Michigan Neural Distinctiveness (MiND) study protocol: investigating the scope, causes, and consequences of age-related neural dedifferentiation

Abstract

Background Aging is often associated with behavioral impairments, but some people age more gracefully than others. Why? One factor that may play a role is individual differences in the distinctiveness of neural representations. Previous research has found that neural activation patterns in visual cortex in response to different visual stimuli are often more similar (i.e., less distinctive) in older vs. young participants, a phenomenon referred to as age-related neural dedifferentiation. Furthermore, older people whose neural representations are less distinctive tend to perform worse on a wide range of behavioral tasks. The Michigan Neural Distinctiveness (MiND) project aims to investigate the scope of neural dedifferentiation (e.g., does it also occur in auditory, motor, and somatosensory cortex?), one potential cause (age-related reductions in the inhibitory neurotransmitter gamma-aminobutyric acid (GABA)), and the behavioral consequences of neural dedifferentiation. This protocol paper describes the study rationale and methods being used in complete detail, but not the results (data collection is currently underway). Methods The MiND project consists of two studies: the main study and a drug study. In the main study, we are recruiting 60 young and 100 older adults to perform behavioral tasks that measure sensory and cognitive function. They also participate in functional MRI (fMRI), MR spectroscopy, and diffusion weighted imaging sessions, providing data on neural distinctiveness and GABA concentrations. In the drug study, we are recruiting 25 young and 25 older adults to compare neural distinctiveness, measured with fMRI, after participants take a placebo or a benzodiazepine (lorazepam) that should increase GABA activity. Discussion By collecting multimodal imaging measures along with extensive behavioral measures from the same subjects, we are linking individual differences in neurochemistry, neural representation, and behavioral performance, rather than focusing solely on group differences between young and old participants. Our findings have the potential to inform new interventions for age-related declines. Trial registration This study was retrospectively registered with the ISRCTN registry on March 4, 2019. The registration number is ISRCTN17266136 .

RETRACTED: Tracking Age Differences in Neural Distinctiveness across Representational Levels

“…For example, using MR spectroscopy to quantify GABA concentrations in occipital voxels, Simmonite et al (2019) found that lower occipital GABA levels in older adults were associated with declines in fluid processing abilities. Furthermore, Chamberlain et al (2019;preprint) reported that individual differences in the category specificity of face versus house representations were linked to individual differences in VVC GABA concentrations in older adults, indicating a role of GABA in age-related neural dedifferentiation (see also Cassady et al, 2019;Gagnon et al, 2019;Lalwani et al, 2019). These findings substantiate the key role of proficient (particularly GABAergic) neuromodulation for high-fidelity (i.e., stable and distinct) neural representations and cognitive performance and lay the ground for future studies aiming to understand how agerelated deficits in neuromodulation are related to neural dedifferentiation across representational levels.…”

Cortical Engagement Metrics During Reactive Balance Are Associated With Distinct Aspects of Balance Behavior in Older Adults

“…Older adults show greater prefrontal cortical activity during a wide range of motor tasks, including interlimb coordination tasks (Heuninckx et al, 2008) and steady-state walking (Chen et al, 2017;Mirelman et al, 2017;Hawkins et al, 2018). Whether age-related differences in prefrontal cortical activity play a beneficial (i.e., compensatory; Clark et al, 2019) or detrimental (i.e., age-related neural dedifferentiation; Payer et al, 2006;Gagnon et al, 2019) role in motor function in older adults remains controversial (for review see Seidler et al, 2010) and may depend on the context and challenge of the motor task (e.g., level of complexity and difficulty; Clark, 2015). In contrast to younger adults, older adults utilize motor control strategies that require higher levels of cognitive processing, which are effective at slower speeds but less effective during fast speed motor performance (Boisgontier and Nougier, 2013).…”

Prefrontal-motor and somatosensory-motor cortical network interactions during reactive balance are associated with distinct aspects of balance behavior in older adults

“…compensatory) (Clark et al, 2019) or detrimental (i.e. agerelated neural dedifferentiation) (Gagnon et al, 2019;Payer et al, 2006) role in motor function in older adults remains controversial (for review see R. D. Seidler et al, 2010) and may depend on the context and challenge of the motor task (e.g. level of complexity and difficulty) (Clark, 2015).…”