A New Method for Assessing Stroke Recovery

Post by Anastasia Sares

What's the science?

Stroke is a serious brain injury caused by the blockage or bursting of blood vessels that normally carry oxygen to the brain. This leads to the death of some neurons, which affects the ability of the brain to function. For example, many stroke patients have movement and speech-related difficulties. However, the brain does have the ability to “bounce back” somewhat from a stroke, reconfiguring itself so that lost functions are regained. Doctors aren’t able to fully predict how much an individual will recover, as recovery depends on a number of factors. This week in Brain, Tscherpel and colleagues demonstrate how a combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) can be used to reveal a patient’s potential for motor recovery.

How did they do it?

Transcranial magnetic stimulation, or TMS, involves stimulating the brain by using quick magnetic pulses applied to the scalp. The magnetic pulse interferes with the electrical signaling of the neurons, causing some neurons to fire while inhibiting others. Electroencephalography, or EEG, is a technique to measure the electrical signals coming from the brain. By combining TMS and EEG, we can deliver magnetic pulses to a brain area (the motor cortex, in this case) and also measure how the brain responds to that stimulation. The authors used this technique on a group of stroke patients with different levels of severity and compared them with healthy volunteers of the same age range. They evaluated them within the first two weeks of their stroke and followed up about 3 months afterward in order to track their recovery.

What did they find?

The healthy volunteers with no stroke showed “a sequence of positive and negative deflections” in response to the TMS stimulation, much like ripples. In contrast, some of the stroke patients showed fewer ripples, with the most extreme cases having only one single larger peak of activity. Features of the electrical response were correlated with the patients’ severity at the first visit and also with recovery at the next visit (note that recovery did not depend on the initial severity of the stroke). By looking at the patients’ brain structure, the authors also determined that these abnormalities in the electrical response were related to deep brain structures and white matter, not the neurons in the motor cortex. This indicates that recovery may depend on white matter connections between different regions. 

What's the impact?

Doctors have existing tools that can measure the severity of a stroke (motor-evoked potentials, for example), and predict recovery to some extent. However, these tools cannot fully predict recovery, especially for those with severe strokes. TMS and EEG are less expensive than other brain imaging techniques like MRI or PET, so this technique warrants further investigation for tracking stroke recovery in a clinical setting.

Tscherpel et al. Brain responsivity provides an individual readout for motor recovery after stroke. Brain (2020). Access the original scientific publication here.

Brain Synchronization During Inter-Group Hostility

Post by D. Chloe Chung

What's the science?

When we belong to a certain group of people who share similar thoughts or goals with us, we feel safe and work together to accomplish things as a group that we could have not achieved on our own. Despite this benefit, such group mentality and behavior can also lead to negative situations as it can reduce our sense of individuality, prompting us to act in a riskier way, and amplifying hostility towards opponent groups. Previous studies have shown that neural activity of specific brain areas can be synchronized across people who experience collective thinking and group behavior, but this idea has not been tested in the context of group-level hostility. This week in Nature Neuroscience, Yang and colleagues used a non-invasive imaging technique to investigate the neural mechanism underlying inter-group hostility.

How did they do it?

The authors recruited 546 male participants at the age of 18 to 30 and randomly divided them into 182 three-person groups. Two groups were matched to have 24 rounds of competition, where one group was assigned to be the “attacker group” that can aggress the opposite “defender group”. Each participant was given a hypothetical budget from which one could contribute a portion to the team’s ability to defeat the opponent team (“fighting capacity”). If the attacker group had a larger sum of fighting capacity, they could claim the remaining budget of the defender group. However, if the defender group had a larger or equal sum of fighting capacity, both groups could keep their remaining budget. Importantly, if the groups were selected to engage in the in-group bonding exercise, participants wore the same-color team vest (black or white, based on what each person chose during the survey prior to competition) and discussed shared preferences within the group. On the contrary, if the groups were selected to be in the no-bonding control group, they did not wear team vests and discussed neutral topics. During the competition, participants underwent functional near-infrared spectroscopy (fNIRS) to measure individual brain activity in two regions that are important for decision-making: the right dorsolateral prefrontal cortex (rDLPFC) and right temporoparietal junction (rTPJ).

What did they find?

The authors found that defender groups made more contributions towards their fighting capacity than attacker groups. Also, participants who underwent the in-group bonding exercise sacrificed more for the group by making larger contributions and displayed more coordinated behaviors with the same group members. The authors observed that in-group bonding decreased neural activity in the DLPFC, the brain region known to be involved in the inhibition of impulses. Conversely, in-group bonding increased functional connectivity between the rDLPFC and the rTPJ, a brain region that becomes activated during cooperation. These data suggest that an in-bonding exercise can modulate neural activity, resulting in disinhibition and higher risk-taking for the group’s collective goal. Interestingly, the authors found that neural activities in both the rDLPFC and the rTPJ were more synchronized in the in-group bonding condition, specifically in the attacker group. When rDLPFC activity was more synchronized within the group, it was also more likely that the attackers would make a larger contribution to fighting capacity, indicating that neural synchronization has a meaningful link to how people express hostility in a group.

What’s the impact?

The authors utilized functional neuroimaging to reveal the neural mechanisms that underlie inter-group conflicts, providing further evidence for neural synchronization as an important mechanism in inter-group hostility. Their findings suggest that group-level hostility, which can be enhanced by in-group bonding, may be mediated by collectively decreased risk aversion among group members. During this modern era where conflicts between groups with various values and ideologies are not uncommon, this study sheds important light on what happens in our brains when we become hostile towards others.

Yang et al. Within-group synchronization in the prefrontal cortex associates with intergroup conflict (2020). Access the original scientific publication here.

The Dentate Gyrus Discriminates Learned Sensory Information

Post by Deborah Joye

What's the science?

To help us navigate an unpredictable world, our brain continuously learns about the environment and integrates important information into a cognitive map. But how does our brain learn about important stimuli and incorporate them into a cognitive map of the environment? One role of the hippocampus is learning about non-spatial stimuli such as sounds and smells, but we don’t know exactly how learning new associations changes that information in the hippocampus. In general, evidence suggests that the cortex sends generalized sensory representations to the hippocampus. The hippocampus takes that general representation and enhances distinctions between important and unimportant sensory memories. This process helps us use previously learned information to safely and productively engage with our environment (like, “that smells like a rotten egg, so it might make you sick”). This week in Neuron, Woods, and colleagues demonstrate that specialized cells in the hippocampus create an internal representation of particular odors that predicts behavioral ability to differentiate smells.

How did they do it?

To test how cells in the hippocampus represent olfactory stimuli, the authors used two-photon microscopy to monitor cellular activation (measured by increases in calcium) in awake mice. Mice were exposed to various odors as the authors studied cellular activity in dentate gyrus granule cells of the hippocampus. The authors also studied cellular activity in lateral entorhinal cortex cells, one of the primary input regions into the hippocampus. To investigate whether the lateral entorhinal cortex is the main input of olfactory information into the dentate gyrus, the authors blocked cellular communication between these two regions using a form of tetanus toxin and imaged cellular activity in each region during odor exposure and behavioral tasks.

To test the extent to which dentate gyrus granule cells and lateral entorhinal cortex cells change their responses with learning, the authors trained mice on both fear and reward-based learning tasks and recorded activity in cells from each region before and after conditioning. In the fear-learning task, mice were first allowed to explore three contexts with distinct ambient odors. Mice were then trained to associate one odor with a mild foot shock (creating a fear association) and then were later tested with that same odor to determine how fearfully the mouse responded when exposed to that smell by measuring freezing behavior. In the reward-learning task, mice were trained to associate an odor with a sucrose reward and the authors measured this learned association by quantifying appetitive behavior (in this case, licking before the reward).

What did they find?

The authors found that dentate gyrus granule cells can represent odors based on how the population of cells fire, and that they require input from the lateral entorhinal cortex to do so. Mice with blocked communication between the lateral entorhinal cortex and the dentate gyrus did not show cellular activity in the dentate gyrus granule cells that predicted odor discrimination. The authors also found that the ability for dentate gyrus granule cells to accurately classify odors correlated with the mouse’s ability to behaviorally discriminate between odors. Mice that had the lowest smell decoder accuracy predicted by dentate gyrus cell firing were the worst at behaviorally discriminating between similar odors. Similarly, mice that had the highest smell decoder accuracy amongst dentate gyrus cells were the best at discriminating between similar smells. Finally, the authors found that in response to both fear and reward training, dentate gyrus granule cells change their responses to stimuli to set apart mental representations of the conditioned odor relative to unconditioned odors. Specifically, dentate gyrus cells began to respond more to the conditioned odor versus the unconditioned ones.

What's the impact?

This study uses olfaction as a novel way to study memory formation in the hippocampus. The authors expand on previous work investigating upstream regions in the odor recognition circuit but are the first to demonstrate how dentate gyrus cells change an external odor stimulus into an internal representation that can be stored, acted upon, and modified by learning. These data potentially identify a location in the cortex-hippocampal circuit where information is modified into a behaviorally relevant format. This work has implications for the study of memory formation in the hippocampus in health and disease because the loss of smell is an early risk factor for neurodegenerative diseases such as Alzheimer’s disease, and the earliest aggregation of brain-damaging plaques happens specifically in the lateral entorhinal cortex, which this study highlights as an important region in odor discrimination.

Woods et al., The Dentate Gyrus Classifies Cortical Representations of Learned Stimuli, Neuron (2020). Access the original scientific publication here.