NEI R01 EY031226 – Mediators and Moderators of Perceptual Learning
This project addresses fundamental issue of specificity and generality of training in the context of Perceptual Learning (PL). PL broadly encompasses the set of mechanisms through which experience with the environment gives rise to changes in perceptual processing. The potential broader impacts of PL are immense. Careful research in this domain can greatly enhance our basic understanding of the perceptual systems and the plasticity of these systems.
Furthermore, translational approaches underpinned by the basic science of PL are becoming increasingly prominent. This includes a host of emerging translational approaches for the rehabilitation of both perceptual deficits and for cognitive training, which are believed to share cortical plasticity mechanisms. However, while existing research provides evidence that PL approaches can improve perceptual skills, our ability to develop effective interventions is limited by a lack of understanding of the behavioral outcomes associated with different PL approaches. Here we suggest that to understand and maximally exploit PL, it is necessary to know how training with different tasks and in different individuals gives rise to different outcomes.
One major obstacle to successful translation of PL is that the field to-date has been strongly driven by “novel” and “provocative” findings demonstrated via small N studies with very few projects digging deep to achieve robust and reliable results. In turn, not surprisingly, the field of PL, like many others in psychology, has suffered from numerous replication challenges. Furthermore, perhaps because following in direct footsteps runs counter to the tendencies noted above, it is surprisingly rare for different research groups to use identical training tasks or outcome tests. This is problematic given research showing that small changes in task-procedures can give rise to large differences in learning outcome.
Here we overcome these limitations by comparing a large number of different training tasks using common outcome measures and in a large subject population. Each of these tasks involves a different “critical feature” for learning proposed by a given research group. However, these tasks have never been directly compared or contrasted. The outcome of the proposed research will be of tremendous value to both basic understanding of PL as well as how to translate PL to help those with visual needs. We will achieve robust and reliable results by training a large sample of participants on PL tasks and assess the outcomes via a common set of measures. We will also collect a broad assessment of individual differences, which will provide a unique dataset that can resolve controversies in the literature and lead to new understandings.
Our proposed analytical approach tests central key hypothesis in the field, explores the extent to which different training approaches leads to systematically different profiles of learning, and examines how these can differ based upon the individuals being trained. Further by releasing our training and testing tools as well as the data collected, we will enable other groups to model results, replicate our studies, and make well specified modifications of training tasks with known outcomes to guide future research.
NIMH R01MH111742 – Understanding Mediating and Moderating Factors that Determine Transfer of Working Memory Training
The overall objective of this project is to understand of the factors mediating and moderating transfer of learning in the context of training Working Memory (WM) systems. There is accumulating evidence that WM training impacts performance in a wide variety of tasks, however, to date, knowledge is extremely limited regarding the underlying mechanisms that mediate plasticity in WM systems, and what components of training give rise to transfer to different tasks.
This proposal is transformative in how it applies knowledge derived from plasticity in other brain systems (such as perceptual learning, where there is substantial understanding of mechanisms that drive transfer) to test their impact in WM systems (Aim 1), in the creation of novel measures to asses transfer to real-world cognition (Aim 2), and in the use of online ‘crowd-sourced’ studies to characterize individual differences using a large population (Aim 3).
These studies are particularly important and timely given current state of the field, which is fraught with controversy, and the lack of understanding of the relevant attributes of training and individual differences factors that give rise to successful training outcomes. Understanding the factors that mediate successful learning, as well as the individual differences moderating these is critical to resolve the current controversies and to move towards a theoretical model of training and transfer. Potential for knowledge gain and translational impact is substantial. Understanding how our memory systems work and the mechanisms that guide learning has great potential to be applied broadly in society.
Our acquisition of knowledge in the world intimately relies on WM processes, thus, improvements in WM can benefit almost all aspects of our lives. This has driven a now billion-dollar commercial market that has provided early generation training approaches, which are extremely controversial in the scientific community. The proposed research can shed light on the factors that mediate and moderate these types of cognitive interventions and address the extent to which some procedures may, and others may not, lead to improvements in real world cognition. This can potentially lead to educational, rehabilitative, and technological advancements. For example, WM deficits exist in a wide range of mental health conditions, cases of disease and brain damage, and in cognitive declines with aging, and training approaches that promote better functioning WM systems can promote health and well-being in these groups.
Further this research can elucidate approaches that may not work and help people avoid use of infective procedures. The proposed training software will be created on cross-platform game engines to enable dissemination to diverse populations. In this sense, the research output has innovative and broad impacts that can be directly realized from the proposed research. Many individuals are already using “brain training” products, however, none incorporate the theoretically-driven approaches designed to optimize WM learning with an aim to transfer that training to real world benefit, and that are systematically researched, as proposed here. Programs created in the proposed work will be made publicly available.
NIDCD R01DC015051 – Efficiently Characterizing the Deficits Comprising Central Hearing Loss
Most diagnoses of hearing loss focus on the audiogram, which is not sensitive to dysfunction at many of the additional processing stages associated with auditory perception. For example, recent data from many laboratories, including our own, have shown clear auditory processing deficits both in older listeners and in patients who have suffered traumatic brain injury, despite normal audiograms. Modern auditory neuroscience, computational modeling, and psychoacoustics have provided great insight into the information processing that underlies auditory perception and have identified specific stimuli and tasks for the evaluation of central auditory function, but this information has largely remained in the laboratory.
It is the goal of this proposal to develop and evaluate a set of clinical tests that draw upon modern laboratory tests and theories of auditory system function. These will form the basis of a new clinical test battery for central auditory dysfunction that will support the accurate diagnosis of a much wider range of the difficulties that can lead to auditory complaints.
NSF Small – Understanding Subtle Non-Social Facial Expressivity to Boost Learning and Computer Interaction
This project involves using machine learning on data from depth sensing cameras to understand non-social micro-expressions in learning contexts and to use this information as biofeedback to improve learning.
NewSchools Venture Fund – Developing Low-Cost Mobile App Technology to Assess Ability and Fluctuations in Executive Functions and Math Learning
The project will lead to development and validation of a diverse set of portable tools to assess math skills and EFs for typically developing children in grades 3-6. These tools will establish baselines needed to understand individual student strengths and needs and, relying on machine learning algorithms, use those baselines to constrain a highly efficient set of tests to estimate fluctuations in EF in proximity to math performance.
Our objectives are to (1) leverage considerations for equitable access and participation to develop a platform for tests including a User Portal, (2) establish convergent and discriminant validity, internal consistency and retest reliability of tests in grades 3-6, (3) establish utility of test batteries across multiple contexts and integrate them into learning systems. We will work with focus groups to ensure tasks are respectful of students’ identities, cultural, gender and linguistic diversity.
A key innovation will be to contextualize how EF tests are delivered by enabling active momentary testing on portable devices directly in the classroom so they can be used to inform learning and instruction (Stone and Shiffman 1994; Embretson and Reise 2000). A further innovation making sophisticated momentary testing feasible is to contextualize all historical responses of each student. Conventional test procedures always start from an uninformative baseline and accumulate data toward absolute measures, wasting considerable resources inferring previously determined properties with each repeat test.
Our team has developed the capability of using a comprehensive baseline test battery as a Bayesian prior such that all subsequent test items are optimized for determining fluctuations in EF performance in any moment relative to a current model of each student. These advances will provide teachers with actionable information about which teaching strategy might be most appropriate for those particular students at a particular point in time.
NIDCD R01DC018166 – Enhanced Environments for Psychophysical Evaluation and Training
Speech in noise tests have traditionally involved unrealistic maskers such as broadband noise presented from the same spatial location as the target speech. Our overarching hypothesis is that the experience of listeners in their daily lives will be more strongly related to performance with more ecologically realistic testing environments.
The main goal of this project is to test enhancements to realism to determine which have the greatest impact on the relationship with listener complaints, and which listener abilities (auditory and cognitive) mediate and modulate this relationship. Enhanced environments will be tested that simulate real-world experiences by 1) conducting assessments in synthetic virtual reality environments that include both auditory and visual stimuli and by 2) increasing the motivation of the participants as they perform the tests by adding motivating elements to the testing procedures.
Understanding how different participants respond to a variety of enhancements will provide essential new information about the ways in which realistic experiences differ from traditional laboratory tests. Experiments will involve younger listeners with normal hearing, older listeners with a range of hearing abilities from normal to severely impaired, and a group of listeners with a history of mild traumatic brain injury. These participants will provide a wide range of performance on measures of auditory and cognitive abilities, which can then be used to better understand any effects of the enhancements on self-reported ability to function in complex listening environments.
Upon completion of this project there will exist, freely available, an extensive set of normed, engaging, enhanced auditory assessments with known relationships to various established tests of speech in noise that run on inexpensive consumer-grade equipment.
NIMH R21AG069428-01A1 – Understanding Individual Differences in Working Memory Training and Transfer in Older Adults at Risk of Alzheimer’s Disease and Related Dementias
The overall objective of the project is to understand factors mediating and moderating transfer of learning in the context of training Working Memory (WM) systems in a diverse older adult population that is inclusive of individuals that may be at risk of Alzheimer’s disease and related dementias (AD/ADRD). There is accumulating evidence that WM training can be effective in older adults, however, to date, knowledge is extremely limited regarding the underlying mechanisms that mediate and moderate plasticity in WM systems, and what components of training give rise to transfer.
Specifically, we will investigate whether there is an inhibitory control (IC) phenotype in older adults at risk of dementia that may explain some of the disparate results observed in the literature in terms of WM training outcome. Specific aims are to test an Inhibitory Control (IC) model that predicts individual differences in how gamification of training using an n-back task differentially affects learning and transfer and contrast this with a General Cognitive Ability (GCA) model (Aim 1). We will further test the generalizability of the models using a complex span training (Aim 2), and furthermore, investigate applicability to Multisensory Facilitation (MF) where sounds supporting visual processing of task targets can promote learning and transfer (Aim 3).
This proposal is transformative in that it seeks to understand how individual cognitive strengths and needs in older adults may have different requirements for training interventions. These studies are particularly important and timely given the current state of the field, which is fraught with controversy, and the lack of understanding of the relevant attributes of training and individual differences factors that give rise to successful training outcomes. Understanding the factors is critical to resolve the current controversies and to move towards a theoretical model of training and transfer. Performance in everyday life intimately relies on WM processes, thus, improvements in WM can benefit almost all aspects of our lives. This has driven a now multi-billion-dollar commercial market that has provided early generation training approaches, many of which are targeted at older adult populations who are at risk of AD/ADRD.
The proposed research can shed light on the factors that mediate and moderate these types of cognitive interventions and address the extent to which some procedures may, and others may not, lead to improvements in real world cognition. WM deficits exist in a wide range of mental health conditions, cases of disease and brain damage, and in cognitive aging, and training approaches that promote better functioning WM systems can promote health and well-being in these groups. Further this research can elucidate approaches that may not work and help people avoid use of ineffective procedures. The proposed training software will be created on cross-platform game engines to enable us to bring the lab to the participants. In this sense, the research output has innovative and broad impacts that can be directly realized from the proposed research. Programs created in the proposed work will be made publicly available for research dissemination of personalized interventions that can support diverse populations. Overlap: There are no budgetary, scientific, or committed effort overlaps with this project and the present submission.
NEI R01EY031589 – Characterization of Multiple Factors in Training and Plasticity in Central Vision Loss
Our understanding of perceptual learning (PL) and cortical reorganization has been limited by disconnects between highly specific mechanistic studies applied in basic research, and holistic rehabilitation strategies typically found in the clinic. For example, in the case of Macular Degeneration (MD), one of the most common causes of vision loss (projected to affect almost 200 million people worldwide by 2020), damage to photoreceptors in the macula leads to central vision loss. In the clinic, rehabilitation uses multiple strategies to address the detrimental impact of MD on daily tasks including reading, navigating, and recognizing faces, with little standardization or mechanistic underpinnings.
Currently, the field has limited mechanistic understanding of behavioral outcomes or brain changes, how interventions interact, or key individual differences that may interact with interventions to give rise to differential outcomes. On the other hand, basic researchers conduct detailed behavioral, physiological and neuroimaging studies examining PL. This research shows PL occurring in the visual periphery, however PL is often very specific to training conditions and it is unclear how such PL relates to more ecological conditions of visual system plasticity, such as plasticity that may occur after vision loss in MD.
To bridge these fields, Seitz (MPI) propsed a whole brain framework of PL suggesting how to move beyond the highly specific perceptual learning approaches that domininate the literature to better understand how learning is distributed across brain systems in more ecological contexts. Here we embrace this approach to bridge between mechanistic and more ecological PL contexts, in the context of central vision loss. Key to this framework is to measure how differentially assessing and training vision performance factors of (I) Eye movements, (II) Visual Sensitivity, (III) Spatial Integration, and (IV) Spatial Attention, influence peripheral vision use, and give rise to potentially different profiles of behavioral change, as well as structural and functional brain changes.
We propose 4 specific aims: 1) Determine relationships between training and behavioral change, 2) Determine relationships between behavioral change and brain plasticity in a healthy vision population, 3) and a population with MD, and 4) Determine how individual differences at baseline relate to training outcomes. This work is significant as it will provide information about how different training approaches give rise to different profiles of behavioural and brain changes; bridging between the simplistic training approaches typically studied in basic research and more integrative training approaches found in the clinic. Further, by examining both MD patients and a commonly-used model for MD where normally seeing individuals are trained with a simulated visual scotoma, we can better understand how PL may differ between controls and patients undergoing similar training.
This research has strong translational potential, as mechanistic understanding of visual system plasticity can inform future interventions for patients with low vision. Further, this work illuminates basic mechanisms of brain plasticity after sensory loss that may generalize to other forms of rehabilitation after peripheral or central damage.
U19 AG066567 – Adult Changes in Thought (ACT) Research Program
This proposal is to continue and enhance a longstanding cohort study of older adults enrolled from a healthcare delivery system with extensive records from clinical care. The study identifies incident cases of dementia and Alzheimer’s disease and follows consenting participants to autopsy.
The study provides valuable data on extremely well characterized individuals to serve as a living, learning laboratory for aging research in general, for research on dementia and Alzheimer’s disease, and to facilitate collaborative research with talented investigators across the country and around the world. Our contribution to the project is the development of digital cognitive assessments that can be run in participants’ homes.
NIA R01AG072607 – How LC Integrity in Older Adults Mediates Perceptual and Memory Processes
The overarching goal of this project is to understand how individual differences in the structure and function of Locus Coeruleus (LC) moderate perception and memory in an older adult population. There is substantial evidence that the LC circuit plays a central role in cognitive processes and neuronal loss in LC is known to occur in neurodegenerative disorders such as ADRD and PD. Integrity of LC neurons is hypothesized to mediate the preservation of cognitive abilities during normal aging as well.
To date, however, there exists a dearth of research that either characterizes differential effects of LC integrity or details relationships between LC integrity and cognitive function in older adult humans. More generally, the link between LC activity and cognitive processes has not been well characterized in humans. Historical reasons for this is that the LC has been difficult to image due to its small size and thus most human research makes inferences about LC function by using pupil dilation as a surrogate measure.
To overcome existing limitations in the field, we propose a series of detailed psychophysical and MRI-based studies in older adults aimed to characterize how LC structure and function moderates behavior and in turn how this is mediated by activity in intermediate brain regions known to be involved in perceptual and memory processes. We further propose computational approaches to characterize individual differences in how LC circuit integrity relates to different patterns of cognitive performance across tasks, and advanced neuroimaging methods to localize and image the LC, which have been pioneered by our group.
Using MRI-based methods, we will examine LC integrity using high-resolution neuromelanin-sensitive structural imaging, tractography and functional connectivity. This approach will allow us to identify candidate biomarkers of LC circuit integrity. We will use a series of within-subject designs where we manipulate LC activity and examine whether relationships between LC and behavior and brain regions thought to mediate those behaviors are consistent or not between different perceptual modalities and memory tasks. Overall this study will provide an important and much needed understanding of how LC integrity underlies cognitive declines in older adults.
By combining advanced neuroimaging, well-controlled behavioral assessment, and computational analysis, we expect to uncover previously inaccessible in vivo mechanisms of LC modulation and generate a unique dataset to address fundamental mechanistic questions of how the LC integrity moderates cognition, how this varies across older adults and the extent to which relationships between LC and cognition are generalized or individualized to particular domains. The resulting understanding of LC circuit can help explain how dysfunctional modulatory circuits may generate cognitive declines or be implicated in normal aging and age-related disorders such as Alzheimer’s and Alzheimer’s related disorders. This, in turn, has potential to support non-invasive methods for diagnosing pathologies associated with LC decline and developing new treatments.
NIA R61AG073668 – Following the Sound of Music – Comparing the Effects of Music vs. Non-Music Based Interventions on Auditory and Cognitive Processing in Older Adults
The overall objective of this project is to test the benefits of a music-based intervention on speech-in-competition abilities in an older adult population that includes individuals that may be at risk of Alzheimer’s disease and related dementias (ADRD). Age-related hearing difficulties are prevalent, with speech-in-competition difficulties being a common challenge amongst older adults. Critically, these difficulties and frustrations often lead to social isolation and decreased cognitive engagement, and they are associated with an increased risk of developing ADRD.
There is evidence suggesting that musical training is associated with cognitive advantages in older adults, including preserved ability for speech-in-competition. However, to date, there is extremely limited knowledge and lack of experimental evidence explaining how music might benefit speech-in-competition abilities, along with more basic auditory processes and/or cognitive functions. We aim to contribute to uncovering the underlying mechanisms driving the potential effects of music and attention through an innovative, attention-based music listening intervention that cultivates auditory and attentional skills akin to those developed during formal instrumental training.
To disentangle potential effects of music and attention and to get at the underlying mechanisms of music effects, we will compare outcomes of this attention-based music intervention with those of two active control interventions that consist of either passive music listening or active listening to non-music sounds. Specific aims are to develop and test the feasibility of music and control interventions and assessments targeting auditory processing and cognition (R61; Aim 1); test for intervention-specific improvements in speech-in-competition using a randomized-controlled trial (R33; Aim 2); and determine whether experimental and control interventions differentially impact measures of auditory processing, memory, and attention, and test how these may mediate performance on measures of speech-in-competition (R33; Aim 3).
Long-term objectives are to understand the key mechanisms underlying the benefits of music with the overall goal to inform interventions aimed at mitigating the effects of ADRD. This proposal is transformative in that it utilizes an innovative approach to uncover potential benefits and underlying mechanisms of music by testing the added benefits of interventions and testing their benefits against a broad set of outcomes measures that can be used to further understand the malleability of auditory processes and cognition in aging. In addition, the intervention is cost-effective, easily administrable, and accessible to individuals who may not possess the physical capabilities or resources that formal instrumental practice demands. In addition, music has been shown to provide other benefits including mood regulation and psychological well-being, and as such, the intervention may have benefits that go beyond the auditory or cognitive domain.
NIA R21AG074497 – Building a Shared Infrastructure for Cognitive Assessment in the Service of Cognitive Training Research
Effective measurement of cognitive abilities is fundamental to effective diagnostics, risk assessment and evaluation of interventions targeted towards older adults (OA) and in particular those with Alzheimer’s Disease and related dementias (ADRD). With the saturation of smartphone/tablet technology in modern society a proliferation of mobile cognitive assessments from companies, healthcare providers, and researchers are being developed. However, a difficulty in evaluating such interventions, and in particular making comparison between them is the lack of standardization/interoperability of assessment tools. This is especially the case for early stage/mechanistic studies where it is common for investigators to each use their own labs’ toolset to evaluate intervention outcomes.
Here we address particular needs in the field of cognitive training, as well as for other interventions focused on OA, where the limited standardization and accessibility of cognitive outcome measures makes it difficult to evaluate effectiveness of interventions. This R21/R33 infrastructure proposal seeks to develop shared tools to facilitate effective translation and sharing of cognitive assessment and training procedures.
We accomplish this by leveraging technologies, existing assessment batteries, and know-how from 3 groups that have each independently developed robust systems for cognitive assessment and training that can run on mobile devices (UCR Brain Game Center, UCSF Neuroscape Center, and UCI Working Memory and Plasticity Lab). We target development of systems that allow for interoperability of assessments, enrollment/participant tracking systems, data visualization, and participant compliance systems.
In the R21 phase, we aim to develop such systems and demonstrate that they can be effectively shared across labs, and in the R33 phase these systems will be both tested for robustness in large scale-research projects that will now be able to share outcome measures, and for developing personalized, precision training approaches for participants based upon these assessments. Further, these systems will be documented and will be shared with other scientists groups to reduce the barrier of entry for other groups. The long-term impact of this work will be an infrastructure that will support better comparison across studies of cognitive training, as well as other interventions, that are increasingly being used to ameliorate cognitive declines in older adults such as those related to ADRD.
The key value of this system compared to others is that it will simultaneously support the flexibility required for basic research, by facilitating groups to continue to use their own lab’s software systems, while at the same time providing them with a powerful infrastructure for sharing that allows them to incorporate assessments, server infrastructure and compliance tools into their own studies. This will facilitate comparisons across studies using common outcome measures as well as the ability to use the same assessments in numerous other domains including risk-assessment and longitudinal testing in older adults at risk for ADRD.