Understanding how information flows across distributed brain networks is central to linking brain structure, dynamics and function. Here we present a neuroimaging framework that combines integrated effective connectivity (iEC) and unconstrained signal flow mapping for data-driven identification of human cerebral functional hierarchies. Simulations and empirical validation show that iEC recovers connectome directionality and aligns with histologically defined feedforward and feedback pathways. The iEC-derived hierarchy exhibits a monotonically increasing level along the axis where the sensorimotor, association and paralimbic areas are sequentially ordered, consistent with predictions from the structural model of laminar connectivity. This hierarchy is not fixed but flexibly reorganizes across brain states; it becomes flatter during externally oriented processing and steeper during internally focused conditions, reflecting increased engagement of interoceptive regions. Our study indicates that macroscale directed functional connectivity can reveal biologically grounded, state-dependent principles of signal flow in the human brain.

Gradient mapping has emerged as a powerful approach to summarize high-dimensional functional connectivity into low-dimensional manifolds, revealing hierarchical organization across multiple cortical and subcortical structures. Yet the spinal cord, an essential processing hub for sensorimotor integration, has remained largely absent from this dimensional view of functional organization. Here we use simultaneous corticospinal resting-state fMRI and functional connectivity gradients to place human sensorimotor cortex and cervical spinal cord within a common corticospinal manifold. We show that intrinsic cortical gradients recover key features of somatotopic organization along the sensorimotor strip, whereas spinal gradients exhibit orderly separation of gray and white matter, and of ascending and descending pathways when their geometry respects major anatomical compartments. Furthermore, by contrasting gradients that prioritize structural compartments with those that emphasize functional coupling, we show that corticospinal hierarchies depend jointly on local anatomy and cross-anatomy connectivity. Along this topographic spectrum, spinal input broadens and differentiates cortical gradients axes, while cortical input preserves spinal ones, revealing asymmetric embedding of cortex and cord at rest. Together, these findings incorporate the spinal cord into the gradient-based toolkit for mesoscale brain mapping and extend this approach beyond the cortex, providing an integrated framework in which corticospinal organization is described not as isolated regions and anatomical pathways, but as coupled manifolds spanning the neuraxis.

A bstract Temporal lobe epilepsy is the most common drug-resistant epilepsy, with surgical resection offering the primary path to seizure freedom. Despite standardized approaches, a substantial proportion of patients experience seizure recurrence, and the neurobiological substrates underlying these divergent outcomes remain unclear. We applied an individualized normative modeling framework to multimodal preoperative MRI data in a group that subsequently underwent surgical resection, to characterize patient-specific structural deviations and identify disease epicenters. Patients who became seizure-free exhibited spatially coherent abnormalities localized to the hippocampus and ipsilateral association regions, anchored in agranular limbic territories and enriched for genes linked to calcium-dependent signaling. Non-seizure-free patients, on the other hand, showed a more heterogeneous and distributed pattern of deviations, consistent with a “temporal-plus” network organization, and broader neuromodulatory dysregulation. Crucially, overlap between resected tissue and network-defined epicenters was closely associated with seizure freedom, independent of total resection volume. These findings provide a multiscale framework for precision surgical planning, shifting the focus from standardized tissue removal to targeted disconnection of patient-specific pathological hubs.

Positive and negative schizotypy reflect distinct patterns of subclinical traits in the general population associated with neurodevelopmental and schizophrenia-spectrum pathologies. Yet, a comprehensive characterization of the unique and shared neuroanatomical signatures of these schizotypy dimensions is lacking. Leveraging 3D brain MRI data from 2730 unmedicated healthy individuals, we identified neuroanatomical profiles of positive and negative schizotypy and systematically compared them with disorder-specific, microarchitectural, neurotransmitter-level, and connectome measures. Positive and negative schizotypy were associated with distinct cortical signatures, of predominantly thinner frontal and thicker paralimbic cortical areas, respectively. These cortical signatures of positive and negative schizotypy were differentially linked to brain-wide cortical patterns of schizophrenia-spectrum (clinical high-risk for psychosis, schizophrenia) and neurodevelopmental conditions (ADHD, autism spectrum disorder and 22q11.2 deletion syndrome). Additionally, the positive and negative schizotypy-related cortical profiles mapped onto different local attributes of gene expression, cortical myelination, D1, and histamine receptor distributions. Network models further showed that positive and negative schizotypy cortical signatures were spatially associated with cortical hubs, suggesting that highly interconnected regions are more vulnerable to the morphological differences associated with both schizotypy dimensions. Finally, predominantly sensorimotor-to-association and paralimbic areas emerged as epicenters with connectivity profiles significantly linked to the schizotypy-related cortical patterns. Collectively, this study identified cortical signatures of positive and negative schizotypy traits that are embedded along multiple scales of cortical organization and neuropsychiatric pathologies. Our work yields novel insights into how neurobiology and brain architecture may guide neuroanatomical vulnerability and resilience to psychopathology in the general population.

Autism spectrum disorder (ASD) is a prevalent and heterogeneous neurodevelopmental condition marked by atypical brain connectivity. Understanding ASD neural subtypes at the network level is critical for clarifying its neuroanatomical heterogeneity. Morphometric similarity networks (MSNs), derived from region-to-region similarity across multiple anatomical features, offer a powerful approach for capturing individual-level neural architecture. In this study, MSNs were estimated from seven anatomical features in 348 individuals with ASD and 452 typically developing (TD) controls. Across all ASD participants, the first principal component of MSN values was negatively correlated with social and communication severity. Three ASD subtypes with distinct MSN patterns were identified. Subtype-1, characterized by weaker morphometric similarity values in frontotemporal association regions compared to TD individuals, exhibited the most severe symptoms in social, communication and repetitive behaviors, and displayed hyperconnectivity between the salience and visual networks, and between language and visual networks. Subtype-2 showed greater values of morphometric similarities than TD and less severe social symptoms compared to subtype-1, along with hyperconnectivity between default and salience networks relative to TD. Subtype-3 displayed morphometric similarity values largely comparable to TD and the least severe symptoms out of the three subtypes. Transcriptomic analysis revealed that GABAergic parvalbumin and glutamatergic intratelencephalic-projecting neurons were key cell types differentiating subtypes. These findings suggest the existence of distinct ASD neuroanatomical subtypes defined by regional morphometric similarity, each linked to unique behavioral, functional, and transcriptomic profiles. Morphometric dissimilarity in association regions may serve as a neural signature for ASD subtypes characterized by more severe clinical manifestations.

Reasoning about others' thoughts or beliefs is central to human social behavior. This ability, known as theory of mind (ToM), has been primarily attributed to cortical regions of the default network (DN). However, whether and how subcortical structures, particularly the thalamus, contribute to this high-level computation remains unknown. Here, we investigated human thalamocortical dynamics during a naturalistic ToM movie watching condition, taking a rare dual-modality approach by combining high-field 7T fMRI and intracranial stereoelectroencephalography (sEEG). Across both modalities, ToM events reliably activated the DN, whereas the thalamus lacked canonical local activation. Despite this absence of local activation, the thalamus shared ToM-related representational structure and exhibited enhanced bidirectional interactions with the DN during mentalizing across methods. Crucially, sEEG revealed that the thalamus coordinated DN activity via cross-frequency phase-amplitude coupling (PAC), whereby thalamic low-frequency phase unidirectionally modulated DN high-frequency activity. Furthermore, the strength of thalamic-DN PAC predicted both the activity magnitude and the representational quality of ToM-related information within the dorsomedial DN subsystem. Together, these findings identify the human thalamus as a regulatory hub that gates DN computations during ToM without exhibiting observable localized activity, revealing a previously unrecognized mechanism by which thalamic dynamics coordinate high-level social cognition in humans.

Tauopathies are pathologies wherein phosphorylated insoluble tau aggregates in neurons, leading to dysfunction and degeneration. Positron emission tomography (PET) enables measurement of in vivo tau, with second-generation radiotracers such as [ 18 F]MK6240 showing high tau affinity with minimal off-target binding. While tauopathies are commonly linked to age-related neurodegenerative diseases, notably Alzheimer’s disease (AD), evidence suggests pathophysiological cascades may begin long before clinical onset. Increasingly, tau is recognized in pathologies affecting younger individuals, including autosomal dominant AD, Niemann-Pick disease type C, chronic traumatic encephalopathy, and epilepsy, thus highlighting the importance of normative data in non-geriatric populations. Here, we present a dataset of 33 young to middle-age healthy adults (mean age 34.0±10.4 years, 12 female) with [ 18 F]MK6240 PET data and T1w magnetic resonance imaging. Longitudinal data are also available in a subset of 9 participants with a minimum follow-up time of 1 year. Our dataset aims to support imaging biomarker studies on younger individuals potentially at risk for AD and to advance work in tauopathies affecting non-geriatric populations generally excluded from neurodegeneration studies.

Prior studies have focused on tau spread from the entorhinal cortex along first-order (short-range) connections within anatomical brain space (seed-to-target). Here, we explore tau spread along long-range connections within a novel coordinate space called connectome gradients, which is reflective of the brain's hierarchical organization. Exploring tau spread within this new framework offers insights into long-range connectivity alterations and network susceptibility in Alzheimer's disease (AD). We included 213 participants from TRIAD (103 A- CN, 103 A+ CN, and 75 A+ CI) with diffusion-weighted MRI, resting-state functional MRI, and 18F-MK6240 tau-PET. First, we employed graph theory-based stepwise connectivity analyses to unveil long-range connectivity patterns from the entorhinal cortex to the rest of the brain. Differences in connectivity patterns were compared between A+ vs A- groups, adjusted for age, sex, and APOE-ε4. Second, we investigated the stepwise connectivity patterns in relation to tau within a novel coordinate system spanned by the principal functional and structural connectome gradients. In the preclinical stage (A+ CN) compared to controls (A- CN), we observed connectivity increase through functional gradient space (Figure 1A red). In the clinical stage (A+ CI), connectivity reduced from the entorhinal cortex to the transmodal end of the functional gradient (DMN/limbic; Figure 1A blue) and to the posterior end of the structural gradient (temporo-occipital; Figure 1B blue). Long-range connections from the entorhinal cortex showed increased connectivity toward the unimodal and anterior ends of the functional and structural gradient, respectively (Figure 1A, B red), potentially initiating new paths for tau spread. Indeed, tau–connectivity correlations shifted spatially within gradient space with disease progression (Figure 2), moving from the highest-order (DMN/limbic) cognitive system of the functional gradient in A+ CN to the second-highest order (frontoparietal) system in A+ CI. We employed a novel integration of stepwise connectivity and connectome gradients to enable a better understanding of how connectivity is related to tau spread along the major axes of brain organization. We observed widespread network reorganization in AD and notably that the tau–connectivity correlations shifted between major networks of the functional connectome gradient with disease progression.

Negative symptoms of schizophrenia (SCZ), particularly amotivation, are prominent across both SCZ and bipolar disorder (BD). While orbitofrontal cortex (OFC) alterations have been implicated in the development of negative symptoms, their contributions across disorders remain to be established. Here, we examined how OFC thickness and network associations relate to amotivation compared to diminished expression across the BD-SCZ spectrum. We included 50 individuals with SCZ, 49 with BD, and 122 controls. We assessed amotivation and diminished expression and estimated thickness in the medial and lateral OFC as regions of interest as well as 64 other cortical regions. Across BD and SCZ, reduced right lateral and bilateral medial OFC thickness were specifically associated with amotivation, but not diminished expression or other clinical factors. We then generated intra-individual OFC structural covariance networks to evaluate how the system-level embedding of the OFC would link to brain-wide cortical maps of negative symptoms. We found that medial OFC covariance networks spatially correlated with the brain-wide cortical alterations of both negative symptom dimensions. Further analyses in independent SCZ data from the ENIGMA consortium (n = 4474) revealed associations with lateral OFC covariance networks. Finally, the brain-wide cortical alterations of amotivation were significantly correlated with normative functional and structural white-matter connectivity profiles of the right medial and left lateral OFC as well as adjacent prefrontal and limbic regions. Our work identifies OFC alterations as a possible transdiagnostic signature of amotivation and provides insights into network associations underlying the system-wide cortical alterations of negative symptoms across SCZ and BD.

Introduction Brain structural differences consistent with an older-appearing brain have been reported in people with epilepsy, but the extent to which these differences reflect clinical characteristics vs broader socioeconomic context is unclear. We investigated whether country-level socioeconomic factors are associated with neuroanatomical differences in adults with epilepsy using MRI-based age prediction, along with epilepsy subtype, sex, and clinical factors. Methods Structural MRI and clinical data were collected from 26 epilepsy centres across 12 countries in the Americas, Australia, Europe, Asia and Africa. MRI-based age estimates were estimated using a previously developed prediction model trained on 29,175 healthy subjects. Brain predicted age difference (BrainPAD) was calculated as the difference between MRI-predicted brain age and chronological age. National gross domestic product (GDP) per capita and income inequality (Gini index) were obtained from the World Bank. Associations between BrainPAD and epilepsy subtype (temporal lobe epilepsy, extratemporal epilepsy, and genetic generalised epilepsy), national socioeconomic context (GDP per capita and Gini index), age and sex were assessed using regression models. Results We analyzed 2,109 individuals with epilepsy and 1,041 healthy non-epilepsy controls (57% female; median age = 35; range 17-83). BrainPAD was higher in epilepsy than controls (β 4.2 years, SE 0.4; t=10.6), with increases ranging from 2.5 to 6 years across subtypes. Male sex was associated with 1 year higher BrainPAD relative to females (SE 0.33, t=3.12). There were no main effects of GDP or Gini index; however, significant interactions between were observed. The effect of epilepsy on BrainPAD was greater in countries with lower GDP per capita (t=-2.74) and higher income inequality (t=2.72). Conclusions Clinical factors and socioeconomic context both influence brain structural ageing in epilepsy. These findings highlight the importance of geographic and economic diversity in neuroimaging research and underscore the relevance of global socioeconomic context when interpreting brain health measures.

Introduction: [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) frequently reveals hypometabolism extending beyond the epileptogenic zone in focal cortical dysplasia (FCD). However, it is unclear whether these peripheral hypometabolic areas harbour pathological cells potentially contributing to seizure generation. This study characterized histopathology in the lesion epicentre vs borders of the FDG-PET hypometabolism-informed resections in pediatric patients undergoing epilepsy surgery. Methods: Fourteen children with intractable, extra-temporal focal epilepsy (mean age 9.0±5.0 years; 9 female) were retrospectively reviewed. FDG-PET contributed significantly to surgical planning in all cases, with the resection encompassing the visually-apparent MRI signal abnormalities as well as areas of surrounding hypometabolism when safely feasible. Multiple pathological specimens were obtained from the epicentre and surrounding hypometabolic areas. Overall, 136 specimens were analyzed: 64 epicentre (mean 4.6±3.2/patient) and 72 border (mean 5.1±3.5/patient). Results: Pathology was identified in 75% of epicentre specimens (59% with frank FCD (fFCD) IIa/b, 16% with dysmorphic neurons only (DNO)). Border specimens showed pathology in 62% (31% fFCD IIa/b, 31% DNO). We fitted a Bayesian logistic mixed model with pathology as outcome variable, location as predictor, and subject as a random effect. Compared to negative pathology, the log-odds of fFCD in the epicentre was 1.00 (confidence interval (CI) 0.32, 1.77) and -1.25 in the border (CI -2.17, -0.40). The log-odds of DNO vs negative pathology was non-significant in both locations. All patients achieved Engel Ia status at one-year follow-up with no long-term neurological deficits. Conclusion: These findings suggest a gradient of histopathology, with fFCD concentrated in the epicentre and DNO present in both the epicentre and hypometabolic borders. Thus, FDG-PET may be used to better detect the histopathological borders of FCD type II, and the high seizure-freedom rate presented here supports the inclusion of these surrounding hypometabolic regions in the surgical resection (when safe to do so), potentially improving the likelihood of removing epileptogenic cells.

Temporal lobe epilepsy (TLE), the most common pharmaco-resistant epilepsy in adults, has been linked to structural brain changes extending beyond the mesiotemporal areas. While not traditionally viewed as a neurodegenerative disorder, recent ex-vivo studies have shown elevated levels of misfolded tau protein in TLE. This study investigated tau deposition in TLE patients using the in-vivo PET tracer [18F]MK-6240. We studied 28 TLE patients and 28 healthy controls to assess tau uptake and its relationship with brain connectivity, clinical variables, and cognitive function. Compared to controls, TLE patients exhibited markedly increased [18F]MK-6240 uptake in bilateral superior and medial temporal regions and the parietal cortex, with tau accumulation following regional functional and structural connectivity and cognitive impairment. These findings suggest that tau accumulation contributes to cognitive decline observed in TLE, supporting a potential role of tau in epilepsy-related neurodegeneration.

The amygdala is a subcortical region in the mesiotemporal lobe that plays a key role in emotional and sensory functions. Conventional neuroimaging experiments treat this structure as a single, uniform entity, but there is ample histological evidence for subregional heterogeneity in microstructure and function. The current study characterized subregional structure-function coupling in the human amygdala, integrating post-mortem histology and in vivo MRI at ultra-high fields. Core to our work was a novel neuroinformatics approach that leveraged multiscale texture analysis as well as non-linear dimensionality reduction techniques to identify salient dimensions of microstructural variation in a 3D post-mortem histological reconstruction of the human amygdala. We observed two axes of subregional variation in this region, describing inferior-superior as well as mediolateral trends in microstructural differentiation that in part recapitulated established atlases of amygdala subnuclei. Translating our approach to in vivo MRI data acquired at 7 Tesla, we could demonstrate the generalizability of these spatial trends across 10 healthy adults. We then cross-referenced microstructural axes with functional blood-oxygen-level dependent (BOLD) signal analysis obtained during task-free conditions, and revealed a close association of structural axes with macroscale functional network embedding, notably the temporo-limbic, default mode, and sensory-motor networks. Our novel multiscale approach consolidates descriptions of amygdala anatomy and function obtained from histological and in vivo imaging techniques.

BACKGROUND AND OBJECTIVES:Automated MRI analyses have identified variable patterns of cortical atrophy in Rasmussen syndrome. In this study, we aim to identify imaging phenotypes of Rasmussen syndrome, to clinically characterize these phenotypes, and to validate this imaging-based approach through histopathologic analysis. METHODS:For this retrospective case-control study, individuals with Rasmussen syndrome diagnosed according to the European Consensus Statement and at least one 3D T1-weighted MRI scan (<20 years after onset) were identified from the University Hospital Bonn (1995-2023). Healthy controls were selected from databases at the University Hospital Bonn, Charité University Hospital Berlin, and the Human Connectome Project. Disease epicenters, describing brain regions highly connected to atrophy regions, were mapped individually using network-based atrophy modeling. Subtypes were identified through k-means clustering. Neuropsychological test results and results from neuropathologic analyses of biopsies were ascertained, and correlations between subtype-specific atrophy maps and normative maps (enhancing neuro imaging genetics through meta analysis [ENIGMA] and neuromaps toolbox) were used to characterize atrophy profiles and epicenter susceptibility. RESULTS:The study incorporated 54 individuals with Rasmussen syndrome (median age at MRI: 18 years, range 2-61, 65% female) and 270 healthy individuals (median age at MRI: 26.5 years, range 3-61, 49% female). Four distinct atrophy subtypes were identified (temporoparietal, centrotemporal, frontal, and bilateral). Individuals with the centrotemporal subtype were younger at onset (median 5.5 years) than individuals with temporoparietal (median 11.5 years, p = 0.02) and frontal (median 6 years, p = 0.02) subtypes. Most severe neuropsychological impairment was observed for the temporoparietal and frontal subtypes. In the temporoparietal and frontal subtypes, atrophy occurred preferentially in hubs (r = -0.28, p = 0.006; r = -0.30, p = 0.02). Disease epicenter susceptibility was associated with higher cortical thickness (r = -0.57, p = 0.005), lower myelin content (r = 0.47, p = 0.02), lower cerebral blood flow (r = 0.42, p = 0.03), lower blood volume (r = 0.57, p = 0.006), and lower oxygen metabolism (r = 0.47, p = 0.01). Brain biopsies showing strong inflammation were taken from likely epicenters, whereas biopsies with weaker inflammation came from less likely epicenters (p = 0.04). DISCUSSION:Using Rasmussen syndrome as a model, we validate imaging-based mapping of individual disease epicenters with histopathologic evidence. With further validation, network-based mapping of individual disease epicenters could potentially be used in Rasmussen syndrome to guide biopsy site selection, inform treatment decisions, and improve outcome prognoses.

The default mode network (DMN) is implicated in many aspects of complex thought and behavior. Here, we leverage postmortem histology and in vivo neuroimaging to characterize the anatomy of the DMN to better understand its role in information processing and cortical communication. Our results show that the DMN is cytoarchitecturally heterogenous, containing cytoarchitectural types that are variably specialized for unimodal, heteromodal and memory-related processing. Studying diffusion-based structural connectivity in combination with cytoarchitecture, we found the DMN contains regions receptive to input from sensory cortex and a core that is relatively insulated from environmental input. Finally, analysis of signal flow with effective connectivity models showed that the DMN is unique amongst cortical networks in balancing its output across the levels of sensory hierarchies. Together, our study establishes an anatomical foundation from which accounts of the broad role the DMN plays in human brain function and cognition can be developed.

In humans, many neurobiological features of the cortex-including gene expression patterns, microstructure, and functional connectivity-vary systematically along a sensorimotor-association (S-A) axis of brain organisation. To date, it is still poorly understood whether inter-individual differences in patterns of S-A axis capture these robust spatial relationships across neurobiological properties observed at the group-level. Here, we examine inter-individual differences in structural and functional properties of the S-A axis, namely cortical microstructure, geodesic distances, and the functional gradient, in a sample of young adults from the Human Connectome Project (N = 992, including 328 twins). We quantified heritable variation associated with inter-individual differences in the S-A axis, and assessed whether structural and functional properties that are highly spatially correlated at the group-level also share genetic underpinnings. To consider measurement errors in resting-state functional connectivity data and their impact on properties of the S-A axis, we used a multivariate twin design capable of disentangling individual-level variation in both intra- and inter-individual differences. After accounting for some of the intra-individual variation, we found average heritable individual differences in both the functional gradient h twin 2 = 57 % , cortical microstructure h twin 2 = 43 % , and geodesic distances h twin 2 = 34 % . However, these genetic influences were mostly distinct and deviated from group-level patterns. In particular, we found no significant genetic correlation between the functional gradient and microstructure, while we found both positive and negative genetic associations between the functional gradient and geodesic distances. Our approach highlights the complexity of genetic contributions to brain organisation and may have potential implications for understanding cognitive variability within the S-A axis framework.

Movie-watching is a central aspect of our lives and an important paradigm for understanding the brain mechanisms behind cognition as it occurs in daily life. Contemporary views of ongoing thought argue that the ability to make sense of events in the ‘here and now’ depend on the neural processing of incoming sensory information by auditory and visual cortex, which are kept in check by systems in association cortex. However, we currently lack an understanding of how patterns of ongoing thoughts map onto the different brain systems when we watch a film, partly because methods of sampling experience disrupt the dynamics of brain activity and the experience of movie-watching. Our study established a novel method for mapping thought patterns onto the brain activity that occurs at different moments of a film, which does not disrupt the time course of brain activity or the movie-watching experience. We found moments when experience sampling highlighted engagement with multi-sensory features of the film or highlighted thoughts with episodic features, regions of sensory cortex were more active and subsequent memory for events in the movie was better—on the other hand, periods of intrusive distraction emerged when activity in regions of association cortex within the frontoparietal system was reduced. These results highlight the critical role sensory systems play in the multi-modal experience of movie-watching and provide evidence for the role of association cortex in reducing distraction when we watch films.

BACKGROUND AND OBJECTIVES:Despite informing on the location of functionally relevant white matter tracts, diffusion MRI tractography is not routinely used to guide neurosurgical procedures. The potential of tractography to help avoid postoperative neurologic deficits is not yet fully established. The objective of our study was to assess whether surgeries that incorporated tractography, either alone or in conjunction with other modalities, are associated with a lower risk of long-term postoperative neurologic deficits in patients undergoing resective/ablative intracranial procedures. METHODS:We performed a systematic review with meta-analysis, searching through EMBASE and PubMed databases for all peer-reviewed articles published in English up until December 2024. Studies were included if they reported on intracranial resective or ablative surgeries, if they compared tractography-assisted against non-tractography-assisted approaches, and if they assessed new postoperative neurologic deficits. No restrictions were placed on the age of patients. Studies were assessed for inclusion by 2 independent reviewers, and disagreements were settled by a third. Data extraction was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, quality of studies was evaluated using the GRADE framework, and risk of bias was assessed through a modified version of the Newcastle-Ottawa Quality Assessment Scale for Cohort Studies. Data were pooled using a random-effects model with a Mantel-Haenszel method for estimating risk ratios. The primary outcome consisted in any neurologic deficits present at the last follow-up (≥3 months). RESULTS:Of 5,335 studies initially identified, 8 were included after all stages of review, all of which consisted of resective surgeries. A meta-analysis of 629 patients revealed a 55% risk reduction of postoperative neurologic deficits when tractography was incorporated in the neurosurgical workflow. This benefit was consistent when assessing studies where tractography was exclusively used preoperatively. Furthermore, the incorporation of tractography into intraoperative neuronavigation systems was associated with lower proportions of postoperative neurologic deficits, compared with exclusively preoperative tractography. These benefits were found to be present in several additional subgroup and sensitivity analyses. DISCUSSION:The addition of tractography is associated with a reduced risk of postoperative neurologic deficits in intracranial resective surgeries. Tractography can complement gold standard brain mapping methods such as direct electrical stimulation during awake surgeries or serve as a helpful alternative when electrical stimulation is contraindicated.