Patterns Of Disconnection Research Articles

Multivariate and network lesion mapping reveals distinct architectures of domain-specific post-stroke cognitive impairments

BackgroundThe purpose of this study was to identify patterns of structural disconnection and multivariate lesion-behaviour relationships associated with post-stroke deficits across six commonly impacted cognitive domains: executive function, language, memory, numerical processing, praxis, and visuospatial attention. MethodsStroke survivors (n = 593) completed a brief domain-specific cognitive assessment (the Oxford Cognitive Screen (OCS)) during acute hospitalisation. Network-level and multivariate (sparce canonical correlation) lesion mapping analyses were conducted to identify focal neural correlates and distributed patterns of structural disconnection associated with impairment on each of the 16 OCS measures. ResultsNetwork-level and multivariate lesion mapping analyses identified significant correlates for 12/16 and 10/16 OCS measures, respectively which were largely consistent with correlates reported in past work. Language impairments were reliably localised to network- and voxel-level correlates centred in left fronto-temporal regions. Memory impairments were associated with disconnection in a large network of left hemisphere regions. Number processing deficits were associated with damage to voxels centred in the left insular/opercular cortex, as well as disconnection within the surrounding white matter tracts. Within the domain of attention, different subtypes of visuospatial neglect were linked to distinct but partially overlapping patterns of disconnection and voxel-level damage. Praxis impairment was not linked to any voxel-level regions but was significantly associated with disconnection within the left hemisphere dorsal attention network. ConclusionThese results highlight the utility of routine, domain-specific cognitive assessment and imaging data for theoretically-driven lesion mapping analyses, while providing novel insight into the complex anatomical correlates of common and debilitating post-stroke cognitive impairments.

Deep learning disconnectomes to accelerate and improve long-term predictions for post-stroke symptoms.

This study investigates the efficacy of deep-learning models in expediting the generation of disconnectomes for individualized prediction of neuropsychological outcomes one year after stroke. Utilising a 3D U-Net network, we trained a model on a dataset of N = 1333 synthetic lesions and corresponding disconnectomes, subsequently applying it to N = 1333 real stroke lesions. The model-generated disconnection patterns were then projected into a two-dimensional 'morphospace' via uniform manifold approximation and projection for dimension reduction dimensionality reduction. We correlated the positioning within this morphospace with one-year neuropsychological scores across 86 metrics in a novel cohort of 119 stroke patients, employing multiple regression models and validating the findings in an out-of-sample group of 20 patients. Our results demonstrate that the 3D U-Net model captures the critical information of conventional disconnectomes with a notable increase in efficiency, generating deep-disconnectomes 720 times faster than current state-of-the-art software. The predictive accuracy of neuropsychological outcomes by deep-disconnectomes averaged 85.2% (R 2 = 0.208), which significantly surpassed the conventional disconnectome approach (P = 0.009). These findings mark a substantial advancement in the production of disconnectome maps via deep learning, suggesting that this method could greatly enhance the prognostic assessment and clinical management of stroke survivors by incorporating disconnection patterns as a predictive tool.

Reprint of: Profiling the plight of disconnected youth in America

In a successful transition from youth to adulthood, individuals pass through a sequence of roles involving school, work, and family formation that culminate in their becoming self-sufficient adults. However, some “disconnected” youth spend extended periods of time outside of any role that constitutes an element of the pathway towards adult independence. Assisting these youth requires a systematic understanding of what “disconnection” means, how many disconnected youth there are, who these youth are, and how the scale of the problem has evolved over time. Using the National Longitudinal Surveys of Youth for 1997 and 1979, we address these issues by creating concrete definitions of “disconnection spells” using rich data on youths’ enrollment, work, and personal histories. We estimate a multi-state duration model to account for right censoring and to understand differences across salient sub-groups. Our estimates imply that in the early 2000s, almost 19% and 25% of young men and young women, respectively, experienced a disconnection spell by age 23 using our basic definition. These rates are substantially higher for certain sub-groups defined by race/ethnicity, parental education, and government aid receipt, rising as high as 30+% by age 23. Approximately 60% of youth with a disconnection spell have it last longer than a year, and close to 10% have it last longer than 4 years. However, once reconnected, a majority of youth go at least three years without a re-disconnection spell. Patterns of initial disconnection changed markedly from the 1980s to the 2000s, as young women saw a 12 percentage point decline over time. Moreover, the Black-White gap in disconnection has fallen for women, but increased for men. Our profile of disconnection experiences provides a starting point for government agencies aiming to understand where, how, and with whom to intervene to prevent lengthy disconnection spells.

Clinical and structural disconnectome evaluation in a case of optic aphasia

Optic Aphasia (OA) and Associative Visual Agnosia (AVA) are neuropsychological disorders characterized by impaired naming on visual presentation. From a cognitive point of view, while stimulus identification is largely unimpaired in OA (where access to semantic knowledge is still possible), in AVA it is not. OA has been linked with right hemianopia and disconnection of the occipital right-hemisphere (RH) visual processing from the left hemisphere (LH) language areas.In this paper, we describe the case of AA, an 81-year-old housewife suffering from a deficit in naming visually presented stimuli after left occipital lesion and damage to the interhemispheric splenial pathway. AA has been tested through a set of tasks assessing different levels of visual object processing. We discuss behavioral performance as well as the pattern of lesion and disconnection in relation to a neurocognitive model adapted from Luzzatti and colleagues (1998). Despite the complexity of the neuropsychological picture, behavioral data suggest that semantic access from visual input is possible, while a lesion-based structural disconnectome investigation demonstrated the splenial involvement.Altogether, neuropsychological and neuroanatomical findings support the assumption of visuo-verbal callosal disconnection compatible with a diagnosis of OA.

Narratives of Disconnection: A Life Course Perspective of Methamphetamine Use Among Sexual Minority Men Living with HIV.

Sexual minority men (SMM) are exposed to societal and structural stressors that translate into poor health outcomes. One such outcome is substance use, which research has long documented as a prominent disparity among SMM. Methamphetamine is a particularly deleterious substance for SMM because its use is often framed as a coping response to social and structural stressors. Guided by stress and coping theory and a life course perspective, the purpose of this qualitative study is to assess the development of coping strategies in the context of prominent social and structural determinants among SMM living with HIV who use methamphetamine. Data were collected from 2016 to 2018 via in-depth interviews with 24 SMM living with HIV who use methamphetamine in San Francisco, CA. Mean age of participants was 47 and over half self-identified as ethnoracial minorities. Narrative analysis surfaced a sequential pattern of disconnection at foundational, relational, and recovery levels. This analysis revealed that multi-level stressors were present across the life course that amplified engagement in methamphetamine use. Findings highlight the benefits of holistic, integrated, and trauma-informed approaches to address the function of methamphetamine use as a response to societal, cultural, and institutional processes of stigmatization and discrimination. Peer-based approaches may also be beneficial to reframe the ways in which SMM living with HIV who use methamphetamine form and sustain relationships.

Hayling and stroop tests tap dissociable deficits and network-level neural correlates.

Although many executive function screens have been developed, it is not yet clear whether these assessments are equally effective in detecting post-stroke deficits of initiation and inhibition. This study presents a comparative analysis of the Stroop and Hayling tests aiming to evaluate whether these tests measure the same underlying cognitive functions and to identify the neural correlates of the deficits detected by both tasks. Sixty six stroke survivors and 70 healthy ageing controls completed the Hayling and Stroop tests. Stroke patients were found to exhibit qualitative performance differences across analogous Stroop and Hayling Test metrics intended to tap initiation and inhibition. The Stroop test was found to have high specificity to abnormal performance, but low sensitivity relative to the Hayling Test. Minimal overlap was present between the network-level correlates of analogous Stroop and Hayling Test metrics. Hayling Task strategy use metrics were significantly associated with distinct patterns of disconnection in stroke survivors, providing novel insight into the neural correlates of fine-grained behavioural patterns. Overall, these findings strongly suggest that the functions tapped by the Stroop and Hayling Test are both behaviourally and anatomically dissociable. The Hayling Test was found to offer improved sensitivity and detail relative to the Stroop test. This novel demonstration of the Hayling Test within the stroke population suggests that this task represents an effective measure for quantifying post-stroke initiation and inhibition deficits.

Elastic deformation as a tool to investigate watershed storage connectivity

Storage-discharge relationships and dynamic changes in storage connectivity remain key unknowns in understanding and predicting watershed behavior. In this study, we use Global Positioning System measurements of load-induced Earth surface displacement as a proxy for total water storage change in four climatologically diverse mountain watersheds in the western United States. Comparing total water storage estimates with stream-connected storage derived from hydrograph analysis, we find that each of the investigated watersheds exhibits a characteristic seasonal pattern of connection and disconnection between total and stream-connected storage. We investigate how the degree and timing of watershed-scale connectivity is related to the timing of precipitation and seasonal changes in dominant hydrologic processes. Our results show that elastic deformation of the Earth due to water loading is a powerful new tool for elucidating dynamic storage connectivity and watershed discharge response across scales in space and time.

Profiling the plight of disconnected youth in America

In a successful transition from youth to adulthood, individuals pass through a sequence of roles involving school, work, and family formation that culminate in their becoming self-sufficient adults. However, some “disconnected” youth spend extended periods of time outside of any role that constitutes an element of the pathway towards adult independence. Assisting these youth requires a systematic understanding of what “disconnection” means, how many disconnected youth there are, who these youth are, and how the scale of the problem has evolved over time. Using the National Longitudinal Surveys of Youth for 1997 and 1979, we address these issues by creating concrete definitions of “disconnection spells” using rich data on youths’ enrollment, work, and personal histories. We estimate a multi-state duration model to account for right censoring and to understand differences across salient sub-groups. Our estimates imply that in the early 2000s, almost 19% and 25% of young men and young women, respectively, experienced a disconnection spell by age 23 using our basic definition. These rates are substantially higher for certain sub-groups defined by race/ethnicity, parental education, and government aid receipt, rising as high as 30+% by age 23. Approximately 60% of youth with a disconnection spell have it last longer than a year, and close to 10% have it last longer than 4 years. However, once reconnected, a majority of youth go at least three years without a re-disconnection spell. Patterns of initial disconnection changed markedly from the 1980s to the 2000s, as young women saw a 12 percentage point decline over time. Moreover, the Black-White gap in disconnection has fallen for women, but increased for men. Our profile of disconnection experiences provides a starting point for government agencies aiming to understand where, how, and with whom to intervene to prevent lengthy disconnection spells.

Convergence of visual and motor awareness in human parietal cortex.

Brain lesions sometimes induce a failure of recognition of one's own deficits (anosognosia). Lack of deficit awareness may underlie damage of modality-specific systems, e.g., visual cortex for visual anosognosia or motor/premotor cortex for motor anosognosia. However, focal lesions induce widespread remote structural and functional disconnection, and anosognosia, independent of modality, may also involve common neural mechanisms. Here, we study the neural correlates of Anton syndrome (AS), anosognosia of blindness, and compare them with anosognosia for hemiplegia to test if they share different or common mechanisms. We measured both local damage and patterns of structural-functional disconnection as predicted from healthy normative atlases. AS depends on bilateral striate and extra-striate occipital damage, and disconnection of ventral and dorsal frontoparietal regions involved in attention control. Visual and motor anosognosia each share damage of modality-specific regions, but also involve the disruption of white matter tracts leading to functional disconnection within dorsal frontal-parietal regions that play critical roles in motor control, visuospatial attention, and multi-sensory integration. These results reveal the unique shared combination of content-specific and supra-modal mechanisms in anosognosia. This article is protected by copyright. All rights reserved.

The need for hemispheric separation in pairwise structural disconnection studies.

The development of new approaches indirectly measuring the structural disconnectome has recently led to an increase in studies investigating pairwise structural disconnections following brain damage. Previous studies jointly analyzed patients with left hemispheric and patients with right hemispheric lesions when investigating a behavior of interest. An alternative approach would be to perform analyses separated by hemisphere, which has been applied in only a minority of studies to date. The present simulation study investigated whether joint or separate analyses (or both equally) are appropriate to reveal the ground truth disconnections. In fact, both approaches resulted in very different patterns of disconnection. In contrast to analyses separated by hemisphere, joint analyses introduced a bias to the disadvantage of intra-hemispheric disconnections. Intra-hemispheric disconnections were statistically underpowered in the joint analysis and thus surpassed the significance threshold with more difficulty compared to inter-hemispheric disconnections. This statistical imbalance was also shown by a greater number of significant inter-hemispheric than significant intra-hemispheric disconnections. This bias from joint analyses is based on mechanisms similar to those underlying the "partial injury problem." We therefore conclude that pairwise structural disconnections in patients with unilateral left hemispheric and with unilateral right hemispheric lesions exhibiting a specific behavior (or disorder) of interest should be studied separately by hemisphere rather than in a joint analysis.

Thalamostriatal disconnection underpins long-term seizure freedom in frontal lobe epilepsy surgery.

Around 50% of patients undergoing frontal lobe surgery for focal drug-resistant epilepsy become seizure free post-operatively; however, only about 30% of patients remain seizure free in the long-term. Early seizure recurrence is likely to be caused by partial resection of the epileptogenic lesion, whilst delayed seizure recurrence can occur even if the epileptogenic lesion has been completely excised. This suggests a coexistent epileptogenic network facilitating ictogenesis in close or distant dormant epileptic foci. As thalamic and striatal dysregulation can support epileptogenesis and disconnection of cortico-thalamostriatal pathways through hemispherotomy or neuromodulation can improve seizure outcome regardless of focality, we hypothesize that projections from the striatum and the thalamus to the cortex may contribute to this common epileptogenic network. To this end, we retrospectively reviewed a series of 47 consecutive individuals who underwent surgery for drug-resistant frontal lobe epilepsy. We performed voxel-based and tractography disconnectome analyses to investigate shared patterns of disconnection associated with long-term seizure freedom. Seizure freedom after 3 and 5 years was independently associated with disconnection of the anterior thalamic radiation and anterior cortico-striatal projections. This was also confirmed in a subgroup of 29 patients with complete resections, suggesting these pathways may play a critical role in supporting the development of novel epileptic networks. Our study indicates that network dysfunction in frontal lobe epilepsy may extend beyond the resection and putative epileptogenic zone. This may be critical in the pathogenesis of delayed seizure recurrence as thalamic and striatal networks may promote epileptogenesis and disconnection may underpin long-term seizure freedom.

Longitudinal prediction of motor dysfunction after stroke: a disconnectome study

Motricity is the most commonly affected ability after a stroke. While many clinical studies attempt to predict motor symptoms at different chronic time points after a stroke, longitudinal acute-to-chronic studies remain scarce. Taking advantage of recent advances in mapping brain disconnections, we predict motor outcomes in 62 patients assessed longitudinally two weeks, three months, and one year after their stroke. Results indicate that brain disconnection patterns accurately predict motor impairments. However, disconnection patterns leading to impairment differ between the three-time points and between left and right motor impairments. These results were cross-validated using resampling techniques. In sum, we demonstrated that while some neuroplasticity mechanisms exist changing the structure–function relationship, disconnection patterns prevail when predicting motor impairment at different time points after stroke.

Stroke disconnectome decodes reading networks

Cognitive functional neuroimaging has been around for over 30 years and has shed light on the brain areas relevant for reading. However, new methodological developments enable mapping the interaction between functional imaging and the underlying white matter networks. In this study, we used such a novel method, called the disconnectome, to decode the reading circuitry in the brain. We used the resulting disconnection patterns to predict a typical lesion that would lead to reading deficits after brain damage. Our results suggest that white matter connections critical for reading include fronto-parietal U-shaped fibres and the vertical occipital fasciculus (VOF). The lesion most predictive of a reading deficit would impinge on the left temporal, occipital, and inferior parietal gyri. This novel framework can systematically be applied to bridge the gap between the neuropathology of language and cognitive neuroscience.

Bedrock depth influences spatial patterns of summer baseflow, temperature and flow disconnection for mountainous headwater streams

Abstract. In mountain headwater streams, the quality and resilience of summer cold-water habitat is generally regulated by stream discharge, longitudinal stream channel connectivity and groundwater exchange. These critical hydrologic processes are thought to be influenced by the stream corridor bedrock contact depth (sediment thickness), a parameter often inferred from sparse hillslope borehole information, piezometer refusal and remotely sensed data. To investigate how local bedrock depth might control summer stream temperature and channel disconnection (dewatering) patterns, we measured stream corridor bedrock depth by collecting and interpreting 191 passive seismic datasets along eight headwater streams in Shenandoah National Park (Virginia, USA). In addition, we used multi-year stream temperature and streamflow records to calculate several baseflow-related metrics along and among the study streams. Finally, comprehensive visual surveys of stream channel dewatering were conducted in 2016, 2019 and 2021 during summer low flow conditions (124 total km of stream length). We found that measured bedrock depths along the study streams were not well-characterized by soils maps or an existing global-scale geologic dataset where the latter overpredicted measured depths by 12.2 m (mean) or approximately four times the average bedrock depth of 2.9 m. Half of the eight study stream corridors had an average bedrock depth of less than 2 m. Of the eight study streams, Staunton River had the deepest average bedrock depth (3.4 m), the coldest summer temperature profiles and substantially higher summer baseflow indices compared to the other study steams. Staunton River also exhibited paired air and water annual temperature signals suggesting deeper groundwater influence, and the stream channel did not dewater in lower sections during any baseflow survey. In contrast, Paine Run and Piney River did show pronounced, patchy channel dewatering, with Paine Run having dozens of discrete dry channel sections ranging from 1 to greater than 300 m in length. Stream dewatering patterns were apparently influenced by a combination of discrete deep bedrock (20+ m) features and more subtle sediment thickness variation (1–4 m) depending on local stream valley hydrogeology. In combination, these unique datasets show the first large-scale empirical support for existing conceptual models of headwater stream disconnection based on spatially variable underflow capacity and shallow groundwater supply.

Mapping lesion, structural disconnection, and functional disconnection to symptoms in semantic aphasia

Patients with semantic aphasia have impaired control of semantic retrieval, often accompanied by executive dysfunction following left hemisphere stroke. Many but not all of these patients have damage to the left inferior frontal gyrus, important for semantic and cognitive control. Yet semantic and cognitive control networks are highly distributed, including posterior as well as anterior components. Accordingly, semantic aphasia might not only reflect local damage but also white matter structural and functional disconnection. Here, we characterise the lesions and predicted patterns of structural and functional disconnection in individuals with semantic aphasia and relate these effects to semantic and executive impairment. Impaired semantic cognition was associated with infarction in distributed left-hemisphere regions, including in the left anterior inferior frontal and posterior temporal cortex. Lesions were associated with executive dysfunction within a set of adjacent but distinct left frontoparietal clusters. Performance on executive tasks was also associated with interhemispheric structural disconnection across the corpus callosum. In contrast, poor semantic cognition was associated with small left-lateralized structurally disconnected clusters, including in the left posterior temporal cortex. Little insight was gained from functional disconnection symptom mapping. These results demonstrate that while left-lateralized semantic and executive control regions are often damaged together in stroke aphasia, these deficits are associated with distinct patterns of structural disconnection, consistent with the bilateral nature of executive control and the left-lateralized yet distributed semantic control network.

Golden Eagle Optimized Control for a Dual Stage Photovoltaic Residential System with Electric Vehicle Charging Capability

ABSTRACT In this article, the control of a grid-connected, single-phase, dual-stage photovoltaic (PV) residential system with electric vehicle (EV)-charging capability is being presented. A residential system faces a lot of dynamic conditions such as changing atmospheric condition or random patterns of load connection or disconnection as well as power failure. In this regard, this article proposes the optimization of proportional and integral gains selection of the bidirectional DC/DC converter (BDC) PI controller through golden eagle optimization (GEO) algorithm to improve the system performance. The system is subjected to various induced dynamic conditions simulated in MATLAB Simulink environment and the performance is compared with particle swarm optimization, genetic algorithm, and gains obtained through hit and trial. In comparison with other techniques, GEO algorithm provides optimum BDC PI gains, as a result, the DC-link voltage achieves 1.5 times shorter settling time. During the non-linear load changes and voltage swell condition, the settling time is 2 times shorter. Settling time of the EV battery power shows 1.7 times reduction. The transient response of the PV power also shows dramatic improvement with 3 times faster settling time during solar insolation changes. During the sudden non-linear load changes, the momentary transients die 1.5 times faster. Moreover, a seamless control is developed to achieve a seamless transition from islanded mode to grid connected mode and vice versa. The proposed system achieves unity power factor and complies with the IEEE -519 power quality standard.

FV 24 Connectome-based lesion symptom mapping: Disconnection patterns underlying specific aspects of motor impairment after stroke

Introduction: An accurate prediction of motor impairment from lesion information after stroke remains challenging, highlighting the complexity of structure-function relationships. While corticospinal tract (CST) integrity has been shown to correlate with motor impairment after stroke1, far less is known about the functional relevance of cortico-cortical connections for distinct aspects of motor function. Therefore, we investigated whether it is possible to infer distinct aspects of individual motor impairment and identify crucial task-specific connections using connection-based lesion-symptom mapping (CLSM) in acute stroke patients. Methods: Individual disconnectomes were estimated for 114 ischemic stroke patients using lesion masks designed based on routine MRI data and a normative structural connectome 2 . Relative grip strength and four subtests of the Action Research Arm Test 3 were performed to assess movements with varying demands of multi-joint movements, strength and fine-grained control. Nested and cross-validated support vector regressions (SVR) estimated impairment across motor tasks based on CLSM data and CST damage. Results: For each motor task, CLSM-SVR significantly predicted individual motor impairment (p<0.05 permutation testing) with higher or similar accuracy compared to CST-SVR. CLSM and CST-integrity represented largely independent aspects of variance in motor impairment. Permutation testing identified disconnection patterns underlying SVR predictions (Fig. 1). Discussion: Disconnections between ipsilesional subcortical motor areas and bihemispheric cortical motor areas were indicative of impairment across all motor tasks. Movements relying on fine-grained motor control were impacted by ipsilesional motor-temporal, and -prefrontal disconnections. Multi-joint movements involving proximal musculature relied on diverse interhemispheric (pre-)motor-prefrontal and -temporal connections, which may reflect several compensatory ways of motor execution. In summary, lesion-induced cortico-cortical disconnections were associated with distinct aspects of individual motor impairment, highlighting the potential of CLSM to further our understanding of crucial white matter structures in the human motor network.

Structural brain splitting is a hallmark of Granulin-related frontotemporal dementia

Frontotemporal dementia associated with granulin (GRN) mutations presents asymmetric brain atrophy. We applied a Minimum Spanning Tree plus an Efficiency Cost Optimization approach to cortical thickness data in order to test whether graph theory measures could identify global or local impairment of connectivity in the presymptomatic phase of pathology, where other techniques failed in demonstrating changes.We included 52 symptomatic GRN mutation carriers (SC), 161 presymptomatic GRN mutation carriers (PSC) and 341 non-carriers relatives from the Genetic Frontotemporal dementia research Initiative cohort. Group differences of global, nodal and edge connectivity in (Minimum Spanning Tree plus an Efficiency Cost Optimization) graph were tested via Structural Equation Models.Global graph perturbation was selectively impaired in SC compared to non-carriers, with no changes in PSC. At the local level, only SC exhibited perturbation of frontotemporal nodes, but edge connectivity revealed a characteristic pattern of interhemispheric disconnection, involving homologous parietal regions, in PSC.Our results suggest that GRN-related frontotemporal dementia resembles a disconnection syndrome, with interhemispheric disconnection between parietal regions in presymptomatic phases that progresses to frontotemporal areas as symptoms emerge.

White matter disconnectivity fingerprints causally linked to dissociated forms of alexia

For over 150 years, the study of patients with acquired alexia has fueled research aimed at disentangling the neural system critical for reading. An unreached goal, however, relates to the determination of the fiber pathways that root the different visual and linguistic processes needed for accurate word reading. In a unique series of neurosurgical patients with a tumor close to the visual word form area, we combine direct electrostimulation and population-based streamline tractography to map the disconnectivity fingerprints characterizing dissociated forms of alexia. Comprehensive analyses of disconnectivity matrices establish similarities and dissimilarities in the disconnection patterns associated with pure, phonological and lexical-semantic alexia. While disconnections of the inferior longitudinal and posterior arcuate fasciculi are common to all alexia subtypes, disconnections of the long arcuate and vertical occipital fasciculi are specific to phonological and pure alexia, respectively. These findings provide a strong anatomical background for cognitive and neurocomputational models of reading.

Mapping delusions of space onto a structural disconnectome that decouples familiarity and place networks

Interpretation of space is an important determinant of human behaviour. Delusions of space, or reduplicative paramnesias, are a particularly disturbing form of spatial disorientation characterized by the patients' strong belief of place reduplication, transformation or mislocation. Their occurrence following focal brain damage provides a unique opportunity to unveil the structural-functional basis of space misinterpretations.First, we identified reports of lesion-associated reduplicative paramnesias with brain images available through a systematic review of the literature (n = 24). Each lesion was matched with 4 stroke controls and the sample was randomly split in an exploratory (n = 60) and in a validation (n = 60) dataset. Second, we used 178 7T tractographies to compute structural disconnectome maps and analysed lesion topography and disconnection patterns. Delusions of space were significantly associated with structural disconnection of right ventrolateral prefrontal and right temporal regions, and this finding was replicated in the validation sample. Third, we performed a functional meta-analysis of syndrome-related terms. We demonstrated that the structural disconnectomes of delusions of space were spatially correlated with the functional meta-analytic maps of familiarity and place, and replicated the previous evidence that the lesion topography maps are spatially correlated with belief-related functional networks. No association was found with control terms.These results reveal that structural disconnection putatively mediates functional changes associated with reduplicative paramnesias and provide a possible neural basis for the content specificity for places that characterizes these delusional beliefs.