Short Association Fibers of the Dorsolateral Prefrontal Cortex are Measurable with Tractography
Poster No:
1782
Submission Type:
Abstract Submission
Authors:
Matthew Amandola1, Michael Kim2, Bennett Landman2, Kurt Schilling2
Institutions:
1Vanderbilt University Institute of Imaging Science, Nashville, TN, 2Vanderbilt University, Nashville, TN
First Author:
Co-Author(s):
Introduction:
The dorsolateral prefrontal cortex (dl-PFC) is an advanced association region of the brain and facilitates complex cognitive functioning such as working memory (Levy & Goldman-Rakic, 2000). Past histological research in non-human primates (NHP) show that beyond distant cortical connections from long association fibers, the dl-PFC is highly interconnected with other PFC areas via short association fibers (SAF; Barbas & Pandya, 1989; Petrides & Pandya, 1999, 2006). However, despite clear patterns of connectivity demonstrated by NHP tract-tracing studies, the short range connections of the dl-PFC remain unclear in the human brain. Here, we reconstruct the SAFs of the dl-PFC previously seen in histology, with region-of-interest (ROI) selection guided by tract-tracing studies, and suggest the feasibility of reconstructing small, intrinsic cortico-cortical connections which resemble both the connections and absence of connections measured by histology.
Methods:
We aimed to reconstruct the SAFs of the dl-PFC, with ROIs selected if they demonstrated connectivity in the NHP tract-tracing regions. The dl-PFC was defined by Brodmann areas (BA) 9, 46, and 9/46, and prefrontal regions included the frontal pole, orbitofrontal PFC, anterior cingulate cortex, frontal eye field, and ventrolateral PFC (Figure 1; Barbas & Pandya, 1989; Petrides & Pandya, 1999, 2006; Haber et al., 2022). ROIs were extracted from the HCP Multi-modal Parcellation Atlas (Glasser et al., 2016). Anatomically constrained probabilistic tractography was performed on 177 subjects from the Human Connectome Project (HCP) database (Van Essen et al., 2012), using the MRTrix3 software package (Tournier et al., 2019). Data were corrected for susceptibility induced distortions, motion corrected, and EDDY corrected using FSL (Jenkinson et al., 2012), and ROIs were transformed to each subject's native space. Outlier removal was conducted on the resulting tracts.
·Figure 1 - Dorsolateral PFC Histological Connections
Results:
We found that the SAFs we reconstructed with tractography exhibited a strong resemblance to the patterns of short-range connectivity demonstrated by tract-tracing literature (Figure 2). This is particularly true for BA 9, which shared all the strong connections in prefrontal regions listed in the histological literature. Overall, BA 9/46 also showed close resemblance to histological findings. BA 46 deviated the most from the tract-tracing literature, lacking connectivity with the anterior cingulate (BA 32), and BA 47. Interestingly, both areas 46 and 9/46 lacked the sparse connections to the orbitofrontal PFC (BA 13, 14) typically observed in tract-tracing literature. Finally, we found that connections to the dl-PFC which lacked histological evidence were accurately reflected in our results, suggesting that while probabilistic tractography is often vulnerable to false trajectories (Maier-Hein et al., 2017), our methodology seems highly specific.
·Figure 2 - Dorsolateral PFC Short Association Fibers Measured with Tractography
Conclusions:
Our study suggests that the intrinsic connections of the dl-PFC, as well as its local connectivity to the rest of the PFC, are able to be reconstructed and studied using probabilistic tractography. Our results also suggest that these prefrontal local connections closely resemble connections of the NHP tract-tracing literature, particularly in BA 9 and 9/46. Additionally, our results suggest that our ROI selection, tractography logic, and processing pipeline are relatively robust to spurious tracts, as most connections with little or no histological evidence were accurately reflected by our methodology. This study pipeline provides an accessible avenue to non-invasively measure the intrinsic connections of the dl-PFC, and can be used in combination with diffusion metrics to provide insights into the neurological underpinnings of related cognitive processes such as working memory and executive functioning. Future directions include assessing these prefrontal connections in clinical populations as potential biomarkers for neurological disorders.
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Cortical Anatomy and Brain Mapping 2
White Matter Anatomy, Fiber Pathways and Connectivity 1
Keywords:
Tractography
White Matter
WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC
Other - Short association fibers; U-fibers; superficial white matter; dorsolateral prefrontal cortex
1|2Indicates the priority used for review
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Provide references using APA citation style.
Barbas, H., & Pandya, D. N. (1989). Architecture and intrinsic connections of the prefrontal cortex in the rhesus monkey. Journal of Comparative Neurology, 286(3), 353–375. https://doi.org/10.1002/cne.902860306
Petrides, M., & Pandya, D. N. (1999). Dorsolateral prefrontal cortex: Comparative cytoarchitectonic analysis in the human and the macaque brain and corticocortical connection patterns. The European Journal of Neuroscience, 11(3), 1011–1036. https://doi.org/10.1046/j.1460-9568.1999.00518.x
Petrides, M., & Pandya, D. N. (2006). Efferent association pathways originating in the caudal prefrontal cortex in the macaque monkey. The Journal of Comparative Neurology, 498(2), 227–251. https://doi.org/10.1002/cne.21048
Haber, S. N., Liu, H., Seidlitz, J., & Bullmore, E. (2022). Prefrontal connectomics: From anatomy to human imaging. Neuropsychopharmacology, 47(1), 20–40. https://doi.org/10.1038/s41386-021-01156-6
Glasser, M. F., Coalson, T. S., Robinson, E. C., Hacker, C. D., Harwell, J., Yacoub, E., Ugurbil, K., Andersson, J., Beckmann, C. F., Jenkinson, M., Smith, S. M., & Van Essen, D. C. (2016). A multi-modal parcellation of human cerebral cortex. Nature, 536(7615), 171–178. https://doi.org/10.1038/nature18933
Van Essen, D. C., Ugurbil, K., Auerbach, E., Barch, D., Behrens, T. E. J., Bucholz, R., Chang, A., Chen, L., Corbetta, M., Curtiss, S. W., Della Penna, S., Feinberg, D., Glasser, M. F., Harel, N., Heath, A. C., Larson-Prior, L., Marcus, D., Michalareas, G., Moeller, S., … WU-Minn HCP Consortium. (2012). The Human Connectome Project: A data acquisition perspective. NeuroImage, 62(4), 2222–2231. https://doi.org/10.1016/j.neuroimage.2012.02.018
Tournier, J.-D., Smith, R., Raffelt, D., Tabbara, R., Dhollander, T., Pietsch, M., Christiaens, D., Jeurissen, B., Yeh, C.-H., & Connelly, A. (2019). MRtrix3: A fast, flexible and open software framework for medical image processing and visualisation. NeuroImage, 202, 116137. https://doi.org/10.1016/j.neuroimage.2019.116137
Jenkinson, M., Beckmann, C. F., Behrens, T. E. J., Woolrich, M. W., & Smith, S. M. (2012). FSL. NeuroImage, 62(2), 782–790. https://doi.org/10.1016/j.neuroimage.2011.09.015
Maier-Hein et al. (2017) The challenge of mapping the human connectome based on diffusion tractogra