Tuber Locations Associated with Infantile Spasms Map to a Common Brain Network

Cohen, Alexander L.; Mulder, Brechtje P. F.; Prohl, Anna K.; Soussand, Louis; Davis, Peter E.; Kroeck, Mallory R; McManus, Peter; Gholipour, Ali; Scherrer, Benoît; Bebin, E. Martina; Wu, Joyce; Northrup, Hope; Krueger, Darcy A.; Şahin, Mustafa; Warfield, Simon K.; Fox, Michael; Peters, Jurriaan M.

doi:10.1002/ana.26015

Cited by 40 publications

(33 citation statements)

References 64 publications

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“…LNM is a new, but extensively validated technique that compares structural lesion locations to normalized resting state functional connectivity maps to identify brain networks disrupted by a given lesion. [11][12][13][14][15][16][17][18][19][20] In brief, resting state functional connectivity between each lesion location and all other brain voxels was computed using a large connectome database from healthy young individuals (n = 1,000, mean age = 21.3 years, range = 18-35 years, 42.7% male). 30 Functional connectivity results were combined across the 1,000 subjects using a random effects analysis, producing a single "lesion network map" for each patient.…”

Section: Lesion Network Mappingmentioning

confidence: 99%

“…lesion-induced syndromes to neuroanatomy. [11][12][13][14][15][16][17][18][19][20] The technique compares lesion locations to normalized resting state functional connectivity maps to determine grouplevel differences. 20,21 Both blindsight patients and blindsight-negative controls have a brain injury causing conscious vision loss, but only blindsight patients have unconscious visual perception.…”

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confidence: 99%

“…Lesion network mapping (LNM) is a new technique that accounts for lesion connectivity and can help link rare lesion‐induced syndromes to neuroanatomy 11–20 . The technique compares lesion locations to normalized resting state functional connectivity maps to determine group‐level differences 20,21 .…”

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confidence: 99%

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Network Localization of Unconscious Visual Perception in Blindsight

Kletenik

Ferguson

Bateman

et al. 2022

Annals of Neurology

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Objective: Blindsight is a disorder where brain injury causes loss of conscious but not unconscious visual perception. Prior studies have produced conflicting results regarding the neuroanatomical pathways involved in this unconscious perception. Methods: We performed a systematic literature search to identify lesion locations causing visual field loss in patients with blindsight (n = 34) and patients without blindsight (n = 35). Resting state functional connectivity between each lesion location and all other brain voxels was computed using a large connectome database (n = 1,000). Connections significantly associated with blindsight (vs no blindsight) were identified. Results: Functional connectivity between lesion locations and the ipsilesional medial pulvinar was significantly associated with blindsight (family wise error p = 0.029). No significant connectivity differences were found to other brain regions previously implicated in blindsight. This finding was independent of methods (eg, flipping lesions to the left or right) and stimulus type (moving vs static). Interpretation: Connectivity to the ipsilesional medial pulvinar best differentiates lesion locations associated with blindsight versus those without blindsight. Our results align with recent data from animal models and provide insight into the neuroanatomical substrate of unconscious visual abilities in patients.

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Section: Lesion Network Mappingmentioning

confidence: 99%

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confidence: 99%

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Network Localization of Unconscious Visual Perception in Blindsight

Kletenik

Ferguson

Bateman

et al. 2022

Annals of Neurology

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“…In the recent work by Cohen et al, 6 the authors applied a novel and exciting method of “lesion mapping” to a large cohort of children with and without ES to identify the networks underlying the development of ES. Cohen’s work extends the functional connectivity-based lesion mapping technique described by Boes et al 7 Specifically, Boes et al found that particular functional deficits can be better predicted by an individual lesion’s functional connectivity than by its specific location in the brain.…”

Section: Commentarymentioning

confidence: 99%

“…Cohen et al 6 have applied this concept of lesion network mapping to TSC using neuroimaging data gathered for the TSC Autism Centre of Excellence Network (TACERN). TACERN is a multicentre prospective study in which patients were enrolled in the first year of life and followed longitudinally through 36 months.…”

Section: Commentarymentioning

confidence: 99%

Infantile Spasms in Tuberous Sclerosis Complex: Lesion or Network?

Joshi¹,

Bear²

2021

Epilepsy Curr

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Objective: Approximately 50% of patients with tuberous sclerosis complex develop infantile spasms, a sudden onset epilepsy syndrome associated with poor neurological outcomes. An increased burden of tubers confers an elevated risk of infantile spasms, but it remains unknown whether some tuber locations confer higher risk than others. Here, we test whether tuber location and connectivity are associated with infantile spasms. Methods: We segmented tubers from 123 children with (n = 74) and without (n = 49) infantile spasms from a prospective observational cohort. We used voxelwise lesion symptom mapping to test for an association between spasms and tuber location. We then used lesion network mapping to test for an association between spasms and connectivity with tuber locations. Finally, we tested the discriminability of identified associations with logistic regression and cross-validation as well as statistical mediation. Results: Tuber locations associated with infantile spasms were heterogenous, and no single location was significantly associated with spasms. However, >95% of tuber locations associated with spasms were functionally connected to the globi pallidi and cerebellar vermis. These connections were specific compared to tubers in patients without spasms. Logistic regression found that globus pallidus connectivity was a stronger predictor of spasms (odds ratio [OR] = 1.96, 95% confidence interval [CI] = 1.10-3.50, P = .02) than tuber burden (OR = 1.65, 95% CI = .90-3.04, P = .11), with a mean receiver operating characteristic area under the curve of .73 (±.1) during repeated cross-validation. Interpretation: Connectivity between tuber locations and the bilateral globi pallidi is associated with infantile spasms. Our findings lend insight into spasm pathophysiology and may identify patients at risk.

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Mapping Lesion-Related Epilepsy to a Human Brain Network

et al. 2023

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ImportanceIt remains unclear why lesions in some locations cause epilepsy while others do not. Identifying the brain regions or networks associated with epilepsy by mapping these lesions could inform prognosis and guide interventions.ObjectiveTo assess whether lesion locations associated with epilepsy map to specific brain regions and networks.Design, Setting, and ParticipantsThis case-control study used lesion location and lesion network mapping to identify the brain regions and networks associated with epilepsy in a discovery data set of patients with poststroke epilepsy and control patients with stroke. Patients with stroke lesions and epilepsy (n = 76) or no epilepsy (n = 625) were included. Generalizability to other lesion types was assessed using 4 independent cohorts as validation data sets. The total numbers of patients across all datasets (both discovery and validation datasets) were 347 with epilepsy and 1126 without. Therapeutic relevance was assessed using deep brain stimulation sites that improve seizure control. Data were analyzed from September 2018 through December 2022. All shared patient data were analyzed and included; no patients were excluded.Main Outcomes and MeasuresEpilepsy or no epilepsy.ResultsLesion locations from 76 patients with poststroke epilepsy (39 [51%] male; mean [SD] age, 61.0 [14.6] years; mean [SD] follow-up, 6.7 [2.0] years) and 625 control patients with stroke (366 [59%] male; mean [SD] age, 62.0 [14.1] years; follow-up range, 3-12 months) were included in the discovery data set. Lesions associated with epilepsy occurred in multiple heterogenous locations spanning different lobes and vascular territories. However, these same lesion locations were part of a specific brain network defined by functional connectivity to the basal ganglia and cerebellum. Findings were validated in 4 independent cohorts including 772 patients with brain lesions (271 [35%] with epilepsy; 515 [67%] male; median [IQR] age, 60 [50-70] years; follow-up range, 3-35 years). Lesion connectivity to this brain network was associated with increased risk of epilepsy after stroke (odds ratio [OR], 2.82; 95% CI, 2.02-4.10; P &lt; .001) and across different lesion types (OR, 2.85; 95% CI, 2.23-3.69; P &lt; .001). Deep brain stimulation site connectivity to this same network was associated with improved seizure control (r, 0.63; P &lt; .001) in 30 patients with drug-resistant epilepsy (21 [70%] male; median [IQR] age, 39 [32-46] years; median [IQR] follow-up, 24 [16-30] months).Conclusions and RelevanceThe findings in this study indicate that lesion-related epilepsy mapped to a human brain network, which could help identify patients at risk of epilepsy after a brain lesion and guide brain stimulation therapies.

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Tuber Locations Associated with Infantile Spasms Map to a Common Brain Network

Cited by 40 publications

References 64 publications

Network Localization of Unconscious Visual Perception in Blindsight

Network Localization of Unconscious Visual Perception in Blindsight

Infantile Spasms in Tuberous Sclerosis Complex: Lesion or Network?

Mapping Lesion-Related Epilepsy to a Human Brain Network

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