Uncertainty-Aware Functional Parcellation of the Neonatal Thalamus Using a Large dHCP rs-fMRI Cohort

Poster No:

955 

Submission Type:

Abstract Submission 

Authors:

Hamza Kebiri1,2, Farnaz Delavari2, Dimitri Van De Ville3,4,1, João Jorge5, Meritxell Bach-Cuadra1,2

Institutions:

1CIBM - Center for Biomedical Imaging, Switzerland, 2Department of Radiology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland, 3Department of Radiology and Medical Informatics, University of Geneva, Geneva, Switzerland, 4Neuro-X Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Geneva, Switzerland, 5CSEM – Swiss Center for Electronics and Microtechnology, Bern, Switzerland

First Author:

Hamza Kebiri  
CIBM - Center for Biomedical Imaging|Department of Radiology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL)
Switzerland|Lausanne, Switzerland

Co-Author(s):

Farnaz Delavari  
Department of Radiology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL)
Lausanne, Switzerland
Dimitri Van De Ville  
Department of Radiology and Medical Informatics, University of Geneva|Neuro-X Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL)|CIBM - Center for Biomedical Imaging
Geneva, Switzerland|Geneva, Switzerland|Switzerland
João Jorge  
CSEM – Swiss Center for Electronics and Microtechnology
Bern, Switzerland
Meritxell Bach-Cuadra  
CIBM - Center for Biomedical Imaging|Department of Radiology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL)
Switzerland|Lausanne, Switzerland

Introduction:

Resting-state functional MRI (rs-fMRI) has transformed our understanding of brain activity by mapping intrinsic functional connectivity networks without task-driven stimulation. This approach has provided valuable insights into the developing brain, where connectivity patterns form the foundation of sensory, motor, and cognitive functions. Among brain regions, the thalamus is known as a central hub that integrates sensory information and facilitates high-order processing, connecting cortical and subcortical areas. Its major role in consciousness, attention, memory, and motor coordination underscores its functional complexity.
In adults, the thalamus is known to function as a complex of multiple units, named the thalamic nuclei, each associated with various functional roles. However, the differentiation of these functional units is less known in developing brains, especially during the neonatal period. Newborns exhibit immature thalamic maturation and connectivity, and while structural imaging studies have advanced our understanding of its anatomy, the formation and maturation of its functional subdivisions are still unclear. In this study, we aim to investigate when and how these functional units emerge and whether this process involves distinct thalamic nuclei.

Methods:

Prior work [1-5] explored thalamic rs-fMRI with limited neonatal cohorts (20-112) and BOLD timepoints (150-350). Our study leverages a large neonatal dataset (730) from the developing Human Connectome Project (dHCP), acquired with 2300 timepoints of Blood Oxygenation Level Dependent (BOLD) fMRI, to map the functional parcellation of the thalamus in neonates aged 37–44 weeks post-conception. Using these rs-fMRI data, we identified functional connectivity profiles for each thalamic voxel across 40 cortical and subcortical regions. Instead of classical winner-takes-all strategies, we propose using k-means clustering with bootstrapping on the voxel-wise connectivity vectors, identifying clusters of voxels with similar connectivity profiles along with uncertainty quantification using majority voting (Figure 1).
Supporting Image: Figure1.png
   ·Our proposed method to parcellate the thalamus using k-means clustering on 40 the regions of interest (ROIs) in the left. The 41 weeks age group thalamic clusters are shown along with the uncertainty
 

Results:

The results revealed five distinct thalamic clusters with connectivity patterns progressively resembling those seen in adults. Thalamic clusters exhibited broad, overlapping connectivity to the superior temporal gyrus, parietal lobe, and frontal regions, indicating reduced specialization [1,4,5]. However, as development progressed, distinct functional units began to emerge. Notably, the pulvinar cluster (as also depicted but less symmetrical in [3,4]), associated with sensory integration, was delineated, along with medial and ventrolateral clusters implicated in salience and motor functions, respectively. This is in line with the ventrolateral sensorimotor unit found in [2,4] and to some extent to the somatosensory nucleus found in [3]. A dorsal thalamic cluster, linked to higher-order cognition, showed a marked increase in volume and connectivity strength, particularly after 41 weeks. Finally, a small noisy cluster, with poor connections to all brain regions was discarded.

Age-related trends highlighted increasing symmetry and reduced uncertainty in clustering results, reflecting the thalamus's gradual functional specialization and hemispheric coordination (Figure 2). Moreover, global connectivity analyses revealed a transient surge at approximately 41 weeks, corresponding to a critical period of thalamic-cortical network maturation.
Supporting Image: Figure2.png
   ·Clustering bootstrapping variability across development
 

Conclusions:

Our rs-fMRI study advances current understanding of thalamus's functional development in neonates by demonstrating an increased functional differentiation and connectivity robustness in developmental trajectory. This work not only provides a framework for understanding typical development but also may establish a baseline for investigating deviations in perinatal brain disorders. Future research could explore the integration of structural and functional data to uncover the interplay between connectivity and microstructural maturation.

Lifespan Development:

Early life, Adolescence, Aging 1

Modeling and Analysis Methods:

Connectivity (eg. functional, effective, structural) 2
fMRI Connectivity and Network Modeling
Methods Development

Neuroanatomy, Physiology, Metabolism and Neurotransmission:

Subcortical Structures

Keywords:

Development
FUNCTIONAL MRI
MRI
PEDIATRIC
Segmentation
Thalamus

1|2Indicates the priority used for review

Abstract Information

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Please indicate below if your study was a "resting state" or "task-activation” study.

Resting state

Healthy subjects only or patients (note that patient studies may also involve healthy subjects):

Healthy subjects

Was this research conducted in the United States?

No

Were any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.

Yes

Were any animal research approved by the relevant IACUC or other animal research panel? NOTE: Any animal studies without IACUC approval will be automatically rejected.

No

Please indicate which methods were used in your research:

Functional MRI

For human MRI, what field strength scanner do you use?

3.0T

Which processing packages did you use for your study?

Other, Please list  -   Nilearn in Python; ITK/ITK-Snap

Provide references using APA citation style.

[1] Alcauter, S (2014). Development of thalamocortical connectivity during infancy and its cognitive correlations. Journal of Neuroscience, 34(27), 9067-9075.
[2] Cai, Y. (2017). Functional thalamocortical connectivity development and alterations in preterm infants during the neonatal period. Neuroscience, 356, 22-34.
[3] Ferradal, S. L (2019). System-specific patterns of thalamocortical connectivity in early brain development as revealed by structural and functional MRI. Cerebral Cortex, 29(3), 1218-1229.
[4] Toulmin, H (2015). Specialization and integration of functional thalamocortical connectivity in the human infant. Proceedings of the National Academy of Sciences, 112(20), 6485-6490.
[5] Toulmin, H (2021). Functional thalamocortical connectivity at term equivalent age and outcome at 2 years in infants born preterm. Cortex, 135, 17-29.

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