Thalamic Stroke: An Opportunity to Study the Brain Mechanisms of Sleep–Wake and Cognition

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Comments to authors –

 

In this review, the authors discuss the role of different thalamic nuclei in sleep – wakefulness and other cognitive functions. In addition, they summarize the current literature on the adverse effects of thalamic stroke on sleep and cognitive abilities, from human clinical studies and rodent models of stroke. The functions of thalamus are only broadly understood and distinct roles of each thalamic nuclei is still being explored. Hence summarizing the disruption of these behaviors post thalamic stroke could be important to understand the interplay between sleep and cognition and their regulation by the thalamus. The review is well-written and informative, the summary of previous literature is concisely presented in Table 1 and Figs.1 – 3. My recommendation is ‘ACCEPT’, I have few minor comments and suggestions –

1.     Suggestion to modify current Fig.2 to please include two new panels beside 2A and 2B where the authors summarize the current literature on dysregulated sleep / cognitive abilities for each thalamic nuclei respectively. The authors have mentioned this in detail in the text, however a pictorial summary of the individual functions of thalamic nuclei before and after thalamic stroke will be very informative for the readers. This would enhance the current knowledge already shown in Fig.2 and provide a compare – contrast for the readers to better understand the roles of the thalamus and their corresponding dysregulation post stroke.

 

2.     There are few minor typos in lines 168, 259, 382 and 415.

Author Response

In this review, the authors discuss the role of different thalamic nuclei in sleep – wakefulness and other cognitive functions. In addition, they summarize the current literature on the adverse effects of thalamic stroke on sleep and cognitive abilities, from human clinical studies and rodent models of stroke. The functions of thalamus are only broadly understood and distinct roles of each thalamic nuclei is still being explored. Hence summarizing the disruption of these behaviors post thalamic stroke could be important to understand the interplay between sleep and cognition and their regulation by the thalamus. The review is well-written and informative, the summary of previous literature is concisely presented in Table 1 and Figs.1 – 3. My recommendation is ‘ACCEPT’, I have few minor comments and suggestions –

Thank you for your kind feedback. We greatly appreciate it.

1. Suggestion to modify current Fig.2 to please include two new panels beside 2A and 2B where the authors summarize the current literature on dysregulated sleep / cognitive abilities for each thalamic nuclei respectively. The authors have mentioned this in detail in the text, however a pictorial summary of the individual functions of thalamic nuclei before and after thalamic stroke will be very informative for the readers. This would enhance the current knowledge already shown in Fig.2 and provide a compare – contrast for the readers to better understand the roles of the thalamus and their corresponding dysregulation post stroke.

Thank you for this valuable suggestion. While we acknowledge the importance of summarizing the functions of individual thalamic nuclei before and after thalamic stroke, we would like to explain some challenges that might make this task difficult.

• Vascular lesions of the thalamus can encompass several anatomic groups of nuclei. This diversity makes it challenging to create a concise summary for each nucleus.
• Thalamic nuclei are relatively small, and studies in thalamic stroke patients often focus on the thalamus as a whole or thalamic vascular territories encompassing different nuclei rather than specific nuclei.
• Limited data is available to compare sleep/cognitive functioning in patients with different thalamic vascular lesions. The study by Scharf et al. is a notable exception.

In our current Figure 2, we have attempted to depict the general functions of the main groups of thalamic nuclei. However, given the large number of thalamic nuclei and the complexity of their interactions, it is challenging to represent individual arrows from each nucleus without overwhelming the diagram with too many arrows.

We hope that our efforts in Figure 2 provide a useful overview of thalamic functions. We remain open to further suggestions for improving the clarity and informativeness of the Figure and will consider any feasible enhancements in the context of these challenges.

2. There are few minor typos in lines 168, 259, 382 and 415.

Thank you for pointing this out. We have updated these lines accordingly.

Reviewer 2 Report

Comments and Suggestions for Authors

 Minor editing is needed for the manuscript to be accepted

Line 93: Use ‘Among’ instead  of between

Line 94: Authors mention that : in primate, thalamus is densely connected with cortex and they cite a paper that mostly talks about rodents

 

Line 124: Authors should cite a few references for ‘faster shifts in neuronal activity in the hypothalamus

 

Line 259 : check for sentence formation

 

 

In Fig 2: the thalamus schematic looks similar to fig 1 but the abbreviations for some regions have been changed and it doesn’t reflect in the abbreviations section below for example ‘APul’ is changed to Pua etc. Is there a reason for this change?

Comments on the Quality of English Language

 Minor editing is needed for the manuscript to be accepted

Line 93: Use ‘Among’ instead  of between

Line 94: Authors mention that : in primate, thalamus is densely connected with cortex and they cite a paper that mostly talks about rodents

 

Line 124: Authors should cite a few references for ‘faster shifts in neuronal activity in the hypothalamus

 

Line 259 : check for sentence formation

 

 

In Fig 2: the thalamus schematic looks similar to fig 1 but the abbreviations for some regions have been changed and it doesn’t reflect in the abbreviations section below for example ‘APul’ is changed to Pua etc. Is there a reason for this change?

Author Response

Minor editing is needed for the manuscript to be accepted

Thank you for your feedback and for highlighting the aspects to improve.

Line 93: Use ‘Among’ instead of between

We have updated the line accordingly.

Line 94: Authors mention that : in primate, thalamus is densely connected with cortex

We have updated the reference accordingly.

Line 124: Authors should cite a few references for ‘faster shifts in neuronal activity in the hypothalamus

We added few references to substantiate our statement.

Line 259: check for sentence formation

We have updated the line accordingly.

In Fig 2: the thalamus schematic looks similar to fig 1 but the abbreviations for some regions have been changed and it doesn’t reflect in the abbreviations section below for example ‘APul’ is changed to Pua etc. Is there a reason for this change?

Thank you for pointing this out. After the discussion among co-authors, we decided to be consistent with the adapted variation of the parcellation. Therefore, we have updated the Figure 1 to fully match the Figure 2. The parcellation is adapted from Carrera, 2002, and is well-established in the field.

Reviewer 3 Report

Comments and Suggestions for Authors

The article presents a thorough examination of the intricate relationship between the thalamus, sleep, and cognition, drawing upon a wide array of clinical and experimental investigations. It is evident from the literature that the thalamus assumes a pivotal role in the regulation of both sleep and cognitive functions. This review explores various facets of this intricate relationship and discusses how thalamic stroke serves as a valuable window for studying the tridirectional interaction among the thalamus, sleep, and cognition.

 

1. Comprehensive Coverage:

The article offers an extensive and all-encompassing analysis of the subject matter. It encompasses the multifaceted role of the thalamus in the regulation of sleep, cognitive functions, and the intricate interplay between these domains. It effectively integrates insights derived from clinical studies, experimental models, and translational research, thus providing a holistic perspective on the topic at hand.

 

2. Clarity and Organization:

The article exhibits a well-structured format with distinct sections addressing various facets of the thalamus's role in sleep and cognition. The logical flow between each section enhances the reader's understanding of this complex subject, facilitating comprehension and retention of key concepts.

 

3. Exploration of Future Avenues:

The article appropriately identifies areas warranting further investigation.. This emphasis on future research directions enhances the scholarly value of the article.

 

 

In summary, this article provides a comprehensive and scientifically robust exploration of the thalamus's pivotal role in the regulation of sleep and cognition. Its strengths lie in its depth of coverage, well-organized structure, and the emphasis placed on avenues for future research, thereby contributing significantly to our understanding of this intricate.

Author Response

Thank you for your kind feedback. We greatly appreciate it.