Reviewer 1 : Dr Dido

نویسندگان

  • Ingar M Zielinski
  • Marjolein Baas
  • Marijtje LA Jongsma
  • Ingar Zielinski
  • Bert Steenbergen
  • Pauline Aarts
  • Marijtje Jongsma
  • Dido Green
چکیده

1. The methods are unclear in the abstract. The participants should be in the first line of the methods. The study design then needs to be stated upfront – prospective cross sectional study. The primary outcome EEG and variables (ERP, N1...) then need comment on (there is no mention of EEG in the abstract). It is hard to follow as the design is not specified or EEG mentioned. # 1: We agree with the reviewer that the methods written in the abstract needed clarification. We have changed the order according to the reviewers’ comment and added the name of the study design. (page 2) However, we do not fully agree with the reviewers’ suggestion concerning the study design. As we did not follow the children over time, we do not agree to label this design a prospective design. We do however agree that this was a cross-sectional design and changed this accordingly (page 2 in Abstract and page 9 under ‘Methods’). Furthermore, we also added some information about the different ERP components to the abstract as well as mentioned that these components were extracted from the ongoing EEG. (page 2) 2. It is also unclear in the abstract what the clinical implications are of the study. Why is it important to understand the general delay in cognitive control of motor behavior and how will this lead to a change in assessment and treatment of children with cerebral palsy? # 2: The clinical implications have been added to the conclusion section of the abstract. (page 3) Methods 3. The VOAA-DDD-R is not a common assessment. Could you please include a couple of lines about its psychometric properties (Refer to Houwink 2014). This is very important that the reader is confident in how DD has been assessed and children are grouped. # 3: We agree with the reviewer that further information about the VOAA-DDD-R is needed. This information has been added in the reviewed version of the manuscript. (page 8, under ‘Participants’; also see reviewer 1, comment #5). 4. More information about the population would be useful. What was the sensation like for children in both groups? What was their cognition like? It would be very interesting to know how function relates to the both groups. Do the children with DD perform as well on functional measures like the Assisting Hand Assessment? These are really important factors in this study. # 4: More information about the children concerning their visual capacity and their cognitive functioning has been added in the revised manuscript (Page 8 (last paragraph) & 9 (first paragraph); also see reviewer 1, comment #6). As indicator for cognitive functioning of these children we used the information on whether they were attending a regular or special school. However, we do not have scores of the Assisting Hand Assessment for every child, as we did not mean to include this data to our study. To indicate manual ability we used scores of the Manual Ability Classification System. Design 5. Can you please review the study design? I would consider it a prospective cross sectional study. # 5: The study design has been added. Please see point # 1 for further elaboration. 6. For readers who have not familiar with EEG it would be useful to have a brief line about the different variables (ERP, N1...) this is covered in methods but difficult to flick back and forwards. # 6: We think that the reviewer is commenting on the Result section. We added some information of all components to the Result section (Page 13, second paragraph). Conclusion 7. The link to clinical implications here is important and well explained. What therapies aimed at motor neglect might the authors recommend? Have these therapies been trailed in children with cerebral palsy? # 7: We could not agree more with the reviewers’ opinion that the clinical implications of these motor neglect findings are very important, especially as there does not even seem to be a valid diagnostic tool for diagnosing motor neglect in children. More studies are therefore warranted to elaborate on the phenomenon of motor neglect in unilateral CP as well as to study the efficacy of therapies when treating children with unilateral CP and DD. In our revised version of the manuscript, we added a line to the conclusion that “To our knowledge, there are no therapies for children with unilateral cerebral palsy directly aiming at reducing motor neglect” (page 21, under ‘Conclusion’). Reviewer3: Prof Rodney C. Scott 1. The main issue for this reviewer relates to the biological underpinnings of the ERP data. The authors seem to be arguing that DD is related to cognitive control of movement during the task and that the ERP provides insight into that process. As I understand it the authors are suggesting that in the absence of DD neural circuits are formed and that those circuits lead to changes in ERP parameters. However, there is something about the initial injury that leads to the DD in the first place and therefore it seems possible that the ERP is simply a reflection of that underlying brain injury and is entirely unrelated to subsequent brain development. It is not possible to establish whether this is true as there are no data on the nature, site, severity etc of the injury that is leading to the hemiplegia. Without this information it is extremely difficult to establish what the ERP data are saying about the biology of DD. # 1: We do agree with the reviewer that the missing information about the underlying brain injury might pose difficulties in interpreting the results. In the revised manuscript we have emphasized this in our study limitations (page 20, last paragraph). However, to answer our main aim about the underlying factors of DD, we did use a control group of children with similar brain lesions leading to very similar motor deficits. All of the children participating at our study were diagnosed with unilateral CP, indicating that all of these children had unilateral brain lesions affecting the motor areas of the barin. Furthermore, the control group used in the current study did not differ in terms of hand capacity, side of affected hand or cognitive ability. These findings give further indications that the associated brain lesions were comparable between both groups. We do however still agree with the reviewer that the ERP differences between children with unilateral CP with and without DD might reflect a subtle differences in affected brain areas between the two groups. We do nevertheless think that both hypotheses (DD as result initial injury vs. DD as result of developmental delay) are not mutually exclusive. We propose that especially the reduced N1 component might be a reflection of the initial injury to different brain networks. We have elaborated on this subject in the revised manuscript. (page19, last paragraph, & and 20, first paragraph) 2. It would be helpful to know what the N1, P2 etc components are measuring in biological terms i.e. what is it in the structure or function of the brain that makes the waveforms. With this information it will be easier to make inferences on the biological relevance of the data presented. # 2: We thank the reviewer for pointing this out and agree that we did not add sufficient information about the underlying brain mechanisms related to the different ERP components in our initial manuscript. In the revised manuscript we did add this information. In our revised introduction we added information about the meaning of every component typically observed in go/nogo-experiments (N1, P2, N2, & P3). In addition, information about the brain structures related to the N2 and P3 components was added (page 7, second paragraph). In our Discussion section we added more information about the meaning as well as about the underlying brain mechanisms of the N1 component (page 19, first paragraph). 3. a) The second major issue relates to the age of the participants. The age range is from 5-12 years and it is possible that there is maturation of the ERP across that age range. This should be explored. # 3a: Please see reaction to comment number 9 of the first reviewer (Dr Dido Green). b) In addition, if DD is a function of cognitive development then one might expect that the children with DD show little change over time whilst those without DD show a marked change. It appears that these data are available and could be analyzed using regression methods. # 3b: Thank you for this very interesting comment. We fully agree with the reviewer that if DD is a function of cognitive development, we should explore the influence of age as soon as we find group differences. We therefore added these analyses to our revised manuscript (page 12, second paragraph). As a result of these adaptations we are convinced that the manuscript has greatly improved and provides an even more in depth analysis of DD. As shown in the Result section, age is actually predicting the amplitude of the go-P3 in the DD group, but not in the control group (page 15, last paragraph). This finding indicates that in the control group there are no developmental changes with respect to cognitive load and response preparation. This indicates, that even in the youngest children of this group, this cognitive function had already been fully developed. In the DD group however, the P3 amplitude of the goP3 decreased as the children got older. This finding gives a strong indication that the enhancement of the P3 following go-stimuli (increased mental effort related to response preparation in the DD group) indeed seems to be related to a developmental delay in this group. However, no effects of age were observed with respect to the N1 component. The reduced N1 component (spatial attention deficits in the DD group) does not seem to be related to a developmental delay. The interpretation of these finding have been added to the discussion. (page 20, first paragraph) 4. It is interesting that the behavioral and ERP data show a bilateral deficit despite an apparently unilateral lesion. This suggests that in children with DD the ‘normal’ side of the brain is either itself injured in which case the child would have bilateral DD, or that the abnormal hemisphere is somehow influencing the normal side in a way that leads to a decrease in performance. This needs to be addressed in the manuscript. # 4: Thank you for pointing this out. A possible explanation for this finding has been added to the revised manuscript. (page 20, second paragraph ) 5. It is very difficult to see the different lines in Fig 2. I wonder whether it is possible to either separate out the groups or to use lines that are more distinguishable # 5: We think that the reviewer is commenting on figure 3 instead of figure 2. We do agree with the reviewer that the lines used in Figure 3 were not easy to distinguish. However, if we separated the groups, we would lose the visual representation about the group differences. We therefore choose to use colored lines instead of black and grey lines in our revised manuscript and hope that they now easier to distinguish.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Methodological Issues of Using Placebos in Interventions Based on Digital Technology

INTERVENTIONS BASED ON DIGITAL TECHNOLOGY William Farr, Ian Male, Dido Green, Christopher Morris, Heather Gage, Sarah Bailey, Sandra Speller, Val Colville, Mandy Jackson, Stephen Bremner, Anjum Memon Sussex Community NHS Trust; Oxford Brookes University; University of Exeter Medical School; Parent partnership advisors, Sussex Community NHS Trust; University of Surrey; Brighton and Sussex Medica...

متن کامل

Association of door-in to door-out time with reperfusion delays and outcomes among patients transferred for primary percutaneous coronary intervention.

CONTEXT Patients with ST-elevation myocardial infarction (STEMI) requiring interhospital transfer for primary percutaneous coronary intervention (PCI) often have prolonged overall door-to-balloon (DTB) times from first hospital presentation to second hospital PCI. Door-in to door-out (DIDO) time, defined as the duration of time from arrival to discharge at the first or STEMI referral hospital, ...

متن کامل

Association Between Hospital Practices and Door-in-door-out Time in ST-segment Elevation Myocardial Infarction.

BACKGROUND Current guidelines suggest a "door-in-door-out" (DIDO) time of 30 minutes or shorter for patients with ST-segment elevation myocardial infarction (STEMI) who arrive at a STEMI referral hospital and are transferred to a STEMI-receiving center for primary percutaneous coronary intervention. Experts previously identified 18 system practices as critical for reducing DIDO times. The objec...

متن کامل

Dido gene expression alterations are implicated in the induction of hematological myeloid neoplasms.

The myelodysplastic/myeloproliferative diseases (MDS/MPDs) are a heterogeneous group of myeloid neoplasms that share characteristics with chronic myeloproliferative diseases and myelodysplastic syndromes. The broad spectrum of clinical manifestations makes MDS/MPDs extremely difficult to diagnose and treat, with a median survival time of 1-5 years. No single gene defect has been firmly associat...

متن کامل

The Isoperimetric Problem

This refers to the legend of Dido. Virgil’s version has it that Dido, daughter of the king of Tyre, fled her home after her brother had killed her husband. Then she ended up on the north coast of Africa, where she bargained to buy as much land as she could enclose with an oxhide. So she cut the hide into thin strips, and then she faced, and presumably solved, the problem of enclosing the larges...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره   شماره 

صفحات  -

تاریخ انتشار 2014