An Electrophysiological Examination of Semantic and Syntactic Anomaly Processing in Sentences: Effects of Aging and Focal Brain Lesions

Event-related brain potentials (ERPs) have the capacity to tap into language comprehension as it unfolds in real time. ERPs may, therefore, not only provide essential information on the temporal dynamics of language comprehension, but may also contribute to an adequate characterization of the temporal and functional locus of comprehension deficits. A prerequisite for pathological ERP studies is a comprehensive understanding of the electrophysiological correlates of the processing of different types of linguistic information (e.g., semantic and syntactic). These ERP correlates have been extensively researched in young healthy adults. Application of the functional interpretations of ERP components to a poststroke aphasic population, however, requires the consideration of the effects of normal aging, as the CVA etiology is predominantly associated with advanced age. Few studies have investigated age-related changes in language-related ERP components. Thus, one of the major objectives of this thesis was to determine whether potential nonpathological agerelated differences in auditory language comprehension were reflected in the electrophysiological response observed to semantic and syntactic anomalies, thus providing an essential foundation from which to interpret ERP findings in aphasia. The electrophysiological response to auditory sentence-embedded semantic and syntactic (phrase structure) anomalies was first established in a group of healthy young adults, who showed a small, centroparietally distributed negativity starting at around 200 ms post stimulus onset for syntactic anomalies. Semantic anomalies elicited a robust N400. A bilateral, widely distributed P600 was observed for both semantic and syntactic anomalies. The results are discussed in terms of their functional significance with a special focus on the P600, which, in the domain of language processing, may reflect processes of reanalysis and repair that are not exclusively based on syntactic information but may also include semantic aspects of the sentence. To provide a comprehensive description of age-related effects on the established ERP correlates, differences between young and elderly subjects were investigated and the effects of advancing age were examined in a larger number of senior subjects of a wider, welldefined age range. These experiments clearly demonstrated that changes in the processing of semantic and syntactic anomalies occur with normal aging. Older adults, like young adults, processed the meaning of sentences online and sentence context had a facilitating effect as indicated by larger N400s to semantically incongruous than to congruous constructions. However, the N400 (effect) was significantly smaller in elderly compared to young adults, and it was further demonstrated that the auditory N400 effect was systematically reduced with advancing age. Possible mechanisms explaining age-related N400 reductions, including less selective activation and/or less efficient predictive use of context, are discussed. Peak latencies of the N400 (effect), on the other hand, were not affected by normal aging, thus indicating that with the processing of natural connected speech, integration of a word into the higher-order meaning representation of the preceding sentence context is not delayed. Furthermore, processes of reanalysis and repair in the presence of a semantic or syntactic anomaly, as reflected in the P600, were comparable in magnitude and timing for young and elderly subjects. However, P600 effects were found to be slightly larger over more anterior recording sites in older elderly compared to middleaged adults, although this increase in effect size was not systematic with age. As temporal alterations in language processing have been identified as a possible cause of comprehension deficits observed in poststroke aphasic individuals, the potential temporal aspects of such deficits and recovery thereof were investigated in the last two studies presented in this thesis. A dissociation between syntactic and semantic ERP results was observed in a patient exhibiting a mild comprehension deficit, especially with regard to late positivities. The P600 to syntactic anomalies was reduced and clearly delayed in the patient, possibly indicating delayed or incomplete access or use of word category information necessary for the construction of phrase structure. The temporal dynamics of recovery from aphasic comprehension deficits were investigated in a longitudinal case study. The patient had recovered considerably from her initial mild-moderate comprehension deficit, as indicated by her performance on offline language tests. At the last of three consecutive assessments spanning the first eight months post stroke, she showed an electrophysiological response to semantic anomalies which was comparable to that observed in healthy elderly control subjects. In contrast, the patients response to syntactically anomalous constructions was different at all assessments. Possible accounts for the observed discrepancy as well as methodological implications of the obtained results are discussed. The series of studies presented in this thesis served to provide a comprehensive investigation into the electrophysiological correlates of auditory language comprehension in healthy young, healthy elderly and poststroke aphasic subjects, highlighting the capacity of the ERP methodology to reveal valuable information on temporal as well as functional aspects of language processing, its impairment and recovery

Real-world evidence study on tolerance and growth in infants fed an infant formula with two human milk oligosaccharides vs mixed fed and exclusively breastfed infants

Abstract Introduction Human milk oligosaccharides (HMOs) are important components of human milk having diverse functions in the development of infants. Randomized controlled trials (RCTs) have demonstrated that infant formulas with the HMOs 2′-fucosyllactose (2′FL) and lacto-N-neotetraose (LNnT) are safe, well-tolerated, and support normal growth. This study aimed to generate real-world evidence (RWE) on growth and gastrointestinal (GI) tolerance in infants consuming a formula with 1 g/L 2′FL and 0.5 g/L LNnT, including a mixed feeding group not studied before in RCTs. Participants and methods This 8-week open-label prospective multicenter study was conducted in Germany and Austria, and included groups of healthy, exclusively breastfed infants (BF), exclusively formula-fed infants (FF) who received the HMO-formula, and infants mixed fed with both HMO formula and human milk (MF). Co-primary outcomes were anthropometry and gastrointestinal tolerance via validated Infant Gastrointestinal Symptom Questionnaire (IGSQ). Secondary outcomes included formula satisfaction and adverse events (AEs). Results One-hundred six infants completed the study (46 FF, 22 MF, and 38 BF). Mean anthropometric z-scores were comparable between groups and generally within ± 0.5 of WHO medians at week 8. IGSQ composite scores demonstrated good GI tolerance in all groups with no significant group differences at week 4 or 8. IGSQ composite scores in FF improved during the course of the study and parents provided high satisfaction ratings for the HMO-formula. Four potentially product-related AEs were reported in FF (no in MF). Conclusions In this RWE study examining an infant formula with HMOs, growth and GI tolerance outcomes were confirming the good tolerance and safety of this early feeding option previously reported in RCTs