Functional magnetic resonance imaging of cerebellar activation and lateralization during  verbal and visuospatial tasks*☆●
Mi-Hyun Choi1, Su-Jeong Lee1, Jae-Woong Yang1, Jin-Seung Choi1, Hyung-Sik Kim1, Jeong-Han Yi1, Gye-Rae Tack1, Soon-Cheol Chung1, Byung-Chan Min2, Se-Jin Park3, Jong-Rak Park4, Jae-Hoon Jun1

1Department of Biomedical Engineering, Research Institute of Biomedical Engineering, College of Biomedical & Health Science, Konkuk University, Chungju, South Korea
2Department of Industrial & Management Engineering, Hanbat National University, Daejeon, South Korea
3Division of Technology Services, National Center for Standard Reference Data, Korea Research Institute of Standards and Science, Daejeon, South Korea
4Department of Photonic Engineering, Chosun University, Gwangju, South Korea
Mi-Hyun Choi☆, Studying for doctorate, Department of Biomedical Engineering, Research Institute of Bio-medical Engineering, College of Biomedical & Health Science, Konkuk University, Chungju, South Korea

Corresponding author: Jae-Hoon Jun, Ph.D., Asso-ciate professor, Department of Biomedical Engineering, Research Institute of Bio-medical Engineering, College of Biomedical & Health Science, Konkuk University, Chungju, South Korea
jjun81@kku.ac.kr

Abstract
BACKGROUND: Previous studies have analyzed cerebral activation and lateralization of cognitive functions, as well as cerebellar function with reference to high-level cognitive processing. However, there has been very little research on systematization and diversification. In particular, there are no reports on cerebellar lateralization, although reliable results have been reported on cerebral lateralization.
OBJECTIVE: This study analyzed cerebellar activation and lateralization in relation to verbal and visuospatial tasks using functional magnetic resonance imaging (fMRI).
DESIGN, TIME AND SETTING: A block design for fMRI observation was performed at the fMRI Laboratory, Brain Science Research Center, Korea Advanced Institute of Science and Technology from May 2006 to September 2008.
PARTICIPANTS: Sixteen healthy, male, college students, aged (23.3 ± 0.5) years, and 16 healthy, male, college students, aged (21.5 ± 2.3) years, participated in the study, respectively.
METHODS: Verbal and visuospatial tasks were presented while functional brain images were acquired using a 3T fMRI system. Verbal analogy testing required the subject to select the word with the same relationship as one of the given words. Verbal antonym testing required the subject to select the word with a different meaning among four words. Visuospatial tasks involved selecting a shape that corresponded to a given figure with four examples, as well as selecting a development figure of a diagram.
MAIN OUTCOME MEASURES: Changes in cerebellar activation and lateralization between two cognition tasks.
RESULTS: Bilateral hemisphere lobules VI and IX, right hemisphere lobule VIII, bilateral hemisphere lobules Crus I, and vermis lobule IV, V, and VI were closely related to verbal tasks in comparison to visuospatial tasks. Conversely, bilateral hemisphere lobules IV and V, as well as the right hemisphere lobule VI, were closely related to visuospatial tasks compared to verbal tasks. There was no great difference between the number of activated voxels in the cerebellums during the tasks, and cerebellar lateralization was not observed.
CONCLUSION: In the cerebellum, the activation region, but not lateralization, was different between verbal and visuospatial tasks.
Key Words: cerebellum; lateralization; functional magnetic resonance imaging; verbal and visuospatial tasks; neuroimaging; neural regeneration

INTRODUCTION
  
Functional magnetic resonance imaging (fMRI) has been used extensively to study cognitive functions, such as verbal and visuospatial perception, as well as cerebral lateralization in these tasks. During verbal tasks, the inferior frontal lobe, including Broca, parietal and temporal lobes, and Wernicke, play important roles[1-5]. In visuospatial tasks, the occipital lobe, parietal lobe, and frontal lobe are activated, and the parietal lobe plays an especially important role[6-13]. Previous studies have focused on cerebral lateralization, functional asymmetry of cerebral function, hemispheric dominance, and lateralization of cognitive functions. Right-handed people exhibit the speech center in the left cerebral hemisphere, and the right cerebral hemisphere is activated by complex visual and spatial processing[14].
The cerebellum is closely related to verbal, visuospatial, mnemonic, and informational tasks. In general, activation is observed in cerebellar regions, such as bilateral hemisphere lobules IV, V, and VI, the right hemisphere lobule VIII, bilateral hemisphere lobules Crus I and II, and the vermis lobule IV, V, VI, and VII, while performing verbal tasks[15-17]. Previous studies have shown cerebellar activation in bilateral hemisphere lobules IV, V, and VI, bilateral hemisphere lobules Crus I and II, and the vermis lobule VI and VII, during visuospatial tasks[18-20].
Following damage to the cerebellum, reaction time increases, and task performance, inference, deduction, calculation, visuospatial ability, verbal commands, and memory recall have been shown to decrease[20-22]. Although studies have focused on cerebellar function with regard to high-level cognitive processing, little is known about systematization and diversification.
The present study aimed to ascertain cerebellar regions involved in verbal and visuospatial tasks through the use of fMRI. Differences in cerebellar activation between the two tasks, as well as whether cerebellar lateralization occurred during each task, was determined.

SUBJECTS AND METHODS

Design
A block design for fMRI observation.
Time and setting
The study was performed at the fMRI Laboratory, Brain Science Research Center, Korea Advanced Institute of Science and Technology from May 2006 to September 2008.
Subjects
Students from Konkuk University were recruited for the study. A total of 16 healthy, college students, as well as 16 additional healthy, age- and gender-matched, college students, participated in the fMRI study of verbal and visuospatial tasks, respectively. All subjects were right-handed, as evaluated by the revised Edinburgh test[23]. None of the participants reported a history of psychiatric or neurological disorders. All subjects provided informed consent. All examinations were performed according to regulations of the Institutional Review Committee.
Methods
Imaging acquisition
Imaging was conducted using a 3.0T ISOL Technology FORTE (ISOL Technology, Korea) equipped with whole-body gradients and a quadrature head coil. Single-shot echoplanar fMRI scans were acquired in 35 continuous slices, parallel to the anterior commissure-posterior commissure (AC-PC) line. The fMRI parameters included the following: repetition time/echo time (TR/TE) of 3 000/35 ms; 60° flip angle; 240-mm field of view; 64 × 64 matrix; 4-mm slice thickness; and 3.75-mm in-plane resolution. T1-weighted anatomic images were obtained using a 3-D FLAIR sequence (TR/TE = 280/14 ms, flip angle = 60, FOV = 240 mm, matrix = 256 × 256, slice thickness = 4 mm).
Verbal and visuospatial tasks
Verbal task consisted of verbal analogy and antonym tasks: 28 items were selected from Korean versions of an intelligence test and a general aptitude battery (GATB)[24-25]. The verbal analogy test required the subject to select one of a group of words with the same meaning as a given word. Verbal antonym testing required the subject to select a word that had a different meaning from four words[5].
A visuospatial task: 28 items for the visuospatial task were selected from Korean versions of an intelligence test, an aptitude test, and the GATB[24-26]. The selected items were (1) choosing a figure with the same shape of a given diagram from four examples and (2) locating the next figure in a series of diagrams[9-12].
Korean versions of the tests do not differ from existing well-known standard tests. The intelligence test, GATB, and aptitude tests were translated into Korean from the Wechsler Adult Intelligence Scale (WAIS-R)[27-28].
Verbal and visuospatial test: the experiment consisted of four blocks (8 minutes total); each block (2 minutes each) consisted of control (1 minute) and cognitive (1 minute) items. The control and cognitive tasks were presented using SuperLab 1.07 (Cedrus, USA). Items were projected to a screen, and subjects were instructed to provide the correct answers. In response to control tasks, subjects were instructed to press a button corresponding to the number (1, 2, 3, or 4) projected on the screen. In the cognition task, subjects were asked to press a button to correctly identify the item number projected on the screen (7 trials/block).
Data analysis
The anatomical images were taken prior to acquiring all functional images, which were realigned using SPM99. The realigned scans were co-registered to the participant anatomical images obtained from each session. The scans were then normalized to the SPM99 template (Wellcome Department of Cognitive Neurology, London, UK), which uses the space defined by the Montreal Neurologic Institute (MNI). The functional map was smoothed with a 7-mm isotropic Gaussian kernel prior to statistical analysis, which was performed individually and as a group using the general linear model and the theory of Gaussian random fields implemented in SPM99. Using the subtraction procedure (cognition tasks – control tasks), activated areas in the cerebellum during cognitive tasks were color-coded using the t-score. The double subtraction method (verbal tasks – visuospatial tasks and visuospatial tasks – verbal tasks) was used to analyze differences in cerebellar activation between the two cognition tasks.
Finally, the number of bilateral cerebellum voxels were calculated using WFU Pick Atlas (Wake Forest University, USA), which is a SPM99 toolbox. The cerebellum lateralization index (LI) was calculated for each task. LI was calculated using the formula (left - right)/(left + right), where “left” represented the number of activated voxels in the left cerebellum, and “right” represented those in the right cerebellum. A positive LI represented more activation in the left cerebellum, and a negative index represented greater activation in the right cerebellum. The independent paired t-test in SPSS (version 12.0, SPSS, Chicago, IL, USA) was used to determine significant differences in the number of activated voxels between the left and right cerebellum.

RESULTS

Quantitative analysis of participants
Sixteen healthy, male, college students, as well as an additional 16 healthy, male, college students, were included in this fMRI study of verbal and visuospatial tasks. Demographic results of subjects are shown in Table 1.

Cerebellar activation areas and lateralization
Figure 1A shows significantly activated cerebellar regions (corrected P < 0.05) during verbal tasks. Significant activation was observed in the left hemisphere lobule IV and V, bilateral hemisphere lobules VI, VIII, and IX, bilateral hemisphere lobules Crus I and II, and vermis lobule IV, V, VI, VII, VIII, IX, and X. Figure 1B depicts cerebellar regions that were significantly activated (corrected P < 0.05) during visuospatial tasks. Significant activation was observed in bilateral hemisphere lobules IV, V, and VI, bilateral hemisphere lobules Crus I and II, and vermis lobule VII, VIII, and IX. 

Figure 2 reveals contrasting effects between verbal and visuospatial tasks using the double subtraction method (corrected P < 0.05). Figure 2A shows the cerebellar region activated only in performing verbal tasks, and Figure 2B shows the region activated only in performing visuospatial tasks. The Montreal Neurological Institute (MNI) coordinates and z-scores of each activated area are shown in Tables 2 and 3.
Table 4 shows the number of activated voxels in the left and right cerebellum, as well as the lateralization index (LI) for verbal and visuospatial tasks. There was no significant difference between the number of activated voxels in the cerebellums for the two tasks, and cerebellar lateralization was not observed      (P > 0.05).

DISCUSSION

The cerebellar regions activated by visuospatial tasks in the present study were similar to previously described results[18-20]. Cerebellar activation from visuospatial tasks was greater than cerebellar activation from verbal tasks, which was consistent with previous studies[15-17].
Based on double-subtraction analysis, the regions of cerebellar activation differed to some degree in the process of performing two tasks. Previous studies reported that the right cerebral hemisphere was dominant for visuospatial tasks and the left cerebral hemisphere was dominant for verbal tasks[26-28]. However, in the cerebellum, there was no significant difference between hemispheres with regard to the number of activated voxels for tasks. Therefore, lateralization was not observed. The vermis, which is located between cerebellar hemispheres, occupies a wide range. The vermis was significantly activated in both tasks, compared to other regions, which suggested that the cerebellum was not easily lateralized. Lateralization was analyzed in each region except for the vermis, because its activation could affect lateralization. Nevertheless, cerebellar lateralization was not observed. Further studies are needed to determine the role of cerebellar and cerebral lateralization during cognitive tasks.
Previous cognitive studies on schizophrenia patients revealed that cerebral lateralization could be an indicator for psychosis[29-31]. The present study demonstrated cerebellar lateralization in normal individuals during verbal and spatial tasks. However, further studies are needed to determine the degree of cerebellar lateralization in neurological diseases, as well as whether a cerebral lateralization index could be an indicator for psychosis.
In summary, the cerebellar activation region varied between verbal and visuospatial tasks, but lateralization was not different.

Acknowledgments
This paper was supported by Konkuk University.

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 (Edited by Borgwardt S, Ito S/Ji H/Song LP)