Patricia Goldman-Rakic’s primate microelectrode work in the 1980s and 1990s identified persistent neuronal firing in dorsolateral prefrontal cortex during the delay period of working-memory tasks. This delay-activity, sustained for seconds at a time without sensory input, provided the cellular substrate for behavioural working memory and established DLPFC as the most-studied cortical correlate of “thought” in the modern neuroscience era.

Miller and Cohen’s 2001 integrative theory placed DLPFC at the apex of cognitive control, with top-down signals to other cortical regions biasing competition in favour of goal-relevant representations. The theory has held up well: DLPFC activity correlates with task-set maintenance across an enormous variety of paradigms, and the strength of this maintenance signal predicts performance.

The clinical impact of these basic-science findings is most visible in psychiatry. Repetitive transcranial magnetic stimulation of left DLPFC was FDA-approved for treatment-resistant depression in 2008, on the basis that hypoactive left DLPFC is a reproducible imaging finding in depression and that experimentally upregulating DLPFC activity produces clinical benefit. Similar protocols are being trialled for OCD, PTSD, and substance-use disorders.