Structural cerebellar correlates of cognitive and motor dysfunctions in cerebellar degeneration

Abstract

See King et al. (doi:10.1093/aww348) for a scientific commentary on this article.Detailed mapping of clinical dysfunctions to the cerebellar lobules in disease populations is necessary to establish the functional significance of lobules implicated in cognitive and motor functions in normal subjects. This study constitutes the first quantitative examination of the lobular correlates of a broad range of cognitive and motor phenomena in cerebellar disease. We analysed cross-sectional data from 72 cases with cerebellar disease and 36 controls without cerebellar disease. Cerebellar lobule volumes were derived from a graph-cut based segmentation algorithm. Sparse partial least squares, a variable selection approach, was used to identify lobules associated with motor function, language, executive function, memory, verbal learning, perceptual organization and visuomotor coordination. Motor dysfunctions were chiefly associated with the anterior lobe and posterior lobule HVI. Confrontation naming, noun fluency, recognition, and perceptual organization did not have cerebellar associations. Verb and phonemic fluency, working memory, cognitive flexibility, immediate and delayed recall, verbal learning, and visuomotor coordination were variably associated with HVI, Crus I, Crus II, HVII B and/or HIX. Immediate and delayed recall also showed associations with the anterior lobe. These findings provide preliminary anatomical evidence for a functional topography of the cerebellum first defined in task-based functional magnetic resonance imaging studies of normal subjects and support the hypotheses that (i) cerebellar efferents target frontal lobe neurons involved in forming action representations and new search strategies; (ii) there is greater involvement of the cerebellum when immediate recall tasks involve more complex verbal stimuli (e.g. longer words versus digits); and (iii) it is involved in spontaneous retrieval of long-term memory. More generally, they provide an anatomical background for studies that seek the mechanisms by which cognitive and motor dysfunctions arise from cerebellar degeneration. Beyond replicating these findings, future research should employ experimental tasks to probe the integrity of specific functions in cerebellar disease, and new imaging methods to quantitatively map atrophy across the cerebellum.

Keywords: brain atrophy; cerebellar function; cognitive control; motor control; structural MR imaging.

Figure 1

Pearson correlations between cerebellar volumes and motor and cognitive test scores. The colours of the squares denote strength and direction of correlations, and crosses mark the correlations that did not attain statistical significance (P < 0.05). The signs of motor and mixed tests were inverted so that high scores corresponded to good performance. This held true by default for all the cognitive tests.

Figure 2

Associations between cerebellar volumes and motor and cognitive test scores. Associations were derived with the sparse partial least squares approach. Colours illustrate the direction and size of the coefficients (Table 2). (A) Motor tests: (i) Functional Staging for Ataxia; (ii) ICARS posture; (iii) ICARS kinetic; (iv) ICARS speech; (v) ICARS oculomotor. (B) Mixed tests: (i) TMT A; (ii) TMT B; (iii) Grooved Pegboard. (C) Cognitive tests: (i) Boston Naming Test; (ii) Noun fluency; (iii) Verb fluency; (iv) COWA (F, A and S); (v) Digit Span forward; (vi) Digit Span backward; (vii) RAVLT I; (viii) RAVLT delayed recall; (ix) RAVLT recognition; (x) Hooper Visual Organization.

Figure 3

Associations between cerebellar volumes and residuals obtained from linear regressions of combinations of motor and cognitive test scores. Associations were derived with the sparse partial least squares approach. Colours illustrate the direction and size of the coefficients (shown in Table 3). (i) TMT B adjusted for TMT A; (ii) Grooved Pegboard adjusted for ICARS speech and ICARS oculomotor; (iii) Noun fluency adjusted for ICARS speech; (iv) Verb fluency adjusted for ICARS speech; (v) COWA adjusted for ICARS speech; (vi) Digit Span backward adjusted for Digit Span forward; (vii) RAVLT I adjusted for Digit Span forward; (viii) RAVLT V adjusted for RAVLT I; (ix) RAVLT delayed recall adjusted for RAVLT recognition.