Author response:
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Joint Public Review:
Summary:
In this study, Daniel et al. used three cognitive tasks to investigate behavioral signatures of cerebellar degeneration. In the first two tasks, the authors found that if an equation was incorrect, reaction times slowed significantly more for cerebellar patients than for healthy controls. In comparison, the slowing in the reaction times when the task required more operations was comparable to normal controls. In the third task, the authors show increased errors in cerebellar patients when they had to judge whether a letter string corresponded to an artificial grammar.
</blockquote>
<blockquote>
Strengths:
Overall, the work is methodologically sound and the manuscript well written. The data do show some evidence for specific cognitive deficits in cerebellar degeneration patients.
</blockquote>
<blockquote>
Weaknesses:
The current version has some weaknesses in the visual presentation of results. Overall, the study lacks a more precise discussion on how the patterns of deficits relate to the hypothesized cerebellar function. The reviewers and the editor agreed that the data are interesting and point to a specific cognitive deficit in cerebellar patients. However, in the discussion, we were somewhat confused about the interpretation of the result: If the cerebellum (as proposed in the introduction) is involved in forming expectations in a cognitive task, should they not show problems both in the expected (1+3 =4) and unexpected (1+3=2) conditions? Without having formed the correct expectation, how can you correctly say "yes" in the expected condition? No increase in error rate is observed - just slowing in the unexpected condition. But this increase in error rate was not observed. If the patients make up for the lack of prediction by using some other strategy, why are they only slowing in the unexpected case? If the cerebellum is NOT involved in making the prediction, but only involved in detecting the mismatch between predicted and real outcome, why would the patients not show specifically more errors in the unexpected condition?
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Thank you for asking these important questions and initiating this interesting discussion. While decision error and processing efficiency are probably not fully orthogonal and are related to each other, they are still not necessarily the same internal construct. The data from Experiments 1 and 2 suggest impaired processing efficiency rather than increased decision error. Reaction time slowing without increased error rates suggests that the CA group can form expectations but respond more slowly, possibly due to reduced processing efficiency. Our data suggest that the cerebellum is not essential for forming expectations in familiar tasks, but plays a critical role in processing their violations, particularly when such violations require coordination or internal monitoring.
Relatedly, there are two unresolved key questions regarding cerebellar contributions to expectations-related processes. These questions are relevant to both motor and non-motor domains and were not fully addressed even in the previous, well-studied motor domain. The first is regarding distinguishing between cerebellar contributions to the formation of expectation versus its contributions to violation of expectation (VE). While previous experimental manipulations(1–6) have provided important insights, some may have confounded different internal constructs due to task design limitations (e.g., lack of baseline conditions). Notably, some of these previous studies did not include control conditions (e.g., correct trials) where there was no violation of expectation. In addition, other studies did not include a control measure (e.g., complexity effect) which limits their ability to infer the specific cerebellar role in the expectation manipulation.
In Experiments 1 and 2, the CA group did not show impairments in the complexity manipulation. Solving these problems requires the formation of expectations during the reasoning process. Given the intact performance of the CA group, these results suggest that the CA group is not impaired in forming expectations. However, in both Experiments 1 and 2, patients exhibited selective impairments in solving incorrect problems compared to correct problems. Since expectation formation is required in both conditions, but only incorrect problems involve a violation of expectation, we hypothesize that the cerebellum is involved in VE processes. We suggest that the CA group can form expectations in familiar tasks, but are impaired in processing unexpected outcomes compared to expected outcomes. This supports the notion that the cerebellum contributes to violation of expectations rather than to generating them.
But there is also a second important question. While our findings point to a both unique and consistent cerebellar role in VE processes in sequential tasks, we do not aim to generalize this role to all forms of expectations(2,7,8). Importantly, previous experimental paradigms(1–6), aiming to assess VE, utilized tasks that manipulated errors or probability-related processes, but did not fully dissociate these constructs. In our Experiments 1 and 2, we specifically manipulated error signals derived from previous top-down effects. However, in Experiment 3, the participant’s VE was derived from within-task processes. In Experiment 3, expectations were formed either by statistical learning or by rule-based learning. During the test stage, when evaluating sensitivity to correct and incorrect problems, the CA group showed deficits only when expectations were formed based on rules. These findings suggest that cerebellar patients may retain the general ability to form expectations. However, their deficit appears to be specific to processing rule-based VE, but not statistically derived VE. This pattern of results aligns with the results of Experiments 1 and 2 where the rules are known and based on pre-task knowledge.
Thus, the current experimental design used in three different experiments provides a valuable novel experimental perspective, allowing us to distinguish between some, but not all, of the processes involved in the formation of expectations and their violations. For instance, to our knowledge, this is the first study to demonstrate a selective impairment in rule-based VE processing in cerebellar patients, across both numerical reasoning and artificial grammar tasks.
If feasible, we propose that future studies will disentangle different forms of VE by operationalizing them in experimental tasks in an orthogonal manner. This will allow us, as a scientific community, to achieve a more detailed, well-defined cerebellar motor and non-motor mechanistic account.

Jörn Diedrichsen

Tamar Makin

eLife Assessment
This valuable investigation provides new and solid evidence for a specific cognitive deficit in cerebellar degeneration patients. The authors use three tasks that modulate complexity and error presence to show specific slowing of reaction times in the presence of errors but not with task complexity. While the authors interpret these findings as indicating that the cerebellum is required for the processing of violations of expectations, the exact patterns of results may suggest alternative interpretations. Nonetheless, the work provides a new, invaluable data point in describing the cognitive contribution of cerebellar processing.

anonymous

Joint Public Review:
Summary:
In this study, Daniel et al. used three cognitive tasks to investigate behavioural signatures of cerebellar degeneration. In the first two tasks, the authors found that if an equation was incorrect, reaction times slowed significantly more for cerebellar patients than for healthy controls. In comparison, the slowing in the reaction times when the task required more operations was comparable to normal controls. In the third task, the authors show increased errors in cerebellar patients when they had to judge whether a letter string corresponded to an artificial grammar.
Strengths:
Overall, the work is methodologically sound and the manuscript well written. The data do show some evidence for specific cognitive deficits in cerebellar degeneration patients.
Weaknesses:
The current version has some weaknesses in the visual presentation of results. Overall, the study lacks a more precise discussion on how the patterns of deficits relate to the hypothesized cerebellar function.
The reviewers and the editor agreed that the data are interesting and point to a specific cognitive deficit in cerebellar patients. However, in the discussion, we were somewhat confused about the interpretation of the result:
If the cerebellum (as proposed in the introduction) is involved in forming expectations in a cognitive task, should they not show problems both in the expected (1+3 =4) and unexpected (1+3=2) conditions? Without having formed the correct expectation, how can you correctly say "yes" in the expected condition? No increase in error rate is observed - just slowing in the unexpected condition. But this increase in error rate was not observed. If the patients make up for the lack of prediction by using some other strategy, why are they only slowing in the unexpected case?
If the cerebellum is NOT involved in making the prediction, but only involved in detecting the mismatch between predicted and real outcome, why would the patients not show specifically more errors in the unexpected condition?

High Cognitive Violation of Expectations is Compromised in Cerebellar Ataxia

Figures and data

Demographic and medical summary table of the CA and NT groups in each Experiment. Mean ± SEM.

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