Dav dav Ripples Synchronize tib neeg Cortical Activity thaum pw tsaug zog, Waking, thiab nco nco Part 2

Hippocampal Sharpwave Ripples Ua rau Cortical Ripples thaum NREM.

Thaum cov txiaj ntsig saum toj no qhia tau hais tias cortical ripples ua ntej hippocampal ripples thaum sawv ntxov, lawv qhov kev txiav txim thaum lub sij hawm NREM zoo li yog ib daim duab sib xyaw, uas peb xav tias yog nyob ntawm seb cov hippocampal ripples tshwm sim hauv cov ntsiab lus ntawm lub suab nrov lossis ntxaiv (2, 21, 22). Peb pom tias hippocampal sharp-wave ripples ho preceded corticalripples los ntawm ∼250 ms (SI Appendix, Fig. S4A; P=0.002, two-sided binomial test, expect value=0.5), whereas spindle ripples tau concurrent (SI Appendix, Fig. S4B; P=1).

Kev sib raug zoo ntawm hippocampal ripples thiab nco yog ib qho kev txaus siab heev. Lub hippocampus yog ib thaj chaw tseem ceeb tshaj plaws hauv lub hlwb. Nws yog nyob rau hauv lub cev lobe thiab muaj feem xyuam nrog kev txawj ntse xws li kev kawm thiab kev nco. Hippocampal ripples yog hom tshwj xeeb ntawm lub hlwb ua haujlwm uas xav tias muaj feem xyuam nrog kev nco encoding thiab cov ntaub ntawv sib xyaw. Nyob rau hauv xyoo tas los no, cov kws tshawb fawb tau ua kom tsis muaj zog los tshawb nrhiav cov txheej txheem sab hauv ntawm hippocampal ripples thiab nco.

Kev tshawb fawb qhia tau hais tias hippocampal ripples yog cov hluav taws xob ua haujlwm ntawm cov hlwb tshwj xeeb hauv hippocampus, uas feem ntau tshwm sim thaum lub hlwb nyob hauv lub xeev ntsiag to. Kev tsim cov txheej txheem ntawm hippocampal ripples yuav tsum muaj kev sib cuam tshuam ntawm ntau yam, suav nrog kev tswj cov noob, cov paj hlwb hloov pauv, thiab lwm yam. Thaum hippocampal ripples daim ntawv, lawv pab ntxiv dag zog rau cov txheej txheem nco encoding.

Ib txoj kev tshawb fawb ib zaug tau pom tias lub zog ntawm hippocampal ripples muaj kev cuam tshuam zoo nrog lub zog nco. Thaum lub paj hlwb nyob hauv lub xeev ntsiag to, cov neurons hauv hippocampus tsim cov hluav taws xob tshwj xeeb uas muaj "thaws" "-zoo li daim ntawv, pab kev nco kom hloov pauv thiab khaws cia rau hauv lub hlwb. Tib lub sijhawm, hippocampal ripples kuj tuaj yeem txhim kho cov kev nco. synchronization ntawm neurons nyob rau hauv lub hlwb, ntxiv dag zog rau kev sib txuas thiab cov ntaub ntawv kis tau tus mob ntawm txawv neurons.

Raws li cov txiaj ntsig kev tshawb fawb saum toj no, peb tuaj yeem txiav txim siab tias hippocampal ripples yog qhov tseem ceeb rau lub hlwb lub cim xeeb encoding thiab cia. Los ntawm kev txhawb nqa kev ua si hauv hippocampus thiab ntxiv dag zog rau kev sib txuas ntawm cov neurons muaj feem xyuam, peb tuaj yeem txhim kho kev khaws cia thiab khaws cov kev nco hauv lub hlwb. Nyob rau tib lub sijhawm, peb tseem tuaj yeem tsim qhov chaw zoo dua rau lub hlwb thiab txhawb kev tsim cov hippocampal ripples los ntawm kev noj zaub mov zoo, kev tawm dag zog, thiab tswj kev puas siab puas ntsws, yog li ua tiav cov txiaj ntsig kev nco zoo dua.

Hauv cov ntsiab lus, kev sib raug zoo ntawm hippocampal ripples thiab nco yog thaj tsam ntawm kev tshawb fawb hnyav. Los ntawm kev kawm tob txog nws cov txheej txheem sab hauv, peb tuaj yeem tshawb nrhiav txoj hauv kev txhim kho kev nco tau zoo dua, yog li coj tau txiaj ntsig ntau dua rau kev kawm tus kheej thiab kev txhim kho kev ua haujlwm. Cia peb ua haujlwm ua ke los tsim ib puag ncig zoo rau peb lub hlwb thiab dhau los ua tus qauv zoo ntawm peb tus kheej! Nws tuaj yeem pom tau tias peb yuav tsum txhim kho kev nco, thiab Cistanche deserticola tuaj yeem txhim kho kev nco, vim Cistanche deserticola tseem tuaj yeem tswj hwm qhov sib npaug ntawm cov neurotransmitters, xws li nce qib ntawm acetylcholine thiab kev loj hlob. Cov khoom no yog qhov tseem ceeb rau kev nco thiab kev kawm. Tsis tas li ntawd, Nqaij kuj tuaj yeem txhim kho cov ntshav khiav thiab txhawb nqa cov pa oxygen, uas tuaj yeem ua kom lub hlwb tau txais cov as-ham txaus thiab lub zog, yog li txhim kho lub hlwb tseem ceeb thiab kev ua siab ntev.

Nyem paub cov tshuaj ntxiv los txhawb kev nco

Cov txiaj ntsig no txhawb cov lus qhia yav dhau los uas cov suab nrov thiab cov ntxaiv ripples ua rau muaj feem cuam tshuam rau kev sib koom ua ke.Txhua yam, raws li kev kwv yees los ntawm cov qauv ntawm hippocampo-cortical kev sib cuam tshuam rau kev nco, hippocampal ripples feem ntau ua rau cortical thaum pw tsaug zog, thiab cortical feem ntau ua rau hippocampal thaum sawv ntxov.

Cortical Ripple Kev sib koom ua ke tau yooj yim los ntawm kev ua kom thoob plaws ntau qhov chaw.

Hauv txhua tus neeg mob, peb pom tias thaum ob qhov chaw cortical corippled, ib lossis ntau qhov chaw ntxiv tuaj yeem koom nrog lawv (SI Appendix, Fig. S5). Txhawm rau kuaj yog tias ob qhov chaw cortical corippling ua rau nws muaj feem ntau rau lwm qhov chaw tseem yuav ua rau ripple, peb suav qhov χ2 qhov kev ntsuas ntawm qhov sib npaug rau txhua pawg ua tau ntawm peb cortical raws nyob rau hauv qhov tsis muaj kev xav tias kev sib koom ua ke ntawm cov channel A thiab B tsis muaj kev cuam tshuam rau kev sib koom ua ke. Qhov tshwm sim ntawm Aand C. Peb pom muaj kev sib koom ua ke ntawm qhov thib peb hauv qhov nruab nrab ntawm 14.1% ntawm triplets thaum lub sij hawm NREM thiab 38.8% thaum sawv ntxov (tus neeg mob tshwj xeeb cov txiaj ntsig tau tshaj tawm hauv SIAppendix, Table 4, χ2 kev sim ntawm proportions, FDR- kho P qhov tseem ceeb thoob plaws channel triplets hauv cov neeg mob).

In further support that rippling is facilitated through activation across multiple sites, we found that the number of ripple co-occurrences relative to chance increased with the number of locations rippling (>2) (Fig. 2D). Qhov kev nce ntxiv tau hais, xws li qhov pom ntawm tus lej ntawm kev sib koom ua ke rau lub hauv paus ntawm 25% ntawm tag nrho cov channel tau nce los ntawm afactor ntawm ∼104 thaum sawv ntxov thiab ∼5 × 103 thaum lub sij hawm NREM. Yog li, rippling zoo li yuav pib ntau rippling, tawm tswv yim muaj peev xwm ntawm tus kheej txhawb kev sib kis.

Cortical Ripples sib koom ua ke nyob thoob plaws qhov deb.

Bindingby ripples xav kom lawv sib koom ua ke thoob plaws corticalareas. Peb piv cov xwm txheej tshwm sim ntawm cortico-corticalripple kev sib koom ua ke (piv txwv li, qhov tshwm sim ntawm qhov ripple hauv ib qhov chaw cortical muab ib qho ripple hauv lwm qhov chaw cortical, xav tau ntau dua lossis sib npaug rau 25-ms sib tshooj) tiv thaiv cov teeb meem dawb streamline nrug deb ntawm. cortical chaw. Streamline nrug tau suav nrog 360 parcels ntawm HCP-MMP1.0 atlas (23), raws li txiav txim los ntawm probabilistic diffusion MRI tractography (24), andare pejxeem nruab nrab (25).

Peb pom tias cortico-corticalrippling qhov tshwm sim tsis txo qis nrog cov kab mob fiber ntau nyob rau hauv NREM (Daim duab 2E, r=0.04, P=0.22, linear mix-effects nrog tus neeg mob raws li cov nyhuv random) tab sis theej tau tuav mus txog rau 25-cm sib cais, hla lobes, thiab nruab nrab ntawm hemispheres.Thaum sawv ntxov, ripple probabilities kuj tseem nyob thoob plaws qhov kev ncua deb, txawm tias muaj kev sib raug zoo tsis muaj zog tab sis tseem ceeb (Fig. 2F, r=0 .10, P=4 × 105).Saib SI Appendix, Fig. S6A thiab B rau cov neeg mob ib leeg.

Ripples nyob rau hauv tag nrho cov Cortical Areas koom nrog HippocampalRipples.

Nws tau tshaj tawm yav dhau los tias kev sib txuas sib txuas tshwm sim nyob nruab nrab ntawm parahippocampal gyrus thiab 16.4% ntawm lateral temporal electrodes tab sis tsuas yog 3.3% ntawm rolandic (8), tej zaum xav txog qhov chaw anatomical ntawm lub hippocampus ntawm lub apex ntawm lub cortical hierarchy (26). Txawm li cas los xij, peb pom tias hippocampal ripples tau tshwm sim nrog ripples hauv txhua qhov chaw cortical ntawm kwv yees li sib npaug ntawm NREM thiab waking.

Noj cov myelination Performance index raws li ib qho kev ntsuas ntawm txoj hauj lwm nyob rau hauv lub corticalhierarchy [cov cheeb tsam koom nrog yog tsawg myelinated (27)], peb nrhiav tau ib tug tsis muaj zog tab sis tseem ceeb tshwm sim thaum lub sij hawm NREM tab sis tsis waking. Thaum lub sij hawm NREM, hippocampo-cortical co-cuam tshuam tau zoo correlated nrog myelination (SI Appendix, Fig. S7; r=0.15, P=0.01), qhia tias hippocampal ripples me ntsis yuav tshwm sim nrog ripples hauv thawj qhov chaw cortical.

Cortico-Cortical thiab Hippocampo-Cortical Ripple Kev tshwm sim ua ntej rov nco qab.

. Yog hais tias ripples nyob rau hauv txawv cheeb tsam cortical khi lub ntsiab ntawm lub cim xeeb, nws yuav tsum tau hais tias corticalripples co-cuam tshuam ua ntej cued nco, uas yuav tsum tau kom cov ntsiab lus no coactivated. Txhawm rau ntsuas qhov kev xav no, peb tau txheeb xyuas cov ntaub ntawv ua haujlwm nco txog cov neeg ua haujlwm ntawm tsib tus neeg mob SEEG (Fig.3A thiab SI Appendix, Tables 1 thiab 5). Ua ntej ncua cuedrecall, muaj qhov nce ntxiv ntawm qhov tshwm sim ntawm cortical ripple (P=1} × 1011; linear mix-effects model nrog tus neeg mob raws li qhov tshwm sim random) ntawm 330% ntawm lub caij nyoog (xws li kev sim, yog li lub caij nyoog tau txiav txim nyias rau tam sim ntawd thiab ncua sij hawm rov hais dua), thiab qhov nce ntxiv ntawm cortico-cortical ripple cooccurrence ntawm 758% piv rau lub caij nyoog (P=0.0004; Fig.3B–E).

Tsis tas li ntawd, cortical ripple tshwm sim (P=0.002) thiab cortico-cortical (P=0.002) thiab hippocampo-cortical (P=0.008) ripple co-occurrence modulations tau ntau dua ua ntej ncuavs. Kev rov qab los tam sim ntawd, uas tau sib koom tib yam stimuli thiab cov lus teb. Thaum kawg, cortico-cortical (P=0.04) thiab hippocampo-cortical (P=0.004) rippling tau txhim kho ua ntej qhov tseeb vs. tsis raug ncua sij hawm rov qab los. , uas tsis yog rau cortical (P=0.08) lossis hippocampal (P=0.94) ripples feem ntau.

Qhov tseem ceeb, ncua sij hawm tab sis tsis rov qab tam sim ntawm cov neeg koom tes ua ke yog qhov cuam tshuam loj heev los ntawm kev puas tsuaj hippocampal (12). Cov ntaub ntawv no qhia tau tias nce rippling ntawm qhov chaw cortical thiab nruab nrab ntawm lub hippocampus thiab cortex thaum lub sij hawm hippocampal-dependent retrieval ofnovel ua ke ntawm yav tas los unrelated khoom. Qhov kev tshawb pom no txhawb nqa qhov kev xav tias hippocampo-cortical thiab corticocortical rippling tuaj yeem pab txhawb rau kev tsim kho dua tshiab ntawm kev nco txog tib neeg.

Txij li thaum lub xeev lub hlwb tuaj yeem cuam tshuam rau kev rov qab ua haujlwm, peb tau sim seb puas muaj qhov sib txawv ntawm alpha (7 txog 13 Hz) analytic amplitudebetween cov lus teb raug thiab tsis raug. Peb pom tsis muaj qhov txawv txav hauv qhov txhais tau tias alpha analytic amplitude hla corticalchannels hauv ±1-s qhov rais nyob ib ncig ntawm lub sij hawm teb rau correctvs. tsis raug rau ib qho ntawm tsib tus neeg mob uas muaj cov ntaub ntawv ua haujlwm sib koom ua ke (P=0.24 txog 0.64 thiab t=0.36 txog 1.6, ib-sab ob-samplet-test, FDR-kho P qhov txiaj ntsig rau ntau tus neeg mob).

Cortical Ripples Phase-Xauv thoob plaws thaj tsam thoob plaws.

Theem-locked oscillations nyob rau hauv qhov chaw dav tau pom tias yog qhov kev sib koom ua ke ("binding") ntawm cov khoom sib txawv ntawm cov xwm txheej thoob plaws cortical nto. Rau txhua tus khub channel, peb suav cov theem ntsuas tus nqi (PLV), ib qho kev ntsuas ntawm qhov sib xws ntawm 70- rau 100-Hz theem ntawm qhov chaw, ywj siab ntawm amplitude (28), thoob plaws tag nrho lawv cov rippleevents hauv NREM los yog waking. Thov nco ntsoov tias qhov sib xws ntsuas ntawm qhov sib txawv ripples, ntawm txhua 1-ms bin txheeb ze rau qhov chaw ripple, tsis nyob hauv coripples.

Peb pom cov PLV tseem ceeb ntawm kev sib koom ua ke ntawm txhua qhov piv txwv corticalregions, suav nrog nruab nrab ntawm hemispheres, hauv ob lub xeev (Daim duab 4A–C).Muaj ntau tus khub channel nrog cov kev hloov pauv PLV tseem ceeb thaum NREM tshaj li sawv (Daim duab 4C thiab SI Daim Ntawv Ntxiv, Table 6; post-FDR P < 0.05, randomization test; nonsignificant results in SI Appendix, Fig. S8A and B).

Ib qho piv txwv ntawm ib theem zoo ib yam ntawm ob qhov chaw cortical hla ob lub ripples yog qhia hauv daim duab 4A. Rau txhua tus khub channel, PLV tau ntsuas ntawm txhua qhov latency txheeb ze rau qhov nruab nrab ntawm lawv cov ripple (Fig. 4B), thiab cov chav kawm lub sij hawm no tau nruab nrab ntawm txhua qhov tseem ceeb ntawm cov khub (Fig. 4C). Qhov nce PLV tau mus rau tag nrho lub sijhawm thaum cov chaw tau rippling thiab sawv sai sai los ntawm qhov pib. Lub sijhawm PLV chav kawm tau zoo heev uas zoo sib xws hauv cov khub sib txuas. Thaum pw tsaug zog 2,106 / 2,275 cortico-cortical channel khub muaj ntau tshaj 40 qhov sib koom ua ke, yuav tsum muaj kev kwv yees PLV. Ntawm cov no, 26.3% (554/2,106) muaj cov kev hloov pauv PLV tseem ceeb.

Thaum sawv ntxov, 1,939/2,275 muaj ntau tshaj 40 qhov sib koom ua ke, thiab 13.9% (269/1,939) ntawm cov no muaj qhov tseem ceeb PLV modulations (SI Appendix, Table 6).Zoo li qhov peb pom rau kev sib koom ua ke (SI Appendix, Fig.S3A ), cortico-cortical ripple ncov PLVs thoob plaws channel khub sib raug zoo ntawm NREM thiab waking (SIAppendix, Fig. S3B; r=0.20, P=4} × 1022, qhov tseem ceeb ntawm kev ua haujlwm). Hauv cov ntsiab lus, cov khub nyob deb ntawm qhov chaw thoob plaws hauv lub cortex tau pom tias muaj cov theem sib xws thaum lub sij hawm ripples hauv NREM thiab waking.

Phase-locked ripples Muaj qhov dav dav ntawm Phase Lagsin NREM piv rau Waking thiab Tej zaum txawv nyob rau hmo.

Tom qab ua kom pom qhov tseem ceeb ntawm kev kaw qhov nruab nrab ntawm qhov chaw corticalrippling, peb tau soj ntsuam qhov kev faib tawm ntawm lub voj voog ncig lub kaum sab xis ntawm qhov chaw ua khub. Peb pom tias thaum lub sij hawm NREM qhov nruab nrab lub kaum sab xis rau qhov sib txawv cortical site khub uas muaj qhov tseem ceeb ripple theem locking muaj ib tug ncaj txawm faib los ntawm {{0}} mus rau 2π radians (Fig. 4D, Sab laug). Txawm li cas los xij, thaum sawv ntxov, ripple theem lags hla cov khub tended tobe ∼0 lossis ∼π (Fig. 4D, Hauv qab Txoj Cai).

Qhov sib txawv no tseem ceeb (P {{{0}}} × 108, χ2=29}.8, df=1; siv suav hauv 0 ± π/6 lossis π ± π/6 vs. sab nraum cov kab no rau NREM vs. waking). Qhov kev soj ntsuam no qhia tias muaj kev nyiam ntau dua rau zerophase lag thaum sawv ntxov. Peb muab pov thawj hauv qab no tias ∼0 thiab ∼π lags yog qhov ua haujlwm sib npaug thiab tej zaum yuav yog vim muaj qhov sib txawv ntawm cov khoom siv hluav taws xob zoo sib cuag nrog cov txheej txheem tocortical. Qhov no tej zaum yuav muaj feem xyuam rau qhov kev xav ntau dua ntawm kev sib tw rau ob peb ntawm zero latency thaum sawv ntxov (Daim duab 2A).

Peb kuj tau sim seb puas yog theem lag luam thaum lub sij hawm NREM sib txawv ib hmos. Rau txhua tus neeg mob uas muaj ntau hmo pw tsaug zog (n {{{0}}}), peb tau muab piv rau ripple theem lags ntawm txhua qhov ua tau pw tsaug zog hmo hauv cov khub channel uas muaj cov kev hloov pauv PLV tseem ceeb. Peb pom tias 51.8% (1,256/2,426) ntawm cov khub zoo li no muaj qhov sib txawv ntawm cov theem qis ntawm hmo ntuj (Daim duab 4E; post FDR P < 0.05, Watson-Williams test; yam tsawg kawg 30 ripplesper hmo ib khub channel). Cov kev sib txawv ntawm cov ripple phaselags ntawm cov chaw cortical tshwj xeeb qhia tias lawv tuaj yeem koom nrog hauv kev sib koom ua ke nyob rau hmo ntuj, zoo li yuav tshwm sim, piv txwv li, thaum rov ua haujlwm cortical sawv cev cuam tshuam nrog kev nco sib txawv. Cov xwm txheej zoo sib xws tau raug sau tseg hauv cov qauv cortical loj (29).

Ripples Phase-Lock Robustly hla qhov ntev.

Txij li kev nco txog cov yam ntxwv sib koom ua ke sib txawv ntawm cov ntsiab lus uas tau muab tso rau hauv qhov chaw cortical thoob plaws hauv ob qho tib si hemispheres, ib qho txheej txheem neurophysiological txhawb nqa lawv cov kev sib koom ua ke, sib sau ua ke, lossis rov qab yuav tsum zoo ib yam ua haujlwm hla cov kev deb. Yog li, muab hais tias cortico-cortical rippleco-ces tshwm sim muaj me ntsis kom tsis txhob muaj qhov kev ncua deb (kuaj txog 200 mm; Fig. 2E thiab F), peb xav tias corticocortical ripple theem xauv kuj tsis txo nrog kev ncua.

Tseeb tiag, peb pom tias, zoo li kev sib koom ua ke, qhov sib npaug ntawm cov channel khub nrog cov kev hloov pauv tseem ceeb PLV (Fig. 4F; r=0.07, P=0.36, linear mix-effects with the patientas ib qho random nyhuv) thiab qhov loj ntawm cov PLV modulations (Fig. 4G; r=0.05, P=0.67) tsis tau decremented nrog intervening fiber ntau nyob deb ntawm NREM. Thaum sawv ntxov, muaj qhov txo qis hauv qhov kev faib ua feem ntawm cov khub channel nrog cov kev hloov pauv tseem ceeb PLV nrog kev ncua deb, tshwj xeeb tshaj yog nyob rau hauv luv luv (Fig. 4F; r=0.07, P=0.001), tab sis tsis muaj decrement nyob rau hauv qhov loj ntawm qhov tseem ceeb channel pairPLV modulations nrog nyob deb (Daim duab. 4G; r=0.004, P=0.94). Yog li, physiological kev txiav txim txhawb los ntawm rippling yuav spanthe tag nrho cortical nto.

Phase Locking nce nrog ntau qhov chaw Cortical Corippling.

Ripples feem ntau raug kaw hla ntau qhov chaw, suav nrog nruab nrab ntawm hemispheres (Fig. 4H), thiab raws li tau piav qhia saum toj no peb pom tias ob qhov chaw corippling ua rau nws muaj feem ntau tias qhov thib peb yog corippling. Cov kev tshawb pom no tsa cov lus nug ntawm seb qhov kev ua kom muaj kev sib txuas lus sib txuas ua kom yooj yim dua kev sib koom ua ke. Peb pom qhov muaj zog zoo linearcorrelation ntawm tus naj npawb ntawm qhov chaw rippling thiab cortico-cortical ripple theem-xauv ncov amplitude (Fig. 4I).

Cov txiaj ntsig no tau pom dua thaum ΔPLV (peak PLVminus baseline PLV) tau siv los hloov lub ncov PLV (ΔPLV:n {{0}}}/17 cov neeg mob tseem ceeb thaum NREM, n=1/17 tseem ceeb thaum sawv ntxov, tom qab FDR P < 0.05, qhov tseem ceeb ntawm r). Totest seb puas muaj ntau dua corippling tsuas yog vim muaj ntau dua rippleamplitude, peb ntsuas qhov nruab nrab 70- rau 100-Hz analyticamplitude ntawm coripples thiab pom tias tsuas yog 2/17 cov neeg mob inNREM thiab 0/17 cov neeg mob hauv waking muaj kev sib raug zoo. (post-FDR P < 0.05, qhov tseem ceeb ntawm r), thiab qhov tseem ceeb ntawm kev sib raug zoo yog ob qho tib si tsis zoo, qhia tau tias kev sib koom ua ke ntau dua tsis yog vim muaj ntau dua amplitude. Nyob rau hauv tas li ntawd, kev sib koom ua ke ntawm ripples txhawb ntxiv kev sib koom ua ke, uas txhim kho theem kev kaw haujlwm.

Cortico-Cortical Coripples muaj qhov sib npaug ntawm theem lag luam hla cov voj voog ua tiav.

Peb xav tias ib khub ntawm qhov chaw yuav ua tau zoo "theem-xauv" hla cov voj voog txuas ntxiv vim qhov ripple oscillation zaus ntawm ∼90 Hz yog qhov sib xws ntawm cov ripples thiab qhov chaw. Rau txhua qhov ripple los ntawm txhua tus khub cortico-cortical channel, peb suav cov PLV hla lub lags nruab nrab ntawm ob lub ripples siv lawv tsib lub ncov ze tshaj plaws rau lub sijhawm ripple thiab pom qhov tseem ceeb hauv-ripple phaselocking rau 98.3% ntawm 807,213 ripples thaum lub sij hawm NREM thiab 98.0% ntawm 1,348,696 ripples thaum sawv ntxov (P < 0.05; randomization test, n=1, 000 random theem lags, FDR kho hla ripples). Yog li, nyob rau hauv-ripple theem xauv yog tam sim no nyob rau hauv yuav luag tag nrho cov cortico-cortical coripples.

Hippocampo-Cortical Pairs Tsis tshua muaj, Yog Puas Tau, Phase-Lock.

Cortico-cortical theem locking tuaj yeem raug tsav los ntawm kev sib txuas ntawm kev sib txuas cortical oscillators, lub hauv paus tsav tsheb mechanism, ora ua ke. Txij li thaum hippocampal ripples sib zog ua ke nrog cortical ripples (Daim duab 2B), peb tau tshawb xyuas seb lub hippocampus tsav lub sij hawm kaw ntawm ripples hauv lub cortex los ntawm kev sim yog tias muaj theem xauv ntawm hippocampo-cortical coripples.

Rau hippocampo-cortical khub thaum pw tsaug zog, 277/461 muaj ntau dua 40 kev sib koom ua ke, thiab 1.4% (4/277) ntawm cov no muaj cov kev hloov pauv PLV tseem ceeb. Thaum sawv ntxov, 333/461 ntawm hippocampo-cortical channel khub muaj ntau tshaj 40 qhov sib koom ua ke, thiab 0.3% (1/333) ntawm cov no muaj qhov tseem ceeb PLV kev hloov pauv (SI Appendix, Fig. S8C–F thiab Table S6).

Kev soj ntsuam ntawm electrode trajectories qhia tias cov hippocampal kev sib cuag nrog PLVs tseem ceeb nrog cortical siteswere tej zaum nyob rau hauv lub subicular complex es tsis yog thehippocampus kom zoo, raws li kev tshawb nrhiav nyob rau hauv nas uasripple propagation ntawm lub hippocampus mus rau retrosplenial cortex isvia subiculum (10). Yog li, nws tsis zoo li tias cortico-corticalripple theem xauv yog tsav los ntawm cov khoom siv los ntawm hippocampal ripple, uas txhawb cov kev xav tias cortico-cortical ripple theem locking yog tsav intracortical.

Cortical Ripples yog txuam nrog nce thiab PhaseModulated Ib-Unit firing.

Rau ripples kom muaj lub luag haujlwm hauv kev sib txuas lus thiab kev sib koom ua ke ntawm cov ntaub ntawv ntawm cov chaw nyob debcortical yuav tsum muaj cov kev ua haujlwm neuronal muaj peev xwm ua haujlwm nrog ripple tshwm sim thiab theem. Peb tau soj ntsuam microarrayrecordings los ntawm tib neeg lateral temporal cortex granular / supragranular khaubncaws sab nraud povtseg nyob rau hauv peb cov neeg mob (SI Appendix, Table 7) thaum lub sij hawm NREM los ntsuam xyuas seb ripples modulate lub zos ib leeg-unit spiking.

Peb tau kuaj pom spikes thiab txheeb lawv rau hauv putative pyramidal (PY) thiab interneuron (IN) units raws li cov duab waveform thiab spike lub sij hawm tus yam ntxwv raws li yav tas los txoj kev (30) thiab xyuas kom meej tias cov units muaj lub ncov loj teeb liab-rau-noiseratios (PY: 9.1 ± 3.4; IN: 5.2 ± 2.9), muaj qhov sib txawv me me uas yog<3 ms (PY: 0.2 ± 0.3%; IN: 0.3 ± 0.6%; low percentages indicate minimal contamination by other units), and were well-isolated from one another based on the projection test (31) (PY: 95.4 ± 86.0 SD; IN: 82.8 ± 83.4 SD). 

Peb kuj tau soj ntsuam cov ripples kaw los ntawm array's microcontacts nrog theaverage spike waveform ntawm txhua chav tsev rho tawm thaum lub sij hawm ntawm cov spikes ntawm chav tsev channel los tiv thaiv chav sib kis kab mob ntawm LFP. Peb pom tias cortical ripples tau txuam nrog kev tua ib leeg (daim duab 5A thiab B). PY tau nce 255% thiab IN tau nce 297% nce ntawm cov nqi nce thaum lub sij hawm ripples piv rau cov hauv paus ntsiab lus (tseem xaiv lub sijhawm nyob nruab nrab ntawm cov ripples uas tau sib npaug ntawm tus lej thiab lub sijhawm rau cov ripples).

Tsis tas li ntawd, chav tsev tua hluav taws tau muaj zog theem-modulated los ntawm ripples (Fig. 5A), nrog 49% (32/66) ntawm PY thiab 71% (24/34) ntawm IN muaj qhov tseem ceeb 70- rau 100- Hz theem modulations thaum lub sij hawm hauv zos ripples (Fig. 5C; post-FDR P < 0 . 17}}.5, yam tsawg kawg 30 spikesper unit hla ripples).

Yog li, txij li chav tsev spiking yog ua ke rau lub hauv paus ripple theem, thiab txij li cov theem ripple yog synchronized ntawm longdistances, cov ntaub ntawv no qhia tias ripples tswj chav tsev spike lub sij hawm ntawm dav sib cais nyob rau hauv lub cortex, uas yuav enablephase xaiv, coincidence nrhiav, reentrant processing, andspike- lub sij hawm-nyob ntawm plasticity. Cov txheej txheem neurophysiological yooj yim no yuav cuam tshuam rau kev sib koom tes ntawm kev sib koom tes ntawm tes ntawm thaj chaw cortical, qhov tseem ceeb ntawm kev khi.

Corippling nce Putative Unit-Activity Correlation ntawm Distant Cortical Sites.

Peb qhov kev tshawb pom tias cov ripples feem ntau raug kaw nyob rau hauv qhov chaw nyob deb thiab qhov chaw tua hluav taws yog theem-xauv rau hauv zos ripples ua ke qhia tias chav tua hluav taws kuj muaj feem cuam tshuam rau cov chaw nyob deb. Peb tsis tuaj yeem kuaj qhov no ncaj qha vim peb tsis tau ua cov ntaub ntawv kaw lus microelectrode ntawm chav nyob hauv ntau qhov chaw sib cais los ntawm ntau dua ∼5 mm.

Rather, as an indirect test, we used >200-Hz analytic amplitude los ntawm SEEG cov ntaubntawv povthawj siv raws li tus proxy rau chav tsev firing (32). Thaum sawv ntxov, tab sis tsis yog NREM, qhov kev ntsuas no tau sib cuam tshuam ntau dua thaum cov chaw cortical tau rippling vs. thaum lawv tsis (Fig. 5D, P=8} × 10303, ob-sided paired t-test). Kev sib raug zoo ntawm qhov chaw rippling tsis tau txo qis hauv qhov kev ncua deb ntawm qhov chaw (Fig. 5E).

Raws li tau piav qhia saum toj no, ripple theem lags nruab nrab ntawm channelstended ze rau 0 lossis π, tshwj xeeb tshaj yog thaum sawv. Qhov no tuaj yeem qhia tau tias kev corippling qee zaum sawv cev rau lub xeev ntawm kev sib txuas lus tsis txaus ntseeg, lossis tsuas yog tias peb cov kev sib txawv ntawm SEEG muaj kev sib txawv sib txawv rau hauv zos ripple-generatingdipoles. Tseeb tiag, qhov 3-mm bipolar SEEG kev sib cuag sib cais yog qhov loj txaus los sau los ntawm ntau lub ripple dipoles nrog cov kev taw qhia sib txawv. Nyob rau hauv nas, ripple generators nyob ∼1 mm2 ofcortical nto (5), thiab cellular generators nyob rau hauv ntau txheej sib cais los ntawm ∼1 mm (10).

Txhawm rau ntsuas cov kev xav no, peb piv cov kev sib raug zoo ntawm cov kev ntsuas amplitudes ntawm {{{0}} Hz high-passed signals ntawm qhov chaw, thaum cov chaw muaj cov theem lags ntawm 0 ± π/6 vs. π ± π / 6 (nruab nrab nyob rau hauv cov kab no rau txhua tus khub channel). Tsis pom muaj qhov sib txawv tseem ceeb rau NREM lossis waking (NREM: P=0}.07; waking: P=0.17; ob-sided khub t-test, n=2,275 channel khub) , yog li qhia tias cov lags nyob ze 0 thiab π yog qhov ua haujlwm sib npaug, raws li xav tau yog tias lawv yog vim qhov sib txawv me ntsis ntawm qhov chaw electrode txheeb ze rau cortical lamina.

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