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.  

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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.

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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.

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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. 

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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.

X-Chromosome Insufficiency Alters the Structure and Function of the Human Visual Cortex

Post by Lincoln Tracy

What's the science?

Turner syndrome is a genetic condition in females caused by the absence of a part of, or an entire, X chromosome. Women with Turner syndrome have specific cognitive deficits relating to the ability to perceive spatial relationships between objects and the ability to select and monitor goal-related behaviors. Previous research suggests that women and girls with Turner syndrome have structural changes in the parieto-occipital cortex (the part of the brain responsible for the integration of sensory information and the processing of visual information) when compared to typically developing controls. Specifically, females with Turner syndrome are reported to have a smaller volume of parieto-occipital cortex with a thicker surface. Despite knowing that these structural changes exist, it is not known whether abnormal processing of visual information occurs in females with Turner syndrome. This week in The Journal of Neuroscience, Green and colleagues used functional magnetic resonance imaging (fMRI) and population receptive field (pRF) mapping to investigate receptive field processing in Turner syndrome.

How did they do it?

The authors recruited 24 girls (aged 7-14 years) with Turner syndrome and 28 typically developing girls of the same age to act as controls. All 52 participants had an MRI scan where they watched a screen that showed a flickering black and white checkerboard pattern in either expanding rings or rotating wedges to obtain and assess data for the pRFs. pRFs can be used to generate topographic maps of the visual field (i.e. the total area an individual can see) using representations of the polar angle (the angle from the horizontal axis) and eccentricity (the distance from fixation). Data from the MRI scans were used to determine the volume, surface area, and cortical thickness of the early visual areas V1-V3. Visual field coverage (the locations within a visual field that evoke a response from voxels within a brain map) in these areas were also drawn from the MRI data. Outside of the MRI scanner the girls completed the Picture Puzzles test, one of the tests from the NEPSY-II battery, which tests visuospatial processing. The relationship between performance on the Picture Puzzles test and pRF properties was compared.

What did they find?

First, the authors found that girls with Turner syndrome and typically developing girls showed a similar organization of polar angle and eccentricity maps. These maps were then used to define visual field maps for V1-V3. Using these maps, the authors then showed that while there were no differences in total brain volume between girls with Turner syndrome and typically developing girls, the cortical volume and surface area of the V1-V3 visual field maps were smaller in girls with Turner syndrome. There were no differences in V1-V3 cortical thickness between girls with Turner syndrome and typically developing girls. Second, they found that despite Turner syndrome and typically developing participants having similar pRF size for V1-V3, participants with Turner syndrome had less pRF eccentricity in visual areas V1-V3 (meaning that their pRF was closer to the center of their gaze). Third, visual field coverage was determined by comparing how the pRFs from V1-V3 fit together in the visual field. There were no differences between participants with Turner syndrome and typically developing girls in the visual field coverage of V1-V3, nor were there differences in the polar angle and eccentricity maps. Fourth, they found that participants with Turner syndrome performed worse in the Picture Puzzles task compared to the typically developing group. Performance in the Picture Puzzles task was found to be negatively correlated with pRF size and eccentricity in girls with Turner syndrome. There was no correlation between performance in the Picture Puzzles task and the cortical volume of V1-V3 in either the participants with Turner syndrome or typically developing girls.

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What's the impact?

The authors have demonstrated that Turner syndrome may negatively affect the functional properties of brain regions responsible for visual processing, which may in turn influence behavior. The findings of this study may serve as a novel approach for investigating how other regions of the brain are affected by Turner syndrome. Furthermore, the authors provide a target for interventions to improve the visuospatial deficits observed in Turner syndrome. Taken together, these results suggest a fundamental change in our understanding of how variations in sex chromosome pairings affect visuospatial development in humans.

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Green et al. X-Chromosome Insufficiency Alters Receptive Fields across the Human Early Visual Cortex. Journal of Neuroscience (2019).Access the original scientific publication here.