Neonatal ultrasound results following very preterm birth predict adolescent behavioral and cognitive outcome.

This study investigated the association between different neonatal ultrasonographic classifications and adolescent cognitive, educational, and behavioral outcomes following very preterm birth. Participants included a group of 120 adolescents who were born very preterm (<33 weeks of gestation), subdivided into three groups according to their neonatal cerebral ultrasound (US) classifications: (a) normal (N = 69), (b) periventricular hemorrhage (PVH, N = 37), and (c) PVH with ventricular dilatation (PVH + DIL, N = 14), and 50 controls. The cognitive functions assessed were full-scale IQ, phonological and semantic verbal fluency, and visual-motor integration. Educational outcomes included reading and spelling; behavioral outcomes were assessed with the Rutter Parents' Scale and the Premorbid Adjustment Scale (PAS). Adolescent outcome scores were compared among the four groups. A main effect for group was observed for full-scale IQ, Rutter Parents' Scale total scores, and PAS total scores, after controlling for gestational age, socioeconomic status and gender, with the PVH + DIL group showing the most impaired scores compared to the other groups. The current results demonstrate that routine neonatal ultrasound classifications are associated with later cognitive and behavioral outcome. Neonatal ultrasounds could aid in the identification of subgroups of children who are at increased risk of neurodevelopmental problems. These at risk subgroups could then be referred to appropriate early intervention services.

Ketamine-induced disruption of verbal self-monitoring linked to superior temporal activation.

INTRODUCTION: Misattribution of distorted self-generated speech in patients with schizophrenia has been associated with increased lateral temporal activation. As a pharmacological model of schizophrenia, we tested whether ketamine would induce the same effects in healthy individuals. METHODS: Participants were 8 healthy male volunteers who were naïve to ketamine (mean age: 28 years). Ketamine (0.23 mg/kg bolus followed by 0.64 mg/kg/h) and placebo infusions were administered in a double-blind, randomised order, during 2 functional magnetic resonance imaging (fMRI) sessions. Each fMRI session consisted of a verbal self-monitoring task in which auditory feedback was experimentally modified. RESULTS: Ketamine was associated with psychotic and dissociative symptoms. Participants made more misattributions of distorted self-generated speech (P < 0.02) during the ketamine infusion. Ketamine led to reduced activation in the left superior temporal cortex during self-distorted speech, regardless of whether the speech was identified correctly or not, as compared to the placebo infusion. Misidentification of speech that had been distorted was not associated with any increase in brain activation in during the placebo infusion, however ketamine-induced misattributions were associated with a relative increase in left superior temporal cortex activation. DISCUSSION: These data are consistent with the notion that self-monitoring impairments underlie psychotic symptoms and suggest that N-methyl-D-aspartate (NMDA) receptor dysfunction may mediate self-monitoring deficits and psychotic phenomena in schizophrenia.

The corpus callosum and empathy in adults with a history of preterm birth.

Reduced posterior corpus callosum (CC) area has been consistently observed in children and adolescents born very preterm (VPT). CC structural differences are also observed in people diagnosed with empathy disorders. This study examined empathy in relation to CC size in VPT adults and controls. CC area was manually measured for 17 VPT adults and 9 controls. Participants completed the Interpersonal Reactivity Index (Davis, 1980) and the Empathy Quotient (Baron-Cohen & Wheelwright, 2004). VPT adults had reduced posterior CC area in contrast to controls, and a positive linear trend was observed between posterior CC size and gestational age. No between-group empathy differences were observed, although self-reported personal distress in response to social situations was higher in VPT adults, and negatively associated with anterior CC area. We conclude that VPT adults have a smaller posterior CC, which is associated with gestational age, and elevated social distress, which may be mediated by anterior CC size.

A functional MRI study of verbal fluency in adults with bipolar disorder and their unaffected relatives.

BACKGROUND: Individuals with a history of bipolar disorder demonstrate abnormalities of executive function, even during euthymia. The neural architecture underlying this and its relationship with genetic susceptibility for illness remain unclear. METHOD: We assessed 18 remitted individuals with bipolar disorder, 19 of their unaffected first degree relatives and 19 healthy controls using functional magnetic resonance imaging (fMRI) and a paced verbal fluency task with two levels of difficulty. RESULTS: Bipolar patients made significantly more errors in the easy level of the verbal fluency task than their relatives or controls. Analysis of variance of fMRI data demonstrated a significant main effect of group in a large cluster including retrosplenial cortex and adjacent precuneate cortex (x=7, y=-56, x=15). All three groups showed deactivation in these areas during task performance relative to a neutral or rest condition. Group differences comprised a lesser amount of deactivation in unaffected relatives compared with controls in the easy condition [F(2, 55)=3.42, p=0.04] and in unaffected relatives compared with bipolar patients in the hard condition [F(2, 55)=4.34, p=0.018]. Comparison with the control group indicated that both bipolar patients and their relatives showed similar deficits of deactivation in retrosplenial cortex and reduced activation of left prefrontal cortex. CONCLUSIONS: Bipolar disorder may be associated with an inherited abnormality of a neural network incorporating left prefrontal cortex and bilateral retrosplenial cortex.

Preterm babies grown up: understanding a hidden public health problem.

Even when they have grown up, the survivors of preterm birth are at increased risk of psychiatric illness. As the incidence of preterm birth is increasing, there is now a growing population of adults whose mental health needs have been neglected.

The effect of COMT, BDNF, 5-HTT, NRG1 and DTNBP1 genes on hippocampal and lateral ventricular volume in psychosis.

BACKGROUND: Morphometric endophenotypes which have been proposed for psychotic disorders include lateral ventricular enlargement and hippocampal volume reductions. Genetic epidemiological studies support an overlap between schizophrenia and bipolar disorder, and COMT, BDNF, 5-HTT, NRG1 and DTNBP1 genes have been implicated in the aetiology of both these disorders. This study examined associations between these candidate genes and morphometric endophenotypes for psychosis. METHOD: A total of 383 subjects (128 patients with psychosis, 194 of their unaffected relatives and 61 healthy controls) from the Maudsley Family Psychosis Study underwent structural magnetic resonance imaging and genotyping. The effect of candidate genes on brain morphometry was examined using linear regression models adjusting for clinical group, age, sex and correlations between members of the same family. RESULTS: The results showed no evidence of association between variation in COMT genotype and lateral ventricular, and left or right hippocampal volumes. Neither was there any effect of the BDNF, 5-HTTLPR, NRG1 and DTNBP1 genotypes on these regional brain volumes. CONCLUSIONS: Abnormal hippocampal and lateral ventricular volumes are among the most replicated endophenotypes for psychosis; however, the influences of COMT, BDNF, 5-HTT, NRG1 and DTNBP1 genes on these key brain regions must be very subtle if at all present.

Psychiatric disorder in young adults born very preterm: role of family history.

OBJECTIVE: To investigate whether young adults born very preterm (VPT) (<33 weeks) are at increased risk for psychiatric illness in adulthood and whether a family history of psychiatric disorder further increases this risk. METHODS: We assessed 169 VPT and 101 term born individuals using the Clinical Interview Schedule - Revised. RESULTS: Young adults born VPT had an increased risk for psychiatric disorder compared to controls (OR=3.1, 95% CI=1.1-8.6, p=0.03). Those born VPT who had a history of psychiatric disorder in a first-degree relative, had an increase in risk for psychiatric disorder compared to those born VPT without a family history (OR=5.2, 95% CI=1.8-14.9, p=0.002). CONCLUSION: Individuals born VPT are at increased risk of psychiatric illness in young adulthood compared to controls. In addition, a family history of psychiatric disorder in a first-degree relative may leave young adults born VPT particularly vulnerable to psychiatric illness.

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.

Cognitive and motor function and the size of the cerebellum in adolescents born very pre-term.

Individuals born before 33 weeks' gestation are at risk of brain lesions, which have the potential to disrupt subsequent neurodevelopment. As a result they manifest an increased incidence of neuromotor signs and cognitive deficits, which can still be detected in adolescence. The cerebellum is known to be involved in both the co-ordination of movement and in cognitive processes. We therefore set out to establish whether cognitive and motor impairments in adolescents born very pre-term are associated with abnormalities of the cerebellum as revealed by volumetric analysis of brain MRI scans. The volume of the whole cerebellum was determined manually using a PC-based Cavalieri procedure in 67 adolescents born very pre-term and 50 age-matched, full-term born controls. Cognitive and neurological assessments were performed at 1, 4, 8 and 14-15 years of age as part of the long-term follow-up of the pre-term subjects. The pre-term-born subjects had significantly reduced cerebellar volume compared with term-born controls (P<0.001). This difference was still present after controlling for potential confounders. There was no association between cerebellar volume and motor neurological signs. However, there were significant associations between cerebellar volume and several cognitive test scores, in particular the Wechsler Intelligence Scale for Children-Revised, the Kaufman Assessment Battery for Children and the Schonnel reading age. This provides further evidence implicating the cerebellum in cognition and suggests that cerebellar abnormalities may underlie some of the cognitive deficits found in individuals born very pre-term.

Functional MR imaging during odor stimulation: preliminary data.

PURPOSE: To determine the locations and extent of activation in areas of the brain at functional magnetic resonance (MR) imaging with olfactory stimulation and to determine whether accommodation or amplification of brain activation occurs with sequential olfactory stimulation. MATERIALS AND METHODS: Five adult men with normal senses of smell underwent multisection, gradient-echo, echo-planar imaging according to a blood-oxygen-level-dependent experimental paradigm. Odorants that nearly exclusively stimulate the olfactory system and odorants that stimulate the olfactory and trigeminal nerves were compared by using repetitive imaging procedures. RESULTS: Activation with olfactory nerve-mediated odorants was demonstrated in the orbitofrontal cortex (Brodmann area 11) with a right-sided predominance. Mild cerebellar stimulation was also observed. With repeated testing, overall activation with olfactory nerve-mediated odorants declined. Odorants that also stimulated the trigeminal nerve produced additional cingulate, temporal, cerebellar, and occipital activation. Activation with combined trigeminal and olfactory system odors increased more than sixfold with repeated testing. CONCLUSION: Olfactory nerve-mediated and combined olfactory and trigeminal nerve-mediated odorants activate different regions of the brain. Orbitofrontal stimulation spreads to all parts of the brain when a trigeminal component is added. Habituation (deactivation) occurs with repeated testing of olfactory nerve-mediated odorants, while, paradoxically, activation increases with repeated exposure to odors that also stimulate the trigeminal nerve.

Dynamic multi-planar EPI of the urinary bladder during voiding with simultaneous detrusor pressure measurement.

Magnetic resonance imaging gives high quality images of the urinary bladder with excellent contrast. We report here the first application of dynamic, multi-slice, echo planar imaging to a study of urinary bladder emptying. Changes in urinary bladder volumes and rates of urine expulsion from the bladder have been measured simultaneously with bladder pressure. The method shows promise for clinical applications involving compromised bladder function, for reappraising bladder contraction strength-volume relationships, and for investigating the rate of change of length, three-dimensional shape, and wall tension in different parts of the bladder during micturition.

Activation of area V5 by visual perception of motion demonstrated with echoplanar MR imaging.

Cortical activation in visual association areas known to be responsible for the perception of motion was investigated in two volunteers who viewed a projected animated cartoon periodically "run" and "frozen" during collection of echoplanar MR images. Ten axial, contiguous, 5 mm thick, T2-weighted, gradient-echo images (TE 40 ms, TR 3000 ms) depicting BOLD contrast were acquired through the occipital lobe using a GE Signa 1.5 T system with an advanced NMR operating console. Images were analysed by time series regression modelling estimating power in the MR signal at the ON-OFF frequency of motion. Highly significant activation in response to motion perception was identified in both subjects bilaterally in area V5.