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.

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.

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.

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.

Adaptive working memory training improved brain function in human immunodeficiency virus-seropositive patients.

OBJECTIVE: We aimed to evaluate the effectiveness of an adaptive working memory (WM) training (WMT) program, the corresponding neural correlates, and LMX1A-rs4657412 polymorphism on the adaptive WMT, in human immunodeficiency virus (HIV) participants compared to seronegative (SN) controls. METHODS: A total of 201 of 206 qualified participants completed baseline assessments before randomization to 25 sessions of adaptive WMT or nonadaptive WMT. A total of 74 of 76 (34 HIV, 42 SN) completed adaptive WMT and all 40 completed nonadaptive WMT (20 HIV, 20 SN) and were assessed after 1 month, and 55 adaptive WMT participants were also assessed after 6 months. Nontrained near-transfer WM tests (Digit-Span, Spatial-Span), self-reported executive functioning, and functional magnetic resonance images during 1-back and 2-back tasks were performed at baseline and each follow-up visit, and LMX1A-rs4657412 was genotyped in all participants. RESULTS: Although HIV participants had slightly lower cognitive performance and start index than SN at baseline, both groups improved on improvement index (>30%; false discovery rate [FDR] corrected p < 0.0008) and nontrained WM tests after adaptive WMT (FDR corrected, p ≤ 0.001), but not after nonadaptive WMT (training by training type corrected, p = 0.01 to p = 0.05) 1 month later. HIV participants (especially LMX1A-G carriers) also had poorer self-reported executive functioning than SN, but both groups reported improvements after adaptive WMT (Global: training FDR corrected, p = 0.004), and only HIV participants improved after nonadaptive WMT. HIV participants also had greater frontal activation than SN at baseline, but brain activation decreased in both groups at 1 and 6 months after adaptive WMT (FDR corrected, p < 0.0001), with normalization of brain activation in HIV participants, especially the LMX1A-AA carriers (LMX1A genotype by HIV status, cluster-corrected-p < 0.0001). INTERPRETATION: Adaptive WMT, but not nonadaptive WMT, improved WM performance in both SN and HIV participants, and the accompanied decreased or normalized brain activation suggest improved neural efficiency, especially in HIV-LMX1A-AA carriers who might have greater dopaminergic reserve. These findings suggest that adaptive WMT may be an effective adjunctive therapy for WM deficits in HIV participants. ANN NEUROL 2017;81:17-34.

Limited microstructural and connectivity deficits despite subcortical volume reductions in school-aged children born preterm with very low birth weight.

Preterm birth and very low birth weight (VLBW, ≤1500 g) are worldwide problems that burden survivors with lifelong cognitive, psychological, and physical challenges. In this multimodal structural magnetic resonance imaging (MRI) and diffusion MRI (dMRI) study, we investigated differences in subcortical brain volumes and white matter tract properties in children born preterm with VLBW compared to term-born controls (mean age=8 years). Subcortical brain structure volumes and cortical thickness estimates were obtained, and fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) were generated for 18 white matter tracts. We also assessed structural relationships between white matter tracts and cortical thickness of the tract endpoints. Compared to controls, the VLBW group had reduced volumes of thalamus, globus pallidus, corpus callosum, cerebral white matter, ventral diencephalon, and brain stem, while the ventricular system was larger in VLBW subjects, after controlling for age, sex, IQ, and estimated total intracranial volume. For the dMRI parameters, group differences were not significant at the whole-tract level, though pointwise analysis found shorter segments affected in forceps minor and left superior longitudinal fasciculus - temporal bundle. IQ did not correlate with subcortical volumes or dMRI measures in the VLBW group. While the deviations in subcortical volumes were substantial, there were few differences in dMRI measures between the two groups, which may reflect the influence of advances in perinatal care on white matter development.

Memory function and hippocampal volumes in preterm born very-low-birth-weight (VLBW) young adults.

The hippocampi are regarded as core structures for learning and memory functions, which is important for daily functioning and educational achievements. Previous studies have linked reduction in hippocampal volume to working memory problems in very low birth weight (VLBW; ≤ 1500 g) children and reduced general cognitive ability in VLBW adolescents. However, the relationship between memory function and hippocampal volume has not been described in VLBW subjects reaching adulthood. The aim of the study was to investigate memory function and hippocampal volume in VLBW young adults, both in relation to perinatal risk factors and compared to term born controls, and to look for structure-function relationships. Using Wechsler Memory Scale-III and MRI, we included 42 non-disabled VLBW and 61 control individuals at age 19-20 years, and related our findings to perinatal risk factors in the VLBW-group. The VLBW young adults achieved lower scores on several subtests of the Wechsler Memory Scale-III, resulting in lower results in the immediate memory indices (visual and auditory), the working memory index, and in the visual delayed and general memory delayed indices, but not in the auditory delayed and auditory recognition delayed indices. The VLBW group had smaller absolute and relative hippocampal volumes than the controls. In the VLBW group inferior memory function, especially for the working memory index, was related to smaller hippocampal volume, and both correlated with lower birth weight and more days in the neonatal intensive care unit (NICU). Our results may indicate a structural-functional relationship in the VLBW group due to aberrant hippocampal development and functioning after preterm birth.

Visual-motor deficits relate to altered gray and white matter in young adults born preterm with very low birth weight.

Individuals born preterm and at very low birth weight (birth weight ≤ 1500 g) are at an increased risk of perinatal brain injury and neurodevelopmental deficits over the long term. This study examined whether this clinical group has more problems with visual-motor integration, motor coordination, and visual perception compared to term-born controls, and related these findings to cortical surface area and thickness and white matter fractional anisotropy. Forty-seven preterm-born very low birth weight individuals and 56 term-born controls were examined at 18-22 years of age with a combined cognitive, morphometric MRI, and diffusion tensor imaging evaluation in Trondheim, Norway. Visual-motor skills were evaluated with the Beery-Buktenica Developmental Test of Visual-Motor Integration-V (VMI) copying test and its supplemental tests of motor coordination and visual perception. 3D T1-weighted MPRAGE images and diffusion tensor imaging were done at 1.5 T. Cortical reconstruction generated in FreeSurfer and voxelwise maps of fractional anisotropy calculated with Tract-Based Spatial Statistics were used to explore the relationship between MRI findings and cognitive results. Very low birth weight individuals had significantly lower scores on the copying and motor coordination tests compared with controls. In the very low birth weight group, VMI scores showed significant positive relationships with cortical surface area in widespread regions, with reductions of the superior temporal gyrus, insula, and medial occipital lobe in conjunction with the posterior ventral temporal lobe. Visual perception scores also showed positive relationships with cortical thickness in the very low birth weight group, primarily in the lateral occipito-temporo-parietal junction, the superior temporal gyrus, insula, and superior parietal regions. In the very low birth weight group, visual-motor performance correlated positively with fractional anisotropy especially in the corpus callosum, inferior fronto-occipital fasciculus bilaterally, and anterior thalamic radiation bilaterally, driven primarily by an increase in radial diffusivity. VMI scores did not demonstrate a significant relationship to cortical surface area, cortical thickness, or diffusion measures in the control group. Our results indicate that visual-motor integration problems persist into adulthood for very low birth weight individuals, which may be due to structural alterations in several specific gray-white matter networks. Visual-motor deficits appear related to reduced surface area of motor and visual cortices and disturbed connectivity in long association tracts containing visual and motor information. We conjecture that these outcomes may be due to perinatal brain injury or aberrant cortical development secondary to injury or due to very preterm birth.

Regular moderate exercise during pregnancy does not have an adverse effect on the neurodevelopment of the child.

AIM: Current U.S. guidelines suggest that pregnant women should exercise regularly during pregnancy, and we examined the neurodevelopment of the children whose mothers had taken that advice. METHODS: This Norwegian study included 188 children whose mothers had followed a structured exercise protocol and 148 control children whose mothers had not. Their cognitive, language and motor skills were assessed at 18 months of age by the Bayley Scales of Infant Development-III and daily life functioning with the Ages and Stages Questionnaire. RESULTS: No significant differences were found between the two groups. Subgroup analyses revealed that the children whose mothers had exercised had a slightly lower motor composite score (mean: 97.6, 95% CI: 96.0-99.2) than the control group (mean: 100.0, 95% CI: 98.6-101.5) (p = 0.03). Boys in the intervention group had lower fine motor scores (mean: 10.6, 95% CI: 10.3-11.0) than boys in the control group (mean: 11.5, 95% CI: 11.0-11.9) (p = 0.01). CONCLUSION: Our main finding was that regular moderate exercise during pregnancy does not adversely affect neurodevelopment in children. The lower motor scores in the subgroup analyses are probably clinically insignificant, but the lower fine motor scores for boys in the intervention group warrant further research.

Brain morphometry and cognition in young adults born small for gestational age at term.

OBJECTIVES: To examine brain volumes and cortical surface area and thickness and to relate these brain measures to cognitive function in young adults born small for gestational age (SGA) at term compared with non-SGA control patients. STUDY DESIGN: This population-based follow-up study at age 20 years included 58 term-born SGA (birth weight <10th percentile, mean: 2915 g) and 81 non-SGA controls (birth weight ≥ 10th percentile, mean: 3707 g). Brain volumes and cortical surface area and thickness were investigated with magnetic resonance imaging, which was successfully obtained in 47 SGA patients and 61 control patients. Cognitive function was assessed using the Wechsler Adult Intelligence Scale, 3rd edition. A subgroup analysis was performed in the SGA group among subjects diagnosed with fetal growth restriction (FGR) based on repeated fetal ultrasound measurements. RESULTS: The SGA group showed regional reductions in cortical surface area, particularly in the frontal, parietal, and temporal lobes. Total brain volume, cortical gray matter, cerebral white matter, and putamen volumes were reduced in the SGA group compared with control patients, but there were no differences in specific subcortical brain structure volumes when correcting for intracranial volume. Reductions were most pronounced among SGA subjects with FGR. No associations were found between brain measures and IQ measures in either group. CONCLUSION: Young adults born SGA at term show a global reduction in brain volume as well as regional reductions in cortical surface area. We speculate whether these reductions may be confined to those exposed to FGR. None of the brain measures correlated with cognition.

Executive functions in very-low-birth-weight young adults: a comparison between self-report and neuropsychological test results.

Executive functions are goal-directed control mechanisms that modulate the operation of other cognitive processes. Preterm born very-low-birth-weight (VLBW: birth weight<1500 grams) children have more problems with attention/executive function than their term born peers. The objective of this study is to examine if VLBW young adults had more self-reported attention/ executive problems and lower neuropsychological test results than controls. Furthermore, to investigate the relationship between self-reported attention/executive problems, general cognitive ability (IQ) and test results. Forty-two VLBW [mean birth weight 1237 (219) grams, and gestational age 29.3 (2.4) weeks] and 63 term born controls at age 19 years completed The BRIEF-A self-report of attention/executive functions in everyday life. The Wechsler Adult Intelligence Scale III was used to obtain IQ scores; subtests from Delis-Kaplan were used to assess attention/executive function. There were no differences between the VLBW young adults and controls on any of the BRIEF-A measures, but the VLBW subjects had lower scores on 8 of the 18 neuropsychological subtests (p<.01). Some correlations between BRIEF-A and the Stroop and TMT tests were found in the VLBW group. VLBW young adults do not report more problems regarding attention/executive function in daily life than controls despite lower results on several neuropsychological tests.

Neuropsychological deficits in young adults born small-for-gestational age (SGA) at term.

Reduced IQ, learning difficulties and poor school performance have been reported in small-for-gestational-age (SGA) subjects. However, few studies include a comprehensive neuropsychological assessment. Our aim was to study neuropsychological functioning in young adults born SGA at term. A comprehensive neuropsychological test battery was administered to 58 SGA subjects (birth weight <10th centile) born at term, and 81 term non-SGA controls (birth weight ≥10th centile). The SGA group obtained significantly (p < .01) lower scores on the attention, executive and memory domains compared to non-SGA controls and showed higher risk of obtaining scores below -1.5 SD on the memory domain (odds ratio = 13.3, 95% confidence interval: 1.57, 112.47). At a subtest level, the SGA group obtained lower scores on most neuropsychological tests, with significant differences on 6 of 46 measures: the Trail Making Test 3 (letter sequencing), the Wechsler Memory Scale mental control and the auditory immediate memory scale, the Design Fluency, the Stroop 3 (inhibition) and the Visual Motor Integration (VMI) motor coordination subtest. Young adults born SGA score more poorly on neuropsychological tests compared with non-SGA controls. Differences were modest, with more significant differences in the memory domain.

Small for gestational age and intrauterine growth restriction decreases cognitive function in young adults.

OBJECTIVE: To examine the effect on adult cognitive function of being born small for gestational age (SGA), and to evaluate whether cognitive function is related to intrauterine growth restriction (IUGR). STUDY DESIGN: Fifty-nine SGA subjects (birth weight <10th percentile) and 81 controls (birth weight ≥10th percentile) born at term underwent cognitive assessment with the Wechsler Adult Intelligence Scale-Third Edition at age 19-20 years. Repeated ultrasound measures of fetal growth were available for weeks 25, 33, and 37 in a subgroup of 29 SGA subjects and 75 control subjects, and these were data used to dichotomize the 29 SGA subjects into those with IUGR and those without IUGR. IUGR was defined as growth deviating more than -2 SD from the mean value of the control group. The effect of maternal smoking during pregnancy was considered as well. Group differences were analyzed using a general linear model, controlling for sex and socioeconomic status. RESULTS: The SGA group had lower full IQ scores than the control group (mean difference, -6.3; 95% CI, -2.8 to -9.7; P = .001), including lower scores on 6 of the Wechsler Adult Intelligence Scale-Third Edition subtests. In the SGA subgroup with repeated ultrasound measures, 6 of 29 subjects (21%) had IUGR, and these subjects also had a lower IQ compared with controls (mean difference, -14.0; 95% CI: -4.8 to -23.3; P = .003). Maternal smoking during pregnancy was related to lower IQ in the control group but not in the SGA group, independent of IUGR or non-IUGR status. CONCLUSION: IQ scores were lower in young adults born SGA compared with controls. Our analysis suggest that this outcome is related to IUGR.

Cognitive control deficits in adolescents born with very low birth weight (≤ 1500 g): evidence from dichotic listening.

The objective of the paper is to explore bottom-up auditory and top-down cognitive processing abilities as part of long-term outcome assessment of preterm birth. Fifty-five adolescents (age 13-15) born with very low birth weight (VLBW) were compared to 80 matched controls born to term, using three consonant-vowel dichotic listening (DL) instruction conditions (non-forced, forced-right and forced-left). DL scores were correlated with cortical gray matter thickness derived from T1-weighted structural MRI volumes using FreeSurfer to examine group differences also in the neural correlates of higher cognitive processes. While showing normal bottom-up processing, VLBW adolescents displayed impaired top-down controlled conflict processing related to significant cortical thickness differences in left superior temporal gryus and anterior cingulate cortex. Preterm birth with VLBW induces fundamental changes in brain function and structure posing a risk for long-term neurocognitive impairments. Deficits emerge in situations of increasing cognitive conflict and can be related to measures of executive functions as well as morphology.

Being born small for gestational age reduces white matter integrity in adulthood: a prospective cohort study.

BACKGROUND: Being born small for gestational age (SGA) (birth weight <10th percentile) is connected to decreased white matter (WM) integrity in newborns and increased prevalence of psychiatric symptoms in adulthood. The aims of this study were to investigate whether being born SGA at term affects WM integrity in young adulthood and to explore possible relationships between fractional anisotropy (FA) and pre- and perinatal factors and cognitive and psychiatric outcomes in adulthood in SGA and controls. METHODS: Diffusion tensor imaging and tract-based spatial statistics were conducted to test for voxelwise differences in FA in SGAs (n = 46) and controls (n = 57) at 18-22 y. RESULTS: As compared with controls SGAs had reduced FA in ventral association tracts and internal/external capsules. In the SGAs, no relationship was found between FA and intrauterine head growth in the third trimester, although total intelligence quotient was negatively correlated to FA. In controls, a positive correlation was found between FA and brain growth in the third trimester and maternal smoking. No relationship was found between FA and psychiatric measures in SGAs or controls. CONCLUSION: These results demonstrate that being born SGA leads to reduced WM integrity in adulthood, and suggest that different factors modulate the development of WM in SGA and control groups.

Mental health, quality of life and social relations in young adults born with low birth weight.

BACKGROUND: Being born with low birth weight may have an impact on different aspects of mental health, psychosocial functioning and well-being; however results from studies in young adulthood have so far yielded mixed findings. The aim of this study was to assess the long-term impact in young adulthood on self-reported mental health, health-related quality of life, self-esteem and social relations by investigating differences between two low birth weight groups and a control group. METHODS: In a follow-up at 20 years of age, 43 preterm VLBW (birth weight ≤ 1500 g), 55 term SGA (birth weight < 10th percentile) and 74 control subjects completed the Adult Self-Report (ASR) of the Achenbach System of Empirically Based Assessment, the Adult Autism Spectrum Quotient (AQ), the Short Form 36 Health Survey, the Self-Perception Profile for Adolescents-Revised, and the Wechsler Adult Intelligent Scale III assessment. RESULTS: The VLBW and SGA groups reported significantly more mental health problems than controls. The VLBW group predominantly had internalizing problems, and the non-significant association with ASR Total score was reduced by the Intelligence Quotient (IQ). The SGA group had increased scores on both internalizing and externalizing problems, and the association with ASR Total score remained significant after adjusting for IQ in this group. Both low birth weight groups reported less interaction with friends and lower quality of life related to mental health domains than controls. Self-esteem scores were lower than in the control group for athletic competence (VLBW) and social acceptance (SGA). CONCLUSION: Our findings suggest that self-reported mental health and well-being in young adulthood may be adversely affected by low birth weight, irrespective of whether this is the result of premature birth or being born SGA at term.

Young adults born preterm with very low birth weight demonstrate widespread white matter alterations on brain DTI.

Preterm birth with very low birth weight (VLBW, ≤1500 g) is connected to reduced white matter (WM) integrity in childhood and adolescence. These changes in WM are correlated to motor, sensory and neuropsychological impairments. CNS myelination continues into the early twenties, but the consequences of this for WM integrity in VLBWs have not been explored. DTI and tract based spatial statistics (TBSS) was carried out to test for voxelwise differences in fractional anisotropy (FA), eigenvalues and mean diffusivity (MD) between a preterm VLBW group (n=49) and a control group born at term (n=59) at 18-22 years of age. TBSS was also used to explore the relationship between perinatal clinical data and general cognitive ability (total IQ), respectively, and the DTI metrics (FA and MD), with gender and age as a confounder. In the VLBW group several major WM tracts particularly in the posterior region had significantly reduced FA caused by an increase in the two lowest eigenvalues. MD was significantly increased in the VLBWs in 50% of the same regions as the FA changes, but encompassing also more peripheral WM. In the VLBW group, FA was found to correlate positively with birth weight and negatively with number of days in intensive care and on mechanical ventilator, particularly in the corpus callosum. FA was found to correlate positively with total IQ in the young preterm adults. In the controls there was no correlation between FA and total IQ. Our results indicate that the neurologic sequelae of preterm birth with VLBW are a lifelong condition inducing structural and functional impairments also in adulthood in VLBW survivors. The greatest risk of having reduced WM integrity in adulthood was found in the most immature VLBW neonates requiring mechanical ventilation and long-term intensive care.

Computerized working memory training improves function in adolescents born at extremely low birth weight.

OBJECTIVE: To evaluate the effect of a computerized working memory training program on both trained and non-trained verbal aspects of working memory and executive and memory functions in extremely low birth weight (ELBW; <1000 g) infants. STUDY DESIGN: Sixteen ELBW infants and 19 term-born control subjects aged 14 to 15 years participated in the training program, and 11 adolescents were included as a non-intervention group. Extensive neuropsychological assessment was performed before and immediately after training and at a 6-month follow-up examination. Both training groups used the CogMed RM program at home 5 days a week for 5 weeks. RESULTS: Both groups improved significantly on trained and non-trained working memory tasks and on other memory tests indicating a generalizing effect. Working memory capacity was improved, and effects were maintained at the 6-month follow-up examination. There was no significant improvement in the non-intervention group at the 6-week follow-up examination. CONCLUSIONS: The computerized training program Cogmed RM was an effective intervention tool for improving memory and reducing core learning deficits in adolescents born at ELBW.

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 profile in young adults born preterm at very low birthweight.

AIM: the aim of this study was to assess cognitive function at the age of 19 years in individuals of very low birthweight (VLBW; ≤ 1500g) and in term-born comparison individuals. METHOD: in this hospital-based follow-up study, 55 VLBW participants (30 males, 25 females; mean birthweight 1217g, SD 233g; mean gestational age 29.1wks, SD 2.5wks) and 81 comparison individuals (42 males, 39 females; mean birthweight 3707g, SD 433g; mean gestational age 39.7wks, SD 1.2wks) were examined with a standardized IQ test (Wechsler Adult Intelligence Scale III) to assess general cognitive ability. RESULTS: over half (53%) of the VLBW participants achieved a low IQ score (defined as >1SD below the mean in the comparison group; odds ratio 6.4 vs comparison individuals; 95% confidence interval 2.8-14.4; p<0.001). None of the VLBW group, compared with 22% of the comparison individuals, achieved a high IQ score (>1SD above the comparison mean). VLBW participants scored lower than comparison individuals on full, verbal, and performance IQ, as well as on all four indices (p ≤0.001). The subtest profile indicated problems on all subtests, but especially on those related to arithmetic and visual-perceptual tasks. INTERPRETATIONS: few studies have undertaken a comprehensive assessment of general cognitive outcome (IQ) among young adults of VLBW. Our results indicate that VLBW seems to have a global and lasting impact on cognitive ability. Full-scale IQ assessment may reveal important learning problems in young adults of VLBW, and should be performed to inform appropriate assistance to enhance academic achievement and the chances of permanent employment as adults.