Neuroimaging the sleeping brain: Insight on memory functioning in infants and toddlers.

Episodic memory, or the ability to remember past events with specific detail, is central to the human experience and is related to learning and adaptive functioning in a variety of domains. In typically developing children, episodic memory emerges during infancy and improves during early childhood and beyond. Developmental processes within the hippocampus are hypothesized to be primarily responsible for both the early emergence and persistence of episodic memory in late infancy and early childhood. However, these hypotheses are based on non-human models. In-vivo investigations in early human development of hippocampal processes have been significantly limited by methodological challenges in acquiring neuroimaging data, particularly task-related functional neuroimaging data, from infants and toddlers. Recent studies in adults have shown neural activity in the brain regions supporting episodic memory during slow-wave sleep using functional magnetic resonance imaging (fMRI), and fMRI has been increasingly utilized in infancy and early childhood to address other research questions. We review initial evidence and present preliminary data showing the promise of this approach for examining hippocampal contribution to how infants and toddlers remember individual events, and their association with information about the context in which the event occurred. Overall, our review, integrated with the presentation of some preliminary data provides insight on leveraging sleep to gain new perspectives on early memory functioning

Early development of sleep and brain functional connectivity in term-born and preterm infants

The proper development of sleep and sleep-wake rhythms during early neonatal life is crucial to lifelong neurological well-being. Recent data suggests that infants who have poor quality sleep demonstrate a risk for impaired neurocognitive outcomes. Sleep ontogenesis is a complex process, whereby alternations between rudimentary brain states-active vs. wake and active sleep vs. quiet sleep-mature during the last trimester of pregnancy. If the infant is born preterm, much of this process occurs in the neonatal intensive care unit, where environmental conditions might interfere with sleep. Functional brain connectivity (FC), which reflects the brain's ability to process and integrate information, may become impaired, with ensuing risks of compromised neurodevelopment. However, the specific mechanisms linking sleep ontogenesis to the emergence of FC are poorly understood and have received little investigation, mainly due to the challenges of studying causal links between developmental phenomena and assessing FC in newborn infants. Recent advancements in infant neuromonitoring and neuroimaging strategies will allow for the design of interventions to improve infant sleep quality and quantity. This review discusses how sleep and FC develop in early life, the dynamic relationship between sleep, preterm birth, and FC, and the challenges associated with understanding these processes. Impact Sleep in early life is essential for proper functional brain development, which is essential for the brain to integrate and process information. This process may be impaired in infants born preterm. The connection between preterm birth, early development of brain functional connectivity, and sleep is poorly understood. This review discusses how sleep and brain functional connectivity develop in early life, how these processes might become impaired, and the challenges associated with understanding these processes. Potential solutions to these challenges are presented to provide direction for future research.Peer reviewe

Neural indicators of fatigue in chronic diseases : A systematic review of MRI studies

The authors would like to thank the Sir Jules Thorn Charitable Trust for their financial support.Peer reviewedPublisher PD

Ictal Functional Neuroimaging of Childhood Absence Epilepsy

Absence seizures in Childhood Absence Epilepsy (CAE) are 5 10 second episodes of impaired consciousness that are characterized on electroencephalography (EEG) by frontally-predominant, 3 4 Hz spike and wave discharges (SWD). The aims of this study were to use simultaneous EEG, functional magnetic resonance imaging (fMRI), and behavioral testing to identify the neural networks involved in absence seizures as well as to examine the timecourse of those ictal fMRI changes. It was hypothesized that absence seizures involve wide-reaching neural networks including the areas traditionally associated with normal attention processing and that absence seizures produce fMRI signal changes not only during the seizure, but before and after it as well. In this study, we recorded 88 absence seizures from a cohort of 42 children with pure CAE. These seizures were recorded as subjects participated in simultaneous EEG-fMRI scanning while engaged in a continuous performance task (CPT) of attentional vigilance or a repetitive tapping task (RTT) requiring repetitive motor activity. Using a novel, voxel-based percent fMRI change analysis combined with a volume of interest analysis, the second-by-second fMRI signal timecourse of the absence seizures were examined across numerous brain regions of interest, from 20 seconds before seizure onset through 40 seconds after seizure onset. EEG frequency analysis revealed seizures with a mean duration of 6.6 seconds and an abrupt onset and ending that were comprised of frontally-predominant, 3 4 Hz SWD. Ictal behavioral testing demonstrated abrupt onset of impairments during periods of SWD. These behavioral impairments were typical of CAE absence seizures in that impairments were greater in the CPT of attentional vigilance (omission error rate, OER = 81%) than in RTT testing (OER = 39 %) (p \u3c 0.003). The ictal fMRI changes we observed varied depending upon the method of fMRI signal analysis used. Using the traditional general liner model, and assuming the standard hemodynamic response (HRF) function, this study replicated results consistent with previous ictal absence fMRI studies showing ictal activations primarily in the thalamus and ictal deactivations in traditional default mode areas. Using a more data-driven, novel voxel-based fMRI percentage change analysis to examine the ictal fMRI timecourse on a second-by-second basis, both ictally as well as pre- and post- ictally, this study, however, demonstrated ictal involvement of diverse brain regions before, during, and after the seizure. Activation was demonstrated up to 16 seconds before seizure onset, starting first in the parietal and orbital-medial frontal cortices and progressing to lateral frontal and lateral temporal cortices followed by the occipital and Rolandic cortices and finally the thalamus. Deactivation followed a similar anatomic progression and lasted up to 17 seconds after the end of SWD. These findings reveal a complex and long-lasting sequence of fMRI changes in CAE absence seizures that are not detectable by conventional HRF modeling and are important in the understanding and eventual treatment of absence seizures associated with CAE

Mapping the Effect of Interictal Epileptic Activity Density During Wakefulness on Brain Functioning in Focal Childhood Epilepsies With Centrotemporal Spikes

Childhood epilepsy with centrotemporal spikes (CECTS) is the most common type of \u201cself-limited focal epilepsies.\u201d In its typical presentation, CECTS is a condition reflecting non-lesional cortical hyperexcitability of rolandic regions. The benign evolution of this disorder is challenged by the frequent observation of associated neuropsychological deficits and behavioral impairment. The abundance (or frequency) of interictal centrotemporal spikes (CTS) in CECTS is considered a risk factor for deficits in cognition. Herein, we captured the hemodynamic changes triggered by the CTS density measure (i.e., the number of CTS for time bin) obtained in a cohort of CECTS, studied by means of video electroencephalophy/functional MRI during quite wakefulness. We aim to demonstrate a direct influence of the diurnal CTS frequency on epileptogenic and cognitive networks of children with CECTS. A total number of 8,950 CTS (range between 27 and 801) were recorded in 23 CECTS (21 male), with a mean number of 255 CTS/patient and a mean density of CTS/30 s equal to 10,866 \ub1 11.46. Two independent general linear model models were created for each patient based on the effect of interest: \u201cindividual CTS\u201d in model 1 and \u201cCTS density\u201d in model 2. Hemodynamic correlates of CTS density revealed the involvement of a widespread cortical\u2013subcortical network encompassing the sensory-motor cortex, the Broca's area, the premotor cortex, the thalamus, the putamen, and red nucleus, while in the CTS event-related model, changes were limited to blood\u2013oxygen-level-dependent (BOLD) signal increases in the sensory-motor cortices. A linear relationship was observed between the CTS density hemodynamic changes and both disease duration (positive correlation) and age (negative correlation) within the language network and the bilateral insular cortices. Our results strongly support the critical role of the CTS frequency, even during wakefulness, to interfere with the normal functioning of language brain networks