Consistently lower volumes across thalamus nuclei in very premature-born adults.

Lasting thalamus volume reduction after preterm birth is a prominent finding. However, whether thalamic nuclei volumes are affected differentially by preterm birth and whether nuclei aberrations are relevant for cognitive functioning remains unknown. Using T1-weighted MR-images of 83 adults born very preterm (≤ 32 weeks' gestation; VP) and/or with very low body weight (≤ 1,500 g; VLBW) as well as of 92 full-term born (≥ 37 weeks' gestation) controls, we compared thalamic nuclei volumes of six subregions (anterior, lateral, ventral, intralaminar, medial, and pulvinar) across groups at the age of 26 years. To characterize the functional relevance of volume aberrations, cognitive performance was assessed by full-scale intelligence quotient using the Wechsler Adult Intelligence Scale and linked to volume reductions using multiple linear regression analyses. Thalamic volumes were significantly lower across all examined nuclei in VP/VLBW adults compared to controls, suggesting an overall rather than focal impairment. Lower nuclei volumes were linked to higher intensity of neonatal treatment, indicating vulnerability to stress exposure after birth. Furthermore, we found that single results for lateral, medial, and pulvinar nuclei volumes were associated with full-scale intelligence quotient in preterm adults, albeit not surviving correction for multiple hypotheses testing. These findings provide evidence that lower thalamic volume in preterm adults is observable across all subregions rather than focused on single nuclei. Data suggest the same mechanisms of aberrant thalamus development across all nuclei after premature birth.

Human Claustrum Connections: Robust In Vivo Detection by DWI-Based Tractography in Two Large Samples.

Despite substantial neuroscience research in the last decade revealing the claustrum's prominent role in mammalian forebrain organization, as evidenced by its extraordinarily widespread connectivity pattern, claustrum studies in humans are rare. This is particularly true for studies focusing on claustrum connections. Two primary reasons may account for this situation: First, the intricate anatomy of the human claustrum located between the external and extreme capsule hinders straightforward and reliable structural delineation. In addition, the few studies that used diffusion-weighted-imaging (DWI)-based tractography could not clarify whether in vivo tractography consistently and reliably identifies claustrum connections in humans across different subjects, cohorts, imaging methods, and connectivity metrics. To address these issues, we combined a recently developed deep-learning-based claustrum segmentation tool with DWI-based tractography in two large adult cohorts: 81 healthy young adults from the human connectome project and 81 further healthy young participants from the Bavarian longitudinal study. Tracts between the claustrum and 13 cortical and 9 subcortical regions were reconstructed in each subject using probabilistic tractography. Probabilistic group average maps and different connectivity metrics were generated to assess the claustrum's connectivity profile as well as consistency and replicability of tractography. We found, across individuals, cohorts, DWI-protocols, and measures, consistent and replicable cortical and subcortical ipsi- and contralateral claustrum connections. This result demonstrates robust in vivo tractography of claustrum connections in humans, providing a base for further examinations of claustrum connectivity in health and disease.

Inverted U-shape-like functional connectivity alterations in cognitive resting-state networks depending on exercise intensity: An fMRI study.

Acute physical activity influences cognitive performance. However, the relationship between exercise intensity, neural network activity, and cognitive performance remains poorly understood. This study examined the effects of different exercise intensities on resting-state functional connectivity (rsFC) and cognitive performance. Twenty male athletes (27.3 ± 3.6 years) underwent cycling exercises of different intensities (high, low, rest/control) on different days in randomized order. Before and after, subjects performed resting-state functional magnetic resonance imaging and a behavioral Attention Network Test (ANT). Independent component analysis and Linear mixed effects models examined rsFC changes within ten resting-state networks. No significant changes were identified in ANT performance. Resting-state analyses revealed a significant interaction in the Left Frontoparietal Network, driven by a non-significant rsFC increase after low-intensity and a significant rsFC decrease after high-intensity exercise, suggestive of an inverted U-shape relationship between exercise intensity and rsFC. Similar but trend-level rsFC interactions were observed in the Dorsal Attention Network (DAN) and the Cerebellar Basal Ganglia Network. Explorative correlation analysis revealed a significant positive association between rsFC increases in the right superior parietal lobule (part of DAN) and better ANT orienting in the low-intensity condition. Results indicate exercise intensity-dependent subacute rsFC changes in cognition-related networks, but their cognitive-behavioral relevance needs further investigation.

Amyloid and SCD jointly predict cognitive decline across Chinese and German cohorts.

INTRODUCTION: Subjective cognitive decline (SCD) in amyloid-positive (Aß+) individuals was proposed as a clinical indicator of Stage 2 in the Alzheimer's disease (AD) continuum, but this requires further validation across cultures, measures, and recruitment strategies. METHODS: Eight hundred twenty-one participants from SILCODE and DELCODE cohorts, including normal controls (NC) and individuals with SCD recruited from the community or from memory clinics, underwent neuropsychological assessments over up to 6 years. Amyloid positivity was derived from positron emission tomography or plasma biomarkers. Global cognitive change was analyzed using linear mixed-effects models. RESULTS: In the combined and stratified cohorts, Aß+ participants with SCD showed steeper cognitive decline or diminished practice effects compared with NC or Aß- participants with SCD. These findings were confirmed using different operationalizations of SCD and amyloid positivity, and across different SCD recruitment settings. DISCUSSION: Aß+ individuals with SCD in German and Chinese populations showed greater global cognitive decline and could be targeted for interventional trials. HIGHLIGHTS: SCD in amyloid-positive (Aß+) participants predicts a steeper cognitive decline. This finding does not rely on specific SCD or amyloid operationalization. This finding is not specific to SCD patients recruited from memory clinics. This finding is valid in both German and Chinese populations. Aß+ older adults with SCD could be a target population for interventional trials.

Indirect evidence for altered dopaminergic neurotransmission in very premature-born adults.

While animal models indicate altered brain dopaminergic neurotransmission after premature birth, corresponding evidence in humans is scarce due to missing molecular imaging studies. To overcome this limitation, we studied dopaminergic neurotransmission changes in human prematurity indirectly by evaluating the spatial co-localization of regional alterations in blood oxygenation fluctuations with the distribution of adult dopaminergic neurotransmission. The study cohort comprised 99 very premature-born (<32 weeks of gestation and/or birth weight below 1500 g) and 107 full-term born young adults, being assessed by resting-state functional MRI (rs-fMRI) and IQ testing. Normative molecular imaging dopamine neurotransmission maps were derived from independent healthy control groups. We computed the co-localization of local (rs-fMRI) activity alterations in premature-born adults with respect to term-born individuals to different measures of dopaminergic neurotransmission. We performed selectivity analyses regarding other neuromodulatory systems and MRI measures. In addition, we tested if the strength of the co-localization is related to perinatal measures and IQ. We found selectively altered co-localization of rs-fMRI activity in the premature-born cohort with dopamine-2/3-receptor availability in premature-born adults. Alterations were specific for the dopaminergic system but not for the used MRI measure. The strength of the co-localization was negatively correlated with IQ. In line with animal studies, our findings support the notion of altered dopaminergic neurotransmission in prematurity which is associated with cognitive performance.

Subjective cognitive decline and stage 2 of Alzheimer disease in patients from memory centers.

INTRODUCTION: It is uncertain whether subjective cognitive decline (SCD) in individuals who seek medical help serves the identification of the initial symptomatic stage 2 of the Alzheimer's disease (AD) continuum. METHODS: Cross-sectional and longitudinal data from the multicenter, memory clinic-based DELCODE study. RESULTS: The SCD group showed slightly worse cognition as well as more subtle functional and behavioral symptoms than the control group (CO). SCD-A+ cases (39.3% of all SCD) showed greater hippocampal atrophy, lower cognitive and functional performance, and more behavioral symptoms than CO-A+. Amyloid concentration in the CSF had a greater effect on longitudinal cognitive decline in SCD than in the CO group. DISCUSSION: Our data suggests that SCD serves the identification of stage 2 of the AD continuum and that stage 2, operationalized as SCD-A+, is associated with subtle, but extended impact of AD pathology in terms of neurodegeneration, symptoms and clinical progression.

Coherent Structural and Functional Network Changes after Thalamic Lesions in Essential Tremor.

BACKGROUND: Magnetic resonance-guided focused ultrasound of the ventral intermediate nucleus is a novel incisionless ablative treatment for essential tremor (ET). OBJECTIVE: The aim was to study the structural and functional network changes induced by unilateral sonication of the ventral intermediate nucleus in ET. METHODS: Fifteen essential tremor patients (66.2 ± 15.4 years) underwent probabilistic tractography and functional magnetic resonance imaging (MRI) during unilateral postural tremor-eliciting tasks using 3-T MRI before, 1 month (N = 15), and 6 months (N = 10) post unilateral sonication. RESULTS: Tractography identified tract-specific alterations within the dentato-thalamo-cortical tract (DTCT) affected by the unilateral lesion after sonication. Relative to the treated hand, task-evoked activation was significantly reduced in contralateral primary sensorimotor cortex and ipsilateral cerebellar lobules IV/V and VI, and vermis. Dynamic causal modeling revealed a significant decrease in excitatory drive from the cerebellum to the contralateral sensorimotor cortex. CONCLUSIONS: Thalamic lesions induced by sonication induce specific functional network changes within the DTCT, notably reducing excitatory input to ipsilateral sensorimotor cortex in ET. ©[2022] International Parkinson and Movement Disorder Society. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The BDNFVal66Met SNP modulates the association between beta-amyloid and hippocampal disconnection in Alzheimer's disease.

In Alzheimer's disease (AD), a single-nucleotide polymorphism in the gene encoding brain-derived neurotrophic factor (BDNFVal66Met) is associated with worse impact of primary AD pathology (beta-amyloid, Aß) on neurodegeneration and cognitive decline, rendering BDNFVal66Met an important modulating factor of cognitive impairment in AD. However, the effect of BDNFVal66Met on functional networks that may underlie cognitive impairment in AD is poorly understood. Using a cross-validation approach, we first explored in subjects with autosomal dominant AD (ADAD) from the Dominantly Inherited Alzheimer Network (DIAN) the effect of BDNFVal66Met on resting-state fMRI assessed functional networks. In seed-based connectivity analysis of six major large-scale networks, we found a stronger decrease of hippocampus (seed) to medial-frontal connectivity in the BDNFVal66Met carriers compared to BDNFVal homozogytes. BDNFVal66Met was not associated with connectivity in any other networks. Next, we tested whether the finding of more pronounced decrease in hippocampal-medial-frontal connectivity in BDNFVal66Met could be also found in elderly subjects with sporadically occurring Aß, including a group with subjective cognitive decline (N = 149, FACEHBI study) and a group ranging from preclinical to AD dementia (N = 114, DELCODE study). In both of these independently recruited groups, BDNFVal66Met was associated with a stronger effect of more abnormal Aß-levels (assessed by biofluid-assay or amyloid-PET) on hippocampal-medial-frontal connectivity decreases, controlled for hippocampus volume and other confounds. Lower hippocampal-medial-frontal connectivity was associated with lower global cognitive performance in the DIAN and DELCODE studies. Together these results suggest that BDNFVal66Met is selectively associated with a higher vulnerability of hippocampus-frontal connectivity to primary AD pathology, resulting in greater AD-related cognitive impairment.

Aberrant Claustrum Microstructure in Humans after Premature Birth.

Several observations suggest an impact of prematurity on the claustrum. First, the claustrum's development appears to depend on transient subplate neurons of intra-uterine brain development, which are affected by prematurity. Second, the claustrum is the most densely connected region of the mammalian forebrain relative to its volume; due to its effect on pre-oligodendrocytes, prematurity impacts white matter connections and thereby the development of sources and targets of such connections, potentially including the claustrum. Third, due to its high connection degree, the claustrum contributes to general cognitive functioning (e.g., selective attention and task switching/maintaining); general cognitive functioning, however, is at risk in prematurity. Thus, we hypothesized altered claustrum structure after premature birth, with these alterations being associated with impaired general cognitive performance in premature born persons. Using T1-weighted and diffusion-weighted magnetic resonance imaging in 70 very preterm/very low-birth-weight (VP/VLBW) born adults and 87 term-born adults, we found specifically increased mean diffusivity in the claustrum of VP/VLBW adults, associated both with low birth weight and at-trend with reduced IQ. This result demonstrates altered claustrum microstructure after premature birth. Data suggest aberrant claustrum development, which is potentially related with aberrant subplate neuron and forebrain connection development of prematurity.

Characteristics of subjective cognitive decline associated with amyloid positivity.

INTRODUCTION: The evidence for characteristics of persons with subjective cognitive decline (SCD) associated with amyloid positivity is limited. METHODS: In 1640 persons with SCD from 20 Amyloid Biomarker Study cohort, we investigated the associations of SCD-specific characteristics (informant confirmation, domain-specific complaints, concerns, feelings of worse performance) demographics, setting, apolipoprotein E gene (APOE) ε4 carriership, and neuropsychiatric symptoms with amyloid positivity. RESULTS: Between cohorts, amyloid positivity in 70-year-olds varied from 10% to 76%. Only older age, clinical setting, and APOE ε4 carriership showed univariate associations with increased amyloid positivity. After adjusting for these, lower education was also associated with increased amyloid positivity. Only within a research setting, informant-confirmed complaints, memory complaints, attention/concentration complaints, and no depressive symptoms were associated with increased amyloid positivity. Feelings of worse performance were associated with less amyloid positivity at younger ages and more at older ages. DISCUSSION: Next to age, setting, and APOE ε4 carriership, SCD-specific characteristics may facilitate the identification of amyloid-positive individuals.

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 â€‹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.

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.

Decreased cortical thickness mediates the relationship between premature birth and cognitive performance in adulthood.

Cortical thickness (CTh) reflects cortical properties such as dendritic complexity and synaptic density, which are not only vulnerable to developmental disturbances caused by premature birth but also highly relevant for cognitive performance. We tested the hypotheses whether CTh in young adults is altered after premature birth and whether these aberrations are relevant for general cognitive abilities. We investigated CTh based on brain structural magnetic resonance imaging and surface-based morphometry in a large and prospectively collected cohort of 101 very premature-born adults (<32 weeks of gestation and/or birth weight [BW] below 1,500 g) and 111 full-term controls at 26 years of age. Cognitive performance was assessed by full-scale intelligence quotient (IQ) using the Wechsler Adult Intelligence Scale. CTh was reduced in frontal, parietal, and temporal associative cortices predominantly in the left hemisphere in premature-born adults compared to controls. We found a significant positive association of CTh with both gestational age and BW, particularly in the left hemisphere, and a significant negative association between CTh and intensity of neonatal treatment within limited regions bilaterally. Full-scale IQ and CTh in the left hemisphere were positively correlated. Furthermore, CTh in the left hemisphere acted as a mediator on the association between premature birth and full-scale IQ. Results provide evidence that premature born adults have widespread reduced CTh that is relevant for their general cognitive performance. Data suggest lasting reductions in cortical microstructure subserving CTh 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.

MRI follow-up after magnetic resonance-guided focused ultrasound for non-invasive thalamotomy: the neuroradiologist's perspective.

PURPOSE: Magnetic resonance-guided focused ultrasound (MRgFUS) systems are increasingly used to non-invasively treat tremor; consensus on imaging follow-up is poor in these patients. This study aims to elucidate how MRgFUS lesions evolve for a radiological readership with regard to clinical outcome. METHODS: MRgFUS-induced lesions and oedema were retrospectively evaluated based on DWI, SWI, T2-weighted and T1-weighted 3-T MRI data acquired 30 min and 3, 30 and 180 days after MRgFUS (n = 9 essential tremor, n = 1 Parkinson's patients). Lesions were assessed volumetrically, visually and by ADC measurements and compared with clinical effects using non-parametric testing. RESULTS: Thirty minutes after treatment, all lesions could be identified on T2-weighted images. Immediate oedema was rare (n = 1). Lesion volume as well as oedema reached a maximum on day 3 with a mean lesion size of 0.4 ± 0.2 cm3 and an oedema volume 3.7 ± 1.2 times the lesion volume. On day 3, a distinct diffusion-restricted rim was noted that corresponded well with SWI. Lesion shrinkage after day 3 was observed in all sequences. Lesions were no longer detectable on DWI in n = 7/10, on T2-weighted images in n = 4/10 and on T1-weighted images in n = 4/10 on day 180. No infarcts or haemorrhage were observed. There was no correlation between lesion size and initial motor skill improvement (p = 0.99). Tremor reduction dynamics correlated strongly with lesion shrinkage between days 3 and 180 (p = 0.01, R = 0.76). CONCLUSION: In conclusion, cerebral MRgFUS lesions variably shrink over months. SWI is the sequence of choice to identify lesions after 6 months. Lesion volume is arguably associated with intermediate-term outcome.

Affective Modulation after High-Intensity Exercise Is Associated with Prolonged Amygdalar-Insular Functional Connectivity Increase.

Acute moderate exercise has been shown to induce prolonged changes in functional connectivity (FC) within affect and reward networks. The influence of different exercise intensities on FC has not yet been explored. Twenty-five male athletes underwent 30 min of "low"- (35% < lactate threshold (LT)) and "high"- (20% > LT) intensity exercise bouts on a treadmill. Resting-state fMRI was acquired at 3 Tesla before and after exercise, together with the Positive and Negative Affect Scale (PANAS). Data of 22 subjects (3 dropouts) were analyzed using the FSL feat pipeline and a seed-to-network-based analysis with the bilateral amygdala as the seed region for determining associated FC changes in the "emotional brain." Data were analyzed using a repeated measures ANOVA. Comparisons between pre- and post-exercise were analyzed using a one-sample t-test, and a paired t-test was used for the comparison between "low" and "high" exercise conditions (nonparametric randomization approach, results reported at p < 0.05). Both exercise interventions induced significant increases in the PANAS positive affect scale. There was a significant interaction effect of amygdalar FC to the right anterior insula, and this amygdalar-insular FC correlated significantly with the PANAS positive affect scale (r = 0.47, p = 0.048) in the "high"-intensity exercise condition. Our findings suggest that mood changes after exercise are associated with prolonged alterations in amygdalar-insular FC and occur in an exercise intensity-dependent manner.

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.

A machine learning investigation of volumetric and functional MRI abnormalities in adults born preterm.

Imaging studies have characterized functional and structural brain abnormalities in adults after premature birth, but these investigations have mostly used univariate methods that do not account for hypothesized interdependencies between brain regions or quantify accuracy in identifying individuals. To overcome these limitations, we used multivariate machine learning to identify gray matter volume (GMV) and amplitude of low frequency fluctuations (ALFF) brain patterns that best classify young adults born very preterm/very low birth weight (VP/VLBW; n = 94) from those born full-term (FT; n = 92). We then compared the spatial maps of the structural and functional brain signatures and validated them by assessing associations with clinical birth history and basic cognitive variables. Premature birth could be predicted with a balanced accuracy of 80.7% using GMV and 77.4% using ALFF. GMV predictions were mediated by a pattern of subcortical and middle temporal reductions and volumetric increases of the lateral prefrontal, medial prefrontal, and superior temporal gyrus regions. ALFF predictions were characterized by a pattern including increases in the thalamus, pre- and post-central gyri, and parietal lobes, in addition to decreases in the superior temporal gyri bilaterally. Decision scores from each classification, assessing the degree to which an individual was classified as a VP/VLBW case, were predicted by the number of days in neonatal hospitalization and birth weight. ALFF decision scores also contributed to the prediction of general IQ, which highlighted their potential clinical significance. Combined, the results clarified previous research and suggested that primary subcortical and temporal damage may be accompanied by disrupted neurodevelopment of the cortex.

Automated quantitative evaluation of brain MRI may be more accurate for discriminating preterm born adults.

OBJECTIVE: To investigate the structural brain abnormalities and their diagnostic accuracy through qualitative and quantitative analysis in term born and very preterm birth or with very low birth weight (VP/VLBW) adults. METHODS: We analyzed 3-T MRIs acquired in 2011-2013 from 67 adults (27 term born controls, mean age 26.4 years, 8 females; 40 VP/VLBWs, mean age 26.6 years, 16 females). We compared automatic segmentations of the white matter, deep gray matter and cortical gray matter, manual corpus callosum measurements and visual ratings of the ventricles and white matter with t tests, logistic regression, and receiver operator characteristic (ROC) curves. RESULTS: Automatic segmentation correctly classified 84% of cases; visual ratings correctly classified 63%. Quantitative volumetry based on automatic segmentation revealed higher ventricular volume, lower posterior corpus callosum, and deep gray matter volumes in VP/VLBW subjects compared to controls (p < 0.01). Visual rating and manual measurement revealed a thinner corpus callosum in VP/VLBW adults (p = 0.04) and deformed lateral ventricles (p = 0.03) and tendency towards more "dirty" white matter (p = 0.06). Automatic/manual measures combined with visual ratings correctly classified 87% of cases. Stepwise logistic regression identified three independent features that correctly classify 81% of cases: ventricular volume, deep gray matter volume, and white matter aspect. CONCLUSION: Enlarged and deformed lateral ventricles, thinner corpus callosum, and "dirty" white matter are prevalent in preterm born adults. Their visual evaluation has low diagnostic accuracy. Automatic volume quantification is more accurate but time consuming. It may be useful to ask for prematurity before initiating further diagnostics in subjects with these alterations. KEY POINTS: • Our study confirms prior reports showing that structural brain abnormalities related to preterm birth persist into adulthood. • In the clinical practice, if large and deformed lateral ventricles, small and thin corpus callosum, and "dirty" white matter are visible on MRI, ask for prematurity before considering other diagnoses. • Although prevalent, visual findings have low accuracy; adding automatic segmentation of lateral ventricles and deep gray matter nuclei improves the diagnostic accuracy.

Left frontal hub connectivity delays cognitive impairment in autosomal-dominant and sporadic Alzheimer's disease.

Patients with Alzheimer's disease vary in their ability to sustain cognitive abilities in the presence of brain pathology. A major open question is which brain mechanisms may support higher reserve capacity, i.e. relatively high cognitive performance at a given level of Alzheimer's pathology. Higher functional MRI-assessed functional connectivity of a hub in the left frontal cortex is a core candidate brain mechanism underlying reserve as it is associated with education (i.e. a protective factor often associated with higher reserve) and attenuated cognitive impairment in prodromal Alzheimer's disease. However, no study has yet assessed whether such hub connectivity of the left frontal cortex supports reserve throughout the evolution of pathological brain changes in Alzheimer's disease, including the presymptomatic stage when cognitive decline is subtle. To address this research gap, we obtained cross-sectional resting state functional MRI in 74 participants with autosomal dominant Alzheimer's disease, 55 controls from the Dominantly Inherited Alzheimer's Network and 75 amyloid-positive elderly participants, as well as 41 amyloid-negative cognitively normal elderly subjects from the German Center of Neurodegenerative Diseases multicentre study on biomarkers in sporadic Alzheimer's disease. For each participant, global left frontal cortex connectivity was computed as the average resting state functional connectivity between the left frontal cortex (seed) and each voxel in the grey matter. As a marker of disease stage, we applied estimated years from symptom onset in autosomal dominantly inherited Alzheimer's disease and cerebrospinal fluid tau levels in sporadic Alzheimer's disease cases. In both autosomal dominant and sporadic Alzheimer's disease patients, higher levels of left frontal cortex connectivity were correlated with greater education. For autosomal dominant Alzheimer's disease, a significant left frontal cortex connectivity × estimated years of onset interaction was found, indicating slower decline of memory and global cognition at higher levels of connectivity. Similarly, in sporadic amyloid-positive elderly subjects, the effect of tau on cognition was attenuated at higher levels of left frontal cortex connectivity. Polynomial regression analysis showed that the trajectory of cognitive decline was shifted towards a later stage of Alzheimer's disease in patients with higher levels of left frontal cortex connectivity. Together, our findings suggest that higher resilience against the development of cognitive impairment throughout the early stages of Alzheimer's disease is at least partially attributable to higher left frontal cortex-hub connectivity.