Peer review of: Rapid fast-delta decay following prolonged wakefulness marks a phase of wake-inertia in (2020)

REVIEWERS' COMMENTS:
Reviewer #1 (Remarks to the Author):
I do not have any further comments on the manuscript.
Reviewer #2 (Remarks to the Author):
By Hubbard et al.
 Rapid decay in fast delta following prolonged wakefulness marks a phase of wake-inertia in NREM
 sleep
My first comment on the sentence “Its acceptance is so wide-spread that EEG δ power has now
become equivalent to the underlying sleep homeostatic process and any interventions affecting the
manifestation of SWs are taken as proof of altered sleep homeostasis.” is welcomed with the
response that this was clearly meant as criticism to current practice of how many in the field
represent the two process model. I am sorry, but I apparently missed the point there, and I am
afraid those that are already misrepresenting the model will find confirmation in this sentence
instead of criticism. I think criticism on the misconceptions of the popular version should be
expressed clearer than that. The addition of an extra sentence “However, it should be obvious that
many such interventions can dissociate SW expression from the underlying sleep homeostatic
process and must therefore be interpreted with caution” , in my mind, does not help, as it does not
make the previous sentence clearer. My suggestion is to take out the last two sentences (line 695
to 700) to avoid feeding the misconception. The sentences do not add to the argument the authors
want to make, anyway.
The second point is about the time-spend-in-NREMS and REM sleep not being considered in the
two-process model. Basically I agree with the authors, and I see the point of the authors, but do
think that the issue was presented very black-and-white in the previous version of the manuscript.
And that is probably because also this manuscript this is not the place to start a review/discussion
on this subject. In my opinion, in the original model (Borbely 1982. Daan et al 1984), which
mainly talks about human sleep wake regulation, it is very clear where the extra sleep goes,
humans are monophasic sleepers and they increase time-spend in sleep by extending rest, or
introducing a nap during the active phase. It is therefore not surprising that the more elaborate
model for humans (Acherman et al 1993) mainly focusses on SWA in NREM sleep. And I agree,
more should be done to investigate the time-spend in sleep axis. The problem starts in rodent
sleep, which is more polyphasic. For rodents it is possible to sleep more (or less) without changing
the time spend in rest. The change made in the last sentence is in my view a good solution. Thank
you.
 Thank you for removing ‘discovered’ from the abstract, and for changing the argument about the
 slopes and amplitudes of the slow-waves.
All minor comments were taken care of.
Reviewer #3 (Remarks to the Author):
 Unfortunately, a careful reading the critiques of R1 and R2 along with the authors’ responses has
 reduced enthusiasm for the publication of this manuscript in Nature Communications, a high
 impact multidisciplinary journal that publishes research in a broad range of topics. In the authors’
 own words, “We disagree and although a rebuttal is hardly a suitable platform to discuss these
 matters in a fair and constructive manner.....”. The authors do not take their own advice and their
 lengthy responses to R1 & R2 are seldom helpful. More importantly, the authors’ responses to R1
 and R2 consistently fail to describe the specific changes they have made to the manuscript to
 address the reviewer’s concerns (and where). Similarly, they fail to indicate when/if changes to the
 manuscript have NOT been made in response the reviewer’s comments. For example, are the data
 in the two “rebuttal figures” incorporated into the revised manuscript and, if so, how and where?
 There are many other instances where the authors are not stating how the reviewer’s concerns
 have been addressed in the revised manuscript.
 Minor points:
 R1 Q2. The authors response to the response to R1 Q2 was impossible to follow because they refer
 to Suppl Fig 4 when they meant Suppl Fig 5.
 R1 Q3. The authors response here seems contradictory since they say: “Concurrent with our
 observations in the cingulate, we find that CMT silencing increases δ2 activity (but not δ1 activity)
 in the visual cortex. Interestingly, CMT silencing did not affect δ1 nor δ2 dynamics in the barrel
 cortex.” And, in the next sentences later they say, “Evidence of this out-of-circuit property was
 further confirmed with additional new data we provided showing that 10 seconds of CMT silencing
 during NREM sleep suppresses both δ1 and δ2 activity in the cingulate and visual cortex but not in
 the barrel cortex.”
 The term “wake-inertia” is now included in the title of the manuscript, but is not adequately
 defined.