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.

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.

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.

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.

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.

Altered visual repetition suppression in Fragile X Syndrome: New evidence from ERPs and oscillatory activity.

Fragile X Syndrome (FXS) is a neurodevelopmental genetic disorder associated with cognitive and behavioural deficits. In particular, neuronal habituation processes have been shown to be altered in FXS patients. Yet, while such deficits have been primarily explored using auditory stimuli, less is known in the visual modality. Here, we investigated the putative alteration of repetition suppression using faces in FXS patients compared to controls that had the same age distribution. Electroencephalographic (EEG) signals were acquired while participants were presented with 18 different faces, each repeated ten times successively. The repetition suppression effect was probed by comparing the brain responses to the first and second presentation, based on task-evoked event-related potentials (ERP) as well as on task-induced oscillatory activity. We found different patterns of habituation for controls and patients both in ERP and oscillatory power. While the N170 was not affected by face repetition in controls, it was altered in FXS patients. Conversely, while a repetition suppression effect was observed in the theta band (4-8Hz) over frontal and parieto-occipital areas in controls, it was not seen in FXS patients. These results provide the first evidence for diminished ERP and oscillatory habituation effects in response to face repetitions in FXS. These findings extend previous observations of impairments in learning mechanisms and may be linked to deficits in the maturation processes of synapses caused by the mutation. The present study contributes to bridging the gap between animal models of synaptic plasticity dysfunctions and human research in FXS.

Brain signal complexity rises with repetition suppression in visual learning.

Neuronal activity associated with visual processing of an unfamiliar face gradually diminishes when it is viewed repeatedly. This process, known as repetition suppression (RS), is involved in the acquisition of familiarity. Current models suggest that RS results from interactions between visual information processing areas located in the occipito-temporal cortex and higher order areas, such as the dorsolateral prefrontal cortex (DLPFC). Brain signal complexity, which reflects information dynamics of cortical networks, has been shown to increase as unfamiliar faces become familiar. However, the complementarity of RS and increases in brain signal complexity have yet to be demonstrated within the same measurements. We hypothesized that RS and brain signal complexity increase occur simultaneously during learning of unfamiliar faces. Further, we expected alteration of DLPFC function by transcranial direct current stimulation (tDCS) to modulate RS and brain signal complexity over the occipito-temporal cortex. Participants underwent three tDCS conditions in random order: right anodal/left cathodal, right cathodal/left anodal and sham. Following tDCS, participants learned unfamiliar faces, while an electroencephalogram (EEG) was recorded. Results revealed RS over occipito-temporal electrode sites during learning, reflected by a decrease in signal energy, a measure of amplitude. Simultaneously, as signal energy decreased, brain signal complexity, as estimated with multiscale entropy (MSE), increased. In addition, prefrontal tDCS modulated brain signal complexity over the right occipito-temporal cortex during the first presentation of faces. These results suggest that although RS may reflect a brain mechanism essential to learning, complementary processes reflected by increases in brain signal complexity, may be instrumental in the acquisition of novel visual information. Such processes likely involve long-range coordinated activity between prefrontal and lower order visual areas.

Transcranial direct current stimulation of the dorsolateral prefrontal cortex modulates repetition suppression to unfamiliar faces: an ERP study.

Repeated visual processing of an unfamiliar face suppresses neural activity in face-specific areas of the occipito-temporal cortex. This "repetition suppression" (RS) is a primitive mechanism involved in learning of unfamiliar faces, which can be detected through amplitude reduction of the N170 event-related potential (ERP). The dorsolateral prefrontal cortex (DLPFC) exerts top-down influence on early visual processing. However, its contribution to N170 RS and learning of unfamiliar faces remains unclear. Transcranial direct current stimulation (tDCS) transiently increases or decreases cortical excitability, as a function of polarity. We hypothesized that DLPFC excitability modulation by tDCS would cause polarity-dependent modulations of N170 RS during encoding of unfamiliar faces. tDCS-induced N170 RS enhancement would improve long-term recognition reaction time (RT) and/or accuracy rates, whereas N170 RS impairment would compromise recognition ability. Participants underwent three tDCS conditions in random order at ∼72 hour intervals: right anodal/left cathodal, right cathodal/left anodal and sham. Immediately following tDCS conditions, an EEG was recorded during encoding of unfamiliar faces for assessment of P100 and N170 visual ERPs. The P3a component was analyzed to detect prefrontal function modulation. Recognition tasks were administered ∼72 hours following encoding. Results indicate the right anodal/left cathodal condition facilitated N170 RS and induced larger P3a amplitudes, leading to faster recognition RT. Conversely, the right cathodal/left anodal condition caused N170 amplitude and RTs to increase, and a delay in P3a latency. These data demonstrate that DLPFC excitability modulation can influence early visual encoding of unfamiliar faces, highlighting the importance of DLPFC in basic learning mechanisms.