Complex cognitive functions such as working memory and decision-making require information maintenance over seconds to years, from transient sensory stimuli to long-term contextual cues. While theoretical accounts predict the emergence of a corresponding hierarchy of neuronal timescales, direct electrophysiological evidence across the human cortex is lacking. Here, we infer neuronal timescales from invasive intracranial recordings. Timescales increase along the principal sensorimotor-to-association axis across the entire human cortex, and scale with single-unit timescales within macaques. Cortex-wide transcriptomic analysis shows direct alignment between timescales and expression of excitation- and inhibition-related genes, as well as genes specific to voltage-gated transmembrane ion transporters. Finally, neuronal timescales are functionally dynamic: prefrontal cortex timescales expand during working memory maintenance and predict individual performance, while cortex-wide timescales compress with aging. Thus, neuronal timescales follow cytoarchitectonic gradients across the human cortex, and are relevant for cognition in both short- and long-terms, bridging microcircuit physiology with macroscale dynamics and behavior.

17Complex cognitive functions such as working memory and decision-making require information 18 maintenance over many timescales, from transient sensory stimuli to long-term contextual cues. 19While theoretical accounts predict the emergence of a corresponding hierarchy of neuronal 20 timescales, direct evidence in the human cortex is lacking. Here, we use a novel computational 21 approach to infer neuronal timescales from human intracranial recordings and find that 22 timescales gradually increase along the principal sensorimotor-to-association axis. Cortex-wide 23 transcriptomic analysis further shows a direct alignment between timescales and expression of 24 excitation-and inhibition-related genes, as well as genes specific to voltage-gated 25 transmembrane ion transporters. Finally, neuronal timescales are functionally dynamic: 26 prefrontal cortex timescales expand during working memory maintenance and predict individual 27 performance, while cortex-wide timescales compress with aging. Thus, neuronal timescales 28 follow cytoarchitectonic gradients across the human cortex, and are relevant for cognition in 29both short-and long-terms, bridging microcircuit physiology with macroscale dynamics and 30 behavior. 31 32One-sentence summary 33Human cortical timescales is associated with synaptic and ion channel genes, lengthens with 34 working memory maintenance, and shortens in aging. 35

Our ability to sustain attention for prolonged periods of time is limited. Studies on the relationship between lapses of attention and psychophysiological markers of attentional state, such as pupil diameter, have yielded contradicting results. Here, we investigated the relationship between tonic fluctuations in pupil diameter and performance on a demanding sustained attention task. We found robust linear relationships between baseline pupil diameter and several measures of task performance, suggesting that attentional lapses tended to occur when pupil diameter was small. However, these observations were primarily driven by the joint effects of time-on-task on baseline pupil diameter and task performance. The linear relationships disappeared when we statistically controlled for time-on-task effects and were replaced by consistent inverted U-shaped relationships between baseline pupil diameter and each of the task performance measures, such that most false alarms and the longest and most variable response times occurred when pupil diameter was both relatively small and large. Finally, we observed strong linear relationships between the temporal derivative of pupil diameter and task performance measures, which were largely independent of time-on-task. Our results help to reconcile contradicting findings in the literature on pupil-linked changes in attentional state, and are consistent with the adaptive gain theory of locus coeruleus-norepinephrine function. Moreover, they suggest that the derivative of baseline pupil diameter is a potentially useful psychophysiological marker that could be used in the on-line prediction and prevention of attentional lapses.