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Amnestic mild cognitive impairment (aMCI) has been established as a significant risk factor for Alzheimer‟s disease (AD) and in many cases this state appears to represent an early or incipient stage of AD. Due to difficulties with the diagnosis and prognosis of aMCI and AD, as well as with the projected significant socioeconomic ramifications of AD, there is a need to establish sensitive and reliable biomarkers. The application of event related potentials (ERPs) has been recommended in this context due to their reliability, non-invasive nature, inexpense and relatively widespread availability. This thesis aims to further assess the potential efficacy of ERP markers for such applications. These aims are pursued via investigations of ERPs in healthy ageing, MCI and AD utilising an explicit recognition task that requires the use of key cognitive/memory processes which are often impaired in aMCI and AD. Two ERP effects were analysed: the N400effect which is assumed to index familiarity or trace strength, and the Late Positive Complex (LPC) which appears to index recollection or decision-related factors such as accuracy. Chapter 3 reports ERP and recognition accuracy comparisons between samples of 15 young (mean age = 21.73 years) and 15 older, cognitively healthy adults (mean age = 66.67 years). ERP data were acquired during performance of a word recognition task with high and low memory load conditions (long and short encoding lists, respectively). At test, participants were required to make old/new judgements to visually presented words. There was a trend for young participants to perform more accurately than the older sample, especially on the long list; although these differences only approached significance. However, the N400 old/new effect was found to be significantly reduced in the old compared with the young participants across memory load conditions. LPC old/new effects were generally not observed and this is likely due to the nature of the task which generally places minimal demands on controlled retrieval processes. These results indicate that the N400 effect may be more sensitive to the deleterious effects of ageing on recognition memory-related process(s) than behavioural measures of memory accuracy. Consistent with the view that the N400 indexes familiarity, these results are in accordance with other evidence that familiarity is affected in healthy ageing. The same methodology was used to compare ERPs between aMCI (n = 11) and healthy older adults (n = 11) in Chapter 4. The aMCI participants performed significantly worse than vi healthy elderly participants in discriminating „old‟ from „new‟ words. In the corresponding ERP data, healthy control sample demonstrated significant N400 old/new effects at parietal electrode locations, whereas aMCI participants failed to demonstrate significant N400 old/new effects at any electrode location. Again, LPC effects were not observed in either sample. The absence of significant N400 effects in aMCI participants may reflect a disruption of familiarity-based recognition in aMCI. These results converge with other evidence that the N400 effect may be a sensitive ERP marker useful for detecting, monitoring and/or predicting amnestic related cognitive decline. There are reported variations in underlying causes and sequelae of aMCI (e.g., not all progress to AD). Chapter 5 reports an exploratory investigation aimed at determining whether baseline ERPs differentiate between aMCI participants on the basis of their clinical diagnosis at follow-up. Baseline ERP data were compared in a small sample (n = 7) of aMCI participant who remained cognitively stable at 12-month follow-up (SMCI) with two aMCI participants who progressed to meet an AD diagnosis (PMCI) at the latter time-point. There was a trend for PMCI participants to display smaller old/new effects. However, only one participant displayed significantly smaller N400 old/new effects under low memory load conditions. Interestingly, this participant was also more impaired in baseline cognitive functioning. Chapter 6 examines the relationship between baseline ERPs and performance on neuropsychological assessment at 12-month follow-up in a sample of aMCI and AD participants (n =13) in order to investigate whether ERPs may prove informative for prognoses regarding general trajectories of cognitive decline, irrespective of diagnostic status. Smaller N400 old/new effects (at Fz and CPz) were associated with poorer performance on tasks assessing global cognitive functioning and auditory attention span. Reduced LPC old/new differences were related to poorer performance on tasks assessing global cognitive functioning, verbal learning and memory and better performance on a task assessing working memory at follow-up. In contrast to these results, no relationships were observed between ERP effects and concurrent performance on neuropsychological assessment in this sample, or in 42 elderly participants (including healthy, aMCI and AD), as described in Chapter 7. Taken together these results suggest that ERPs may be more sensitive in predicting future rather than concurrent cognitive functioning and may provide a more objective measure/classification of cognitive impairment vii irrespective of diagnosis. These outcomes are particularly novel as the relationship between baseline ERP data and follow-up neuropsychological measures does not appear to have been systematically reported in the literature to date. Collectively these findings indicate that ERP measure(s), particularly the N400 old/new effect, are sensitive to neurocognitive changes associated with ageing and aMCI, and may prove a useful biomarker for the early detection of AD. This is interesting as the effects of healthy ageing and pathological decline on the N400 from explicit recognition tasks have not been thoroughly explored. Moreover, the N400 (and perhaps, to a lesser degree, LPC) effect(s) appear to have substantial value for informing future prognoses of subsequent cognitive trajectories, at least for persons with amnestic impairment. These results may have significant clinical implications pertaining to the selection and application of efficacious therapeutic interventions in aMCI and AD.

This work concerns the investigation of the neuronal mechanisms at the basis of language acquisition and processing, and the complex interactions of language and attention processes in the human brain. In particular, this research was motivated by two sets of existing neurophysiological data which cannot be reconciled on the basis of current psycholinguistic accounts: on the one hand, the N400, a robust index of lexico-semantic processing which emerges at around 400ms after stimulus onset in attention demanding tasks and is larger for senseless materials (meaningless pseudowords) than for matched meaningful stimuli (words); on the other, the more recent results on the Mismatch Negativity (MMN, latency 100-250ms), an early automatic brain response elicited under distraction which is larger to words than to pseudowords. We asked what the mechanisms underlying these differential neurophysiological responses may be, and whether attention and language processes could interact so as to produce the observed brain responses, having opposite magnitude and different latencies. We also asked questions about the functional nature and anatomical characteristics of the cortical representation of linguistic elements. These questions were addressed by combining neurocomputational techniques and neuroimaging (magneto-encephalography, MEG) experimental methods. Firstly, a neurobiologically realistic neural-network model composed of neuron-like elements (graded response units) was implemented, which closely replicates the neuroanatomical and connectivity features of the main areas of the left perisylvian cortex involved in spoken language processing (i.e., the areas controlling speech output – left inferior-prefrontal cortex, including Broca’s area – and the main sensory input – auditory – areas, located in the left superior-temporal lobe, including Wernicke’s area). Secondly, the model was used to simulate early word acquisition processes by means of a Hebbian correlation learning rule (which reflects known synaptic plasticity mechanisms of the neocortex). The network was “taught” to associate pairs of auditory and articulatory activation patterns, simulating activity due to perception and production of the same speech sound: as a result, neuronal word representations distributed over the different cortical areas of the model emerged. Thirdly, the network was stimulated, in its “auditory cortex”, with either one of the words it had learned, or new, unfamiliar pseudoword patterns, while the availability of attentional resources was modulated by changing the level of non-specific, global cortical inhibition. In this way, the model was able to replicate both the MMN and N400 brain responses by means of a single set of neuroscientifically grounded principles, providing the first mechanistic account, at the cortical-circuit level, for these data. Finally, in order to verify the neurophysiological validity of the model, its crucial predictions were tested in a novel MEG experiment investigating how attention processes modulate event-related brain responses to speech stimuli. Neurophysiological responses to the same words and pseudowords were recorded while the same subjects were asked to attend to the spoken input or ignore it. The experimental results confirmed the model’s predictions; in particular, profound variability of magnetic brain responses to pseudowords but relative stability of activation to words as a function of attention emerged. While the results of the simulations demonstrated that distributed cortical representations for words can spontaneously emerge in the cortex as a result of neuroanatomical structure and synaptic plasticity, the experimental results confirm the validity of the model and provide evidence in support of the existence of such memory circuits in the brain. This work is a first step towards a mechanistic account of cognition in which the basic atoms of cognitive processing (e.g., words, objects, faces) are represented in the brain as discrete and distributed action-perception networks that behave as closed, independent systems.

The purpose of this study is to add to the knowledge of reading development by investigating reading processes from a neurocognitive and educational perspective. This study seeks to provide some insight about reading development for the neuroscience field. The goals of this study are to attain a clearer picture of reading development by using both behavioral assessments and event-related potentials (ERPs), and to begin to bridge the gap between both fields of study. Children between the ages of 7 and 13 were placed in one of two groups depending on their reading comprehension levels for the first analyses, and reading fluency levels for the second analyses. Children were asked to read active, active violation, passive and passive violation sentences, that had been manipulated to contain primed semantic context. Brain waves were recorded during the task. Repeated measures ANOVAS were used to analyze the mean N400 like amplitudes for the groups for the sentence ending target words. The lower fluency group had the largest amplitudes for all sentence types even though the sentences were two grade levels below their actual fluency levels; decoding and reading rate were not a problem for them in the reading task. Also, the lower fluency group processed the anomalous sentences very differently than the lower comprehension group whose average age was close to the same. Other N400 like amplitudes differences among the groups were observed. Implications for reading education consist of reintroducing the sentence processing exercises back into the classroom instruction in order to improve reading comprehension skills among fluent readers with comprehension problems.

The study of human face-processing has granted insight into key adaptions across various social and biological functions. However, there is an overall lack of consistency regarding digital alteration styles of human-face stimuli. In order to investigate this, two independent studies were conducted examining unique effects of image construction and presentation. In the first study, three primary forms of stimuli presentation styles (color, black and white, cutout) were used across iterations of non-thatcherized/thatcherized and non-inverted/inverted presentations. Outcome measures included subjective reactions measured via ratings of perceived “grotesqueness,” and objective outcomes of N170 event-related potentials (ERPs) measured via encephalography. Results of subjective measures indicated that thatcherized images were associated with an increased level of grotesque perception, regardless of overall condition variant and inversion status. A significantly larger N170 component was found in response to cutout-style images of human faces, thatcherized images, and inverted images. Results suggest that cutout image morphology may be considered a well-suited image presentation style when examining ERPs and facial processing of otherwise unaltered human faces. Moreover, less emphasis can be placed on decision making regarding main condition morphology of human face stimuli as it relates to negatively valent reactions. The second study explored commonalities between thatcherized and uncanny images. The purpose of the study was to explore commonalities between these two styles of digital manipulation and establish a link between previously disparate areas of human-face processing research. Subjective reactions to stimuli were measured via participant ratings of “off-putting.” ERP data were gathered in order to explore if any unique effects emerged via N170 and N400 presentations. Two main “morph continuums” of stimuli, provided by Eduard Zell (see Zell et al., 2015), with uncanny features were utilized. A novel approach of thatcherizing images along these continuums was used. thatcherized images across both continuums were regarded as more off-putting than non-thatcherized images, indicating a robust subjective effect of thatcherization that was relatively unimpacted by additional manipulation of key featural components. Conversely, results from brain activity indicated no significant differences of N170 between level of shape stylization and their thatcherized counterparts. Unique effects between continuums and exploratory N400 results are discussed.

The purpose of this study was to compare event-related potential (ERP) effects of speech processing and effects in sentence reading elicited by sentences containing gapping structures, or a "missing" verb. N400 and P600 waveforms were collected in 20 adults between 18 and 30 years of age. Two experiments were conducted with each participant. In the two experiments ERP recordings were collected as sentences, some containing gapping structures, were presented to the subjects. In one experiment sentences were presented through headphones in sentences spoken at normal rate and with normal intonation. In the second experiment sentences with the same gapping structures were presented on a computer screen word by word at a rate of four words per second. Results suggest that all gapping structures are processed at approximately the same time. Amplitude and topography differences were seen between stimuli types and modalities.

Many questions remain unanswered regarding the intricacies of the human brain, especially with regard to the complexities of language processing. One essential component of human sentence processing is the ability to detect, decipher, and recover from errors in the interpretation of both verbal and written language. This process of repair of ungrammatical sentences and revision or reinterpretation of ambiguous sentences has been studied extensively in recent years. A variety of tools have been developed, including the use of event-related potentials (ERPs) in order to assess how language is processed and developed, and to help better identify the nature of these processes. The purpose of this study was to compare event-related potential effects of speech processing of spoken and written sentences containing both incorrect and correct semantic and syntactic information. Specifically, sentences containing correct and incorrect gapping structures, each with a "missing" verb, were presented along with other grammatical and ungrammatical sentences in order to elicit and measure the P300, N400, and P600 amplitudes and latencies. The aim was to determine some of the commonalities and differences in these electrophysiological responses via the auditory and visual modalities. Two experiments were conducted with each participant, one in the auditory modality, and one within the visual using two sets of stimuli. Amplitude and topography differences were noted within and between modalities for each of the components (P300, N400, and P600), as well as between stimulus types. Significant findings suggest that in the adolescent population, incorrect gapping structures are generally processed as semantic errors, as evidenced by the N400 response, followed by the P600 response in both the auditory and visual modalities. The exact nature of the P600 component within gapping structures remains unclear. Of particular interest was the involvement of the occipital area of the brain for the processing of gapping structures. Minimal differences were noted overall between adolescents and the adult populations.

This study investigated the neurophysiology of semantic language processing in children, ages 5 to 12 years. A well-established marker of semantic processing, the N400 event related potential (ERP), was analyzed within and across child age groups. Child N400s were recorded in response to correct sentences, semantically incorrect sentences, and syntactically incorrect sentences. N400s were also recorded across ear condition to examine potential processing differences. Children across all age groups consistently demonstrated N400s in the semantic error condition. N400s were also regularly observed in the syntactic error condition; especially, for younger children. Younger children also demonstrated N400s even in response to correct sentence types. Interestingly, clear N400 effects (i.e. N400 amplitude differences between correct and semantically incorrect sentences) were only observed for one age group. While these findings indicate that children across all age groups detect semantic errors, the ability to consistently parse error types develops later.

Event related potentials (ERPs) may provide specific information about how particular aspects of language are processed by the brain over time. This study investigated the electrophysiology of language processing in two children with language impairment (LI) when compared to five typically developing children. The N400, P600, and the early left anterior negativity (ELAN) were analyzed after participants listened to linguistically correct, syntactically incorrect, and semantically incorrect sentences. Participants were instructed to indicate whether the sentences were correct or incorrect. Latency and amplitude of the ERP components were compared between the two groups of participants and sentence types. Results from the current study concerning the typically developing children suggest that, at least by eight years of age, typically developing children may process linguistic information similarly to adults with regard to the areas of the brain that are activated during the processing of linguistic stimuli. When comparing results from participants with LI and their typically developing counterparts, results indicate that children with LI exhibit slower real-time language processing than typically developing children. Results also indicate that children with LI require more effort than typically developing children in processing linguistic information as indicated by the amplitude of the N400 and the ELAN. In analyzing the P600 in both groups of participants, results indicate that syntactic processing may be intact in children with LI as well as typical children. Results concerning the N400 and the ELAN were variable between the two participants with LI indicating that children with LI may be heterogeneous even in the presence of similar tasks. Results obtained from the ELAN may also indicate that the ELAN is not fully mature at eight years of age.

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