Review Reports

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This case report documents the intensive multidisciplinary rehabilitation of a 70-year-old patient with unilateral spatial neglect (USN) following a right thalamic hemorrhagic stroke, incorporating adjunctive EEG-neurofeedback (EEG-NF) targeting the sensorimotor rhythm. Addressing the points outlined would strengthen the overall quality and impact of the research.

1. The manuscript addresses a highly relevant clinical problem: the disability caused by USN after stroke and the need for effective multidisciplinary interventions. By focusing on a thalamic lesion, it addresses an important subcortical node in the spatial attention network that is less frequently described than cortical neglect.
2. The background effectively identifies research gaps regarding the network-based model of neglect and the preliminary nature of EEG-NF evidence. The references are appropriate, including foundational works and very recent (2024–2026) literature in neurology and rehabilitation.
3. The authors are commendably transparent that clinical improvements cannot be attributed specifically to neurofeedback because treatments were delivered concurrently. To improve the study, the authors could discuss how future research might employ a multiple-baseline single-case experimental design to better isolate the effects of the NF component.
4. qEEG Robustness The use of the weighted Phase Lag Index (wPLI) for connectivity analysis is a robust technical choice, as it minimizes the confounding influence of volume conduction. However, the 19-channel montage remains a limitation for source-level interpretation, which the authors correctly acknowledge.
5. The results provide a high-quality, nuanced picture of recovery: neglect-specific and functional gains were significant, while motor recovery was more limited. This finding logically suggests that improved attentional engagement can drive functional independence even when physical hemiparesis persists.
6. The exploratory qEEG results revealed a broad redistribution of power rather than a narrow normalization of the trained 12–15 Hz band. This suggests that the impact of NF in stroke may be a global state-dependent effect on cortical vigilance rather than a specific frequency modulation, providing an interesting hypothesis for future studies.

< !--a=1--> Comments on the Quality of English Language

Could be improved

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Author Response

Dear Editor and Reviewers,

We sincerely thank you for your careful evaluation of our manuscript and for the constructive comments and suggestions, which helped us improve the clarity, rigor, and overall quality of the work.
All substantive changes made in response to the Reviewers’ comments are highlighted in blue in the revised manuscript for ease of reading. In addition, the manuscript underwent minor language and stylistic editing to improve clarity, concision, and readability. These editorial changes did not alter the scientific content, results, or interpretation of the study.

Reviewer 1 – Comment 1

The manuscript addresses a highly relevant clinical problem: the disability caused by USN after stroke and the need for effective multidisciplinary interventions. By focusing on a thalamic lesion, it addresses an important subcortical node in the spatial attention network that is less frequently described than cortical neglect.

Response:
We thank the Reviewer for this positive assessment. We agree that the thalamic localization represents an important aspect of the present case, particularly within contemporary network-based models of spatial neglect. We have retained this focus throughout the Introduction and Discussion while maintaining a cautious interpretation of the relationship between the thalamo-mesencephalic lesion and the observed clinical phenotype.

 

Reviewer 1 – Comment 2

The background effectively identifies research gaps regarding the network-based model of neglect and the preliminary nature of EEG-NF evidence. The references are appropriate, including foundational works and very recent (2024–2026) literature in neurology and rehabilitation.

Response:
We thank the Reviewer for this encouraging comment. We have preserved the network-based framework of spatial neglect and the deliberately cautious presentation of EEG-neurofeedback as an emerging and still preliminary approach. As part of the revision, the neurofeedback literature has also been further contextualized in relation to previous neglect-specific studies and current research directions.

 

Reviewer 1 – Comment 3

The authors are commendably transparent that clinical improvements cannot be attributed specifically to neurofeedback because treatments were delivered concurrently. To improve the study, the authors could discuss how future research might employ a multiple-baseline single-case experimental design to better isolate the effects of the NF component.

Response:
We thank the Reviewer for this valuable methodological suggestion. We agree that the concurrent delivery of EEG-NF and the other rehabilitation components represents the principal limitation to treatment-specific inference in the present case. We have therefore expanded the Limitations section to discuss the potential value of multiple-baseline single-case experimental designs in future hypothesis-driven studies. The following text has been added to the revised manuscript and is highlighted in blue for ease of reading:

“Future hypothesis-driven studies could strengthen causal inference by adopting single-case experimental designs with repeated measurements across baseline and intervention phases. In particular, a multiple-baseline design with staggered introduction of EEG-NF across participants, behaviors, or outcome domains could help distinguish changes temporally associated with the neurofeedback component from spontaneous recovery, repeated testing, and the effects of concurrent rehabilitation. Such designs also remain feasible in clinically heterogeneous neurorehabilitation populations [31]. Such designs would complement subsequent controlled group studies rather than replace them.”

We also added an appropriate methodological reference on single-case experimental designs in rehabilitation (Krasny-Pacini and Evans, 2018).

 

Reviewer 1 – Comment 4

qEEG Robustness. The use of the weighted Phase Lag Index (wPLI) for connectivity analysis is a robust technical choice, as it minimizes the confounding influence of volume conduction. However, the 19-channel montage remains a limitation for source-level interpretation, which the authors correctly acknowledge.

Response:
We thank the Reviewer for highlighting this aspect of the electrophysiological methodology. We agree that wPLI provides a useful sensor-level measure while reducing the influence of zero-lag synchronization potentially related to volume conduction. At the same time, the 19-channel montage does not support reliable source-level localization. This limitation was already explicitly acknowledged in the manuscript and has been retained in the revised version. Accordingly, all connectivity findings continue to be described as exploratory sensor-level observations rather than evidence of source-specific network reorganization.

 

Reviewer 1 – Comment 5

The results provide a high-quality, nuanced picture of recovery: neglect-specific and functional gains were significant, while motor recovery was more limited. This finding logically suggests that improved attentional engagement can drive functional independence even when physical hemiparesis persists.

Response:
We thank the Reviewer for highlighting this clinically relevant dissociation. We agree that the discrepancy between the marked neglect-related and cognitive-functional improvements and the comparatively limited motor recovery deserves particular emphasis. We have therefore revised the corresponding paragraph of the Discussion, while deliberately avoiding a causal interpretation that cannot be supported by the present single-case design. The revised text, highlighted in blue in the manuscript for ease of reading, reads:

“The dissociation between marked improvements in neglect-related and cognitive-functional outcomes and the more limited change in the FIM motor score is clinically noteworthy. Causal mediation cannot be inferred from this case. Nevertheless, improved attentional engagement, spatial exploration, and participation in rehabilitation may have supported greater functional independence despite persistent motor impairment. This is consistent with the recognized impact of spatial neglect on post-stroke functional outcomes [24].”

This wording allows us to acknowledge the clinically meaningful pattern identified by the Reviewer while maintaining appropriate caution regarding causal relationships.

 

Reviewer 1 – Comment 6

The exploratory qEEG results revealed a broad redistribution of power rather than a narrow normalization of the trained 12–15 Hz band. This suggests that the impact of NF in stroke may be a global state-dependent effect on cortical vigilance rather than a specific frequency modulation, providing an interesting hypothesis for future studies.

Response:
We thank the Reviewer for this insightful interpretation. We agree that the electrophysiological findings do not support a simple or selective normalization of the trained 12–15 Hz band. We have therefore expanded the corresponding paragraph of the Discussion to acknowledge the possibility that the observed spectral redistribution may reflect broader state-dependent changes rather than narrowly frequency-specific modulation. Importantly, we have framed this interpretation explicitly as hypothesis-generating, because the present design cannot establish that these changes were specifically induced by EEG-NF. The following text has been added and is highlighted in blue in the revised manuscript for ease of reading:

“One possible interpretation is that this distributed pattern reflects broader state-dependent changes in cortical activation, arousal, or vigilance rather than a narrowly frequency-specific modulation of the trained 12–15 Hz band. However, this interpretation remains hypothesis-generating. Resting-state EEG was acquired only before and after the rehabilitation period. The present design therefore cannot determine whether these changes were related to EEG-NF, spontaneous recovery, concurrent rehabilitation, or differences in physiological state between recording sessions.”

We believe that this addition incorporates the Reviewer’s valuable hypothesis while preserving the cautious interpretation required by the uncontrolled single-case design.

 

Reviewer 2 Report

Comments and Suggestions for Authors Respected Editor, Please find below my review of the manuscript entitled “Integrated Neurorehabilitation Including EEG-Neurofeedback for Unilateral Spatial Neglect After Right Thalamo-Mesencephalic Intracerebral Hemorrhage: A Case Report”, which has been submitted to Neurology International. The current case report describes the multidisciplinary rehabilitation of a patient with unilateral spatial neglect following a right thalamo-mesencephalic hemorrhagic stroke, including adjunctive EEG-based neurofeedback. The manuscript is clinically relevant because evidence regarding neurofeedback for post-stroke spatial neglect remains limited. The report is comprehensive and incorporates clinical, neuropsychological, functional, and exploratory qEEG assessments. The manuscript demonstrates several strengths. The case is thoroughly documented, and the rehabilitation protocol is clearly described. The authors appropriately refrain from making causal claims about the specific effects of neurofeedback. The use of standardized outcome measures, Reliable Change Index analyses, and detailed EEG methodology enhances the scientific rigor. However, several limitations should be addressed.

1. The readability of the manuscript requires improvement. It is substantially longer than a typical case report, particularly in the Methods and Results sections. Condensing procedural details and relocating technical EEG descriptions to the Supplementary Material would enhance clarity.
2. The discussion of study limitations should be rewritten. Principal limitations, including the single-case design, absence of a control condition, concurrent multidisciplinary rehabilitation, potential for spontaneous recovery, limited generalizability, and the exploratory nature of the qEEG analyses, should be explicitly stated and enumerated.
3. The literature review should be strengthened. The discussion should be expanded by comparing the present case with previously reported cases (if any) or small case series of EEG-neurofeedback for unilateral spatial neglect, particularly following subcortical or thalamic stroke. Briefly discussing relevant ongoing clinical trials, current research directions, and remaining knowledge gaps would further contextualize the findings.

In conclusion, the current case report is well-documented and addresses an important topic in post-stroke neurorehabilitation. Strengths include thorough assessment and careful interpretation. To improve the manuscript, I recommend making it more concise, clearly outlining study limitations, and expanding the comparison with published cases and ongoing research. These changes will enhance its clarity and relevance. Therefore, I recommend a major revision before the manuscript can be considered for publication.  

Author Response

Dear Editor and Reviewers,

We sincerely thank you for your careful evaluation of our manuscript and for the constructive comments and suggestions, which helped us improve the clarity, rigor, and overall quality of the work.
All substantive changes made in response to the Reviewers’ comments are highlighted in blue in the revised manuscript for ease of reading. In addition, the manuscript underwent minor language and stylistic editing to improve clarity, concision, and readability. These editorial changes did not alter the scientific content, results, or interpretation of the study.

 

Reviewer 2 – Comment 1
 The readability of the manuscript requires improvement. It is substantially longer than a typical case report, particularly in the Methods and Results sections. Condensing procedural details and relocating technical EEG descriptions to the Supplementary Material would enhance clarity.

Response:
 We thank the Reviewer for this important suggestion. We agree that the original manuscript contained a level of procedural and electrophysiological detail that could reduce readability for a case-report format. We therefore substantially condensed the Methods and Results sections while preserving the information necessary to understand the intervention and the main findings.

Specifically, we shortened the description of the multidisciplinary rehabilitation program and EEG-NF protocol, avoiding duplication with Tables 1 and 2. We also condensed Sections 2.3.2 and 2.4.2 and relocated detailed EEG preprocessing parameters, spectral-estimation procedures, regional definitions, sensitivity analyses, and wPLI implementation to a new Supplementary Methods section.

The qEEG Results section was similarly shortened so that the main manuscript now emphasizes the principal spectral and connectivity patterns, while complete numerical results remain available in Supplementary Tables S2–S3 and Supplementary Figures S1–S2.

For example, the revised Results now state:

“During EO, absolute delta and theta power increased broadly across regions, while alpha changes were spatially heterogeneous. SMR and higher-frequency activity generally increased, although the magnitude of change varied considerably across regions. During EC, delta, theta, and alpha power increased across regions. By contrast, SMR and beta-band changes were more region dependent and included reductions over temporal regions.”

and:

“Sensor-level wPLI also showed condition- and frequency-dependent changes rather than a uniform connectivity pattern. Notable findings included reduced frontal theta connectivity and increased frontal beta-2 connectivity during EO, together with increased beta-2 and low-gamma connectivity and reduced frontal–occipital alpha connectivity during EC.”

All changes introduced in response to this comment are highlighted in blue in the revised manuscript for ease of reading.

 

Reviewer 2 – Comment 2
 The limitations should be rewritten more explicitly and enumerated, including the single-case design, lack of a control condition, concurrent multidisciplinary rehabilitation, possible spontaneous recovery, limited generalizability, and exploratory nature of the qEEG findings.

Response:
 We thank the Reviewer for this helpful suggestion. We agree that, although these limitations were acknowledged in the original manuscript, they were presented within a single narrative paragraph and could be stated more explicitly. We have therefore substantially revised Section 4.1. Limitations, organizing the main methodological constraints sequentially and explicitly addressing the single-case design, absence of a control condition, concurrent multidisciplinary rehabilitation, spontaneous recovery and repeated-testing effects, limited generalizability, lack of long-term follow-up, psychometric limitations of exploratory RCI estimates, and the exploratory nature of the qEEG analyses.

The revised section, highlighted in blue in the manuscript for ease of reading, now states:

“Several limitations should be explicitly acknowledged. First, this is an uncontrolled single-case report and therefore does not permit causal inference regarding treatment efficacy. Second, EEG-NF was delivered concurrently with physiotherapy, speech and language therapy, and conventional cognitive stimulation; consequently, the specific contribution of EEG-NF cannot be separated from that of the other rehabilitation components. Third, the patient was assessed during the post-acute recovery period. Spontaneous neurological recovery, repeated-testing effects, changes in arousal or engagement, and the cumulative intensity of rehabilitation may all have contributed to the observed clinical changes [27,28].”

We further added:

“Fourth, the findings have limited generalizability because they derive from a single patient with a specific right thalamo-mesencephalic hemorrhagic lesion, clinical profile, and individualized rehabilitation program. Fifth, no long-term follow-up was available, preventing assessment of the durability of the observed clinical and electrophysiological changes.”

Finally, the revised section explicitly clarifies the exploratory status of the electrophysiological analyses:

“Seventh, the qEEG analyses were exploratory and based on only two assessment time points. This precluded characterization of within-treatment electrophysiological trajectories and formal EEG–behavior association analyses. In addition, the 19-channel montage and sensor-level wPLI approach did not permit reliable source-level localization, while higher-frequency measures remain particularly sensitive to low baseline values and residual physiological noise. Accordingly, the electrophysiological findings should be regarded as descriptive and hypothesis-generating rather than as evidence of a treatment-specific neurophysiological mechanism.”

In addition, consistent with the methodological suggestion raised by Reviewer 1, we added a final paragraph proposing multiple-baseline single-case experimental designs as a potential strategy for future studies seeking to better isolate the specific contribution of EEG-NF.

All changes introduced in response to this comment are highlighted in blue in the revised manuscript for ease of reading.

Reviewer 2 – Comment 3
 The literature review should be strengthened by comparing the present case with previous cases or small series of EEG-neurofeedback for unilateral spatial neglect, particularly following subcortical or thalamic stroke. Ongoing trials, current directions, and remaining knowledge gaps should also be briefly discussed.

Response:
 We thank the Reviewer for this important suggestion. We performed a targeted update of the literature on EEG-based neurofeedback for post-stroke spatial neglect, with particular attention to lesion location, previous clinical studies, registered trials, and emerging EEG/BCI approaches. We consequently expanded both the Introduction and Discussion. All additions are highlighted in blue in the revised manuscript for ease of reading.

First, we added the original acute-phase EEG-NF study by Saj et al. (2018), which was not explicitly cited in the submitted version, and more clearly distinguished it from the subsequent 2021 perspective article. The revised Introduction now states:

“Ros et al. [6] trained five patients with left visuospatial neglect after right-hemisphere stroke across six daily sessions of P4 alpha downregulation. Neurofeedback control improved progressively, and restoration of the resting alpha-rhythm dynamic range was associated with better visuospatial search performance [6]. Saj et al. [32] subsequently applied a single 30-min P4 alpha-downregulation session to four patients in the acute phase after right-hemisphere stroke. All patients reduced posterior alpha power during training and showed immediate improvement in neglect measures. However, the difference between pre-treatment and 1-week follow-up was not significant [32].”

We also substantially expanded the Discussion to directly compare these protocols with the present case and with the prospectively registered EEG-NF neglect trial ISRCTN85291842. In particular, we added:

“A prospectively registered pragmatic open randomized trial specifically addressing post-stroke neglect (ISRCTN85291842) adopted a partially similar frequency-contingency approach. That protocol rewarded either SMR (12–15 Hz) or beta-1 (15–18 Hz) while inhibiting theta (4–7 Hz) and high-beta (22–30 Hz) activity across 30 planned sessions [33]. Importantly, however, that trial required right-hemisphere cortical involvement as an inclusion criterion, and the registry record does not provide study results [33].”

With regard to lesion location, our review did not identify an EEG-NF study specifically designed around thalamic or other subcortical neglect as a lesion-defined subgroup. We therefore added the following cautious statement:

“Importantly, in the literature reviewed for the present report, we did not identify an EEG-NF study specifically designed to investigate thalamic or other subcortical neglect as a lesion-defined subgroup, nor a study stratifying EEG-NF outcomes according to lesion location [6,32,33]. Thus, the present case provides clinical documentation of EEG-NF embedded within multidisciplinary rehabilitation in a patient with a right thalamo-mesencephalic hemorrhagic lesion, but it should not be interpreted as evidence of lesion-specific efficacy.”

We also reviewed registered studies. A targeted search of ClinicalTrials.gov and ISRCTN did not identify an actively recruiting trial specifically evaluating EEG-NF as a treatment for post-stroke spatial neglect at the time of revision; the dedicated EEG-NF study ISRCTN85291842 is listed as completed. We therefore avoided suggesting that a currently recruiting neglect-specific EEG-NF trial exists.

Finally, we added recent 2026 literature addressing current research directions, including adaptive VR–BCI rehabilitation and EEG connectivity-based characterization of spatial neglect. The revised Discussion now states:

“Current research directions are increasingly extending beyond single-frequency neurofeedback toward adaptive EEG-based BCI, VR-integrated closed-loop systems, and network-informed rehabilitation targets [2,34,35].”

and:

“These developments remain exploratory and do not establish the efficacy of EEG-NF for USN; key priorities include appropriately controlled and lesion-stratified studies, repeated electrophysiological measurements, standardized neglect outcomes, and longer-term assessment of functional transfer [7,34,35].”

We believe these additions provide a more explicit comparison with the existing EEG-NF literature while clarifying the particular knowledge gap concerning thalamic and other subcortical lesions and avoiding overstatement of the current evidence.

 

 

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Thank you to the author for the thorough revisions. All the issues have been fully addressed, and I have no further comments.

Recommendation: Accept

< !--a=1--> Comments on the Quality of English Language

Could be improved

 

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