In 2004, Francis Crick, one of the 20th centurys greatest scientific minds, died of colon cancer. Crick was best known for describing the structure of DNA in the 1950s with collaborator James Watson, but over the last couple of decades of his life his research focused on perhaps the biggest scientific question of them all: how does our brain generate what we consider to be consciousness?

The last paper Crick ever penned homed in on a small and still relatively mysterious brain region called the claustrum. Co-authored with Christof Koch, Crick was reportedly still editing the manuscript in hospital the day he died. Subsequently published in 2005, the paper presented a novel hypothesis - the claustrum may be key to our experience of consciousness, unifying and co-ordinating disparate brain areas to help generate our singular experience.

The claustrum is a thin, irregular, sheet-like neuronal structure hidden beneath the inner surface of the neocortex in the general region of the insula, wrote Crick and Koch in the landmark paper. Its function is enigmatic. Its anatomy is quite remarkable in that it receives input from almost all regions of cortex and projects back to almost all regions of cortex.

The extraordinarily unique way the claustrum connects different brain regions fascinated Crick. While some researchers had previously suggested the claustrum could potentially be the brains epicenter of consciousness, Crick and Koch presented a different analogy to describe the role of this mysterious brain region.

We think that a more appropriate analogy for the claustrum is that of a conductor coordinating a group of players in the orchestra, the various cortical regions, the pair wrote. Without the conductor, the players can still play but they fall increasingly out of synchrony with each other. The result is a cacophony of sounds.

A new study, published in the journal Current Biology, is describing in unprecedented detail how the claustrum communicates with other brain regions. The project, an international collaboration between researchers in Sweden and Singapore, somewhat backs up Cricks "consciousness conductor" hypothesis, revealing the claustrum is less like a singular hub for cortical inputs and more like a collection of specialized synaptic pathways connecting specific cortical regions.

We found that the synaptic connectivity between the cortex and claustrum is in fact organized into functional connectivity modules, much like the European route E4 highway or the underground system, says Gilad Silberberg, lead author on the study, from the Karolinska Institutet.

Another recent and even more focused study zoomed in on the claustrums role in coordinating slow-wave brain activity. A team from Japans RIKEN Center for Brain Science generated a transgenic mouse model in which they could artificially activate neurons in the claustrum through optogenetic light stimulation.

Yoshihiro Yoshihara

The research discovered slow-wave activity across a number of brain regions increased in tandem with neural firing in the claustrum. Slow-wave brain activity is most often linked to a key period of sleep associated with memory consolidation and synaptic homeostasis.

We think the claustrum plays a pivotal role in triggering the down states during slow-wave activity, through its widespread inputs to many cortical areas, says Yoshihiro Yoshihara, team leader on the new RIKEN research. The claustrum is a coordinator of global slow-wave activity, and it is so exciting that we are getting closer to linking specific brain connections and actions with the ultimate puzzle of consciousness.

So, if increased claustrum activity seems to orchestrate a kind of synchronized slowing down of brain activity across a number of different cortical regions, what happens when claustrum activity is suppressed?

One hypothesis has suggested dysfunctional claustrum activity could play a role in the subjective effects of psychedelic drugs. One of the fundamental neurophysiological characteristics of a psychedelic experience is widespread dysregulation of cortical activity. Brain networks that dont normally communicate will suddenly spark up connections under the influence of psilocybin or LSD. So a team from Johns Hopkins University set out to investigate exactly how psilocybin influences claustrum activity.

Due to the claustrums location in the brain its activity has traditionally been quite difficult to study in humans. However, a recently developed functional magnetic resonance imaging (fMRI) technique has afforded researchers a new and detailed way to measure claustrum activity. The Johns Hopkins study recruited 15 subjects to measure claustrum activity after either a placebo or a dose of psilocybin.

The study found psilocybin reduced claustrum neural activity between 15 and 30 percent. The overall reductions in claustrum activity also directly correlated with the subjective psychedelic effects of the drug.

More specifically, psilocybin seemed to significantly alter how the claustrum communicated with a number of brain regions fundamentally involved in attentional tasks and sensory processing. For example, under the influence of psilocybin, functional connectivity between the right claustrum and the auditory and default mode networks significantly decreased, while right claustrum connectivity with the fronto-parietal task control network increased.

Our findings move us one step closer to understanding mechanisms underlying how psilocybin works in the brain, says Frederick Barrett, one of the authors on the new study. This will hopefully enable us to better understand why its an effective therapy for certain psychiatric disorders, which might help us tailor therapies to help people more.

As Barrett suggests, this new insight into the effect psilocybin has on claustrum activity may shine a light on how this psychedelic drug generates its beneficial therapeutic effects. Psilocybin in particular has been found to be significantly useful in treating major depression and substance abuse disorders. The Johns Hopkins scientists hypothesize psilocybins action on the claustrum may play a key role in both the subjective effects of this psychedelic drug, and its beneficial therapeutic outcomes.

Further research is certainly necessary to verify this hypothesis, and the next step for the Johns Hopkins team will be to use this new claustrum imaging technique to investigate the brain region in subjects with a variety of psychiatric disorders. Fifteen years on from Francis Cricks passing his final work is still inspiring new research. The new wave of psychedelic science, in tandem with novel neuroimaging techniques, brings us closer and closer to understanding how our brains create consciousness.

The new study was published in the journal Neuroimage.

Source: Johns Hopkins Medicine

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