Estimating statistical power for structural equation models in developmental cognitive science: A tutorial in R : Power simulation for SEMs.

Determining the compositional structure and dimensionality of psychological constructs lies at the heart of many research questions in developmental science. Structural equation modeling (SEM) provides a versatile framework for formalizing and estimating the relationships among multiple latent constructs. While the flexibility of SEM can accommodate many complex assumptions on the underlying structure of psychological constructs, it makes a priori estimation of statistical power and required sample size challenging. This difficulty is magnified when comparing non-nested SEMs, which prevents the use of traditional likelihood-ratio tests. Sample size estimates for SEM model fit comparisons typically rely on generic rules of thumb. Such heuristics can be misleading because statistical power in SEM depends on a variety of model properties. Here, we demonstrate a Monte Carlo simulation approach for estimating a priori statistical power for model selection when comparing non-nested models in an SEM framework. We provide a step-by-step guide to this approach based on an example from our memory development research in children.

Speaker Competence Affects Prefrontal Theta and Occipital Alpha Power during Selective Word Learning in Preschoolers.

In the present study, we investigated the cognitive processes underlying selective word learning in preschoolers. We measured rhythmic neural activity in the theta (4-8 Hz) and alpha frequency range (7-12 Hz) in 67 four-year-olds. EEG was recorded during anticipation and encoding of novel labeling events performed by a speaker who had previously shown either competence (correct) or incompetence (incorrect) in labeling familiar objects. In both groups, children selected the target object equally often upon recall. However, children observing the incompetent speaker revealed weaker representations of novel words indicated by an increased likelihood for selecting familiar but incorrect items upon recall. Modulations in theta and alpha power suggest differential processing of novel label-object pairs depending on the speakers' competence. In the incompetent, but not the competent, speaker condition, increases in prefrontal theta power during anticipation and encoding were related to increased recall success. Findings suggest that theta power in the present study reflects cognitive control. In both conditions, occipital alpha power-indicating attentional processes-reflected familiarity with novel items, but in opposite directions. In familiar item trials, alpha power was increased observing the incompetent and decreased observing the competent speaker. Thus, both cognitive control and attention processes during word learning are differentially affected by speaker characteristics.

Age differences in generalization, memory specificity, and their overnight fate in childhood.

Memory enables generalization to new situations, and memory specificity that preserves individual episodes. This study investigated generalization, memory specificity, and their overnight fate in 141 4- to 8-year-olds (computerized memory game; 71 females, tested 2020-2021 in Germany). The results replicated age effects in generalization and memory specificity, and a contingency of generalization on object conceptual properties and interobject semantic proximity. Age effects were stronger in generalization than in memory specificity, and generalization was more closely linked to the explicit regularity knowledge in older than in younger children. After an overnight delay, older children retained more generalized and specific memories and showed greater gains but only in generalization. These findings reveal distinct age differences in generalization and memory specificity across childhood.

Sleep spindle maturity promotes slow oscillation-spindle coupling across child and adolescent development.

The synchronization of canonical fast sleep spindle activity (12.5-16 Hz, adult-like) precisely during the slow oscillation (0.5-1 Hz) up peak is considered an essential feature of adult non-rapid eye movement sleep. However, there is little knowledge on how this well-known coalescence between slow oscillations and sleep spindles develops. Leveraging individualized detection of single events, we first provide a detailed cross-sectional characterization of age-specific patterns of slow and fast sleep spindles, slow oscillations, and their coupling in children and adolescents aged 5-6, 8-11, and 14-18 years, and an adult sample of 20- to 26-year-olds. Critically, based on this, we then investigated how spindle and slow oscillation maturity substantiate age-related differences in their precise orchestration. While the predominant type of fast spindles was development-specific in that it was still nested in a frequency range below the canonical fast spindle range for the majority of children, the well-known slow oscillation-spindle coupling pattern was evident for sleep spindles in the adult-like canonical fast spindle range in all four age groups-but notably less precise in children. To corroborate these findings, we linked personalized measures of fast spindle maturity, which indicate the similarity between the prevailing development-specific and adult-like canonical fast spindles, and slow oscillation maturity, which reflects the extent to which slow oscillations show frontal dominance, with individual slow oscillation-spindle coupling patterns. Importantly, we found that fast spindle maturity was uniquely associated with enhanced slow oscillation-spindle coupling strength and temporal precision across the four age groups. Taken together, our results suggest that the increasing ability to generate adult-like canonical fast sleep spindles actuates precise slow oscillation-spindle coupling patterns from childhood through adolescence and into young adulthood.

Cells in the brain are wired together like an electric circuit that can relay information from one area of the brain to the next. Even when sleeping, the human brain continues to send signals to process information it has encountered during the day. This results in two patterns of electrical activity that define the sleeping brain: slowly repeating waves (or slow oscillations) and rapid bursts of activity known as sleep spindles. Although slow oscillations and sleep spindles are generated in different regions of the brain, they often happen at the same time. This syncing of activity is thought to help different parts of the brain to communicate with each other. Such communication is essential for new memories to become stable and last a long time. In children, slow oscillations and sleep spindles appear together less frequently, suggesting that these co-occurring patterns of electrical activity develop as humans grow into adults. Here, Joechner et al. set out to understand what drives slow oscillations and sleep spindles to start happening at the same time. The team used a technique called electroencephalography (or EEG for short) to study the brain activity of children, teenagers and adults as they slept. This revealed that slow oscillations and sleep spindles occur together less often in children compared to teenagers and adults. Moreover, the slow oscillations and sleep spindles observed in the children had very different physical characteristics to those observed in adults. Further analyses showed that the more similar the children's sleep spindles were to adult spindles, the more consistently they appeared at the same time as the slow oscillations. The findings of Joechner et al. suggest that as children grow up, their sleep spindles become more adult-like, causing the spindles to happen at the same time as slow oscillations more consistently. This indicates that brain circuits that generate sleep spindles may play an essential role in developing successful communication networks in the human brain. In the future, this work may ultimately provide new insights into how age-related changes to the brain contribute to cognitive development, and suggests sleep as a potential intervention target for neurodevelopmental disorders.

The integrity of dopaminergic and noradrenergic brain regions is associated with different aspects of late-life memory performance.

Changes in dopaminergic neuromodulation play a key role in adult memory decline. Recent research has also implicated noradrenaline in shaping late-life memory. However, it is unclear whether these two neuromodulators have distinct roles in age-related cognitive changes. Here, combining longitudinal MRI of the dopaminergic substantia nigra-ventral tegmental area (SN-VTA) and noradrenergic locus coeruleus (LC) in younger (n = 69) and older (n = 251) adults, we found that dopaminergic and noradrenergic integrity are differentially associated with memory performance. While LC integrity was related to better episodic memory across several tasks, SN-VTA integrity was linked to working memory. Longitudinally, we found that older age was associated with more negative change in SN-VTA and LC integrity. Notably, changes in LC integrity reliably predicted future episodic memory. These differential associations of dopaminergic and noradrenergic nuclei with late-life cognitive decline have potential clinical utility, given their degeneration in several age-associated diseases.

Declining locus coeruleus-dopaminergic and noradrenergic modulation of long-term memory in aging and Alzheimer's disease.

Memory is essential in defining our identity by guiding behavior based on past experiences. However, aging leads to declining memory, disrupting older adult's lives. Memories are encoded through experience-dependent modifications of synaptic strength, which are regulated by the catecholamines dopamine and noradrenaline. While cognitive aging research demonstrates how dopaminergic neuromodulation from the substantia nigra-ventral tegmental area regulates hippocampal synaptic plasticity and memory, recent findings indicate that the noradrenergic locus coeruleus sends denser inputs to the hippocampus. The locus coeruleus produces dopamine as biosynthetic precursor of noradrenaline, and releases both to modulate hippocampal plasticity and memory. Crucially, the locus coeruleus is also the first site to accumulate Alzheimer's-related abnormal tau and severely degenerates with disease development. New in-vivo assessments of locus coeruleus integrity reveal associations with Alzheimer's markers and late-life memory impairments, which likely stem from impaired dopaminergic and noradrenergic neurotransmission. Bridging research across species, the reviewed findings suggest that degeneration of the locus coeruleus results in deficient dopaminergic and noradrenergic modulation of hippocampal plasticity and thus memory decline.

Age differences in neural distinctiveness during memory encoding, retrieval, and reinstatement.

Robust evidence points to mnemonic deficits in older adults related to dedifferentiated, i.e. less distinct, neural responses during memory encoding. However, less is known about retrieval-related dedifferentiation and its role in age-related memory decline. In this study, younger and older adults were scanned both while incidentally learning face and house stimuli and while completing a surprise recognition memory test. Using pattern similarity searchlight analyses, we looked for indicators of neural dedifferentiation during encoding, retrieval, and encoding-retrieval reinstatement. Our findings revealed age-related reductions in neural distinctiveness during all memory phases in visual processing regions. Interindividual differences in retrieval- and reinstatement-related distinctiveness were strongly associated with distinctiveness during memory encoding. Both item- and category-level distinctiveness predicted trial-wise mnemonic outcomes. We further demonstrated that the degree of neural distinctiveness during encoding tracked interindividual variability in memory performance better than both retrieval- and reinstatement-related distinctiveness. All in all, we contribute to meager existing evidence for age-related neural dedifferentiation during memory retrieval. We show that neural distinctiveness during retrieval is likely tied to recapitulation of encoding-related perceptual and mnemonic processes.

Age-related declines in neural selectivity manifest differentially during encoding and recognition.

One important factor contributing to age-related memory decline is the loss of distinctiveness with which information is represented in brain activity. This loss in neural selectivity may be driven by neural attenuation (i.e., reduced activation to target stimuli) or neural broadening (i.e., increased activation to nontarget stimuli). In this fMRI study, we assessed age differences in neural selectivity during first encoding, repeated encoding, and recognition, as well as the underlying pattern (broadening vs. attenuation). We found lower neural selectivity in older compared to younger adults during all memory stages. Crucially, while reduced selectivity in older adults was due to neural broadening during first encoding, it was driven by neural attenuation during recognition, but revealed no clear pattern during repeated encoding. Our findings suggest that intrinsic differences between memory stages may interact with neural activity to manifest as either neural broadening or attenuation. Moreover, despite these differential patterns, neural selectivity was highly correlated across memory stages, indicating that one common mechanism may underly distinct expressions of age-related neural dedifferentiation.

Age differences in diffusivity in the locus coeruleus and its ascending noradrenergic tract.

The noradrenergic locus coeruleus (LC) is a small brainstem nucleus that promotes arousal and attention. Recent studies have examined the microstructural properties of the LC using diffusion-weighted magnetic resonance imaging and found unexpected age-related differences in fractional anisotropy - a measure of white matter integrity. Here, we used two datasets (Berlin Aging Study-II, N = 301, the Leipzig Study for Mind-Body-Emotion Interactions, N = 220), to replicate published findings and expand them by investigating diffusivity in the LC's ascending noradrenergic bundle. In younger adults, LC fractional anisotropy was significantly lower, compared to older adults. However, in the LC's ascending noradrenergic bundle, we observed significantly higher fractional anisotropy in younger adults, relative to older adults. These findings indicate that diffusivity in the LC versus the ascending noradrenergic bundle are both susceptible to structural changes in aging that have opposing effects on fractional anisotropy.

Locus coeruleus integrity is related to tau burden and memory loss in autosomal-dominant Alzheimer's disease.

Abnormally phosphorylated tau, an indicator of Alzheimer's disease, accumulates in the first decades of life in the locus coeruleus (LC), the brain's main noradrenaline supply. However, technical challenges in in-vivo assessments have impeded research into the role of the LC in Alzheimer's disease. We studied participants with or known to be at-risk for mutations in genes causing autosomal-dominant Alzheimer's disease (ADAD) with early onset, providing a unique window into the pathogenesis of Alzheimer's largely disentangled from age-related factors. Using high-resolution MRI and tau PET, we found lower rostral LC integrity in symptomatic participants. LC integrity was associated with individual differences in tau burden and memory decline. Post-mortem analyses in a separate set of carriers of the same mutation confirmed substantial neuronal loss in the LC. Our findings link LC degeneration to tau burden and memory in Alzheimer's, and highlight a role of the noradrenergic system in this neurodegenerative disease.

Spectral pattern similarity analysis: Tutorial and application in developmental cognitive neuroscience.

The human brain encodes information in neural activation patterns. While standard approaches to analyzing neural data focus on brain (de-)activation (e.g., regarding the location, timing, or magnitude of neural responses), multivariate neural pattern similarity analyses target the informational content represented by neural activity. In adults, a number of representational properties have been identified that are linked to cognitive performance, in particular the stability, distinctiveness, and specificity of neural patterns. However, although growing cognitive abilities across childhood suggest advancements in representational quality, developmental studies still rarely utilize information-based pattern similarity approaches, especially in electroencephalography (EEG) research. Here, we provide a comprehensive methodological introduction and step-by-step tutorial for pattern similarity analysis of spectral (frequency-resolved) EEG data including a publicly available pipeline and sample dataset with data from children and adults. We discuss computation of single-subject pattern similarities and their statistical comparison at the within-person to the between-group level as well as the illustration and interpretation of the results. This tutorial targets both novice and more experienced EEG researchers and aims to facilitate the usage of spectral pattern similarity analyses, making these methodologies more readily accessible for (developmental) cognitive neuroscientists.

Noradrenergic modulation of rhythmic neural activity shapes selective attention.

During moments involving selective attention, the thalamus orchestrates the preferential processing of prioritized information by coordinating rhythmic neural activity within a distributed frontoparietal network. The timed release of neuromodulators from subcortical structures dynamically sculpts neural synchronization in thalamocortical networks to meet current attentional demands. In particular, noradrenaline modulates the balance of cortical excitation and inhibition, as reflected by thalamocortical alpha synchronization (~8-12 Hz). These neuromodulatory adjustments facilitate the selective processing of prioritized information. Thus, by disrupting effective rhythmic coordination in attention networks, age-related locus coeruleus (LC) degeneration can impair higher levels of neural processing. In sum, findings across different levels of analysis and modalities shed light on how the noradrenergic modulation of neural synchronization helps to shape selective attention.

Electrophysiological indicators of sleep-associated memory consolidation in 5- to 6-year-old children.

In adults, the synchronized interplay of sleep spindles (SP) and slow oscillations (SO) supports memory consolidation. Given tremendous developmental changes in SP and SO morphology, it remains elusive whether across childhood the same mechanisms as identified in adults are functional. Based on topography and frequency, we characterize slow and fast SPs and their temporal coupling to SOs in 24 pre-school children. Further, we ask whether slow and fast SPs and their modulation during SOs are associated with behavioral indicators of declarative memory consolidation as suggested by the literature on adults. Employing an individually tailored approach, we reliably identify an inherent, development-specific fast centro-parietal SP type, nested in the adult-like slow SP frequency range, along with a dominant slow frontal SP type. Further, we provide evidence that the modulation of fast centro-parietal SPs during SOs is already present in pre-school children. However, the temporal coordination between fast centro-parietal SPs and SOs is weaker and less precise than expected from research on adults. While we do not find evidence for a critical contribution of SP-SO coupling for memory consolidation, crucially, slow frontal and fast centro-parietal SPs are each differentially related to sleep-associated consolidation of items of varying quality. Whereas a higher number of slow frontal SPs is associated with stronger maintenance of medium-quality memories, a higher number of fast centro-parietal SPs is linked to a greater gain of low-quality items. Our results demonstrate two functionally relevant inherent SP types in pre-school children although SP-SO coupling is not yet fully mature.

Effects of age differences in memory formation on neural mechanisms of consolidation and retrieval.

Episodic memory decline is a hallmark of cognitive aging and a multifaceted phenomenon. We review studies that target age differences across different memory processing stages, i.e., from encoding to retrieval. The available evidence suggests that age differences during memory formation may affect the quality of memory representations in an age-graded manner with downstream consequences for later processing stages. We argue that low memory quality in combination with age-related neural decline of key regions of the episodic memory network puts older adults in a double jeopardy situation that finally results in broader memory impairments in older compared to younger adults.

Tracking Age Differences in Neural Distinctiveness across Representational Levels.

The distinctiveness of neural information representation is crucial for successful memory performance but declines with advancing age. Computational models implicate age-related neural dedifferentiation on the level of item representations, but previous studies mostly focused on age differences of categorical information representation in higher-order visual regions. In an age-comparative fMRI study, we combined univariate analyses and whole-brain searchlight pattern similarity analyses to elucidate age differences in neural distinctiveness at both category and item levels and their relation to memory. Thirty-five younger (18-27 years old) and 32 older (67-75 years old) women and men incidentally encoded images of faces and houses, followed by an old/new recognition memory task. During encoding, age-related neural dedifferentiation was shown as reduced category-selective processing in ventral visual cortex and impoverished item specificity in occipital regions. Importantly, successful subsequent memory performance built on high item stability, that is, high representational similarity between initial and repeated presentation of an item, which was greater in younger than older adults. Overall, we found that differences in representational distinctiveness coexist across representational levels and contribute to interindividual and intraindividual variability in memory success, with item specificity being the strongest contributor. Our results close an important gap in the literature, showing that older adults' neural representation of item-specific information in addition to categorical information is reduced compared with younger adults.SIGNIFICANCE STATEMENT A long-standing hypothesis links age-related cognitive decline to a loss of neural specificity. While previous evidence supports the notion of age-related neural dedifferentiation of category-level information in ventral visual cortex, whether or not age differences exist at the item level was a matter of debate. Here, we observed age group differences at both levels as well as associations between both categorical distinctiveness and item specificity to memory performance, with item specificity being the strongest contributor. Importantly, age differences in occipital item specificity were largely due to reduced item stability across repetitions in older adults. Our results suggest that age differences in neural representations can be observed across the entire cortical hierarchy and are not limited to category-level information.

Memory specificity is linked to repetition effects in event-related potentials across the lifespan.

The specificity with which past experiences can be remembered varies across the lifespan, possibly due to differences in how precisely information is encoded. Memory formation can be investigated through repetition effects, the common finding that neural activity is altered when stimuli are repeated. However, whether differences in this indirect measure of memory formation relate to lifespan differences in memory specificity has not yet been established. In the present study, we examined repetition effects in event-related potentials and their relation to recognition. During incidental encoding, children (aged 7-9 years), young adults (18-30 years), and older adults (65-76 years) viewed repeated object images from different categories. During subsequent recognition, we distinguished memory for the specific items versus the general categories. We identified repetition suppression in all age groups, and repetition enhancement for adults. Furthermore, individual item recognition performance comprising lure discrimination was positively associated with the magnitude of the neural repetition effects, which did not differ between groups, indicating common neural mechanisms of memory formation. Our findings demonstrate that neural repetition effects reflect the formation of highly specific memory representations and highlight their significance as a neural indicator of individual differences in episodic memory encoding across the lifespan.

Locus coeruleus MRI contrast is associated with cortical thickness in older adults.

There is growing evidence that neuronal integrity of the noradrenergic locus coeruleus (LC) is important for later-life cognition. Less understood is how LC integrity relates to brain correlates of cognition, such as brain structure. Here, we examined the relationship between cortical thickness and a measure reflecting LC integrity in 229 older and 67 younger adults. Using a magnetic resonance imaging sequence which yields high signal intensity in the LC, we assessed the contrast between signal intensity of the LC and that of neighboring pontine reference tissue. The FreeSurfer software suite was used to quantify cortical thickness. LC contrast was positively related to cortical thickness in older adults, and this association was prominent in parietal, frontal, and occipital regions. Brain regions where LC contrast was related to cortical thickness include portions of the frontoparietal network which have been implicated in noradrenergically modulated cognitive functions. These findings provide novel evidence for a link between LC structure and cortical brain structure in later adulthood.

Noradrenergic Responsiveness Supports Selective Attention across the Adult Lifespan.

Selectively attending to relevant information while blocking out distractors is crucial for goal-directed behavior, yet with advancing age, deficits emerge in attentional selectivity. Decrements in attention have been associated with altered noradrenergic activity in animals. However, research linking noradrenergic functioning to attention in aging humans is scarce, likely reflecting long-standing methodological challenges in noninvasive assessments. We studied whether age-related differences in the noradrenergic system predict differences in attention. We measured pupil dilation, a noninvasive marker of arousal-related norepinephrine (NE) release, while concurrently recording the EEG of male younger (N = 39; 25.2 ± 3.2 years) and older adults (N = 38; 70.6 ± 2.7 years). Arousal was modulated on a trial-by-trial basis using fear-conditioned (CS+) stimuli. During conditioning, pupil and EEG markers related to heightened arousal were identified. Afterward, in a dichotic listening task, participants were cued to direct attention to either the left or right ear while highly similar syllable pairs were presented simultaneously to both ears. During the dichotic listening task, presentation of fear-conditioned stimuli reinstated the acquired arousal response, as reflected in pupil and EEG α-ß band responses. Critically, pupil dilation to CS+ was correlated with stronger EEG α-ß desynchronization, suggesting a common dependence on NE release. On a behavioral level, stronger arousal reactions were associated with better attention. In particular, structural equation modeling revealed that the responsiveness of the NE system is associated with attention on a latent construct level, measured by several indicator tasks. Overall, our results suggest that the responsiveness of the NE system supports attention across the lifespan.SIGNIFICANCE STATEMENT In old age, the ability to selectively process relevant aspects of the environment fades. Animal research suggests that the neuromodulator norepinephrine helps to maintain selective attention. We tested younger and older adults across a variety of attention tasks. In addition, we used arousing stimuli to experimentally activate participants' noradrenergic system while recording pupillometry and EEG to infer its functional capacity. Older adults showed compromised attention and reduced noradrenergic responsiveness as indicated by interrelated pupil and EEG markers. Crucially, in both age groups, a more responsive noradrenergic system was strongly associated with attention. Our findings link animal and human studies on the neural underpinning of attention in aging and underscore the importance of the noradrenergic system in late-life cognition.