Learning difficulties

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More than 10% of all babies are born preterm every year, and prematurity is a well-established risk factor for cognitive impairment at some level.

Prematurity affects working memory in particular

In a recent German study involving 1326 8-year-old children, it was found that being born preterm specifically affected the ability to solve tasks with a high cognitive load (i.e. greater demands on working memory), whereas tasks with a low load were largely unaffected.

These findings are consistent with other research suggesting that prematurity is associated in particular with difficulties in math, in complex problem-solving, and in simultaneous processing (such as occurs in recognition of spatial patterns).

There was also a clear dividing line, with deficits disproportionally higher for children born before the 34th week of pregnancy compared with children born after week 33.

Rate of cognitive impairment in premature infants

A Swedish study of 491 toddlers (2 ½ years) who had been born extremely preterm (less than 27 gestational weeks) found that 42% of them had no disability (compared with 78% of controls), 31% had mild disability, 16% had moderate disability, and 11% had severe disability. Unsurprisingly, there was an increase in moderate or severe disabilities with greater prematurity. There was no gender difference.

Cognitive impairment in premies linked to smaller brain tissue in specific regions

Why are some individuals affected by prematurity, why others aren’t? An analysis of brain imaging data of 97 adolescents who had very low birth weights, and whose academic progress has been followed, found that more than half of the babies that weighed less than 1.66 pounds and more than 30% of those less than 3.31 pounds at birth later had academic deficits. Academic deficits were linked to smaller brain volumes, and in particular to reduced volume of the caudate and corpus callosum, which are involved in connectivity, executive attention and motor control.

J. Jäkel, N. Baumann, D. Wolke (2013): Effects of gestational age at birth on cognitive performance: a function of cognitive workload demands, PLOS ONE, http://dx.plos.org/10.1371/journal.pone.0065219

[3444] Serenius F KK. Neurodevelopmental outcome in extremely preterm infants at 2.5 years after active perinatal care in sweden. JAMA [Internet]. 2013 ;309(17):1810 - 1820. Available from: http://dx.doi.org/10.1001/jama.2013.3786

[3442] Clark, C A, Fang H, Espy KA, Filipek PA, Juranek J, Bangert B, Hack M, Gerry H. Relation of neural structure to persistently low academic achievement: A longitudinal study of children with differing birth weights. Neuropsychology. 2013 ;27(3):364 - 377.

http://www.eurekalert.org/pub_releases/2013-05/rb-pba052713.php (1st study)

http://www.eurekalert.org/pub_releases/2013-04/tjnj-sen042513.php (2nd study)

http://www.eurekalert.org/pub_releases/2013-06/uoo-rbv061013.php (3rd study)

It’s always difficult in human studies to disentangle the effects of lifestyle factors. Alcohol is a case in point, and in particular the vexed question of whether any alcohol is safe during pregnancy. A new study, however, has avoided the complication of co-occurring lifestyle and environment factors by looking directly at genetic variants.

This study, believed to be the first substantial one of its kind, used genetic variation to investigate the effects of moderate (<6 units of alcohol per week) drinking during pregnancy among a large group of women and their children. Since the individual variations that people have in their DNA are not connected to lifestyle and social factors, the approach removes that potential complication.

The study, involving 4,167 children, found that four genetic variants in alcohol-metabolizing genes were strongly related to lower IQ at age eight. But this effect was only seen among the children of women who were moderate drinkers (heavy drinkers were not included in the study), pointing to the effect requiring exposure to alcohol in the womb.

Ten SNPs from four genes previously implicated in alcohol metabolism, intake, or dependency, were analyzed. Four SNPs (particular variants) were related to children’s scores on the cognitive test (WISC), of which three are rare and one quite common. There was an additive effect, with carriers of multiple ‘bad’ alleles being more affected.

There was some evidence that only drinking one or two drinks a week was not harmful to the fetus, but because the numbers of women were relatively small, and individual variability was high, this can’t be assessed with any great certainty.

The critical factor appears to be metabolism of alcohol, with mothers who are ‘fast' metabolizers being safer for their fetus than mothers who metabolize alcohol more slowly.

Mothers' alcohol intake was based on questionnaires completed when they were 18 weeks and 32 weeks pregnant. ‘Moderate’ was defined as between one and six drinks a week. All participants were of white-European origin.

An Australian study of 3796 14-year-olds has found that those who had been reported as having suffered abuse or neglect (7.9%) scored the equivalent of some three IQ points lower than those who had not been maltreated, after accounting for a large range of socioeconomic and other factors. Abuse and neglect were independent factors: those who suffered both (and 74% of those who suffered neglect also suffered abuse) were doubly affected.

Last year I reported on a study involving 210 subjects aged 7 to 31 that found that in contrast to the adult brain, most of the tightest connections in a child's brain are between brain regions that are physically close to each other. As the child grows to adulthood, the brain switches from an organization based on local networks based on physical proximity to long-distance networks based on functionality. Now the same researchers, using five-minute scans from 238 people aged 7 to 30, have looked at nearly 13,000 functional (rather than structural) connections and identified 200 key ones. On the basis of these 200 connections, the brains could be identified as belonging to a child (7-11) or an adult (25-30) with 92% accuracy, and adolescents or adults with 75% accuracy. Moreover, the most important factor in predicting development (accounting for about 68%) was the trimming of the vast number of childhood connections.

Apart from emphasizing the importance of pruning connections in brain development, the main value of this research is in establishing an effective analytic method and baseline measurements for normal development. It is hoped that this will eventually help researchers work out indicators for various developmental disorders.

Neurofibromatosis type 1 (NF1) is the most common cause of learning disabilities, caused by a mutation in a gene that makes a protein called neurofibromin. Mouse research has now revealed that these mutations are associated with higher levels of the inhibitory neurotransmitter GABA in the medial prefrontal cortex. Brain imaging in humans with NF1 similarly showed reduced activity in the prefrontal cortex when performing a working memory task, with the levels of activity correlating with task performance. It seems, therefore, that this type of learning disability is a result of too much GABA in the prefrontal cortex inhibiting the activity of working memory. Potentially they could be corrected with a drug that normalizes the excess GABA's effect. The researchers are currently studying the effect of the drug lovastatin on NF1 patients.

A new automated vocal analysis technology can discriminate pre-verbal vocalizations of very young children with autism with 86% accuracy. The LENA™ (Language Environment Analysis) system also differentiated typically developing children and children with autism from children with language delay. The processor fits into the pocket of specially designed children's clothing and records everything the child vocalizes. LENA could not only enable better early diagnosis of autism spectrum disorders, but also allow parents to continue and supplement language enrichment therapy at home and assess their own effectiveness for themselves.

Older news items (pre-2010) brought over from the old website

New screening tool helps identify children at risk

An exam, called the NICU (neonatal intensive care unit) Network Neurobehavioral Scale (NNNS), has been created to identify newborns who may have problems with school readiness and behavior at age four. This opens up the possibility of early intervention to prevent these problems. The screening exam has been tested on 1248 babies, mostly black and on public assistance. Five discrete behavioral profiles were reliably identified; the most extreme negative profile was found in 5.8% of the infants. Infants with poor performance were more likely to have behavior problems at age three, school readiness problems at age four, and low IQ at 4 ½ — 40% had clinically significant problems externalizing (impulsivity and acting out), internalizing (anxiety, depression, withdrawn personalities), and with school readiness (delays in motor, concepts and language skills), and 35% had low IQ.

[596] Liu J, Bann C, Lester B, Tronick E, Das A, Lagasse L, Bauer C, Shankaran S, Bada H. Neonatal neurobehavior predicts medical and behavioral outcome. Pediatrics [Internet]. 2010 ;125(1):e90-98 - e90-98. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19969621


Cognitive dysfunction reversed in mouse model of Down syndrome

Down syndrome is characterized by specific learning impairments (for example, difficulties in using spatial and contextual information to form new memories, but less difficulty at remembering information linked to sensory cues) that point to the hippocampus as a problem area. Investigation has revealed that the problem lies in degeneration of the locus coeruleus, which sends norepinephrine to neurons in the hippocampus. Now a study using genetically engineered mice has found that norepinephrine precursor drugs improved performance in the mice within a few hours. However, the effect did wear off quite quickly too. Other research has looked at acetylcholine, which also acts at the hippocampus. The present findings suggest the best medication regimen will be one that improves both norepinephrine and acetylcholine signals. Locus coeruleus degeneration is also seen in dementia; Alzheimer’s develops among those with Down syndrome at a significantly higher rate than in the general population.

Salehi, A. et al. 2009. Restoration of Norepinephrine-Modulated Contextual Memory in a Mouse Model of Down Syndrome. Science Translational Medicine, 1 (7), 7-17.

http://www.eurekalert.org/pub_releases/2009-11/uoc--cdr111609.php http://www.the-scientist.com/blog/display/56154/

Testing one time is not enough

A study demonstrating the perils of one-time testing gave 16 common cognitive and neuropsychological tests to groups of people ages 18-39, 50-59 and 60-97 years. The variation between scores on the same test given three times during a two-week period was as big as the variation between the scores of people in different age groups. “It's as if on the same test, someone acted like a 20-year-old on a Monday, a 45-year-old on Friday, and a 32-year-old the following Wednesday”. The study makes clear the dangers of diagnosing learning disability, progressive brain disease or impairment from head injury on the basis of testing on a single occasion. The researcher suggests we should view cognitive abilities as a distribution of many potential levels of performance instead of as one stable short-term level; that people have a range of typical performances, a one-person bell curve. It may also be that within-person variability could be a useful diagnostic marker in itself — for example, extreme fluctuations might be an early warning of mental decline.

[921] Salthouse TA. Implications of within-person variability in cognitive and neuropsychological functioning for the interpretation of change. Neuropsychology [Internet]. 2007 ;21(4):401 - 411. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17605573


Common cholesterol-lowering drug reverses learning disabilities in mice

Following their discovery that neurofibromatosis 1 (NF1) — the leading genetic cause of learning disabilities — is linked to dysfunction in a protein called Ras, researchers have successfully used a commonly prescribed cholesterol-lowering statin drug (lovastatin) to reverse the learning deficits in mice. Clinical trials with humans are being planned.

[1348] Li W, Cui Y, Kushner S, Brown R, Jentsch J, Frankland P, Cannon T, Silva A. The HMG-CoA Reductase Inhibitor Lovastatin Reverses the Learning and Attention Deficits in a Mouse Model of Neurofibromatosis Type 1. Current Biology [Internet]. 2005 ;15(21):1961 - 1967. Available from: http://www.cell.com/current-biology/abstract/S0960-9822(05)01113-9


More light on a common developmental disorder

Chromosome 22q11.2 deletion syndrome is the most common genetic deletion syndrome, and causes symptoms such as heart defects, cleft palate, abnormal immune responses and cognitive impairments. Two related studies have recently cast more light on these cognitive impairments. Previously it was known that numerical abilities were impaired more than verbal skills. The new study found children with the chromosome deletion performed more poorly on experiments designed to test visual attention orienting, enumerating, and judging numerical magnitudes. All three tasks relate to how the children mentally represent objects and the spatial relationships among them, supporting previous arguments that such visual-spatial skills are a fundamental foundation to the later learning of counting and mathematics. The second study found that such children had changes in the shape, size and position of the corpus callosum, the main bridge between the two hemispheres.

[1139] Simon TJ, Bearden CE, Mc-Ginn DMD, Zackai E. Visuospatial and Numerical Cognitive Deficits in Children with Chromosome 22Q11.2 Deletion Syndrome. Cortex [Internet]. 2005 ;41(2):145 - 155. Available from: http://www.sciencedirect.com/science/article/B8JH1-4S0JBRK-7/2/ad6567fc8ae7be0ddb6387920387fc1a

[812] Simon TJ, Ding L, Bish JP, McDonald-McGinn DM, Zackai EH, Gee J. Volumetric, connective, and morphologic changes in the brains of children with chromosome 22q11.2 deletion syndrome: an integrative study. NeuroImage [Internet]. 2005 ;25(1):169 - 180. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15734353