Biology subjects

Polk, T. A.

Publications and source records attributed to Polk, T. A..

9 recordsLinked to original sources

bioRxiv2022

Modulation of neural variability: Age-related reduction, GABAergic basis, and behavioral implications

Moment-to-moment neural variability has been shown to scale positively with the complexity of stimulus input. However, the mechanisms underlying the ability to align variability to input complexity are unknown. Using a combination of computational modeling, fMRI, MR spectroscopy, and pharmacological intervention, we investigated the role of aging and GABA in neural variability during visual processing. We found that participants expressed higher variability when viewing more complex stimuli. Such variability modulation was associated with higher baseline visual GABA levels and was reduced in older adults. When pharmacologically increasing GABA activity, we found that participants with lower baseline GABA levels showed higher drug- related increase in variability modulation, consistent with an inverted-U account. Finally, higher baseline GABA and variability modulation were jointly associated with better visual-discrimination performance. These results suggest that GABA plays an important role in how humans utilize neural variability to adapt to the complexity of the visual world.

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bioRxiv2022

Age-related differences in GABA: Impact of analysis technique

Previous research using magnetic resonance spectroscopy (MRS) has indicated that GABA levels decline in multiple brain regions over the course of healthy aging. However, brain atrophy also occurs during healthy aging, and as a result the tissue composition of MRS voxels (i.e., the percentage of grey matter, white matter, and cerebrospinal fluid in the voxel) may also differ between age groups. Many authors therefore argue for applying a correction to GABA estimates in order to control for differences in tissue composition. Here, we use data from a large healthy aging study to investigate the influence of three tissue correction strategies on age-group differences in GABA. We also evaluate the use of different analysis packages and reference metabolites on group differences. A 3T MEGA-PRESS sequence was used to obtain spectra from seven voxels placed in the visual, auditory, and sensorimotor cortex of 58 young adults (aged 18-29 years) and 85 older adults. We obtained several different estimates of GABA concentrations from the spectra using two analysis software packages (Gannet 3.1 and LCModel), three reference metabolites (water, creatine and N-acetylaspartate) and four tissue correction strategies. Young adults consistently demonstrated significantly higher GABA concentrations in the visual, auditory, and sensorimotor cortex when we used an uncorrected GABA estimate referenced either to water or creatine. When uncorrected GABA was referenced to N-acetylaspartate, age-related differences were observed only in the right ventral visual cortex. Similarly, when any of the four tissue corrections were applied to the data, only age-related differences in the left and right ventral visual cortex voxels remained. Correlations between GABA concentration estimates obtained from different software packages were moderate, as were correlations between uncorrected GABA estimates when different baseline metabolites were used. Correlations between all tissue corrections we explored were extremely high. These results confirm that reports of age-related differences in GABA concentrations are driven, at least in part, by changes in tissue composition.

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bioRxiv2021

Age-related declines in neural distinctiveness correlate across brain areas and result from both decreased reliability and increased confusability

According to the neural dedifferentiation hypothesis, age-related reductions in the distinctiveness of neural representations contribute to sensory, cognitive, and motor declines associated with aging: neural activity associated with different stimulus categories becomes more confusable with age and behavioural performance suffers as a result. Initial studies investigated age-related dedifferentiation in the visual cortex, but subsequent research has revealed declines in other brain regions, suggesting that dedifferentiation may be a general feature of the aging brain. In the present study, we used functional magnetic resonance imaging to investigate age-related dedifferentiation in the visual, auditory, and motor cortices. Participants were 58 young adults and 79 older adults. The similarity of activation patterns across different blocks of the same condition was calculated (within-condition correlation, a measure of reliability) as was the similarity of activation patterns elicited by different conditions (between-category correlations, a measure of confusability). Neural distinctiveness was defined as the difference between the mean within- and between-condition similarity. We found age-related reductions in neural distinctiveness in the visual, auditory, and motor cortices, which were driven by both decreases in within-category similarity and increases in between-category similarity. There were significant positive cross-region correlations between neural distinctiveness in different regions. These correlations were driven by within-category similarities, a finding that indicates that declines in the reliability of neural activity appear to occur in tandem across the brain. These findings suggest that the changes in neural distinctiveness that occur in healthy aging result from changes in both the reliability and confusability of patterns of neural activity

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bioRxiv2019

Neural Correlates of Working Memory Training: Evidence for Plasticity in Older Adults

Brain activity typically increases with increasing working memory (WM) load, regardless of age, before reaching an apparent ceiling. However, older adults exhibit greater brain activity and reach ceiling at lower loads than younger adults, possibly reflecting compensation at lower loads and dysfunction at higher loads. We hypothesized that WM training would bolster neural efficiency, such that the activation peak would shift towards higher memory loads after training. Pre-training, older adults showed greater recruitment of the WM network than younger adults across all loads, with decline at the highest load. Ten days of adaptive training on a verbal WM task improved performance and led to greater brain responsiveness at higher loads for both groups. For older adults the activation peak shifted rightward towards higher loads. Finally, training increased task-related functional connectivity in older adults, both within the WM network and between this task-positive network and the task-negative/default-mode network. These results provide new evidence for functional plasticity with training in older adults and identify a potential signature of improvement at the neural level.

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bioRxiv2019

Effects of Aging on the Encoding of Spatial Direction in the Human Brain

Human aging is characterized by impaired spatial cognition and reductions in the distinctiveness of category-specific fMRI activation patterns. Yet, little is know about age-related decline in neural distinctiveness of spatial information. Here, we asked whether neural tuning functions of walking direction are broadened in older versus younger adults. To test this idea, we developed a novel method that allowed us to investigate changes in fMRI-measured pattern similarity while participants navigated in different directions in a virtual spatial navigation task. We expected that directional tuning functions would be broader in older adults, and thus activation patterns that reflect neighboring directions would be less distinct as compared to non-adjacent directions. Because loss of distinctiveness leads to more confusions when information is read out by downstream areas, we analyzed predictions of a decoder trained on these representations and asked (1) whether decoder confusions between two directions increase proportionally to their angular similarity, (2) and how this effect may differ between age groups. Evidence for tuning-function-like signals was found in the retrosplenial complex and primary visual cortex. Significant age differences in tuning width, however, were only found in the primary visual cortex, suggesting that less precise visual information could lead to worse directional signals in older adults. Yet, age differences in visual tuning were not related to behavior. Instead, directional information encoded in RSC correlated with memory on task. These results shed new light on neural mechanisms underling age-related spatial navigation impairments and introduce a novel approach to measure tuning specificity using fMRI.

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bioRxiv2019

Age-related differences in white matter: Comparing fixel based and tensor based analyses

Aging is associated with widespread alterations in cerebral white matter (WM). Most prior studies of age differences in WM have used diffusion tensor imaging (DTI), but typical DTI metrics (e.g., fractional anisotropy; FA) can reflect multiple neurobiological features, making interpretation challenging. Here, we used fixel-based analysis (FBA) to investigate age-related WM differences observed using DTI in a sample of 45 older and 25 younger healthy adults. Age- related FA differences were widespread but were strongly associated with differences in multifiber complexity (CX), suggesting that they reflected differences in crossing fibers in addition to structural differences in individual fiber segments. FBA also revealed a frontolimbic locus of age-related effects and provided insights into distinct microstructural changes underlying them. Specifically, age differences in fiber density were prominent in fornix, bilateral anterior internal capsule, forceps minor, body of the corpus callosum and corticospinal tract, while age differences in fiber cross section were largest in cingulum bundle and forceps minor. These results provide novel insights into specific structural differences underlying major WM differences associated with aging.

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bioRxiv2019

GABA levels in ventral visual cortex decline with age and are associated with neural distinctiveness

Age-related neural dedifferentiation - a decline in the distinctiveness of neural representations in the aging brain-has been associated with age-related declines in cognitive abilities. But why does neural distinctiveness decline with age? Based on prior work in non-human primates and more recent work in humans, we hypothesized that the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) declines with age and is associated with neural dedifferentiation in older adults. To test this hypothesis, we used magnetic resonance spectroscopy (MRS) to measure GABA and functional MRI (fMRI) to measure neural distinctiveness in the ventral visual cortex in a set of older and younger participants. Relative to younger adults, older adults exhibited lower GABA levels and less distinct activation patterns for faces and houses in the ventral visual cortex. Furthermore, individual differences in GABA within older adults positively predicted individual differences in neural distinctiveness. These results provide novel support for the view that age-related reductions of GABA contribute to age-related reductions in neural distinctiveness (i.e., neural dedifferentiation) in the human ventral visual cortex.

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bioRxiv2018

Neural distinctiveness declines with age in auditory cortex and is associated with auditory GABA levels.

Neural activation patterns in the ventral visual cortex in response to different categories of visual stimuli (e.g., faces vs. houses) are less selective, or distinctive, in older adults than in younger adults, a phenomenon known as age-related neural dedifferentiation. Previous work in animals suggests that age-related reductions of the inhibitory neurotransmitter, gamma aminobutyric acid (GABA), may play a role in this age-related decline in neural distinctiveness. In this study, we investigated whether neural dedifferentiation extends to auditory cortex and whether individual differences in GABA are associated with individual differences in neural distinctiveness in humans. 20 healthy young adults (ages 18-29) and 23 healthy older adults (over 65) completed a functional magnetic resonance imaging (fMRI) scan, during which neural activity was estimated while they listened to foreign speech and music. GABA levels in the auditory, ventrovisual and sensorimotor cortex were estimated in the same individuals in a separate magnetic resonance spectroscopy (MRS) scan. Relative to the younger adults, the older adults exhibited both (1) less distinct activation patterns for music vs. speech stimuli and (2) lower GABA levels in the auditory cortex. Also, individual differences in auditory GABA levels (but not ventrovisual or sensorimotor GABA levels) predicted individual differences in neural distinctiveness in the auditory cortex in the older adults. These results demonstrate that age-related neural dedifferentiation extends to the auditory cortex and suggest that declining GABA levels may play a role in neural dedifferentiation in older adults.\n\nSignificance StatementPrior work has revealed age-related neural dedifferentiation in the visual cortex. GABA levels also decline with age in several parts of the human cortex. Here, we report that these two age-related changes are linked; neural dedifferentiation is associated with lower GABA levels in older adults. We also show that age-related neural dedifferentiation extends to auditory cortex, suggesting that it may be a general feature of the aging brain. These findings provide novel insights into the neurochemical basis of age-related neural dedifferentiation in humans and also offer a potential new avenue for investigating age-related declines in central auditory processing.

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bioRxiv2018

Michigan Neural Distinctiveness (MiND) project: Investigating the scope, causes, and consequences of age-related neural dedifferentiation

BackgroundAging 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).\n\nMethods/DesignThe 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 (MRS), and diffusion weighted imaging (DWI) 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 (1) a benzodiazepine (lorazepam) that should increase GABA activity or (2) a placebo.\n\nDiscussionBy collecting multimodal imaging measures (fMRI, MRS, DWI) 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.

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