In 1906 Holmes was appointed as director of clinical research at Queen Square, where he commenced collaborating with Henry Head (1861–1940) in 1908. This led to the first accurate account of the functions of the optic thalamus and its relation to the cerebral cortex. The two men complemented one another because Head was imaginative and enthusiastic as well as speculative, whereas Holmes insisted upon attention to detail and would never bend facts to fit a hypothesis. At times this led to clashes between the two, but they continued a close collaboration until the outbreak of the 1st World War.