Age-related neural dedifferentiation and cognition

doi:10.1016/j.cobeha.2020.01.006

Current Opinion in Behavioral Sciences

Volume 32, April 2020, Pages 7-14

https://doi.org/10.1016/j.cobeha.2020.01.006 Get rights and content

This review focuses on possible contributions of neural dedifferentiation to age-related cognitive decline. Neural dedifferentiation is held to reflect a breakdown in the functional specificity of brain regions and networks that compromises the fidelity of neural representations supporting episodic memory and related cognitive functions. The evidence for age-related dedifferentiation is robust when it is operationalized as neural selectivity for different categories of perceptual stimuli or as decreased segregation or modularity of resting-state functional brain networks. Neural dedifferentiation for perceptual categories appears to demonstrate a negative, age-invariant relationship with performance on tests of memory and fluid processing. Whether this pattern extends to network-level measures of dedifferentiation cannot currently be determined due to insufficient evidence. The existing data highlight the importance of further examination of neural dedifferentiation as a factor contributing to episodic memory and to cognitive performance more generally.

Introduction

Many cognitive abilities decline in the course of healthy aging, including episodic memory, executive control and processing speed [1]. Identifying the factors that cause and moderate cognitive aging is a pressing concern given the rapid rate at which the population is aging [2]. One factor that has received increased interest recently is neural dedifferentiation. This term refers to findings suggesting that neural processing becomes less selective with increasing age. Neural dedifferentiation is hypothesized to compromise the fidelity and efficiency of the neural representations and processes that support episodic memory and other aspects of cognition [3,4].

The concept of dedifferentiation originated from behavioral findings reporting an age-related increase in correlations between different cognitive and sensory abilities [5] (recently termed ‘static’ cognitive dedifferentiation; see Ref. [6^••]). Although these findings have not held up to recent scrutiny (cf. [7]), they motivated early investigations aimed at identifying a neural counterpart [3,4].

We provide an update on studies that examined age-related neural dedifferentiation with fMRI (for more extensive treatment of some of the topics discussed below, see Ref. [7]). First, we provide a brief review of research in non-human animals that suggests a mechanistic basis for neural dedifferentiation. Then, we provide a selective review of fMRI studies examining dedifferentiation at three different levels of investigation (individual items, perceptual categories, and functional networks — a level that was not covered previously [7]). Finally, we review findings examining relationships between different indices of neural differentiation and cognitive performance, with an emphasis on dedifferentiation of functional networks.

Section snippets

Age-related dedifferentiation in non-human animals

Animal research has operationalized neural dedifferentiation in terms of the broadening of receptive fields of single neurons. Initial studies [8,9] reported reduced orientation and directional selectivity of neurons in striate cortex (V1) of senescent macaques. Similar findings have been reported in other feature-selective cortical regions and stimulus modalities (e.g. in Refs. [10, 11, 12]) and in other non-human animal species [13,14]. It remains to be seen whether these findings extend to

Item-level neural dedifferentiation

Staying with research on humans, several studies have examined age-related neural dedifferentiation for individual items (Figure 1). One approach is to quantify neural pattern similarity between successive repetitions of the same item relative to different items, under the assumption that reduced pattern similarity reflects neural dedifferentiation (see also Ref. [17]). One study reported null effects of age for repetitions of brief movie clips during a memory encoding task [18,19]. Another

Category-level neural dedifferentiation

Category-level dedifferentiation has mainly been operationalized as a reduction in the selectivity of fMRI BOLD activity elicited by different visual categories (e.g. images of scenes, objects, or faces; see Figure 2) [7,27,28,29^•]. These studies are rooted in the large literature documenting category-selective neural responses in different regions of ventral occipital-temporal cortex [30]. Importantly, analogous findings have been reported in both motor [31] and auditory [15,32] cortical

Dedifferentiation at the network level

Spontaneous (‘resting state’) brain activity measured with fMRI demonstrates systematic patterns of inter-regional correlations that can be decomposed into highly reproducible large-scale brain networks (sometimes referred to as ‘systems’, ‘communities’, or ‘sub-networks’; for review, see Ref. [40]). The application of graph theoretic analyses to these patterns of resting state connectivity enables quantification of the extent to which the brain (characterized as a distributed set of ‘nodes’)

Relationships with cognitive performance

Neural dedifferentiation has been proposed as an important factor contributing to age-related cognitive decline [3,4] (see Ref. [7] for a recent review). This may be particularly important for explaining age-related declines in episodic memory because the encoding and retrieval processes supporting episodic memory depend upon high fidelity neural representations [18,19,25,26^••,29^•]. The foregoing proposal is supported by evidence that neural dedifferentiation at both the item [23,25,26^••] and

Concluding remarks

There is robust evidence in humans for age-related neural dedifferentiation at the item-levels, category-levels, and network-level of analysis. It is possible that these findings, which rely exclusively on fMRI, might be confounded by age differences in neurovascular function [55]. We note however that several of the measures used in the studies reviewed here are insensitive to age differences in neurovascular coupling [7]. Moreover, it is difficult to reconcile findings that neural

Conflict of interest statement

Nothing declared.

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

• of special interest
•• of outstanding interest

Acknowledgements

This work was supported by the National Institutes of Health [grant number AG039103] and the National Science Foundation [grant number 1633873]. The authors thank Micaela Chan and Gagan Wig for providing the images for Figure 3.

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³: All authors contributed equally to this paper.

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Age-related neural dedifferentiation and cognition

Introduction

Section snippets

Age-related dedifferentiation in non-human animals

Item-level neural dedifferentiation

Category-level neural dedifferentiation

Dedifferentiation at the network level

Relationships with cognitive performance

Concluding remarks

Conflict of interest statement

References and recommended reading

Acknowledgements

Trends Cogn Sci

Curr Opin Neurobiol

Nat Neurosci

Front Syst Neurosci

Sci Rep

J Neurosci

Philos Trans R Soc B Biol Sci

Neuron

Proc Natl Acad Sci U S A

J Cogn Neurosci

Trends Cogn Sci

Front Aging Neurosci

Cereb Cortex

Front Aging Neurosci

Cereb Cortex

Trajectories of normal cognitive aging

Psychol Aging

Department of Economic and Social Affairs, Population Division: World Population Prospects: The 2017 Revision, Key Findings and Advance Tables

Emergence of a powerful connection between sensory and cognitive functions across the adult life span: a new window to the study of cognitive aging?

Psychol Aging

Coupled cognitive changes in adulthood: a meta-analysis

Psychol Bull

Neural dedifferentiation in the aging brain

Trends Cogn Sci

GABA and its agonists improved visual cortical function in senescent monkeys

Science

Aging affects contrast response functions and adaptation of middle temporal visual area neurons in rhesus monkeys

Neuroscience

Differential effects of aging on fore- and hindpaw maps of rat somatosensory cortex

PLoS One

Decreased proportion of GABA neurons accompanies age-related degradation of neuronal function in cat striate cortex

Brain Res Bull

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

NeuroImage

Sensorimotor network segregation declines with age and is linked to GABA and to sensorimotor performance

NeuroImage

Memory reactivation in healthy aging: evidence of stimulus-specific dedifferentiation

J Neurosci

How multiple retrievals affect neural reactivation in young and older adults

J Gerontol Ser B

Reduced fidelity of neural representation underlies episodic memory decline in normal aging

Cereb Cortex