Serotonin is Involved in Persistence

What's the science?

Serotonin is a neurochemical in the brain important for feelings of happiness. A current theory of serotonin function suggests that serotonin is involved in patience and inhibiting actions. Currently, we do not understand whether this involves patience in the sense of behavioral inhibition (i.e. not acting) or patience in the form continuing to act (i.e. persistence).This week in Nature Communications, Lottem and colleagues show that serotonin release in the brain is responsible for persistent behavior in mice.

How did they do it?

They used optogenetics to activate serotonin neurons (in the dorsal raphe nucleus) in the brains of mice during a foraging experiment. During foraging, animals explore an area for food or water, and at some point, they must give up and move on to a different area. This means the animal requires active patience (persistence) when exhausting their search in a given area. Water-restricted mice were required to “nose poke” to obtain a water reward while foraging an area. The probability of obtaining water at each reward station was reduced with each nose poke. The authors used a higher number of nose pokes as a measure of persistence, while a reduced number of nose pokes meant inhibition of behavior. They also used video tracking to measure how long it took for mice to switch to another area.

What did they find?

Mice exhibited optimal foraging behavior, meaning they optimized the trade-off between time spent searching an area for water and leaving to find reward in another area. The mice that received serotonin neuron stimulation performed a greater number of nose pokes compared to mice who did not receive stimulation. They also took longer to leave an area (but not to move in general) suggesting they were more persistent. The authors modelled this leaving behavior using a proportional hazards model to show that serotonin neuron stimulation reduced the probability of a mouse leaving an area.

What's the impact?

This is the first study to show that serotonin neuron firing is responsible for active persistent behavior. Previously, it was hypothesized that serotonin was involved in patience through inhibiting behavior. We now know that serotonin neuron firing is involved in persistence. This extends what we know about the role of serotonin in behavior.

Reach out to study author Dr. Zachary F. Mainen on Twitter @zmainen and @mainenlab

E. Lottem et al., Activation of serotonin neurons promotes active persistence in a probabilistic foraging task. Nature Communications (2018). Access the original scientific publication here.

Synchrony Between Brains is Associated with Pain Relief During Social Touch

What's the science?

Skin-to-skin touch has been shown to reduce pain - for example, in a baby undergoing a medical procedure or in a person experiencing experimental pain. How this pain relief happens is unclear. When a person experiences pain, some of the same brain regions that activate are also active when expressing empathy for another person in pain. This week in PNAS, Goldstein and colleagues explored brain-to-brain synchrony during social touch to understand how it is related to pain perception.  

How did they do it?

They measured brain activity using electroencephalography (EEG) in two individuals (one man and one woman) simultaneously, 1) while the individuals were sitting together - not touching 2) sitting together - holding hands and 3) sitting in separate rooms. Then they repeated these scenarios as the woman was subjected to mild heat pain on her arm. The aim was to understand whether brain-to-brain synchrony was enhanced while one experiences pain and touch, and whether this was related to pain relief and their partner’s empathy. Neural activity in frontal and central brain regions was measured at the ‘alpha-mu’ frequency (8-12Hz). This frequency band has been shown to be involved in inter-brain interaction (when brain activity synchronizes in social interaction).

What did they find?

When partners held hands, the male partner was more empathetic, meaning he was more likely to accurately guess what level of pain his partner reported experiencing. Women reported lower pain overall when holding hands, indicating that touch reduced pain. While experiencing both pain and touch, there was a greater degree of inter-brain synchrony between partners than during any other experimental condition - predominantly between sensory brain regions in women and the right hemisphere of the brain in their male partners. In the touch + pain condition, pain reduction in women during touch was correlated with strong synchrony between the sensory brain regions and frontal brain regions in their partner.

Artistic rendering of Figure 2: Inter-brain coupling.

What's the impact?

This is the first study to assess brain communication between different individuals during pain to understand the brain mechanisms underlying touch-related pain relief during social interaction. These findings suggest that certain patterns of inter-brain communication are related to pain relief by social touch. 

Reach out to study authors Dr. Pavel Goldstein and Dr. Guillaume Dumas on Twitter: @pavelgoldstein and @introspection

P. Goldstein et al., Brain-to-brain coupling during handholding is associated with pain reduction. PNAS (2018). Access the original scientific publication here.

Genetic Risk Score for Alzheimer’s Disease Predicts Early Cognitive Impairment

What's the science?

Alzheimer’s disease pathology in the brain occurs years before symptoms show up. Identifying younger adults who may be genetically at risk is crucial so that therapies can be given early on in the disease. This week in Molecular Psychiatry, Logue and colleagues demonstrate how a genetic risk score can help to predict cognitive problems.

How did they do it?

They analyzed genetic data for 1176 participants in their 50’s, some of whom were diagnosed with mild cognitive impairment, a condition preceding Alzheimer’s disease involving memory and thinking problems. Using genetic polymorphisms (changes in the DNA code) that are known to increase risk for Alzheimer’s disease, they created a score for each individual based on the number of risk alleles they had and the likelihood that they would increase risk. They then tested whether this score was associated with increased odds of having mild cognitive impairment, after accounting for other factors that can increase Alzheimer’s risk: age, depression, hypertension, diabetes and head trauma. They also tested a second score after removing the effect of APOE (a gene known to drastically increase risk) to ensure that the risk score was not driven by APOE alone.

What did they find?

A genetic risk score was associated with higher chances of having mild cognitive impairment (impaired memory specifically). The risk score was able to predict who had mild cognitive impairment, even after excluding the effects of APOE. Diabetes was associated with a greater risk of mild cognitive impairment (specifically non-memory related cognitive impairment). This risk score was better able to predict mild cognitive impairment than age, other risk factors and APOE alone.

What's the impact?

This is the first study to show that an Alzheimer’s disease risk score can predict mild cognitive impairment in younger adults in their 50’s. Previously, most studies attempted to predict cognitive problems in older adults, however, by this time Alzheimer’s pathology in the brain can be too advanced for therapies to work. Genetic risk scores may be able to predict cognitive problems at an earlier stage, so that therapies can be used to slow Alzheimer’s disease.

M Logue et al., Use of an Alzheimer’s disease polygenic risk score to identify mild cognitive impairment in adults in their 50s. Molecular Psychiatry (2018). Access the original scientific publication here.