Local hippocampal fast gamma rhythms precede brain-wide hyperemic patterns during spontaneous rodent REM sleep

May combine two claims.

VS events are present in nearly all brain regions but more prominent and stronger in all sub-regions of the dorsal hippocampus.

“were present in nearly all brain regions but more prominent and stronger in all sub-regions of the dorsal hippocampus [Fig. 1b].”

May combine two claims.

Vascular activity during REMS fluctuates between moderate CBV levels matching AW levels (REM-TONIC) and massive CBV spikes (REM-PHASIC), called vascular surges (VS).

“This vascular activity during REMS fluctuated between moderate CBV levels matching AW levels (REM-TONIC) and massive CBV spikes (REM-PHASIC), which we called vascular surges (VS, red shaded boxes, Fig. 1b) and were present in nearly all brain regions but more prominent and stronger in all sub-regions of the dorsal hippocampus [Fig. 1b].”

• Also stated in: § Introduction · plain

  “We show that vascular activity also divides into tonic and phasic regimes, the latter exhibiting transient brain-wide hyperemic patterns, which we called vascular surges (VS).”

May combine two claims.

VS outmatched wake levels in nearly all brain regions, occasionally reaching up to a 100% increase in cortical and hippocampal regions compared to quiet wake.

“VS amplitude was strongest in the dorsal hippocampus and outmatched wake levels in nearly all brain regions, occasionally reaching up to a 100% increase in the cortical and hippocampal regions compared to a quiet wake state.”

May combine two claims.

AW/QW amplification resulted in a 6.0% increase, while REM/QW reached a 15.9% increase in the hippocampus; this level increased to 31.9% when considering phasic REM epochs.

“Overall, AW/QW amplification resulted in a 6.0% increase, while REM/QW reached a 15.9% increase in the hippocampus; this level increased to 31.9% when considering phasic REM epochs [Fig. 2c and Supplementary Tables 2–3].”

May combine two claims.

QW and NREM vascular regimes were relatively similar to baseline, except in the thalamus, which was hypoactive during NREM (Cohen's d = −0.24, p < 10−3).

“As expected, QW and NREM vascular regimes were relatively similar to baseline, except in the thalamus, which was hypoactive during NREM (Cohen’s d = −0.24, p < 10−3, two-tailed Mann–Whitney test).”

May combine two claims.

Functional connectivity across states showed same patterns for NREM and AW, consisting of a co-active cortex, thalamus and hippocampus, whereas functional coupling across regions was stronger in AW and strongest in REM (QW: Rpear_mean = .76, std = .11; NREM: .73, std = .07; AW: .88, std = .11; REM: .93, std = .04).

“We then assessed functional connectivity across states and found the same patterns for NREM and AW, consisting of a co-active cortex, thalamus and hippocampus, whereas functional coupling across regions was stronger in AW and strongest in REM (QW: Rpear_mean = .76, std = .11; NREM: Rpear_mean = .73, std = .07; AW: Rpear_mean = .88, std = .11; REM: Rpear_mean = .93, std = .04) [Fig. 2b].”

May combine two claims.

All animals displayed stronger cortex-hippocampus, thalamus-cortex, and hippocampus-thalamic coupling during REMS than any other sleep and wake state.

“We found stronger inter-individual variability especially between AW-QW functional coupling, but all animals displayed stronger cortex-hippocampus, thalamus-cortex, and hippocampus-thalamic coupling during REMS than any other sleep and wake state, confirming the fact that functional coupling between distant brain areas increases during REMS [Supplementary Table 1].”

May combine two claims.

VS events typically lasted 5 to 30 s but could extend to over a minute in cortical regions.

“These VS events, which we detected using a population activity threshold [Supplementary Fig. 2], typically lasted 5 to 30 s but could extend to over a minute in cortical regions.”

May combine two claims.

Not all regions show the same amplification ratio between AW, REM and REM-phasic epochs, the strongest being observed in the dorsal hippocampus, dorsal thalamus, and retrosplenial cortex.

“Not all regions show the same amplification ratio between the AW, REM and REM-phasic epochs, the strongest being observed in the dorsal hippocampus, dorsal thalamus, and retrosplenial cortex.”

May combine two claims.

Dorsal hippocampus and dorsal thalamus were strongly activated during REMS in all animals (Dorsal Hippocampus: from 19.46 to 29.21%; Dorsal Thalamus: from 17.23 to 24.11%; Cortex: from 10.02 to 20.78%).

“This analysis confirmed that dorsal hippocampus and dorsal thalamus were strongly activated during REMS in all animals (Dorsal Hippocampus: from 19.46 to 29.21%; Dorsal Thalamus: from 17.23 to 24.11%; Cortex: from 10.02 to 20.78%), that this effect was even stronger during REM-PHASIC periods (Dorsal Hippocampus: from 39.99 to 49.78 %; Dorsal Thalamus: from 37.91 to 47.81%; Cortex: from 17.24 to 37”

Probably not a substantial claim: may not pass S3 (load-bearing).

The duration of VS events displayed high variability in four out of five animals.

“The profile of VS events was remarkably constant over all five animals (around four to six VS events per REM episode) and though the duration of VS events displayed high variability this was observed in four out of five animals.”

May combine two claims.

REM and REM-phasic strongly outmatched baseline CBV levels, more strongly in hippocampal regions (Cohen's d = 1.77 and 3.87, p < 10−3).

“AW was significantly higher than QW (Cohen’s d = 1.06, p < 10−3, two-tailed Mann–Whitney test), especially in the cortical regions, while REM (and REM-phasic) strongly outmatched baseline levels, doing so more strongly in hippocampal regions (Cohen’s d = 1.77 and 3.87, p < 10−3, two-tailed Mann–Whitney test) [Fig. 2a and Supplementary Fig. 4].”

May combine two claims.

Strongest co-occurrences (over 75% in the mid and fast gamma bands for all three regions) with highest coupling in the hippocampus (Low-Gamma: 368/611; Mid-Gamma: 441/611; High-Gamma: 458/611; Theta: 428/611).

“We found strongest co-occurrences (over 75% in the mid and fast gamma bands for all three regions) with highest coupling in the hippocampus (Low-Gamma: 368/611; Mid-Gamma: 441/611; High-Gamma: 458/611; Theta: 428/611).”

May combine two claims.

The mean delays (around 1.5 s) found were somewhat shorter than the ones found in the above study (about 1.9-2 s)29, with significant inter-episodes variability.

“Although the mean delays (around 1.5 s) we found were somewhat shorter than the ones found in the above study (about 1.9–2 s)29, we found significant inter-episodes variability, which might explain this discrepancy, apart from the notable experimental set-up differences (species, head-fixed vs. head-free) and arousal state (sleep vs. wakefulness).”

• cites [29] Mateo, C., Knutsen, P. M., Tsai, P. S., Shih, A. Y. & Kleinfeld, D. Entrainment of arteriole vasomotor fluctuations by neural activity is a basis of blood-oxygenation-level-dependent “resting-state” connectivity. Neuron 96, 936–948.e3 (2017). sourceNot checked yet

  Not checked in the free run.

May combine two claims.

The complementary approach yielded similar results, albeit with weaker co-occurrence ratios (between 65 and 70% for all three main regions) showing a weak tendency for LFP activity to occur more often preceding VS events than for CBV activity to follow electrical activation.

“The second approach consisted in detecting LFP burst events and searching for CBV peaks in the timing window following electrical activity. This yielded similar results, albeit with weaker co-occurrence ratios (between 65 and 70% for all three main regions) showing a weak tendency for LFP activity to occur more often preceding VS events than for CBV activity to follow electrical activation.”

May combine two claims.

Cross-correlations showed peaks in the positive LFP-CBV delay timing window moderately for theta and very robustly for mid and high-gamma bands with LFP leading CBV response by a delay varying between 1 to 3 s.

“We found peaks in the positive LFP-CBV delay timing window moderately for the theta band and very robustly for the mid and high-gamma bands with LFP leading CBV response by a delay in a time interval varying between 1 to 3 s.”

May combine two claims.

Mean cross-correlations maxima between 0.6 and 0.7 for all three main regions (Thalamus: Rmean = 0.64 at lag = 1.35 s; Hippocampus: Rmean = 0.69 at lag = 1.52 s; Hippocampus: Rmean = 0.64 at lag = 1.65 s relatively to high-gamma oscillations).

“As expected this showed a strong neurovascular coupling in the mid and fast gamma bands, with mean cross-correlations maxima between 0.6 and 0.7 for all three main regions (Thalamus: Rmean = 0.64 obtained at lag = 1.35 s; Hippocampus: Rmean = 0.69 obtained at lag = 1.52 s; Hippocampus: Rmean = 0.64 obtained at lag = 1.65 s relatively to high-gamma oscillations).”

May combine two claims.

REMS is a state of vascular hypersynchrony characterized by phasic massive spikes in CBV levels and is strongest in hippocampal regions.

“These results show that REMS is a state of vascular hypersynchrony that is characterized by phasic massive spikes in CBV levels and is strongest in hippocampal regions.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The association between fast gamma oscillations and whole-brain vascular hyperactivity has also been observed under anesthesia in previous EEG-fMRI and intrinsic optical signal (IOS)-fMRI studies.

“which was also observed under anesthesia in previous EEG-fMRI and intrinsic optical signal (IOS)-fMRI studies35,36.”

• cites [35] Logothetis, N. K., Pauls, J., Augath, M., Trinath, T. & Oeltermann, A. Neurophysiological investigation of the basis of the fMRI signal. Nature 412, 150–157 (2001). sourceNot checked yet

  Not checked in the free run.

• cites [36] Niessing, J. Hemodynamic signals correlate tightly with synchronized gamma oscillations. Science 309, 948–951 (2005). sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Neurovascular coupling is faster in the thalamic regions and slower in the cortical regions compared to the hippocampus.

“This confirmed that neurovascular coupling is faster in the thalamic regions and slower in the cortical regions compared to the hippocampus.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Fast gamma oscillations have previously been described in rodents.

“but have previously been described in rodents37.”

• cites [37] Schomburg, E. W. et al. Theta phase segregation of input-specific gamma patterns in entorhinal-hippocampal networks. Neuron 84, 470–485 (2014). sourceNot checked yet

  Not checked in the free run.

May combine two claims.

The detection limit corresponds to speed in venules and arterioles but may exclude capillaries where numerous neurovascular processes occur.

“This corresponds to speed in venules and arterioles but may exclude capillaries where numerous neurovascular processes occur44.”

• cites [44] Drake, C. & Iadecola, C. The role of neuronal signaling in controlling cerebral blood flow. Brain Lang. 102, 141–152 (2007). sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based). May combine two claims.

The vascular patterns suggest that the underlying mechanisms are energetically costly in terms of neurovascular regulation and thus must have been preserved only due to a significant evolutionary benefit, yet to be determined.

“These vascular patterns suggest that the underlying mechanisms are energetically costly in terms of neurovascular regulation and thus must have been preserved only due to a significant evolutionary benefit, yet to be determined.”

Probably not a substantial claim: may not pass S4 (based).

The prosthetic skull material has tissue-like acoustic impedance that allows undistorted propagation of ultrasound waves at the acoustic gel-prosthesis and prosthesis-saline interfaces.

“This material has tissue-like acoustic impedance that allows undistorted propagation of ultrasound waves at the acoustic gel-prosthesis and prosthesis-saline interfaces.”

Probably not a substantial claim: may not pass S3 (load-bearing).

BOLD-based connectivity patterns spread brain-wide during REMS.

“BOLD-based connectivity patterns spread brain-wide during REMS24”

• cites [24] Chow, H. M. et al. Rhythmic alternating patterns of brain activity distinguish rapid eye movement sleep from other states of consciousness. PNAS 110, 10300–10305 (2013). sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Newborn sleep displays high-amplitude vascular activity during early active sleep.

“newborn sleep display high-amplitude vascular activity during early active sleep40”

• cites [40] Demene, C. et al. Functional ultrasound imaging of brain activity in human newborns. Sci. Transl. Med. 9, eaah6756 (2017). sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

The current design relies on power Doppler to estimate relative cerebral blood volume, which is a limitation.

“Our current design also suffers some limitations as it relies on power Doppler to estimate relative cerebral blood volume.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Removing the first 60 components of the singular value decomposition optimally exploited the spatiotemporal dynamics of the full Doppler film for clutter rejection, largely outperforming conventional clutter-rejection filters used in Doppler ultrasound.

“removing the N = 60 first components of the singular value decomposition, which optimally exploited the spatiotemporal dynamics of the full Doppler film for clutter rejection, largely outperforming conventional clutter-rejection filters used in Doppler ultrasound47.”

• cites [47] Demene, C. et al. Spatiotemporal clutter filtering of ultrafast ultrasound data highly increases doppler and fUltrasound sensitivity. IEEE Trans. Med. Imaging 34, 2271–2285 (2015). sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Power Doppler is essentially blind to blood vessels whose direction is quasi parallel to the transducer array (+/−15°), which thus do not contribute to the measured CBV.

“Moreover, power Doppler is essentially blind to blood vessels whose direction is quasi parallel to the transducer array (+/−15°), which thus do not contribute to the measured CBV.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The division into delta, theta, low-gamma, mid-gamma, high-gamma, and ripple frequency bands has been thoroughly described and proven to be functionally relevant for hippocampal electrographic recordings.

“This division has been thoroughly described and proven to be functionally relevant for hippocampal electrographic recordings38.”

• cites [38] Belluscio, M. A., Mizuseki, K., Schmidt, R., Kempter, R. & Buzsaki, G. Cross-frequency phase-phase coupling between theta and gamma oscillations in the hippocampus. J. Neurosci. 32, 423–435 (2012). sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Bar diagrams shown in Fig. 2c are computed by averaging the mean values of 17 recordings on four animals for the coronal planes and 11 recordings in four animals for the diagonal planes.

“Bar diagrams shown in Fig. 2c are computed by averaging the mean values of 17 recordings on four animals for the coronal planes and 11 recordings in four animals for the diagonal planes.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Statistics in Fig. 2a are computed on n = 7 animals over 30 recording sessions.

“Statistics in Fig. 2a are computed on n = 7 animals over 30 recording sessions.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The histograms presented in Fig. 3e were computed on n = 7 animals over 35 REM episodes, which lasted more than 30 s.

“The histograms presented in Fig. 3e were computed on n = 7 animals over 35 REM episodes, which lasted more than 30 s.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The customized registration algorithm converged quickly and provided robust registration for any ultrasound plane, including diagonal planes, provided it did not start too far from the actual position.

“Provided the algorithm did not start too far from the actual position, it converged quickly and provided robust registration for any ultrasound plane, including diagonal planes.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The study recorded from seven animals over coronal and diagonal planes for a total of 35 running-sleep sessions, yielding 62 total REM episodes, 30 of which lasted more than 30 s.

“In total, we recorded from seven animals over the coronal and diagonal planes for a total of 35 running-sleep sessions; thus, 62 total REM episodes were obtained (30 of which lasted more than 30 s).”

Probably not a substantial claim: may not pass S3 (load-bearing).

Matrices shown in Fig. 2b are computed by averaging matrices from 17 recordings (coronal planes) on four animals.

“Matrices shown in Fig. 2b are computed by averaging matrices from 17 recordings (coronal planes) on four animals.”

May combine two claims.

Fast gamma oscillations displayed typical phase-amplitude coupling patterns for all recordings robustly across animals, and the electrode diameters and stability of recordings decrease the probability that fast gamma events arose from correlated spiking activity.

“we observed that fast gamma oscillations displayed typical phase-amplitude coupling patterns for all recordings robustly across animals. The size of our electrode diameters (25 to 50 microns) and the stability of our recordings throughout sessions decrease the probability that fast gamma events arose from correlated spiking activity.”