and 3D US acquired on the same day was used to validate ventricular and brain volume measurements in comparison to MRI. Lateral ventricles were segmented on both the US (manually and with a proposed automatic fusion-based approach) and MRI, while brain volumes were estimated with an automatic segmentation method. Volumetric 3D US measurements were then evaluated with respect to age distribution. For the comparison between MRI and 3D US, strong inter-class correlations (ICC) were found for the ventricle volumes (manual: 5.9% ± 2.5% difference (ICC = 0.99); automatic: 6.0% ± 2.6% difference (ICC = 0.98)), as well as the total brain size, with a 3.0% ± 1.3% difference (ICC = 0.98). There was no statistically significant difference based on t-test and f-test for the lateral ventricles volume (t-test: p = 0.542) and (f-test: p = 0.738) and for the total brain volume (t-test: p = 0.412) and (f-test: p = 0.685) between MRI and 3D US. This study demonstrates that 3D US can be used to automatically assess lateral ventricular and total brain volumes with no significant difference to the MRI acquisitions. The highest correlations were obtained for infants under 8 months when the fontanelle is open.

Auditory repetition suppression alterations in relation to cognitive functioning in fragile X syndrome: a combined EEG and machine learning approach.

BACKGROUND: Fragile X syndrome (FXS) is a neurodevelopmental genetic disorder causing cognitive and behavioural deficits. Repetition suppression (RS), a learning phenomenon in which stimulus repetitions result in diminished brain activity, has been found to be impaired in FXS. Alterations in RS have been associated with behavioural problems in FXS; however, relations between RS and intellectual functioning have not yet been elucidated. METHODS: EEG was recorded in 14 FXS participants and 25 neurotypical controls during an auditory habituation paradigm using repeatedly presented pseudowords. Non-phased locked signal energy was compared across presentations and between groups using linear mixed models (LMMs) in order to investigate RS effects across repetitions and brain areas and a possible relation to non-verbal IQ (NVIQ) in FXS. In addition, we explored group differences according to NVIQ and we probed the feasibility of training a support vector machine to predict cognitive functioning levels across FXS participants based on single-trial RS features. RESULTS: LMM analyses showed that repetition effects differ between groups (FXS vs. controls) as well as with respect to NVIQ in FXS. When exploring group differences in RS patterns, we found that neurotypical controls revealed the expected pattern of RS between the first and second presentations of a pseudoword. More importantly, while FXS participants in the ≤ 42 NVIQ group showed no RS, the > 42 NVIQ group showed a delayed RS response after several presentations. Concordantly, single-trial estimates of repetition effects over the first four repetitions provided the highest decoding accuracies in the classification between the FXS participant groups. CONCLUSION: Electrophysiological measures of repetition effects provide a non-invasive and unbiased measure of brain responses sensitive to cognitive functioning levels, which may be useful for clinical trials in FXS.

Alterations of visual and auditory evoked potentials in fragile X syndrome.

BACKGROUND: Fragile X Syndrome (FXS) is the most common monogenic form of intellectual disability and one of the few known monogenic causes of autism. It is caused by a trinucleotide repeat expansion in the FMR1 ('Fragile X Mental Retardation 1') gene, which prevents expression of the 'Fragile X Mental Retardation Protein' (FMRP). In FXS, the absence of FMRP leads to altered structural and functional development of the synapse, while preventing activity-based synapse maturation and synaptic pruning, which are essential for normal brain development and cognitive development. Possible impairments in information processing can be non-invasively investigated using electrophysiology. METHODS: We compared auditory (AEP) and visual (VEP) evoked potentials in twelve adolescents and young adults (10-22 years) affected by FXS to healthy controls matched by chronological age (N=12) and developmental age of cognitive functioning (N=9; 5-7 years), using analysis of variance. RESULTS: In the visual modality, the N70 and N2 amplitude have been found increased in FXS in comparison to the chronological, but not the developmental control group at occipital sites, whereas in the auditory modality N1, P2 and N2 amplitude as well as N2 latency have been found increased in FXS, relative to both chronological and developmental control groups at mid-central sites. CONCLUSIONS: The AEP/VEP profile suggests disruptions in sensory processing specific to FXS that exceed immaturity of physiological activity. In addition, the auditory modality seems to be more affected than the visual modality. Results are discussed in light of possible underlying neuronal mechanisms, including deficits in synaptic pruning and neuronal inhibition that might account for a hyperreactive nervous system in FXS.