Generative Lesion Pattern Decomposition of Cognitive Impairment after Stroke

Bonkhoff, Anna K.; Lim, Jae‐Sung; Bae, Hee‐Joon; Weaver, Nick A.; Kuijf, Hugo J.; Biesbroek, J. Matthijs; Rost, Natalia S.; Bzdok, Danilo

doi:10.2139/ssrn.3682001

Cited by 4 publications

(9 citation statements)

References 47 publications

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“…The full model for the BN outcome explained a total variance of R 2 =0.51, and the Bayesian models for the PF and SF explained R 2 =0.37, respectively. Considering our white matter results, the predictive performance for naming and speech fluency matches previous research on grey matter lesions due to stroke (Bonkhoff, Lim, Bae, Weaver, Kuijf, et al, 2021). For each lesion atom, we show the predictive role in explaining language function separately for women and men.…”

Section: Figure 2 Multivariate Latent-factor Discovery Deconvolves Un...supporting

confidence: 85%

“…As such, even subtle differences in lateralization align with the current neuroanatomical knowledge of the language pathways (Thiebaut de . We confirmed a well-fitted approximation of the underlying distribution as performed for model checking in previous research (Bonkhoff, Lim, Bae, Weaver, Kuijf, et al, 2021;Kiesow et al, 2021).…”

Section: Figure 2 Multivariate Latent-factor Discovery Deconvolves Un...supporting

confidence: 81%

“…This unsupervised machine-learning algorithm can identify the topological form and patient-specific combination of lesion pattern expressions that make up the white matter disconnection inflicted by stroke. In accordance with our recent stroke studies (Bonkhoff, Lim, Bae, Weaver, Kuijf, et al, 2021;Bonkhoff, Schirmer, Bretzner, Hong, et al, 2021), the derived sum-of-parts representation was henceforth referred to as lesion atoms. Predicting language outcome at 3 months post-stroke from patient-specific lesion fingerprints…”

Section: Data-led Deconvolution Of Hidden Lesion Atomsmentioning

confidence: 64%

“…We adjusted for age-specific effects by considering the bare age and its squared value and, therefore, captured possible u-shaped effects. Our parametric model specification also included sex as a covariate to take into account outcome differences that were independent and dependent of the lesion configurations captured in the NNMF-derived lesion atom representations (see (Bonkhoff, Lim, Bae, Weaver, Kuijf, et al, 2021;Bonkhoff, Schirmer, Bretzner, Hong, et al, 2021)). Samples from the posterior distribution of the model parameters were drawn by the No U-Turn Sampler (NUTS, (Hoffman et al, 2014)), a kind of Monte Carlo Markov Chain algorithm (in our setting defaulted to draws=5,000).…”

Section: Code Availabilitymentioning

confidence: 99%

“…Clinically, ischemic stroke generally affects male and female patients differently in terms of incidence, severity, survival, and potential for recovery (Bonkhoff, Karch, Weber, Wellmann, & Berger, 2021; Bushnell et al, 2014; Dehlendorff et al, 2015). In fact, women generally suffer strokes with more severe neuropsychological consequences compared to those of men (Bonkhoff, Schirmer, Bretzner, Hong, et al, 2021; Silva et al, 2010). Similar lesion volume effects were noted in cases of aphasia, in which smaller ischemic stroke lesions were capable of producing aphasia in women than men (Hier et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

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Bayesian stroke modeling details sex biases in the white matter substrates of aphasia

Kernbach

Hartwigsen²,

Lim

et al. 2022

Preprint

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Ischemic cerebrovascular events often lead to aphasia. Previous work provided hints that such strokes may affect women and men in distinct ways. Women tend to suffer strokes with more disabling language impairment, even if the lesion size is comparable to men. In 1,401 patients, we isolated data-led representations of anatomical lesion patterns and hand-tailored a Bayesian analytical solution to carefully model the degree of sex divergence in predicting language outcomes ~3 months after stroke. We located lesion-outcome effects in the left-dominant language network that highlight the ventral pathway as a core lesion focus across different tests of language performance. We provide newly detailed evidence for sex-specific brain-behavior associations in the domain-general networks associated with cortico-subcortical pathways, with unique contributions of the fornix in women and cingular fiber bundles in men. Our collective findings suggest diverging white matter substrates in how stroke causes language deficits in women and men. Clinically acknowledging such sex disparities has the potential to improve personalized treatment for stroke patients worldwide.

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Section: Figure 2 Multivariate Latent-factor Discovery Deconvolves Un...supporting

confidence: 85%

Section: Figure 2 Multivariate Latent-factor Discovery Deconvolves Un...supporting

confidence: 81%

Section: Data-led Deconvolution Of Hidden Lesion Atomsmentioning

confidence: 64%

Section: Code Availabilitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Bayesian stroke modeling details sex biases in the white matter substrates of aphasia

Kernbach

Hartwigsen²,

Lim

et al. 2022

Preprint

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The relevance of rich club regions for functional outcome post‐stroke is enhanced in women

Bonkhoff

Schirmer

Bretzner

et al. 2022

Human Brain Mapping

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This study aimed to investigate the influence of stroke lesions in predefined highly interconnected (rich‐club) brain regions on functional outcome post‐stroke, determine their spatial specificity and explore the effects of biological sex on their relevance. We analyzed MRI data recorded at index stroke and ~3‐months modified Rankin Scale (mRS) data from patients with acute ischemic stroke enrolled in the multisite MRI‐GENIE study. Spatially normalized structural stroke lesions were parcellated into 108 atlas‐defined bilateral (sub)cortical brain regions. Unfavorable outcome (mRS > 2) was modeled in a Bayesian logistic regression framework. Effects of individual brain regions were captured as two compound effects for (i) six bilateral rich club and (ii) all further non‐rich club regions. In spatial specificity analyses, we randomized the split into “rich club” and “non‐rich club” regions and compared the effect of the actual rich club regions to the distribution of effects from 1000 combinations of six random regions. In sex‐specific analyses, we introduced an additional hierarchical level in our model structure to compare male and female‐specific rich club effects. A total of 822 patients (age: 64.7[15.0], 39% women) were analyzed. Rich club regions had substantial relevance in explaining unfavorable functional outcome (mean of posterior distribution: 0.08, area under the curve: 0.8). In particular, the rich club‐combination had a higher relevance than 98.4% of random constellations. Rich club regions were substantially more important in explaining long‐term outcome in women than in men. All in all, lesions in rich club regions were associated with increased odds of unfavorable outcome. These effects were spatially specific and more pronounced in women.

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Association of Infarct Topography and Outcome After Endovascular Thrombectomy in Patients With Acute Ischemic Stroke

et al. 2022

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Background and Objectives:The care of patients with large vessel occlusion (LVO) stroke has been revolutionized by endovascular thrombectomy (EVT). While EVT has a large effect size, most patients treated with EVT remain disabled or die within 90 days. A better understanding of outcomes may influence EVT selection criteria, novel therapies, and prognostication. We sought to identify associations between outcomes and brain regions involved in ischemic lesions.Methods:For this cohort study, consecutive patients with LVO who were treated with EVT and underwent post-EVT MRI were identified from a tertiary referral center (2011-2019). Acute ischemic lesions were manually segmented from DWI and spatially normalized. Individual lesions were parcellated (atlas-defined 94 cortical regions, 14 subcortical nuclei, 20 white matter tracts) and reduced to ten essential lesion patterns using unsupervised dimensionality reduction techniques. Ninety-day modified Rankin Scale (mRS>2) was modeled via Bayesian regression, taking the ten lesion patterns as inputs, and controlling for lesion size, age, sex, acute NIH Stroke Scale (NIHSS), alteplase, prior stroke, intracerebral hemorrhage, and good reperfusion (TICI2b-3). In comparative analyses, 90-day mRS was modeled considering covariates and compartment-wise relevance for acute stroke severity and 90-day mRS were evaluated.Results:There were 151 patients with LVO identified (age: 68±15 years; 52% female). The median NIHSS was 16 (IQR 13-20); 56% had mRS>2. Lesion locations predictive of 90-day mRS involved bilateral, but left-hemispherically more pronounced pre- and postcentral gyri, insular and opercular cortex, as well as left putamen and caudate (area under the curve: 0.91, highest probability density interval (HPDI) covering 90%-certainty: 0.90–0.92). The lesion location model outperformed the simpler model relying on covariates only (Bayesian model comparison of weight: 97% to the model with vs. 3% to that without lesion location). While lesions affecting subcortical nuclei had the highest relevance for stroke severity (posterior distribution mean: 0.75, 90%-HDPI=0.256–1.31), lesions affecting white matter tracts had the highest relevance for 90-day mRS (0.656, 90%-HDPI=0.0864–1.12).Discussion:These data describe the significance for outcomes of specific brain regions involved in ischemic lesions on MRI after EVT. Future work in additional datasets is needed to confirm these granular findings.

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Generative Lesion Pattern Decomposition of Cognitive Impairment after Stroke

Cited by 4 publications

References 47 publications

Bayesian stroke modeling details sex biases in the white matter substrates of aphasia

Bayesian stroke modeling details sex biases in the white matter substrates of aphasia

The relevance of rich club regions for functional outcome post‐stroke is enhanced in women

Association of Infarct Topography and Outcome After Endovascular Thrombectomy in Patients With Acute Ischemic Stroke

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