PDF: http://www.pnas.org/content/ea...06/04/1408296111.full.pdf+html
Significance
How does the brain recover consciousness after significant perturbations such as anesthesia? The simplest answer is that as the anesthetic washes out, the brain follows a steady and monotonic path toward consciousness. We show that this simple intuition is incorrect. We varied the anesthetic concentration to parametrically control the magnitude of perturbation to brain dynamics while analyzing the characteristics of neuronal activity during recovery of consciousness. We find that, en route to consciousness, the brain passes through several discrete activity states. Although transitions between certain of these activity states occur spontaneously, transitions between others are not observed. Thus, the network formed by these state transitions gives rise to an ordered sequence of states that mediates recovery of consciousness.
Abstract
It is not clear how, after a large perturbation, the brain explores the vast space of potential neuronal activity states to recover those compatible with consciousness. Here, we analyze recovery from pharmacologically induced coma to show that neuronal activity en route to consciousness is confined to a low-dimensional subspace. In this subspace, neuronal activity forms discrete metastable states persistent on the scale of minutes. The network of transitions that links these metastable states is structured such that some states form hubs that connect groups of otherwise disconnected states. Although many paths through the network are possible, to ultimately enter the activity state compatible with consciousness, the brain must first pass through these hubs in an orderly fashion. This organization of metastable states, along with dramatic dimensionality reduction, significantly simplifies the task of sampling the parameter space to recover the state consistent with wakefulness on a physiologically relevant timescale.
Three lines of evidence indicate that these clusters represent
attractor states of the thalamocortical dynamics: (i) The tran-
sitions between states are abrupt (e.g., Fig. S3), and the paucity
of points between the peaks of the probability distribution (Fig.
3B group data, Fig. S5 individual experiments) suggests that the
system does not spend a significant amount of time between the
densely occupied states. (ii) Dwell times within each state may
last up to several minutes (Fig. S7A). (iii) Fluctuations die down
when the system arrives into the clusters and increase between
clusters (Fig. S8). The decrease in the amplitude of fluctuations
associated with the arrival into densely populated regions of the
parameter space suggests stabilization of neuronal activity.
Interesantno istrazivanje.
Ako je tacno, izgleda da mozak ima specificnu "boot" sekvencu koja se izvrsava svaki dan prilikom prelaza iz nesvesnog stanja (spavanje) u svesno i ta sekvenca nije "random walk" kroz prostor mogucih parametara vec uredjena (autori koriste analogiju sa proteinima gde protein, takodje, prolazi kroz sekvencu diskretnih stanja tokom procesa "savijanja").
Ta tranzicija, ili "bootstrap" proces se sastoji iz nekolicine razlicitih stanja neuralne mreze koja su stabilna na nivou minuta. Povratak svesti zahteva uredjen sekvencijalni prolaz kroz specificna stanja. Period izmedju stanja je vrlo kratak. Takodje, analizom aktivnosti se neka od stanja identifikuju kao "habovi", zato sto kroz ta stanja mreza mora da prodje na putu do "bootovanja" svesti.
Tranzicija izmedju stanja je pracenja sa gradualnim opadanjem "bursting" aktivnosti koja je specificna za nesvesna stanja (delta i spori ritam). U pocetku procesa prolaza kroz sekvencu su prisutne fluktuacije sa periodicnim skokovima "burst" aktivnosti u periodima prolaza izmedju stanja, dok unutar samih stanja burst aktivnost opada. U toku "boot" sekvence se smanjuje kolicina "burst" aktivnosti sto verovatno ukazuje da je sam proces prolaska kroz stanja povezan sa stabilizovanjem zeljene neuralne aktivnosti koja je neophodna za uspostavljanje svesti. To je vrlo tezak problem koji CNS ima svaki dan, posto ogromna vecina mogucih aktivnosti u mrezi nisu kompatibilna sa svescu i mali lokalizovani problemi (aktivnost razlicita od zeljene) mogu izazvati globalni gubitak svesti kao u, recimo epilepticnim napadima.
Zasto je ovo uopste bitno, osim kao pomoc na putu za razumevanje funkcionisanja centralnog nervnog sistema?
Postoji jos jedna stvar: trenutni monitori dubine anestezije su bazirani na pracenju parametara koji nisu uvek garancija da pacijent nije svestan u toku operacije. "Svesnost u toku anestezije" je vrlo ozbiljan problem koji se desava u toku odredjenog procenta operacija i cesto je pracen traumama zato sto pacijent koji je parcijalno svestan cesto nije u stanju da komunicira sa lekarima koji ga operisu.
Zbog toga je bolje poznavanje obrasca neuralne aktivnosti u CNS-u koji vodi ka povratku svesti je vrlo bitan cilj istrazivanja, kako bi se mogli dizajnirati bolji monitori dubine anestezije.
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