Towards a mechanistic understanding of the human subcortex

Forstmann, Birte U.; Hollander, Gilles de; Maanen, Leendert van; Alkemade, Anneke; Keuken, Max C.

doi:10.1038/nrn.2016.163

Cited by 88 publications

(98 citation statements)

References 138 publications

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“…The field's preponderance for the cerebral cortex, coupled with technical challenges inherent to subcortical imaging [32][33][34] , has led to the subcortex remaining a terra incognita 35 . Through the provision of high-quality, ultra-high field strength MRI data, collaborative initiatives such as the HCP 18 herald new opportunities to overcome some of the challenges associated with reliably imaging this deep and anatomically complex brain structure.…”

Section: Discussionmentioning

confidence: 99%

Topographic organization of the human subcortex unveiled with functional connectivity gradients

Margulies

Breakspear

Zalesky

2020

Preprint

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Understanding the topographic organization of the human brain remains a major goal in neuroscience. Brain atlases are fundamental to this goal, yet many contemporary human atlases cover only the cerebral cortex, leaving the subcortex a terra incognita. We revealed the astoundingly complex topographic organization of the human subcortex by disambiguating smooth connectivity gradients from discrete areal boundaries in resting-state fMRI data acquired from more than 1000 healthy adults. This unveiled four hierarchical scales of subcortical organization, recapitulating well-known anatomical nuclei at the coarsest scale and delineating 27 new bilateral regions at the finest. Ultra-high field strength fMRI corroborated and extended this hierarchy, enabling delineation of finer subdivisions of hippocampus and amygdala, while task-evoked fMRI revealed a subtle reorganization of subcortical topography in response to changing cognitive demands. A new subcortical atlas was delineated, personalized to account for individual connectivity differences and utilized to uncover reproducible relationships between subcortical connectivity and individual variation in human behaviors. The new atlas enables holistic connectome mapping and characterization of cortico-subcortical connectivity.

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Section: Discussionmentioning

confidence: 99%

Topographic organization of the human subcortex unveiled with functional connectivity gradients

Margulies

Breakspear

Zalesky

2020

Preprint

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“…A growing body of empirical evidence suggests that to-date we are only starting to understand the function of these nuclei and their subdivisions for human behavior and cognition in health (1) and disease (2)(3)(4)(5). One reason for this lack of understanding is due to severe technical difficulties in assessing these nuclei in-vivo in humans using non-invasive conventional magnetic resonance imaging (MRI) (6). Here, we show that the visual lateral geniculate nucleus (LGN) and its cytoarchitectonic subdivisions can be identified in humans both in-vivo and postmortem using advanced microstructure-informed quantitative MRI strategies.…”

Section: Introductionmentioning

confidence: 99%

“…The investigation of the LGN's main neuronal layers (often coined as M and P subdivisions) in humans in-vivo faces considerable challenges. First, the LGN's small size, ranging from only 91-157 mm 3 in humans (12), and deep location within the brain makes it difficult to map the LGN using non-invasive MR imaging techniques (6). Second, conventional image resolutions in invivo MR examinations (structural MRI ~1mm, functional MRI ~2.5mm isotropic resolution) are likely insufficient to fully disentangle distinct signal contributions of M and P subdivisions due to partial volume effects (13).…”

Section: Introductionmentioning

confidence: 99%

Mapping the Human Visual Thalamus and its Cytoarchitectonic Subdivisions Using Quantitative MRI

Müller-Axt

Eichner

Rusch

et al. 2020

Preprint

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The human lateral geniculate nucleus (LGN) of the visual thalamus is a key subcortical processing site for visual information analysis. A non-invasive assessment of the LGN and its functionally and microstructurally distinct magnocellular (M) and parvocellular (P) subdivisions in-vivo in humans is challenging, because of its small size and location deep inside the brain. Here we tested whether recent advances in high-field structural quantitative MRI (qMRI) can enable MR-based mapping of human LGN subdivisions. We employed ultra-high resolution 7 Tesla qMRI of a post-mortem human LGN specimen and high-resolution 7 Tesla in-vivo qMRI in a large participant sample. We found that a quantitative assessment of the LGN and a differentiation of its subdivisions was possible based on microstructure-informed MR-contrast alone. In both the post-mortem and in-vivo qMRI data, we identified two components of shorter and longer longitudinal relaxation time (T1) within the LGN that coincided with the known anatomical locations of a dorsal P and a ventral M subdivision, respectively. Through a subsequent ground truth histological examination of the same post-mortem LGN specimen, we showed that the observed T1 contrast pertains to cyto- and myeloarchitectonic differences between LGN subdivisions. These differences were based on cell and myelin density, but not on iron content. Our qMRI-based mapping strategy overcomes shortcomings of previous fMRI-based mapping approaches. It paves the way for an in-depth understanding of the function and microstructure of the LGN in humans. It also enables investigations into the selective contributions of LGN subdivisions to human behavior in health and disease.

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“…Recently, it has been shown that using binarized VTAs (that would model all-or-nothing activations) could predict slightly less variance in clinical outcomes in comparison to using CONNECTIVITY LINKS STN-DBS WITH DEPRESSIVE SYMPTOMS 6 weighted VTAs such as the E-field gradient vector magnitudes 20 . Binary VTAs are based on specific thresholds that assume a certain type of axon diameter and orientation and do not grasp the anatomical complexity of the subcortex 25 . To account for this general limitation of the VTA concept, we repeated all analyses using the unthresholded E-field magnitude instead of the VTAs 26 .…”

Section: Localization Of Dbs Electrodesmentioning

confidence: 99%

Left prefrontal impact links subthalamic stimulation with depressive symptoms

Irmen

Horn

Mosley

et al. 2019

Preprint

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AbstractObjectiveSubthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson’s Disease (PD) not only stimulates focal target structures but also affects distributed brain networks. The impact this network modulation has on non-motor DBS effects is not well characterized. By focusing on the affective domain, we systematically investigate the impact of electrode placement and associated structural connectivity on changes in depressive symptoms following STN-DBS which have been reported to improve, worsen or remain unchanged.MethodsDepressive symptoms before and after STN-DBS surgery were documented in 116 PD patients from three DBS centers (Berlin, Queensland, Cologne). Based on individual electrode reconstructions, the volumes of tissue activated (VTA) were estimated and combined with normative connectome data to identify structural connections passing through VTAs. Berlin and Queensland cohorts formed a training and cross-validation dataset used to identify structural connectivity explaining change in depressive symptoms. The Cologne data served as test-set for which depressive symptom change was predicted.ResultsStructural connectivity was linked to depressive symptom change under STN-DBS. An optimal connectivity map trained on the Berlin cohort could predict changes in depressive symptoms in Queensland patients and vice versa. Furthermore, the joint training-set map predicted changes in depressive symptoms in the independent test-set. Worsening of depressive symptoms was associated with left prefrontal connectivity.InterpretationFibers linking the STN electrode with left prefrontal areas predicted worsening of depressive symptoms. Our results suggest that for the left STN-DBS lead, placement impacting fibers to left prefrontal areas should be avoided to maximize improvement of depressive symptoms.

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Towards a mechanistic understanding of the human subcortex

Cited by 88 publications

References 138 publications

Topographic organization of the human subcortex unveiled with functional connectivity gradients

Topographic organization of the human subcortex unveiled with functional connectivity gradients

Mapping the Human Visual Thalamus and its Cytoarchitectonic Subdivisions Using Quantitative MRI

Left prefrontal impact links subthalamic stimulation with depressive symptoms

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