Exploring the Nature of Neural Correlates of Language, Attention and Memory: Reliability and Validity Studies of Event Related Potentials

Comparing data from different subfields of research may help in understanding emerging patterns and refining interpretations. This is especially true in neuroscience because brain functions can be studied at multiple levels of analysis, spatially and temporally, and with a variety of complementary measurement techniques. Within the ERP domain, several subfields of research have evolved over time, typically reflecting the specific time-window of interest and brain function investigated. The current investigation focused on three widely studied ERP effects reflecting a variety of key brain functions: the N400 effect, the P3b effect and the Left Parietal effect. The N400 effect has attracted researchers interested in language processing, the P3b effect researchers interested in attentional processes and the Left Parietal effect researchers focused on episodic recollection. Even though the ERP technology constitutes a common thread across these subfields, there is often a lack of communication across groups of researchers. The literatures on the N400 effect, P3b effect and Left Parietal effect have been written by relatively non-overlapping groups of researchers, and as such the kind of analysis carried out in the current thesis is not a common one, as it compares effects investigated within different subfields. Specifically, the approach taken in the current thesis involves assessment of the comparative reliability of the three effects of interest, and at the same time allowing refining their validity. Results showed that all three effects were found to be reliable at the group level and the N400 effect and the P3b effect were also found to be reliable at the single participant level. A correlational analysis involving all three effects yielded a significant correlation between the P3b and the Left Parietal effect but not between the P3b and the N400, or between the Left Parietal effect and the N400. Following up on the significant correlation, suggesting a convergence between the P3b effect and the Left Parietal effect, a probability manipulation of the Left Parietal effect was carried out to investigate if the old/new effect is sensitive to probability changes similarly to the P3b. The size of the Left Parietal effect was found to be sensitive to the relative probability of old and new items, in a manner consistent with the P3b effect‟s sensitivity to probability manipulations. The results pointing to a relationship between the P3b effect and the Left Parietal effect suggest that attentional processes sensitive to probability may temporally overlap and confound memory processes as indexed by the Left Parietal effect. The N400 effect, in the initial correlational study, was found to be independent from attentional processes as reflected by the P3b, and from episodic recollection as indexed by the Left Parietal effect. The validity of the N400 effect as a measure of semantic processing was then assessed by manipulating associative relationships while keeping constant semantic relationships, with results showing that the effect can be clearly modulated by associative changes when semantic relatedness is kept constant. The same association norms were then used in an old/new recognition experiment to assess if the Bilateral-Frontal old/new effect behaves in reaction to association relationships similarly or differently from the N400, in the attempt of assessing if the N400 is only a measure of associative relationships or also a measure of the process of familiarity. The observed pattern suggests independence between the N400 and the Bilateral Frontal effect. Overall, the N400 effect was found to be independent from memory processes occurring in the same time window, but, contrary to the dominant interpretation of the effect, the effect was modulated by changes in association strength while keeping semantic relatedness constant, suggesting that the N400 effect may be sensitive to a contiguity-based associative learning process not constrained to the linguistic domain

Heterogeneous profiles of coupled sleep oscillations in human hippocampus

Cross-frequency coupling of sleep oscillations is thought to mediate memory consolidation. While the hippocampus is deemed central to this process, detailed knowledge of which oscillatory rhythms interact in the sleeping human hippocampus is lacking. Combining intracranial hippocampal and non-invasive electroencephalography from twelve neurosurgical patients, we characterized spectral power and coupling during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Hippocampal coupling was extensive, with the majority of channels expressing spectral interactions. NREM consistently showed delta–ripple coupling, but ripples were also modulated by slow oscillations (SOs) and sleep spindles. SO–delta and SO–theta coupling, as well as interactions between delta/theta and spindle/beta frequencies also occurred. During REM, limited interactions between delta/theta and beta frequencies emerged. Moreover, oscillatory organization differed substantially between i) hippocampus and scalp, ii) sites along the anterior-posterior hippocampal axis, and iii) individuals. Overall, these results extend and refine our understanding of hippocampal sleep oscillations

Functional network correlates of language and semiology in epilepsy

Epilepsy surgery is appropriate for 2-3% of all epilepsy diagnoses. The goal of the presurgical workup is to delineate the seizure network and to identify the risks associated with surgery. While interpretation of functional MRI and results in EEG-fMRI studies have largely focused on anatomical parameters, the focus of this thesis was to investigate canonical intrinsic connectivity networks in language function and seizure semiology. Epilepsy surgery aims to remove brain areas that generate seizures. Language dysfunction is frequently observed after anterior temporal lobe resection (ATLR), and the presurgical workup seeks to identify the risks associated with surgical outcome. The principal aim of experimental studies was to elaborate understanding of language function as expressed in the recruitment of relevant connectivity networks and to evaluate whether it has value in the prediction of language decline after anterior temporal lobe resection. Using cognitive fMRI, we assessed brain areas defined by parameters of anatomy and canonical intrinsic connectivity networks (ICN) that are involved in language function, specifically word retrieval as expressed in naming and fluency. fMRI data was quantified by lateralisation indices and by ICN_atlas metrics in a priori defined ICN and anatomical regions of interest. Reliability of language ICN recruitment was studied in 59 patients and 30 healthy controls who were included in our language experiments. New and established language fMRI paradigms were employed on a three Tesla scanner, while intellectual ability, language performance and emotional status were established for all subjects with standard psychometric assessment. Patients who had surgery were reinvestigated at an early postoperative stage of four months after anterior temporal lobe resection. A major part of the work sought to elucidate the association between fMRI patterns and disease characteristics including features of anxiety and depression, and prediction of postoperative language outcome. We studied the efficiency of reorganisation of language function associated with disease features prior to and following surgery. A further aim of experimental work was to use EEG-fMRI data to investigate the relationship between canonical intrinsic connectivity networks and seizure semiology, potentially providing an avenue for characterising the seizure network in the presurgical workup. The association of clinical signs with the EEG-fMRI informed activation patterns were studied using the data from eighteen patients’ whose seizures and simultaneous EEG-fMRI activations were reported in a previous study. The accuracy of ICN_atlas was validated and the ICN construct upheld in the language maps of TLE patients. The ICN construct was not evident in ictal fMRI maps and simulated ICN_atlas data. Intrinsic connectivity network recruitment was stable between sessions in controls. Amodal linguistic processing and the relevance of temporal intrinsic connectivity networks for naming and that of frontal intrinsic connectivity networks for word retrieval in the context of fluency was evident in intrinsic connectivity networks regions. The relevance of intrinsic connectivity networks in the study of language was further reiterated by significant association between some disease features and language performance, and disease features and activation in intrinsic connectivity networks. However, the anterior temporal lobe (ATL) showed significantly greater activation compared to intrinsic connectivity networks – a result which indicated that ATL functional language networks are better studied in the context of the anatomically demarked ATL, rather than its functionally connected intrinsic connectivity networks. Activation in temporal lobe networks served as a predictor for naming and fluency impairment after ATLR and an increasing likelihood of significant decline with greater magnitude of left lateralisation. Impairment of awareness served as a significant classifying feature of clinical expression and was significantly associated with the inhibition of normal brain functions. Canonical intrinsic connectivity networks including the default mode network were recruited along an anterior-posterior anatomical axis and were not significantly associated with clinical signs

Motivated learning influences strategic retrieval processing - an ERP and behavioral approach

Reward anticipation during learning is known to support memory formation but its role on processes engaged at the time of retrieval is so far unclear. Retrieval orientations, as a reflection of strategic or controlled retrieval processing, are one aspect of retrieval that might be modulated by reward. These processes can be measured using event-related potentials (ERPs) elicited by retrieval cues from tasks with different retrieval requirements, such as changes in the class of targeted memory information. To determine whether retrieval orientations of this kind are modulated by reward during learning, the effect of high and low reward expectancy on ERP correlates of retrieval orientation was investigated in two separate experiments. In Experiment 1 reward manipulation at study was associated with later memory performance, whereas in Experiment 2, reward was directly linked to accuracy in a study task. In both studies, participants performed a recognition memory exclusion task 24 hours later. In addition to a previously reported material-specific effect of retrieval orientation, a frontally distributed, reward-associated retrieval orientation effect was found in both experiments. These findings were interpreted as indicating that reward motivation during learning leads to the adoption of a reward-associated retrieval orientation to support the retrieval of highly motivational information. Thus, ERP retrieval orientation effects not only reflect retrieval processes related to the sought-for materials but also relate to the reward conditions with which items were combined during encoding. In Experiments 3a-d, effects of positive (potential gain of money) and negative incentives (potential loss of money) during learning on later memory performance were behaviorally investigated in a cross-cultural context with a similar experimental design as used in Experiment 1. Independent of participants’ origin (China or Germany), memory performance was better when the positive or negative incentive to memorize an item was high. However, a cross-cultural effect was found in the experiments that used negative incentives during learning. The magnitude of the differences in memory accuracy for items previously studied in apprehension of potential high loss of money compared to low loss was significantly higher in Chinese than in German participants. This effect might reflect that Chinese participants were more sensitive to the pending loss of money than German participants. The findings reported here provide new insights into how strategic retrieval processes and accurate memory judgments are affected by motivated learning and into how cross-cultural influences might act on these