Cross-region neuron co-firing mediated by ripple oscillations supports distributed working memory representations.

High-frequency ([~]90Hz) ripple oscillations may promote integrative processing in mammalian brains. Previous work has demonstrated that the co-occurrence of these ripple oscillations is associated with enhanced temporal binding of neural activity between human cortical neurons separated by up to 12mm. However, it remains unclear whether co-ripple facilitation of neuronal coupling supports cognitive processing, or if it occurs at greater distances. Here, we analyze intracranial recordings from patients implanted with microwire electrodes in the hippocampus, amygdala, ventromedial prefrontal cortex, anterior cingulate cortex, and pre-supplementary motor area, bilaterally, during a working memory task. We demonstrate that ripple oscillations significantly increase in all recorded regions, during encoding, maintenance and retrieval. Furthermore, co-occurrence of ripples increases between brain regions, associated with [~]30% increases in cross-region co-firing, both without decrement over distances up to 220 mm. These increases in cross-regional co-rippling and associated co-firing scale with memory load during maintenance and retrieval. Critically, during retrieval, co-ripples promote the reinstatement of the stimulus-specific long-distance co-firing patterns observed during encoding, especially during rapid recognition. Our findings reveal that ripple oscillations orchestrate long-range neural communication that supports distributed neural representations during human cognition.