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Different lines of evidence implicate the prefrontal cortex (especially the anterior cingulate cortex, ACC), dopaminergic, and cholinergic substrates in this modulation. We studied here the activity of these substrates at increasing time on task (requiring increasing levels of cognitive effort) in trials within blocks with differing reward levels. In the cortex, while peaking in the ACC, activity associated with time on task was extensive, also including activity decrements outside the default mode network, primarily involving motor and somatosensory regions. Information about reward levels was carried in the ventral striatum, consistent with its motivational role, but did not reflect trade-offs with increasing efforts during time on task. Instead, the ventral tegmental area and parts of the basal forebrain (BF) corresponding to the cholinergic Ch4 nuclei increased in activity with time on task and were sensitive to reward levels. This BF activity is consistent with a cholinergic role in driving compensatory efforts modulated by reward levels. These findings identify the BF as a neuroimaging phenotype associated with sustaining task sets and cognitive efforts.<\/jats:p>","DOI":"10.1038\/s41598-026-37370-9","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T17:55:53Z","timestamp":1770659753000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Functional imaging of time on task and the involvement of dopaminergic and cholinergic substrates in cognitive effort and reward"],"prefix":"10.1038","volume":"16","author":[{"given":"Chiara","family":"Orsini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia E.","family":"Bosch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Labek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Viviani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,9]]},"reference":[{"key":"37370_CR1","volume-title":"The Psychology of Vigilance","author":"DR Davies","year":"1982","unstructured":"Davies, D. 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