Multiple sclerosis is associated with differences in semantic memory structure.

OBJECTIVE: Although language is often considered to be largely intact in multiple sclerosis (MS), word-finding difficulties are a common complaint. Recent work suggests that declines in language are not solely the result of motoric and cognitive slowing that is most strongly associated with MS. Network science approaches have been effectively used to examine network structure as it relates to clinical conditions, aging, and language. The present study utilizes a network science approach to investigate whether individuals with MS exhibit less interconnected and resilient semantic networks compared to age-matched neurotypical peers. METHOD: We used semantic fluency data from 89 participants with MS and 88 neurotypical participants to estimate and analyze the semantic network structure for each participant group. Additionally, we conducted a percolation analysis to examine the resilience of each network. RESULTS: Network measures showed that individuals with MS had lower local and global clustering coefficients, longer average shortest path lengths, and higher modularity values compared to neurotypical peers. Small-worldness, network portrait divergence measures, and community detection analyses were consistent with these results and indicated that macroscopic properties of the two networks differed and that the semantic network for individuals with MS was more fractured than the neurotypical peer network. Moreover, a spreading activation simulation and percolation analysis suggested that the semantic networks of individuals with MS are less flexible and activation degrades faster than those of age-matched neurotypical participants. CONCLUSIONS: These differing semantic network structures suggest that language retrieval difficulties in MS partially result from decline in language-specific factors. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Multilingual Language Diversity Protects Native Language Production under Different Control Demands.

The use of multiple languages has been found to influence individuals' cognitive abilities. Although some studies have also investigated the effect of multilingualism on non-native language proficiency, fewer studies have focused on how multilingual experience affects native language production. This study investigated the effect of multilingualism on native language production, specifically examining control demands through a semantic Go/No-Go picture naming task. The multilingual experience was quantified using language entropy, which measures the uncertainty and diversity of language use. Control demands were achieved by manipulating the proportion of Go (i.e., naming) trials in different conditions. Results showed that as control demands increased, multilingual individuals exhibited poorer behavioral performance and greater brain activation throughout the brain. Moreover, more diverse language use was associated with higher accuracy in naming and more interconnected brain networks with greater involvement of domain-general neural resources and less domain-specific neural resources. Notably, the varied and balanced use of multiple languages enabled multilingual individuals to respond more efficiently to increased task demands during native language production.

Resting State Network Segregation Modulates Age-Related Differences in Language Production.

Older adults typically exhibit decline in language production. However, how the brain supports or fails to support these processes is unclear. Moreover, there are competing hypotheses about the nature of age-related neural changes and whether age-related increases in neural activity reflect compensation or a decline in neural efficiency. In the current study, we investigated the neural bases of language production focusing on resting state functional connectivity. We hypothesized that language production performance, functional connectivity, and their relationship would differ as a function of age. Consistent with prior work, older age was associated with worse language production performance. Functional connectivity analyses showed that network segregation within the left hemisphere language network was maintained across adulthood. However, increased age was associated with lower whole brain network segregation. Moreover, network segregation was related to language production ability. In both network analyses, there were significant interactions with age-higher network segregation was associated with better language production abilities for younger and middle-aged adults, but not for older adults. Interestingly, there was a stronger relationship between language production and the whole brain network segregation than between production and the language network. These results highlight the utility of network segregation measures as an index of brain function, with higher network segregation associated with better language production ability. Moreover, these results are consistent with stability in the left hemisphere language network across adulthood and suggest that dedifferentiation among brain networks, outside of the language network, is a hallmark of aging and may contribute to age-related language production difficulties.

Task difficulty modulates age-related differences in functional connectivity during word production.

Older adults typically report increased difficulty with language production, while its neural bases are less clear. The current study investigated the neural bases of age-related differences in language production at the word level and the modulating effect of task difficulty, focusing on task-based functional connectivity. Using an English phonological Go/No-Go picture naming task, task difficulty was manipulated by varying the proportion of naming trials (Go trials) and inhibition trials (No-Go trials) across runs. Behaviorally, compared to younger adults, older adults performed worse, and showed larger effects of task difficulty. Neurally, older adults had lower within language network connectivity compared to younger adults. Moreover, older adults' language network became less segregated as task difficulty increased. These results are consistent with the Compensation-Related Utilization of Neural Circuits Hypothesis, suggesting that the brain becomes less specified and efficient with increased task difficulty, and that these effects are stronger among older adults (i.e., more dedifferentiated).

Age differences in semantic network structure: Acquiring knowledge shapes semantic memory.

Computational research suggests that semantic memory, operationalized as semantic memory networks, undergoes age-related changes. Previous work suggests that concepts in older adults' semantic memory networks are more separated, more segregated, and less connected to each other. However, cognitive network research often relies on group averages (e.g., young vs. older adults), and it remains unclear if individual differences influence age-related disparities in language production abilities. Here, we analyze the properties of younger and older participants' individual-based semantic memory networks based on their semantic relatedness judgments. We related individual-based network measures-clustering coefficient (CC; connectivity), global efficiency, and modularity (structure)-to language production (verbal fluency) and vocabulary knowledge. Similar to previous findings, we found significant age effects: CC and global efficiency were lower, and modularity was higher, for older adults. Furthermore, vocabulary knowledge was significantly related to the semantic memory network measures: corresponding with the age effects, CC and global efficiency had a negative relationship, while modularity had a positive relationship with vocabulary knowledge. More generally, vocabulary knowledge significantly increased with age, which may reflect the critical role that the accumulation of knowledge within semantic memory has on its structure. These results highlight the impact of diverse life experiences on older adults' semantic memory and demonstrate the importance of accounting for individual differences in the aging mental lexicon. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Cerebral White Matter Mediation of Age-Related Differences in Picture Naming Across Adulthood.

As people age, one of the most common complaints is difficulty with word retrieval. A wealth of behavioral research confirms such age-related language production deficits, yet the structural neural differences that relate to age-related language production deficits remains an open area of exploration. Therefore, the present study used a large sample of healthy adults across adulthood to investigate how age-related white matter differences in three key left-hemisphere language tracts may contribute to age-related differences in language ability. Specifically, we used diffusion tensor imaging to measure fractional anisotropy (FA) and radial diffusivity (RD) which are indicators of white matter structure. We then used a series of path models to test whether white matter from the superior longitudinal fasciculus (SLF), the inferior longitudinal fasciculus, and the frontal aslant tract (FAT) mediated age-related differences in one form of language production, picture naming. We found that FA, as well as RD from the SLF and FAT mediated the relation between age and picture naming performance, whereas a control tract (corticospinal) was not a mediator. Moreover, differences between mediation of picture naming and a control naming condition suggest that left SLF has a greater role in higher-order aspects of naming, such as semantic and lexical selection whereas left FAT is more sensitive to sensorimotor aspects of fluency or speech motor planning. These results suggest that dorsal white matter contributes to age-related differences in generating speech and may be particularly important in supporting word retrieval across adulthood.

Neural sensitivity to semantic neighbors is stable across the adult lifespan.

As we age, language reflects patterns of both stability and change. On the one hand, vocabulary and semantic abilities are largely stable across the adult lifespan, yet lexical retrieval is often slower and less successful (i.e., slower picture naming times, increased tip of the tongue incidents). Although the behavioral bases of these effects have been well established, less is known about the brain regions that support these age-related differences. We used functional Magnetic Resonance Imaging (fMRI) to examine the neural basis of picture naming. Specifically, we were interested in whether older adults would be equally sensitive to semantic characteristics, specifically the number of semantic near neighbors. Near neighbors, defined here as items with a high degree of semantic feature overlap, were of interest as these are thought to elicit competition among potential candidates and increase naming difficulty. Consistent with prior reports, pictures with more semantic near neighbors were named more slowly and less accurately for all adults. Additionally, this interference for naming times was larger as age increased, starting around 30 years old. In contrast to the age-related behavioral slowing, the neural basis of these effects was stable across adulthood. Across all adults, a number of language-relevant regions including left posterior middle temporal gyrus and left inferior frontal gyrus, pars triangularis were sensitive to the number of near neighbors. Our results suggest that although middle-aged and older adults' picture naming is more slowed by increased semantic competition, the brain regions supporting semantic processes remain stable across the adult lifespan.

Language immersion and language training: Two paths to enhanced language regulation and cognitive control.

When bilinguals switch languages they regulate the more dominant language to enable spoken production in the less dominant language. How do they engage cognitive control to accomplish regulation? We examined this issue by comparing the consequences of training on language switching in two different contexts. Chinese-English bilinguals were immersed in English (L2) while studying abroad (this study) or in Chinese (L1) in their native language environment (Zhang et al., 2015). In each study, participants performed the AX-CPT task while EEG was recorded and were then trained on language switching. While Zhang et al. found that training enhanced proactive control in the L1 context, there were no effects of training under L2 immersion conditions. Critically, L2 immersed bilinguals revealed enhanced proactive control at pre-test and greater L1 inhibition on language switching relative to L1 immersed bilinguals. We hypothesize that L2 immersion creates a natural training context that increases reliance on proactive control to enable regulation of the L1.

The neural bases of multimodal sensory integration in older adults.

Although hearing often declines with age, prior research has shown that older adults may benefit from multisensory input to a greater extent when compared to younger adults, a concept known as inverse effectiveness. While there is behavioral evidence in support of this phenomenon, less is known about its neural basis. The present fMRI study examined how older and younger adults processed multimodal auditory-visual (AV) phonemic stimuli which were either congruent or incongruent across modalities. Incongruent AV pairs were designed to elicit the McGurk effect. Behaviorally, reaction times were significantly faster during congruent trials compared to incongruent trials for both age groups, and overall older adults responded more slowly. The interaction was not significant suggesting that older adults processed the AV stimuli similarly to younger adults. Although there were minimal behavioral differences, age-related differences in functional activation were identified: Younger adults elicited greater activation than older adults in primary sensory regions including superior temporal gyrus, the calcarine fissure, and left post-central gyrus. In contrast, older adults elicited greater activation than younger adults in dorsal frontal regions including middle and superior frontal gyri, as well as dorsal parietal regions. These data suggest that while there is age-related stability in behavioral sensitivity to multimodal stimuli, the neural bases for this effect differed between older and younger adults. Our results demonstrated that older adults underrecruited primary sensory cortices and had increased recruitment of regions involved in executive function, attention, and monitoring processes, which may reflect an attempt to compensate.

Cerebral white matter connectivity, cognition, and age-related macular degeneration.

Age-related macular degeneration (AMD) is a common retina disease associated with cognitive impairment in older adults. The mechanism(s) that account for the link between AMD and cognitive decline remain unclear. Here we aim to shed light on this issue by investigating whether relationships between cognition and white matter in the brain differ by AMD status. In a direct group comparison of brain connectometry maps from diffusion weighted images, AMD patients showed significantly weaker quantitative anisotropy (QA) than healthy controls, predominantly in the splenium and left optic radiation. The QA of these tracts, however, did not correlate with the visual acuity measure, indicating that this group effect is not directly driven by visual loss. The AMD and control groups did not differ significantly in cognitive performance.Across all participants, better cognitive performance (e.g. verbal fluency) is associated with stronger connectivity strength in white matter tracts including the splenium and the left inferior fronto-occipital fasciculus/inferior longitudinal fasciculus. However, there were significant interactions between group and cognitive performance (verbal fluency, memory), suggesting that the relation between QA and cognitive performance was weaker in AMD patients than in controls.This may be explained by unmeasured determinants of performance that are more common or impactful in AMD or by a recruitment bias whereby the AMD group had higher cognitive reserve. In general, our findings suggest that neural degeneration in the brain might occur in parallel to AMD in the eyes, although the participants studied here do not (yet) exhibit overt cognitive declines per standard assessments.

Age-related differences in resting-state and task-based network characteristics and cognition: a lifespan sample.

Aging is often associated with cognitive and neural decline, but how these factors interact is still not fully understood. Recently, functional connectivity, or the degree to which brain regions are concurrently active, has provided insight into age-related differences. However, functional connectivities during task and rest differ and few studies have examined how these relate to a broad range of cognitive functions. The present study investigated the effect of age on cognition, whole-brain functional connectivity during resting-state and task, and their relationships across the adult lifespan. Cognition was broadly assessed using a battery of cognitive assessments and mean network characteristics were calculated across the whole brain. Behaviorally, increased age was associated with worse recall, executive function, and verbal working memory abilities but better language performance. Neurally, increased age was associated with lower overall within- and between-network functional connectivities during both rest and task, and these age-connectivity relationships were stronger during task performance. Connectivity was also related to cognition, and for all participants, these relationships were strongest during rest. Specifically, higher resting-state between-network functional connectivity was associated with poorer cognition for all adults and poorer language ability among older adults. Collectively, these findings demonstrate that while age effects were strongest during the task, resting-state functional connectivity was most closely tied to cognition. Moreover, these results are theoretically consistent with dedifferentiation accounts of cognition and aging and show that less differentiated functional connectivities are associated with cognitive costs for both older and younger adults.

Quantifying flexibility in thought: The resiliency of semantic networks differs across the lifespan.

Older adults tend to have a broader vocabulary compared to younger adults - indicating a richer storage of semantic knowledge - but their retrieval abilities decline with age. Recent advances in quantitative methods based on network science have investigated the effect of aging on semantic memory structure. However, it is yet to be determined how this aging effect on semantic memory structure relates to its overall flexibility. Percolation analysis provides a quantitative measure of the flexibility of a semantic network, by examining how a semantic memory network is resistant to "attacks" or breaking apart. In this study, we incorporated percolation analyses to examine how semantic networks of younger and older adults break apart to investigate potential age-related differences in language production. We applied the percolation analysis to 3 independent sets of data (total N = 78 younger, 78 older adults) from which we generated semantic networks based on verbal fluency performance. Across all 3 datasets, the percolation integrals of the younger adults were larger than older adults, indicating that older adults' semantic networks were less flexible and broke down faster than the younger adults'. Our findings provide quantitative evidence for diminished flexibility in older adults' semantic networks, despite the stability of semantic knowledge across the lifespan. This may be one contributing factor to age-related differences in language production.

The intensity and connectivity of spontaneous brain activity in a language network relate to aging and language.

Neuroimaging studies often either look at functional activation in response to an explicit task, or functional connectivity (i.e., interregional correlations) during resting-state. Few studies have looked at the intensity of brain activity or its relationship with age, behavior, and language. The current study investigated both intensity (i.e., the Amplitude of Low-Frequency Fluctuations, ALFF) and the functional connectivity of spontaneous brain activity during rest and their relationship with age and language. A life-span sample of individuals (N = 152) completed a battery of neuropsychological tests to assess basic cognitive functions and resting-state functional MRI data to assess spontaneous brain activity. Focusing on an extend language network, the mean ALFF and total degree were calculated for this network. We found that increased age was associated with more intense activity (i.e., higher ALFF) but lower within-network connectivity. Additionally, these increases in activity within the language network during resting-state were related to worse language ability, particularly in younger adults, supporting a dedifferentiation account of cognition. Our results support the utility of using resting-state data as an indicator of cognition and support the role of ALFF as a potential biomarker in characterizing the relationships between resting-state brain activity, age, and cognition.

Neural sensitivity to phonological characteristics is stable across the lifespan.

Aging is often associated with declines in language production. For example, compared to younger adults, older adults experience more tip-of-the-tongue (TOT) states, show decreased speed and accuracy in naming objects, and have more pauses and fillers in speech, all of which indicate age-related increases in retrieval difficulty. While prior work has suggested that retrieval difficulty may be phonologically based, it is unclear whether there are age-related differences in the organization of phonological information per se or whether age-related difficulties may arise from accessing that information. Here we used fMRI to investigate the neural and behavioral basis of phonological neighborhood denisty (PND) effects on picture naming across the lifespan (N=91, ages 20-75). Consistent with prior work, behavioral results revealed that higher PND led to faster picture naming times and higher accuracies overall, and that older adults were less accurate in their responses. Consistent with the behavioral analyses, fMRI analyses showed that increasing PND was associated with decreased activation in auditory and motor language regions, including bilateral superior temporal gyri and bilateral precentral gyri. Interestingly, although there were age-related increases in functional activation to picture naming, there were no age-related modulations of neural sensitivity to PND. Overall, these results suggest that having a large cohort of phonological neighbors facilitates language production, and although aging is associated with increases in language production difficulty, sensitivity to phonological features during language production is stable across the lifespan.

Investigating the effects of phonological neighbors on word retrieval and phonetic variation in word naming and picture naming paradigms.

Phonological neighbors have been shown to affect word processing. Prior work has shown that when a word with an initial voiceless stop has a contrasting initial voiced stop neighbor, Voice Onset Times (VOTs) are longer. Higher phonological neighborhood density (PND) has also been shown to facilitate word retrieval latency, and be associated with longer VOTs. However, these effects have rarely been investigated with picture naming, which is thought to be a more semantically driven task. The current study examined the effects of phonological neighbors on word retrieval times and phonetic variation, and how these effects differed in word naming and picture naming paradigms. Results showed that PND was positively correlated with longer VOT in both paradigms. Furthermore, the effect of initial stop neighbors on VOTs was only significant in word naming. These results highlight the influence of phonological neighbors on word production in different paradigms, support interactive models of word production, and suggest that hyper-articulation in speech does not solely depend on communicative context.

Stronger right hemisphere functional connectivity supports executive aspects of language in older adults.

Healthy older adults commonly report increased difficulties with language production. This could reflect decline in the language network, or age-related declines in other cognitive abilities that support language production, such as executive function. To examine this possibility, we conducted a whole-brain resting-state functional connectivity (RSFC) analysis in older and younger adults using two seed regions-the left posterior superior temporal gyrus and left inferior frontal gyrus. Whole-brain connectivities were then correlated with Stroop task performance to investigate the relationship between RSFC and executive function. We found that overall, younger adults had stronger RSFC than older adults. Moreover, in older, but not younger, adults stronger RSFC between left IFG and right hemisphere executive function regions correlated with better Stroop performance. This suggests that stronger RSFC among older adults between left IFG and right hemisphere regions may serve a compensatory function.

Lexical frequency affects functional activation and accuracy in picture naming among older and younger adults.

As individuals age, they experience increased difficulties producing speech, especially with infrequent words. Older adults report that word retrieval difficulties frequently occur and are highly frustrating. However, little is known about how age affects the neural basis of language production. Moreover, age-related increases in brain activation are often observed, yet there is disagreement about whether such increases represent a form of neural compensation or dedifferentiation. We used functional magnetic resonance imaging (fMRI) to determine if there are age-related differences in functional activation during picture naming and whether such differences are consistent with a compensatory, dedifferentiation, or hybrid account that factors in difficulty. Healthy younger and older adults performed a picture-naming task with stimuli that varied in lexical frequency-our proxy for difficulty. Both younger and older adults were sensitive to lexical frequency behaviorally and neurally. However, younger adults performed more accurately overall and engaged both language (bilateral insula and temporal pole) and cognitive control (bilateral superior frontal gyri and left cingulate) regions to a greater extent than older adults when processing lower frequency items. In both groups, poorer performance was associated with increases in functional activation consistent with dedifferentiation. Moreover, there were age-related differences in the strength of these correlations, with better performing younger adults modulating the bilateral insula and temporal pole and better performing older adults modulating bilateral frontal pole and precuneus. Overall, these findings highlight the influence of task difficulty on fMRI activation in older adults and suggest that as task difficulty increases, older and younger adults rely on different neural resources. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

White matter disconnection is related to age-related phonological deficits.

Older adults have more language production difficulties than younger adults but display largely comparable language comprehension abilities. The Transmission Deficit Hypothesis suggests that production difficulties stem from an age-related increase in phonological signal transmission failures, while the semantic system, being more redundant than the phonological system, allows comprehension to be relatively preserved despite signal failures. Though the neural instantiation of the Transmission Deficit Hypothesis remains an open question, white matter represents one important factor to investigate. Metrics indicative of white matter connectivity across the brain, namely, Radial Diffusivity (RD) and Fractional Anisotropy (FA) have also been linked to age-related cognitive differences including naming difficulties. Using a Picture-Word Interference (PWI) task with 18 younger and 19 older healthy adults, we found that, across ages, better picture naming in the presence of phonological distractors was associated with lower RD across dorsal (r = -.35, p = .03), ventral (r = -.34, p = .04), and fronto-striatal (r = -.33, p = .04) tracts, and higher FA along dorsal tracts (r = .43, p = .008). The pattern of lower RD and higher FA, which is thought to reflect better white matter structure, points to the dorsal stream tracts as critical for performance on the PWI task. Moreover, the effects of RD and FA on performance were attenuated by the effect of age, reflecting the shared variance between age and white matter as it relates to language production ability.

Shared neural recruitment across working memory and motor control tasks as a function of task difficulty and age.

Past research suggests that working memory (WM) and motor control may engage similar cognitive and neural mechanisms in older adults, particularly when task difficulty increases. However, much of this evidence arises from comparisons across behavioral and imaging studies that test only one of the foregoing functional domains. The current study used fMRI within the same group of older adults to investigate whether WM and motor control recruit common mechanisms, and whether recruitment increased with task demand and age. A conjunction analysis across WM and motor tasks revealed engagement of several frontoparietal regions as a function of increasing task demand. A separate conjunction analysis which included age as a predictor showed comparable regions exhibit increased recruitment with both increasing task demand and age. Results suggest that the recruitment of common frontoparietal regions across WM and motor tasks in response to task difficulty is maintained across the older adult lifespan.