Stephanie Forkel

Publications

Displaying 1 - 16 of 16
  • Dulyan, L., Guzmán Chacón, E. G., & Forkel, S. J. (2025). Navigating neuroanatomy. In J. H. Grafman (Ed.), Encyclopedia of the human brain (2nd ed.). Amsterdam: Elsevier.

    Abstract

    This chapter introduces the origins and development of our current anatomical terminology. It scrutinizes the historical evolution and etymological significance of the over 1900 official anatomical terms in the current nomenclature, underscoring their impact on the contemporary comprehension of cognitive neuroanatomy. The chapter traces unification efforts from the Basel Nomina Anatomica in 1895 to the 1998 Terminologia Anatomica, noting challenges arising from outdated terminology in light of recent anatomical advancements.

    Highlighting the influence of terminologies on interpretations of brain anatomy, the chapter explores several anatomical mapping methods such as surface, sectional, connectional, and functional anatomy. It illuminates discrepancies and controversies, exemplified by divergent interpretations of the number of brain lobes and the definitions of 'Broca' and 'Wernicke' areas.

    The chapter explores anatomical terms' historical and cultural underpinnings, encompassing mythonyms, eponyms, and cultural influences on nomenclature. It critically examines the implications of these terminologies on contemporary research and shows that Large Language Models mirror these discrepancies. It underscores the need for more inclusive and culturally sensitive approaches in anatomical education.

    Lastly, we advocate for updating anatomical nomenclature, suggesting that a deeper understanding of these terminologies could provide insights and aid in resolving ongoing debates in the field. This examination sheds light on historical knowledge and emphasizes the dynamic interplay between language, culture, and anatomy in shaping our comprehension of the neurobiology of the brain and how we navigate neuroanatomy in the 21st century.
  • Dulyan, L., Bortolami, C., & Forkel, S. J. (2025). Asymmetries in the human brain. In C. Papagno, & P. Corballis (Eds.), Cerebral Asymmetries: Handbook of Clinical Neurology (pp. 15-36). Amsterdam: Elsevier.

    Abstract

    The human brain is an intricate network of cortical regions interconnected by white matter pathways, dynamically supporting cognitive functions. While cortical asymmetries have been consistently reported, the asymmetry of white matter connections remains less explored. This chapter provides a brief overview of asymmetries observed at the cortical, subcortical, cytoarchitectural, and receptor levels before exploring the detailed connectional anatomy of the human brain. It thoroughly examines the lateralization and interindividual variability of 56 distinct white matter tracts, offering a comprehensive review of their structural characteristics and interindividual variability. Additionally, we provide an extensive update on the asymmetry of a wide range of white matter tracts using high-resolution data from the Human Connectome Project (7T HCP www.humanconnectome.org). Future research and advanced quantitative analyses are crucial to understanding fully how asymmetry contributes to interindividual variability. This comprehensive exploration enhances our understanding of white matter organization and its potential implications for brain function.
  • Forkel, S. J., Bortolami, C., Dulyan, L., Barrett, R. L. C., & Beyh, A. (2025). Dissecting white matter pathways: A neuroanatomical approach. In F. Dell'Acqua, M. Descoteaux, & A. Leemans (Eds.), Handbook of Diffusion MR Tractography (pp. 397-421). Amsterdam: Elsevier.

    Abstract

    The brain is the most magnificent structure, and we are only at the cusp of unraveling some of its complexity. Neuroanatomy is the best tool to map the brain's structural complexity. As such, neuroanatomy is not just an academic exercise; it serves our fundamental understanding of the neurobiology of cognition and improves clinical practice. A deepened anatomical understanding has advanced our conceptual grasp of the evolution of the brain, interindividual variability of cognition in health and disease, and the conceptual shift toward the emergence of cognition. For the past 20 years, diffusion imaging tractography has dramatically facilitated these advances by enabling the study of the delicate networks that orchestrate brain processes (for review, see Thiebaut de Schotten and Forkel, 2022). Several steps are consistent across all studied populations and brain states (health/disease) when analyzing tractography data. We discuss various considerations for dissections across populations and give practical tips on common pitfalls and features to improve the visualization of the dissections. We briefly discuss specific considerations for manual dissections in nonhuman primates. Lastly, we provide an atlas of regions of interest (ROIs) for the most commonly delineated white matter connections in the human brain.
  • Satoer, D., Dulyan, L., & Forkel, S. J. (2025). Oncology: Brain asymmetries in language-relevant brain tumors. In C. Papagno, & P. Corballis (Eds.), Cerebral Asymmetries: Handbook of Clinical Neurology (pp. 65-87). Amsterdam: Elsevier.

    Abstract

    Brain tumors are classified as rare diseases, with an annual occurrence of 300,000 cases and account for an annual loss of 241,000 lives, highlighting their devastating nature. Recent advancements in diagnosis and treatment have significantly improved the management and care of brain tumors. This chapter provides an overview of the common types of primary brain tumors affecting language functions—gliomas and meningiomas. Techniques for identifying and mapping critical language areas, including the white matter language system, such as awake brain tumor surgery and diffusion-weighted tractography, are pivotal for understanding language localization and informing personalized treatment approaches. Numerous studies have demonstrated that gliomas in the dominant hemisphere can lead to (often subtle) impairments across various cognitive domains, with a particular emphasis on language. Recently, increased attention has been directed toward (nonverbal) cognitive deficits in patients with gliomas in the nondominant hemisphere, as well as cognitive outcomes in patients with meningiomas, a group historically overlooked. A patient-tailored approach to language and cognitive functions across the pre-, intra-, and postoperative phases is mandatory for brain tumor patients to preserve quality of life. Continued follow-up studies, in conjunction with advanced imaging techniques, are crucial for understanding the brain's potential for neuroplasticity and optimizing patient outcomes.
  • Barrett, R. L. C., Dawson, M., Dyrby, T. B., Krug, K., Ptito, M., D'Arceuil, H., Croxson, P. L., Johnson, P. J., Howells, H., Forkel, S. J., Dell'Acqua, F., & Catani, M. (2020). Differences in Frontal Network Anatomy Across Primate Species. The Journal of Neuroscience, 40(10), 2094-2107. doi:10.1523/JNEUROSCI.1650-18.2019.

    Abstract

    The frontal lobe is central to distinctive aspects of human cognition and behavior. Some comparative studies link this to a larger frontal cortex and even larger frontal white matter in humans compared with other primates, yet others dispute these findings. The discrepancies between studies could be explained by limitations of the methods used to quantify volume differences across species, especially when applied to white matter connections. In this study, we used a novel tractography approach to demonstrate that frontal lobe networks, extending within and beyond the frontal lobes, occupy 66% of total brain white matter in humans and 48% in three monkey species: vervets (Chlorocebus aethiops), rhesus macaque (Macaca mulatta) and cynomolgus macaque (Macaca fascicularis), all male. The simian–human differences in proportional frontal tract volume were significant for projection, commissural, and both intralobar and interlobar association tracts. Among the long association tracts, the greatest difference was found for tracts involved in motor planning, auditory memory, top-down control of sensory information, and visuospatial attention, with no significant differences in frontal limbic tracts important for emotional processing and social behaviour. In addition, we found that a nonfrontal tract, the anterior commissure, had a smaller volume fraction in humans, suggesting that the disproportionally large volume of human frontal lobe connections is accompanied by a reduction in the proportion of some nonfrontal connections. These findings support a hypothesis of an overall rearrangement of brain connections during human evolution.
  • Forkel, S. J., Rogalski, E., Drossinos Sancho, N., D'Anna, L., Luque Laguna, P., Sridhar, J., Dell'Acqua, F., Weintraub, S., Thompson, C., Mesulam, M.-M., & Catani, M. (2020). Anatomical evidence of an indirect pathway for word repetition. Neurology, 94, e594-e606. doi:10.1212/WNL.0000000000008746.

    Abstract



    Objective: To combine MRI-based cortical morphometry and diffusion white matter tractography to describe the anatomical correlates of repetition deficits in patients with primary progressive aphasia (PPA).

    Methods: The traditional anatomical model of language identifies a network for word repetition that includes Wernicke and Broca regions directly connected via the arcuate fasciculus. Recent tractography findings of an indirect pathway between Wernicke and Broca regions suggest a critical role of the inferior parietal lobe for repetition. To test whether repetition deficits are associated with damage to the direct or indirect pathway between both regions, tractography analysis was performed in 30 patients with PPA (64.27 ± 8.51 years) and 22 healthy controls. Cortical volume measurements were also extracted from 8 perisylvian language areas connected by the direct and indirect pathways.

    Results: Compared to healthy controls, patients with PPA presented with reduced performance in repetition tasks and increased damage to most of the perisylvian cortical regions and their connections through the indirect pathway. Repetition deficits were prominent in patients with cortical atrophy of the temporo-parietal region with volumetric reductions of the indirect pathway.

    Conclusions: The results suggest that in PPA, deficits in repetition are due to damage to the temporo-parietal cortex and its connections to Wernicke and Broca regions. We therefore propose a revised language model that also includes an indirect pathway for repetition, which has important clinical implications for the functional mapping and treatment of neurologic patients.
  • Forkel, S. J., & Thiebaut de Schotten, M. (2020). Towards metabolic disconnection – symptom mapping. Brain, 143(3), 718-721. doi:10.1093/brain/awaa060.

    Abstract

    This scientific commentary refers to ‘Metabolic lesion-deficit mapping of human cognition’ by Jha etal.
  • Friedrich, P., Forkel, S. J., & Thiebaut de Schotten, M. (2020). Mapping the principal gradient onto the corpus callosum. NeuroImage, 223: 117317. doi:10.1016/j.neuroimage.2020.117317.

    Abstract

    Gradients capture some of the variance of the resting-state functional magnetic resonance imaging (rsfMRI) signal. Amongst these, the principal gradient depicts a functional processing hierarchy that spans from sensory-motor cortices to regions of the default-mode network. While the cortex has been well characterised in terms of gradients little is known about its underlying white matter. For instance, comprehensive mapping of the principal gradient on the largest white matter tract, the corpus callosum, is still missing. Here, we mapped the principal gradient onto the midsection of the corpus callosum using the 7T human connectome project dataset. We further explored how quantitative measures and variability in callosal midsection connectivity relate to the principal gradient values. In so doing, we demonstrated that the extreme values of the principal gradient are located within the callosal genu and the posterior body, have lower connectivity variability but a larger spatial extent along the midsection of the corpus callosum than mid-range values. Our results shed light on the relationship between the brain's functional hierarchy and the corpus callosum. We further speculate about how these results may bridge the gap between functional hierarchy, brain asymmetries, and evolution.

    Additional information

    supplementary file
  • Friedrich, P., Thiebaut de Schotten, M., Forkel, S. J., Stacho, M., & Howells, H. (2020). An ancestral anatomical and spatial bias for visually guided behavior. Proceedings of the National Academy of Sciences of the United States of America, 117(5), 2251-2252. doi:10.1073/pnas.1918402117.

    Abstract

    Human behavioral asymmetries are commonly studied in the context of structural cortical and connectional asymmetries. Within this framework, Sreenivasan and Sridharan (1) provide intriguing evidence of a relationship between visual asymmetries and the lateralization of superior colliculi connections—a phylogenetically older mesencephalic structure. Specifically, response facilitation for cued locations (i.e., choice bias) in the contralateral hemifield was associated with differences in the connectivity of the superior colliculus. Given that the superior colliculus has a structural homolog—the optic tectum—which can be traced across all Vertebrata, these results may have meaningful evolutionary ramifications.
  • Howells, H., Puglisi, G., Leonetti, A., Vigano, L., Fornia, L., Simone, L., Forkel, S. J., Rossi, M., Riva, M., Cerri, G., & Bello, L. (2020). The role of left fronto-parietal tracts in hand selection: Evidence from neurosurgery. Cortex, 128, 297-311. doi:10.1016/j.cortex.2020.03.018.

    Abstract

    Strong right-hand preference on the population level is a uniquely human feature, although its neural basis is still not clearly defined. Recent behavioural and neuroimaging literature suggests that hand preference may be related to the orchestrated function and size of fronto-parietal white matter tracts bilaterally. Lesions to these tracts induced during tumour resection may provide an opportunity to test this hypothesis. In the present study, a cohort of seventeen neurosurgical patients with left hemisphere brain tumours were recruited to investigate whether resection of certain white matter tracts affects the choice of hand selected for the execution of a goal-directed task (assembly of jigsaw puzzles). Patients performed the puzzles, but also tests for basic motor ability, selective attention and visuo-constructional ability, preoperatively and one month after surgery. An atlas-based disconnectome analysis was conducted to evaluate whether resection of tracts was significantly associated with changes in hand selection. Diffusion tractography was also used to dissect fronto-parietal tracts (the superior longitudinal fasciculus) and the corticospinal tract. Results showed a shift in hand selection despite the absence of any motor or cognitive deficits, which was significantly associated with frontal and parietal resections rather than other lobes. In particular, the shift in hand selection was significantly associated with the resection of dorsal rather than ventral fronto-parietal white matter connections. Dorsal white matter pathways contribute bilaterally to control of goal-directed hand movements. We show that unilateral lesions, that may unbalance the cooperation of the two hemispheres, can alter the choice of hand selected to accomplish movements.
  • Milham, M., Petkov, C. I., Margulies, D. S., Schroeder, C. E., Basso, M. A., Belin, P., Fair, D. A., Fox, A., Kastner, S., Mars, R. B., Messinger, A., Poirier, C., Vanduffel, W., Van Essen, D. C., Alvand, A., Becker, Y., Ben Hamed, S., Benn, A., Bodin, C., Boretius, S. Milham, M., Petkov, C. I., Margulies, D. S., Schroeder, C. E., Basso, M. A., Belin, P., Fair, D. A., Fox, A., Kastner, S., Mars, R. B., Messinger, A., Poirier, C., Vanduffel, W., Van Essen, D. C., Alvand, A., Becker, Y., Ben Hamed, S., Benn, A., Bodin, C., Boretius, S., Cagna, B., Coulon, O., El-Gohary, S. H., Evrard, H., Forkel, S. J., Friedrich, P., Froudist-Walsh, S., Garza-Villarreal, E. A., Gao, Y., Gozzi, A., Grigis, A., Hartig, R., Hayashi, T., Heuer, K., Howells, H., Ardesch, D. J., Jarraya, B., Jarrett, W., Jedema, H. P., Kagan, I., Kelly, C., Kennedy, H., Klink, P. C., Kwok, S. C., Leech, R., Liu, X., Madan, C., Madushanka, W., Majka, P., Mallon, A.-M., Marche, K., Meguerditchian, A., Menon, R. S., Merchant, H., Mitchell, A., Nenning, K.-H., Nikolaidis, A., Ortiz-Rios, M., Pagani, M., Pareek, V., Prescott, M., Procyk, E., Rajimehr, R., Rautu, I.-S., Raz, A., Roe, A. W., Rossi-Pool, R., Roumazeilles, L., Sakai, T., Sallet, J., García-Saldivar, P., Sato, C., Sawiak, S., Schiffer, M., Schwiedrzik, C. M., Seidlitz, J., Sein, J., Shen, Z.-m., Shmuel, A., Silva, A. C., Simone, L., Sirmpilatze, N., Sliwa, J., Smallwood, J., Tasserie, J., Thiebaut de Schotten, M., Toro, R., Trapeau, R., Uhrig, L., Vezoli, J., Wang, Z., Wells, S., Williams, B., Xu, T., Xu, A. G., Yacoub, E., Zhan, M., Ai, L., Amiez, C., Balezeau, F., Baxter, M. G., Blezer, E. L., Brochier, T., Chen, A., Croxson, P. L., Damatac, C. G., Dehaene, S., Everling, S., Fleysher, L., Freiwald, W., Griffiths, T. D., Guedj, C., Hadj-Bouziane, F., Harel, N., Hiba, B., Jung, B., Koo, B., Laland, K. N., Leopold, D. A., Lindenfors, P., Meunier, M., Mok, K., Morrison, J. H., Nacef, J., Nagy, J., Pinsk, M., Reader, S. M., Roelfsema, P. R., Rudko, D. A., Rushworth, M. F., Russ, B. E., Schmid, M. C., Sullivan, E. L., Thiele, A., Todorov, O. S., Tsao, D., Ungerleider, L., Wilson, C. R., Ye, F. Q., Zarco, W., & Zhou, Y.-d. (2020). Accelerating the Evolution of Nonhuman Primate Neuroimaging. Neuron, 105(4), 600-603. doi:10.1016/j.neuron.2019.12.023.

    Abstract

    Nonhuman primate neuroimaging is on the cusp of a transformation, much in the same way its human counterpart was in 2010, when the Human Connectome Project was launched to accelerate progress. Inspired by an open data-sharing initiative, the global community recently met and, in this article, breaks through obstacles to define its ambitions.

    Additional information

    supplementary information
  • Waymel, A., Friedrich, P., Bastian, P.-A., Forkel, S. J., & Thiebaut de Schotten, M. (2020). Anchoring the human olfactory system within a functional gradient. NeuroImage, 216: 116863. doi:10.1016/j.neuroimage.2020.116863.

    Abstract

    Margulies et al. (2016) demonstrated the existence of at least five independent functional connectivity gradients in the human brain. However, it is unclear how these functional gradients might link to anatomy. The dual origin theory proposes that differences in cortical cytoarchitecture originate from two trends of progressive differentiation between the different layers of the cortex, referred to as the hippocampocentric and olfactocentric systems. When conceptualising the functional connectivity gradients within the evolutionary framework of the Dual Origin theory, the first gradient likely represents the hippocampocentric system anatomically. Here we expand on this concept and demonstrate that the fifth gradient likely links to the olfactocentric system. We describe the anatomy of the latter as well as the evidence to support this hypothesis. Together, the first and fifth gradients might help to model the Dual Origin theory of the human brain and inform brain models and pathologies.
  • Croxson, P., Forkel, S. J., Cerliani, L., & Thiebaut De Schotten, M. (2018). Structural Variability Across the Primate Brain: A Cross-Species Comparison. Cerebral Cortex, 28(11), 3829-3841. doi:10.1093/cercor/bhx244.

    Abstract

    A large amount of variability exists across human brains; revealed initially on a small scale by postmortem studies and,
    more recently, on a larger scale with the advent of neuroimaging. Here we compared structural variability between human
    and macaque monkey brains using grey and white matter magnetic resonance imaging measures. The monkey brain was
    overall structurally as variable as the human brain, but variability had a distinct distribution pattern, with some key areas
    showing high variability. We also report the first evidence of a relationship between anatomical variability and evolutionary
    expansion in the primate brain. This suggests a relationship between variability and stability, where areas of low variability
    may have evolved less recently and have more stability, while areas of high variability may have evolved more recently and
    be less similar across individuals. We showed specific differences between the species in key areas, including the amount of
    hemispheric asymmetry in variability, which was left-lateralized in the human brain across several phylogenetically recent
    regions. This suggests that cerebral variability may be another useful measure for comparison between species and may add
    another dimension to our understanding of evolutionary mechanisms.
  • Forkel, S. J., & Catani, M. (2018). Lesion mapping in acute stroke aphasia and its implications for recovery. Neuropsychologia, 115, 88-100. doi:10.1016/j.neuropsychologia.2018.03.036.

    Abstract

    Patients with stroke offer a unique window into understanding human brain function. Mapping stroke lesions poses several challenges due to the complexity of the lesion anatomy and the mechanisms causing local and remote disruption on brain networks. In this prospective longitudinal study, we compare standard and advanced approaches to white matter lesion mapping applied to acute stroke patients with aphasia. Eighteen patients with acute left hemisphere stroke were recruited and scanned within two weeks from symptom onset. Aphasia assessment was performed at baseline and six-month follow-up. Structural and diffusion MRI contrasts indicated an area of maximum overlap in the anterior external/extreme capsule with diffusion images showing a larger overlap extending into posterior perisylvian regions. Anatomical predictors of recovery included damage to ipsilesional tracts (as shown by both structural and diffusion images) and contralesional tracts (as shown by diffusion images only). These findings indicate converging results from structural and diffusion lesion mapping methods but also clear differences between the two approaches in their ability to identify predictors of recovery outside the lesioned regions.
  • Forkel, S. J., & Catani, M. (2018). Structural Neuroimaging. In A. De Groot, & P. Hagoort (Eds.), Research Methods in Psycholinguistics and the Neurobiology of Language: A Practical Guide (pp. 288-308). Hoboken: Wiley. doi:10.1002/9781394259762.ch15.

    Abstract

    Structural imaging based on computerized tomography (CT) and magnetic resonance imaging (MRI) has progressively replaced traditional post‐mortem studies in the process of identifying the neuroanatomical basis of language. In the clinical setting, the information provided by structural imaging has been used to confirm the exact diagnosis and formulate an individualized treatment plan. In the research arena, neuroimaging has permitted to understand neuroanatomy at the individual and group level. The possibility to obtain quantitative measures of lesions has improved correlation analyses between severity of symptoms, lesion load, and lesion location. More recently, the development of structural imaging based on diffusion MRI has provided valid solutions to two major limitations of more conventional imaging. In stroke patients, diffusion can visualize early changes due to a stroke that are otherwise not detectable with more conventional structural imaging, with important implications for the clinical management of acute stroke patients. Beyond the sensitivity to early changes, diffusion imaging tractography presents the possibility of visualizing the trajectories of individual white matter pathways connecting distant regions. A pathway analysis based on tractography is offering a new perspective in neurolinguistics. First, it permits to formulate new anatomical models of language function in the healthy brain and allows to directly test these models in the human population without any reliance on animal models. Second, by defining the exact location of the damage to specific white matter connections we can understand the contribution of different mechanisms to the emergence of language deficits (e.g., cortical versus disconnection mechanisms). Finally, a better understanding of the anatomical variability of different language networks is helping to identify new anatomical predictors of language recovery. In this chapter we will focus on the principles of structural MRI and, in particular, diffusion imaging and tractography and present examples of how these methods have informed our understanding of variance in language performances in the healthy brain and language deficits in patient populations.
  • Vanderauwera, J., De Vos, A., Forkel, S. J., Catani, M., Wouters, J., Vandermosten, M., & Ghesquière, P. (2018). Neural organization of ventral white matter tracts parallels the initial steps of reading development: A DTI tractography study. Brain and Language, 183, 32-40. doi:10.1016/j.bandl.2018.05.007.

    Abstract

    Insight in the developmental trajectory of the neuroanatomical reading correlates is important to understand related cognitive processes and disorders. In adults, a dual pathway model has been suggested encompassing a dorsal phonological and a ventral orthographic white matter system. This dichotomy seems not present in pre-readers, and the specific role of ventral white matter in reading remains unclear. Therefore, the present longitudinal study investigated the relation between ventral white matter and cognitive processes underlying reading in children with a broad range of reading skills (n = 61). Ventral pathways of the reading network were manually traced using diffusion tractography: the inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF) and uncinate fasciculus (UF). Pathways were examined pre-reading (5–6 years) and after two years of reading acquisition (7–8 years). Dimension reduction for the cognitive measures resulted in one component for pre-reading cognitive measures and a separate phonological and orthographic component for the early reading measures. Regression analyses revealed a relation between the pre-reading cognitive component and bilateral IFOF and left ILF. Interestingly, exclusively the left IFOF was related to the orthographic component, whereas none of the pathways was related to the phonological component. Hence, the left IFOF seems to serve as the lexical reading route, already in the earliest reading stages.

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