Inside Out, the Disney-Pixar movie released in 2015, was an interesting way to draw people’s attention to how emotions and memory work. Focused on what went on in a young girl’s mind, it gave us an insight into formation and segregation of memories as well as the key emotions that make one react to incidents in daily life. Although not depicting accurate scientific facts, it did do a great job in conveying the message that all emotions are vital in helping us get through our lives.

Memories comprise of experiences, or are related to specific events, are termed as “episodic memories” . Deficits in episodic, working or emotional memory performance often contribute to neuropsychological disorders such as Posttraumatic Stress Disorder or Schizophrenia.

But, what are the genetic and neuronal bases of memory? How do people react differently to emotional events and what are the consequences?

Understanding the factors and processes underlying memory is vital for developing medication and treating disorders. Researchers at the Divisions of Cognitive and Molecular Neuroscience at the Department of Psychology, University of Basel are working on getting insights into some of these questions and have carried out a number of interesting studies. They aim at investigating inter individual differences in memory performance and relate these to inter individual differences in EEG, (f)MRI and genetics (DNA variations, expression, methylation).

Episodic memory is tightly linked to the activity of a particular brain region, the hippocampus. The famous case of H.M, who had his hippocampi removed in order to stop the severe seizures he was suffering from, but later was never able to form new episodic memories again, shows the importance of this region.

Episodic memory impairment is also associated with age-related neurodegenerative conditions, such as Alzheimer disease. To find out whether specific groups of genes were involved in normal memory processes as well as development of conditions like Alzheimer’s disease, the researchers began a multicenter collaborative study in 2008 and assessed healthy, young adults as well as elderly people without dementia for episodic memory performance ( doi: 10.1001/jamapsychiatry.2015.1309).

We met postdoctoral researchers Dr. David Coynel and Dr. Matthias Fastenrath to know more about the studies and get an insight into neuroimaging.

The brain is a complex structure and several factors are responsible for each function. Though some brain regions may be more involved in certain activities, yet all of the regions may be communicating with each other differently. This network connectivity also influences brain functions and mental health.

Figure 1: Investigating brain connectivity using diffusion MRI. Image: Dr. David Coynel

The image above (Figure 1) illustrates how brain connectivity is investigated using diffusion MRI. The first image represents the region from which we want to investigate the connections (the little purple dot), in the visual cortex. The second image represents the connections of this region, spanning local connections in other areas of the occipital cortex, connections to homologous regions in the other hemisphere, and long-range connections to the temporal lobe. The colors correspond to the local orientation of the fibers: red=left-right; blue=up-down; green=front-back.

In the study investigating episodic memory, all participants underwent a picture delayed free recall task, in which they were asked to rate several pictures based on emotional arousal and valence (pleasant to unpleasant) and later had to recall the images seen. Interestingly, the ratings of such pictures have been found to be different in the case of people suffering from disorders like schizophrenia, borderline personality disorder etc.

In a subset of the sample, the brain activity was also measured using functional magnetic resonance imaging (fMRI ) during the task. The brain activations can be seen below in Figure 2.

Figure 2: Brain activity measured during the encoding of pictures. Image: Dr.Matthias Fastenrath

The image depicts the contrasting brain activity measured during the encoding of pictures. Hippocampal activity was seen in the case of pictures that were successfully recalled while not in cases when pictures were not recalled.

Gene set enrichment analysis carried out showed consistent associations between calcium signaling pathway genes and human episodic memory performance.

The research team identified a set of 26 genes that were significantly enriched in the different groups of young and elderly healthy people.

This suggests that genes involved in calcium signaling are also related to episodic memory performance through adulthood and gives us a deeper insight into memory processes.

This gene set was also seen to be enriched in a large group of people with sporadic Alzheimer’s Disease. However, the calcium signaling genes possibly also play a role in other neurodegenerative disorders and we cannot presume they have an exclusive role in the development of Alzheimer’s Disease.

Additionally, the research group investigated working memory processes and emotional arousal in people. It is known that emotional events are better remembered than neutral ones. But, emotional arousal is dysregulated in many psychiatric disorders, and is considered to be one of the main symptoms leading to diagnosis of mood and anxiety disorders.

NTRK2 is a gene known to be related to psychiatric disorders. The research team wanted to investigate whether it also had an influence on arousal ratings in young, healthy individuals, and whether it was related to white matter properties of the brain as well. Participants of this study ( published in 2016 at doi:10.1038/tp.2016.20) were first asked to rate pictures depicting positive,negative and neutral emotions and these ratings were recorded. Using diffusion MRI, white matter properties in the brain were investigated. Genetic association analysis showed that the gene NTRK2 indeed plays a role in inter-individual differences in emotional arousal for positive pictures, and in white matter properties.

This has been a step further into understanding processes underlying emotion arousal and shall pave the way for further research in the field.