Abstract. – This exploration of how the unique susceptibility of the modern human brain to neurodegenerative illnesses appears to be related to that brain’s acquisition of complex cognitive functions is informed by both neuroscientific data and present understanding of recent human evolution. The near-absence of such pathologies in other extant primates prompts an analysis of the differences between the human and ape brains, which relate both to relative size and structure. Relevant human brain illnesses implicate specific brain areas in these pathologies, such as the frontal cortex, temporal and parietal lobes, limbic system, and basal ganglia in illness like schizophrenia, bipolar disorder, Parkinson’s disease, and others. The expansion of these same areas has also facilitated the advanced cognitive abilities marking the emergence of Homo sapiens. The authors then explore the questions of when, in this process, the brain diseases first established themselves in the genome, and why natural evolutionary processes failed to select against them. Based on the similarly deleterious introduction of gracility in formerly robust human populations, attributed to breeding mate selection becoming influenced by cultural constructs, the hypothesis is proposed that the dramatic rise of culture over the past 40,000 years or so also rendered the toleration of these brain pathologies possible. Just as the modern human has become a fetalised, neotenous form of ape through unintended self-domestication, a similar process also protected unfavourable mutations of recent encephalisation, such as demyelination, against natural selection. [Human evolution, cognitive functions, brain abilities, brain pathologies, natural selection]