Abnormal segregation patterns in the left frontoparietal and default mode networks of the non-lesioned hemisphere are robustly associated with neglect severity, revealing 'the maladaptive dominance of the non-lesioned hemisphere's intrinsic architecture' as a previously overlooked aspect of neglect pathophysiology.
Key Findings
Results
Abnormal segregation patterns in the left frontoparietal and default mode networks of the non-lesioned hemisphere were robustly associated with neglect severity and spatial attentional bias in chronic spatial neglect patients.
Study used resting-state fMRI data from patients with chronic left spatial neglect following right hemisphere stroke.
Functional connectivity gradient analysis was applied to investigate macroscale functional reorganization in the non-lesioned left hemisphere.
Both neglect severity and spatial attentional bias were used as outcome measures for the association analyses.
The study characterized this as reflecting 'maladaptive dominance of the non-lesioned hemisphere's intrinsic architecture.'
Results
The gradient capturing the unimodal-to-transmodal hierarchy in the left hemisphere was associated with neglect severity.
This gradient represents a well-established macroscale organizational axis of the cortex from primary sensory/motor regions to higher-order transmodal regions.
The association was found specifically in the non-lesioned (left) hemisphere of neglect patients.
Gradients related to the frontoparietal control network were also specifically altered in neglect patients.
This finding implicates large-scale hierarchical cortical organization in the persistence of chronic neglect.
Results
Single-subject analyses confirmed the presence of abnormal segregation patterns in 11 of the 13 patients included in the study.
The total patient sample consisted of 13 patients with chronic left spatial neglect.
11 out of 13 patients (approximately 85%) showed the identified pattern at the individual level.
This individual-level confirmation strengthens the clinical relevance of the group-level findings.
The study design combined group-level gradient analyses with single-subject approaches.
Results
Greater structural integrity of the left inferior fronto-occipital fasciculus (IFOF) was positively associated with the abnormal functional dynamics observed in the non-lesioned hemisphere.
The left IFOF is a white matter tract in the non-lesioned hemisphere, distinct from the right-hemisphere lesioned tracts typically studied in neglect.
The association was positive, meaning greater structural integrity of the left IFOF corresponded to greater abnormality in the functional gradient patterns.
This links structural white matter properties of the intact hemisphere to its functional reorganization in neglect.
The finding suggests the intact hemisphere's white matter architecture contributes to maladaptive functional dynamics.
Background
There is robust prior evidence for right-hemisphere frontoparietal dysfunction, interhemispheric structural disconnection, and maladaptive activity in the left hemisphere as contributors to neglect persistence, but the specific impact on left hemisphere functional reorganization was previously poorly understood.
Spatial neglect is characterized by 'a failure to attend to the contralesional left space' and frequently persists into the chronic stage.
Prior work established roles for right-hemisphere frontoparietal dysfunction and interhemispheric structural disconnection.
The specific impact of right frontoparietal dysfunction on functional (re)organization of the non-lesioned left hemisphere was identified as a gap in knowledge.
This study introduced 'a novel application of functional connectivity gradient analysis' to address this gap.
Discussion
The authors propose a new framework for understanding neglect as an emergent property of large-scale network imbalance, with implications for diagnosis, intervention, and models of hemispheric asymmetries and conscious access.
The framework combines 'innovative gradient-based metrics with classical lesion approaches.'
The findings have 'clinical implications for diagnosis and intervention.'
The results also have 'theoretical consequences for models of hemispheric asymmetries and conscious access.'
The study repositions neglect pathophysiology to include the non-lesioned hemisphere's intrinsic architecture as a key factor.
What This Means
This research suggests that chronic spatial neglect — a condition where stroke patients fail to pay attention to the left side of their world — is not only caused by damage to the right side of the brain, but is also shaped by abnormal organization in the undamaged left hemisphere. The researchers used a technique called functional connectivity gradient analysis on brain resting-state MRI scans from 13 patients with persistent spatial neglect, and found that the left hemisphere showed disrupted patterns of network segregation, particularly in regions involved in attention control and high-level cognition. These disruptions were strongly linked to how severe each patient's neglect was, and were confirmed at the individual patient level in 11 of the 13 cases.
The study also found that the structural integrity of a white matter fiber tract in the undamaged left hemisphere (the inferior fronto-occipital fasciculus) was positively associated with these abnormal functional patterns, suggesting that the left hemisphere's own wiring contributes to its maladaptive reorganization after right-hemisphere stroke. This implies that the intact brain's response to injury — rather than just the injury itself — plays an important role in why neglect persists over time.
This research matters because it opens a new way of thinking about spatial neglect: instead of focusing only on the damaged right hemisphere, clinicians and researchers may also need to consider how the surviving left hemisphere becomes dysfunctionally dominant. This could eventually inform new approaches to diagnosing neglect and designing rehabilitation strategies that target network-level imbalances across both hemispheres, not just the lesioned side.
Takamura Y, Lunven M, Serhan Y, Bourlon C, Ovadia-Caro S, Bartolomeo P. (2026). Disrupted integration-segregation balance in the intact hemisphere in chronic spatial neglect.. Brain structure & function. https://doi.org/10.1007/s00429-026-03137-1