{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T17:12:26Z","timestamp":1779210746842,"version":"3.51.4"},"update-to":[{"DOI":"10.12688\/f1000research.169799.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000}}],"reference-count":42,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001333","name":"Rhodes University","doi-asserted-by":"publisher","award":["PGSD05\/2022"],"award-info":[{"award-number":["PGSD05\/2022"]}],"id":[{"id":"10.13039\/501100001333","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["TTK200408511634"],"award-info":[{"award-number":["TTK200408511634"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009467","name":"University of the Witwatersrand, Johannesburg","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009467","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns3:p>Background The human immunodeficiency virus (HIV) crosses the blood-brain barrier, compromising cortical networks and cognition. Neuropharmacological intervention in the form of combination antiretroviral therapy (cART) does not reverse cognitive decline in pediatric and adolescent HIV. In search of options to enhance cognition in affected adolescents, we evaluated the effectiveness of attention training. Methods The training was evaluated by pairing participants\u2019 outcomes on the Stroop Colour Word Test (SCWT), a test of attention and inhibitory control, to brain hemodynamic responses measured by functional near-infrared spectrometry (fNIRS) both prior to, and after, the training. Changes in oxygenated haemoglobin in the prefrontal cortex during the SCWT were compared in 15 HIV+ participants who received attention training with that of 13 HIV+ participants who did not receive the intervention. Results Intragroup analyses showed differences in oxygenated haemoglobin levels between congruent and incongruent conditions of the SCWT only for participants who received the attention training. Specifically, improved behavioural performance on SCWT for the attention group was associated with a significant decrease in oxygenated haemoglobin in the dorsolateral prefrontal cortex, and frontopolar brain areas in the training group. Decreased hemodynamic activation in the training group suggests greater neural efficiency in completing cognitive tasks. Conclusions Findings suggest that customised attention training maybe an effective complementary adjunct to cART for children and adolescents living with HIV.<\/ns3:p>","DOI":"10.12688\/f1000research.169799.2","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T06:59:07Z","timestamp":1777013947000},"page":"1000","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Shining Light into Adolescent HIV Neuroplasticity: A Study of the Prefrontal Cortex Using Functional Near Infrared Spectrometry"],"prefix":"10.12688","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2592-6171","authenticated-orcid":false,"given":"Sizwe","family":"Zondo","sequence":"first","affiliation":[{"name":"Psychology Grahamstown Eastern Cape Rhodes University Psychology Clinic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kate","family":"Cockcroft","sequence":"additional","affiliation":[{"name":"Psychology Johannesburg Gauteng University of the Witwatersrand Johannesburg School of Human and Community Development"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Candida","family":"da Silva Ferreira Barreto","sequence":"additional","affiliation":[{"name":"Neuroergonomics & Neuroimaging Lab Philadelphia Pennsylvania Drexel University School of Biomedical Engineering Science and Health Systems"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2495-3159","authenticated-orcid":false,"given":"Aline","family":"Ferreira Correia","sequence":"additional","affiliation":[{"name":"Psychology Johannesburg Gauteng University of the Witwatersrand Johannesburg School of Human and Community Development"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"key":"ref2","doi-asserted-by":"publisher","first-page":"2164","DOI":"10.3389\/fpsyg.2019.02164","article-title":"The Stroop effect occurs at multiple points along a cascade of control: Evidence from cognitive neuroscience approaches.","volume":"10","author":"M Banich","year":"2019","journal-title":"Front. 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Sens."}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/14-1000\/v2\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/14-1000\/v2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/14-1000\/v2\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T17:04:08Z","timestamp":1779210248000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/14-1000\/v2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,24]]},"references-count":42,"URL":"https:\/\/doi.org\/10.12688\/f1000research.169799.2","relation":{"has-version":[{"id-type":"doi","id":"10.12688\/f1000research.169799.1","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.197457.r478731","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.197457.r478731","asserted-by":"object"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,24]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/14-1000\/v2#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.197457.r478731, Nerrolyn Ramstrand, J\u00f6nk\u00f6ping University, J\u00f6nk\u00f6ping, 19 May 2026, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/14-1000\/v2#referee-response-478731","order":0,"name":"referee-response-478731","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.187175.r425390, Kaylee Van Wyhe, Stellenbosch University, Stellenbosch, Western Cape, 05 Jan 2026, version 1, 3 approved with reservations","URL":"https:\/\/f1000research.com\/articles\/14-1000\/v1#referee-response-425390","order":1,"name":"referee-response-425390","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Sizwe Zondo<\/b>; \n<i>Posted: 09 Mar 2026<\/i>; This manuscript presents an innovative and timely investigation of prefrontal cortical hemodynamics in adolescents living with HIV using functional near-infrared spectroscopy (fNIRS). The authors examine neural changes associated with an attention-training intervention and pair these findings with behavioural outcomes on the Stroop Colour\u2013Word Test (SCWT). The topic is highly relevant to the field of pediatric neuroHIV, and the study offers promising insights into neuroplasticity in adolescents. Overall, I am supportive of the manuscript and believe it makes a meaningful contribution. My comments below are intended to strengthen clarity, contextual accuracy, and methodological transparency.  \n<b>Major Comments<\/b> &nbsp;  \n<b>Title and overall framing<\/b> The title is engaging, well constructed, and suitably reflects the study\u2019s scope. I note that its clarity and precision support the paper\u2019s impact and readability.  \n<b>Response:<\/b> We thank the reviewer for this positive comment.  \n<b>2. Appropriateness of fNIRS<\/b> The authors\u2019 decision to use fNIRS is well justified, especially given its portability, tolerance for movement, and ability to measure both oxygenated and deoxygenated hemoglobin, all suited to pediatric and adolescent populations. This strengthens the methodological rationale.   \n<b>Introduction<\/b> \n<b>3. Update epidemiological statistics<\/b> The introduction references UNAIDS 2019 estimates. More recent estimates are available (e.g., 2022 and 2024 updates). Revising these statistics will ensure accuracy and reinforce the contemporary relevance of the study. \n<b>Response:<\/b> We have since updated the epidemiological data \u2013 and included the latest reference from WHO \/ UNAIDS (2024).   \n<b>4. ART toxicity statement needs clarification<\/b> The introduction states that combination ART is \u201ctoxic,\u201d referencing Yuan &amp; Kaul (2019). This framing is historically accurate for older regimens but does not reflect current treatment realities. Contemporary cART regimens are significantly safer, well-tolerated, and overwhelmingly beneficial, improving survival, preventing disease progression, and completely preventing HIV transmission when virally suppressed. I strongly recommend clarifying this distinction to avoid reinforcing outdated or stigmatizing narratives. A brief note highlighting reduced toxicity in newer regimens would enhance scientific accuracy. \n<b>Response:<\/b> Thank you for this important point, we have since rephrased the section and subsequently included a note detailing reduced neurotoxicity of current cART regimens.   \n<b>5. Outdated literature on cognitive deficits<\/b> The paper relies on Milligan &amp; Cockcroft (2017) to support statements about executive functioning deficits. Given the rapid advancements in pediatric neuroHIV research, it would strengthen the introduction to reference more recent evidence. \n<b>Response: <\/b>  In addition to the above key reference, we have updated the section by including a meta-analysis reference (2024) that indicates the persistence of cognitive deficits in this group.   \n<b>6. Missing behavioural interpretation from Chang et al. (2001)<\/b> The introduction uses Chang et al. (2001) to discuss altered brain activation patterns but omits a key behavioural context: whether hyperactivation was associated with comparable accuracy but slower processing speed. Including the behavioural outcomes would give a more complete foundation for discussing BOLD-like hemodynamic responses and compensatory hyperactivation in HIV. \n<b>Response:<\/b> Thank you for this observation \u2013 we have since included a section expanding on the above, by highlighting accuracy levels as noted by the authors.&nbsp;   \n<b>7. Language and terminology regarding HIV<\/b> The manuscript frequently uses \u201cHIV+.\u201d It is recommended to adopt people-first, non-stigmatizing terminology, such as \u201cadolescents living with HIV (ALWH).\u201d Applying consistent, person-first language will align the manuscript with current global guidelines. \n<b>Response:<\/b> This observation is welcome and has been adopted into the manuscript when speaking in general terms pertaining to individuals living with HIV. However, the term \u2018HIV+\u2019 is retained for easier reporting and consistency within the manuscript, so as not to confuse \u2018adults\u2019 and \u2018adolescents\u2019 living with HIV.   \n<b>Methods<\/b>  \n<b>8. Participant viral suppression status<\/b> The methods section states that all participants were on cART but does not indicate whether they were virally suppressed. Viral load status is a critical clinical characteristic that can meaningfully influence neurocognitive functioning. Please clarify suppression status if available. \n<b>Response:<\/b> We thank the reviewer for this important point. Data for the study was collected at children\u2019s homes \u2013 with one nurse available at one of the homes. As noted in the discussion section, while all participants were receiving combination antiretroviral therapy, concomitant viral load measurement was not available on the children\u2019s medical records and had to be directly sourced from the provincial hospital. The absence of viral load data is noted in the Limitations and Discussion section. We further agree that viral suppression status is clinically important, and an influential factor in neurocognitive functioning. This key data variable will be collected on the Phase 2 of our study.   \n<b>9. Age categorisation using WHO groupings<\/b> Participants are divided into 0\u201313 and 14\u201318 age groups using WHO categories. While I understand the rationale, this results in a wide \u201c0\u201313\u201d group containing 11 participants across a period of rapid neurodevelopment (childhood \u2192 early adolescence). Given the mean age of 17 years, it would be scientifically more meaningful to report exact ages or narrower developmental bands. Prefrontal cortex maturation differs substantially between a 7-year-old, a 12-year-old, and a 17-year-old. Reporting mean age, SD, and a narrower range would improve interpretability. \n<b>Response:<\/b> This point is well taken, and a limitation of the study. The authors acknowledge that recategorization of the age variable, although expedient, would mean reanalysis of imaging data. We will however seek to take this consideration in future publications emerging from the current work.&nbsp; &nbsp;  \n<b>10. Education levels<\/b> Rather than reporting \u201cprimary vs secondary schooling,\u201d providing duration of education (e.g., mean years of schooling completed) would offer greater developmental and socio-demographic insight. \n<b>Response:<\/b>&nbsp; This is a much-appreciated observation. From the data collected at the HIV shelters, we could not ascertain the mean years of schooling completed; this data was either not available, or not forthcoming, as its availability could indirectly affect donor funding for certain populations of children. Nonetheless, the authors acknowledge the implication of this oversight for developmental and socio-demographic interpretability.   \n<b>11. Outlier participant<\/b> One participant was excluded for responding to fewer than 38% of trials and pressing the same key for all SCWT conditions. It would be useful to report:  the participant\u2019s age whether they were virally suppressed whether their behavioural pattern suggested non-engagement, motor difficulty, or attentional impairment  This information strengthens transparency around exclusion criteria and may offer insight into neurodevelopmental or behavioural variability within the cohort. \n<b>Response:<\/b> Thank you for this observation. The relevant information has been incorporated into the manuscript. As indicated on the manuscript revisions, no data was available pertaining to viral suppression (CD4+ count), for research participants.  \n<b>Discussion and Conclusion<\/b>   \n<b>12. Real-world implications and applicability<\/b> The discussion is strong, but I encourage the authors to briefly comment on the feasibility and clinical implications of implementing attention training in real-world settings. For example:  approximate duration of training per session potential cost or resource requirements suitability for low-resource or community-based environments whether the intervention can be delivered by non-specialists  Even a brief, context-aware comment would enhance translational value. \n<b>Response:<\/b> We thank the reviewer for this suggestion. The Discussion section has been revised to include a brief comment on the feasibility and clinical implications of implementing attention training in real-world settings such as where the study was executed. Specifically, we comment on approximate sessions, their duration, and the use of pencil paper cognitive interventions for potential rehabilitation delivery by non-specialist facilitators.  \n<b>13. Excellent summary of limitations<\/b> The limitations section is thorough, well-considered, and enhances credibility. I agree that factors such as HIV genotype, age of cART initiation, neurobiological heterogeneity, and short-separation channel absence are meaningful limitations. The acknowledgement of sample attrition in vulnerable populations is also appropriate. \n<b>Response:<\/b> We thank the reviewer for this helpful comment.   \n<b>Concluding Remarks<\/b>  This is an important and innovative study that meaningfully advances our understanding of neuroplasticity in adolescents living with HIV. The combination of fNIRS with behavioural assessment is commendable, and the findings offer promising indications that attention training may serve as a valuable adjunct to cART. Addressing the points above, primarily related to updated epidemiological data, clarifying ART statements, refining participant descriptions, and strengthening real-world context, will improve clarity and enhance the manuscript\u2019s impact. I am supportive of publication following these revisions. \n<b>Response:<\/b> We thank the reviewer for all the above comments, and other observations to strengthen the academic integrity of this work.","URL":"https:\/\/f1000research.com\/articles\/14-1000\/v2#referee-comment-15631","order":2,"name":"referee-comment-15631","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.187175.r441630, Taylor Fitzpatrick-Schmidt, Louisiana State University Health Sciences Center, New Orleans, Louisiana, 06 Jan 2026, version 1, 3 approved with reservations","URL":"https:\/\/f1000research.com\/articles\/14-1000\/v1#referee-response-441630","order":3,"name":"referee-response-441630","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Sizwe Zondo<\/b>; \n<i>Posted: 09 Mar 2026<\/i>; This study investigated the impact of attention training on cognitive performance using the Stroop Color Word Test and cortical hemodynamic responses, a proxy for neural activation, using functional near-infrared spectroscopy (fNIRS) in HIV-positive adolescents. Overall, the manuscript is well-written and has several strengths, including its focus on an understudied population and the integration of both behavioral and neuroimaging measures. I recommend addressing the following points within the scope of this article.  \n<b>Abstract<\/b> Overall, the abstract clearly conveys the main findings and take-home message of the study. It could be strengthened by briefly reporting the behavioral results in the Results section, even though the results are not significant, and adding a short sentence to provide interpretation of the changes in oxygenated hemoglobin as done in the discussion (e.g., greater neural efficiency), as described in the Discussion section of the main body. This would help more clearly link the Results and Conclusions sections. \n<b>Response:<\/b> Thank you for your comment. The abstract has since been revised to explicitly report the behavioural results. Additionally, a brief interpretive statement has been added to contextualize the observed changes in oxygenated haemoglobin levels.  \n<b>Introduction<\/b> The introduction effectively establishes the importance of studying interventions targeting cognitive deficits in HIV-positive children and adolescents and provides a solid overview of prior neuroimaging work in this population. This section could be streamlined by reducing methodological detail from previous studies and by placing greater emphasis on the rationale for focusing on attention at the targeted cognitive domain and the prefrontal cortex as the primary region of interest. &nbsp; \n<b>Response:<\/b> It is acknowledged that the focus on attention is not emphasized \u2013 to rectify this anomaly the manuscript has added a section on the construct of attention and linked this construct to prefrontal lobe anatomy and the regions of interest of the study. &nbsp;  \n<b>Methods and Results<\/b> The Methods and Results sections are generally well-organized. The following points may further strengthen these sections:  If available, include information on age at HIV diagnosis and indicators of disease severity (e.g., CD4 count, viral load), as these variables may influence baseline cognitive task performance. &nbsp;  \n<b>Response:<\/b> Thank you for this comment. Unfortunately, at the time of data collection, this critical medical data was not available to the researchers. The research was executed at data sites that care for children living with HVI and not at tertiary clinical sites where the data might be easily available. The sites were unfortunately unable to provide this key biomarker data, except for medication other relevant data. &nbsp; &nbsp;  Consider conducting correlational analyses to investigate associations between behavioral performance and neuroimaging results.  \n<b>Response: <\/b>  We thank the reviewer for this constructive suggestion. We agree that examining associations between behavioural performance and hemodynamic responses would further clarify the functional significance of the observed neuroimaging findings. While the current study was primarily designed to evaluate group-level differences, correlational analyses examining brain\u2013behaviour relationships are currently underway as part of an ongoing extension of the study dataset. These analyses will form the basis of a subsequent manuscript submission focusing on neurocognitive\u2013hemodynamic coupling. The article we are currently working will investigate associations, as well as (b) efficiency index analysis, and (c) implement moderation models to investigate cognition (all attention and NEPSY measures) by group and hemodynamic responses  Given baseline differences between treatment and control groups (especially age and sex), consider adjusting analyses for relevant covariate, if the sample size permits.  \n<b>Response: <\/b>  Thank you very much for this suggestion. This implementation is being extended to form part of the above noted article (the power analysis is weak at this stage, due to a small sample size). &nbsp;  Including p-values in Table 2 (even for non-significant results) would improve transparency.  \n<b>Response: <\/b>  We have since revised the Table 2 with the necessary statistics for replicability and transparency.   \n<b>Discussion<\/b> Overall, the discussion effectively integrates the results of this study with the existing literature. A couple points to consider:  Consider introducing study limitations earlier in the Discussion rather than in the Conclusions. In addition to those already noted, the inclusion of only HIV-positive participants should be acknowledged as a limitation.  \n<b>Response: <\/b>  Thank you for the suggestion, we have since created a Limitations section to the manuscript and noted the above limitation.  Expanding on how these findings inform future research, such as examining other cognitive domains (e.g., memory), would further strengthen this section.  \n<b>Response: <\/b>  We have incorporated this suggestion and the importance of translational research in the Discussion section.  We thank the reviewer for all the above observations which we believe have strengthened the academic integrity of this work.","URL":"https:\/\/f1000research.com\/articles\/14-1000\/v2#referee-comment-15632","order":4,"name":"referee-comment-15632","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This study is supported by funding from the South African National Research Foundation, Thuthuka Grant (TTK200408511634), the Rhodes University Research Grant (PGSD05\/2022) and funding from the University of the Witwatersrand. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":5,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}