Event-related brain potentials in the study of inhibition: cognitive control, source localization and age-related modulations

In the previous 15 years, a variety of experimental paradigms and methods have been employed to study inhibition. In the current review, we analyze studies that have used the high temporal resolution of the event-related potential (ERP) technique to identify the temporal course of inhibition to understand the various processes that contribute to inhibition. ERP studies with a focus on normal aging are specifically analyzed because they contribute to a deeper understanding of inhibition. Three time windows are proposed to organize the ERP data collected using inhibition paradigms: the 200 ms period following stimulus onset; the period between 200 and 400 ms after stimulus onset; and the period between 400 and 800 ms after stimulus onset. In the first 200 ms, ERP inhibition research has primarily focused on N1 and P1 as the ERP components associated with inhibition. The inhibitory processing in the second time window has been associated with the N2 and P3 ERP components. Finally, in the third time window, inhibition has primarily been associated with the N400 and N450 ERP components. Source localization studies are analyzed to examine the association between the inhibition processes that are indexed by the ERP components and their functional brain areas. Inhibition can be organized in a complex functional structure that is not constrained to a specific time point but, rather, extends its activity through different time windows. This review characterizes inhibition as a set of processes rather than a unitary process

Event-Related Brain Potentials in the Study of Inhibition: Cognitive Control, Source Localization and Age-Related Modulations

In the previous 15 years, a variety of experimental paradigms and methods have been employed to study inhibition. In the current review, we analyze studies that have used the high temporal resolution of the event-related potential (ERP) technique to identify the temporal course of inhibition to understand the various processes that contribute to inhibition. ERP studies with a focus on normal aging are specifically analyzed because they contribute to a deeper understanding of inhibition. Three time windows are proposed to organize the ERP data collected using inhibition paradigms: the 200 ms period following stimulus onset; the period between 200 and 400 ms after stimulus onset; and the period between 400 and 800 ms after stimulus onset. In the first 200 ms, ERP inhibition research has primarily focused on N1 and P1 as the ERP components associated with inhibition. The inhibitory processing in the second time window has been associated with the N2 and P3 ERP components. Finally, in the third time window, inhibition has primarily been associated with the N400 and N450 ERP components. Source localization studies are analyzed to examine the association between the inhibition processes that are indexed by the ERP components and their functional brain areas. Inhibition can be organized in a complex functional structure that is not constrained to a specific time point but, rather, extends its activity through different time windows. This review characterizes inhibition as a set of processes rather than a unitary process

Neural differentiation is moderated by age in scene- but not face-selective cortical regions

The aging brain is characterized by neural dedifferentiation, an apparent decrease in the functional selectivity of category-selective cortical regions. Age-related reductions in neural differentiation have been proposed to play a causal role in cognitive aging. Recent findings suggest, however, that age-related dedifferentiation is not equally evident for all stimulus categories and, additionally, that the relationship between neural differentiation and cognitive performance is not moderated by age. In light of these findings, in the present experiment, younger and older human adults (males and females) underwent fMRI as they studied words paired with images of scenes or faces before a subsequent memory task. Neural selectivity was measured in two scene-selective (parahippocampal place area (PPA) and retrosplenial cortex (RSC)] and two face-selective [fusiform face area (FFA) and occipital face area (OFA)] regions using both a univariate differentiation index and multivoxel pattern similarity analysis. Both methods provided highly convergent results, which revealed evidence of age-related reductions in neural dedifferentiation in scene-selective but not face-selective cortical regions. Additionally, neural differentiation in the PPA demonstrated a positive, age-invariant relationship with subsequent source memory performance (recall of the image category paired with each recognized test word). These findings extend prior findings suggesting that age-related neural dedifferentiation is not a ubiquitous phenomenon, and that the specificity of neural responses to scenes is predictive of subsequent memory performance independently of age

Atypical Neurophysiology Underlying Episodic and Semantic Memory in Adults with Autism Spectrum Disorder

Individuals with autism spectrum disorder (ASD) show atypicalities in episodic memory (Boucher et al. in Psychological Bulletin, 138 (3), 458-496, 2012). We asked participants to recall the colours of a set of studied line drawings (episodic judgement), or to recognize line drawings alone (semantic judgement). Cycowicz et al. (Journal of Experimental Child Psychology, 65, 171-237, 2001) found early (300 ms onset) posterior old-new event-related potential effects for semantic judgements in typically developing (TD) individuals, and occipitally focused negativity (800 ms onset) for episodic judgements. Our results replicated findings in TD individuals and demonstrate attenuated early old-new effects in ASD. Late posterior negativity was present in the ASD group, but was not specific to this time window. This non-specificity may contribute to the atypical episodic memory judgements characteristic of individuals with ASD

Elaboration versus suppression of cued memories: influence of memory recall instruction and success on parietal lobe, default network, and hippocampal activity.

Functional imaging studies of episodic memory retrieval consistently report task-evoked and memory-related activity in the medial temporal lobe, default network and parietal lobe subregions. Associated components of memory retrieval, such as attention-shifts, search, retrieval success, and post-retrieval processing also influence regional activity, but these influences remain ill-defined. To better understand how top-down control affects the neural bases of memory retrieval, we examined how regional activity responses were modulated by task goals during recall success or failure. Specifically, activity was examined during memory suppression, recall, and elaborative recall of paired-associates. Parietal lobe was subdivided into dorsal (BA 7), posterior ventral (BA 39), and anterior ventral (BA 40) regions, which were investigated separately to examine hypothesized distinctions in sub-regional functional responses related to differential attention-to-memory and memory strength. Top-down suppression of recall abolished memory strength effects in BA 39, which showed a task-negative response, and BA 40, which showed a task-positive response. The task-negative response in default network showed greater negatively-deflected signal for forgotten pairs when task goals required recall. Hippocampal activity was task-positive and was influenced by memory strength only when task goals required recall. As in previous studies, we show a memory strength effect in parietal lobe and hippocampus, but we show that this effect is top-down controlled and sensitive to whether the subject is trying to suppress or retrieve a memory. These regions are all implicated in memory recall, but their individual activity patterns show distinct memory-strength-related responses when task goals are varied. In parietal lobe, default network, and hippocampus, top-down control can override the commonly identified effects of memory strength

From Cue to Recall : The Temporal Dynamics of Long-Term Memory Retrieval

A fundamental function of long-term memory is the ability to retrieve a specific memory when encountering a retrieval cue. The purpose of this dissertation was to further our understanding of such cued recall by investigating the temporal dynamics from the presentation of the retrieval cue until the target memory is recalled. Retrieval cues are often related with several memories. When such a retrieval cue is presented, the associated memories will compete for retrieval and this retrieval competition needs to be handled in order to retrieve the sought after target memory. Study 1 and Study 2 investigated the temporal dynamics of such competitive semantic cued recall. Interestingly, previous research has shown that the ability to retrieve the currently relevant target memory comes with a cost, namely retrieval-induced forgetting of the competing memories. These studies also investigated the role of competitor activation and target retrieval in this forgetting phenomenon. Study 1 investigated the electrophysiological correlates of reactivation of competing currently irrelevant memories and the role of such competitor activation in retrieval-induced forgetting. Competitor activation was related to an FN400 event-related potential (ERP) effect and this effect predicted increased levels of retrieval-induced forgetting, indicating that this forgetting effect is dependent on competitor activation. Study 2 examined processes involved in target retrieval in a similar competitive semantic cued recall task. The main finding in this study was that attempts to retrieve the target memory were related to a late posterior negativity ERP effect. Another important finding was that behavioural and ERP measures of target retrieval were unrelated to retrieval-induced forgetting. Retrieval cues can sometimes elicit involuntary retrieval of unwanted memories. Such memory intrusions are a core symptom of post-traumatic stress disorder. Study 3 investigated the temporal dynamics of such memory intrusions. One of the key findings was that memory intrusions were related to a negative slow wave ERP effect possibly reflecting the activation of the intruding memory in working memory. Taken together the findings in the dissertation indicate that cued recall involves several cognitive processes ranging from early automatic memory reactivation to conscious processes such as working memory activation and recollection. The findings have implications for cognitive theories of memory and have relevance for several clinical conditions including depression and post-traumatic stress disorder

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

Hippocampal and cortical mechanisms at retrieval explain variability in episodic remembering in older adults

Age-related episodic memory decline is characterized by striking heterogeneity across individuals. Hippocampal pattern completion is a fundamental process supporting episodic memory. Yet, the degree to which this mechanism is impaired with age, and contributes to variability in episodic memory, remains unclear. We combine univariate and multivariate analyses of fMRI data from a large cohort of cognitively normal older adults (N=100) to measure hippocampal activity and cortical reinstatement during retrieval of trial-unique associations. Trial-wise analyses revealed that (a) hippocampal activity scaled with reinstatement strength, (b) cortical reinstatement partially mediated the relationship between hippocampal activity and associative retrieval, (c) older age weakened cortical reinstatement and its relationship to memory behaviour. Moreover, individual differences in the strength of hippocampal activity and cortical reinstatement explained unique variance in performance across multiple assays of episodic memory. These results indicate that fMRI indices of hippocampal pattern completion explain within-and across-individual memory variability in older adults