Age-related slowing down in the motor initiation in elderly adults

Age-related changes in the human brain functioning crucially affect the motor system, causing increased reaction time, low ability to control and execute movements, difficulties in learning new motor skills. The lifestyle and lowered daily activity of elderly adults, along with the deficit of motor and cognitive brain functions, might lead to the developed ambidexterity, i.e., the loss of dominant limb advances. Despite the broad knowledge about the changes in cortical activity directly related to the motor execution, less is known about age-related differences in the motor initiation phase. We hypothesize that the latter strongly influences the behavioral characteristics, such as reaction time, the accuracy of motor performance, etc. Here, we compare the neuronal processes underlying the motor initiation phase preceding fine motor task execution between elderly and young subjects. Based on the results of the whole-scalp sensor-level electroencephalography (EEG) analysis, we demonstrate that the age-related slowing down in the motor initiation before the dominant hand movements is accompanied by the increased theta activation within sensorimotor area and reconfiguration of the theta-band functional connectivity in elderly adults.


Materials and methods
Comment: In methods sec>on, you talk about background recording before recording ac>ve phase. You could simply say 5 minutes Eyes Open Res>ng state. They don't appear to be any different to me. In the ac>ve phase you say you have 60 fine motor tasks per par>cipant and 30 tasks per hand. The dura>on of the beep short or long provides cue which hand (dominant vs. non-dominant) to use. This is fine, but how different are these 60 tasks actually from each other. Are they really all different or similar? Could you provide a sta>s>cal summary or similarity measure to point out the differences between categories of finer motor task categories. If the task categories are dissimilar then the motor signal or changes in motor signals would be more enhanced irrespec>ve of the age category. In this regard, just a clarifica>on will suffice. I am a bit confused as the Experimental paradigm presented in figure 1 clearly shows a single motor task (I guess squeezing wrist of one hand with the other) Answer: We thank the reviewer for this comment. Indeed, the experimental task in the original manuscript was described in misleading form. We should have used a term 'repe22ons' instead of 'tasks', since each par2cipant was asked to perform mul2ple repe22ons of the same fine motor task (squeezing a hand into a wrist a]er the audio signal and holding it un2l the second signal) using either le] or right hand (30 repe22ons per hand, 60 in total). We clarified this point in the revised version of the manuscript. We also corrected the descrip2on of the background recordings accordingly.
Comment: In line 124, authors suggest that a priory knowledge about the cor>cal ac>va>on during movements execu>on implies that motor brain response is determined as a pronounced event-related desynchroniza>on (ERD) of mu-oscilla>ons in the contralateral area of the motor cortex. Therefore, they recorded and analysed ac>vity from symmetric sensors C3 and C4 respec>vely to record mu band response >me (MBRT).
I am wondering based on the recent literature (which is by the way not referenced) Transient human movement is served by a specific pa9ern of neural oscillatory ac>vity, par>cularly in the beta band (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). Briefly, prior to and during movement, there is a strong decrease in beta ac>vity rela>ve to baseline levels, known as the peri-movement beta event-related desynchroniza>on (ERD), which begins about 1.0 s before movement onset and dissipates shortly aber movement concludes. Actually, roughly 500 ms following s>mulus offset or the comple>on of an actual voluntary or passive movement, or imagined movement, the beta rhythm increases in magnitude with respect to a baseline period preceding the event. This period of ERS is oben termed the post-movement beta rebound (PMBR). Could you please comment why are you not looking at this Beta ERD. Is not that relevant? I guess post-movement you should also check PMBR for frequency and amplitude. May be something interes>ng out there.
Answer: We thank the reviewer for this valuable remark. Indeed, the level of neocor2cal beta-band oscilla2ons is considered as relevant marker of declined motor performance in healthy ageing and disease. Also, a peri-movement beta-band ERD emerging slightly before the motor ac2on is known to be associated with motor planning [Heinrichs-Graham E., et al. (2016). Journal of cogni>ve neuroscience]. According to the reviewer's comment we have discussed this topic in the intro sec2on. We have also modified the analysis of MBRT by addi2onal considera2on of MBRT in the beta-band (see Fig.2 and subsec2on 'Motor brain response 2me analysis' in the Results sec2on). Specifically, during this analysis we have found that beta-band MBRT reflects the same proper2es as a mu-band MBRT (the fastest brain response has been observed in RH condi2on in YA group). Also, we observed that beta-band MBRT is significantly lower than mu-band MBRT, that is consistent with the exis2ng literature and reviewer's comment. We suppose, that the provided extended analysis of MBRT has gained the relevance of our conclusions. We also thank the reviewer for an interes2ng idea's for the con2nua2on of a current research.
Comment: Based on my understanding of the aging literature on motor signals, older adults exhibited an almost threefold increase in spontaneous beta power in the primary motor cor>ces, as well as significantly stronger beta ERD in the same regions compared to younger adults. Furthermore, it has been shown that during simple movements, these beta-band oscilla>ons reliably peak in the precentral gyri bilaterally with stronger ac>vity contralateral to movement, while more complex movements (and some simple movements) also induce ac>vity in the supplementary motor area and bilateral premotor cor>ces, postcentral gyri, parietal cor>ces, and cerebellum. Perhaps, it would be necessary to discuss about this in the intro and discussion sec>on.
Answer: We agree with the reviewer's comment. We have added a discussion about a significance of periand post-movement beta oscilla2ons in the intro sec2on. However, in the current study we were mostly focused on the pre-movement neuronal ac2vity (a]er the audio cue and before mu-and beta-band ERD) and the provided sta2s2cal analysis in spa2o-temporal domain did not reveal any significant age-related changes in cor2cal ac2va2on besides the increased theta-band ac2vity in central-parietal sensors within this 2me frame. Maybe, this could be a consequence of experimental design and, par2cularly, a quite simple motor task, which execu2on may not strongly involve complex motor planning opera2ons usually associated with early beta-band ERD.

Results
Comment: On the contrary, the between-subject differences were found in the spa>al cluster, which included Cp3, Cpz, and Cp4 sensors (dorsal stream region of the sensorimotor area). Did you carry out a source analysis or else how are you actually talking about Ventral and Dorsal regions? I thought you have restricted your analysis at the sensor level. I wouldn't talk about network based on sensor based func>onal connec>vity in the >me or frequency domain. Spa>al resolu>on is too poor to argue for this even if you observed spectro-temporal signatures. For example, you men>on distributed frontoparietal network. If I ask you how many areas do you think FPN comprise of then how would you answer? Please s>ck to sensor level analysis of your brain signals and connec>vity pa9erns among sensor groups to discern changes. I don't agree that talking about brain areas, ventral and dorsal streams etc. and above all networks makes much sense. You would probably admit networks in this case is loosely defined. This is also not a MEG Study.
Answer: We agree with the reviewer's opinion. We have modified the Results sec2on by s2cking to the sensor-level descrip2on of the obtained results and excluding misleading formula2ons.

Discussion
Comment: I enjoyed reading the discussion sec2on. Having said that I think the authors need to seriously look at some of their asser2ons. One thing is to see a change and other is to speculate about those change.
Many of the formula2ons and interpreta2ons are at this point remain unverified and specula2ve. Not a clear demonstra2on yet. However the good thing is that the authors have cited and covered references which are most relevant to their findings based on mainly two types of analysis 2me-frequency and func2onal connec2vity. Further, they discussed various mechanisms which render support to their empirical observa2ons and relates to exis2ng literature. In par2cular, this is one of the key reason why instead of lis2ng a series of plausible mechanisms, the authors could iden2fy and evaluate quan2ta2vely one or two key mechanisms highlighted in the discussion sec2on. For example, the observa2on of increase in theta band ac2vity/power in the Frontal sensors and in the sensors near sensorimotor areas could be sensorimotor integra2on (provided by Bland's model) mechanisms or this could be long range connec2vity change between distal brain areas leading to an eleva2on in the theta band power. Also, I don't like the fact that you keep men2oning throughout the ar2cle about brain areas while you actually carry out all of your analysis primarily at the EEG sensor level. They clearly do not commensurate with each other. Please, see my previous comments on this issue persistent in this manuscript.
Answer: First, we would like to thank the reviewer for a posi2ve feedback to our discussion sec2on. Here, we also agree with the reviewer's opinion that many interpreta2ons and formula2ons are rather specula2ve. In the revised version of the Manuscript, we have tried to clarify and modify the most unsuccessful conclusions and formula2on, to be less specula2ve and mostly associated with our observa2ons.

Minor
Comment: Line number 190 may have a typo. Please check. Same paYern of typo recurring throughout the manuscript. Actually spoYed them in several other places in this manuscript. Please revisit those sec2ons where these typos are present and rec2fy.
Answer: We guess, that this typo is a 'pre-motor phase'. We have corrected this typo by replacing it with a 'pre-movement phase' or 'motor ini2a2on phase'.