Human decisions about when to act originate within a basal forebrain–nigral circuit
Open accessAbstract
Decisions about when to act are critical for survival in humans as in animals, but how a desire is translated into the decision that an action is worth taking at any particular point in time is incompletely understood. Here we show that a simple model developed to explain when animals decide it is worth taking an action also explains a significant portion of the variance in timing observed when humans take voluntary actions. The model focuses on the current environment’s potential for reward, the timing of the individual’s own recent actions, and the outcomes of those actions. We show, by using ultrahigh-field MRI scanning, that in addition to anterior cingulate cortex within medial frontal cortex, a group of subcortical structures including striatum, substantia nigra, basal forebrain (BF), pedunculopontine nucleus (PPN), and habenula (HB) encode trial-by-trial variation in action time. Further analysis of the activity patterns found in each area together with psychophysiological interaction analysis and structural equation modeling suggested a model in which BF integrates contextual information that will influence the decision about when to act and communicates this information, in parallel with PPN and HB influences, to nigrostriatal circuits. It is then in the nigrostriatal circuit that action initiation per se begins.
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7T fMRI allowed measurement of BOLD activity even in small subcortical regions such as the DRN and MBD-associated nuclei.
“7T fMRI allowed us to measure blood-oxygen-level-dependent (BOLD) activity even in small subcortical regions such as the dorsal raphe nucleus (DRN)15”
From Two prefrontal-subcortical circuits estimate controllability and reflect its impact on learning (2026) · cites this paper as [16]
The Discussion (page not provided) says ultrahigh-field fMRI enabled extraction of BOLD signals from small basal forebrain, midbrain, and brainstem structures. It does not identify the dorsal raphe nucleus or MBD-associated nuclei as structures measured, so those specific examples are not supported by this paper. (LLM, conf=0.86)
Experimental — accuracy not yet measuredAI and activity in dopaminergic midbrain areas such as SN have been reported when people evaluate whether and when to initiate an action.
“AI and activity in dopaminergic midbrain areas such as SN have been reported when people evaluate whether and when to initiate an action28,41.”
From Interpretable abstractions of artificial neural networks predict behavior and neural activity during human information gathering (2026) · cites this paper as [41]
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- [45]Khalighinejad N., Priestley L., Jbabdi S., Rushworth M., Human decisions about when to act originate within a basal forebrain-nigral circuit, v4. Dryad. Available at 10.5061/dryad.prr4xgxhv. Deposited 23 April 2020. PMC7260969 32385157 · DOI
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- Authors
- Khalighinejad, N., Priestley, L., Jbabdi, S., & Rushworth, M. F. S.
- Affiliations
- University of Oxford (GB)
- Wellcome Centre for Integrative Neuroimaging, Centre for Functional Magnetic Resonance Imaging of the Brain, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom
- Corresponding author
- Khalighinejad, Nima
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2020-05-08
- Volume
- 117
- Issue
- 21
- Pages
- 11799-11810
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC7260969
- OpenAlex
- W3015366503
- Cited by
- 29
- References
- 47
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 3 · 2023: 2 · 2022: 5 · 2021: 5 · 2020: 2 · 2019: 1
- FWCI
- 1.87
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, public-domain)
- DRYAD (public-domain)
- Funders
- Wellcome (WT101092MA, WT100973AIA, 203139/Z/16/Z)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Motor Control and Adaptation
- Keywords
- action timing, basal forebrain, substantia nigra, pedunculopontine nucleus, habenula, striatum, anterior cingulate cortex, voluntary action, reward prediction, action initiation, ultra-high field MRI, psychophysiological interaction
- MeSH terms
- Adult, Decision Making, Female, Humans, Magnetic Resonance Imaging, Male, Models, Neurological, Nerve Net, Substantia Nigra, Basal Forebrain
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