Topographical layer imaging as a tool to track neurodegenerative disease spread in M1

Schreiber, Stefanie; Northall, Alicia; Weber, Miriam; Vielhaber, Stefan; Kuehn, Esther

doi:10.1038/s41583-020-00404-w

Cited by 12 publications

(19 citation statements)

References 6 publications

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“…This provides a mechanistic explanation as to why topographical organization is often maintained after learning or with deprivation, such as in amputees [42], [43], and as to why body representations are often preserved in older age [44]. However, as these borders also differ between individuals, our findings open up the investigation of these borders as a possible mechanism in neurodegenerative diseases that involve topographical disease spread [45].…”

Section: Discussionmentioning

confidence: 80%

“…This indicates the existence of topographic-specific age-related plasticity in M1. This is of particular relevance for neurodegenerative diseases where topographic-specific iron accumulation has been linked to symptom severity in affected body parts [49], [50], and identified as a mechanism for topographical disease spread [45]. This finding may also explain why older adults often show particularly deteriorated walking and balance behavior, which is critically associated with reduced independence and executive function in late life [51].…”

Section: Discussionmentioning

confidence: 99%

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Layer-Specific Vulnerability is a Mechanism of Topographic Map Aging

Northall

Doehler

Weber

et al. 2022

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Age-related cortical plasticity reveals insights into the mechanisms underlying the stability and flexibility of neuronal circuits. Classical parcellation has long demonstrated the importance of microstructural features yet 3D approaches have rarely been applied to human brain organization in-vivo. We acquired functional and structural 7T-MRI and behavioral data of living younger and older adults to investigate human primary motor cortex (M1) aging, employing 3D parcellation techniques. We identify distinct cortical fields in M1 based on quantitative tissue contrast, which are, along with the myelin-poor borders between them, stable with age. We also show age-related iron accumulation, particularly in the output layer 5b and the lower limb field. Our data offers a new model of human M1 with distinct cortical fields, a mechanistic explanation for the stability of topographic organization in the context of aging and plasticity, and highlights the specific vulnerability of output signal flows to cortical plasticity.

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Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Layer-Specific Vulnerability is a Mechanism of Topographic Map Aging

Northall

Doehler

Weber

et al. 2022

Preprint

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“…To test for these assumptions, one could perform longitudinal sampling with our tool to track tongue kinematic features with disease progression. Accurately quantifying bulbar dysfunction is further necessary to identify corresponding brain changes to the bulbar area of M1 by using neuroimaging methods (7,28). In addition, our measure could be used to track tongue movement training success to improve outcomes in dysphagia, as previously demonstrated with specialized equipment to measure tongue pressure in patients following acquired brain injury and stroke (4).…”

Section: Discussionmentioning

confidence: 95%

“…In ALS, these symptoms are caused by the degeneration of upper and lower motor neurons that support the bulbar muscles in the tongue and throat. While only one-third of patients with ALS first present with bulbar symptoms (so-called "bulbar-onset ALS"), the majority of patients with lower or upper limb-onset ALS will experience bulbar impairment with disease progression because the disorder spreads through the topographically-organized motor system (5)(6)(7). Difficulty swallowing, clinically termed dysphagia, causes malnutrition and even respiratory infections in patient populations.…”

Section: Introductionmentioning

confidence: 99%

An Automated Tongue Tracker for Quantifying Bulbar Function in ALS

et al. 2022

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IntroductionBulbar symptoms, including difficulty swallowing and speaking, are common in amyotrophic lateral sclerosis (ALS) and other neurological disorders, such as stroke. The presence of bulbar symptoms provides important information regarding clinical outcomes, such as survival time after diagnosis. Nevertheless, there are currently no easily accessible, quantitative methods to measure bulbar function in patients.MethodsWe developed an open-source tool called Tongue Tracker (TT) to quantify bulbar function by training a neural network to track kinematic tongue features of short video clips of lateral tongue movements. We tested 16 healthy controls and ten patients with ALS, of whom two patients were clinically diagnosed with bulbar-onset type and eight patients were clinically diagnosed with limb-onset type. Of the limb-onset patients, five patients also showed symptoms of bulbar impairment.ResultsWe validated TT by comparing the results with manual delineation of tongue movements in the clips. We demonstrate an early-stage bulbar-onset patient who showed fewer and slower tongue sweeps compared to healthy controls and limb-onset patients and we show that five bulbar-impaired limb-onset patients have a different tongue kinematic profile compared to healthy controls.DiscussionTT may serve to detect quantitative markers of bulbar dysfunction in ALS and other motor disorders, such as stroke, by identifying signatures of spasticity or muscle weakness that affects tongue movement speed and/or tongue movement topography.

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“…Neurosci. https://doi.org/10.1038/s41583 02000404w (2020)) 2 . Their comment adds an important technical point about the direc tionality of myelin gradients.…”

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confidence: 99%