The relevance of posterior thalamo-cortical connectivity for visual short-term memory capacity

Visual short-term memory (vSTM) capacity represents the maximum number of visual items that can be perceived and stored into vSTM. One way to measure it is by using simple psycho-physical experiments together with the theory of visual attention (TVA) computational framework in which visual processing is conceived as a race between objects to be consciously perceived and stored into vSTM. The neural theory of visual attention (NTVA), which gives an interpretation of the TVA at both the cellular and systemic level, suggests that recurrent loops between posterior thalamus and visual cortices are relevant for vSTM capacity. Nevertheless, no clear evidence for the role of posterior thalamus and its connection to visual cortices in vSTM capacity has been found thus far. This thesis investigated the role of posterior thalamo-cortical connectivity in vSTM capacity in healthy young individuals as well as in two populations that have shown to exhibit both vSTM capacity impairments and posterior cortical and subcortical white matter damages: healthy aging and premature birth. We found that vSTM capacity in healthy young adults was significantly associated with the tracts connecting posterior thalamus to occipital cortices and their microstructure. However, this association was modified in elderly individuals and in young adults born prematurely, in which the recruitment of additional, cortico-cortical, tracts, takes place. Together, these findings bring the first structural evidence for the NTVA model with respect to the relevance of posterior thalamo-cortical tracts for vSTM capacity and show how alterations of these tracts affect vSTM capacity

The relevance of posterior thalamo-cortical connectivity for visual short-term memory capacity

Visual short-term memory (vSTM) capacity represents the maximum number of visual items that can be perceived and stored into vSTM. One way to measure it is by using simple psycho-physical experiments together with the theory of visual attention (TVA) computational framework in which visual processing is conceived as a race between objects to be consciously perceived and stored into vSTM. The neural theory of visual attention (NTVA), which gives an interpretation of the TVA at both the cellular and systemic level, suggests that recurrent loops between posterior thalamus and visual cortices are relevant for vSTM capacity. Nevertheless, no clear evidence for the role of posterior thalamus and its connection to visual cortices in vSTM capacity has been found thus far. This thesis investigated the role of posterior thalamo-cortical connectivity in vSTM capacity in healthy young individuals as well as in two populations that have shown to exhibit both vSTM capacity impairments and posterior cortical and subcortical white matter damages: healthy aging and premature birth. We found that vSTM capacity in healthy young adults was significantly associated with the tracts connecting posterior thalamus to occipital cortices and their microstructure. However, this association was modified in elderly individuals and in young adults born prematurely, in which the recruitment of additional, cortico-cortical, tracts, takes place. Together, these findings bring the first structural evidence for the NTVA model with respect to the relevance of posterior thalamo-cortical tracts for vSTM capacity and show how alterations of these tracts affect vSTM capacity

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

Complex Grey Matter Structure Segmentation in Brains via Deep Learning: Example of the Claustrum

Segmentationand parcellation of the brain has been widely performed on brain MRI using atlas-based methods. However, segmentation of the claustrum, a thin and sheet-like structure between insular cortex and putamen has not been amenable to automatized segmentation, thus limiting its investigation in larger imaging cohorts. Recently, deep-learning based approaches have been introduced for automated segmentation of brain structures, yielding great potential to overcome preexisting limitations. In the following, we present a multi-view deep-learning based approach to segment the claustrum in T1-weighted MRI scans. We trained and evaluated the proposed method on 181 manual bilateral claustrum annotations by an expert neuroradiologist serving as reference standard. Cross-validation experiments yielded median volumetric similarity, robust Hausdor? distance and Dice score of 93.3%, 1.41mm and 71.8% respectively which represents equal or superior segmentation performance compared to human intra-rater reliability. Leave-one-scanner-out evaluation showed good transfer-ability of the algorithm to images from unseen scanners, however at slightly inferior performance. Furthermore, we found that AI-based claustrum segmentation benefits from multi-view information and requires sample sizes of around 75 MRI scans in the training set. In conclusion, the developed algorithm has large potential in independent study cohorts and to facilitate MRI-based research of the human claustrum through automated segmentation. The software and models of our method are made publicly available.Comment: submitted to a journa

Linking the impact of aging on visual short-term memory capacity with changes in the structural connectivity of posterior thalamus to occipital cortices

Aging impacts both visual short-term memory (vSTM) capacity and thalamo-cortical connectivity. According to the Neural Theory of Visual Attention, vSTM depends on the structural connectivity between posterior thalamus and visual occipital cortices (PT-OC). We tested whether aging modifies the association between vSTM capacity and PT-OC structural connectivity. To do so, 66 individuals aged 20–77 years were assessed by diffusion-weighted imaging used for probabilistic tractography and performed a psychophysical whole-report task of briefly presented letter arrays, from which vSTM capacity estimates were derived. We found reduced vSTM capacity, and aberrant PT-OC connection probability in aging. Critically, age modified the relationship between vSTM capacity and PT-OC connection probability: in younger adults, vSTM capacity was negatively correlated with PT-OC connection probability while in older adults, this association was positive. Furthermore, age modified the microstructure of PT-OC tracts suggesting that the inversion of the association between PT-OC connection probability and vSTM capacity with aging might reflect age-related changes in white-matter properties. Accordingly, our results demonstrate that age-related differences in vSTM capacity links with the microstructure and connectivity of PT-OC tracts

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

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

Reduced apparent fiber density in the white matter of premature-born adults

Premature-born adults exhibit lasting white matter alterations as demonstrated by widespread reduction in fractional anisotropy (FA) based on diffusion-weighted imaging (DWI). FA reduction, however, is non-specific for microscopic underpinnings such as aberrant myelination or fiber density (FD). Using recent advances in DWI, we tested the hypothesis of reduced FD in premature-born adults and investigated its link with the degree of prematurity and cognition. 73 premature- and 89 mature-born adults aged 25–27 years underwent single-shell DWI, from which a FD measure was derived using convex optimization modeling for microstructure informed tractography (COMMIT). Premature-born adults exhibited lower FD in numerous tracts including the corpus callosum and corona radiata compared to mature-born adults. These FD alterations were associated with both the degree of prematurity, as assessed via gestational age and birth weight, as well as with reduced cognition as measured by full-scale IQ. Finally, lower FD overlapped with lower FA, suggesting lower FD underlie unspecific FA reductions. Results provide evidence that premature birth leads to lower FD in adulthood which links with lower full-scale IQ. Data suggest that lower FD partly underpins FA reductions of premature birth but that other processes such as hypomyelination might also take place

Hippocampal subfield volumes are nonspecifically reduced in premature‐born adults

Reduced global hippocampus volumes have been demonstrated in premature‐born individuals, from newborns to adults; however, it is unknown whether hippocampus subfield (HCSF) volumes are differentially affected by premature birth and how relevant they are for cognitive performance. To address these questions, we investigated magnetic resonance imaging (MRI)‐derived HCSF volumes in very premature‐born adults, and related them with general cognitive performance in adulthood. We assessed 103 very premature‐born (gestational age [GA] <32 weeks and/or birth weight <1,500 g) and 109 term‐born individuals with cognitive testing and structural MRI at 26 years of age. HCSFs were automatically segmented based on three‐dimensional T1‐ and T2‐weighted sequences and studied both individually and grouped into three functional units, namely hippocampus proper (HP), subicular complex (SC), and dentate gyrus (DG). Cognitive performance was measured using the Wechsler‐Adult‐Intelligence‐Scale (full‐scale intelligence quotient [FS‐IQ]) at 26 years. We observed bilateral volume reductions for almost all HCSF volumes in premature‐born adults and associations with GA and neonatal treatment intensity but not birth weight. Left‐sided HP, SC, and DG volumes were associated with adult FS‐IQ. Furthermore, left DG volume was a mediator of the association between GA and adult FS‐IQ in premature‐born individuals. Results demonstrate nonspecifically reduced HCSF volumes in premature‐born adults; but specific associations with cognitive outcome highlight the importance of the left DG. Data suggest that specific interventions toward hippocampus function might be promising to lower adverse cognitive effects of prematurity