Encoding of cerebellar dentate neuronal activity during visual attention in rhesus macaques
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Curated by eLife
eLife assessment
This important study examined neuronal activity in the dentate nucleus of the cerebellum when monkeys performed a difficult perceptual decision-making task. The authors provide convincing evidence that the cerebellum represents sensory, motor, and behavioral outcome signals that are sent to the attentional system, but further analysis focusing on the disparity of performance between animals would improve the quality of the paper. This paper is of great general interest in that it shows the involvement of the cerebellum in cognitive processes at the neuronal level.
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Abstract
The role of cerebellum in controlling eye movements is well established, but its contribution to more complex forms of visual behavior has remained elusive. To study cerebellar activity during visual attention we recorded extracellular activity of dentate nucleus (DN) neurons in two non-human primates (NHPs). NHPs were trained to read the direction indicated by a peripheral visual stimulus while maintaining fixation at the center, and report the direction of the cue by performing a saccadic eye movement into the same direction following a delay. We found that single unit DN neurons modulated spiking activity over the entire time-course of the task, and that their activity often bridged temporally separated intra-trial events, yet in a heterogeneous manner. To better understand the heterogeneous relationship between task structure, behavioral performance and neural dynamics, we constructed a behavioral, an encoding and a decoding model. Both NHPs showed different behavioral strategies, which influenced the performance. Activity of the DN neurons reflected the unique strategies, with the direction of the visual stimulus frequently being encoded long before an upcoming saccade. Retrograde labeling of the recording location indicated that these neurons receive predominantly inputs from Purkinje cells in the lateral cerebellum as well as neurons of the principal olive and medial pons, all regions known to connect with neurons in the prefrontal cortex contributing to planning of saccades. Together, our results highlight that DN neurons can dynamically modulate their activity during a visual attention task, comprising not only sensorimotor but also cognitive attentional components.
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eLife assessment
This important study examined neuronal activity in the dentate nucleus of the cerebellum when monkeys performed a difficult perceptual decision-making task. The authors provide convincing evidence that the cerebellum represents sensory, motor, and behavioral outcome signals that are sent to the attentional system, but further analysis focusing on the disparity of performance between animals would improve the quality of the paper. This paper is of great general interest in that it shows the involvement of the cerebellum in cognitive processes at the neuronal level.
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Reviewer #1 (Public Review):
Summary:
Recordings were made from the dentate nucleus of two monkeys during a decision-making task. Correlates of stimulus position and stimulus information were found to varying degrees in the neuronal activities.
Strengths:
A difficult decision-making task was examined in two monkeys.
Weaknesses:
One of the monkeys did not fully learn the task. The manuscript lacked a coherent hypothesis to be tested, and no attempt was made to consider the possibility that this part of the brain may have little to do with the task that was being studied.
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Reviewer #2 (Public Review):
The authors trained monkeys to discriminate peripheral visual cues and associate them with planning future saccades of an indicated direction. At the same time, the authors recorded single-unit neural activity in the cerebellar dentate nucleus. They demonstrated that substantial fractions of DN cells exhibited sustained modulation of spike rates spanning task epochs and carrying information about stimulus, response, and trial outcome. Finally, tracer injections demonstrated this region of the DN projects to a large number of targets including several known to interconnect the visual attention network. The data compellingly demonstrate the authors' central claims, and the analyses are well-suited to support the conclusions. Importantly, the study demonstrates that DN cells convey many motor and nonmotor …
Reviewer #2 (Public Review):
The authors trained monkeys to discriminate peripheral visual cues and associate them with planning future saccades of an indicated direction. At the same time, the authors recorded single-unit neural activity in the cerebellar dentate nucleus. They demonstrated that substantial fractions of DN cells exhibited sustained modulation of spike rates spanning task epochs and carrying information about stimulus, response, and trial outcome. Finally, tracer injections demonstrated this region of the DN projects to a large number of targets including several known to interconnect the visual attention network. The data compellingly demonstrate the authors' central claims, and the analyses are well-suited to support the conclusions. Importantly, the study demonstrates that DN cells convey many motor and nonmotor variables related to task execution, event sequencing, visual attention, and arguably decision-making/working memory.
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Author response:
General comment:
"This important study examined neuronal activity in the dentate nucleus of the cerebellum when monkeys performed a difficult perceptual decision-making task. The authors provide convincing evidence that the cerebellum represents sensory, motor, and behavioral outcome signals that are sent to the attentional system, but further analysis focusing on the disparity of performance between animals would improve the quality of the paper. This paper is of great general interest in that it shows the involvement of the cerebellum in cognitive processes at the neuronal level."
We thank you for these general comments, and we agree with all of them.
Public Reviews (Reviewer #1):
Summary:
Recordings were made from the dentate nucleus of two monkeys during a decision-making task. Correlates of stimulus position and …
Author response:
General comment:
"This important study examined neuronal activity in the dentate nucleus of the cerebellum when monkeys performed a difficult perceptual decision-making task. The authors provide convincing evidence that the cerebellum represents sensory, motor, and behavioral outcome signals that are sent to the attentional system, but further analysis focusing on the disparity of performance between animals would improve the quality of the paper. This paper is of great general interest in that it shows the involvement of the cerebellum in cognitive processes at the neuronal level."
We thank you for these general comments, and we agree with all of them.
Public Reviews (Reviewer #1):
Summary:
Recordings were made from the dentate nucleus of two monkeys during a decision-making task. Correlates of stimulus position and stimulus information were found to varying degrees in the neuronal activities.
We agree with this summary.
Strengths:
A difficult decision-making task was examined in two monkeys.
We agree with this statement.
Weaknesses:
One of the monkeys did not fully learn the task. The manuscript lacked a coherent hypothesis to be tested, and no attempt was made to consider the possibility that this part of the brain may have little to do with the task that was being studied.
We understand these comments. It is correct that one of the monkeys did not fully learn the task, but it should be noted that both monkeys learned significantly above chance level, and we therefore find the recordings of both monkeys useful. We tested the hypothesis that neurons of the nucleus dentate can dynamically modulate their activity during a visual attention task, comprising not only sensorimotor but also cognitive attentional components. We agree that this hypothesis should be spelled out more explicitly in the introduction, which we will do in the revised version. We also appreciate the comment of this Reviewer that in our original submission we did not show our attempt to consider the possibility that this part of the brain may have little to do with the task that was being studied. We in fact did consider this possibility in that we applied muscimol to the dentate nucleus in one of the monkeys. The data of this one successful experiment show that the behaviour was reversibly affected in line with our hypothesis. Given that this only concerned one of the monkeys, we preferred not to present these data in the article. However, as the Reviewer correctly points out that this question remains hanging in the air, we will show them in our formal rebuttal letter. Please note that we decided to focus at the end of our research project on the tracing experiments, showing in both monkeys the connections of the dentate nucleus with the regions that are involved in attention. As a result, both monkeys have been sacrificed and we cannot expand upon our muscimol experiments anymore (which would have been useful indeed).
Last but not least, given the comments of the Reviewers, we will also add a Supplementary figure to Figure 2, in which we will present the data for both monkeys separately and provide our interpretation. This may help to strengthen our conclusions.
Public Reviews (Reviewer #2):
The authors trained monkeys to discriminate peripheral visual cues and associate them with planning future saccades of an indicated direction. At the same time, the authors recorded single-unit neural activity in the cerebellar dentate nucleus. They demonstrated that substantial fractions of DN cells exhibited sustained modulation of spike rates spanning task epochs and carrying information about stimulus, response, and trial outcome. Finally, tracer injections demonstrated this region of the DN projects to a large number of targets including several known to interconnect the visual attention network. The data compellingly demonstrate the authors' central claims, and the analyses are well-suited to support the conclusions. Importantly, the study demonstrates that DN cells convey many motor and nonmotor variables related to task execution, event sequencing, visual attention, and arguably decision-making/working memory.
We thank the Reviewer for this positive and constructive feedback.
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