Review Reports

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This manuscript explores the interaction between theta oscillations and oculomotor processes and their role in cognition. Overall, the manuscript is well organized and provides a useful overview of the field. However, some aspects should be refined to improve clarity and conceptual precision.

The proposed “working model” provides a useful synthesis of the literature, although its novelty relative to existing frameworks is not entirely clear. The manuscript would benefit from a more explicit discussion of what is conceptually new in the model and, if possible, from outlining specific testable predictions that follow from it.

In some sections, the interpretation of the findings could be more cautious. In particular, results based primarily on phase-locking, coherence, or correlational observations are occasionally described in causal terms. Clarifying this distinction would strengthen the overall rigor of the review.

At times, theta, alpha, and low-beta frequencies are discussed together (e.g., extending up to ~9–22 Hz). While this reflects parts of the literature, a clearer distinction between frequency bands and their proposed functional roles would improve conceptual clarity.

The manuscript could also benefit from discussion of recent work on rhythmic attentional sampling and the relationship between attention and oculomotor control. In particular, studies showing that attentional rhythms can occur independently of overt eye movements (e.g., Gaillard et al., 2022, Nature Communications) would provide a useful complement to the current framework.

Minor comments

Some sections are somewhat repetitive and could likely be streamlined. The clinical section is interesting and generally well referenced, however, relative to the main theme of the review, it becomes disproportionately extensive. A more concise and better contextualized clinical discussion would help maintaining the focus of the manuscript.

Author Response

Comment 1: The proposed “working model” provides a useful synthesis of the literature, although its novelty relative to existing frameworks is not entirely clear. The manuscript would benefit from a more explicit discussion of what is conceptually new in the model and, if possible, from outlining specific testable predictions that follow from it.
Response 1: We have added a new paragraph (lines 303-323) that explicitly states what is conceptually new in our working model. We also outline three testable predictions that follow from this framework regarding pre-saccadic phase, post-fixation theta-gamma coupling, and disruption of saccade-related relay signals.

Comment 2: In some sections, the interpretation of the findings could be more cautious. In particular, results based primarily on phase-locking, coherence, or correlational observations are occasionally described in causal terms. Clarifying this distinction would strengthen the overall rigor of the review.
Response 2: We agree that several passages described phase-locking, coherence, and cross-frequency coupling findings in causal terms, and we have revised the manuscript to more carefully distinguish correlational evidence from findings derived from direct experimental manipulation. We softened causal verbs (e.g., "demonstrates," "ensures," "gates," "synchronizes," "primes," "uses") to associative language (e.g., "is associated with," "is consistent with," "co-occurs with") throughout. Reworded descriptions of V1/V4 theta-paced rhythms and laminar phase-reset findings to reflect correlative rather than direct evidence (lines 101-103). Revised ACC-FEF, hippocampal, and amygdala-hippocampal coherence findings to clarify that coherence is associated with, rather than causally responsible for, behavioral outcomes (lines 106-120). Changed language describing theta oscillations as "gating" or "functioning as" oculomotor coordinators to indicate these are proposed models rather than established mechanisms (lines 152-160, 174-176, 197-200, 251-253, 266-268). Softened summary statements about hippocampal theta "organizing" memory encoding and "cueing" SEMs to reflect the correlational nature of the underlying phase–behavior associations. Revised the epilepsy section to clarify that IEDs are associated with desynchronized theta-oculomotor activity rather than causally producing behavioral deficits (lines 440-442). Expanded the concluding statement (lines 544-549) to explicitly acknowledge that direct manipulations (e.g., optogenetic SC stimulation, tACS, DBS) provide causal support for select components of the model, while much of the supporting evidence remains correlational. We believe these revisions more accurately reflect the evidentiary basis of each finding and strengthen the rigor of the review.

Comment 3: At times, theta, alpha, and low-beta frequencies are discussed together (e.g., extending up to ~9–22 Hz). While this reflects parts of the literature, a clearer distinction between frequency bands and their proposed functional roles would improve conceptual clarity.
Response 3: We thank the reviewer for this point. We have added prose defining theta (4-8 Hz), alpha (~8-12 Hz), and low-beta (~13-22 Hz) and their functional roles, and revised the manuscript to label each cited finding by its actual frequency band. Studies previously described as "theta" that report effects at 8-12 Hz (e.g., Premereur et al., 2012) are now correctly labeled as alpha and alpha/low-beta, respectively. We also clarify that frontoparietal alpha/low-beta rhythms may operate alongside, rather than as part of, hippocampal and midbrain theta dynamics.

Comment 4: The manuscript could also benefit from discussion of recent work on rhythmic attentional sampling and the relationship between attention and oculomotor control. In particular, studies showing that attentional rhythms can occur independently of overt eye movements (e.g., Gaillard et al., 2022, Nature Communications) would provide a useful complement to the current framework.
Response 4: We thank the reviewer for this helpful suggestion. We added a short new paragraph (lines 317-320) discussing recent work on rhythmic attentional sampling, including the Gaillard et al. (2020) report that attentional rhythms can occur independently of overt eye movements. We use this work to clarify the scope of our model.

Comment 5: Some sections are somewhat repetitive and could likely be streamlined. The clinical section is interesting and generally well referenced, however, relative to the main theme of the review, it becomes disproportionately extensive. A more concise and better contextualized clinical discussion would help maintaining the focus of the manuscript.
Response 5: We agree that the clinical section had become disproportionately verbose and that several mechanistic findings were described redundantly. We streamlined the mechanistic sections by removing redundant descriptions of Rajkai et al. (2008) and Shaverdi et al. (2023), and have condensed the clinical. These revisions remove ~65 lines of redundant content while preserving the substantive findings.

Reviewer 2 Report

Comments and Suggestions for Authors

This thorough review that effectively summarizes the bidirectional relationship between theta oscillations and saccadic eye movements (SEMs). The manuscript provides a compelling framework linking active vision, oculomotor dynamics, and cognitive processing in healthy populations and individuals with neurological disorders. I recommend minor revisions based on the constructive points below.

1. Typographical Errors: There are a few minor typographical errors and missing words in the text that need to be corrected. For example, in the "Clinical Implications and Future Directions" section, "the absence of visual input" should be changed to "the absence of visual input." Also, check for missing words, such as instances where "saccades" is written as "s" (e.g., "preceded s toward," "cognitive control over s," and "an anti-paradigm").

2. Figure 1 clarity: While Figure 1 provides an excellent conceptual and systems-level summary of oculomotor processing, the diagram contains typographical inconsistencies. Specifically, the text inside the boxes uses the numbers "0" and "8" instead of the Greek letter "θ" (e.g., "8 pacemaker," "executive 0," and "0 reset"). Please ensure that the θ symbol is rendered correctly and consistently throughout the graphics and captions.3. Review Methodology: Although this is a narrative review, the manuscript would benefit from a brief paragraph outlining the search strategy. This paragraph should include the databases used, the inclusion/exclusion criteria, and the timeframe. This will enhance the reproducibility and rigor of the literature selection process.

4. Clinical Feasibility Discussion: The authors convincingly argue for using eye tracking and EEG as biomarkers in the sections on Parkinson's disease, Alzheimer's disease, and epilepsy. However, it would be beneficial to include a brief discussion of the practical limitations and challenges of using high-density EEG and high-resolution eye tracking in routine clinical settings, particularly for patients with advanced motor or cognitive decline.

Author Response

Comment 1: Typographical Errors: There are a few minor typographical errors and missing words in the text that need to be corrected. For example, in the "Clinical Implications and Future Directions" section, "the absence of visual input" should be changed to "the absence of visual input." Also, check for missing words, such as instances where "saccades" is written as "s" (e.g., "preceded s toward," "cognitive control over s," and "an anti-paradigm").
Response 1: We thank the reviewer for catching these errors and apologize for the oversight. We have corrected the missing word "saccades" throughout the manuscript, corrected "he absence" to "in the absence", and fixed additional typographical errors including "hen" to "when", "theta-mediate" to "theta-mediated", "correlated" to "correlate", and "theta– coupling" to "theta-SEM coupling". We also addressed duplicated words (lines 478, 511-512, 526), punctuation and capitalization errors (lines 141, 307, 371, 509, 618), and several other minor errors identified during a thorough proofreading pass.

Comment 2: Figure 1 clarity: While Figure 1 provides an excellent conceptual and systems-level summary of oculomotor processing, the diagram contains typographical inconsistencies. Specifically, the text inside the boxes uses the numbers "0" and "8" instead of the Greek letter "θ" (e.g., "8 pacemaker," "executive 0," and "0 reset"). Please ensure that the θ symbol is rendered correctly and consistently throughout the graphics and captions.
Response 2: Updated the theta-symbol in Figure 1 to be more clear.

Comment 3: Review Methodology: Although this is a narrative review, the manuscript would benefit from a brief paragraph outlining the search strategy. This paragraph should include the databases used, the inclusion/exclusion criteria, and the timeframe. This will enhance the reproducibility and rigor of the literature selection process.
Response 3: We agree that briefly outlining the search strategy will improve the transparency and reproducibility. We have added a short paragraph to the introduction section (lines 66-76) describing our approach, including the databases searched, the search terms and keyword combinations used, and the timeframe of included studies. We have also noted that, consistent with the narrative format of this review, studies were selected to provide representative coverage of foundational and contemporary work rather than through a systematic screening protocol. We believe this addition strengthens the rigor of the review and thank the reviewer for the suggestion.

Comment 4: Clinical Feasibility Discussion: The authors convincingly argue for using eye tracking and EEG as biomarkers in the sections on Parkinson's disease, Alzheimer's disease, and epilepsy. However, it would be beneficial to include a brief discussion of the practical limitations and challenges of using high-density EEG and high-resolution eye tracking in routine clinical settings, particularly for patients with advanced motor or cognitive decline.
Response 4: We thank the reviewer for the suggestion. We have added a brief paragraph to the Therapeutic Modulation section (lines 524-534) addressing the practical limitations of high-density EEG and high-resolution eye-tracking in routine clinical use, including labor-intensive setup, lack of standardized protocols, tremor-related artifact contamination in PD, calibration challenges, and the particular difficulty of reliable use in patients with advanced motor or cognitive decline.

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The authors have adequately addressed my comments and concerns.