Cortical Microstructure & Aging (CM-Age)
Final Report Abstract
We live in an aging society: The German mean age is 46 years - 15 years above the international average - and a German citizen can currently expect to live for around 80 years. Age-related motor, sensory and cognitive decline, however, start early, around the age of 40, and often progress rapidly. The project ‘Cortical Microstructure & Aging’ (CM-Age) used 7 Tesla Magnetic Resonance Imaging (MRI), layer-specific data modelling, and behavioral test batteries to develop a more precise model of human cortical aging and associated behavioral phenotypes using the primary somatosensory cortex (SI) as a model system. The first question targeted by CM-Age was if myelin-poor borders in human SI, so-called ‘septa’, contribute to age-related loss-of-function. The conclusion was that septa do not play a major role for age-related loss-of-function in healthy aging, and that their formation and maintenance is not dependent on steady sensory input. Critically, CM-Age discovered that septa contribute to pathology spread in neurodegenerative diseases. This was deduced from the finding that septa degenerate more and earlier then surrounding tissue in patients with amyotrophic lateral sclerosis (ALS). This finding motivates extended research on the contribution of septa for pathological aging. The second question targeted by CM-Age was which sensory map characteristics define the aging sensory cortex. We first concluded that an often used model to describe dysfunctional sensory map architectures in aging, the ‘de-differentiation model’, is not sufficient. In a second, more comprehensive study, we combined layer-specific structural MRI, layer-specific functional fMRI, and behavioral investigations in younger and older adults with 2-Photon calcium imaging and histology of younger and older mice. Using these data, we developed a novel model of the aging sensory cortex characterized by (1) preserved superficial layers, (2) a widened input channel, evidenced by an enlarged and more myelinated layer IV as well as a greater sensory input signal in layer IV, and (3) thinner and more myelinated deep layers likely due to overall cell loss and more PV+ cells driving age-related changes in excitation-inhibition balance. CM-Age concludes that layer-specific plasticity paradigms need to be developed to stop or reverse age-related loss-of-function that specifically target deep and middle layers of SI.
Publications
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The organizational principles of de-differentiated topographic maps - Data. Dryad Digital Repository
Liu P.; Chrysidou A.; Doehler J.; Wolbers T. & Kuehn E.
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Aging Myeloarchitecture of Large-Scale Body-Part Representations in M1 at 7T-MRI. 27th Annual Meeting of Organization for Human Brain Mapping (OHBM), Virtual Meeting.
Northall, A.; Doehler, J.; Tellez, I.; Weber, M.; Schreiber, S. & Kuehn, E.
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Functional Mechanisms of Aging in S1 using Bayesian Population Receptive Field Mapping at 7T MRI. 27th Annual Meeting of the Organization for Human Brain Mapping (OHBM).
Liu, P.; Doehler, J.; Wolbers, T. & Kuehn, E.
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Functional Mechanisms of Aging in S1 using Bayesian Population Receptive Field Mapping at 7T MRI. Brain In Depth (BID) Symposium.
Liu, P.; Doehler, J.; Wolbers, T. & Kuehn, E.
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Layer-Specific Myeloarchitecture of Human S1 Hand Area in Younger and Older Adults at 7T-MRI. 27th Annual Meeting of Organization for Human Brain Mapping (OHBM), Virtual Meeting.
Doehler, J.; Northall, A.; Bazin, P.-L.; Hänelt, D.; Villringer, A.; Wolbers, T. & Kuehn, E.
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Layer-specific myeloarchitecture of human S1 hand area in younger and older adults at 7T-MRI. Brain In Depth (BID) Conference, Virtual Meeting.
Doehler, J.; Northall, A.; Fracasso, A.; Lohmann, A.; Bazin, P.-L.; Wolbers, T. & Kuehn, E.
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The fine-grained inhibitory functional architecture of neighboring representations in primary somatosensory cortex of humans and mice. Society for Neuroscience (SfN).
Liu, P.; Henschke, J.U.; Stoll, S.; Doehler, J.; Schwarzkopf, D.S.; Pakan, J.M.P. & Kuehn, E.
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Layer-specific vulnerability is a mechanism of topographic map aging. Neurobiology of Aging, 128, 17-32.
Northall, Alicia; Doehler, Juliane; Weber, Miriam; Vielhaber, Stefan; Schreiber, Stefanie & Kuehn, Esther
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Multimodal layer modelling reveals in vivo pathology in amyotrophic lateral sclerosis. Brain, 147(3), 1087-1099.
Northall, Alicia; Doehler, Juliane; Weber, Miriam; Tellez, Igor; Petri, Susanne; Prudlo, Johannes; Vielhaber, Stefan; Schreiber, Stefanie & Kuehn, Esther
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Reduced dimension stimulus decoding and column-based modeling reveal architectural differences of primary somatosensory finger maps between younger and older adults. NeuroImage, 283, 120430.
Kalyani, Avinash; Contier, Oliver; Klemm, Lisa; Azañon, Elena; Schreiber, Stefanie; Speck, Oliver; Reichert, Christoph & Kuehn, Esther
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The 3D Structural Architecture of the Human Hand Area Is Nontopographic. The Journal of Neuroscience, 43(19), 3456-3476.
Doehler, Juliane; Northall, Alicia; Liu, Peng; Fracasso, Alessio; Chrysidou, Anastasia; Speck, Oliver; Lohmann, Gabriele; Wolbers, Thomas & Kuehn, Esther
