363 research outputs found
A probabilistic atlas of the human thalamic nuclei combining ex vivo MRI and histology
The human thalamus is a brain structure that comprises numerous, highly
specific nuclei. Since these nuclei are known to have different functions and
to be connected to different areas of the cerebral cortex, it is of great
interest for the neuroimaging community to study their volume, shape and
connectivity in vivo with MRI. In this study, we present a probabilistic atlas
of the thalamic nuclei built using ex vivo brain MRI scans and histological
data, as well as the application of the atlas to in vivo MRI segmentation. The
atlas was built using manual delineation of 26 thalamic nuclei on the serial
histology of 12 whole thalami from six autopsy samples, combined with manual
segmentations of the whole thalamus and surrounding structures (caudate,
putamen, hippocampus, etc.) made on in vivo brain MR data from 39 subjects. The
3D structure of the histological data and corresponding manual segmentations
was recovered using the ex vivo MRI as reference frame, and stacks of blockface
photographs acquired during the sectioning as intermediate target. The atlas,
which was encoded as an adaptive tetrahedral mesh, shows a good agreement with
with previous histological studies of the thalamus in terms of volumes of
representative nuclei. When applied to segmentation of in vivo scans using
Bayesian inference, the atlas shows excellent test-retest reliability,
robustness to changes in input MRI contrast, and ability to detect differential
thalamic effects in subjects with Alzheimer's disease. The probabilistic atlas
and companion segmentation tool are publicly available as part of the
neuroimaging package FreeSurfer
A probabilistic atlas of the human thalamic nuclei combining ex vivo MRI and histology
The human thalamus is a brain structure that comprises numerous, highly specific nuclei. Since these nuclei are known to have different functions and to be connected to different areas of the cerebral cortex, it is of great interest for the neuroimaging community to study their volume, shape and connectivity in vivo with MRI. In this study, we present a probabilistic atlas of the thalamic nuclei built using ex vivo brain MRI scans and histological data, as well as the application of the atlas to in vivo MRI segmentation. The atlas was built using manual delineation of 26 thalamic nuclei on the serial histology of 12 whole thalami from six autopsy samples, combined with manual segmentations of the whole thalamus and surrounding structures (caudate, putamen, hippocampus, etc.) made on in vivo brain MR data from 39 subjects. The 3D structure of the histological data and corresponding manual segmentations was recovered using the ex vivo MRI as reference frame, and stacks of blockface photographs acquired during the sectioning as intermediate target. The atlas, which was encoded as an adaptive tetrahedral mesh, shows a good agreement with previous histological studies of the thalamus in terms of volumes of representative nuclei. When applied to segmentation of in vivo scans using Bayesian inference, the atlas shows excellent test-retest reliability, robustness to changes in input MRI contrast, and ability to detect differential thalamic effects in subjects with Alzheimer's disease. The probabilistic atlas and companion segmentation tool are publicly available as part of the neuroimaging package FreeSurfer.The authors would like to thank Professor Karla Miller (Oxford) for
her help with the design of the ex vivo MRI acquisition; Ms. Mercedes
I~niguez de Onzo~no and Mr. Francisco Romero (UCLM) for their careful
technical laboratory help; and Mr. Gonzalo Artacho (UCLM) for his help
with the digitization and curation of his organization of histological data.
This project has received funding from the European Union's Horizon
2020 research and innovation program under the Marie Sklodowska-
Curie grant agreement No 654911 (project “THALAMODEL”) and by
the European Research Council (ERC) Starting Grant agreement No
677697 (“BUNGEE-TOOLS”). It was also funded by the Spanish Ministry
of Economy and Competitiveness(MINECO TEC-2014-51882-P, RYC-
2014-15440, PSI2015-65696, and SEV-2015-0490), the Basque Government
(PI2016-12), and UCLM Internal Research Groups grants.
Support for this research was also provided in part by the National
Institute of Biomedical Imaging and Bioengineering (P41EB015896,
1R01EB023281, R01EB006758, R21EB018907, R01EB019956), the
National Institute on Aging (5R01AG008122, R01AG016495), the National
Institute of Diabetes and Digestive and Kidney Diseases (1-R21-DK-
108277-01), the National Institute of Neurological Disorders and Stroke
(R01NS0525851, R21NS072652, R01NS070963, R01NS083534,
5U01NS086625), and was made possible by the resources provided by
Shared Instrumentation Grants 1S10RR023401, 1S10RR019307, and 1S-
10RR023043. Additional support was provided by the NIH Blueprint for
Neuroscience Research (5U01-MH093765), part of the multiinstitutional
Human Connectome Project. In addition, B.F. has a financial
interest in CorticoMetrics, a company whose medical pursuits focus
on brain imaging and measurement technologies. B.F.’s interests were
reviewed and are managed by Massachusetts General Hospital and
Partners HealthCare in accordance with their conflict of interest policies.
Data collection and sharing for this project was funded by the
Alzheimer's Disease Neuroimaging Initiative (National Institutes of
Health Grant U01 AG024904) and DOD ADNI (DOD award number
W81XWH-12-2-0012). ADNI is funded by the National Institute on
Aging, the National Institute of Biomedical Imaging and Bioengineering,
and through generous contributions from the following:
AbbVie, Alzheimers Association; Alzheimers Drug Discovery Foundation;
Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb
Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals,
Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd
and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare;
IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development,
LLC.; Johnson & Johnson Pharmaceutical Research & Development
LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale
Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies;
Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging;
Servier; Takeda Pharmaceutical Company; and Transition Therapeutics.
The Canadian Institutes of Health Research is providing funds to
support ADNI clinical sites in Canada. Private sector contributions are
facilitated by the Foundation for the National Institutes of Health
(www.fnih.org). The grantee organization is the Northern California
Institute for Research and Education, and the study is coordinated by
the Alzheimers Therapeutic Research Institute at the University of
Southern California. ADNI data are disseminated by the Laboratory for
Neuro Imaging at the University of Southern California
The thalamus as a putative biomarker in neurodegenerative disorders
Objective: This review provides a brief account of the clinically relevant functional neuroanatomy of the thalamus, before considering the utility of various modalities utilised to image the thalamus and technical challenges therein, and going on to provide an overview of studies utilising structural imaging techniques to map thalamic morphology in the spectrum of neurodegenerative disorders.
Methods: A systematic search was conducted for peer-reviewed studies involving structural neuroimaging modalities investigating the morphology (shape and/ or size) of the thalamus in the spectrum of neurodegenerative disorders.
Results: Whilst the precise role of the thalamus in the healthy brain remains unclear, there is a large body of knowledge accumulating which defines more precisely its functional connectivity within the connectome, and a burgeoning literature implicating its involvement in neurodegenerative disorders. It is proposed that correlation of clinical features with thalamic morphology (as a component of a quantifiable subcortical connectome) will provide a better understanding of neuropsychiatric dysfunction in various neurodegenerative disorders, potentially yielding clinically useful endophenotypes and disease biomarkers.
Conclusions: Thalamic biomarkers in the neurodegenerative disorders have great potential to provide clinically meaningful knowledge regarding not only disease onset and progression, but may yield targets of and perhaps a way of gauging response to future disease-modifying modalities
Neuroimaging biomarkers associated with clinical dysfunction in Parkinson disease
Parkinson disease (PD) is the second most common neurodegenerative disorder in the world, directly affecting 2-3% of the population over the age of 65. People diagnosed with the disorder can experience motor, autonomic, cognitive, sensory and neuropsychiatric symptoms that can significantly impact quality of life. Uncertainty still exists about the pathophysiological mechanisms that underlie a range of clinical features of the disorder, linked to structural as well as functional brain changes.
This thesis thus aimed to uncover neuroimaging biomarkers associated with clinical dysfunction in PD. A 'hubs-and-spokes' neural circuit-based approach can contribute to this aim, by analysing the component elements and also the interconnections of important brain networks. This thesis focusses on structures within basal ganglia-thalamocortical neuronal circuits that are linked to a range functions impacted in the disorder, and that are vulnerable to the consequences of PD pathology. This thesis investigated neuronal 'hubs' by studying the morphology of the caudate nucleus, putamen, thalamus and neocortex. The caudate nucleus, putamen and thalamus are all vital subcortical 'hubs' that play important roles in a number of functional domains that are compromised in PD. The neocortex, on the other hand, has a range of 'hubs' spread across it, regions of the brain that are crucial for neuronal signalling and communication. The interconnections, or 'spokes', between these hubs and other brain regions were investigated using seed-based resting-state functional connectivity analyses. Finally, a morphological analysis was used to investigate possible structural changes to the corpus callosum, the major inter-hemispheric white matter tract of the brain, crucial to effective higher-order brain processes.
This thesis demonstrates that the caudate nucleus, putamen, thalamus, corpus callosum and neocortex are all atrophied in PD participants with dementia. PD participants also demonstrated a significant correlation between volumes of the caudate nuclei and general cognitive functioning and speed, while putamina volumes were correlated with general motor function. Cognitively unimpaired PD participants demonstrated minimal morphological alterations compared to control participants, however they demonstrated significant increases in functional connectivity of the caudate nucleus, putamen and thalamus with areas across the frontal lobe, and decreases in functional connectivity with parietal and cerebellar regions. PD participants with mild cognitive impairment and dementia show decreased functional connectivity of the thalamus with paracingulate and posterior cingulate cortices, respectively.
This thesis contributes a deeper understanding of the relationship between structures of basal ganglia-thalamocortical neuronal circuits, corpus callosal and neocortical morphology, and the clinical dysfunction associated with PD. This thesis suggests that functional connectivity changes are more common in early stages of the disorder, while morphological alterations are more pronounced in advanced disease stages
Diffusion tensor imaging of frontal lobe white matter tracts in schizophrenia
We acquired diffusion tensor and structural MRI images on 103 patients with schizophrenia and 41 age-matched normal controls. The vector data was used to trace tracts from a region of interest in the anterior limb of the internal capsule to the prefrontal cortex. Patients with schizophrenia had tract paths that were significantly shorter in length from the center of internal capsule to prefrontal white matter. These tracts, the anterior thalamic radiations, are important in frontal-striatal-thalamic pathways. These results are consistent with findings of smaller size of the anterior limb of the internal capsule in patients with schizophrenia, diffusion tensor anisotropy decreases in frontal white matter in schizophrenia and hypothesized disruption of the frontal-striatal-thalamic pathway system
Thalamic nuclei segmentation from T-weighted MRI: unifying and benchmarking state-of-the-art methods with young and old cohorts
The thalamus and its constituent nuclei are critical for a broad range of
cognitive and sensorimotor processes, and implicated in many neurological and
neurodegenerative conditions. However, the functional involvement and
specificity of thalamic nuclei in human neuroimaging is underappreciated and
not well studied due, in part, to technical challenges of accurately
identifying and segmenting nuclei. This challenge is further exacerbated by a
lack of common nomenclature for comparing segmentation methods. Here, we use
data from healthy young (Human Connectome Project, 100 subjects) and older
healthy adults, plus those with minor cognitive impairment and Alzheimers
disease (Alzheimers Disease Neuroimaging Initiative, 540 subjects), to
benchmark four state of the art thalamic segmentation methods for T1 MRI
(FreeSurfer, HIPS-THOMAS, SCS-CNN, and T1-THOMAS) under a single segmentation
framework. Segmentations were compared using overlap and dissimilarity metrics
to the Morel stereotaxic atlas. We also quantified each methods estimation
of thalamic nuclear degeneration across Alzheimers disease progression, and
how accurately early and late mild cognitive impairment, and Alzheimers disease
could be distinguished from healthy controls. We show that HIPS-THOMAS produced
the most effective segmentations of individual thalamic nuclei and was also
most accurate in discriminating healthy controls from those with mild cognitive
impairment and Alzheimers disease using individual nucleus volumes. This
work is the first to systematically compare the efficacy of anatomical thalamic
segmentation approaches under a unified nomenclature. We also provide
recommendations of which segmentation method to use for studying the functional
relevance of specific thalamic nuclei, based on their overlap and dissimilarity
with the Morel atlas.Comment: 10 figures, 4 tables, 3 supplemental figures, 2 supplemental table
Recommended from our members
Cortical and subcortical contributions to human cognitive flexibility
Cognitive flexibility enables individuals to respond adaptively to an ever-changing world.
Neurally, flexibility is underpinned by involvement from across the cerebrum, and there is evidence
from animal and human neuroscience suggesting that integration of cortical and thalamic signals
in the striatum is necessary for appropriate behavioural control. A commonly used assay of
flexibility is reversal learning, an associative learning task with high inter-species translatability.
Evidence from animal literature has clearly defined the importance of the striatal cholinergic
system in regulating striatal activity and output from the basal ganglia, and there is nascent evidence
suggesting this system operates in a similar way in humans. However, there is a need to further
disentangle the role of cortical, striatal, and thalamic regions during reversal learning in humans to
better understand how the system works, and whether it has heterogeneous functionality in different
contexts. Furthermore, as studying these processes is not trivial, further methodological work is
required to enable us to understand the system.
In chapter two we systematically assess an automated parcellation technique for identifying specific
thalamic nuclei. Despite generally being treated as a homologous structure in neuroimaging work,
nuclei within the thalamus have dissociable roles, and have diverse contributions to cognitive
functioning, including reversal learning. We found mixed efficacy for segmentations across the
thalamus, with some regions being more accurately defined relative to a “gold standard” atlas than
others. Crucially, we find that the centromedian and parafascicular nuclei, which have an important
role in reversal learning, are clearly defined and have little overlap with contiguous regions. These
results show we can use this automated parcellation technique to identify specific thalamic nuclei
that are relevant for cognitive flexibility and use these parcellations to study functionally relevant
processes.
Recent work has demonstrated that the functional relevance of the striatal cholinergic system can
be studied in vivo using magnetic resonance spectroscopy by separating the peaks of different
metabolites. But this non-conventional approach has not yet been widely adopted, and work is
needed to determine its reliability. Chapter three presents test-retest reliability data on the use of
magnetic resonance spectroscopy to study cholinergic activity in the striatum and cortex. We find
measures of choline containing compounds are highly correlated when peaks are separated and
when they are not. Across time we find that choline concentrations are relatively inconsistent, and
that this was due to changes in the functionally relevant metabolite choline. Conversely,
metabolites that we think are not functionally relevant were stable over time. We believe these
differences may underly differences in acetylcholine function over time and may explain some
intra-individual behavioural variability.
In chapter four we use functional magnetic resonance imaging and psychophysiological interaction
analysis to study corticostriatal and thalamostriatal connectivity during serial reversal learning.
Functional connectivity between the centromedian-parafascicular nuclei of the thalamus and the
associative dorsal striatum, and between the lateral-orbitofrontal cortex and the associative dorsal
striatum was related to processing feedback during reversal learning. Specifically, thalamostriatal
connectivity was found across the task, and may reflect a general error signal used to identify
potential changes in context. Conversely, corticostriatal connectivity was found to be specific to
when behaviour changed and suggests this may be a mechanism for the implementing adaptive
change. We also show findings from exploratory work that may explain further how the cortex
supports flexibility during reversal learning.
Lastly, we used magnetic resonance spectroscopy to investigate whether the state of the cholinergic
system at rest is related to reversal learning performance and latent measures of behaviour using
computational modelling. Choline concentrations at rest showed significant functional relevance
to our measures of reversal learning. More specifically, we found that errors during reversal
learning, and learning rates for positive and negative prediction errors, explained significant
variance in choline. However, the relationship between choline levels and task performance
presented here differ from previous work which instead used a multi-alternative reversal learning
task, and suggests that the striatal cholinergic system may have dissociable roles in different
contexts.
Overall, we show that the striatum, its cholinergic interneuron system, and its afferent projections
from the cortex and thalamus, are associated with performance during serial reversal learning.
Moreover, these findings suggest that the system may operate in separable ways in different
contexts which may be dependent on internal representations of task structure
Human thalamocortical connections and their involvement in language systems.
139 p.During evolution the expansion of the neocortex has been linked with the emergence of higher level cognitive functions, such as reasoning, abstract thinking, or language in human beings. Current research on cognitive neuroscience is mainly focused on the cerebral cortex. Whereas the thalamus is a structure that has extensive white-matter connections with the cerebral cortex, its expansion during evolution is parallel to the expansion of the neocortex. The thalamocortical connections are involved in communication between cortical areas. Thus, to fully understand the neural basis of cognition, a better understanding of the role of the thalamus in cortical function is necessary. The present doctoral dissertation is focused on the structure and function of the thalamus: the first study proposes a reproducible protocol to reconstruct the first-order thalamic white-matter tracts from diffusion-weighted imaging data; the second study investigates the higher-order thalamic white-matter tracts and a similar protocol is proposed to reconstruction those tracts; the third study uses task-based fMRI to examine the involvement of first-order thalamic nuclei in the main language systems.the current dissertation successfully reconstructed first-order and higher-order thalamic white-matter tracts from DWI data, and has proved high reproducibility of the reconstruction protocol. This protocol could benefit the tractography community to better understand the structural connectivity of the thalamus with cortical and subcortical structures and facilitate the research on thalamocortical pathways in humans. We also found evidence for differences in the processing of linguistic and nonlinguistic stimuli in first-order thalamic nuclei through a task-based fMRI study. These results suggest that the first-order thalamic nuclei play roles in human language that are beyond relaying sensory information from periphery to cerebral cortex. These findings are important to push forward our understanding on the role of subcortical structures, such as the thalamus, in human language functions, and to urge a revisitation of existing language models taking the thalamus into consideration
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