M Cuddy

Cognitive maturation in preterm and term born adolescents

Background: Adolescence is a critical period of brain structural reorganisation and maturation of cognitive abilities. This relatively late developmental reorganisation may be altered in individuals who were born preterm. Methods: We carried out longitudinal neuropsychological testing in 94 very preterm individuals (VPT; before 33 weeks’ gestation) and 44 term born individuals at mean ages of 15.3 years (adolescence) and 19.5 years (young adulthood). Results: Full scale, verbal and performance IQ and phonological verbal fluency were significantly lower in the VPT group than the term group at both ages. Repeated measures ANOVA showed only one group by time point interaction for semantic verbal fluency (F = 10.25; df = 107; p = 0.002). Paired-sample t tests showed that semantic verbal fluency increased significantly in the term group over adolescence (t = −5.10; df = 42; p<0.001), but did not increase in the VPT group (t = 0.141; df = 69; p = 0.889). For verbal IQ, there was a significant interaction between time point and sex (F = 4.48; df = 1; p = 0.036) with paired-sample t tests showing that verbal IQ decreased in males between adolescence and adulthood (t = 3.35; df = 71; p = 0.001), but did not change significantly in females (t = 0.20; df = 52; p = 0.845). Conclusion: Decrements of intellectual functioning in VPT individuals persist into adulthood. Additionally, there is a deficit in the adolescent maturation of semantic verbal fluency in individuals born VPT.

Neurological abnormalities in young adults born preterm

Objective: Individuals born before 33 weeks’ gestation (very preterm, VPT) have an increased likelihood of neurological abnormality, impaired cognitive function, and reduced academic performance in childhood. It is currently not known whether neurological signs detected in VPT children persist into adulthood or become attenuated by maturation of the CNS. Method: We assessed 153 VPT individuals and 71 term-born controls at 17–18 years old, using a comprehensive neurological examination. This examination divides neurological signs into primary and integrative domains, the former representing the localising signs of classical neurology, and the latter representing signs requiring integration between different neural networks or systems. Integrative signs are sub-divided into three groups: sensory integration, motor confusion, and sequencing. The VPT individuals have been followed up since birth, and neonatal information is available on them, along with the results of neurological assessment at 4 and 8 years of age and neuropsychological assessment at 18 years of age. Results: The total neurology score and primary and integrative scores were significantly increased in VPT young adults compared to term-born controls. Within the integrative domain, sensory integration and motor confusion scores were significantly increased in the VPT group, but sequencing was not significantly different between the VPT and term groups. Integrative neurological abnormalities at 18 were strongly associated with reduced IQ but primary abnormalities were not. Conclusions: Neurological signs are increased in VPT adults compared to term-born controls, and are strongly associated with reduced neuropsychological function.

Diffusion tensor MRI of the corpus callosum and cognitive function in adults born preterm

Very preterm birth (before 33 weeks gestation) is associated with the white matter damage, and a common sequel is reduced size and altered shape of the corpus callosum. We used diffusion tensor MRI to assess the corpus callosum in 63 very preterm and 45 term-born young adults. Indices of white matter microstructure [fractional anisotropy (FA) and mean diffusivity (MD)] were obtained for the genu, body and splenium. Very preterm females had higher MD in the genu than term-born females, indicating altered white matter microstructure. This was associated with lower performance IQ. The groups demonstrated different patterns of correlations between verbal learning and tract-specific FA and MD, consistent with the reorganization of white matter structure in adults born very preterm.

Preterm birth and structural brain alterations in early adulthood

Alterations in cortical development and impaired neurodevelopmental outcomes have been described following very preterm (VPT) birth in childhood and adolescence, but only a few studies to date have investigated grey matter (GM) and white matter (WM) maturation in VPT samples in early adult life. Using voxel-based morphometry (VBM) we studied regional GM and WM volumes in 68 VPT-born individuals (mean gestational age 30 weeks) and 43 term-born controls aged 19–20 years, and their association with cognitive outcomes (Hayling Sentence Completion Test, Controlled Oral Word Association Test, Visual Reproduction test of the Wechsler Memory Scale-Revised) and gestational age. Structural MRI data were obtained with a 1.5 Tesla system and analysed using the VBM8 toolbox in SPM8 with a customized study-specific template. Similarly to results obtained at adolescent assessment, VPT young adults compared to controls demonstrated reduced GM volume in temporal, frontal, insular and occipital areas, thalamus, caudate nucleus and putamen. Increases in GM volume were noted in medial/anterior frontal gyrus. Smaller subcortical WM volume in the VPT group was observed in temporal, parietal and frontal regions, and in a cluster centred on posterior corpus callosum/thalamus/fornix. Larger subcortical WM volume was found predominantly in posterior brain regions, in areas beneath the parahippocampal and occipital gyri and in cerebellum. Gestational age was associated with GM and WM volumes in areas where VPT individuals demonstrated GM and WM volumetric alterations, especially in temporal, parietal and occipital regions. VPT participants scored lower than controls on measures of IQ, executive function and non-verbal memory. When investigating GM and WM alterations and cognitive outcome scores, subcortical WM volume in an area beneath the left inferior frontal gyrus accounted for 14% of the variance of full-scale IQ (F = 12.9, p < 0.0001). WM volume in posterior corpus callosum/thalamus/fornix and GM volume in temporal gyri bilaterally, accounted for 21% of the variance of executive function (F = 9.9, p < 0.0001) and WM in the posterior corpus callosum/thalamus/fornix alone accounted for 17% of the variance of total non-verbal memory scores (F = 9.9, p < 0.0001). These results reveal that VPT birth continues to be associated with altered structural brain anatomy in early adult life, although it remains to be ascertained whether these changes reflect neurodevelopmental delays or long lasting structural alterations due to prematurity. GM and WM alterations correlate with length of gestation and mediate cognitive outcome.

Psychiatric diagnoses and behaviour problems from childhood to early adolescence in young people with severe intellectual disabilities

BACKGROUND While general population studies indicate an increase in the rate of psychiatric disorder in adolescence, little is known about the course of mental health and behaviour problems between childhood and adolescence in young people with severe intellectual disabilities. METHOD From a sample of 111 children with severe intellectual disability who had been identified from the registers of six special schools at 4-11 years of age, 82 were traced and reassessed 5 years later at the age of 11-17 years. Behaviour problems were assessed by means of parental interviews conducted in the family home and parent and teacher questionnaires. Parental reports of psychiatric diagnoses were checked against health records. RESULTS With most behaviour problems, including aggression, destructive behaviour and self-injury, there was little difference in rates between the two assessment occasions. However, in spite of this overall pattern of stability, the rates of some behaviour problems, including overactivity, showed significant reductions between childhood and early adolescence. Persistence rates for most behaviour problems appeared comparable to those reported for similar behaviours in general population studies of children. There was no significant difference in the proportion of cases with psychiatric diagnoses between the two assessment occasions, although brief psychotic episodes emerged in three cases in adolescence. CONCLUSIONS The findings suggest that the prevalence of mental health and behavioural problems in young people with severe learning disabilities remains relatively stable between childhood and adolescence, although some specific behaviour problems diminish. However, a small minority of children may develop severe psychiatric disorders in adolescence.

Factors associated with the risk of behaviour problems in adolescents with severe intellectual disabilities

BACKGROUND Little is known about the factors affecting the risk of behavioural and emotional problems in young people with severe intellectual disability (ID), although such evidence as there is suggests that there may be differences between the pattern of risk factors in this group and those that operate in general population samples of the same age. METHOD From a sample of 111 children with severe ID who had been initially identified from the registers of six special schools at 4-11 years, 82 were traced and reassessed on average 5 years 4 months later. The relationships between potential risk factors and behaviour problems, reported here for 11:00-17:04 year olds, were assessed by means of parental interview conducted in the family home. RESULTS Behaviour problems were associated with the severity of ID and the severity of autistic symptomatology. Perhaps surprisingly, they were also more common in pre-pubertal than post-pubertal adolescents. Family factors such as a history of interrupted/disrupted maternal care, parental criticism of the child and aggressive parental disciplinary practices were also associated with behaviour problems, although the direction of causation was unclear. Several factors, including gender, social disadvantage and epilepsy, well established as risk factors in children without ID, were not significantly associated with behaviour problems in the present sample. CONCLUSION The findings suggest that the pattern of factors associated with behaviour problems in children with severe ID differs from that found both in the general population and in children with mild ID.

Processing and memory for emotional and neutral material in amyotrophic lateral sclerosis

Several studies have reported changes in emotional memory and processing in people with ALS (pwALS). In this study, we sought to analyse differences in emotional processing and memory between pwALS and healthy controls and to investigate the relationship between emotional memory and self-reported depression. Nineteen pwALS and 19 healthy controls were assessed on measures of emotional processing, emotional memory, verbal memory and depression. Although pwALS and controls did not differ significantly on measures of emotional memory, a subgroup of patients performed poorly on an emotional recognition task. With regard to emotional processing, pwALS gave significantly stronger ratings of emotional valence to positive words than to negative words. Higher ratings of emotional words were associated with better recall in controls but not pwALS. Self-reported depression and emotional processing or memory variables were not associated in either group. In conclusion, the results from this small study suggest that a subgroup of pwALS may show weakened ‘emotional enhancement’, although in the current sample this may reflect general memory impairment rather than specific changes in emotional memory. Nonetheless, different patterns of processing of emotionally-salient material by pwALS may have care and management-related implications.

White matter alterations to cingulum and fornix following very preterm birth and their relationship with cognitive functions

Abstract Very preterm birth (VPT; <32 weeks of gestation) has been associated with impairments in memory abilities and functional neuroanatomical brain alterations in medial temporal and fronto‐parietal areas. Here we investigated the relationship between structural connectivity in memory‐related tracts and various aspects of memory in VPT adults (mean age 19) who sustained differing degrees of perinatal brain injury (PBI), as assessed by neonatal cerebral ultrasound. We showed that the neurodevelopmental consequences of VPT birth persist into young adulthood and are associated with neonatal cranial ultrasound classification. At a cognitive level, VPT young adults showed impairments specific to effective organization of verbal information and visuospatial memory, whereas at an anatomical level they displayed reduced volume of memory‐related tracts, the cingulum and the fornix, with greater alterations in those individuals who experienced high‐grade PBI. When investigating the association between these tracts and memory scores, perseveration errors were associated with the volume of the fornix and dorsal cingulum (connecting medial frontal and parietal lobes). Visuospatial memory scores were associated with the volume of the ventral cingulum (connecting medial parietal and temporal lobes). These results suggest that structural connectivity alterations could underlie memory difficulties in preterm born individuals. HighlightsVery preterm born adults exhibit memory and learning impairments.White matter tracts implicated in memory are altered following perinatal brain injury.Structural alterations to memory tracts may underlie specific memory impairments.