Periodic Reporting for period 4 - Set-to-change (Set to change: early life factors restricting and promoting neurocognitive plasticity through life)
Período documentado: 2023-04-01 hasta 2024-12-31
Neurodevelopmental origins of functional variation through the lifespan are increasingly acknowledged. Evidence converges on early life factors being important for both normal individual differences in adult brain and cognition and risk of developing neurodegenerative disease in old age. As much evidence points to factors from early life stages being important, we need to investigate to what extent these are genetic and environmental, and how cognitive functioning can be impacted at different ages. This is critical, as possibly stable individual differences in how our brains adapt to the environment lay at the heart of understanding lifespan changes in cognition.
The objective is to test whether and how early life environmental factors and genetic makeup interact to regulate neurocognitive plasticity through the lifespan.
We will test differences in neurocognitive plasticity by longitudinal training of younger and older adults (18-80 years) of identical and different genetic makeup, namely mono- and dizygotic twins, with varying degrees of prenatal environmental variance, as indexed by their extent of discordance in birth weight. We will employ a novel and ecologically valid memory intervention, utilizing navigation with true locomotion, retrospective and prospective memory, in virtual reality (VR).
Two of the main questions we want to investigate is:
1. Are we neurodevelopmentally set to change through life in certain ways?
2. If so, which early life factors are important to adult and old age brain and cognition, and to what extent are they environmental or genetic in origin?
The objective is to test whether and how early life environmental factors and genetic makeup interact to regulate neurocognitive plasticity through the lifespan.
We will test differences in neurocognitive plasticity by longitudinal training of younger and older adults (18-80 years) of identical and different genetic makeup, namely mono- and dizygotic twins, with varying degrees of prenatal environmental variance, as indexed by their extent of discordance in birth weight. We will employ a novel and ecologically valid memory intervention, utilizing navigation with true locomotion, retrospective and prospective memory, in virtual reality (VR).
Two of the main questions we want to investigate is:
1. Are we neurodevelopmentally set to change through life in certain ways?
2. If so, which early life factors are important to adult and old age brain and cognition, and to what extent are they environmental or genetic in origin?
Twins have been assessed with brain MRI, cognitive, health and epigenetic measures. A total of 227 individuals have participated in assessments at either 1,2,3 or 4 time points.The total number of assessments are at the moment above 600 with time point 4 participants still being recruited. 22 training intervention groups including a total 118 participants took part in the training intervention. The training sessions have amounted to over 590 hours of in-lab virtual reality cogntive training and 970 hours of laptop based training at home.
One of the project’s most innovative methods is PlastiCity, an immersive virtual reality (VR)-based navigation training program. This intervention combines spatial navigation tasks with physical movement on a stationary bike, directly targeting hippocampal-dependent memory functions, which are known to decline with age. VR technology enables the introduction of novel tasks and stimuli while collecting fine-grained behavioral data, including movement patterns, position tracking, and head and eye movements in real-time. This setup also trains complex cognitive processes, such as prospective memory—the ability to remember to carry out future actions, a skill difficult to train using traditional lab-based methods.
Participants were instructed to complete specific tasks while navigating virtual routes, enhancing prospective memory, executive functioning, and monitoring abilities. The intervention allowed us to gather detailed behavioral data, from precise measures like reaction times and movement patterns to broader performance metrics such as the number of targets reached or deviations from the shortest path. A key strength of the VR setup is its reliance on true locomotion via stationary bikes, making the experience more ecologically valid.
Expanding on PlastiCity, we developed MiniCity, a laptop-based spatial memory and planning task designed for broader accessibility. This virtual navigation game challenges participants to identify landmarks within a city divided into distinct thematic zones, allowing researchers to assess spatial cognition without requiring VR equipment.
Finally, Ursa Mirror refines motor learning analysis using the Mirror Tracing Task (MTT), providing high-resolution measures of motor control and learning, particularly relevant for aging and neurodegenerative research.
A key finding, as demonstrated by Walhovd et al. (2024), is the link between lower BW and reduced cortical volume. A reduction of 600g (approximately one standard deviation) was associated with a 1.1–1.6% decrease in cortical volume. Even among genetically identical MZ twins, differences in BW predicted variations in brain structure and function, emphasizing the significant role of non-genetic early-life factors. It was also shown that differences in birth weight appeared to have a stable effect across the lifespan.
In a recent presentation, as a part of a peer-reviewed conference proceeding, Walhovd et al. (2024) showed preliminary results indicating that training with PlastiCity led to measurable increases in hippocampal volume. Furthermore, differences in birth weight among MZ twins showed that the higher BW twin tended to train more and achieve higher levels of cognitive performance.
Moreover, we find that changes in functional connectivity with training, and with a higher training time, the lower birth weight twin becomes in terms of brain structural parameters more similar to the higher birth weight twin with training. These preliminary results have been presented at the AAIC- Alzheimer's Association International Conference (2024)and the HBM-Human Brain Mapping conferences summer 2023, and the findings attracted much interest.
One of the project’s most innovative methods is PlastiCity, an immersive virtual reality (VR)-based navigation training program. This intervention combines spatial navigation tasks with physical movement on a stationary bike, directly targeting hippocampal-dependent memory functions, which are known to decline with age. VR technology enables the introduction of novel tasks and stimuli while collecting fine-grained behavioral data, including movement patterns, position tracking, and head and eye movements in real-time. This setup also trains complex cognitive processes, such as prospective memory—the ability to remember to carry out future actions, a skill difficult to train using traditional lab-based methods.
Participants were instructed to complete specific tasks while navigating virtual routes, enhancing prospective memory, executive functioning, and monitoring abilities. The intervention allowed us to gather detailed behavioral data, from precise measures like reaction times and movement patterns to broader performance metrics such as the number of targets reached or deviations from the shortest path. A key strength of the VR setup is its reliance on true locomotion via stationary bikes, making the experience more ecologically valid.
Expanding on PlastiCity, we developed MiniCity, a laptop-based spatial memory and planning task designed for broader accessibility. This virtual navigation game challenges participants to identify landmarks within a city divided into distinct thematic zones, allowing researchers to assess spatial cognition without requiring VR equipment.
Finally, Ursa Mirror refines motor learning analysis using the Mirror Tracing Task (MTT), providing high-resolution measures of motor control and learning, particularly relevant for aging and neurodegenerative research.
A key finding, as demonstrated by Walhovd et al. (2024), is the link between lower BW and reduced cortical volume. A reduction of 600g (approximately one standard deviation) was associated with a 1.1–1.6% decrease in cortical volume. Even among genetically identical MZ twins, differences in BW predicted variations in brain structure and function, emphasizing the significant role of non-genetic early-life factors. It was also shown that differences in birth weight appeared to have a stable effect across the lifespan.
In a recent presentation, as a part of a peer-reviewed conference proceeding, Walhovd et al. (2024) showed preliminary results indicating that training with PlastiCity led to measurable increases in hippocampal volume. Furthermore, differences in birth weight among MZ twins showed that the higher BW twin tended to train more and achieve higher levels of cognitive performance.
Moreover, we find that changes in functional connectivity with training, and with a higher training time, the lower birth weight twin becomes in terms of brain structural parameters more similar to the higher birth weight twin with training. These preliminary results have been presented at the AAIC- Alzheimer's Association International Conference (2024)and the HBM-Human Brain Mapping conferences summer 2023, and the findings attracted much interest.
While the project was significantly delayed by the pandemic, we were still able to disseminate preliminary findings. The PI, Walhovd, was asked to give a series of keynote lectures and invited presentations, including at the International Neuropsychological Society Conference in Sand Diego, and at the Dallas Aging and Cognition Conference in 2023. She was then invited to write a perspective paper in Trends in Cognitive Science (Walhovd et al., 2023), where she with colleagues summarized the main perspectives of the project research, synthesizing the findings of many cross-disciplinary papers in the field. This paper has already been well cited (https://pubmed.ncbi.nlm.nih.gov/?linkname=pubmed_pubmed_citedin&from_uid=37563042(se abrirá en una nueva ventana)) and constitutes a reference for students interested in early life factors in a life span perspective. In the paper, it is shown how we should be careful regarding the timing and quantity of modifiable influences on brain and cognition. It is shown how individual differences in the level of brain and cognition, many of which present already at birth and early in development, appear stable, larger, and more pervasive than differences in change across the lifespan. In line with the project framework developed, it is argued that incorporating early-life factors, including genetics, and investigating both level and change will reduce the risk of ascribing undue importance and causality to proximate factors in adulthood and older age. This has implications for both mechanistic understanding and prevention.
There is currently a growing acceptance of the idea and evidence that influences on early brain development affect the brain and its function throughout life. I think there is evidence of this, as seen by the increasing number of papers published in the field, the citations our papers received from others, my invitations to give lectures and keynote speeches on the topic, and the specific recognition of our work in invited presentations, as listed below.
There is currently a growing acceptance of the idea and evidence that influences on early brain development affect the brain and its function throughout life. I think there is evidence of this, as seen by the increasing number of papers published in the field, the citations our papers received from others, my invitations to give lectures and keynote speeches on the topic, and the specific recognition of our work in invited presentations, as listed below.