Segregated fronto-cerebellar circuits revealed by intrinsic functional connectivity
Open accessAbstract
Multiple, segregated fronto-cerebellar circuits have been characterized in nonhuman primates using transneuronal tracing techniques including those that target prefrontal areas. Here, we used functional connectivity MRI (fcMRI) in humans (n = 40) to identify 4 topographically distinct fronto-cerebellar circuits that target 1) motor cortex, 2) dorsolateral prefrontal cortex, 3) medial prefrontal cortex, and 4) anterior prefrontal cortex. All 4 circuits were replicated and dissociated in an independent data set (n = 40). Direct comparison of right- and left-seeded frontal regions revealed contralateral lateralization in the cerebellum for each of the segregated circuits. The presence of circuits that involve prefrontal regions confirms that the cerebellum participates in networks important to cognition including a specific fronto-cerebellar circuit that interacts with the default network. Overall, the extent of the cerebellum associated with prefrontal cortex included a large portion of the posterior hemispheres consistent with a prominent role of the cerebellum in nonmotor functions. We conclude by providing a provisional map of the topography of the cerebellum based on functional correlations with the frontal cortex.
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Word retrieval is accompanied by activation in the right vermal and hemispheric components of lobule VI and Crus I and II of lobule VII in the posterior lateral cerebellum.
“and this was accompanied by activation in the right vermal and hemispheric components of lobule VI and Crus I and II of lobule VII in the posterior lateral cerebellum (Krienen and Buckner, 2009; Murdoch, 2010; Stoodley and Shamahmann, 2009, 2010).”
From A review and synthesis of the first 20years of PET and fMRI studies of heard speech, spoken language and reading (2012) · cites this paper as Krienen and Buckner, 2009
Polysynaptic connections between the cerebellum and the cortex have been demonstrated in anatomic tracing and functional connectivity studies.
“Polysynaptic connections between the cerebellum and the cortex have been demonstrated both in anatomic tracing studies and functional connectivity studies9,10,11,12,13.”
From Regulation of autism-relevant behaviors by cerebellar-prefrontal cortical circuits (2020) · cites this paper as [9]
Connectivity exists between the left mPFC and Rcrus1 in humans and primates.
“We and others previously demonstrated connectivity between the left mPFC and Rcrus1 in humans and primates8,9,10.”
From Regulation of autism-relevant behaviors by cerebellar-prefrontal cortical circuits (2020) · cites this paper as [9]
Functional connections exist between the cerebellar cortex and cerebral cortical areas in the regulation of complex non-motor behavior.
“support functional connections between the cerebellar cortex and cerebral cortical areas in the regulation of complex non-motor behavior3,9,10,19.”
From Regulation of autism-relevant behaviors by cerebellar-prefrontal cortical circuits (2020) · cites this paper as [9]
The interaction of the cerebellum with higher-order intrinsic connectivity networks could modulate executive function, mentalizing, and salience detection, functions critical for social cognition and social interaction.
“Specifically, the interaction of the cerebellum with higher-order intrinsic connectivity networks (Habas et al., 2009, Krienen and Buckner, 2009) could similarly modulate executive function, mentalizing, and salience detection − functions critical for social cognition and social interaction (Menon, 2011).”
From The impact of atypical sensory processing on social impairments in autism spectrum disorder (2018) · cites this paper as Krienen and Buckner, 2009
These patterns of size-independently co-evolving brain structures correspond to brain systems that have been described in electrophysiological and anatomical tract-tracing studies in non-human primates and MRI studies in humans.
“These patterns of size-independently co-evolving brain structures correspond to brain systems that have been described in electrophysiological and anatomical tract-tracing studies in non-human primates [27–31] and MRI studies in humans [32–35]”
From Brain reorganization, not relative brain size, primarily characterizes anthropoid brain evolution (2013) · cites this paper as [33]
PC7 loads on structures associated with cortico-cerebellar connectivity (cerebrocerebellum and frontal motor areas).
“while PC7 loads on structures associated with cortico-cerebellar connectivity (cerebrocerebellum and frontal motor areas) [33,61,62] (table 1).”
From Brain reorganization, not relative brain size, primarily characterizes anthropoid brain evolution (2013) · cites this paper as [33]
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- Authors
- Krienen, F. M., & Buckner, R. L.
- Affiliations
- Harvard University (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Krienen, Fenna M.
- Venue
- Cerebral Cortex
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-07-10
- Volume
- 19
- Issue
- 10
- Pages
- 2485-2497
- ISSN
- 1047-3211 (ISSN-L)
- 1460-2199
- PMC
- PMC2742600
- OpenAlex
- W2153254791
- Cited by
- 782
- References
- 70
- Citations by year
- 2026: 21 · 2025: 46 · 2024: 30 · 2023: 37 · 2022: 48 · 2021: 62 · 2020: 51 · 2019: 49 · 2018: 49 · 2017: 40 · 2016: 50 · 2015: 46 · 2014: 54 · 2013: 61 · 2012: 56
- FWCI
- 21.85
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Cerebral Cortex (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- Howard Hughes Medical Institute
- National Institute on Aging (AG021910, R01AG021910)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Life Sciences › Neuroscience › Cognitive Neuroscience › Motor Control and Adaptation
- Keywords
- cerebellum, prefrontal cortex, functional connectivity, motor cortex, dorsolateral prefrontal cortex, medial prefrontal cortex, anterior prefrontal cortex, hemispheric lateralization, default mode network
- MeSH terms
- Adolescent, Adult, Brain Mapping, Cerebellum, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Motor Cortex, Neural Pathways, Prefrontal Cortex
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