Resting-state functional connectivity of the vermal and hemispheric subregions of the cerebellum with both the cerebral cortical networks and subcortical structures
Highlights
► The human cerebellum is a functionally heterogeneous structure. ► Cerebellar subregions show different functional connectivity (FC) patterns. ► The cerebellar FC patterns reflect its functional integration and segregation. ► The functional organization of the cerebellum underlies its complex functions.
Introduction
The human cerebellum is thought to be a heterogeneous structure consisting of the vermis and two hemispheres, and it has been anatomically divided into lobules designated I–X (Schmahmann et al., 1999). Traditionally, the cerebellum has been regarded as a part of the motor system, serving motor-related functions such as posture maintenance (Ouchi et al., 1999, Ouchi et al., 2001) and motor control (Kasahara et al., 2010, Spencer et al., 2007). Recently, evidence from neuroimaging and clinical studies has supported the idea that the cerebellum is also involved in cognitive (Kirschen et al., 2008, Marien et al., 2001) and emotional functions (Gundel et al., 2003, Scheuerecker et al., 2007).
Most of our knowledge about the functions of cerebellar subregions comes from task-based neuroimaging studies. For example, in the cerebellar vermis, lobules I–V are involved in motor-related processing (Brown et al., 2006, Debaere et al., 2001, Ouchi et al., 1999, Ouchi et al., 2001); lobules VI and VII participate in controlling eye movements (Jenkinson and Miall, 2010); lobules III–V and VIII are activated during pain-related processes (Dimitrova et al., 2003, Dimitrova et al., 2004, Maschke et al., 2002); and lobules IX–X are involved in spatial orientation and balance (Walker et al., 2010, Yakusheva et al., 2008). In the cerebellar hemispheres, sensorimotor function is represented in lobules I–V (Grodd et al., 2001, Salmi et al., 2010) and occasionally in lobules VI and VIII (Stoodley and Schmahmann, 2009, Stoodley and Schmahmann, 2010); cognitive processing is subserved by lobules VI–VIII (Stoodley and Schmahmann, 2009, Stoodley and Schmahmann, 2010); lobule IX is found to be activated during the experiences of thirst (Parsons et al., 2000) and the sensation of acupuncture stimulation (Hui et al., 2005); and lobule X contributes to controlling gaze and balance (Shaikh et al., 2011).
However, task-based studies can only reveal a subset of regions in a functional network (Finn et al., 2010, Jenkins and Ranganath, 2010). For example, a working memory task can only activate a subset of brain regions of the memory network, while an episodic memory task can activate another subset of brain regions of the memory network. Recently, resting-state functional connectivity (rsFC) analysis, a technique with the potential to capture the full distribution of regions belonging to a functional network, has been used to parcellate heterogeneous brain structures (Anwander et al., 2007, Deen et al., 2011) and to investigate specific rsFC patterns of each subregion (Margulies et al., 2009, Yu et al., 2011, Zhang and Li, 2012). These findings have greatly improved our understanding of the functional organization of certain brain structures.
rsFC analysis has made important contributions to the understanding of neural circuitry, including: revealing strong rsFCs between the dentate nucleus and the parietal and prefrontal cortices (Allen et al., 2005); identifying 4 topographically distinct fronto-cerebellar circuits (Krienen and Buckner, 2009); subdividing the cerebellum into a primary sensorimotor zone and a supramodal zone (O'Reilly et al., 2010); categorizing cerebellar subregions into different functional networks (Habas et al., 2009); and mapping the organization of cerebro-cerebellar circuits (Buckner et al., 2011). However, several questions regarding rsFC patterns of cerebellar subregions have not yet been addressed: (1) What are the rsFC patterns of the vermal subregions? (2) Do the rsFC patterns differ among vermal, paravermal, and lateral hemispheric subregions? (3) What are the rsFCs of cerebellar subregions with the intrinsic connectivity networks (ICNs) and deep subcortical nuclei?
In the present study, we aimed to address these questions by analyzing resting-state functional magnetic resonance imaging (fMRI) data in 228 healthy young adults. We first compared rsFCs between paravermal and lateral hemispheric subregions (lobules VI, Crus I and Crus II) with large horizontal diameters and found subtle differences. We therefore defined lateral hemispheric subregions as regions of interest (ROIs) of the cerebellar hemisphere. We then analyzed rsFC patterns of 10 vermal subregions and compared them with corresponding hemispheric ROIs using voxel-based rsFC analysis. Finally, we used ROI-based rsFC analysis to investigate rsFCs of cerebellar subregions with the 9 ICNs and several deep subcortical nuclei.
Section snippets
Subjects
A total of 228 healthy young adults (126 females and 102 males; mean age 22.9 ± 2.3 years) were selected from 324 subjects who participated in an imaging genetic study. All subjects were right-handed (Oldfield, 1971) native Chinese speakers who did not suffer from any neurologic or psychiatric illnesses or exhibit visible lesions on conventional brain MR images. Each subject signed a written informed consent form that was approved by the Medical Research Ethics Committee of Tianjin Medical
Intrinsic connectivity networks
According to ICA, we extracted 9 meaningful ICNs (Fig. 2), which is very similar to the results of previous studies (Damoiseaux et al., 2006). These ICNs included the visual network (VN), auditory network (AN), sensorimotor network (SMN), anterior default-mode network (DMN), posterior DMN, left frontal–parietal network (FPN) (Smith et al., 2009), right FPN, task-positive network (TPN) (Veer et al., 2010), and salience network (SN) (Habas et al., 2009). The VN is composed of the primary,
Discussion
In the present study, we systematically mapped rsFC patterns of subregions of the human cerebellum. We found that rsFC patterns of vermal and hemispheric subregions were a reflection of both functional integration and segregation in the cerebellum. The functional integration is characterized by several subregions involved in the same functional network, whereas the functional segregation refers to different subregions involved in different functional networks.
Conclusion
Unlike previous rsFC studies, we systematically studied the rsFC patterns of vermal subregions and found that the same vermal and hemispheric subregions showed either different patterns or different strengths in rsFCs with the cerebrum. We found that different subregions of lobules VII and VIII had different rsFCs, and we elucidated the rsFC patterns between cerebellar subregions and 9 ICNs, thalamic subregions, the red nucleus, the basal ganglia, the hippocampus, and the amygdala. Our results
Acknowledgments
This work was supported by the National Basic Research Program of China (973 program, No. 2011CB707801) and the Natural Science Foundation of China (Nos. 30870694 and 30730036).
References (121)
- et al.
Magnetic resonance imaging of cerebellar–prefrontal and cerebellar–parietal functional connectivity
NeuroImage
(2005) - et al.
Listening to rhythms activates motor and premotor cortices
Cortex
(2009) - et al.
Lying about facial recognition: an fMRI study
Brain Cogn.
(2009) - et al.
Subcortical structures involved in pain processing: evidence from single-trial fMRI
Pain
(2002) - et al.
The neural basis of motor sequencing: an fMRI study of healthy subjects
Neurosci. Lett.
(2006) - et al.
Cerebrocerebellar networks during articulatory rehearsal and verbal working memory tasks
NeuroImage
(2005) - et al.
Temporal dynamics of cerebro-cerebellar network recruitment during a cognitive task
Neuropsychologia
(2005) - et al.
Distinct critical cerebellar subregions for components of verbal working memory
Neuropsychologia
(2012) - et al.
Brain areas involved in interlimb coordination: a distributed network
NeuroImage
(2001) A spatially unbiased atlas template of the human cerebellum
NeuroImage
(2006)
A probabilistic MR atlas of the human cerebellum
NeuroImage
MRI atlas of the human cerebellar nuclei
NeuroImage
Cerebellar activation during leg withdrawal reflex conditioning: an fMRI study
Clin. Neurophysiol.
The cerebellum and cognition
Eur. J. Paediatr. Neurol.
Musical and verbal semantic memory: two distinct neural networks?
NeuroImage
Learning in trance: functional brain imaging studies and neuropsychology
J. Physiol. Paris
Functional connectivity between task-positive and task-negative brain areas and its relation to working memory performance
Magn. Reson. Imaging
Neural representation of interval encoding and decision making
Brain Res. Cogn. Brain Res.
The neural regions sustaining episodic encoding and recognition of objects
Brain Cogn.
The integrated response of the human cerebro-cerebellar and limbic systems to acupuncture stimulation at ST 36 as evidenced by fMRI
NeuroImage
Effects of midline and lateral cerebellar lesions on motor coordination and spatial orientation
Brain Res.
The lateralized linguistic cerebellum: a review and a new hypothesis
Brain Lang.
Cognitive, linguistic and affective disturbances following a right superior cerebellar artery infarction: a case study
Cortex
The impact of global signal regression on resting state correlations: are anti-correlated networks introduced?
NeuroImage
The cerebellum in the cerebro-cerebellar network for the control of eye and hand movements—an fMRI study
Prog. Brain Res.
The assessment and analysis of handedness: the Edinburgh inventory
Neuropsychologia
Human emotion and memory: interactions of the amygdala and hippocampal complex
Curr. Opin. Neurobiol.
Is the cerebellum ready for navigation?
Prog. Brain Res.
Three-dimensional MRI atlas of the human cerebellum in proportional stereotaxic space
NeuroImage
Hemispheric lateralization of functions related to emotion
Brain Cogn.
The contribution of the cerebellum to speech production and speech perception: clinical and functional imaging data
Cerebellum
Connectivity-based parcellation of Broca's area
Cereb. Cortex
The effect of tapping finger and mode differences on cortical and subcortical activities: a PET study
Exp. Brain Res.
Neural correlates of coherent audiovisual motion perception
Cereb. Cortex
Scaling of neural responses to visual and auditory motion in the human cerebellum
J. Neurosci.
An information–maximization approach to blind separation and blind deconvolution
Neural Comput.
The neural basis of human dance
Cereb. Cortex
The organization of the human cerebellum estimated by intrinsic functional connectivity
J. Neurophysiol.
Experience sampling during fMRI reveals default network and executive system contributions to mind wandering
Proc. Natl. Acad. Sci. U. S. A.
Some visual and other connections to the cerebellum of the pigeon
J. Comp. Neurol.
Control of goal-directed and stimulus-driven attention in the brain
Nat. Rev. Neurosci.
Consistent resting-state networks across healthy subjects
Proc. Natl. Acad. Sci. U. S. A.
The amygdala: vigilance and emotion
Mol. Psychiatry
Three systems of insular functional connectivity identified with cluster analysis
Cereb. Cortex
Cerebellar responses evoked by nociceptive leg withdrawal reflex as revealed by event-related FMRI
J. Neurophysiol.
Evidence for segregated and integrative connectivity patterns in the human basal ganglia
J. Neurosci.
A comparison of visceral and somatic pain processing in the human brainstem using functional magnetic resonance imaging
J. Neurosci.
Longitudinal evidence for functional specialization of the neural circuit supporting working memory in the human brain
J. Neurosci.
The human brain is intrinsically organized into dynamic, anticorrelated functional networks
Proc. Natl. Acad. Sci. U. S. A.
Trajectories in the spinal cord and the mediolateral spread in the cerebellar cortex of spinocerebellar fibers from the unilateral lumbosacral enlargement in the chicken
Brain Behav. Evol.
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These authors contributed equally to this work.