Elsevier

NeuroImage

Volume 61, Issue 4, 16 July 2012, Pages 1213-1225
NeuroImage

Resting-state functional connectivity of the vermal and hemispheric subregions of the cerebellum with both the cerebral cortical networks and subcortical structures

https://doi.org/10.1016/j.neuroimage.2012.04.011Get rights and content

Abstract

The human cerebellum is a heterogeneous structure, and the pattern of resting-state functional connectivity (rsFC) of each subregion has not yet been fully characterized. We aimed to systematically investigate rsFC pattern of each cerebellar subregion in 228 healthy young adults. Voxel-based analysis revealed that several subregions showed similar rsFC patterns, reflecting functional integration; however, different subregions displayed distinct rsFC patterns, representing functional segregation. The same vermal and hemispheric subregions showed either different patterns or different strengths of rsFCs with the cerebrum, and different subregions of lobules VII and VIII displayed different rsFC patterns. Region of interest (ROI)-based analyses also confirmed these findings. Specifically, strong rsFCs were found: between lobules I–VI and vermal VIIb–IX and the visual network; between hemispheric VI, VIIb, VIIIa and the auditory network; between lobules I–VI, VIII and the sensorimotor network; between lobule IX, vermal VIIIb and the default-mode network; between lobule Crus I, hemispheric Crus II and the fronto-parietal network; between hemispheric VIIb, VIII and the task-positive network; between hemispheric VI, VIIb, VIII and the salience network; between most cerebellar subregions and the thalamus; between lobules V, VIIb and the midbrain red nucleus; between hemispheric Crus I, Crus II, vermal VIIIb, IX and the caudate nucleus; between lobules V, VI, VIIb, VIIIa and the pallidum and putamen; and between lobules I–V, hemispheric VIII, IX and the hippocampus and amygdala. These results confirm the existence of both functional integration and segregation among cerebellar subregions and largely improve our understanding of the functional organization of the human cerebellum.

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).

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    These authors contributed equally to this work.

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