depression memory

Unexpectedly big wins improve two kinds of memory

May 6, 2019

Science Daily/Brown University

Researchers have discovered that instances in which outcomes are better than expected -- finding an unexpectedly good parking spot, for example, or spotting a $20 bill on the sidewalk -- improves memories of specific events. This is in addition to the long-established role that unexpectedly good outcomes have in influencing what are called integrated memories.


Remembering where you parked your car this morning is an example of specific episodic memory, while remembering good places to park in general is an example of an integrated memory.


"Our new finding is that incidental, irrelevant details from specific events -- whether the tree I parked beside was a spruce or a maple -- are also strengthened by unexpectedly good outcomes," said Matt Nassar, an assistant professor of neuroscience at Brown University and the study's corresponding author. "This finding has potential ramifications for how people with depression remember things, which is a focus of our future research. We'd like to be able to develop potential therapies for patients, but we're not there yet."


Since reward-prediction error -- the formal name for that instances in which outcomes are better than expected -- involves the release of the neurotransmitter dopamine in a specific brain area, the findings unveil new implications for treating depression, which has been linked to imbalances in key neurotransmitters including serotonin, norepinephrine and dopamine.


This means that someone with depression may not encode positive memories as effectively as an individual without depression, said Nassar, who is affiliated with Brown's Carney Institute for Brain Science. And when someone with depression looks back on past events, they might remember the negative events better than the positive events, which has the potential to spur a negative feedback loop, he said.


For study co-author Daniel Dillon, a researcher at McLean Hospital and Harvard Medical School, exploring the clinical connection between depression and memory is the primary research focus. The findings were published on Monday, May 6, in the journal Nature Human Behaviour.


The research team's experiment comprised both a learning phase and a memory phase. For each round during the learning task, participants were shown a point value between 1 and 100, shown an image of a living or inanimate object, given the option to gamble on whether they would win the "coin-flip" by playing or passing, and then informed if they won or lost. If the participants lost the round, they lost 10 points; if they won the round, they received the previously conveyed points for the round. At the end of 160 rounds, participants' point totals were converted into a small amount of money, typically less than $5, Nassar said.


After the learning phase, participants were tested on their memory for the specific images they saw. The researchers found that participants were much better at remembering the specific image from rounds where they had a high likelihood of winning compared to high-value rounds or rounds they chose not to play. They were not informed that the specific image would be important. They were only told that the general category of the object (living or inanimate) would determine the probability they would win.


The experiment, which was partly the senior thesis project of Anthony Jang, an undergraduate who earned his bachelor's degree from Brown in 2015, included more than 250 participants recruited through Amazon Mechanical Turk, a platform for crowdsourced work that serves as a convenient option for recruiting many participants for experiments.


While some of the participants paid close attention to the value of each round and the probability of winning for each category, the results of other participants were far more random, Nassar said. The people who paid more attention during the gambling rounds did better during the memory portion of the experiment, which he was able to incorporate into his computational model of the participants' memories.


The researchers also found that participants were equally good at remembering specific images from high value rounds they won when they were tested 5 minutes after the learning task as when they were tested 24 hours later, after a period of memory consolidation. That finding that surprised Nassar.


"There's a really nice study from 2010 by Ingrid Bethus and colleagues where they clearly show in rodents that dopamine doesn't help memory performance shortly after the learning experience, but it has a huge effect at 24 hours," Nassar said. "We spent quite a bit of time trying to rectify our results with that study because they don't line up. The tasks were quite different, given the two species involved. In the future, we hope to get a task that is more comparable to figure out the source of the timing differences."


In addition to attempting to determine the source of the memory consolidation differences, members of the research team are planning to rerun the experiment with participants with depression to see if they exhibit any memory differences.


Also, Nassar will continue his work determining the neural circuits involved in connecting reward-prediction error to episodic memories as well as untangling the interaction between the episodic memory system and integrated memory system.

Three types of depression identified

October 31, 2018

Science Daily/Okinawa Institute of Science and Technology (OIST) Graduate University

Scientists have used brain imaging to identify three sub-types of depression -- including one that is unresponsive to commonly prescribed serotonin boosting drugs.


According to the World Health Organization, nearly 300 million people worldwide suffer from depression and these rates are on the rise. Yet, doctors and scientists have a poor understanding of what causes this debilitating condition and for some who experience it, medicines don't help.


Scientists from the Neural Computational Unit at the Okinawa Institute of Science and Technology Graduate University (OIST), in collaboration with their colleagues at Nara Institute of Science and Technology and clinicians at Hiroshima University, have for the first time identified three sub-types of depression. They found that one out of these sub-types seems to be untreatable by Selective Serotonin Reuptake Inhibitors (SSRIs), the most commonly prescribed medicines for the condition. The study was published in the journal Scientific Reports.


Serotonin is a neurotransmitter that influences our moods, interactions with other people, sleep patterns and memory. SSRIs are thought to take effect by boosting the levels of serotonin in the brain. However, these drugs do not have the same effect on everyone, and in some people, depression does not improve even after taking them. "It has always been speculated that different types of depression exist, and they influence the effectiveness of the drug. But there has been no consensus," says Prof. Kenji Doya.


For the study, the scientists collected clinical, biological, and life history data from 134 individuals -- half of whom were newly diagnosed with depression and the other half who had no depression diagnosis- using questionnaires and blood tests. Participants were asked about their sleep patterns, whether or not they had stressful issues, or other mental health conditions.


Researchers also scanned participants' brains using magnetic resonance imaging (MRI) to map brain activity patterns in different regions. The technique they used allowed them to examine 78 regions covering the entire brain, to identify how its activities in different regions are correlated. "This is the first study to identify depression sub-types from life history and MRI data," says Prof. Doya.


With over 3000 measurable features, including whether or not participants had experienced trauma, the scientists were faced with the dilemma of finding a way to analyze such a large data set accurately. "The major challenge in this study was to develop a statistical tool that could extract relevant information for clustering similar subjects together," says Dr. Tomoki Tokuda, a statistician and the lead author of the study. He therefore designed a novel statistical method that would help detect multiple ways of data clustering and the features responsible for it. Using this method, the researchers identified a group of closely-placed data clusters, which consisted of measurable features essential for accessing mental health of an individual. Three out of the five data clusters were found to represent different sub-types of depression.


The three distinct sub-types of depression were characterized by two main factors: functional connectivity patterns synchronized between different regions of the brain and childhood trauma experience. They found that the brain's functional connectivity in regions that involved the angular gyrus -- a brain region associated with processing language and numbers, spatial cognition, attention, and other aspects of cognition -- played a large role in determining whether SSRIs were effective in treating depression.


Patients with increased functional connectivity between the brain's different regions who had also experienced childhood trauma had a sub-type of depression that is unresponsive to treatment by SSRIs drugs, the researchers found. On the other hand, the other two subtypes -- where the participants' brains did not show increased connectivity among its different regions or where participants had not experienced childhood trauma -- tended to respond positively to treatments using SSRIs drugs.


This study not only identifies sub-types of depression for the first time, but also identifies some underlying factors and points to the need to explore new treatment techniques. "It provides scientists studying neurobiological aspects of depression a promising direction in which to pursue their research," says Prof. Doya. In time, he and his research team hope that these results will help psychiatrists and therapists improve diagnoses and treat their patients more effectively.

Depression linked to memory problems and brain aging

May 9, 2018

Science Daily/American Academy of Neurology

Depression in older adults may be linked to memory problems, according to new research. The study also showed that older people with greater symptoms of depression may have structural differences in the brain compared to people without symptoms.


"Since symptoms of depression can be treated, it may be possible that treatment may also reduce thinking and memory problems," said study author Adina Zeki Al Hazzouri, PhD, MS, of the University of Miami Miller School of Medicine in Florida. "With as many as 25 percent of older adults experiencing symptoms of depression, it's important to better understand the relationship between depression and memory problems."


The study involved 1,111 people who were all stroke-free with an average age of 71. The majority were Caribbean Hispanic. At the beginning of the study, all had brain scans, a psychological exam and assessments for memory and thinking skills. Their memory and thinking skills were tested again an average of five years later.


At the start of the study, 22 percent of participants had greater symptoms of depression. This was defined as a score of 16 or higher on a test with a range of 0-60, which is considered at risk for clinical depression. For the test, participants reported how often in the past week they agreed with statements such as "I was bothered by things that usually don't bother me" and "I did not feel like eating." Researchers found after adjusting for age, race, anti-depressive medications, and other variables, greater symptoms of depression were linked to worse episodic memory. Scores on tests were lower by 0.21 of a standard deviation compared to those without greater symptoms of depression. Episodic memory is a person's ability to remember specific experiences and events.


Researchers also found those with greater symptoms of depression had differences in the brain including smaller brain volume as well as a 55 percent greater chance of small vascular lesions in the brain.


Researchers found no evidence of a relationship between greater symptoms of depression and changes in thinking skills over five years.


"Small vascular lesions in the brain are markers of small vessel disease, a condition in which the walls in the small blood vessels are damaged," said Zeki Al Hazzouri. "Our research suggests that depression and brain aging may occur simultaneously, and greater symptoms of depression may affect brain health through small vessel disease."


Zeki Al Hazzouri noted that the study provides information about depression and memory and thinking skills, especially among people who identified as Hispanic, who have been insufficiently studied in previous studies on the topic, even though they can be at increased risk of dementia in late life.


Limitations of the study include that participants had to be healthy enough to have an MRI, so they may have been healthier than the general population. Also, the study was over a five-year period, which may not have been long enough to capture meaningful changes in thinking and memory abilities over time.

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