A Cognitive Role for the Cerebellum?

Abstract & Commentary

By Claire Henchcliffe, MD, DPhil, Assistant Professor, Department of Neurology, Weill Medical College, Cornell University. Dr. Henchcliffe is on the speaker's bureau for GlaxoSmithKline, Eisai, and Boehringer Ingelheim.

Synopsis: The cerebellum may contribute to verbal working memory during the initial phonological encoding and/or by strengthening memory traces rather than by fundamentally subserving covert articulatory rehearsal.

Source: Ravizza SM, et al. Cerebellar Damage Produces Selective Deficits in Verbal Working Memory. Brain. 2006;129:306-320.

The authors present a 3-part series of careful neuropsychological tests, specifically addressing whether cerebellar damage is associated with working memory. Ten subjects with cerebellar stroke and 5 with cerebellar tumor or cyst resection (average age 60.3 years, average education 14.6 years) were compared to control subjects, reporting no neurological deficits (average age 61.2 years, average education 15.2 years). In experiment 1, all 15 patients and controls were tested by digit span (verbal working memory) and spatial span/block tapping (spatial working memory) using the Wechsler Adult Intelligence Scale or Wechsler Memory Scale-Revised. Subjects with cerebellar lesions had significantly lower digit span scores compared to controls (P < 0.005), but similar spatial span scores.

In experiment 2, for the verbal task, a subset of 9 subjects (stroke:8; tumor resection:1) were twice presented a list of 4 words. For the spatial task, 4 out of 9 boxes were highlighted randomly on a computer screen, then were presented a second time. In both tasks, subjects had to judge whether the same order was used in the 2 presentations. Importantly, a delay was introduced prior to response (increasing rehearsal), and subjects responded by single key press rather than verbally. In this condition, there was impairment on both tasks, but a trend to greater impairment on the verbal compared to spatial task. In experiment 3, 8 subjects (stroke:7; tumor resection:1) and controls were presented 8 combinations of lists of words or non-words matched for length (2 vs 4 syllables). In variation (a), subjects were allowed to silently read the word lists. In variation (b), subjects continuously repeated the word 'the' before responding (resulting in articulatory suppression of rehearsal). Subjects with cerebellar lesions had a shorter average span compared to controls, but comparable effects regarding length and articulatory suppression. Brain imaging, available for 13/15 subjects, revealed negative correlation of backward digit span with inferior lobe lesions in experiment 1 (P < 0.05) and, in experiment 2, verbal span negatively correlated with anterior and superior lobe lesions.

Commentary

Clinical observations, published since the early 1990s, either as single case reports or small case series, have challenged the traditional view that the cerebellum is involved only in motor control. The term cerebellar cognitive affective syndrome (CCAS) was proposed to describe cognitive and psychiatric disorders in patients with a variety of cerebellar lesions and disorders.1 Impairment of executive function, spatial cognition, linguistic processing, and dysregulation of affect have all been suggested to associate with cerebellar disease, and functional MRI studies have repeatedly demonstrated cerebellar activation in a variety of cognitive paradigms. However, there remains considerable skepticism regarding validity of the CCAS as a clinical entity. Although the present data do not lay argument to rest, they are an important contribution in support of the CCAS. Findings of these 3 elegant experiments strongly suggest impairment in verbal working memory (VWM) in patients with cerebellar lesions.

Ravizza and colleagues suggest that cerebellar lesions impair VWM because of disturbed sub-vocal rehearsal, given that a) introducing a delay prior to response (ie, increasing rehearsal demand worsened performance) and b) factors thought to affect rehearsal efficiency (articulatory suppression, word length) had no effect in subjects with cerebellar damage. A potential criticism is that subjects' dysarthria or ataxia may have affected their performance. However, such a simple explanation is highly unlikely, as deficits did not improve as motor demand of a response was decreased, and there was no or little impairment on spatial tasks. This study has obvious limitations, including small sample size and heterogeneous cohort, lack of mood evaluation, and inconsistencies in cerebellar regions involved judged by MRI or CT. Despite these limitations, the results have clinical implications. VWM is necessary to maintain information in the brain in order to manipulate that information. Some patients with cerebellar disease complain of difficulties in multitasking, mental flexibility, and linguistic processing. Since the primary task of the cerebellum is traditionally considered motor function, such complaints are often considered to be non-specific. If they are indeed of structural origin, an approach focused on neurorehabilitation may be more effective to alleviate or compensate for such a deficit.

Reference

1. Schmahmann JD, Sherman JC. The Cerebellar Cognitive Affective Syndrome. Brain. 1998;121:561-579.