The Default Network in the Human Brain Is Associated with Loneliness

Post by Amanda McFarlan

What's the science?

Humans have evolved to rely on socialization and, therefore, so has the human brain. What happens to the brain when an individual’s social expectations are not met? Since socialization is such a quintessential part of being human, it is thought that loneliness may result in distinct changes in the brain. Research has shown that loneliness is associated with reduced activity in reward areas of the brain as well as a greater vigilance and detection of negative social information. Still, the study of loneliness in higher-order brain regions that make up the “social brain” is lacking. This week in Nature Communications, Spreng and colleagues used a multimodal approach to investigate whether loneliness is associated with structural and functional changes in the brain.

How did they do it?

The authors used data collected for the UK Biobank initiative to investigate whether differences in brain structure and connectivity between brain regions exist between individuals who self-reported as being lonely and those that did not. In the first set of analyses, the authors used the Bayesian hierarchical approach to examine whether loneliness is associated with variations in gray matter volume, for both regional (localized) brain structure and large-scale brain networks. Next, they investigated how resting-state functional connectivity (which identifies brain regions with correlated activity, termed functional networks) relates to loneliness. Finally, the authors explored whether loneliness was associated with the integrity of white matter tracts in the brain. The authors also examined whether biological sex was associated with loneliness for all three neuroimaging approaches.

What did they find?

The authors found that gray matter volume for brain structures including the posterior superior temporal sulcus, the left temporoparietal junction, the left fusiform gyrus, the right inferior temporal gyrus, right posterior parietal lobe, and the right dorsal anterior cingulate cortex were positively associated with loneliness (high volume associated with high loneliness). Conversely, volume in several regions such as the left dorsal anterior cingulate cortex, the dorsolateral prefrontal cortex, the right central operculum, the right inferior parietal lobule, the left retrosplenial cortex, and the inferior visual cortex was negatively associated with loneliness. At the network level, the authors showed that loneliness was most strongly related to variations in gray matter volume in the default network (a network of brain regions that are typically more active when a person is not paying attention to the external world, i.e. daydreaming).

Next, the authors determined that individuals who self-reported as being lonely had greater resting-state functional connectivity between brain regions in the same network. This link between connectivity pattern and loneliness was expressed more strongly in men compared to women. Finally, the authors found that the structural integrity of white matter tracts originating from the hippocampus was greater in lonely individuals. This anatomical relationship between white matter tracts and loneliness was more prominent in men compared to women.

What’s the impact?

This study shows that loneliness is associated with distinct changes in gray matter volume, white matter tract integrity, and functional connectivity within brain regions. Notably, the authors identified the default network as the network most strongly associated with the neural expression of loneliness. Altogether, the link between loneliness and the default network may reflect increased mental simulation of inner social events in the absence of real-world social interaction.

Spreng et al. The default network of the brain is associated with perceived social isolation. Nature Communications (2020). Access the original scientific publication here.

The “Learning Layer” of the Cortex

Post by Anastasia Sares

What's the science?

The hippocampus is known to play a central role in learning and memory. The brain areas immediately surrounding the hippocampus, like the perirhinal cortex, are also involved. However, mature memories don't rely on the hippocampus —they are stored in a distributed way throughout the cortex (outer layer of the brain). The exact locations and mechanisms for memory storage in the cortex have been a long-standing mystery since the early 20th century. Nevertheless, it is generally assumed that auditory memories will be stored predominantly in the auditory cortex, or a movement memory will be stored in the motor cortex, and so on. The exact location of memories in the cortex is difficult to pin down.

This week in Science, Doron and colleagues demonstrate a new way of locating memory in the cortex. Instead of treating the cortex like a 2D map, they looked at the brain in 3D space, like a forest of trees, and showed that memories are actually stored in a specific sublayer of the cortex, layer 1, atop the forest. They were able to demonstrate that messages crucial for long-term memory formation are sent from the hippocampus to layer 1.

How did they do it?

The authors first traced the paths of neurons from the perirhinal cortex, showing that neurons starting here signal to other parts of the cortex, in layer 1. Next, they taught mice and rats to respond to a small electrical stimulation applied directly to their brain, specifically, the somatosensory cortex (the part of the cortex that processes touch information from the body). When they licked a small apparatus right after receiving stimulation, the animals were rewarded. With this design, the authors could pinpoint exactly where in the cortex the long-term memory would be made: it would be in the same place as the stimulation. In some animals, the authors disrupted the connection between perirhinal cells and layer 1 of the somatosensory cortex, either during or after training on the task. Other animals' connections were left intact as a control.

What did they find?

Compared to the controls, animals with disrupted connections between the perirhinal cortex and layer 1 of somatosensory cortex showed impaired learning, but only if the disruption happened during the learning phase. Expert animals were not affected by this disruption, since their memory for the task had already been formed. For all of the animals, the neurons in the perirhinal cortex fired in response to the stimulus when the animal responded correctly. However, activity in the somatosensory cortex was less robust in the animals whose connections were disrupted. The authors reasoned that the real targets for these signals from perirhinal cells were the large pyramidal neurons in layer 5 of the cortex because their dendrites stretch all the way up to layer 1, where they should capture the signal from the perirhinal cells. In the mice and rats that learned normally, these layer 5 cells changed their firing pattern after a correct response, similar to the perirhinal cells. In the animals with a disrupted layer 1 connection, layer 5 cells were much less responsive.

What's the impact?

This study highlights the central role of layer 1 of the cortex in storing memory. Human memory is extremely complex, and we are growing in our understanding of it every year. Unlocking the mechanisms behind memory formation will aid in the fight against human diseases like Alzheimer's, and may also inform the way we make artificial neural networks, helping machines to learn in a more biological way.

Doron et al.Perirhinal input to neocortical layer 1 controls learning. Science (2020). Access the original scientific publication here.

Dopamine Rewards Information-Seeking

Post by Elisa Guma

What's the science?

Humans have a desire to gain knowledge from their environment, often exhibited via information-seeking behaviours. Despite this being a central human behaviour, little is known about the biological mechanisms that control it. Previous studies have shown that information-seeking activates many of the brain’s reward pathways and dopamine-rich areas. This week in eLife, Vellani and colleagues seek to investigate the impact of dopamine, a neurotransmitter central to motivation and reward, on information-seeking behaviours.

How did they do it?

The authors performed a double-blind pharmacological intervention on 248 participants, who were recruited to perform an information-seeking task; one half of the group received L-DOPA to boost their dopamine levels, and the other half received a placebo. L-DOPA (or levodopa) is a precursor of dopamine which is converted to dopamine in the brain. It is typically used as a treatment for Parkinson’s disease symptoms.

Forty minutes following administration, participants completed a behavioural task consisting of four blocks (50 trials each) in which they had to invest in two of five possible stocks in a simulated stock market. On each trial, participants observed changes in the stock market and were instructed to bid for a chance to either know or remain ignorant about the value of their portfolio. Additionally, they had to decide how much they were willing to pay to secure their choice. The authors performed statistical modeling (linear mixed models) to investigate the effects of L-DOPA administration on information seeking behaviours, and whether or not the valence of the expectation influenced the participants’ decision to seek or avoid information. 

What did they find?

The authors observed that L-DOPA administration did not affect general information-seeking as there were no differences between groups in the number of trials in which participants chose to pay for or avoid information, or not to pay at all. Despite there being no differences in general information seeking, the authors found that information-seeking behaviour was modulated by the expected market outcome: participants were more likely to pay for information when the market was going up, in the hopes of receiving positive information, and more likely to pay to avoid information when the market was going down, in order to avoid negative news.

Interestingly, they found that the L-DOPA group was less affected by the expected valence of the information (whether it was a win or a loss). Specifically, participants in the placebo group desired to learn more information when the market was up vs. down, whereas the L-DOPA group’s desire to seek information was not affected by valence (i.e. they wanted to gain information regardless of whether it might be a win or a loss). Furthermore, when investigating the degree of market change, the L-DOPA group was willing to pay more for information the greater the gains or losses, whereas the placebo group was only willing to pay more for information the greater the gains, but not the losses. Finally, they found that the effects of valence observed in the L-DOPA group were not affected by the participant’s expectations about their outcomes (based on whether they believed their stocks to have increased or decreased).

What's the impact?

This study shows that dopamine plays a critical role in motivating information-seeking, even if it does not directly lead to a reward. By increasing dopamine levels via L-DOPA administration, participants sought out information both about potential wins and losses, contrary to the placebo group who was mostly interested in information about potential wins. Future studies may investigate whether patients with dopamine deficiencies exhibit abnormal patterns of information-seeking.

Vellani et al. A selective effect of dopamine on information-seeking. eLife (2020). Access to the original publication can be found here.