Awake Memory Consolidation Can Bias the Way New Information Is Perceived

Post by Flora Moujaes 

What's the science?

Our brains consist of an estimated 100 billion neurons, which are connected to each other by over 100 trillion synapses. Whenever you experience an event, a specific set of neurons and a pattern of connections is activated. Memories are thought to be stored in these patterns of connections. However, we still don’t fully understand the process through which representations of experiences are consolidated into long-term memory. This week in Trends in cognitive sciences, Tambini and Davachi review new evidence from recent human fMRI studies showing that memory consolidation occurs through reactivations that happen outside of conscious awareness during awake periods, and that memory consolidation can bias on-going cognition.

What do we already know? 

The infamous patient H.M. had his hippocampus and surrounding medial temporal lobe (MTL) surgically removed in 1953, in an attempt to cure his epilepsy. However, the surgery left him unable to form new memories. This indicates that while the hippocampus and MTL are vital for the formation of new memories, long-term memory involves additional storage in cortical networks outside the MTL. Studies across multiple species have since confirmed that the hippocampus is vital for acquiring new memories and that these memories can then be transformed across hippocampal-cortical networks for storage in long-term memory. This transformation is widely believed to involve repeated memory reactivation, both during sleep and ‘offline’ during awake periods.

What’s new? 

The authors propose that repeated memory reactivation in the hippocampus during awake periods is related to memory strengthening. This memory reactivation happens offline, outside of conscious awareness. While more restful states promote memory reactivation, studies have shown it can occur alongside cognitively intensive tasks. Memory reactivation is closely related to the salience of the initial event, as it’s more advantageous to strengthen memories that may provide a greater learning potential. Memory reactivation is also associated with long-term memory storage, as studies have shown reactivation promotes memory integration across hippocampal-cortical networks. What’s also 'new' is that these processes have been studied mostly in animals, however, in this review, the authors summarize evidence that similar mechanisms can be studied in humans using non-invasive measures like fMRI. 

The authors propose that spontaneous reactivation can shape the way in which we experience and interact with the world. For example, emotional arousal is known to increase memory, and so if an emotional memory is consolidated offline while a memory task is being performed, performance on the task might improve. However, it is important to note that the mechanisms underlying the reactivation of memories may be similar to the mechanisms underlying the retrieval of memories, and so future work is needed to help disentangle human reactivation that supports ‘online’ cognition versus consolidation.

What's the bottom line? 

Human neuroimaging studies have shown that memory consolidation through reactivation occurs during awake periods. Tambini and Davachi emphasise memory consolidation is a complex process as: (1) it is related to memory strengthening, (2) it can be used to track the salience of information and thus whether information will get stored in long-term memory, and (3) it can bias the ways in which new information is encountered and processed. Overall, this review furthers our understanding of the process through which experiences are consolidated into long-term memory and highlights many new and exciting avenues for future research. 

Tambini and Davachi. Awake Reactivation of Prior Experiences Consolidates Memories and Biases Cognition. Trends in cognitive sciences (2019). Access the original scientific publication here.

Working Together Changes the Way We Process Others’ Actions

Post by Anastasia Sares

What's the science?

Some time ago, just before the turn of the new millennium, scientists discovered that when one monkey watched another monkey performing an action, like reaching for an object, neurons fired in the brain as if it was performing the action itself. These neurons, often called ‘mirror neurons,’ are the subject of much debate, with some researchers claiming that they underlie things as complex as human empathy, while others remain more skeptical.

In general, humans are great imitators. It takes little effort for us to repeat someone else’s actions, and much more effort to withhold that response (as any child who has played “Simon Says” will tell you). However, we also seem to be very good at performing separate, complementary actions while working towards a goal. Think of lumberjacks sawing a tree trunk, or musicians performing a duet. What supports these uniquely human activities is what Sacheli and colleagues call a “Dyadic Motor Plan,” and this week in Cerebral Cortex, they aimed to find the brain regions involved. The study was performed at the University of Milano-Bicocca, Milan, Italy, in collaboration with the IRCCS Istituto Ortopedico Galeazzi, Milan, Italy.

How did they do it?

Participants completed a music-like task with interactive and non-interactive conditions. With a “partner” (seen via video displayed on a monitor) they took turns performing one of two actions to a wooden cube (either touching the top with the index finger or pinching the sides of the cube). Each action was paired with a musical tone (G or C). The participant always saw the partner’s action and heard the resulting musical note before performing their own action. Each sequence was four actions long — #1 partner, #2 participant, #3 partner, and #4 participant. A small colored square indicating how the participant should respond during each trial was presented at the end of action #1 (after the participant had seen their partner’s first action). In the non-interactive condition, the square’s color indicated a previously-learned sequence of notes that the participant should perform, regardless of what their partner did. In the interactive condition, the color indicated a previously-learned melody that they were expected to continue along with their video partner, cooperating to produce all the necessary notes. In addition to manipulating interactivity, the authors had participants perform some trials in which their action (tap or pinch) matched their partner’s previous action and some in which the actions did not match.  Humans can experience visual interference when they see a partner perform an action different than the one they are about to perform. In other words, it takes more effort to process and execute a non-matching action. The interactive task condition was built so that the partner’s actions could be predicted and were part of a shared goal (i.e., playing a melody together), which should lead to a “dyadic motor plan,” and reduce visual interference.

What did they find?

The authors measured response times as well as brain activity. In the non-interactive condition, the reaction times were longer for non-matching actions: evidence of visual interference. In the interactive condition, however, there was no difference in reaction time between matching and non-matching actions. The authors also found a region of the frontal lobe (the premotor cortex) where the pattern of brain activity differed between conditions. This region was selectively active during the interactive condition regardless of whether the participant’s actions matched their partners, indicating that no differences in brain activity reflected simple imitation of a partner’s action. However, there was an interaction between condition (interactive versus non-interactive) and time during the four-part sequence; the region exhibited greater activity during action #1 versus later in the sequence, before the colored square had been presented. Because the colored square in the interactive condition indicated which goal (melody) participants were working towards with their partner, this brain activity likely reflects the participants' attempt to predict the partner’s next action and musical note.  

The authors interpreted this to mean that when we do something together with a partner, our brain tries to predict our partner's contribution to the shared goal to see whether it meets expectations. They also emphasized that this region of the brain is situated in the frontoparietal network, which is involved with predictions like anticipating a partner’s goals.

What's the impact?

This research shows that pursuing common goals with another member of our species has an impact on how our brains process and react to visual information. Mimicking another’s actions may be helpful in some cases, but the reflex to imitate takes a back seat when we have more information and a better sense of context.

Sacheli et al. How Task Interactivity Shapes Action Observation. Cerebral Cortex (2019). Access the original scientific publication here.

Synaptic Transcription Is Driven by Circadian Rhythm While Protein Expression Is Driven by Sleep in the Mouse Forebrain

Post by Amanda McFarlan 

What's the science?

The sleep-wake cycle is involved in regulating the size of synapses and brain protein expression, so, it is not surprising that it may also be involved in regulating local synaptic transcription and protein expression. In support of this, it has been shown previously that approximately 6% of transcription in the forebrain fluctuates throughout the day, which is thought to be mediated by the sleep-wake cycle. This week in Science, Noya and colleagues investigated the role of sleep and circadian rhythms on the rhythmicity of synaptic transcript and protein expression in the mouse forebrain and found a remarkably different picture than that seen in transcripts in the cell as a whole. 

How did they do it?

The authors collected tissue from the mouse forebrain every 4 hours for one 24-hour period to assess daily rhythms in messenger RNA (mRNA) transcripts and protein expression. They used biochemical homogenization and fractionation to purify synaptoneurosomes (isolated synaptic terminals) and identify mRNAs that were present in these synapses. Then, using isolated synaptoneurosomes, they performed mass spectrometry-based proteomics to identify patterns of protein expression in the synaptic proteome (i.e. all proteins expressed in the synapse) and the total forebrain. Next, the authors investigated the role of the sleep-wake cycle in regulating transcription of synaptic mRNA and protein expression by collecting forebrain tissue every 4 hours for one 24-hour period from mice that were sleep-deprived for four hours prior to sacrifice. They assessed the effect of high sleep pressure (i.e. sleep deprivation/greater amplitude of delta oscillations) on the daily rhythmicity of mRNA and protein expression in forebrain tissue. 

What did they find?

The authors found that 67% of synaptic mRNA transcripts had a rhythmic pattern of expression, with 93% of these transcripts exclusively showing rhythmic patterns of expression in synaptoneurosomes. This suggests that the oscillatory or cyclic pattern of synaptic mRNA expression may be controlled by post-transcriptional mechanisms. They also found that 11.7% of synaptic proteins and 17.2% of proteins in the forebrain showed rhythmic patterns of expression. Next, the authors determined that the rhythmic expression of synaptic mRNA formed two distinct clusters separating mRNA transcripts expressed in the day from those expressed at night. Furthermore, they found that the mRNA transcripts expressed in the day participated in biological processes including synapse organization and transmission, while mRNA transcripts expressed at night participated in biological processes such as metabolism, cell proliferation and development. These distinct patterns of expression and biological roles were also observed in the synaptic proteome, with 75% of rhythmically expressed synaptic proteins showing concomitance with their mRNA counterpart. Finally, the authors determined that the rhythmicity of synaptic mRNA transcript expression was mostly preserved with high sleep pressure, but rhythmicity in protein expression could no longer be detected with high sleep pressure, suggesting that synaptic mRNA expression may be controlled by a molecular clock while protein expression may be gated by sleep-wake pressure.

What's the impact?

This is the first study to show that synaptic mRNA transcripts in the mouse forebrain have a highly rhythmic expression that is controlled post-transcriptionally. The rhythmic expression of mRNA transcripts and their related proteins was shown to be important for distinct biological processes associated with either day or night. These findings provide insight into the mechanisms by which synaptic mRNA and protein expression are regulated in the mouse forebrain. 

Noya et al. The forebrain synaptic transcriptome is organized by clocks but its proteome is driven by sleep (2019). Access the original scientific publication here.