Components of aging

Age-related cognitive decline has been linked to a reduction in attentional resources that are assumed to result from alterations in the aging brain. A core ability that is subject to age-related decline is visual attention, which enables individuals to select the most important information for conscious processing and action. However, visual attention is considered a conglomerate of various functions and the specific components underlying age differences in performance remain little understood. The present PhD project aimed at dissociating age effects on several (sub-) components that concur in visual attention tasks within a neurocognitive approach. Established and theoretically grounded psychological paradigms that allow separating various attentional components were combined with event-related potentials (ERPs), which provide a temporally fine-graded dissociation of cognitive processes involved in a task. 1st Project The first project was designed to determine the origin(s) of age-related decline in visual search, a key paradigm of attention research. To pursue this goal on a micro-level, response time measures in a compound-search task, in which the target-defining feature of a pop-out target (color/shape) was dissociated from the response-defining feature (orientation), were coupled with lateralized ERPs. Several ERP components tracked the timing of processing stages involved in this task, these being (1) allocation of attention to the target, marked by the posterior-contralateral negativity (PCN), (2) target analyses in vSTM, marked by the sustained posterior-contralateral negativity (SPCN), (3) response selection, marked by the stimulus-locked lateralized readiness potential (LRP) and (4) response execution, marked by the response-locked LRP. Slowed response times (RT) in older participants were associated with age differences in all analyzed ERPs, indicating that behavioural slowing accrues across multiple stages within the information processing stream. Furthermore, v behavioral data and ERPs were analyzed with respect to age and carry-over effects from one trial to the next. The intertrial analyses revealed relatively automatic processes – such as dimension weighting facilitating the early stage of visual selection, and response weighting facilitating the late stage of response execution – to be preserved in older age. By contrast, more controlled processes – such as the flexible stimulus-response (S-R) (re-) mapping across trials on the intermediate stages of response selection - were particularly affected by aging. This indicates that besides general slowing, specific age decrements in executively controlled processes contribute to age-related decline in visual search. 2nd Project The second project explored neural markers of individual and age differences in attention parameters formally integrated in Bundesen’s computational Theory of Visual Attention (TVA). According to the model, two parameters of general visual attention capacity, perceptual processing speed C and visual short-term memory (vSTM) storage capacity K are defined and can be modeled mathematically independently for a particular individual. More recently, the neural interpretation of the model (NTVA) suggested that the two functions (at least partly) rely on distinct brain mechanisms. To test this assumption in an empirical approach, individual TVA-based estimates were derived in a standard TVA whole report task, and ERPs of the same participants were recorded in an adapted EEG-compatible version of the task. In the first study of the second project, we explored neurophysiological markers of interindividual differences in the two functions in younger participants. The results revealed distinct ERP correlates to be related to the parameters: Individuals with higher compared to lower processing speed C had significantly smaller posterior N1 amplitudes, suggesting that the rate of object categorization is associated with the efficiency of early visual processing. Individuals with higher compared to lower storage capacity showed stronger contralateral delay activity (CDA) over visual areas, indicating that the limit of vi vSTM relies on topographically-organized sustained activation within the visual system. These results can be regarded as direct neuroscientific evidence for central assumptions of the theoretical framework. In the second study of the second project, the same approach was pursued to investigate whether and how TVA attentional capacity parameters and their neural markers change with aging. First, the same ERP correlates of processing speed and storage capacity indexing individual differences in younger participants (i.e., the posterior N1 marked differences in processing speed C and the CDA marked differences in storage capacity K, respectively) were found to be valid also in the older group. In addition to this, two further components marked performance differences in the parameters exclusively within the older group: Older participants with lower processing speed showed smaller anterior N1 amplitudes relative to faster older and all younger participants, suggesting a selective loss of resources supporting early control of attentional guidance. Older participants with higher storage capacity exhibited a stronger right-central positivity than older participants with lower storage capacity and all younger participants. This pattern is indicative of compensatory recruitment of additional neural resources in high-functioning older individuals, presumably related to enhanced executive control fostering sustained activation of vSTM representations. Again, these findings strongly support the NTVA framework, proposing distinct neural mechanisms underlying processing speed and storage capacity. Furthermore, they show that distinct mechanisms of attentional control determine the two functions in older age

Mulitple ways to the prior occurrence of an event: An electrophysiological dissociation of experimental and conceptually driven familiarity

Contains fulltext : 221784.pdf (publisher's version ) (Closed access)Recent research has shown that familiarity contributes to associative memory when the to-be-associated stimuli are unitized during encoding. However, the specific processes underlying familiarity-based recognition of unitized representations are still indefinite. In this study, we present electrophysiologically dissociable early old/new effects, presumably related to two different kinds of familiarity inherent in associative recognition tasks. In a study-test associative recognition memory paradigm, we employed encoding conditions that established unitized representations of two pre-experimentally unrelated words, e.g. vegetable-bible. We compared event-related potentials (ERP) during the retrieval of these unitized word pairs using different retrieval cues. Word pairs presented in the same order as during unitization at encoding elicited a parietally distributed early old/new effect which we interpret as reflecting conceptually driven familiarity for newly formed concepts. Conversely, word pairs presented in reversed order only elicited a topographically dissociable early effect, i.e. the mid-frontal old/new effect, the putative correlate of experimental familiarity. The late parietal old/new effect, the putative ERP correlate of recollection, was obtained irrespective of word order, though it was larger for words presented in same order. These results indicate that familiarity may not be a unitary process and that different task demands can promote the assessment of conceptually driven familiarity for novel unitized concepts or experimentally-induced increments of experimental familiarity, respectively.13 p

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis