Dav dav Ripples Synchronize tib neeg Cortical Activity thaum pw tsaug zog, Waking, thiab nco nco Part 1

Tshaj tawm lub cim xeeb encoding, sib sau ua ke, thiab muab rov qab xav tau kev sib koom ua ke ntawm cov ntsiab lus encoded nyob rau hauv qhov chaw cortical dav. Cov txheej txheem uas xws li "binding" ntawm cov khoom sib txawv ntawm cov xwm txheej hauv kev puas siab puas ntsws rau hauv kev sib koom ua ke sawv cev tshwm sim yog tsis paub.Qhov "binding-by-synchrony" txoj kev xav qhia tias cov cheeb tsam encoding yog boundby synchronous oscillations enabling enhanced kev sib txuas lus.

Declarative memory encoding yog hais txog kev hloov cov ntaub ntawv mus rau hauv ib daim ntawv uas peb tuaj yeem khaws, txhais, thiab khaws cia. Qhov kev encoding no tuaj yeem ua tau los ntawm ntau txoj hauv kev, xws li txuas cov ntaub ntawv rau peb cov kev paub uas twb muaj lawm (kev nco txog kev sib koom ua ke), faib cov ntaub ntawv mus rau hauv cov txheej txheem (kev cim xeeb), thiab lwm yam. Kev tshaj tawm nco encoding tseem ceeb heev rau peb lub cim xeeb.

Nrog rau kev tshaj tawm lub cim xeeb encoding zoo, peb tuaj yeem nco qab thiab khaws cov ntaub ntawv yooj yim dua. Declarative memory encoding yog tsim nyog rau kev kawm paub tshiab thiab nco ntsoov cov ntaub ntawv tseem ceeb. Yog tsis muaj kev tshaj tawm lub cim xeeb encoding, peb yuav tsis nco qab lossis tsis meej pem ntau yam ntaub ntawv, uas tuaj yeem cuam tshuam rau peb lub neej txhua hnub thiab kev kawm.

Tsis tas li ntawd xwb, tab sis kev tshaj tawm kev nco encoding kuj txhawb kev sib txuas thiab kev sib txuas ntawm cov neurons hauv lub hlwb, yog li txhim kho peb lub peev xwm nco. Nyob rau hauv peb lub hlwb, neurons tsim intricate tes hauj lwm, thiab los ntawm stimulation thiab nco encoding, peb muaj peev xwm txhim khu kev sib txuas thiab kev sib txuas ntawm neurons, uas yog ib qho tseem ceeb rau kev nco mus ntev.

Yog li ntawd, kev tshaj tawm zoo nco encoding tsis tsuas yog pab peb kawm thiab xyaum cov kev paub tshiab tab sis kuj txhawb peb lub peev xwm nco thiab ua rau lub hlwb ua haujlwm. Yog li ntawd, nyob rau hauv peb lub neej niaj hnub, nquag siv ntau txoj kev nco encoding los ntxiv dag zog rau peb lub cim xeeb tshaj tawm encoding muaj txiaj ntsig zoo rau peb lub cim xeeb. Nws pom tau tias peb yuav tsum txhim kho peb lub cim xeeb. Cistanche deserticola tuaj yeem txhim kho kev nco zoo vim Cistanche deserticola yog cov khoom siv tshuaj suav tshuaj suav nrog ntau yam tshwj xeeb, ib qho ntawm kev txhim kho kev nco. Kev ua tau zoo ntawm cov nqaij minced los ntawm ntau yam khoom xyaw uas nws muaj, nrog rau cov kua qaub, polysaccharides, flavonoids, thiab lwm yam. Cov khoom xyaw no tuaj yeem txhawb lub hlwb kev noj qab haus huv ntau txoj hauv kev.

Nyem Paub Short-term Nco yuav ua li cas txhim kho

Txawm li cas los xij, cov pov thawj rau qhov oscillations yog sparse. Luv luv high-frequency oscillations ("ripples") tshwm sim hauv hippocampus thiab cortex thiab pab txhim kho kev nco qab thiab sib sau ua ke. Ntawm no, siv cov ntaub ntawv intracranial hauv tib neeg, peb tshaj tawm tias cov ∼70-ms-ntev, 90-Hz ripples feem ntau ua khub (hauv ± 500 ms), sib koom ua ke ( Ntau dua lossis sib npaug rau {{6} }ms sib tshooj), thiab, qhov tseem ceeb, theem-xauv (haveconsistent theem lags) ntawm dav faib focal cortical qhov chaw thaum pw tsaug zog thiab waking, txawm nyob nruab nrab ntawm hemispheres.

Cortical ripple kev sib koom ua ke yog yooj yim los ntawm kev ua kom thoob plaws ntau qhov chaw thiab theem xauv nce nrog ntau corticalsite corippling. Ripples nyob rau hauv tag nrho cov cheeb tsam cortical sib koom ua ke nrog hippocampal ripples tab sis tsis txhob theem-xauv nrog lawv, ntxiv qhia tias cortico-cortical synchrony yog kho los ntawm kev sib txuas cortico-cortical. Ripple theem lags sib txawv ntawm kev pw tsaug zog hmo ntuj, zoo ib yam nrog kev koom tes hauv kev sib txawv. Thaum sawv ntxov, peb qhia tau hais tias hippocampo-cortical thiab cortico-cortical ripples nce ua ntej kev vam meej ncua kev nco qab thaum khi ntawm qhov cue thiab cov lus teb yog qhov tseem ceeb.

Ripples nce thiab theem-modulateunit firing thiab ripples nce high-frequency correlations ntawm cov cheeb tsam, tawm tswv yim synchronized unit spiking yooj yim kev sib pauv ntaub ntawv. Kev sib koom ua ke, theem synchrony, thiab kev sib raug zoo ntawm kev sib raug zoo yog khaws cia nrog me ntsis txo qis tshaj qhov deb heev (25 cm). Hippocampo-cortico-cortical ripples tshwm sim kom muaj cov khoom tseem ceeb tsim nyog los txhawb kev khi los ntawm synchrony thaum lub sij hawm nco retrievaland tej zaum feem ntau hauv kev paub.

Ripples yog luv luv-frequency oscillations uas tau kawm zoo nyob rau hauv rodenthippocampus thaum lub sij hawm tsis ceev lub qhov muag txav pw (NREM) thaum lawv cim muaj playplay ntawm cov xwm txheej los ntawm yav dhau los waking lub sij hawm thiab yog ib qho tseem ceeb rau kev nco consolidation nyob rau hauv lub cortex (1-4. ). Tsis ntev los no, ripples tau pom nyob rau hauv nas koom nrog cortex tab sis tsis yog thawj qhov kev hnov ​​​​mob lossis lub cev muaj zog cortices thaum pw tsaug zog, nrog kev sib txuas ntxiv rau hippocampal ripples hauv kev pw tsaug zog tom qab kawm (5). Ib txoj kev tshawb fawb ua ntej tau tshaj tawm ripples nyob rau hauv lub waking thiab tsaug zog miv cortex, tshwj xeeb tshaj yog NREM (6). Hauv tib neeg, cortical ripples tsis ntev los no tau txheeb xyuas thaum sawv ntxov thiab tau pom ntau dua nyob rau sab nraud ntawm lub cev dua li hauv rolandic cortex.

Hippocampal ntse nthwv dej-ripple tshwm sim thiab ripplecoupling ntawm parahippocampal gyrus thiab lub sij hawm lub koom haum cortex nce ua ntej nco nco nyob rau hauv tib neeg (7, 8), tej zaum yuav pab txhawb replay ntawm cortical neuronfiring sequences tsim thaum lub sij hawm encoding (9). Hauv nas, ripples tshwm sim ntawm hippocampus thiab ∼1 mm2 ntawm parietal cortex hauv kev pw tsaug zog tom qab kawm (5), hauv cov nas, ripples propagate los ntawm hippocampus mus rau retrosplenial cortex (10), thiab hauv miv, rippleco-ces tshwm sim. tshaj tawm tias txwv tsis pub muaj kev ncua deb (6).

Peb tsis ntev los no tau tshaj tawm, siv tib neeg cov ntaub ntawv kaw tseg, uas ∼70-ms-ntev, ∼90-Hzripples muaj nyob txhua qhov chaw ntawm lub cortex thaum NREM thiab waking (11).Thaum sawv, cortical ripples tshwm sim nyob rau hauv lub zos high-frequency kev ua si peaks. Thaum pw tsaug zog, cortical ripples feem ntau tshwm sim ntawm kev hloov pauv ntawm cortical down-upstate, feem ntau nrog 10- rau 16-Hz cortical pw spindles, thiab chav tsev hauv zos firing qauv raws li tiam neeg los ntawm pyramidal-interneuron tawm tswv yim. Peb pom tias cortical ripples pawg cofiring nyob rau hauv lub qhov rais ntawm spike-lub sij hawm-raws li plasticity. Cov kev tshawb pom no zoo ib yam nrog cov cortical ripples ua rau kev nco ua ke thaum NREM hauv tib neeg.

Thaum muaj yog li qhov kev txaus siab tshwm sim uas hippocampal thiab cortical rippleshave lub luag haujlwm tseem ceeb hauv tib neeg thiab nas nco, tsis muaj dab tsi paub txog lub network khoom ntawm cortical ripples. Tshwj xeeb, nws tsis paub yog tias ripples tshwm sim los yog theem-synchronize ntawm qhov chaw cortical thiab, yog tias muaj, txawm tias qhov no cuam tshuam los ntawm kev nyob deb lossis cuam tshuam nrog kev tsim kho dua tshiab ntawm kev nco qab. Cov no yuav yog cov khoom tseem ceeb rau cortical ripples los koom rau hauv kev sib txuas ntawm cov ntsiab lus sib txawv ntawm kev nco uas tau sawv cev hauv cov corticalareas tsis sib xws, cov ntsiab lus ntawm hippocampus-dependent nco (12).

Kev sib khi ntawm cov ntsiab lus sib txawv ntawm lub cim xeeb yog qhov tshwj xeeb ntawm qhov teeb meem dav dav ntawm yuav ua li cas ntau yam ntsiab lus ntawm kev puas siab puas ntsws koom ua ke rau hauv ib qho kev paub. Feem ntau hais txog qhov sib txawv ntawm qhov pom ntawm ib yam khoom (xws li, xim, duab, qhov chaw, thiab kev ntxhib los mos) muaj feem xyuam nrog ib leeg (13), tab sis "kev sib khi teeb meem" dav dav rau cov ntsiab lus ntawm kev paub txog kev sib koom ua ke hauv ib qho kev nco qab. (14).

Cov nyiaj niaj hnub no feem ntau tso siab rau hierarchical thiab multimodal convergence. Txawm li cas los xij, cov txheej txheem cortical raug faib tawm, thiab nws yuav nyuaj rau sawv cev rau qhov muaj peev xwm sib xyaw ua ke uas muaj nyob rau hauv txhua qhov kev paub nrog kev sib koom ua ke, ua rau muaj kev tawm tswv yim tias lub cev synchronybinds cortical cheeb tsam (15). Qhov kev xav no yog thawj zaug txhawb nqa byphase-locked unit firing thiab hauv zos qhov muaj peev xwm (LFPs) ntawm 40 txog 60 Hz evoked los ntawm qhov yooj yim pom kev stimuli nyob rau hauv lub anesthetizedcat tus thawj pom cortex ntawm qhov deb.<7 mm (16). 

Txawm hais tias qee qhov kev tshawb fawb ntxiv pom cov txiaj ntsig zoo sib xws hauv lwm cov corticalareas, kev coj cwj pwm, thiab hom, raws li xav tau nyob rau hauv kev sib txuas-los ntawm-synchrony hypothesis (17, 18), lwm tus tau ua tiav tsis tiav (19). Synchronous high-gamma oscillations kuj tau raug thuam tias tsis muaj kev cuam tshuam rau neuronalinteraction tshaj li kev ua kom nquag plias (19, 20).

Ntawm no, siv tib neeg intracranial stereoelectroencephalography (SEEG) kaw, peb pom tias ripples tshwm sim thiab, zoo kawg li, theem-synchronize thoob plaws txhua lub lobes thiab nruab nrab ntawm ob lub hemispheres, nrog me ntsis decrement, txawm nyob deb deb. Tsis tas li ntawd, ripple kev sib koom ua ke yog txhim kho ntawm corticalsites nrog rau nruab nrab ntawm cortex thiab hippocampus ua ntej ua tiav ncua kev rov qab los.

Corippling tau nce qib siab tshaj qhov xav tau raws li nws koom nrog ntau qhov chaw ntawm qhov chaw, thiab qhov no tau ua rau muaj zog zuj zus mus rau theem xauv. Tib-unit firingincreased thaum lub sij hawm thiab theem-xauv rau, cortical ripples, muab ib qho yooj yim yuav tsum tau rau ripples los txhim kho kev sib txuas lus viagain modulation thiab coincidence nrhiav kom tau. Txhim kho kev sib txuas lus tau txais kev txhawb nqa los ntawm peb qhov kev tshawb pom ntawm kev sib raug zoo ntawm cov cheeb tsam uas nyob deb heev.

Cov yam ntxwv no qhia tau hais tias faib, theem-xauv cortical ripples muaj cov khoom uas yuav tso cai rau lawv los pab sib koom ua ke sib txawv ntawm lub cim xeeb. Feem ntau, ripples tuaj yeem pab "khi" ntau yam ntawm kev puas siab puas ntsws encoded nyob rau hauv cov cheeb tsam thoob plaws hauv kev sib koom ua ke.

Kev tshwm sim

Ripple Detection thaum NREM thiab Waking. Ripples tau kuaj pom siv intracranial cortical thiab hippocampal kaw nyob rau hauv 17 cov neeg mob (SI Appendix, Table 1) tab tom saib xyuas rau hauv zos qaug dab peg thaum lub sij hawm NREM thiab waking. Bipolar contact derivations tau siv los ntsuas LFPs. Ripples tau kuaj pom tsuas yog onchannels hauv nonlesional, epileptogenic thaj chaw.

Ripples yuav tsum muaj peb lossis ntau lub voj voog ntawm kev nce siab ntawm 70 txog 100Hz analytic amplitude uas tsis muaj cov kev ua ub no lossis cov khoom cuav. Ripples kuj tseem yuav tsum tsis txhob tshwm sim thaum lub sij hawm ntawm cov kab mob sib kis tau kuaj pom ntawm lwm cov channel kom tsis suav nrog cov xwm txheej uas tuaj yeem sib txuas ua ke vim muaj kev ua ub ua no epileptiform.

Cortical ripples tau kuaj pom nyob rau hauv tag nrho cov lobes ntawm ob lub hemispheresduring NREM thiab waking (SI Appendix, Fig. S1A, thiab B; n=273 channels). Cortical thiab hippocampal ripples tsis tu ncua ∼70- rau 85-ms-ntev, ∼90-Hz oscillations. Tshwj xeeb, cortical ripples thaum lub sij hawm NREM muaj qhov nruab nrab thiab SD (dhau qhov nruab nrab ntawm cov channel) zaus ntawm 89.1 ± 0.8 Hz, ceev ntawm 8.4 ± 2.7 min1, amplitude ntawm 5.1 ± 2.4 μV, thiab ntev ntawm 76.5 ± 10.1ms ib.

Thaum sawv ntxov, cortical ripples muaj zaus ntawm 89.5 ± 0.7 Hz, qhov ceev ntawm 5.8 ± 3.4 min1, amplitude ntawm 7.2 ± 3.9 μV, thiab lub sijhawm ntev ntawm 66.6 ± 7.2 ms (Daim duab B. ;n=273 channels). Hippocampal ripples thaum NREM muaj qhov nruab nrab thiab SD zaus ntawm 85.7 ± 2. 35}} ms thiab thaum sawv ntxov muaj zaus ntawm 88.2 ± 1.4 Hz, ceev ntawm 7.4 ± 5.5 min1, amplitude ntawm 18. ). Ib qho SD tsawg dua lossis sib npaug rau 2 Hz inripple zaus nyob rau hauv txhua qhov xwm txheej qhia tau hais tias qhov muaj peev xwm ntawm cov channel hauv zos thiab cov khoom siv hauv lub network underlie ib qho kev sib txuam resonantfrequency.

Cortical Ripples khub niam txiv thiab sib koom ua ke nyob thoob plaws thaj chaw.

Peb xav tias ob peb ripples (tshwm sim nyob rau hauv ± 500 ms ntawm ib leeg) thiab tshwj xeeb tshaj yog kev sib koom ua ke ntawm cov chaw cortical, uas yuav yog ib qho tseem ceeb rau kev sib koom ua ke ntawm cov ntaub ntawv dav dav. Peb pom tias cortical ripples nquag thiab muaj zog ob leeg thaum lub sij hawm ob NREM (n=4,487/4,550 tseem ceeb channel khub, randomization test, post-false discovery rate [FDR] P < 0.05) thiab waking (n=4 ,478/4,550), nruab nrab ntawm tag nrho cov cheeb tsam cortical sampled (Fig. 2A thiab Table 1), suav nrog nruab nrab ntawm hemispheres.

Qhov kev faib ua feem ntawm cortico-cortical channel khub tau sib txuas ua ke thaum lub sij hawm NREM (98.6%) tsis txawv ntawm qhov thaum sawv ntxov (98.4%; P=0.44, χ2=0.61, qib kev ywj pheej [ df]=1). Saib SIAppendix, Fig. S2A thiab B rau cov neeg mob ib leeg.

Critically, peb pom tias luv luv latency coupling ua rau cooccurrence (Ntau tshaj los yog sib npaug rau 25-ms overlap) ntawm no ∼70-ms-ntev ripples, nrog me ntsis tab sis ho muaj peev xwm siab dua thaum sawv ntxov tshaj NREM (Daim duab . 2C). Qhov feem pua ​​​​ntawm cov cortico-corticalchannel khub nrog qhov tseem ceeb ripple kev sib koom ua ke yog siab heev thiab ze li sib npaug thaum NREM (n=2,218/2,275, 97.5%)vs. waking (n=2, 225/2,275, 97.8%).

Peb kuj pom tias qhov tshwm sim ntawm qhov tshwm sim ntawm cortico-cortical ripples thoob plaws cov kab sib txuas ntawm NREM thiab waking (SI Appendix Fig. S3A; r=0.41, P=7} × 10180, qhov tseem ceeb ntawm r) . Nyob rau hauv tas li ntawd, yuav luag tag nrho cov cortico-cortical channel khub khub niam txiv thiab kev sib koom ua ke tshwm sim nyob rau hauv ob qho tib si NREM thiab waking).

Hippocampal thiab Cortical Ripples Ob khub thiab Co-tsim, tshwj xeeb tshaj yog thaum sawv, tab sis ntawm tus nqi qis dua CorticoCortical.

Raws li yav dhau los pom (8), ripples nyob rau hauv ntau hippocampocortical channel khub kuj tau ua ke zoo heev (Daim duab 2B thiab Table 1) thaum lub sij hawm ob qho tib si NREM (n=133/461) thiab waking (n =401/461), tab sis ntawm tus nqi qis dua li cortico-corticalpairs hauv ob lub xeev (NREM: P < 0.00001, χ2=2,832.0, df=1;waking: P < 0.00001, χ2=213.3, df=1). Tsis zoo li cortico-cortical khub, qhov kev faib ua feem ntawm hippocampo-cortical khub yog siab dua thaum sawv ntxov (87.0%) dua NREM (28.9%, P< 0.00001, χ2 = 319.6, df = 1). See SI Appendix, Fig. S2C, and D for individual patients. These findings of cortico-cortical and hippocampo-cortical couplings were maintained when only cortical and hippocampal channels that were free of interictal spikes at any time were analyzed (SI Appendix, Table 2).

Kev sib koom ua ke ntawm tib neeg ripples ntawm cortexand hippocampus tsis tshwm sim uas tau kawm ib sebut kuj yuav tsum tau tshwm sim muab lawv cov coupling.Qhov tseeb, peb pom muaj qhov sib txuam tseem ceeb ntawm ripples hauv 81.1% (n=374} /461) ntawm hippocampo-cortical site khub thaum sawv ntxov thiab 34.7% (n=160/461) thaum NREM. Higherhippocampo-cortical kev sib koom ua ke thaum sawv ntxov piv rau NREM yog qhov tseem ceeb (P < 0 00001, χ2=203.8, df=1). Tsis tas li ntawd, cov feem pua ​​​​ntawm hippocampo-cortical co-cuam tshuam tshwm sim (81.1% waking; 34.7% NREM) yog qhov qis dua rau cortico-cortical site khub (97.5% waking; 97.8% NREM) (NREM: P < 0.00001}, { },328.8, df=1; waking:P < 0.00001, χ2=1,250.1, df=1). Yog li, ripples hauv hippocampal thiab cortical qhov chaw ua ob peb thiab sib koom ua ke, tab sis ntawm tus nqi qis dua ntawm qhov chaw cortical.

Cortical Ripples Ua rau Hippocampal Ripples thaum Waking.

Qee cov qauv nco tau pom tias cov ntaub ntawv raug xa mus thaum sawv ntxov ntawm lub cortex mus rau hippocampus rau kev nco encoding.Thaum sawv ntxov, 22.4% (90/401) ntawm cov khub channel muaj qhov kev txiav txim tseem ceeb (Table 1; post-FDR P <0.05, ob-sidedbinomial xeem, xav tau tus nqi=0.05). Ntawm cov khoom tseem ceeb no, cortical ripples ua rau hippocampal ripples nyob rau hauv 84.4% (76/90). Thaum lub sij hawm NREM, 31.6% (42/133) ntawm hippocampo-corticalpairs uas tau sib txuas ua ke muaj qhov tseem ceeb sidednesspreference, qhov twg ib qho channel 's ripple' .

Thaum hippocampal ripples ua rau cortical ripples nyob rau hauv 66.7% (28/42) ntawm cov khub tseem ceeb no thaum lub sij hawm NREM, cov nyhuv no tau tsav los ntawm tus neeg mob loj (SI Appendix, Table 3), tsis zoo li cov nyhuv ntawm corticalripples ua rau hippocampal ripples thaum lub sij hawm sawv, uas yog consistent. Feem ntau ntawm cov neeg mob (SI Appendix, Table 3).Qhov kev nyiam tag nrho rau cortical ripples ua rau hippocampalripples thaum sawv ntxov piv rau NREM yog qhov tseem ceeb heev (P=4 × 109, χ2=34.5, df=1).

For more information:1950477648nn@gmail.com