Reduced Interhemispheric Coherence and Cognition in Children with Fetal Alcohol Spectrum Disorder (FASD)-A Quantitative EEG Study.

BACKGROUND: Magnetic resonance imaging in fetal alcohol spectrum disorder (FASD) children showed altered connectivity, suggesting underlying deficits in networks, which may be related to cognitive outcome. Functional connectivity has been of interest in neurophysiological research with quantitative electroencephalography (QEEG) as useful tool for measuring pathology, not detectable by normal EEG. The aim of this study was to investigate differences in the EEG interhemispheric coherence (ICoh) in children diagnosed with FASD compared with healthy controls and to relate the results to cognitive scores. METHOD: Analysis of ICoh in 81 FASD children (4-Digit Code) compared with 31 controls. The children underwent cognitive assessment, and EEG was performed and used for analysis. Group comparisons and analysis of covariance interaction models were used to test for differences between FASD and controls but also to look for differences between FASD subgroups. Significant findings were correlated to cognitive scores. RESULTS: Lower ICoh was found in the frontal and temporal derivations in the FASD group. When comparing FASD subgroups, children with fetal alcohol syndrome had lower ICoh occipital. Reduced ICoh in the temporal alpha band was correlated with lower performance IQ in the FASD group. CONCLUSION: Our findings could imply hypoconnectivity between the hemispheres with impact on cognition. We suggest that EEG coherence analysis could be a sensitive parameter in the detection of electrophysiological abnormalities in FASD with possible clinical relevance. These results may indicate that QEEG could be used as biomarker for FASD. However, further research is needed to determine the role of QEEG analysis in the diagnosis of FASD.

Frequency of epilepsy and pathological EEG findings in a Norwegian sample of children with fetal alcohol spectrum disorder: Impact on cognition and adaptive functioning.

BACKGROUND: Fetal alcohol spectrum disorder (FASD) comprises a combination of developmental, cognitive, and behavioral disabilities that occur in children exposed to alcohol prenatally. A higher prevalence of epilepsy and pathological electroencephalographic (EEG) features have also been reported in individuals with FASD. We examined the frequency of epilepsy, pathological EEG findings, and their implications for cognitive and adaptive functioning in children with FASD. METHODS: We conducted a cross-sectional study of 148 children with FASD who underwent a multidisciplinary assessment and a 120-min EEG recording. Group comparisons and regression analyses were performed to test the associations between epilepsy and pathological EEG findings, FASD subgroups and neurocognitive test results and adaptive functioning. RESULTS: The frequency of epilepsy was 6%, which compares with 0.7% in Norway overall. Seventeen percent of children without epilepsy had pathological EEG findings. Attention-deficit hyperactivity disorder (ADHD) was diagnosed in 64% of the children. Children with epilepsy and/or pathological EEG findings had comparable cognitive and adaptive scores to those with normal EEG. However, children with frontal EEG pathology (without epilepsy) had significantly lower scores on the IQ indices Processing speed and Working memory than FASD children without such findings, irrespective of ADHD comorbidity. CONCLUSIONS: There was a greater prevalence of epilepsy among children with FASD than in the general Norwegian population. A greater frequency of EEG pathology was also evident in children without epilepsy, across all FASD subgroups. Irrespective of epilepsy, ADHD comorbidity, and FASD subgroup, children with frontal EEG pathology, despite having a normal total IQ, showed significantly slower processing speed and poorer working memory, which may indicate specific executive function deficits that could affect learning and adaptive functioning.

Working Memory Training in Norwegian Children with Cerebral Palsy (CP) Show Minimal Evidence of Near and No Far Transfer Effects.

In children with cerebral palsy (CP), learning disabilities are well documented, and impairments in executive functions, such as attention, inhibition, shifting and working memory, represent significant burdens on patients, their families and the society. The aim of this study was to evaluate whether Cogmed RM working memory training could improve working memory in children with CP and investigate whether increased working memory capacity would generalize to other cognitive functions. Twenty-eight children completed the training and the results were compared to a waitlist control group (n = 32). The results yielded three main findings. First, children with CP improved with practice on trained working memory tasks. Second, the intervention group showed minimal near transfer effects to non-trained working memory tasks. Third, no effects on cognitive and behavioral far transfer measures were found.

Sleep disturbances in Norwegian children with fetal alcohol spectrum disorders (FASD) with and without a diagnosis of attention-deficit hyperactivity disorder or epilepsy.

BACKGROUND: Fetal alcohol spectrum disorder (FASD) describes a combination of developmental, cognitive, and behavioral disabilities in children with prenatal exposure to alcohol. The literature suggests that there are higher rates of sleep disturbances in these children. Few studies have investigated sleep disturbances in relation to common comorbidities of FASD. We examined the prevalence of disturbed sleep and the relationship between parent-reported sleep problems in different FASD subgroups and comorbidities like epilepsy or attention-deficit hyperactivity disorder (ADHD) and impact on clinical functioning. METHODS: In this prospective cross-sectional survey, caregivers of 53 children with FASD completed the Sleep Disturbance Scale for Children (SDSC). Information about comorbidities was collected, and EEG and assessment of IQ, daily-life executive and adaptive functioning were performed. Group comparisons and ANCOVA interaction models were used to test the associations between different sleep disturbances and clinical factors that could interfere with sleep. RESULTS: An abnormal sleep score on the SDSC was very common, affecting 79% of children (n = 42) with equal prevalence in all FASD subgroups. Difficulty falling asleep was the most common sleep problem, followed by difficulty staying asleep and waking early. The incidence of epilepsy was 9.4%, with an abnormal EEG seen in 24.5%, and a diagnosis of ADHD in 47.2% of children. The distribution of these conditions was equal in all FASD subgroups. Children with signs of sleep disturbance had poorer working memory, executive function, and adaptive functioning. Children with ADHD had a greater prevalence of sleep disturbance than those without ADHD (OR 1.36; 95% CI 1.03 to 1.79). CONCLUSION: Problems with sleep are very common in FASD children and seem independent of FASD subgroup and the presence of epilepsy or a pathological EEG finding, while those with ADHD had more sleep problems. The study underscores the importance of screening for sleep disturbances in all children with FASD as these problems may be treatable.

Atypical brain structure mediates reduced IQ in young adults born preterm with very low birth weight.

Preterm birth with very low birth weight (VLBW) confers heightened risk for perinatal brain injury and long-term cognitive deficits, including a reduction in IQ of up to one standard deviation. Persisting gray and white matter aberrations have been documented well into adolescence and adulthood in preterm born individuals. What has not been documented so far is a plausible causal link between reductions in cortical surface area or subcortical brain structure volumes, and the observed reduction in IQ. The NTNU Low Birth Weight in a Lifetime Perspective study is a prospective longitudinal cohort study, including a preterm born VLBW group (birthweight ≤1500 g) and a term born control group. Structural magnetic resonance imaging data were obtained from 38 participants aged 19, born preterm with VLBW, and 59 term-born peers. The FreeSurfer software suite was used to obtain measures of cortical thickness, cortical surface area, and subcortical brain structure volumes. Cognitive ability was estimated using the Wechsler Adult Intelligence Scale, 3rd Edition, including four IQ-indices: Verbal comprehension, Working memory, Perceptual organization, and Processing speed. Statistical mediation analyses were employed to test for indirect effects of preterm birth with VLBW on IQ, mediated by atypical brain structure. The mediation analyses revealed negative effects of preterm birth with VLBW on IQ that were partially mediated by reduced surface area in multiple regions of frontal, temporal, parietal and insular cortex, and by reductions in several subcortical brain structure volumes. The analyses did not yield sufficient evidence of mediation effects of cortical thickness on IQ. This is, to our knowledge, the first time a plausible causal relationship has been established between regional cortical area reductions, as well as reductions in specific subcortical and cerebellar structures, and general cognitive ability in preterm born survivors with VLBW.

Assessment of cognitive function, structural brain changes and fatigue 6 months after treatment of neuroborreliosis.

BACKGROUND: Complete recovery after adequately treated neuroborreliosis is common, but studies report that some patients experience persistent symptoms like self-reported cognitive problems and fatigue. Persisting symptoms are often termed post-Lyme disease syndrome, of which etiology is not clearly understood. The aim of this study was to investigate cognitive function, possible structural changes in brain regions and level of fatigue. We have not found previous studies on neuroborreliosis that use standardized neuropsychological tests and MRI with advanced image processing to investigate if there are subtle regional changes in cortical thickness and brain volumes after treatment. METHODS: We examined 68 patients treated for neuroborreliosis 6 months earlier and 66 healthy controls, with a comprehensive neuropsychological test protocol, quantitative structural MRI analysis of the brain and Fatigue Severity Scale. RESULTS: We found no differences between the groups in either cognitive function, cortical thickness or brain volumes. The patients had higher score on Fatigue Severity Scale 3.8 vs. 2.9 (p = 0.001), and more patients (25.4%) than controls (5%) had severe fatigue (p = 0.002), but neither mean score nor proportion of patients with severe fatigue differed from findings in the general Norwegian population. CONCLUSION: The prognosis regarding cognitive function, brain MRI findings and fatigue after adequately treated neuroborreliosis is favorable.

Cognitive function in patients with neuroborreliosis: A prospective cohort study from the acute phase to 12 months post treatment.

BACKGROUND: Long-term cognitive problems after neuroborreliosis treatment remain a subject of debate. We have previously shown that cognitive problems are not present in the acute phase of neuroborreliosis, although fatigue is common. The aim of this study was to re-assess the same patient cohort and evaluate long-term outcomes. METHODS: In this follow-up, we re-assessed 58 patients with well-characterized neuroborreliosis 12 months after completing treatment. The same protocol with eight subtests measuring attention and processing speed and the Fatigue Severity Scale (FSS) were used to compare the results from the acute phase to 12 months post treatment. RESULTS: We found no changes in attention or processing speed but a reduction in the level of fatigue (median score on FSS: 4.9 vs. 3.9, p < .001) from the acute phase to 12 months post treatment. CONCLUSION: The patient group did not develop problems with attention or processing speed post treatment, while the level of fatigue decreased.

Cortical Thickness Changes After Computerized Working Memory Training in Patients With Mild Cognitive Impairment.

Background: Adaptive computerized working memory (WM) training has shown favorable effects on cerebral cortical thickness as compared to non-adaptive training in healthy individuals. However, knowledge of WM training-related morphological changes in mild cognitive impairment (MCI) is limited. Objective: The primary objective of this double-blind randomized study was to investigate differences in longitudinal cortical thickness trajectories after adaptive and non-adaptive WM training in patients with MCI. We also investigated the genotype effects on cortical thickness trajectories after WM training combining these two training groups using longitudinal structural magnetic resonance imaging (MRI) analysis in Freesurfer. Method: Magnetic resonance imaging acquisition at 1.5 T were performed at baseline, and after four- and 16-weeks post training. A total of 81 individuals with MCI accepted invitations to undergo 25 training sessions over 5 weeks. Longitudinal Linear Mixed effect models investigated the effect of adaptive vs. non-adaptive WM training. The LME model was fitted for each location (vertex). On all statistical analyzes, a threshold was applied to yield an expected false discovery rate (FDR) of 5%. A secondary LME model investigated the effects of LMX1A and APOE-ε4 on cortical thickness trajectories after WM training. Results: A total of 62 participants/patients completed the 25 training sessions. Structural MRI showed no group difference between the two training regimes in our MCI patients, contrary to previous reports in cognitively healthy adults. No significant structural cortical changes were found after training, regardless of training type, across all participants. However, LMX1A-AA carriers displayed increased cortical thickness trajectories or lack of decrease in two regions post-training compared to those with LMX1A-GG/GA. No training or training type effects were found in relation to the APOE-ε4 gene variants. Conclusion: The MCI patients in our study, did not have improved cortical thickness after WM training with either adaptive or non-adaptive training. These results were derived from a heterogeneous population of MCI participants. The lack of changes in the cortical thickness trajectory after WM training may also suggest the lack of atrophy during this follow-up period. Our promising results of increased cortical thickness trajectory, suggesting greater neuroplasticity, in those with LMX1A-AA genotype need to be validated in future trials.

Early spectral EEG in preterm infants correlates with neurocognitive outcomes in late childhood.

BACKGROUND: Evidence regarding the predictive value of early amplitude-integrated electroencephalography (aEEG)/EEG on neurodevelopmental outcomes at school age and beyond is lacking. We  aimed to investigate whether there is an association between early postnatal EEG and neurocognitive outcomes in late childhood. METHODS: This study is an observational prospective cohort study of premature infants with a gestational age <28 weeks. The total absolute band powers (tABP) of the delta, theta, alpha, and beta bands were analyzed from EEG recordings during the first three days of life. At 10-12 years of age, neurocognitive outcomes were assessed using the Wechsler Intelligence Scale for Children 4th edition (WISC-IV), Vineland adaptive behavior scales 2nd edition, and Behavior Rating Inventory of Executive Function (BRIEF). The mean differences in tABP were assessed for individuals with normal versus unfavorable neurocognitive scores. RESULTS: Twenty-two infants were included. tABP values in all four frequency bands were significantly lower in infants with unfavorable results in the main composite scores (full intelligence quotient, adaptive behavior composite score, and global executive composite score) on all three tests (p < 0.05). CONCLUSIONS: Early postnatal EEG has the potential to assist in predicting cognitive outcomes at 10-12 years of age in extremely premature infants <28 weeks' gestation. IMPACT: Evidence regarding the value of early postnatal EEG in long-term prognostication in preterm infants is limited. Our study suggests that early EEG spectral analysis correlates with neurocognitive outcomes in late childhood in extremely preterm infants. Early identification of infants at-risk of later impairment is important to initiate early and targeted follow-up and intervention.

Working Memory Training in Amnestic and Non-amnestic Patients With Mild Cognitive Impairment: Preliminary Findings From Genotype Variants on Training Effects.

Working memory training (WMT) effects may be modulated by mild cognitive impairment (MCI) subtypes, and variations in APOE-epsilon (APOE-ε) and LMX1A genotypes. Sixty-one individuals (41 men/20 women, mean age 66 years) diagnosed with MCI (31 amnestic/30 non-amnestic) and genotyped for APOE-ε and LMX1A completed 4 weeks/20-25 sessions of WMT. Cognitive functions were assessed before, 4 weeks and 16 weeks after WMT. Except for Processing Speed, the non-amnestic MCI group (naMCI) outperformed the amnestic MCI (aMCI) group in all cognitive domains across all time-points. At 4 weeks, working memory function improved in both groups (p < 0.0001), but at 16 weeks the effects only remained in the naMCI group. Better performance was found after training for the naMCI patients with LMX1A-AA genotype and for the APOE-ε4 carriers. Only the naMCI-APOE-ε4 group showed improved Executive Function at 16 weeks. WMT improved working memory and some non-trained cognitive functions in individuals with MCI. The naMCI group had greater training gain than aMCI group, especially in those with LMX1A-AA genotype and among APOE-ε4-carriers. Further research with larger sample sizes for the subgroups and longer follow-up evaluations is warranted.

Cognitive function, fatigue and Fazekas score in patients with acute neuroborreliosis.

Long-term cognitive problems and fatigue after adequately treated neuroborreliosis has caused uncertainty and debate among patients and health care workers for years. Despite several studies, the prevalence, cause and severity of such complaints are still not clarified. More knowledge about cognitive function, fatigue and MRI findings in the acute phase of neuroborreliosis could possibly contribute to clarification. In the current study, we therefore aimed to address this. Patients with well-characterized acute neuroborreliosis (n = 72) and a matched control group (n = 68) were screened with eight subtests from three different neuropsychological test batteries assessing attention, working memory and processing speed, and with Fatigue Severity Scale. Fazekas score was used to grade white matter hyperintensities on MRI. We found no differences in mean scores on the neuropsychological tests between the groups. The patient group reported significantly higher level of fatigue (Fatigue Severity Scale: 4.8 vs. 2.9, p < .001). There was no significant difference in Fazekas score between the groups. Neuroborreliosis does not seem to affect cognitive functions in the acute state of the disease, while fatigue is common.

Is there an association between full IQ score and mental health problems in young adults? A study with a convenience sample.

BACKGROUND: Intelligence is the aggregate or global capacity of the individual to act purposefully, to think rationally and to deal effectively with the environment. Previous studies have shown that individuals with intellectual disability, IQ < 70, have increased risk of being diagnosed with one or more mental disorders. We wanted to investigate if this also applies to individuals with IQ between 70 and 85. METHODS: In this study, data was abstracted from a longitudinal follow-up study of individuals with low birth weight and a control group. In the present study, mental health of participants with borderline IQ, defined as a full IQ score 70-84, were compared with mental health of a reference group with full IQ scores ≥85. Mental health at age 19 was assessed using the Schedule for Affective Disorder and Schizophrenia for School-age Children Present and Lifetime (K-SADS P/L) whereby scores meeting the diagnostic criteria for a mental disorder were defined as having mental health problems. In addition the participants completed the ADHD-rating scale and the Autism Spectrum Quotient form (AQ). Logistic regression analyses were used to calculate odds ratio (OR) with 95% confidence intervals (CI) for high scores on the K-SADS. RESULTS: Thirty participants with borderline IQ and 146 controls were included. Sixteen (53%) of the participants with borderline IQ met the diagnostic criteria on the K-SADS for any diagnosis compared with 18 (12%) in the reference group (OR: 6.2; CI: 2.6-14.9). In particular the participants with borderline IQ had excess risk of ADHD and anxiety. These associations were slightly attenuated when adjusted for birth weight and parents' socioeconomic status. CONCLUSIONS: 53% of the participants with borderline IQ had increased risk for a research assessed psychiatric diagnosis compared to about one in ten in the reference group. The group with borderline IQ also had higher total scores and higher scores on some sub-scores included in the Autism Spectrum Quotient form. Our results points towards an increased vulnerability for mental illness in individuals with borderline low IQ. TRIAL REGISTRATION: The main study is recorded by the Regional Committee for Health Research Ethics in Mid-Norway (as project number 4.2005.2605).

Reduced hippocampal subfield volumes and memory function in school-aged children born preterm with very low birthweight (VLBW).

BACKGROUND: The hippocampus, an essential structure for learning and memory, has a reduced volume in preterm born (gestational age < 37 weeks) individuals with very low birth weight (VLBW: birth weight < 1500 g), which may affect memory function. However, the hippocampus is a complex structure with distinct subfields related to specific memory functions. These subfields are differentially affected by a variety of neuropathological conditions, but it remains unclear how these subfields may be affected by medical complications following preterm birth which may cause aberrant brain development, and the consequences of this on learning and memory function in children with VLBW. METHODS: Children born preterm with VLBW (n = 34) and term-born controls from the Norwegian Mother and Child Cohort Study (MoBa) (n = 104) underwent structural MRI and a neuropsychological assessment of memory function at primary school age. FreeSurfer 6.0 was used to analyze the volumes of hippocampal subfields which were compared between groups, as was memory performance. Correlations between abnormal hippocampal subfields and memory performance were explored in the VLBW group. RESULTS: All absolute hippocampal subfield volumes were lower in the children with VLBW compared to MoBa term-born controls, and the volumes of the left and right dentate gyrus and the right subiculum remained significantly lower after correcting for total intracranial volume. The VLBW group had inferior working memory performance and the score on the subtest Spatial Span backwards was positively correlated to the volume of the right dentate gyrus. CONCLUSIONS: Hippocampal subfield volumes seem to be differently affected by early brain development related to preterm birth. The dentate gyrus appears particularly susceptible to adverse effects of preterm birth. Reduced working memory function among children with VLBW was associated with smaller volume of right dentate gyrus. This finding demonstrates alterations in hippocampal structure-function relationships associated with early brain development related to preterm birth.

Adaptive Computerized Working Memory Training in Patients With Mild Cognitive Impairment. A Randomized Double-Blind Active Controlled Trial.

OBJECTIVE: We investigated if a 5-week computerized adaptive working memory training program (Cogmed®) of 20 to 25 sessions would be effective in improving the working memory capacity and other neuropsychological functions compared to a non-adaptive working memory training program (active-controlled) in adult patients with mild cognitive impairment (MCI). METHODS: This randomized double-blinded active control trial included 68 individuals aged 43 to 88 years, 45 men and 23 women, who were diagnosed with MCI at four Memory clinics. The study sample was randomized by block randomization to either adaptive or non-adaptive computerized working memory training. All participants completed the training, and were assessed with a comprehensive neuropsychological test battery before the intervention, and at 1 and 4 months after training. RESULTS: Compared to the non-adaptive training group, the adaptive training group did not show significantly greater improvement on the main outcome of working memory performance at 1 and 4 months after training. CONCLUSION: No difference were found between the two types of training on the primary outcome of working memory, or on secondary outcomes of cognitive function domains, in this sample of MCI patients. Hence, the hypothesis that the adaptive training program would lead to greater improvements compared to the non-adaptive training program was not supported. Within group analyses was not performed due to the stringent RCT design.

Corrigendum: Cognitive Profiles and Atrophy Ratings on MRI in Senior Patients With Mild Cognitive Impairment.

[This corrects the article DOI: 10.3389/fnagi.2018.00384.].

Reduced white matter fractional anisotropy mediates cortical thickening in adults born preterm with very low birthweight.

Development of the cerebral cortex may be affected by aberrant white matter development. Preterm birth with very low birth weight (VLBW) has been associated with reduced fractional anisotropy of white matter and changes in cortical thickness and surface area. We use a new methodological approach to combine white and gray matter data and test the hypothesis that white matter injury is primary, and acts as a mediating factor for concomitant gray matter aberrations, in the developing VLBW brain. T1 and dMRI data were obtained from 47 young adults born preterm with VLBW and 73 term-born peers (mean age = 26). Cortical thickness was measured across the cortical mantle and compared between the groups, using the FreeSurfer software suite. White matter pathways were reconstructed with the TRACULA software and projected to their cortical end regions, where cortical thickness was averaged. In the VLBW group, cortical thickness was increased in anteromedial frontal, orbitofrontal, and occipital regions, and fractional anisotropy (FA) was reduced in frontal lobe pathways, indicating compromised white matter integrity. Statistical mediation analyses demonstrated that increased cortical thickness in the frontal regions was mediated by reduced FA in the corpus callosum forceps minor, consistent with the notion that white matter injury can disrupt frontal lobe cortical development. Combining statistical mediation analysis with pathway projection onto the cortical surface offers a powerful novel tool to investigate how cortical regions are differentially affected by white matter injury.

Cognitive Profiles and Atrophy Ratings on MRI in Senior Patients With Mild Cognitive Impairment.

In this cross-sectional study, we sought to describe cognitive and neuroimaging profiles of Memory clinic patients with Mild Cognitive Impairment (MCI). 51 MCI patients and 51 controls, matched on age, sex, and socio-economic status (SES), were assessed with an extensive neuropsychological test battery that included a measure of intelligence (General Ability Index, "GAI," from WAIS-IV), and structural magnetic resonance imaging (MRI). MCI subtypes were determined after inclusion, and z-scores normalized to our control group were generated for each cognitive domain in each MCI participant. MR-images were scored by visual rating scales. MCI patients performed significantly worse than controls on 23 of 31 cognitive measures (Bonferroni corrected p = 0.001), and on 8 of 31 measures after covarying for intelligence (GAI). Compared to nonamnestic MCI patients, amnestic MCI patients had lower test results in 13 of 31 measures, and 5 of 31 measures after co-varying for GAI. Compared to controls, the MCI patients had greater atrophy on Schelten's Medial temporal lobe atrophy score (MTA), especially in those with amnestic MCI. The only structure-function correlation that remained significant after correction for multiple comparisons was the MTA-long delay recall domain. Intelligence operationalized as GAI appears to be an important moderator of the neuropsychological outcomes. Atrophy of the medial temporal lobe, based on MTA scores, may be a sensitive biomarker for the functional episodic memory deficits associated with MCI.

Preterm birth leads to hyper-reactive cognitive control processing and poor white matter organization in adulthood.

Individuals born preterm with very low birth weight (VLBW; birth weight ≤ 1500 g) are at high risk for perinatal brain injuries and deviant brain development, leading to increased chances of later cognitive, emotional, and behavioral problems. Here we investigated the neuronal underpinnings of both reactive and proactive cognitive control processes in adults with VLBW. We included 32 adults born preterm with VLBW (before 37th week of gestation) and 32 term-born controls (birth weight ≥10th percentile for gestational age) between 22 and 24 years of age that have been followed prospectively since birth. Participants performed a well-validated Not-X continuous performance test (CPT) adapted for use in a mixed block- and event-related fMRI protocol. BOLD fMRI and DTI data was acquired on a 3T scanner. Performance on the Not-X CPT was highly similar between groups. However, the VLBW group demonstrated hyper-reactive cognitive control processing and disrupted white matter organization. The hyper-reactive brain activation signature in VLBW adults was associated with lower gestational age, lower fluid intelligence score, and anxiety problems. Automated Multi-Atlas Tract Extraction (AutoMATE) analyses revealed that this disruption of normal brain function was accompanied by poorer white matter organization in the anterior thalamic radiation and the cingulum, as reflected in both reduced fractional anisotropy and increased mean diffusivity. These findings show that the preterm behavioral phenotype is associated with predominantly reactive-, rather than proactive cognitive control processing, as well as white matter abnormalities, that may underlie common difficulties that many preterm born individuals experience in everyday life.

Amplitude-Integrated Electroencephalography Improves the Identification of Infants with Encephalopathy for Therapeutic Hypothermia and Predicts Neurodevelopmental Outcomes at 2 Years of Age.

OBJECTIVES: To examine whether using an amplitude-integrated electroencephalography (aEEG) severity pattern as an entry criterion for therapeutic hypothermia better selects infants with hypoxic-ischemic encephalopathy and to assess the time-to-normal trace for aEEG and magnetic resonance imaging (MRI) lesion load as 24-month outcome predictors. STUDY DESIGN: Forty-seven infants meeting Norwegian therapeutic hypothermia guidelines were enrolled prospectively. Eight-channel EEG/aEEG was recorded from 6 hours until after rewarming, and read after discharge. Neonatal MRI brain scans were scored for summated (range 0-11) regional lesion load. A poor outcome at 2 years was defined as death or a Bayley Scales of Infant-Toddler Development cognitive or motor composite score of <85 or severe hearing or visual loss. RESULTS: Three severity groups were defined from the initial aEEG; continuous normal voltage (CNV; n = 15), discontinuous normal voltage (DNV; n = 18), and a severe aEEG voltage pattern (SEVP; n = 14). Any seizure occurrence was 7% CNV, 50% DNV, and 100% SEVP. Infants with SEVP with poor vs good outcome had a significantly longer median (IQR) time-to-normal trace: 58 hours (9-79) vs 18 hours (12-19) and higher MRI lesion load: 10 (3-10) vs 2 (1-5). A poor outcome was noted in 3 of 15 infants with CNV, 4 of 18 infants with DNV, and 8 of 14 infants with SEVP. Using multiple stepwise linear regression analyses including only infants with abnormal aEEG (DNV and SEVP), MRI lesion load significantly predicted cognitive and motor scores. For the SEVP group alone, time-to-normal trace was a stronger outcome predictor than MRI score. No variable predicted outcome in infants with CNV. CONCLUSIONS: Selection of infants with encephalopathy for therapeutic hypothermia after perinatal asphyxia may be improved by including only infants with an early moderate or severely depressed background aEEG trace.

Neural correlates of adaptive working memory training in a glycogen storage disease type-IV patient.

Glycogen storage disease type-IV has varied clinical presentations and subtypes. We evaluated a 38-year-old man with memory complaints, common symptoms in adult polyglucosan body disease subtype, and investigated cognitive and functional MRI changes associated with two 25-sessions of adaptive working memory training. He showed improved trained and nontrained working memory up to 6-months after the training sessions. On functional MRI, he showed increased cortical activation 1-3 months after training, but both increased and decreased activation 6-months later. Working memory training appears to be beneficial to patients with adult polyglucosan body disease, although continued training may be required to maintain improvements.