Stephanie Forkel

Publications

Displaying 1 - 12 of 12
  • 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efforts from the Basel Nomina Anatomica in 1895 to the 1998 Terminologia Anatomica, noting challenges arising from outdated terminology in light of recent anatomical advancements.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.
  • Besharati, S., Forkel, S. J., Kopelman, M., Solms, M., Jenkinson, P. M., & Fotopoulou, A. (2014). The affective modulation of motor awareness in anosognosia for hemiplegia: Behavioural and lesion evidence. Cortex, 61, 127-140. doi:10.1016/j.cortex.2014.08.016.

    Abstract

    The possible role of emotion in anosognosia for hemiplegia (i.e., denial of motor deficits contralateral to a brain lesion), has long been debated between psychodynamic and neurocognitive theories. However, there are only a handful of case studies focussing on this topic, and the precise role of emotion in anosognosia for hemiplegia requires empirical investigation. In the present study, we aimed to investigate how negative and positive emotions influence motor awareness in anosognosia. Positive and negative emotions were induced under carefully-controlled experimental conditions in right-hemisphere stroke patients with anosognosia for hemiplegia (n = 11) and controls with clinically normal awareness (n = 10). Only the negative, emotion induction condition resulted in a significant improvement of motor awareness in anosognosic patients compared to controls; the positive emotion induction did not. Using lesion overlay and voxel-based lesion-symptom mapping approaches, we also investigated the brain lesions associated with the diagnosis of anosognosia, as well as with performance on the experimental task. Anatomical areas that are commonly damaged in AHP included the right-hemisphere motor and sensory cortices, the inferior frontal cortex, and the insula. Additionally, the insula, putamen and anterior periventricular white matter were associated with less awareness change following the negative emotion induction. This study suggests that motor unawareness and the observed lack of negative emotions about one's disabilities cannot be adequately explained by either purely motivational or neurocognitive accounts. Instead, we propose an integrative account in which insular and striatal lesions result in weak interoceptive and motivational signals. These deficits lead to faulty inferences about the self, involving a difficulty to personalise new sensorimotor information, and an abnormal adherence to premorbid beliefs about the body.

    Additional information

    supplementary file
  • Forkel, S. J., Thiebaut de Schotten, M., Dell’Acqua, F., Kalra, L., Murphy, D. G. M., Williams, S. C. R., & Catani, M. (2014). Anatomical predictors of aphasia recovery: a tractography study of bilateral perisylvian language networks. Brain, 137, 2027-2039. doi:10.1093/brain/awu113.

    Abstract

    Stroke-induced aphasia is associated with adverse effects on quality of life and the ability to return to work. For patients and clinicians the possibility of relying on valid predictors of recovery is an important asset in the clinical management of stroke-related impairment. Age, level of education, type and severity of initial symptoms are established predictors of recovery. However, anatomical predictors are still poorly understood. In this prospective longitudinal study, we intended to assess anatomical predictors of recovery derived from diffusion tractography of the perisylvian language networks. Our study focused on the arcuate fasciculus, a language pathway composed of three segments connecting Wernicke’s to Broca’s region (i.e. long segment), Wernicke’s to Geschwind’s region (i.e. posterior segment) and Broca’s to Geschwind’s region (i.e. anterior segment). In our study we were particularly interested in understanding how lateralization of the arcuate fasciculus impacts on severity of symptoms and their recovery. Sixteen patients (10 males; mean age 60 ± 17 years, range 28–87 years) underwent post stroke language assessment with the Revised Western Aphasia Battery and neuroimaging scanning within a fortnight from symptoms onset. Language assessment was repeated at 6 months. Backward elimination analysis identified a subset of predictor variables (age, sex, lesion size) to be introduced to further regression analyses. A hierarchical regression was conducted with the longitudinal aphasia severity as the dependent variable. The first model included the subset of variables as previously defined. The second model additionally introduced the left and right arcuate fasciculus (separate analysis for each segment). Lesion size was identified as the only independent predictor of longitudinal aphasia severity in the left hemisphere [beta = −0.630, t(−3.129), P = 0.011]. For the right hemisphere, age [beta = −0.678, t(–3.087), P = 0.010] and volume of the long segment of the arcuate fasciculus [beta = 0.730, t(2.732), P = 0.020] were predictors of longitudinal aphasia severity. Adding the volume of the right long segment to the first-level model increased the overall predictive power of the model from 28% to 57% [F(1,11) = 7.46, P = 0.02]. These findings suggest that different predictors of recovery are at play in the left and right hemisphere. The right hemisphere language network seems to be important in aphasia recovery after left hemispheric stroke.

    Additional information

    supplementary information
  • Forkel, S. J. (2014). Identification of anatomical predictors of language recovery after stroke with diffusion tensor imaging. PhD Thesis, King's College London, London.

    Abstract

    Background Stroke-induced aphasia is associated with adverse effects on quality of life and the ability to return to work. However, the predictors of recovery are still poorly understood. Anatomical variability of the arcuate fasciculus, connecting Broca’s and Wernicke’s areas, has been reported in the healthy population using diffusion tensor imaging tractography. In about 40% of the population the arcuate fasciculus is bilateral and this pattern is advantageous for certain language related functions, such as auditory verbal learning (Catani et al. 2007). Methods In this prospective longitudinal study, anatomical predictors of post-stroke aphasia recovery were investigated using diffusion tractography and arterial spin labelling. Patients An 18-subject strong aphasia cohort with first-ever unilateral left hemispheric middle cerebral artery infarcts underwent post stroke language (mean 5±5 days) and neuroimaging (mean 10±6 days) assessments and neuropsychological follow-up at six months. Ten of these patients were available for reassessment one year after symptom onset. Aphasia was assessed with the Western Aphasia Battery, which provides a global measure of severity (Aphasia Quotient, AQ). Results Better recover from aphasia was observed in patients with a right arcuate fasciculus [beta=.730, t(2.732), p=.020] (tractography) and increased fractional anisotropy in the right hemisphere (p<0.05) (Tract-based spatial statistics). Further, an increase in left hemisphere perfusion was observed after one year (p<0.01) (perfusion). Lesion analysis identified maximal overlay in the periinsular white matter (WM). Lesion-symptom mapping identified damage to periinsular structure as predictive for overall aphasia severity and damage to frontal lobe white matter as predictive of repetition deficits. Conclusion These findings suggest an important role for the right hemisphere language network in recovery from aphasia after left hemispheric stroke.

    Additional information

    Link to repository
  • Forkel, S. J., Thiebaut de Schotten, M., Kawadler, J. M., Dell'Acqua, F., Danek, A., & Catani, M. (2014). The anatomy of fronto-occipital connections from early blunt dissections to contemporary tractography. Cortex, 56, 73-84. doi:10.1016/j.cortex.2012.09.005.

    Abstract

    The occipital and frontal lobes are anatomically distant yet functionally highly integrated to generate some of the most complex behaviour. A series of long associative fibres, such as the fronto-occipital networks, mediate this integration via rapid feed-forward propagation of visual input to anterior frontal regions and direct top–down modulation of early visual processing.

    Despite the vast number of anatomical investigations a general consensus on the anatomy of fronto-occipital connections is not forthcoming. For example, in the monkey the existence of a human equivalent of the ‘inferior fronto-occipital fasciculus’ (iFOF) has not been demonstrated. Conversely, a ‘superior fronto-occipital fasciculus’ (sFOF), also referred to as ‘subcallosal bundle’ by some authors, is reported in monkey axonal tracing studies but not in human dissections.

    In this study our aim is twofold. First, we use diffusion tractography to delineate the in vivo anatomy of the sFOF and the iFOF in 30 healthy subjects and three acallosal brains. Second, we provide a comprehensive review of the post-mortem and neuroimaging studies of the fronto-occipital connections published over the last two centuries, together with the first integral translation of Onufrowicz's original description of a human fronto-occipital fasciculus (1887) and Muratoff's report of the ‘subcallosal bundle’ in animals (1893).

    Our tractography dissections suggest that in the human brain (i) the iFOF is a bilateral association pathway connecting ventro-medial occipital cortex to orbital and polar frontal cortex, (ii) the sFOF overlaps with branches of the superior longitudinal fasciculus (SLF) and probably represents an ‘occipital extension’ of the SLF, (iii) the subcallosal bundle of Muratoff is probably a complex tract encompassing ascending thalamo-frontal and descending fronto-caudate connections and is therefore a projection rather than an associative tract.

    In conclusion, our experimental findings and review of the literature suggest that a ventral pathway in humans, namely the iFOF, mediates a direct communication between occipital and frontal lobes. Whether the iFOF represents a unique human pathway awaits further ad hoc investigations in animals.
  • Vergani, F., Mahmood, S., Morris, C., Mitchell, P., & Forkel, S. J. (2014). Intralobar fibres of the occipital lobe: A post mortem dissection study. Cortex, 56, 145-156. doi:10.1016/j.cortex.2014.03.002.

    Abstract

    Introduction

    The atlas by Heinrich Sachs (1892) provided an accurate description of the intralobar fibres of the occipital lobe, with a detailed representation of the short associative tracts connecting different parts of the lobe. Little attention has been paid to the work of Sachs since its publication. In this study, we present the results of the dissection of three hemispheres, performed according to the Klingler technique (1935). Our anatomical findings are then compared to the original description of the occipital fibres anatomy as detailed by Sachs.
    Methods

    Three hemispheres were dissected according to Klingler's technique (1935). Specimens were fixed in 10% formalin and frozen at −15 °C for two weeks. After defreezing, dissection of the white matter fibres was performed with blunt dissectors. Coronal sections were obtained according to the cuts originally described by Sachs. In addition, medial to lateral and lateral to medial dissection of the white matter of the occipital lobe was also performed.

    Results

    A network of short association fibres was demonstrated in the occipital lobe, comprising intralobar association fibres and U-shaped fibres, which are connecting neighbouring gyri. Lateral to the ventricles, longitudinal fibres of the stratum sagittale were also identified that are arranged as external and internal layers. Fibres of the forceps major were also found to be in direct contact with the ventricular walls. We were able to replicate all tracts originally described by Sachs. In addition, a previously unrecognised tract, connecting the cuneus to the lingual gyrus, was identified. This tract corresponds to the “sledge runner”, described in tractography studies.

    Conclusions

    The occipital lobe shows a rich network of intralobar fibres, arranged around the ventricular wall. Good concordance was observed between the Klingler dissection technique and the histological preparations of Sachs.
  • Catani, M., Craig, M. C., Forkel, S. J., Kanaan, R., Picchioni, M., Toulopoulou, T., Shergill, S., Williams, S., Murphy, D. G., & McGuire, P. (2011). Altered integrity of perisylvian language pathways in schizophrenia: Relationship to auditory hallucinations. Biological Psychiatry, 70(12), 1143-1150. doi:10.1016/j.biopsych.2011.06.013.

    Abstract

    Background: Functional neuroimaging supports the hypothesis that auditory verbal hallucinations (AVH) in schizophrenia result from altered functional connectivity between perisylvian language regions, although the extent to which AVH are also associated with an altered tract anatomy is less clear.

    Methods: Twenty-eight patients with schizophrenia subdivided into 17 subjects with a history of AVH and 11 without a history of hallucinations and 59 age- and IQ-matched healthy controls were recruited. The number of streamlines, fractional anisotropy (FA), and mean diffusivity were measured along the length of the arcuate fasciculus and its medial and lateral components.

    Results: Patients with schizophrenia had bilateral reduction of FA relative to controls in the arcuate fasciculi (p < .001). Virtual dissection of the subcomponents of the arcuate fasciculi revealed that these reductions were specific to connections between posterior temporal and anterior regions in the inferior frontal and parietal lobe. Also, compared with controls, the reduction in FA of these tracts was highest, and bilateral, in patients with AVH, but in patients without AVH, this reduction was reported only on the left.

    Conclusions: These findings point toward a supraregional network model of AVH in schizophrenia. They support the hypothesis that there may be selective vulnerability of specific anatomical connections to posterior temporal regions in schizophrenia and that extensive bilateral damage is associated with a greater vulnerability to AVH. If confirmed by further studies, these findings may advance our understanding of the anatomical factors that are protective against AVH and predictive of a treatment response.
  • Forkel, S. J., Dell’Acqua, F., Kalra, L., Williams, S. C., & Catani, M. (2011). Lateralisation of the Arcuate Fasciculus Predicts Aphasia Recovery at 6 Months. Procedia - Social and Behavioral Sciences, 23, 164-166. doi:10.1016/j.sbspro.2011.09.221.
  • Thiebaut de Schotten, M., Dell'Acqua, F., Forkel, S. J., Simmons, A., Vergani, F., Murphy, D. G. M., & Catani, M. (2011). A lateralized brain network for visuospatial attention. Nature Neuroscience, 14, 1245-1246. doi:10.1038/nn.2905.

    Abstract

    Right hemisphere dominance for visuospatial attention is characteristic of most humans, but its anatomical basis remains unknown. We report the first evidence in humans for a larger parieto-frontal network in the right than left hemisphere, and a significant correlation between the degree of anatomical lateralization and asymmetry of performance on visuospatial tasks. Our results suggest that hemispheric specialization is associated with an unbalanced speed of visuospatial processing.

    Additional information

    supplementary material

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