Research Spotlights June 2020

Research Spotlights June 2020

More diversity in daily experiences may increase happiness and well-being

Experiential diversity has been shown to promote well-being in animal models, but little is known if this also be true for humans. In a recent publication, researchers funded by the NCI, NIA, National Science Foundation, and other funders, investigated the relationship between the diversity of personal daily experiences, well-being, and neural pathways in the brain. Previous research has associated the hippocampus and striatum with processing neural signals of place, novelty, and reward. Roaming entropy (RE) indexes the variability in an individual’s physical location over the course of a day and is a quantitative, location-derived metric of experiential diversity. In rodents, increased levels of RE reproduce the key neural and cognitive effects of environmental enrichment. In this study, the researchers examined whether daily RE might serve as an ecologically valid measure of experiential diversity in humans and if daily variations in RE might relate to fluctuations in positive affect.

Researchers used geolocation (GPS) tracking to investigate the effects of location diversity on emotional well-being in three cohorts of participants (n=132, 90 females; age=18-31 years) in New York and Miami. Prior to the start of GPS tracking, participants completed questionnaires to assess emotional state (depression (Beck Depression Inventory (BDI), anxiety (State–Trait Anxiety Inventory (STAI-T)) and to have a GPS application installed on their phones for passive data collection. GPS data was collected continuously for 3–4 months; during this period, participants were prompted to complete a mood questionnaire via their mobile phones. Assessments of mood and sleep were delivered at random times during the day, every other day, via text messaging. At the end of the tracking period, participants completed a second session in the laboratory, during which they completed the BDI and STAI-T. To determine if the link between exploration and positive emotion was associated with brain activity in the hippocampus and striatum, approximately half of the participants underwent MRI scans.

The results showed that on days that a person had more variability in their physical location they reported having more positive emotions such as: "happy," "excited," "strong," "relaxed," and/or "attentive." This association was stronger for individuals who had greater functional coupling of the hippocampus and striatum. These results link diversity in real-world daily experiences to fluctuations in positive affect and identify a hippocampal–striatal circuit associated with this bidirectional relationship.

In summary, these results show a reciprocal link between experiencing new and varied daily activities while exploring our physical environments and our subjective sense of well-being, and positive emotional states. This suggests that a person may feel happier when they have more variety in their daily routines such as going to new places and engaging in a wide variety of activities. Alternatively, the opposite may be true, where positive emotional states may encourage people to seek out these rewarding experiences more often. Taken together with previous findings, this study highlights the beneficial consequences of environmental enrichment across species, demonstrating a connection between real-world exposure to novel and diverse experiences and increases in positive emotions. Mitigation of SARS-CoV-2 transmission (e.g., shelter-in place, physical distancing) may limit experiential diversity, and the findings from this study suggest that this may be associated with reduced positive affect and well-being; however, the researchers note that even small changes that introduce greater variability into the physical or mental routine may potentially yield similar beneficial effects.

Heller AS, Shi TC, Ezie CEC, Reneau TR, Baez LM, Gibbons CJ, Hartley CA. 2020. Association between real-world experiential diversity and positive affect relates to hippocampal–striatal functional connectivity. Nat Neurosci.

False memories may be the result of the brain updating poorly formed memories with incorrect information

Trauma and memory go hand-in-hand toward understanding the potential impact of a traumatic event. Researchers investigated this poorly understood relationship in a recent publication supported by the NIMH and other funders, using a well-established mouse model of fear. They conducted a variety of experiments to better understand the neural processes that are involved in learning about the post-trauma response. The researchers show how memories may be subject to an extinction/updating/learning process(es) or mechanism(s) that can either correct and, at the same time, severely distort the original context memories. This research sheds a more textured insight into the role of context learning, memory formation/consolidation, and fear associated with trauma–providing a new understanding why simple 'extinction' methods may not be sufficient in dealing with fear associated with trauma.

The researchers used a paradigm where they varied the intervening condition between the shock (PSI=Placement Shock Interval) and the fear test (whether the mice acted fearfully or not) to better understand the behavioral and biological mechanisms involved in fear associated with trauma. In sum, they created variation context embedding (learning) and manipulated various conditions, including a new intervening context, time in the new intervening context, re-exposure, updating (new trauma in new context), and biological interventions which impact memory.

First, they demonstrated that learning context (defined by specific cage conditions) is important in associating the trauma (foot shock) to fear (freezing or not moving for once every 4 seconds). The second experiment demonstrated that the extinction of fear is possible, regardless of the level of context learning, if the mice are exposed to the same context with no shock - called an 'extinction session'. They then tested if "re-exposure" (variation in the timing associated with extinction) was associated with a fear response. This showed that 'extinction' is time dependent. They then changed the context post-conditioning to see if they can change or 'update' the association of context encoding and fear. This experiment used a 3-min 'updating' session (exposure to another context with shocks). The researchers then investigated if re-exposure to another context of varying durations could support more learning and erroneous updating and thus cause memory distortion. This last set of experiments demonstrated it is possible to confuse the ability to generalize the fear to other contexts.

In short, the researchers found that fear memories acquired using short intervals of shock and that change in context overgeneralized and resisted long term extinction. On the other hand, re-exposure to the conditioned context changed these deficits whereas exposure to marginally different contexts distorted memory. Both these updating effects required reconsolidation, not new learning. Finally, using simulations, the researchers demonstrated that these findings occur due to the variable nature of context learning.

While these studies were conducted in a mouse model, they have potential therapeutic implications for the etiology and treatment of anxiety disorders, such as PTSD. These findings suggest that updating in the therapy context might be facilitated to promote reconsolidation, because reconsolidation stabilizes updating. This work contrasts with recent ideas of attenuating fear by pharmacologically blocking reconsolidation or extinguishing memories.

Zinn R, Leake J, Krasne FB, Corbit LH, Fanselow MS, Vissel B. 2020. Maladaptive Properties of Context-Impoverished Memories, Current Biology,

Personal accounts of childhood abuse are more correlated with psychopathology than with official records

Childhood abuse and neglect has wide ranging impacts, including the health and happiness of future generations. Recent research supported by the NIMH, NICHD, NIDA, NIAAA, NIA, National Institute of Justice, and other funders assessed if objective measures of childhood abuse and neglect, defined by court records, is a better predictor of adult mental health relative to subjective measures (self-reported childhood abuse). This study defined childhood abuse as physical abuse, sexual abuse or neglect. Furthermore, the researchers defined adult mental health on two dimensions: (1) internalizing disorders, such as depression, dysthymia, generalized anxiety or PTSD and (2) externalizing disorders such as antisocial personality, alcohol abuse and/or dependence, or drug abuse and/or dependence.

The data used were from participants (n = 908) who were identified as victims of child abuse or neglect based on official records from juvenile (family) and adult criminal courts in a metropolitan area in the Midwest United States during 1967–1971. A comparison group was drawn of children without official records of abuse or neglect matched based on age, sex, race/ethnicity and approximate family social class at the time of the child maltreatment (n = 667). Approximately half of the participants were female (48.7%) and about two-thirds white (62.9%). During a follow-up assessment between 1989 and 1995 (mean age 28.7years), 1,196 study participants underwent a 2 hour in-person interview, which included assessment of retrospective reports of childhood physical abuse, sexual abuse and neglect as well as assessment of current and lifetime psychopathology.

The sample was divided into: (1) adult participants who were identified as victims of child maltreatment by virtue of official records but did not retrospectively recall the experience (objective measure); (2) adult participants who were identified as victims of child maltreatment by virtue of official records and also retrospectively recalled the experience (objective and subjective measures); and (3) adult participants who retrospectively recalled being maltreated in childhood but were not identified as victims of child maltreatment by virtue of official records (subjective measure).

The researchers found that even for severe cases of childhood maltreatment identified through court records, the association of the risk of psychopathology with objective indicators of abuse was minimal compared to the association of subjective reports. In contrast, risk of psychopathology linked to subjective reports of childhood maltreatment was high, whether or not the reports were consistent with objective indicators. There are some potential limitations noted by the researchers. For instance, the stronger association of subjective versus objective measures of childhood maltreatment with psychopathology may be due to misclassification. This potentially may occur because official court records of childhood maltreatment are highly specific but not very sensitive, so likely do not capture all cases of maltreatment in the population. Additionally, it is possible that stronger association of subjective versus objective measures of childhood maltreatment with psychopathology could be an artifact of a treatment effect in the objectively measured group.

These findings have important implications for (1) increasing the understanding and defining the mechanisms that explain how child maltreatment affects mental health, (2) the value of subjective data and, (3) how interventions may need to account for the experience of the subject, even if there are no official objective data available.

Danese A, Widom CS. 2020. Objective and Subjective Experiences of Child Maltreatment and Their Relationships with Psychopathology. Nat Hum Behav. doi: 10.1038/s41562-020-0880-3

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