Imaging three-dimensional cerebellar connectivity using diffusion tractography is challenging because of the ubiquitous features of crossing axonal pathways within a folium as well as intersecting pathways from neighboring folia. We applied high-angular resolution diffusion imaging (HARDI) tractography to intact postmortem adult brainstem and cerebellum to examine the 3-dimensional white matter and local gray matter pathways. The middle cerebellar peduncles conveyed fibers from the rostral pons to the lateral and caudal aspects of the cerebellar hemisphere, and from the caudal pons to medial and rostral parts of the cerebellar hemisphere. In the cerebellar cortex, tractography detected tangential coherence superficially in the cerebellar cortex and revealed fibers coursing parallel to the long axis of the folia. These fibers were consistent with the location and direction of parallel fibers in the molecular layer. Crossing with these parallel fibers were tangential fibers running perpendicular to the long axis of the folia, consistent with axons othe cortical interneurons - stellate cells and basket cells. These tangential fibers within the cerebellar cortex were distinct from fibers linking the cerebellar cortex with the deep cerebellar nuclei and the brainstem. Our results show the potential for HARDI tractography to resolve axonal pathways from different neuronal elements within the cerebellar cortex, and improve our understanding of adult cerebellar neural circuitry and connectivity in both white and gray matter.
"The second step would comprise a comparison between in vivo and postmortem tractography in nonhuman species followed by in vivo tractography studies in multiple subjects to address the question of inter-individual anatomical variation. In this respect, Takahashi et al. already demonstrated the ability to reconstruct the superior cerebellar peduncle in postmortem high angular resolution diffusion imaging datasets in both adults (Takahashi et al. 2013) and during developmental stages (Takahashi et al. 2014). Further, the DRTT was studied in 15 healthy subjects and was successfully reconstructed with tractography in all subjects using a 1.5 T MRI scanner (Kwon et al. 2011). "
[Show abstract][Hide abstract] ABSTRACT: Diffusion-weighted imaging (DWI) tractography is a technique with great potential to characterize the in vivo anatomical position and integrity of white matter tracts. Tractography, however, remains an estimation of white matter tracts, and false-positive and false-negative rates are not available. The goal of the present study was to compare postmortem tractography of the dentatorubrothalamic tract (DRTT) by its 3D histological reconstruction, to estimate the reliability of the tractography algorithm in this specific tract. Recent studies have shown that the cerebellum is involved in cognitive, language and emotional functions besides its role in motor control. However, the exact working mechanism of the cerebellum is still to be elucidated. As the DRTT is the main output tract it is of special interest for the neuroscience and clinical community. A postmortem human brain specimen was scanned on a 7T MRI scanner using a diffusion-weighted steady-state free precession sequence. Tractography was performed with PROBTRACKX. The specimen was subsequently serially sectioned and stained for myelin using a modified Heidenhain-Woelke staining. Image registration permitted the 3D reconstruction of the histological sections and comparison with MRI. The spatial concordance between the two modalities was evaluated using ROC analysis and a similarity index (SI). ROC curves showed a high sensitivity and specificity in general. Highest measures were observed in the superior cerebellar peduncle with an SI of 0.72. Less overlap was found in the decussation of the DRTT at the level of the mesencephalon. The study demonstrates high spatial accuracy of postmortem probabilistic tractography of the DRTT when compared to a 3D histological reconstruction. This gives hopeful prospect for studying structure-function correlations in patients with cerebellar disorders using tractography of the DRTT.
Brain Structure and Function 10/2015; DOI:10.1007/s00429-015-1115-7 · 5.62 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Connectome is a term with a short history but a long past. Since the origins of neuroscience the concept of a 'map of neural connections' has been a constant inspiring idea for those who believed the brain as the organ of intellect. A myriad of protoconnectome maps have been produced throughout the centuries, each one reflecting the theory and method of investigation that prevailed at the time. Even contemporary definitions of the connectome rest upon the formulation of a neuronal theory that has been proposed over a hundred years ago. So, what is new? In this article we attempt to trace the development of certain anatomical and physiological concepts at the origins of modern definitions of the connectome. We argue that compared to previous attempts current connectomic approaches benefit from a wealth of imaging methods that in part could justify the enthusiasm for finally succeeding in achieving the goal. One of the unique advantages of contemporary approaches is the possibility of using quantitative methods to define measures of connectivity where structure, function and behaviour are integrated and correlated. We also argue that many contemporary maps are inaccurate surrogates of the true anatomy and a comprehensive connectome of the human brain remains a far distant point in the history to come.
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