Event-related potential alterations in fragile X syndrome

Fragile X Syndrome (FXS) is the most common form of X-linked intellectual disability (ID), associated with a wide range of cognitive and behavioral impairments. FXS is caused by a trinucleotide repeat expansion in the FMR1 gene located on the X-chromosome. FMR1 is expected to prevent the expression of the “fragile X mental retardation protein (FMRP)”, which results in altered structural and functional development of the synapse, including a loss of synaptic plasticity. This review aims to unveil the contribution of electrophysiological signal studies for the understanding of the information processing impairments in FXS patients. We discuss relevant event-related potential (ERP) studies conducted with full mutation FXS patients and clinical populations sharing symptoms with FXS in a developmental perspective. Specific deviances found in FXS ERP profiles are described. Alterations are reported in N1, P2, Mismatch Negativity (MMN), N2, and P3 components in FXS compared to healthy controls. Particularly, deviances in N1 and P2 amplitude seem to be specific to FXS. The presented results suggest a cascade of impaired information processes that are in line with symptoms and anatomical findings in FXS

Développement cérébral normal et convulsions fébriles : étude d'électrophysiologie visuelle

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal

Differential Maturation of Brain Signal Complexity in the Human Auditory and Visual System

Brain development carries with it a large number of structural changes at the local level which impact on the functional interactions of distributed neuronal networks for perceptual processing. Such changes enhance information processing capacity, which can be indexed by estimation of neural signal complexity. Here, we show that during development, EEG signal complexity increases from one month to 5 years of age in response to auditory and visual stimulation. However, the rates of change in complexity were not equivalent for the two responses. Infants’ signal complexity for the visual condition was greater than auditory signal complexity, whereas adults showed the same level of complexity to both types of stimuli. The differential rates of complexity change may reflect a combination of innate and experiential factors on the structure and function of the two sensory systems

Could we use parent report as a valid proxy of child report on anxiety, depression, and distress? : a systematic investigation of father–mother–child triads in children successfully treated for leukemia

Background Systematic assessment of emotional distress is recommended in after care. Yet, it is unclear if parent report may be used as a proxy of child report. The aim of this study was to assess agreements and differences and explore possible moderators of disagreement between child and parent ratings. Methods Sixty‐two young survivors treated for acute lymphoblastic leukemia (9–18 years) and both parents responded to the Beck Youth Inventory (anxiety and depression) and the distress rating scale on the child's status. Parents completed the Brief Symptom Inventory‐18 on their own psychological status. Systematic analyses of agreement and differences were performed. Results Mother–child and father–child agreements were fair on anxiety, depression, and distress (median intraclass correlation coefficient = 0.37). Differences between parents and children were medium sized (median d = 0.55) with parents giving higher scores than their children on anxiety, depression, and distress. Mothers reported distress more frequently than fathers (39 vs. 17%) when children reported none. The child being female and lower parental income were associated with lower agreement in fathers when rating child distress. Higher levels of parental psychological symptoms were consistently associated with lower agreement. Conclusions Parent–child differences when rating adolescent survivors’ difficulties may be more important than previously thought. Parent report probably cannot be considered as a valid proxy of older child report on such internalized domains as anxiety, depression, or distress in the after‐care clinic. Parents’ report is also likely to be influenced by their own mood, a factor that should be corrected for when using their report

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

Objective: Studies have identified 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 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 mixedanalysis 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 150-600ms 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

Screening for distress in pediatric cancer survivors : a systematic comparison of one-step and two-step strategies to minimize detection errors

Background:Childhood cancer survivors should be routinelyscreened for psychological distress. However, existing screeningtools promoted by cancer care institutions, such as the DistressThermometer (DT) generate high rates of errors. The aim of thisstudy is to help refining strategies of screening psychologicaldistress in this population by exploring two-step methods com-bining the DT on step #1 with one question on step #2.Procedure:Data from 255 survivors of childhood acutelymphoblastic leukemia aged 13–40years were analyzed (38%13–18 years, 62% 19þyears, 53% females). We used the DTon step #1 and the individual emotion items from thePediatric Quality of Life Questionnaire (PedsQL) on step #2, todetect distress, depression and anxiety as measured by stand-ard instruments. We compared sensitivity, specificity, negativeand positive predictive values, Youden index, and clinical util-ity indices, in newly developed two-step strategies.Results:The best two-step strategies to screen anxious-depressive distress were DT 2 on step #1, with the item ofSadness on step #2, and DT 2 combined with the item ofConcerns. Two-step strategies outperformed the DT alone onthe correct identification of distressed survivors. However,two-step strategies did not outperform the DT used alone onthe correct detection of no distressed survivors. Results weresimilar when predicting depression or anxiety alone.Conclusion:Completing the DT with one single question onemotions from the PedsQL may minimize the number of par-ticipants falsely identified as distressed, which could be par-ticularly pertinent in resource-limited clinics

Impact of brain overgrowth on sensorial learning processing during the first year of life

Macrocephaly is present in about 2–5% of the general population. It can be found as an isolated benign trait or as part of a syndromic condition. Brain overgrowth has been associated with neurodevelopmental disorders such as autism during the first year of life, however, evidence remains inconclusive. Furthermore, most of the studies have involved pathological or high-risk populations, but little is known about the effects of brain overgrowth on neurodevelopment in otherwise neurotypical infants. We investigated the impact of brain overgrowth on basic perceptual learning processes (repetition effects and change detection response) during the first year of life. We recorded high density electroencephalograms (EEG) in 116 full-term healthy infants aged between 3 and 11 months, 35 macrocephalic (14 girls) and 81 normocephalic (39 girls) classified according to the WHO head circumference norms. We used an adapted oddball paradigm, time-frequency analyses, and auditory event-related brain potentials (ERPs) to investigate differences between groups. We show that brain overgrowth has a significant impact on repetition effects and change detection response in the 10–20 Hz frequency band, and in N450 latency, suggesting that these correlates of sensorial learning processes are sensitive to brain overgrowth during the first year of life

Inconsistencies between measures of cognitive dysfunction in childhood acute lymphoblastic leukemia survivors : description and understanding

Objectives The frequency of cognitive difficulties in childhood cancer survivors varies according to the measurement strategy. The goal of this research is to (a) describe agreements and differences between measures of working memory and attention (b) identify contributors of these differences, such as emotional distress, affects, and fatigue. Methods We used data available for 138 adults successfully treated for childhood acute lymphoblastic leukemia (ALL) (PETALE cohort). Working memory and attention were assessed using subtests from the WAIS‐IV and self‐reported questionnaires (BRIEF‐SR and CAARS‐S:L). Potential contributors included emotional distress, anxiety, depression (BSI‐18), affects (PANAS), and fatigue (PedsQL‐MFS). We explored measurement agreements and differences using diagnostic indices and multivariate regression models. Results The frequencies of working memory and attention deficits were higher when using cognitive tests (15%‐21%) than with self‐reports (10%‐11%). Self‐reported questionnaires showed high specificity (median 0.87) and low sensitivity (median 0.10), suggesting they did not reliably identify positive cases on cognitive tests. We identified negative affectivity as a possible contributor to inconsistencies between self‐report and test results. Conclusions When measuring working memory and attention in childhood ALL survivors, cognitive test results and self‐reports should not be considered equivalent. At best, self‐report may be used for screening (high specificity), but not to assess prevalence in large samples. Self‐reported difficulties are also probably influenced by the negative mood in this population

Contributing factors of unmet needs among young adult survivors of childhood acute lymphoblastic leukemia with comorbidities

Purpose: This study aimed to: (1) describe the domains and levels of unmet needs of young adult survivors of childhood acute lymphoblastic leukemia (cALL) with comorbidities, and (2) to explore the factors associated with higher levels of unmet needs. Unmet need was considered as supportive care needs not met. Methods: The most vulnerable cALL survivors from the PETALE study cohort completed the Short-Form Survivor Unmet Needs Survey, the Brief Pain Inventory and the 15D instrument of health-related quality of life. Demographic and clinical information, including comorbidities, were obtained from medical records or self-reporting. The participants' needs and contributing factors to their needs were evaluated using nonparametric tests. Results: Of the 72 participants, 9 (13%) reported moderate/high levels of overall unmet needs. “Worry about earning money” (56%) and “Dealing with feeling tired” (51%) were the most frequent unmet needs (all levels combined). The factors associated significantly with any domain of unmet needs were: having a comorbidity, reporting altered functional health status, high ALL risk status, pain, age (<26 years), and having previously received psychological support. Conclusion: A minority of young adult survivors of cALL with comorbidities interviewed reported moderate/high levels of unmet needs. However, financial concerns and emotional health and relationship are the two domains of greatest need. Survivors with altered health condition are most at risk of experiencing moderate/high levels of unmet needs. If confirmed in larger samples, interventions should target modifiable contributors of unmet needs such as physical health and comfort, fatigue, and emotional health

Using rare genetic mutations to revisit structural brain asymmetry

Asymmetry between the left and right hemisphere is a key feature of brain organization. Hemispheric functional specialization underlies some of the most advanced human-defining cognitive operations, such as articulated language, perspective taking, or rapid detection of facial cues. Yet, genetic investigations into brain asymmetry have mostly relied on common variants, which typically exert small effects on brain-related phenotypes. Here, we leverage rare genomic deletions and duplications to study how genetic alterations reverberate in human brain and behavior. We designed a pattern-learning approach to dissect the impact of eight high-effect-size copy number variations (CNVs) on brain asymmetry in a multi-site cohort of 552 CNV carriers and 290 non-carriers. Isolated multivariate brain asymmetry patterns spotlighted regions typically thought to subserve lateralized functions, including language, hearing, as well as visual, face and word recognition. Planum temporale asymmetry emerged as especially susceptible to deletions and duplications of specific gene sets. Targeted analysis of common variants through genome-wide association study (GWAS) consolidated partly diverging genetic influences on the right versus left planum temporale structure. In conclusion, our gene-brain-behavior data fusion highlights the consequences of genetically controlled brain lateralization on uniquely human cognitive capacities