How does complex brain activity organize thought and behaviour? Theoretical proposals have long emphasized that intelligent behaviour must be supported by a flexible control system. Numerous brain imaging studies identified a domain-general or “multiple-demand” (MD) brain system co-activated accompanying many tasks and is hypothesised to play a central role in cognitive control. However, the limited spatial localization provided by traditional imaging methods precluded a consensus regarding its anatomy and physiology. To address these limitations, the experiments in chapters 2 and 3 capitalize on novel multi-modal magnetic resonance imaging (MRI) methods developed by the Human Connectome Project. Chapter 2 delineated nine cortical MD patches per hemisphere and subdivided them into 10 regions forming a core of most strongly activated and functionally interconnected regions, surrounded by a penumbra of 17 additional regions. MD activations were also identified in specific subcortical and cerebellar regions. Chapter 3 investigated the relation between the newly defined MD regions and previously identified sensory-biased cortical regions. Contrasting auditory and visual low working memory demands revealed the strongest sensory-biases are localized just outside of MD regions. And additional working memory demands revealed MD activations showed no sensory biases. Chapter 4 used human electrophysiological recordings from the lateral frontal cortex to functionally map cognitive control regions during awake neurosurgeries. By contrasting a hard vs easy cognitive demand, spectral analysis revealed localized power increases in the gamma range (>30 Hz) that overlap with a canonical mask of the fronto-parietal control network. These findings contrast with spatially non-specific power decreases in the beta range (12-30 Hz). Thus, using similar task difficulty manipulations, electrophysiology and MRI functional signals converged on localizing lateral frontal regions related to cognitive control and support their clinical potential for intraoperative mapping of cognitive control. All together, the distributed anatomical organization, mosaic functional preferences, and strong functional interconnectivity of MD regions, suggest a skeleton for integrating and organizing the diverse components of cognitive operations. The precise anatomical delineation of MD regions provides the groundwork for refined analyses of their functions.