Our projects in progress

Are fundamental learning processes predictive of neurodevelopment?

Childhood is a crucial period for the development of the brain mechanisms involved in learning. It is therefore essential to understand the functioning and development of the neural mechanisms of learning. The objective of this study is to evaluate whether the effectiveness of the cerebral learning response, measured between 4-10 months, at 2 years and at 4 years, is predictive of adaptive behaviors and cognitive development at 4 years, in healthy children and children with increased brain growth. The cerebral learning response will be measured in electroencephalography via a repetition learning task. Adaptive Behavior Assessment System - Second Edition (ABAS-II) will evaluate adaptive behaviors, and cognitive development will be measured with the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-IV). This study will reveal the developmental curve of neuronal suppression in young children and evaluate its predictive value on child neurodevelopment, particularly cognitive development and adaptive skills.

Study of brain plasticity in very preterm infants using electroencephalography and magnetic resonance imaging

This project aims to identify mechanisms in the neurodevelopmental trajectory leading the premature child to develop neurodevelopmental deficits (e.g. language and/or motor disorder, intellectual disability) Some risk factors, such as low birth weight, the presence of infections, and altered brain growth (CC), have been identified, but the extent of their consequences is still poorly understood (Lee et al., 2016). The objectives of the study are to assess brain growth and cerebral plasticity (CP; mechanism underlying CC) in very premature babies (24-29 weeks gestation) with MRI and EEG in the child’s first year of life. The cognitive functioning of children will also be established using standardized developmental battery.

 

The clairvoyant brain: sensitive neurodevelopment predictors

Neurodevelopmental disorders, such as attention deficit/hyperactivity disorder, autistic spectrum disorder and intellectual disability, affect over 10% of Canadians. These disorders are usually diagnosed late during development, leading to increased severity and chronicity.

This longitudinal study aims to examine the relationship between brain structure, brain activity in early childhood and neurodevelopment. To achieve this, a longitudinal follow-up will be conducted with young children, from birth to 4 years of age (3 visits: 3-6 months, 24 months and 4 years). The early development of brain structures will be examined using transfontanelle ultrasonography, a noninvasive technique for obtaining images of babies brain. Brain growth will also be assessed by measuring head circumference, a commonly used measure to estimate brain volume. Cerebral activity during learning tasks will be examined using electroencephalography, and child development will be evaluated through questionnaires and neuropsychological tests. Hence, this study will help identify early markers of abnormal brain functioning associated with neurodevelopmental disorders, which in turn could facilitate early diagnosis.

Involvment of the Superior Longitudinal Fasciculus in Visual Short-Term Memory

The principal aim of this project is to better understand involvement of the superior longitudinal fasciculus (SLF) in visual short-term memory. The SLF is the main white matter track that links the parietal and prefrontal cortices. It is involved in short-term memory and working memory. The main objective of this study is to seek if performance on a visual short-term memory task and modulations of electrophysiological markers during the task are linked to white matter integrity in the superior longitudinal fasciculus in healthy adults. In this study, a visual short-term memory task as well as electroencephalography (EEG), magnetoencephalography (MEG) and diffusion tensor imaging (DTI) will be used. The hypothesis is that visual short-term memory tasks and electrophysiological markers used in this protocol will be linked with the integrity of white matter in the superior longitudinal fasciculus in DTI. This study will include 30 healthy participants aged from 20 to 30 years old and from varying levels of education. A protocol identical to the one used in this project will be used in a research on acute lymphoblastic leukemia (ALL) survivors. The results of this project will help to better understand the link between white matter damage and short-term memory deficits in ALL survivors. 

Our completed projects

Stress in children with prior febrile seizures: mechanisms and implication in the cognitive prognosis

Stress is the most important risk factor associated with seizure incidence, frequency and severity. Although numerous animal studies suggest early programming with stress influences seizure disorders and their prognosis, developmental human studies of this link are lacking. Hence, this study aimed at investigating stress biomarkers in children with prior simple or complex febrile seizures, compared to matched controls. The main objectives are 1) studying stress biomarkers in children with past febrile seizures, compared to their peers and 2) study the influence of stress biomarkers on the cognitive prognosis of children with febrile seizures. Results drawn from this study may further our understanding of the link between early-life stress and seizures.

Assessment of cognitive and behavioral aspects in children with Rolandic Epilepsy (RE or Benign Epilepsy with Centro-Temporal Spikes / BECTS)

RE is the most common form of childhood epilepsy. It is caused by the hyperexcitability of a system of neurons in only one hemisphere without apparent brain injury or cerebral structural abnormalities (Capovilla et al., 2009), it is usually well controlled by medication and seizures disappear by adolescence. Although RE is still officially considered as a benign syndrome without cognitive impairments (Berg et Scheffer, 2011), a growing body of literature highlights the existence of a wide range of cognitive deficits (Sarco et al., 2011; Baglietto et al., 2001; Metz-Lutz et Filippini, 2006; Weglage, Demsky, Pietsch, et Kurlemann, 1997). In RE, we know that abnormal epileptic activity is found in central and temporal regions of the brain.

We aim to realize:

1.      an exhaustive neuropsychological and behavioral investigation of children with RE. A standard neuropsychological assessment is conducted for each child and their parents have to complete behavioral and affective questionnaires.

2.      Structural and functional cerebral imaging (MRI)

3.      Electrophysiology (EEG) to assess Visual Working Memory and Attention (SPCN, N2pc), and executive functioning (N2-stop).

We hypothesize that developmental abnormality will be observed in the brain structure, electric activity and tissues, detectable at the onset of RE and cognitive impairments. In addition, we believe that the importance of neuroanatomical and electrophysiological abnormalities will be correlated with the severity of the epilepsy and cognitive deficits.

 

If you are interested to participate, please contact:

Mme Sandrine Mendizabal, sandrine.mendizabal@umontreal.ca

Mme Domitille Malfait, domitille.malfait@umontreal.ca

 

Investigation of mechanisms of cerebral plasticity in humans with or without intellectual disabilities or autism spectral disorder

The aim of this research project is to examine synaptic plasticity in populations with intellectual disability or autism spectrum disorder using electroencephalography and behavioral measures in order to unveil the neuronal mechanisms underlying learning disabilities. Various populations are the main focus, such as Fragile X Syndrome, Down Syndrome, Tuberous sclerosis complex and SYNGAP1 mutation. Learning mechanisms are the central topic of this research. Three age groups, including participants from 5 to 30 years of age, are tested. Data will be compared to an age- and gender-matched control group in order to find specific biomarkers of learning in populations with neurodevelopmental disorders.

Analysis of sub-cortical morphology in benign epilepsy with centrotemporal spikes

Benign epilepsy with centrotemporal spikes (BECTS) is one of the most common childhood epilepsy syndromes, which occurs in children aged from three to 13 years old. Initially, BECTS was considered as benign, but recently some studies have found cognitive and behavioral deficits, which may persist even after remission. Recent neuroimaging studies have found a link between these cognitive deficits and dysfunctions in specific brain structures, which shows the possibility of neuroanatomical alterations in these brain regions. In this research project, we aim to propose an automatic morphological analysis framework in BECTS to detect the subtle neuroanatomical alterations in children with BECTS, compared to normal controls. To this end, we develop a group-wise coregistration and cosegmentation process, which enables automatic segmentation of sub-cortical structures in multiple images. Then, we design a framework for matching 3D sub-cortical surface meshes and investigating the group-wise structural differences between two populations of surfaces, i.e., healthy and pathological subjects. Finally, we propose a methodology to assess the association between morphological alterations and cognition.

Influence of self-esteem development on learning capacities

Our objective in this project is to create a new measurement of self-esteem development trajectory. We want to explore the moderator effect of chronological age on how multiple selves and social comparison are associated with outcomes such as global self- worth and positive affect. We will investigate how affective maturity and development impact these relationships. To do so, we will include a sample of the medically ill, as serious medical conditions have been identified as major disruptors of social development and affective maturity. We will also investigate the moderating role of optimal parenting on the link between experiencing medical illness and child mental health and self-esteem. Finally, we will explore the  relation between self-esteem component and the development of metacognitive abilities. We will administrate questionnaires and neuropsychological tasks to non pathologic and epileptic children aged between 8 and 14.

Neural and anatomical correlates of VSTM contributing to the apparition of difficulties in mathematics in childhood acute lymphoblastic leukemia survivors.

Acute lymphoblastic leukemia is the most common type of cancer in children. Despite efficient treatments allowing a survival rate of more than 80%, it is known that treatments against leukemia can cause cognitive difficulties in survivors, amongst other things difficulties in mathematics and in short-term memory. These difficulties have a negative impact on academic and professional success as well as on quality of life. The treatments administered to cure leukemia can also cause damages in brain white matter, which helps the information to travel from one brain region to another. Despite findings and knowledge on brain functioning, the cause of cognitive difficulties in leukemia survivors remain unknown. This research project aims at explaining the cause of cognitive difficulties in leukemia survivors, specifically concentrating on visual short-term memory (VSTM) and mathematical abilities. The hypothesis is that difficulties in mathematics will be related to deficits in VSTM. We will study VSTM from different angles: we will look at performance on a VSTM task, we will examine cerebral activity related to VSTM using magnetoencephalography (MEG) and we will study anatomical correlates of VSTM using diffusion resonance magnetic imaging (dMRI). A better comprehension of the processes that leads to the apparition of deficits will allow to create prevention and intervention programs targeting this particular population. Ultimately, this research project aims at minimizing the apparition of cognitive difficulties in leukemia survivors, contributing to a better quality of life in that population.

PETALE study

The PETALE study is interested in the long-term side effects of survivors of acute lymphoblastic leukemia (ALL). This study first started in 1989, and examines survivors that were 19 years old or younger at the time of the diagnosis. Also, to qualify this study, they must have been in remission for a minimum of five years. This accounts for approximately 350 patients from the CHU Sainte-Justine.

 

It is important to mention that in recent years, more than 85% of children diagnosed with ALL survive due to improvements of new treatments. However, the medical and psychosocial drawbacks associated with this disease and treatments can be of major significance. 

 

The main objective of this study is to examine if genetic or biological factors can predict the development of known medical complications found in ALL survivors, such as: cardiac complications, a metabolic syndrome, bone complications, and neurocognitive impairments.

http://www.chu-sainte-justine.org/recherche/page.aspx?ID_Menu=2321&ID_Page=5285&ItemID=5a&prov=intranet

The association between cognitive impairment and hippocampal connectivity and integrity following prolonged complex febrile seizures

This study focuses on the cognitive development of babies and children having suffered from early life prolonged complex febrile seizures (CFS), the most prominent seizure disorder between the ages of six months and five years of age. The objectives of the study are two-fold. First, to determine a neuropsychological profile for school-age children having suffered from early life prolonged CFS, especially with regards to learning and memory. Second, to identify a link between the observed cognitive impairments and the development of the hippocampus, a structure related to learning and memory function. As such, cognitive evaluations are performed by means of neuropsychological tests at seizure onset as well as at five years of age. At this age a structural MRI is also performed to evaluate hippocampal integrity (total volume as well as surface-based analyses) as well as a Diffusion-Weighted MRI (DWI) to evaluate hippocampal connectivity (DTI analyses), having a particular interest for the cortico-hippocampal network.

 

Population studied: five year-old children having suffered one or more prolonged complex febrile seizures (15 minutes or more) occurring between the ages of 6 and 24 months without having suffered afebrile seizures.

Construction of a spatio-temporal pediatric brain atlas based on non-linear discriminant manifold learning

Temporal lobe epilepsy (TLE) is the most frequent form of drug-resistant focal epilepsy which is mostly characterized by complex seizures, changes in hippocampal and sulci shapes. Numerous automated segmentation techniques have been proposed to be used in the evaluation of TLE. However, the performance of the available methods is still far from manual segmentation and most of these methods are dedicated to adult’s anatomy. The objective of our project is to develop a morphological predictor for early diagnosis of TLE which can identify differences in hippocampal and sulci shapes to normal populations. An atlas specifically for pediatric population will be created which will enable automatically segmenting the hippocampus, insula and sulci curves. Non-linear manifold embedding will also be used for registration to be able to analyze changes and do early detection of TLE. 

Influence of stress on learning in babies

The aim of this study is to understand how stress in infants affects important cognitive functions such as learning and memory. To do so, we measure brain activity using electroencephalography (EEG) during a learning task. Further, saliva samples are collected during the experimentation. Using these measures, we will investigate the relationship between stress and learning in infants.

System to measure cerebral structures in newborns using 3D ultrasound

In neonates, ultrasound is the initial neuroimaging modality used to detect and follow up on intracranial pathologies, since MRI is challenging due to immobilization, cost and sedation issues. Ultrasound is typically acquired in 2D and interpretations are performed slice by slice. However, recent reports suggest a longitudinal follow-up of structure volumes and shapes may be relevant for investigation of neurodevelopmental disorders. The first objective of this study is to test the diagnostic efficiency of the 3D ultrasound technology to measure total brain volume as well as lateral ventricular volume compared to volumetric measurements obtained from MRI.  Subsequently, an algorithm automatically estimates the volume of the brain in 3D ultrasound with the method validated by MRI images. Then a segmentation of the lateral ventricles is achieved with an image registration and a deformable mesh. This makes it possible to automatically calculate the ventricle volume and to quantify its relative dilatation compared to the brain by extracting the ventricle / brain volume ratio.

 This will allow us to do 3D volume segmentation of the ventricles with 3D ultrasound images, which is easier than using MRI from a clinical perspective. 

Executive and attentional functions in children and adolescents with developmental coordination disorder and the influence of comorbid disorders

Developmental coordination disorder (DCD) is a neurodevelopmental disorder that occurs in approximately 6% of school-aged children and that affects motor skill development and acquisition. In addition to the consequences directly related to the motor disorder, cognitive difficulties have been observed in young people living with DCD, particularly in attentional and executive aspects, but no clear neurocognitive profile has yet been established. Furthermore, DCD is frequently associated with other neurodevelopmental disorders, in which executive and attentional functions can also be impaired. Thus, the primary objective of this project is to exhaustively list attentional and executive profiles found in children and adolescents with a DCD, distinguishing those presenting a DCD alone from those presenting various concomitant disorders by doing a systematic review of the literature. The secondary objective is to investigate executive functioning of children and adolescents with DCD as reported by their relatives in questionnaires from the Behavior Rating Inventory of Executive Function (BRIEF). The results will also be distinguished according to the presence or absence of comorbid disorders in children with DCD. This project will provide a better understanding of the neurocognitive profile of children affected by DCD and the influence of various concurrent disorders, which will facilitate the identification of their needs and the optimization of clinical interventions.

Social evaluation and learning in social contexts in babies

We know that starting at three months of age, babies are able to evaluate others on the basis of their actions, preferring agents showing pro-social behaviour to those presenting antisocial actions. In this study, we aim at investigating if babies are using their social evaluations for learning purposes during the first two years of life. Thus, 8 and 16-moth year old babies will have the choice of learning a task from a pro-social agent (previously seen helping someone) and anti-social agent (previously seen harming someone). Babies’ learning responses will be studied in order to respond to the research question: do babies learn differently from pro and antisocial agents? This study aims at deepening our knowledge of the early development of two distinct social skills: social evaluation and learning in social contexts, both important for proper functioning in society.