Research on cognitive disorders is challenging due to the complexity of functions and numerous variables involved. The main purpose of this book is to effectively address the methodological issues and controversies in cognitive disorders research. First, it reviews the concept of human cognition as a complex activity involving interconnected mental and cerebral processes (its systemic structure), which represent the natural and social-cultural world by means of signs (its mediated, semiotic nature) and result from the internalization (or appropriation by the individual) of external actions and relations with things and persons (its cultural-historical origin). Subsequently, methodological issues are examined, including the use of the systemic and network approach in neuropsychological research, the concepts of single and double dissociation, single-case versus group studies, problems of brain-behavioral correlations using the lesion method and functional neuroimaging, the influence of task-relevant variables (confounders) related to the patient (e.g., age, education), to the lesion (size, etiology), and to the tests and testing conditions (ecological validity, examiners experience). Finally, readers are given the fundamentals of statistics applied to biomedical and psychological research, with illustrative examples of how to calculate Z score, effect size, 2 test, t test, Pearsons correlation coefficient, and simple linear regression. Methodological problems in current cognitive research on early multiple sclerosis, medial temporal lobe epilepsy, mild cognitive impairment and dementia are examined in detail.