Patient-Tailored, Connectivity-Based Forecasts of Spreading Brain Atrophy

Brown, Jesse A.; Deng, Jersey; Neuhaus, John; Sible, Isabel J.; Sias, Ana C.; Lee, Suzee E.; Kornak, John; Marx, Gabe; Karydas, Anna; Spina, Salvatore; Grinberg, Lea T.; Coppola, Giovanni; Geschwind, Dan; Kramer, Joel H.; Gorno‐Tempini, Maria Luisa; Miller, Bruce L.; Rosen, Howard J.; Seeley, William W.

doi:10.2139/ssrn.3339908

Cited by 21 publications

(32 citation statements)

References 69 publications

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“…The spatial correlation between single‐subject atrophy maps was low, and not specific between patient groups. This result is in line with several other studies showing heterogeneity in single‐subject atrophy maps in patients with Alzheimer's disease, 20,31,47 frontotemporal dementia, 48 and semantic primary progressive aphasia 48 . In contrast, the spatial correlation between single‐subject atrophy network maps was high and was specific between patient groups.…”

Section: Discussionsupporting

confidence: 92%

Network Localization of Alien Limb in Patients with Corticobasal Syndrome

Tetreault

Phan

Petersen

et al. 2020

Annals of Neurology

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for the 4 Repeat Tau Neuroimaging Initiative † Objective: Perirolandic atrophy occurs in corticobasal syndrome (CBS) but is not specific versus progressive supranuclear palsy (PSP). There is heterogeneity in the locations of atrophy outside the perirolandic cortex and it remains unknown why atrophy in different locations would cause the same CBS-specific symptoms. In prior work, we used a wiring diagram of the brain called the human connectome to localize lesion-induced disorders to symptom-specific brain networks. Here, we use a similar technique termed "atrophy network mapping" to localize single-subject atrophy maps to symptom-specific brain networks. Methods: Single-subject atrophy maps were generated by comparing cortical thickness in patients with CBS versus controls. Next, we performed seed-based functional connectivity using a large normative connectome to determine brain regions functionally connected to each patient's atrophied locations. Results: Patients with CBS had perirolandic atrophy versus controls at the group level, but locations of atrophy in CBS were heterogeneous outside of the perirolandic cortex at the single-subject level (mean spatial correlation = 0.04). In contrast, atrophy occurred in locations functionally connected to the perirolandic cortex in all patients with CBS (spatial correlation = 0.66). Compared with PSP, patients with CBS had atrophy connected to a network of higher-order sensorimotor regions beyond perirolandic cortex, matching a CBS atrophy network from a recent meta-analysis. Finally, atrophy network mapping identified a symptom-specific network for alien limb, matching a lesion-induced alien limb network and a network associated with agency in healthy subjects. Interpretation: We identified a syndrome-specific network for CBS and symptom-specific network for alien limb using single-subject atrophy maps and the human connectome.

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Section: Discussionsupporting

confidence: 92%

Network Localization of Alien Limb in Patients with Corticobasal Syndrome

Tetreault

Phan

Petersen

et al. 2020

Annals of Neurology

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“…3,6 Therefore, this contrasts with previous approaches in which patterns of deformation are identified by comparison to a control group independently from patient-specific clinical features. [33][34][35] The PLS method used here has been used previously to identify brain-clinical patterns in PD and schizophrenia. 9,36 PLS was performed using the PLSGUI toolbox in MATLAB (https://www.rotman-baycrest.on.ca/index.…”

Section: Pls Analysismentioning

confidence: 99%

A Prodromal Brain‐Clinical Pattern of Cognition in Synucleinopathies

Rahayel

Postuma

Montplaisir

et al. 2020

Annals of Neurology

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Objective Isolated (or idiopathic) rapid eye movement sleep behavior disorder (iRBD) is associated with dementia with Lewy bodies (DLB) and Parkinson's disease (PD). Biomarkers are lacking to predict conversion to a dementia or a motor‐first phenotype. Here, we aimed at identifying a brain‐clinical signature that predicts dementia in iRBD. Methods A brain‐clinical signature was identified in 48 patients with polysomnography‐confirmed iRBD using partial least squares between brain deformation and 27 clinical variables. The resulting variable was applied to 78 patients with iRBD followed longitudinally to predict conversion to a synucleinopathy, specifically DLB. The deformation scores from patients with iRBD were compared with 207 patients with PD, DLB, or prodromal DLB to assess if scores were higher in DLB compared to PD. Results One latent variable explained 31% of the brain‐clinical covariance in iRBD, combining cortical and subcortical deformation and subarachnoid/ventricular expansion to cognitive and motor variables. The deformation score of this signature predicted conversion to a synucleinopathy in iRBD (p = 0.036, odds ratio [OR] = 2.249; 95% confidence interval [CI] = 1.053–4.803), specifically to DLB (OR = 4.754; 95% CI = 1.283–17.618, p = 0.020) and not PD (p = 0.286). Patients with iRBD who developed dementia had scores similar to clinical and prodromal patients with DLB but higher scores compared with patients with PD. The deformation score also predicted cognitive performance over 1, 2, and 4 years in patients with PD. Interpretation We identified a brain‐clinical signature that predicts conversion in iRBD to more severe/dementing forms of synucleinopathy. This pattern may serve as a new biomarker to optimize patient care, target risk reduction strategies, and administer neuroprotective trials. ANN NEUROL 2021;89:341–357

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“…These clinical syndromes arise from neurodegeneration of cortical and subcortical structures within frontal and/or temporal lobes (frontotemporal lobar degeneration or FTLD) and are associated with diverse molecular pathologies ( Miller et al, 1991 ). Converging lines of research associate the early-stages of neurodegenerative diseases to relatively focal atrophy affecting specifically susceptible cell assemblies, later spreading throughout large-scale networks ( Brown et al, 2019 , Raj et al, 2012 , Seeley et al, 2009 , Zeighami et al, 2015 ). Thus, careful clinicopathological investigations of well-defined groups of patients with focal neurodegeneration can deepen our understanding of regional vulnerability to proteinopathies ( Soto and Pritzkow, 2018 , Walsh and Selkoe, 2016 ), and have important implications for both clinical practice and cognitive neuroscience ( Elahi & Miller, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Regional and hemispheric susceptibility of the temporal lobe to FTLD-TDP type C pathology

Borghesani

Battistella

Mandelli

et al. 2020

NeuroImage: Clinical

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Highlights Anterior temporal lobe (ATL) degeneration is most often caused by FTLD-TDP type C pathology. Cases can present with predominantly left (60%) or right (40%) ATL atrophy. Within ATLs, medial regions are more vulnerable than lateral ones. The observed spectrum of clinical phenotypes is driven by atrophy lateralization. Left and right temporal variants of FTD should be considered the same disease.

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Patient-Tailored, Connectivity-Based Forecasts of Spreading Brain Atrophy

Cited by 21 publications

References 69 publications

Network Localization of Alien Limb in Patients with Corticobasal Syndrome

Network Localization of Alien Limb in Patients with Corticobasal Syndrome

A Prodromal Brain‐Clinical Pattern of Cognition in Synucleinopathies

Regional and hemispheric susceptibility of the temporal lobe to FTLD-TDP type C pathology

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