An analysis of MRI derived cortical complexity in premature-born adults : regional patterns, risk factors, and potential significance

Premature birth bears an increased risk for aberrant brain development concerning its structure and function. Cortical complexity (CC) expresses the fractal dimension of the brain surface and changes during neurodevelopment. We hypothesized that CC is altered after premature birth and associated with long-term cognitive development. One-hundred-and-one very premature-born adults (gestational age <32 weeks and/or birth weight <1500 ​g) and 111 term-born adults were assessed by structural MRI and cognitive testing at 26 years of age. CC was measured based on MRI by vertex-wise estimation of fractal dimension. Cognitive performance was measured based on Griffiths-Mental-Development-Scale (at 20 months) and Wechsler-Adult-Intelligence-Scales (at 26 years). In premature-born adults, CC was decreased bilaterally in large lateral temporal and medial parietal clusters. Decreased CC was associated with lower gestational age and birth weight. Furthermore, decreased CC in the medial parietal cortices was linked with reduced full-scale IQ of premature-born adults and mediated the association between cognitive development at 20 months and IQ in adulthood. Results demonstrate that CC is reduced in very premature-born adults in temporoparietal cortices, mediating the impact of prematurity on impaired cognitive development. These data indicate functionally relevant long-term alterations in the brain’s basic geometry of cortical organization in prematurity

Sequelae of premature birth in young adults

Background and Purpose Qualitative studies about the abnormalities appreciated on routine magnetic resonance imaging (MRI) sequences in prematurely born adults are lacking. This article aimed at filling this knowledge gap by (1) qualitatively describing routine imaging findings in prematurely born adults, (2) evaluating measures for routine image interpretation and (3) investigating the impact of perinatal variables related to premature birth. Methods In this study two board-certified radiologists assessed T1-weighted and FLAIR-weighted images of 100 prematurely born adults born very preterm (VP <32 weeks) and/or at very low birth weight (VLBW <1500 g) and 106 controls born at full term (FT) (mean age 26.8 ± 0.7 years). The number of white matter lesions (WML) was counted according to localization. Lateral ventricle volume (LVV) was evaluated subjectively and by measurements of Evans’ index (EI) and frontal-occipital-horn ratio (FOHR). Freesurfer-based volumetry served as reference standard. Miscellaneous incidental findings were noted as free text. Results The LVV was increased in 24.7% of VP/VLBW individuals and significantly larger than in FT controls. This was best identified by measurement of FOHR (AUC = 0.928). Ventricular enlargement was predicted by low gestational age (odds ratio: 0.71, 95% CI 0.51–0.98) and presence of neonatal intracranial hemorrhage (odds ratio: 0.26, 95% CI 0.07–0.92). The numbers of deep and periventricular WML were increased while subcortical WMLs were not. Conclusion Enlargement of the LVV and deep and periventricular WMLs are typical sequelae of premature birth that can be appreciated on routine brain MRI. To increase sensitivity of abnormal LVV detection, measurement of FOHR seems feasible in clinical practice

Decreased BOLD fluctuations in lateral temporal cortices of premature born adults

Lasting volume reductions in subcortical and temporal-insular cortices after premature birth suggest altered ongoing activity in these areas. We hypothesized altered fluctuations in ongoing neural excitability and activity, as measured by slowly fluctuating blood oxygenation of restingstate functional MRI (rs-fMRI), in premature born adults, with altered fluctuations being linked with underlying brain volume reductions. To investigate this hypothesis, 94 very preterm/very low birth weight (VP/VLBW) and 92 full-term born young adults underwent structural and rsfMRI data acquisition with voxel-based morphometry and amplitude of low-frequency fluctuations (ALFF) as main outcome measure. In VP/VLBW adults, ALFF was reduced in lateral temporal cortices, and this reduction was positively associated with lower birth weight. Regions of reduced ALFF overlapped with reduced brain volume. On the one hand, ALFF reduction remained after controlling for volume loss, supporting the functional nature of ALFF reductions. On the other hand, ALFF decreases were positively associated with underlying brain volume loss, indicating a relation between structural and functional changes. Furthermore, within the VP/VLBW group, reduced ALFF was associated with reduced IQ, indicating the behavioral relevance of ALFF decreases in temporal cortices. These results demonstrate long-term impact of premature birth on ongoing BOLD fluctuations in lateral temporal cortices, which are linked with brain volume reductions. Data suggest permanently reduced fluctuations in ongoing neural excitability and activity in structurally altered lateral temporal cortices after premature birth

The association of children’s mathematic abilities with both adults’ cognitive abilities and intrinsic fronto-parietal networks is altered in preterm-born individuals

Mathematic abilities in childhood are highly predictive for long-term neurocognitive outcomes. Preterm-born individuals have an increased risk for both persistent cognitive impairments and long-term changes in macroscopic brain organization. We hypothesized that the association of childhood mathematic abilities with both adulthood general cognitive abilities and associated fronto-parietal intrinsic networks is altered after preterm delivery. 72 preterm- and 71 term-born individuals underwent standardized mathematic and IQ testing at 8 years and resting-state fMRI and full-scale IQ testing at 26 years of age. Outcome measure for intrinsic networks was intrinsic functional connectivity (iFC). Controlling for IQ at age eight, mathematic abilities in childhood were significantly stronger positively associated with adults’ IQ in preterm compared with term-born individuals. In preterm-born individuals, the association of children’s mathematic abilities and adults’ fronto-parietal iFC was altered. Likewise, fronto-parietal iFC was distinctively linked with preterm- and term-born adults’ IQ. Results provide evidence that preterm birth alters the link of mathematic abilities in childhood and general cognitive abilities and fronto-parietal intrinsic networks in adulthood. Data suggest a distinct functional role of intrinsic fronto-parietal networks for preterm individuals with respect to mathematic abilities and that these networks together with associated children’s mathematic abilities may represent potential neurocognitive targets for early intervention

Impaired structural connectivity between dorsal attention network and pulvinar mediates the impact of premature birth on adult visual–spatial abilities

The dorsal attention network (DAN), including frontal eye fields and posterior parietal cortices, and its link with the posterior thalamus, contribute to visual–spatial abilities. Very premature birth impairs both visual–spatial abilities and cortico‐thalamic structural connectivity. We hypothesized that impaired structural DAN‐pulvinar connectivity mediates the effect of very premature birth on adult visual–spatial abilities. Seventy very premature (median age 26.6 years) and 57 mature born adults (median age 26.6 years) were assessed with cognitive tests and diffusion tensor imaging. Perceptual organization (PO) index of the Wechsler Adult Intelligence Scale‐III was used as a proxy for visual–spatial abilities, and connection probability maps in the thalamus, derived from probabilistic tractography from the DAN, were used as a proxy for DAN‐thalamic connectivity. Premature born adults showed decreases in both PO‐index and connection probability from DAN into the pulvinar, with both changes being positively correlated. Moreover, path analysis revealed that DAN‐pulvinar connectivity mediates the relationship between very premature birth and PO‐index. Results provide evidence for long‐term effects of very premature birth on structural DAN‐pulvinar connectivity, mediating the effect of prematurity on adult visual–spatial impairments. Data suggest DAN‐pulvinar connectivity as a specific target of prognostic and diagnostic procedures for visual–spatial abilities after premature birth

Reduced cholinergic basal forebrain integrity links neonatal complications and adult cognitive deficits after premature birth

Background Premature-born individuals have an increased risk for long-term neurocognitive impairments. In animal models, the development of the cholinergic basal forebrain (cBF) is selectively vulnerable to adverse effects of perinatal stressors, and impaired cBF integrity results in lasting cognitive deficits. We hypothesized that in premature-born individuals cBF integrity is impaired and mediates adult cognitive impairments associated with prematurity. Methods We used MRI-based volumetric assessments of a cytoarchitectonically defined cBF region-of-interest to determine differences in cBF integrity between 99 adults who were born very preterm and/or with very low birth weight (VP/VLBW) and 106 term born controls from the same birth cohort. MRI-derived cBF volumes were studied in relation to neonatal clinical complications after delivery as well as intelligence measures (IQ) in adulthood. Results In VP/VLBW adults, cBF volumes were significantly reduced compared to term-born adults (-4.5%, F(1, 202) = 11.82, p = 0.001). Lower cBF volume in VP/VLBW adults was specifically associated with both neonatal complications (rpart(92) = -0.35, p < 0.001) and adult IQ (rpart(88) = 0.33, p = 0.001) even after controlling for global gray matter and white matter volume. In an additional path analytic model, cBF volume significantly mediated the association between neonatal complications and adult cognitive deficits. Conclusions Results provide first time evidence in humans that cBF integrity is impaired after premature birth and links neonatal complications with long-term cognitive outcome. Data suggest that cholinergic system abnormalities may play a relevant role for long-term neurocognitive impairments associated with premature delivery

Neural correlates of executive attention in adults born very preterm

Very preterm birth is associated with an increased prevalence of attention problems and may especially impair executive attention, i.e., top-down control of attentional selection in situations where distracting information interferes with the processing of task-relevant stimuli. While there are initial findings linking structural brain alterations in preterm-born individuals with attention problems, the functional basis of these problems are not well understood. The present study used an fMRI adaptation of the Attentional Network Test to examine the neural correlates of executive attention in a large sample of N = 86 adults born very preterm and/or with very low birth weight (VP/VLBW), and N = 100 term-born controls. Executive attention was measured by comparing task behavior and brain activations associated with the processing of incongruent vs. congruent arrow flanker stimuli. Consistent with subtle impairments of executive attention, the VP/VLBW group showed lower accuracy and a tendency for increased response times during the processing of incongruent stimuli. Both groups showed similar activation patters, especially within expected fronto-cingulo-parietal areas, but no significant between-group differences. Our results argue for a maintained attention-relevant network organization in high-functioning preterm born adults in spite of subtle deficits in executive attention. Gestational age and neonatal treatment variables showed associations with task behavior, and brain activation in the dorsal ACC and lateral occipital areas, suggesting that the degree of prematurity (and related neonatal complications) has subtle modulatory influences on executive attention processing

White matter alterations of the corticospinal tract in adults born very preterm and/or with very low birth weight

White matter (WM) injury, either visible on conventional magnetic resonance images (MRI) or measurable by diffusion tensor imaging (DTI), is frequent in preterm born individuals and often affects the corticospinal tract (CST). The relation between visible and invisible white mater alterations in the reconstructed CST of preterm subjects has so far been studied in infants, children and up to adolescence. Therefore, we probabilistically tracked the CST in 53 term-born and 56 very preterm and/or low birth weight (VP/VLBW, < 32 weeks of gestation and/or birth weight < 1,500 g) adults (mean age 26 years) and compared their DTI parameters (axial, radial, mean diffusivity—AD, RD, MD, fractional anisotropy—FA) in the whole CST and slice-wise along the CST. Additionally, we used the automatic, tract-based-spatial-statistics (TBSS) as an alternative to tractography. We compared control and VP/VLBW and subgroups with and without CST WM lesions visible on conventional MRI. Compared to controls, VP/VLBW subjects had significantly higher diffusivity (AD, RD, MD) in the whole CST, slice-wise along the CST, and in multiple regions along the TBSS skeleton. VP/VLBW subjects also had significantly lower (TBSS) and higher (tractography) FA in regions along the CST, but no different mean FA in the tracked CST as a whole. Diffusion changes were weaker, but remained significant for both, tractography and TBSS, when excluding subjects with visible CST lesions. Chronic CST injury persists in VP/VLBW adults even in the absence of visible WM lesions, indicating long-term structural WM changes induced by premature birth

Aberrant gyrification contributes to the link between gestational age and adult IQ after premature birth

Gyrification is a hallmark of human brain development, starting in the second half of gestation in primary cortices, followed by unimodal and then transmodal associative cortices. Alterations in gyrification have been noted in premature-born newborns and children, suggesting abnormal cortical folding to be a permanent feature of prematurity. Furthermore, both gyrification and prematurity are tightly linked with cognitive performance, indicating a link between prematurity, gyrification, and cognitive performance. To investigate this triangular relation, we tested the following two hypotheses: (i) gyrification is aberrant in premature-born adults; and (ii) aberrant gyrification contributes to the impact of prematurity on adult cognitive performance. One hundred and one very premature-born adults (i.e. adults born before 32 weeks of gestation, and/or with birth weight <1500 g) and 111 mature-born adults were assessed by structural MRI and cognitive testing at 27 years of age. Gyrification was measured by local cortical absolute mean curvature (AMC), evaluated through structural MRI. Cognitive performance was assessed by the Wechsler Adult Intelligence Scale, full-scale IQ test. Two-sample t-tests, regression and mediation analyses were used to assess AMC group differences and the relation between AMC, birth-related variables, and full-scale IQ. Three key findings were identified. First, local AMC was widely increased in fronto-temporo-parietal primary and associative cortices of very premature-born adults. Increase of AMC was inversely associated with gestational age and birth weight and positively associated with medical complications at birth, respectively. Second, increased AMC of temporal associative cortices specifically contributed to the association between prematurity and reduced adult IQ (two-path mediation), indicating that aberrant gyrification of temporal associative cortices is critical for impaired cognitive performance after premature birth. Finally, further investigation of the relationship of gyrification between the early folding postcentral cortices and associative temporal cortices, folding later during neurodevelopment, revealed that the effect of gyrification abnormalities in associative temporal cortices on adult IQ is influenced itself by gyrification abnormalities occurring in the early folding postcentral cortices (three-path mediation). These results indicate that gyrification development across cortical areas in the brain conveys prematurity effects on adult IQ. Overall, these results provide evidence that premature birth leads to permanently aberrant gyrification patterns suggesting an altered neurodevelopmental trajectory. Statistical mediation modelling suggests that both aberrant gyrification itself as well as its propagation across the cortex express aspects of impaired neurodevelopment after premature birth and lead to reduced cognitive performance in adulthood. Thus, markers of gyrification appear as potential candidates for prognosis and treatment of prematurity effects

Ecstasykonsumenten: Neurokognitive und funktionelle Problemkonstellationen und Ansätze zu spezifischen Frühinterventionen

Hintergrund: In den letzten Jahren ist zunehmend deutlich geworden, dass Konsumenten von Ecstasy sich hinsichtlich Gebrauchsmuster und -kontext wie auch Spontanverlauf, Risiken und Konsequenzen von Konsumenten anderer legaler und illegaler Substanzen unterscheiden und möglicherweise eine recht eigenständige Gruppe darstellen. Diese eigenständige Gruppe wird im angelsächsischen Raum zum Teil auch als club drug user bezeichnet. Alarmierend waren die Vermutungen aus Voruntersuchungen, dass club drug-Konsumenten auch nach dem Konsum geringer Mengen von Ecstasy bemerkenswerte und möglicherweise überdauernde neurobiologische Veränderungen mit assoziierten kognitiven Beeinträchtigungen und Störungen aufzeigen. Dies stellt an sich eine mögliche Gefährdung der Konsumenten dar, zusätzlich wiederum können kognitive Veränderungen auch Einfluss nehmen auf den Verlauf des weiteren Suchtmittelkonsums und den Erfolg von Interventionen. Ziel: In der MAYA-Studie (Munich Assessment of Young Adults) werden an einer epidemiologischen Bevölkerungsstichprobe junger Erwachsener (Stichprobe A) sowie an einer klinischen Stichprobe von Ecstasy-Konsumenten (Stichprobe B) die Art und das Ausmaß kognitiver Störungen und Defizite in Abhängigkeit von Gebrauchsmustern und anderen Einflussfaktoren untersucht. Bei der Stichprobe A handelt es sich um ein Subsample der EDSPStudie. Zusätzlich zu den bereits erhobenen Charakterisierungen werden spezifische neurokognitive Maße (vor allem Aufmerksamkeit, Gedächtnis und exekutive Funktionen) und Fragebögen (Impulsivität, BDI, STAI etc.) erhoben. Die Probanden erhalten weiterhin ein Screening mit dem neu eingeführten Instrument WHO ASSIST (Alcohol, Smoking and Substance Involvement Screening Test). Wenn indiziert, wird eine Intervention im Sinne eines Motivational Enhancement durchgeführt. Initiale Auswirkungen werden in einem Telefoninterview sechs Wochen später überprüft. Ergebnisse: Die vorläufigen Ergebnisse beruhen auf einer Teilstichprobe. Insgesamt handelte es sich eher um Konsumenten mit geringgradigem bis moderaten Konsum. Dennoch ließen sich Unterschiede zwischen den Konsumentengruppen (Ecstasy, Cannabis, Alkohol) und den Nichtkonsumenten erkennen. Die Konsumenten von Ecstasy unterschieden sich am ausgeprägtesten von den Kontrollen. Die sich bisher abzeichnenden Unterschiede bei Aufmerksamkeit, Gedächtnis und exekutiven Funktionen scheinen bei der Gedächtnis- und Merkfähigkeit am ausgeprägtesten zu sein. Bei diesen vorläufigen Ergebnissen sind die Untersuchungsgruppen noch sehr heterogen und enthalten z.B. Probanden, die ihren Ecstasykonsum bereits wieder aufgegeben haben.Introduction: In recent years it has become increasingly evident that ecstasy users represent a group distinct from users of other drugs. This is based on consumption patterns, context of use, development of use patterns and other factors. This group of users might be considered "club drug users", given the overlap, similarity of use patterns and consumptions within the class of club drugs. In recent neurobiological research, alarming results have been reported, indicating that persistent neurotoxic effects with concomitant cognitive problems may be induced by ecstasy consumption. Methods: In the Munich Assessment of Young Adults Study (MAYA) two samples of ecstasy users are investigated. Sample A is a sample of users drawn from an ongoing epidemiological longitudinal study of young adults in Munich. Sample B is an additional clinical sample. Both samples are characterized extensively and are neuropsychologically tested for attention, memory and executive functioning. A screening for harmful use is conducted with the German version of the WHO ASSIST (Alcohol, Smoking and Substance Involvement Screening Test). A Motivational Enhancement Intervention is applied when harmful use is detected. With a telephone interview the intervention's initial effect is assessed. Results: Initial results are based on a small sample. Use within the tested population is low to moderate. Still significant differences in attention, memory, and executive functioning could be detected with the current testing. Ecstasy users almost consistently showed the lowest cognitive functioning. The one difference is that ecstasy users were significantly faster in finger tapping and reaction. Note that the results are preliminary. The sample is heterogeneous, including both current and former users. Firmer results will be reported with the full sample size, allowing to further elucidate subgroups and interactions