Encyclopedia of Behavioral Neuroscience, second edition (BEV2)

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Lesion-Symptom Mapping: From Single Cases to the Human Disconnectome

The famous cases of neuroscience, including Henry Gustave Molaison (patient ’H.M’), Phineas Gage, and Louis Victor Leborgne (patient ’Tan’), have critically shaped initial theories about the functioning of the brain and remain highly influential today to the field of human brain mapping. Understanding the functions of the brain and how they came to be associated with specific brain areas and networks has been a vivid field of study since. This association was primarily based on the observation of single patients that allowed principle functions such as perception (Ungerleider and Mishkin, 1982), emotion (Adolphs et al., 2005), memory (Corkin, 2013), attention (Posner et al., 1982), and verbal communication (Lichtheim, 1885) to be identified, localized and subsequently fractionated into more specific cognitive subprocesses. The clinical-anatomical association method based on lesion- symptom mapping is one of the oldest means to study the brain’s structure-function relationship. The earliest reports of the use of lesion mapping methods were based on patients presenting with behavioral peculiarities or a loss of function following a lesion to the brain (e.g., traumatic brain injury, stroke). Behavioral changes were associated with structural damage to a surface area of the brain or a specific brain region (e.g., Broca, 1861; Wernicke, 1874; Sperry 1961; Luria 1966). For centuries, such single cases were carefully described, and together they form the origins of modern neurosciences and neurology (Finger, 1994; Damasio and Damasio, 1989). While these studies greatly enhanced our understanding of the anatomical-functional division of the brain surface (Glasser et al., 2016; Yarkoni et al., 2011), they did not comprehensively map the entire brain and its functions. This is in part due to methodological limitations (e.g., availability of neuroimaging, limited case numbers), conceptual limitations (e.g., localiza- tionism) and the fact that natural lesions (e.g., strokes, tumors) are not homogeneously distributed across the brain (Mah et al., 2014). These limitations are further aggravated by a significant degree of inter-individual variability in the architecture of the brain and location of function (e.g., Uylings et al., 2005; Caulo et al., 2007; Leonard et al., 1998; Eichert et al., 2021; Basso et al., 1985, Vigneau et al., 2006, Forkel et al., 2020b). With the advent of neuroimaging techniques, it became feasible to systematically study ....

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