Functional topography of the cerebellum for motor and cognitive tasks: An fMRI study
Highlights
► We investigated cerebellar functional topography for motor and cognitive tasks. ► Subjects completed motor, language, working memory, spatial, and affective tasks. ► Overt movement activated the anterior lobe and lobule VIII. ► Cognitive measures activated topographically distinct areas in lobules VI and VII. ► Findings are consistent with the localization of cerebro-cerebellar loops.
Introduction
The understanding of human cerebellar function has undergone a paradigm shift. No longer considered purely devoted to motor control, a wider role for the cerebellum in cognitive and affective functions is supported by anatomical, clinical and functional neuroimaging data. However, clinical findings are inconsistent, and cerebellar activation in neuroimaging studies is commonly reported, but often not interpreted, potentially ignoring an important component of functional neural systems. Recent evidence from functional connectivity studies in humans indicates that the cerebellum participates in functional networks with sensorimotor areas engaged in motor control and with association cortices that are involved in cognitive processes (Habas et al., 2009, Krienen and Buckner, 2009, O'Reilly et al., 2010).
We have proposed that there is a functional topography of the cerebellum, based on its linkages with sensorimotor and higher-order brain areas (see Schmahmann, 1991, Schmahmann, 2004, Stoodley and Schmahmann, 2010), such that different cerebellar regions process sensorimotor, cognitive and affective information. This concept is of vital importance to the interpretation of lesion-symptom correlations in clinical studies and cerebellar activation patterns in functional neuroimaging data.
Extensive connections between the cerebellum, spinal cord, and sensorimotor and association areas of the cerebral cortex provide the anatomical substrates for the cerebellar contribution to both movement (Holmes, 1939) and cognition (see Schmahmann and Pandya, 1997). The cerebellum is comprised of ten lobules, grouped as the anterior lobe (lobules I through V); posterior lobe (lobules VI through IX); and the flocculonodular lobe (lobule X). Physiological experiments in cats (Adrian, 1943, Snider and Eldred, 1951) and functional MRI (fMRI) studies in humans (see Grodd et al., 2005) reveal the presence of sensorimotor homunculi in lobules III–VI and lobule VIII. In contrast, association area projections (prefrontal, posterior parietal, and superior temporal, posterior parahippocampal and cingulate areas) are mainly localized to lobules VI and VII (for an overview, see Kelly and Strick, 2003, Stoodley and Schmahmann, 2010).
Focal lesions in stroke patients also provide insights into cerebellar structure–function relationships. Following cerebellar stroke the expected motor syndrome (gait impairment, incoordination of the extremities, disordered eye movements and slurring of speech) is present in some, but not all, patients (Schmahmann et al., 2009). Similarly, not all patients experience the cerebellar cognitive affective syndrome (CCAS; Schmahmann and Sherman, 1998), characterized by deficits in executive function, visual spatial processing, selected aspects of language, and affect. If there are different functional regions in the cerebellum, then one would predict that different clinical symptoms may be present depending on the location of cerebellar damage, and depending on which cerebellar circuits are affected. There is evidence of this in the sensorimotor domain, where the cerebellar motor syndrome is associated with anterior lobe damage (Schmahmann et al., 2009) and dysarthria is associated with damage to the representation of the articulatory apparatus (cerebellar lobule VI; Urban et al., 2003). The CCAS occurs more often following damage to the posterior lobe of the cerebellum (Schmahmann and Sherman, 1998), and damage to right posterolateral cerebellar regions has been linked with language deficits (e.g., Marien et al., 2001). Finally, affective symptoms in children are more likely to be present when cerebellar lesions (Levisohn et al., 2000) or malformations (Tavano et al., 2007) affect the posterior midline vermal regions. Therefore, these clinical findings suggest that different regions of the cerebellum are involved in different functional domains.
Further support for cerebellar functional topography comes from functional neuroimaging data. Resting-state functional connectivity studies have shown that activity in sensorimotor regions correlates with the contralateral cerebellar anterior lobe and lobule VIII, whereas activity in prefrontal, posterior parietal, and superior and middle temporal association areas, as well as the cingulate gyrus and retrosplenial cortex, correlates with activity in cerebellar lobules VI and VII (Krienen and Buckner, 2009, O'Reilly et al., 2010). In a recent meta-analysis of cerebellar activation patterns reported in functional imaging studies, it was apparent that sensorimotor tasks activated the anterior lobe and lobule VIII, whereas language tasks activated right cerebellar regions in lobules VI and VII, and spatial tasks tended to lateralize to the left cerebellar hemisphere (Stoodley and Schmahmann, 2009). These findings are consistent with the contralateral connections between the cerebral cortex and cerebellar hemispheres, and suggest that cerebellar activation patterns in imaging studies reflect the involvement of different cerebro-cerebellar loops in a task-dependent manner.
However, meta-analyses are limited by the combination of data from many different studies, acquired on scanners of different strengths, while subjects completed different task paradigms, yielding data that were analyzed with a variety of techniques and statistical thresholds. Therefore, we used fMRI to investigate cerebellar activation patterns for various tasks within individual subjects, in order to examine the topography of activation peaks for sensorimotor, cognitive and affective tasks. Further, these data provide important information about cerebellar participation in the distributed neural circuits subserving sensorimotor as well as higher-order functions.
In the scanner, nine healthy male young adults performed a set of tasks assessing sensorimotor, linguistic, spatial, working memory and affective processing. Each participant completed five tasks which previously had been shown to engage the cerebellum, including: finger tapping with the right index finger (sensorimotor); generating verbs in response to common nouns (language); mental rotation of letter stimuli (spatial); a 2-back task (working memory); and viewing images from the International Affective Picture Scale (IAPS, affective processing; Lang et al., 2005). Reported task activations represent contrast images controlling for the motor responses associated with each task, with the exception of the finger-tapping paradigm, in which the goal was to highlight activation related to overt movement.
Based on the anatomical projections between the cerebellum and cerebral cortices (see Schmahmann and Pandya, 1997, Stoodley and Schmahmann, 2010), we hypothesized that the overt motor task (finger tapping) would activate regions of the cerebellum to which sensorimotor regions project, namely lobules IV–VI and lobule VIII. We predicted that the cognitive tasks (verb generation, mental rotation, 2-back task), would predominantly activate lobules VI and VII, and that language activation would be right-lateralized and spatial activation left-lateralized. Finally, we anticipated that viewing images from the IAPS scale would engage the posterior vermis of the cerebellum, which on the basis of clinical (Heath, 1977, Levisohn et al., 2000, Schmahmann and Sherman, 1998, Tavano et al., 2007), behavioral (Berman et al., 1978), electrophysiological (Heath and Harper, 1974, Snider and Maiti, 1976), and stimulation studies (Demirtas-Tatildede et al., 2010), is thought to connect with limbic and autonomic regions of the brain.
Section snippets
Participants
Nine healthy, right-handed adult males (mean age 25 years, 6 months) with no history of neurological illness or injury participated in the study. Data from one participant has been reported as a proof-of-principle, single case study (Stoodley et al., 2010). The project was approved by the Institutional Review Board of the Massachusetts General Hospital and all participants provided written, informed consent. Handedness was confirmed by a score > 40 on the Edinburgh Handedness Inventory (Oldfield,
Behavioral performance
Participants scored in the average to above-average range on all subtests of the abbreviated form of the Wechsler Adult Intelligence Scale-III (WAIS-III; The Psychological Corporation, 1997; mean ± standard deviation = 10 ± 3 for each subtest). Mean scores for the Similarities (13.1 ± 2.1), Arithmetic (12.9 ± 1.3), Digit Symbol (13.3 ± 2.7), Information (15.2 ± 1.9), Block design (13.2 ± 3.0), Digit span (13.0 ± 3.0) and Picture completion (10.6 ± 2.5) subtests indicated that all participants were of above-average
Discussion
Our aim was to determine whether the functional topography suggested by the anatomical connectivity of different regions of the cerebellum was evident when participants performed different types of tasks. As all participants performed the full set of tasks, we were able to look at the relative activation patterns for different tasks using the same data acquisition parameters and analysis methods. This is a step beyond previous work surveying the imaging literature and determining whether
Conclusion
Establishing functional subregions of the cerebellum has potentially wide-ranging implications. It helps explain the presence of both the classic cerebellar motor syndrome as well as the CCAS in patients with cerebellar lesions. In addition, structural and functional cerebellar differences have been found in a range of disorders, from schizophrenia to autism, and a deeper understanding of functional topography in the human cerebellum may lead to new insights into the anatomical underpinnings,
Acknowledgments
This study was supported in part by the National Center for Research Resources (P41RR14075); the Massachusetts General Hospital Fund for Medical Discovery (CJS); the National Institutes of Health (071535, EMV); the Birmingham Foundation (JDS) and the MINDlink foundation (JDS). The authors would like to thank Larry Seidman for the use of the n-back task, Peter Hansen for providing stimuli for the mental rotation task, Janet Sherman for help with the psychometric test battery, and Joanna Willms
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