Fetal MRI based brain atlas analysis detects initial in utero effects of prenatal alcohol exposure.

Prenatal alcohol exposure (PAE) can change the normal trajectory of human fetal brain development and may lead to long-lasting neurodevelopmental changes in the form of fetal alcohol spectrum disorders. Currently, early prenatal patterns of alcohol-related central nervous system changes are unclear and it is unknown if small amounts of PAE may result in early detectable brain anomalies. This super-resolution fetal magnetic resonance imaging (MRI) study aimed to identify regional effects of PAE on human brain structure. Fetuses were prospectively assessed using atlas-based semi-automated 3-dimensional tissue segmentation based on 1.5 T and 3 T fetal brain MRI examinations. After expectant mothers completed anonymized PRAMS and TACE questionnaires for PAE, fetuses without gross macroscopic brain abnormalities were identified and analyzed. Linear mixed-effects modeling of regional brain volumes was conducted and multiple comparisons were corrected using the Benjamini-Hochberg procedure. In total, 500 pregnant women were recruited with 51 reporting gestational alcohol consumption. After excluding confounding comorbidities, 24 fetuses (26 observations) were identified with PAE and 52 age-matched controls without PAE were analyzed. Patients with PAE showed significantly larger volumes of the corpus callosum (P ≤ 0.001) and smaller volumes of the periventricular zone (P = 0.001). Even minor (1-3 standard drinks per week) PAE changed the neurodevelopmental trajectory.

Fetal development of functional thalamocortical and cortico-cortical connectivity.

Measuring and understanding functional fetal brain development in utero is critical for the study of the developmental foundations of our cognitive abilities, possible early detection of disorders, and their prevention. Thalamocortical connections are an intricate component of shaping the cortical layout, but so far, only ex-vivo studies provide evidence of how axons enter the sub-plate and cortex during this highly dynamic phase. Evidence for normal in-utero development of the functional thalamocortical connectome in humans is missing. Here, we modeled fetal functional thalamocortical connectome development using in-utero functional magnetic resonance imaging in fetuses observed from 19th to 40th weeks of gestation (GW). We observed a peak increase of thalamocortical functional connectivity strength between 29th and 31st GW, right before axons establish synapses in the cortex. The cortico-cortical connectivity increases in a similar time window, and exhibits significant functional laterality in temporal-superior, -medial, and -inferior areas. Homologous regions exhibit overall similar mirrored connectivity profiles, but this similarity decreases during gestation giving way to a more diverse cortical interconnectedness. Our results complement the understanding of structural development of the human connectome and may serve as the basis for the investigation of disease and deviations from a normal developmental trajectory of connectivity development.

Fetal indusium griseum is a possible biomarker of the regularity of brain midline development in 3T MR imaging: A retrospective observational study.

INTRODUCTION: This study aimed to assess the visibility of the indusium griseum (IG) in magnetic resonance (MR) scans of the human fetal brain and to evaluate its reliability as an imaging biomarker of the normality of brain midline development. MATERIAL AND METHODS: The retrospective observational study encompassed T2-w 3T MR images from 90 post-mortem fetal brains and immunohistochemical sections from 41 fetal brains (16-40 gestational weeks) without cerebral pathology. Three raters independently inspected and evaluated the visibility of IG in post-mortem and in vivo MR scans. Weighted kappa statistics and regression analysis were used to determine inter- and intra-rater agreement and the type and strength of the association of IG visibility with gestational age. RESULTS: The visibility of the IG was the highest between the 25 and 30 gestational week period, with a very good inter-rater variability (kappa 0.623-0.709) and excellent intra-rater variability (kappa 0.81-0.93). The immunochemical analysis of the histoarchitecture of IG discloses the expression of highly hydrated extracellular molecules in IG as the substrate of higher signal intensity and best visibility of IG during the mid-fetal period. CONCLUSIONS: The knowledge of developmental brain histology and fetal age allows us to predict the IG-visibility in magnetic resonance imaging (MRI) and use it as a biomarker to evaluate the morphogenesis of the brain midline. As a biomarker, IG is significant for post-mortem pathological examination by MRI. Therefore, in the clinical in vivo imaging examination, IG should be anticipated when an assessment of the brain midline structures is needed in mid-gestation, including corpus callosum thickness measurements.

Motion correction and volumetric reconstruction for fetal functional magnetic resonance imaging data.

Motion correction is an essential preprocessing step in functional Magnetic Resonance Imaging (fMRI) of the fetal brain with the aim to remove artifacts caused by fetal movement and maternal breathing and consequently to suppress erroneous signal correlations. Current motion correction approaches for fetal fMRI choose a single 3D volume from a specific acquisition timepoint with least motion artefacts as reference volume, and perform interpolation for the reconstruction of the motion corrected time series. The results can suffer, if no low-motion frame is available, and if reconstruction does not exploit any assumptions about the continuity of the fMRI signal. Here, we propose a novel framework, which estimates a high-resolution reference volume by using outlier-robust motion correction, and by utilizing Huber L2 regularization for intra-stack volumetric reconstruction of the motion-corrected fetal brain fMRI. We performed an extensive parameter study to investigate the effectiveness of motion estimation and present in this work benchmark metrics to quantify the effect of motion correction and regularised volumetric reconstruction approaches on functional connectivity computations. We demonstrate the proposed framework's ability to improve functional connectivity estimates, reproducibility and signal interpretability, which is clinically highly desirable for the establishment of prognostic noninvasive imaging biomarkers. The motion correction and volumetric reconstruction framework is made available as an open-source package of NiftyMIC.

Disentangling cortical functional connectivity strength and topography reveals divergent roles of genes and environment.

The human brain varies across individuals in its morphology, function, and cognitive capacities. Variability is particularly high in phylogenetically modern regions associated with higher order cognitive abilities, but its relationship to the layout and strength of functional networks is poorly understood. In this study we disentangled the variability of two key aspects of functional connectivity: strength and topography. We then compared the genetic and environmental influences on these two features. Genetic contribution is heterogeneously distributed across the cortex and differs for strength and topography. In heteromodal areas genes predominantly affect the topography of networks, while their connectivity strength is shaped primarily by random environmental influence such as learning. We identified peak areas of genetic control of topography overlapping with parts of the processing stream from primary areas to network hubs in the default mode network, suggesting the coordination of spatial configurations across those processing pathways. These findings provide a detailed map of the diverse contribution of heritability and individual experience to the strength and topography of functional brain architecture.

The Prenatal Morphomechanic Impact of Agenesis of the Corpus Callosum on Human Brain Structure and Asymmetry.

Genetic, molecular, and physical forces together impact brain morphogenesis. The early impact of deficient midline crossing in agenesis of the Corpus Callosum (ACC) on prenatal human brain development and architecture is widely unknown. Here we analyze the changes of brain structure in 46 fetuses with ACC in vivo to identify their deviations from normal development. Cases of complete ACC show an increase in the thickness of the cerebral wall in the frontomedial regions and a reduction in the temporal, insular, medial occipital and lateral parietal regions, already present at midgestation. ACC is associated with a more symmetric configuration of the temporal lobes and increased frequency of atypical asymmetry patterns, indicating an early morphomechanic effect of callosal growth on human brain development affecting the thickness of the pallium along a ventro-dorsal gradient. Altered prenatal brain architecture in ACC emphasizes the importance of conformational forces introduced by emerging interhemispheric connectivity on the establishment of polygenically determined brain asymmetries.

The Prenatal Origins of Human Brain Asymmetry: Lessons Learned from a Cohort of Fetuses with Body Lateralization Defects.

Knowledge about structural brain asymmetries of human fetuses with body lateralization defects-congenital diseases in which visceral organs are partially or completely incorrectly positioned-can improve our understanding of the developmental origins of hemispheric brain asymmetry. This study investigated structural brain asymmetry in 21 fetuses, which were diagnosed with different types of lateralization defects; 5 fetuses with ciliopathies and 26 age-matched healthy control cases, between 22 and 34 gestational weeks of age. For this purpose, a database of 4007 fetal magnetic resonance imagings (MRIs) was accessed and searched for the corresponding diagnoses. Specific temporal lobe brain asymmetry indices were quantified using in vivo, super-resolution-processed MR brain imaging data. Results revealed that the perisylvian fetal structural brain lateralization patterns and asymmetry indices did not differ between cases with lateralization defects, ciliopathies, and normal controls. Molecular mechanisms involved in the definition of the right/left body axis-including cilium-dependent lateralization processes-appear to occur independently from those involved in the early establishment of structural human brain asymmetries. Atypically inverted early structural brain asymmetries are similarly rare in individuals with lateralization defects and may have a complex, multifactorial, and neurodevelopmental background with currently unknown postnatal functional consequences.

The role of the corpus callosum in language network connectivity in children.

The specific role of the corpus callosum (CC) in language network organization remains unclear, two contrasting models have been proposed: inhibition of homotopic areas allowing for independent functioning of the hemispheres versus integration of information from both hemispheres. This study aimed to add to this discussion with the first investigation of language network connectivity in combination with CC volume measures. In 38 healthy children aged 6-12, we performed task-based functional magnetic resonance imaging to measure language network connectivity, used structural magnetic resonance imaging to quantify CC subsection volumes, and administered various language tests to examine language abilities. We found an increase in left intrahemispheric and bilateral language network connectivity and a decrease in right intrahemispheric connectivity associated with larger volumes of the posterior, mid-posterior, and central subsections of the CC. Consistent with that, larger volumes of the posterior parts of the CC were significantly associated with better verbal fluency and vocabulary, the anterior CC volume was positively correlated with verbal span. Thus, children with larger volumes of CC subsections showed increased interhemispheric language network connectivity and were better in different language domains. This study presents the first evidence that the CC is directly linked to language network connectivity and underlines the excitatory role of the CC in the integration of information from both hemispheres.

The Subplate Layers: The Superficial and Deep Subplate Can be Discriminated on 3 Tesla Human Fetal Postmortem MRI.

The subplate (SP) is a transient structure of the human fetal brain that becomes the most prominent layer of the developing pallium during the late second trimester. It is important in the formation of thalamocortical and cortico-cortical connections. The SP is vulnerable in perinatal brain injury and may play a role in complex neurodevelopmental disorders, such as schizophrenia and autism. Nine postmortem fetal human brains (19-24 GW) were imaged on a 3 Tesla MR scanner and the T2-w images in the frontal and temporal lobes were compared, in each case, with the histological slices of the same brain. The brains were confirmed to be without any brain pathology. The purpose of this study was to demonstrate that the superficial SP (sSP) and deep SP (dSP) can be discriminated on postmortem MR images. More specifically, we aimed to clarify that the observable, thin, hyperintense layer below the cortical plate in the upper SP portion on T2-weighted MR images has an anatomical correspondence to the histologically established sSP. Therefore, the distinction between the sSP and dSP layers, using clinically available MR imaging methodology, is possible in postmortem MRI and can help in the imaging interpretation of the fetal cerebral layers.

Cross-species functional alignment reveals evolutionary hierarchy within the connectome.

Evolution provides an important window into how cortical organization shapes function and vice versa. The complex mosaic of changes in brain morphology and functional organization that have shaped the mammalian cortex during evolution, complicates attempts to chart cortical differences across species. It limits our ability to fully appreciate how evolution has shaped our brain, especially in systems associated with unique human cognitive capabilities that lack anatomical homologues in other species. Here, we develop a function-based method for cross-species alignment that enables the quantification of homologous regions between humans and rhesus macaques, even when their location is decoupled from anatomical landmarks. Critically, we find cross-species similarity in functional organization reflects a gradient of evolutionary change that decreases from unimodal systems and culminates with the most pronounced changes in posterior regions of the default mode network (angular gyrus, posterior cingulate and middle temporal cortices). Our findings suggest that the establishment of the default mode network, as the apex of a cognitive hierarchy, has changed in a complex manner during human evolution - even within subnetworks.

Joint embedding: A scalable alignment to compare individuals in a connectivity space.

A common coordinate space enabling comparison across individuals is vital to understanding human brain organization and individual differences. By leveraging dimensionality reduction algorithms, high-dimensional fMRI data can be represented in a low-dimensional space to characterize individual features. Such a representative space encodes the functional architecture of individuals and enables the observation of functional changes across time. However, determining comparable functional features across individuals in resting-state fMRI in a way that simultaneously preserves individual-specific connectivity structure can be challenging. In this work we propose scalable joint embedding to simultaneously embed multiple individual brain connectomes within a common space that allows individual representations across datasets to be aligned. Using Human Connectome Project data, we evaluated the joint embedding approach by comparing it to the previously established orthonormal alignment model. Alignment using joint embedding substantially increased the similarity of functional representations across individuals while simultaneously capturing their distinct profiles, allowing individuals to be more discriminable from each other. Additionally, we demonstrated that the common space established using resting-state fMRI provides a better overlap of task-activation across participants. Finally, in a more challenging scenario - alignment across a lifespan cohort aged from 6 to 85 - joint embedding provided a better prediction of age (r2 = 0.65) than the prior alignment model. It facilitated the characterization of functional trajectories across lifespan. Overall, these analyses establish that joint embedding can simultaneously capture individual neural representations in a common connectivity space aligning functional data across participants and populations and preserve individual specificity.

Stent-graft surface movement after endovascular aneurysm repair: baseline parameters for prediction, and association with migration and stent-graft-related endoleaks.

OBJECTIVES: To evaluate the influence of baseline parameters on the occurrence of stent-graft surface movement after endovascular aneurysm repair (EVAR) and to investigate its association with migration and stent-graft-related endoleaks (srEL). METHODS: In this retrospective, cross-sectional study, three-dimensional surface models of the stent-graft, delimited by landmarks using custom-built software, were derived from the pre-discharge and last follow-up computed tomography angiography (CTA). Stent-graft surface movement in the proximal anchoring zone between these examinations was considered significant at a threshold of 9 mm. The Cox proportional hazards model was used to determine baseline variables associated with the occurrence of stent-graft surface movement. The association between migration and srEL with stent-graft surface movement was tested with the chi-square and the Fisher exact test, respectively. RESULTS: Stent-graft surface movement was observed in 54 (28.9%) of 187 patients. Multivariate analysis revealed that age ([HR] 1.05; p = 0.017), proximal neck diameter ([HR] 5.07; p < 0.001), infrarenal aortic neck angulation ([HR] 1.02, p = 0.002), and proximal neck length ([HR] 0.62, p < 0.001) were significantly associated with the occurrence of stent-graft surface movement. Migration and srEL occurred in 17 (31.5%) and 5 (9.3%) patients, with and 11 (8.3%) and 2 (1.5%) without stent-graft surface movement (p < 0.001, p = 0.022). CONCLUSIONS: Age, neck diameter, infrarenal neck angulation, and proximal neck length were significantly associated with the occurrence of stent-graft surface movement. Apart from possible use of adjunctive sealing systems, concerned patients may benefit from regular CTA surveillance, enabling timely diagnosis of subtle changes of stent-graft position. KEY POINTS: • Stent-graft surface movement, demonstrating subtle, three-dimensional changes in stent-graft position in the proximal anchoring zone, can be derived from CTA examinations. • Age, proximal neck diameter, and infrarenal neck angulation were significantly associated with an increased incidence of stent-graft surface movement. Stent-graft surface movement is significantly more frequent in patients with stent-graft migration and stent-graft-related endoleaks. • Consideration of risk factors for stent-graft surface movement may help to identify patients who might benefit from regular CTA surveillance and timely diagnosis of subtle changes of stent-graft position, enabling re-interventions to prevent migration and srEL.

Diffeomorphic functional brain surface alignment: Functional demons.

Aligning brain structures across individuals is a central prerequisite for comparative neuroimaging studies. Typically, registration approaches assume a strong association between the features used for alignment, such as macro-anatomy, and the variable observed, such as functional activation or connectivity. Here, we propose to use the structure of intrinsic resting state fMRI signal correlation patterns as a basis for alignment of the cortex in functional studies. Rather than assuming the spatial correspondence of functional structures between subjects, we have identified locations with similar connectivity profiles across subjects. We mapped functional connectivity relationships within the brain into an embedding space, and aligned the resulting maps of multiple subjects. We then performed a diffeomorphic alignment of the cortical surfaces, driven by the corresponding features in the joint embedding space. Results show that functional alignment based on resting state fMRI identifies functionally homologous regions across individuals with higher accuracy than alignment based on the spatial correspondence of anatomy. Further, functional alignment enables measurement of the strength of the anatomo-functional link across the cortex, and reveals the uneven distribution of this link. Stronger anatomo-functional dissociation was found in higher association areas compared to primary sensory- and motor areas. Functional alignment based on resting state features improves group analysis of task based functional MRI data, increasing statistical power and improving the delineation of task-specific core regions. Finally, a comparison of the anatomo-functional dissociation between cohorts is demonstrated with a group of left and right handed subjects.

Disrupted developmental organization of the structural connectome in fetuses with corpus callosum agenesis.

Agenesis of the corpus callosum is a model disease for disrupted connectivity of the human brain, in which the pathological formation of interhemispheric fibers results in subtle to severe cognitive deficits. Postnatal studies suggest that the characteristic abnormal pathways in this pathology are compensatory structures that emerge via neural plasticity. We challenge this hypothesis and assume a globally different network organization of the structural interconnections already in the fetal acallosal brain. Twenty fetuses with isolated corpus callosum agenesis with or without associated malformations were enrolled and fiber connectivity among 90 brain regions was assessed using in utero diffusion tensor imaging and streamline tractography. Macroscopic scale connectomes were compared to 20 gestational age-matched normally developing fetuses with multiple granularity of network analysis. Gradually increasing connectivity strength and tract diffusion anisotropy during gestation were dominant in antero-posteriorly running paramedian and antero-laterally running aberrant pathways, and in short-range connections in the temporoparietal regions. In fetuses with associated abnormalities, more diffuse reduction of cortico-cortical and cortico-subcortical connectivity was observed than in cases with isolated callosal agenesis. The global organization of anatomical networks consisted of less segregated nodes in acallosal brains, and hubs of dense connectivity, such as the thalamus and cingulate cortex, showed reduced network centrality. Acallosal fetal brains show a globally altered connectivity network structure compared to normals. Besides the previously described Probst and sigmoid bundles, we revealed a prenatally differently organized macroconnectome, dominated by increased connectivity. These findings provide evidence that abnormal pathways are already present during at early stages of fetal brain development in the majority of cerebral white matter.

Evolution of cortical geometry and its link to function, behaviour and ecology.

Studies in comparative neuroanatomy and of the fossil record demonstrate the influence of socio-ecological niches on the morphology of the cerebral cortex, but have led to oftentimes conflicting theories about its evolution. Here, we study the relationship between the shape of the cerebral cortex and the topography of its function. We establish a joint geometric representation of the cerebral cortices of ninety species of extant Euarchontoglires, including commonly used experimental model organisms. We show that variability in surface geometry relates to species' ecology and behaviour, independent of overall brain size. Notably, ancestral shape reconstruction of the cortical surface and its change during evolution enables us to trace the evolutionary history of localised cortical expansions, modal segregation of brain function, and their association to behaviour and cognition. We find that individual cortical regions follow different sequences of area increase during evolutionary adaptations to dynamic socio-ecological niches. Anatomical correlates of this sequence of events are still observable in extant species, and relate to their current behaviour and ecology. We decompose the deep evolutionary history of the shape of the human cortical surface into spatially and temporally conscribed components with highly interpretable functional associations, highlighting the importance of considering the evolutionary history of cortical regions when studying their anatomy and function.

Fetal temporal sulcus depth asymmetry has prognostic value for language development.

In most humans, the superior temporal sulcus (STS) shows a rightward depth asymmetry. This asymmetry can not only be observed in adults, but is already recognizable in the fetal brain. As the STS lies adjacent to brain areas important for language, STS depth asymmetry may represent an anatomical marker for language abilities. This study investigated the prognostic value of STS depth asymmetry in healthy fetuses for later language abilities, language localization, and language-related white matter tracts. Less right lateralization of the fetal STS depth was significantly associated with better verbal abilities, with fetal STS depth asymmetry explaining more than 40% of variance in verbal skills 6-13 years later. Furthermore, less right fetal STS depth asymmetry correlated with increased left language localization during childhood. We hypothesize that earlier and/or more localized fetal development of the left temporal cortex is accompanied by an earlier development of the left STS and is favorable for early language learning. If the findings of this pilot study hold true in larger samples of healthy children and in different clinical populations, fetal STS asymmetry has the potential to become a diagnostic biomarker of the maturity and integrity of neural correlates of language.

Effect of corpus callosum agenesis on the language network in children and adolescents.

The present study is interested in the role of the corpus callosum in the development of the language network. We, therefore, investigated language abilities and the language network using task-based fMRI in three cases of complete agenesis of the corpus callosum (ACC), three cases of partial ACC and six controls. Although the children with complete ACC revealed impaired functions in specific language domains, no child with partial ACC showed a test score below average. As a group, ACC children performed significantly worse than healthy controls in verbal fluency and naming. Furthermore, whole-brain ROI-to-ROI connectivity analyses revealed reduced intrahemispheric and right intrahemispheric functional connectivity in ACC patients as compared to controls. In addition, stronger functional connectivity between left and right temporal areas was associated with better language abilities in the ACC group. In healthy controls, no association between language abilities and connectivity was found. Our results show that ACC is associated not only with less interhemispheric, but also with less right intrahemispheric language network connectivity in line with reduced verbal abilities. The present study, thus, supports the excitatory role of the corpus callosum in functional language network connectivity and language abilities.

The impact of hippocampal impairment on task-positive and task-negative language networks in temporal lobe epilepsy.

OBJECTIVE: To study hippocampal integration within task-positive and task-negative language networks and the impact of a diseased left and right hippocampus on the language connectome in temporal lobe epilepsy (TLE). METHODS: We used functional magnetic resonance imaging (fMRI) to study a homogenous group of 32 patients with TLE (17 left) and 14 healthy controls during a verb-generation task. We performed functional connectivity analysis and quantified alterations within the language connectome and evaluated disruptions of the functional dissociation along the anterior-posterior axis of the hippocampi. RESULTS: Connectivity analysis revealed significant differences between left and right TLE compared to healthy controls. Left TLE showed widespread impairment of task-positive language networks, while right TLE showed less pronounced alterations. Particularly right TLE showed altered connectivity for cortical regions that were part of the default mode network (DMN). Left TLE showed a disturbed functional dissociation pattern along the left hippocampus to left and right inferior frontal language regions, while left and right TLE revealed an altered dissociation pattern along the right hippocampus to regions associated with the DMN. CONCLUSIONS: Our results showed an impaired hippocampal integration into active language and the default mode networks, which both may contribute to language impairment in TLE. SIGNIFICANCE: Our results emphasize the direct role of the left hippocampus in language processing, and the potential role of the right hippocampus as a modulator between DMN and task-positive networks.

3T MRI signal intensity profiles and thicknesses of transient zones in human fetal brain at mid-gestation.

In this study we compare temporal lobe (TL) signal intensity (SI) profiles, along with the average thicknesses of the transient zones obtained from postmortem MRI (pMRI) scans and corresponding histological slices, to the frontal lobe (FL) SI and zone thicknesses, in normal fetal brains. The purpose was to assess the synchronization of the corticogenetic processes in different brain lobes. Nine postmortem human fetal brains without cerebral pathologies, from 19 to 24 weeks of gestation (GW) were analyzed on T2-weighted 3T pMRI, at the coronal level of the thalamus and basal ganglia. The SI profiles of the transient zones in the TL correlate well spatially and temporally to the signal intensity profile of the FL. During the examined period, in the TL, the intermediate and subventricular zone are about the size of the subplate zone (SP), while the superficial SP demonstrates the highest signal intensity. The correlation of the SI profiles and the distributions of the transient zones in the two brain lobes, indicates a time-aligned histogenesis during this narrow time window. The 3TpMRI enables an assessment of the regularity of lamination patterns in the fetal telencephalic wall, upon comparative evaluation of sizes of the transient developmental zones and the SI profiles of different cortical regions. A knowledge of normal vs. abnormal transient lamination patterns and the SI profiles is a prerequisite for further advancement of the MR diagnostic tools needed for early detection of developmental brain pathologies prenatally, especially mild white matter injuries such as lesions of TL due to prenatal cytomegalovirus infections, or cortical malformations.

Distributed changes of the functional connectome in patients with glioblastoma.

Glioblastoma might have widespread effects on the neural organization and cognitive function, and even focal lesions may be associated with distributed functional alterations. However, functional changes do not necessarily follow obvious anatomical patterns and the current understanding of this interrelation is limited. In this study, we used resting-state functional magnetic resonance imaging to evaluate changes in global functional connectivity patterns in 15 patients with glioblastoma. For six patients we followed longitudinal trajectories of their functional connectome and structural tumour evolution using bi-monthly follow-up scans throughout treatment and disease progression. In all patients, unilateral tumour lesions were associated with inter-hemispherically symmetric network alterations, and functional proximity of tumour location was stronger linked to distributed network deterioration than anatomical distance. In the longitudinal subcohort of six patients, we observed patterns of network alterations with initial transient deterioration followed by recovery at first follow-up, and local network deterioration to precede structural tumour recurrence by two months. In summary, the impact of focal glioblastoma lesions on the functional connectome is global and linked to functional proximity rather than anatomical distance to tumour regions. Our findings further suggest a relevance for functional network trajectories as a possible means supporting early detection of tumour recurrence.