Insights from simultaneous EEG-fMRI and patient data illuminate the role of the anterior medial temporal lobe in N400 generation.

The N400, a negative event-related potential (ERP) peaking approximately 400 ms after stimulus onset, is known to reflect the processing of semantic information. While scalp recordings have contributed to understanding the psychological processes underlying the N400, they have been limited in identifying its neural basis. However, recent intracranial ERP recordings and fMRI studies have shed light on the crucial role of the anterior medial temporal lobe (AMTL) in semantic information processing. These findings suggest that the N400 partially represents activity in the AMTL structures. To investigate the neural underpinnings of the N400 effect, we simultaneously recorded ERPs and event-related fMRI during a semantic priming paradigm in a sample of 12 young, healthy subjects. Additionally, we collected ERPs and structural brain data from older healthy adults and patients with amnestic mild cognitive impairment (aMCI), a population characterized by neurodegenerative changes in the AMTL. In our fMRI results, we identified bilateral loci in the AMTL as the global maxima. Employing an EEG-informed fMRI analysis, we explored trial-to-trial fluctuations in semantic processing by linking single-trial N400 amplitudes to the Blood Oxygen Level Dependent (BOLD) signal. This approach provided the first direct evidence linking the N400 recorded at the scalp level to the corresponding BOLD signal in the AMTL. Consistent with these findings, patients with aMCI exhibited a diminished N400 effect compared to healthy older adults. Furthermore, voxel-based morphometry analysis revealed a correlation between the magnitude of the N400 effect and the integrity of the AMTL. By integrating data from simultaneous EEG-fMRI, and patient studies, our research advances our understanding of the neural substrate of the N400 and highlights the critical involvement of the AMTL in semantic processing.

Foreign language learning can improve response inhibition in individuals with lower baseline cognition: Results from a randomized controlled superiority trial.

Introduction: The world's population is aging, increasing the prevalence of dementia. Recently, foreign language learning in later life has been suggested to improve cognition and thus support healthy cognitive aging. To date, however, there are only a few studies with conflicting findings. Therefore, the purpose of this study was to examine whether learning a foreign language can improve executive attention and executive functions in healthy older adults. Additionally, we sought to identify factors affecting cognitive change in foreign language learners, such as cognitive reserve, previous foreign knowledge and usage, and global cognition at baseline. Methods: In a randomized-controlled trial, we assigned 34 monolinguals between the ages of 65 and 80 to a language learning or a waiting list control group. The participants enrolled in a Spanish course for beginners that met five days a week for 1.5 h for a total of 3 weeks. The waiting list control group received no intervention but had the opportunity to join the language training at the end of the study. All participants underwent an assessment of executive attention (primary outcome), executive functions, verbal fluency, and attention (secondary outcomes) before, immediately after the course, or after a waiting period of 3 weeks for the control group and 3 months after the course or the waiting period. Results: Foreign language learning did not significantly improve primary or secondary outcomes, neither immediately nor 3 months after the course. However, moderation analyses revealed that participants with lower global baseline cognition tended to improve more on response inhibition than individuals with higher baseline cognition. This relationship was not evident in the waiting list control group. Discussion: Our results suggest that studying a foreign language does not generally improve executive attention or executive functioning. Nevertheless, individuals with poorer baseline cognition may benefit cognitively from foreign language learning in response inhibition, a domain particularly affected by cognitive aging. Our findings highlight the need of focusing dementia prevention efforts on groups that are more vulnerable to cognitive decline. Additionally, more individualized approaches, including utilizing technology-assisted learning, might enable participants to practice at their performance level, increasing the likelihood of discernible cognitive gains. Clinical trial registration: https://drks.de/search/en, identifier DRKS00016552.

High feature overlap reveals the importance of anterior and medial temporal lobe structures for learning by means of fast mapping.

Contrary to traditional theories of declarative memory, it has recently been shown that novel, arbitrary associations can rapidly and directly be integrated into cortical memory networks by means of a learning procedure called fast mapping (FM), possibly bypassing time-consuming hippocampal-neocortical consolidation processes. In the typical FM paradigm, a picture of a previously unknown item is presented next to a picture of a previously known item and participants answer a question referring to an unfamiliar label, thereby incidentally creating associations between the unknown item and the label. However, contradictory findings have been reported and factors moderating rapid cortical integration through FM yet need to be identified. Previous behavioral results showed that rapid semantic integration through FM was boosted if the unknown and the known item shared many features. In light of this, we propose that the perirhinal cortex might be especially qualified to support the rapid incorporation of these associations into cortical memory networks within the FM paradigm, due to its computational mechanisms during the processing of complex and particularly highly similar objects. We therefore expected that a high degree of feature overlap between the unknown and the known item would trigger strong engagement of the perirhinal cortex at encoding, which in turn might enhance rapid cortical integration of the novel picture-label associations. Within an fMRI experiment, we observed greater subsequent memory effects (i.e., stronger activation for subsequent hits than misses) during encoding in the perirhinal cortex and an associated anterior temporal network if the items shared many features than if they shared few features. This indicates that the perirhinal cortex indeed contributes to the acquisition of novel associations by means of FM if feature overlap is high.

Cross-cultural comparison of MMSE and RUDAS in German and Turkish patients with Alzheimer's disease.

OBJECTIVE: Given the increasing cultural, linguistic diversity in Europe, there is a growing need for cognitive screening tools that minimize the influence of linguistic, cultural, and demographic differences as they are the first means to determine the need for further clinical evaluation of individuals with suspected cognitive impairment. This cross-sectional study compared performance on the Mini-Mental State Examination (MMSE) and the Rowland Universal Dementia Assessment Scale (RUDAS) in Alzheimer's Disease (AD) patients in relation to cultural, demographic, and immigration-related factors (acculturation, bilingualism). METHOD: The study comprised Turkish immigrant (n = 21) and monolingual, nonimmigrant German (n = 20) and Turkish (n = 24) patients with AD. All participants were administered cognitive screening tools, measures of depression, and dementia severity. RESULTS: The mean MMSE total score was significantly higher in German patients with AD compared to both patient groups, but did not differ between native-born Turkish and Turkish immigrant groups. After adjustment for years of education, differences in MMSE performance were no longer significant between groups. Furthermore, bilingualism was associated with better performance on the MMSE in Turkish-immigrant patients. The mean RUDAS total scores were similar between groups with and without adjustment for educational level. Performance on the RUDAS was not associated with demographic and immigration-related variables. CONCLUSIONS: The findings highlight the need to consider the educational background, linguistic integration of older non-Western immigrants for the objective characterization of cognitive profiles. The results provide support for the use of the RUDAS, particularly, among older Turkish immigrants with lower educational levels and varying degrees of acculturation, bilingualism. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

High feature overlap and incidental encoding drive rapid semantic integration in the fast mapping paradigm.

Contrary to traditional theories, it has been shown that novel, arbitrary associations can be rapidly integrated into cortical networks through a learning paradigm called fast mapping (FM), possibly bypassing time-consuming hippocampal-neocortical consolidation processes. In the FM paradigm, an unknown item is presented next to a known item and participants answer a question referring to an unfamiliar label, presumably inferring that the label belongs to the unknown item. However, factors driving rapid cortical integration through FM are still under debate. The FM task requires the discrimination between complex objects and the binding of the unknown item to the label. Discriminating between complex and especially highly similar objects is a central function of the perirhinal cortex, a structure also involved in the binding of single elements to a unit. We suggested that triggering perirhinal processing by increasing the demands on item discrimination through increasing feature overlap between the unknown and the known item might foster the binding of the unknown item to the label and their rapid cortical integration. We found lexical integration of the labels after learning through FM, but this was not affected by feature overlap. However, semantic integration of the label immediately after FM encoding was more successful when the items shared many features than when they shared few features. Moreover, effects of rapid semantic integration through FM were reduced if encoding was intentional and if no discrimination was required. This indicates that incidental encoding and a high feature overlap are driving factors for rapid semantic integration through FM. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Does bilingualism influence neuropsychological test performance in older adults? A systematic review.

OBJECTIVE: Using standardized tests which have been normed on monolinguals for the assessment of bilinguals presents challenges to the accurate characterization of cognitive profile as the literature provides compelling evidence for the influence of bilingualism on cognitive abilities. However, little is known about the generalizability of these findings to clinical neuropsychology. The aim of this review was to address this gap by summarizing current evidence on the performance of bilingual older adults on standardized tests routinely used in clinical practice. METHOD: A systematic search of Web of Science, PsycINFO and PubMed was conducted. 27 cross-sectional and longitudinal studies which use at least one standardized neuropsychological test for cognitive impairment were included in the review. Potential demographic (cultural/linguistic background of the participants, immigrant status), clinical (diagnostic status), and methodological confounders (language of test administration, components of bilingualism) were also examined. The review protocol was registered at the PROSPERO International Prospective Register of Systematic Review with registration number CRD42018114658. RESULTS: The results of this review revealed some bilingual advantage on measures of inhibitory control and bilingual disadvantage on measures of verbal fluency in cross-sectional studies. Bilingualism status was not associated with test performance in longitudinal studies. However, findings lack consistency due to demographic variables and methodological differences across studies. CONCLUSION: Neuropsychological tests assessing language domains and, to some extent executive function act as clinically relevant features of bilingualism for neuropsychological evaluation. However, immigration status, acculturation level and language of test administration needs to be taken into account when assessing bilingual older adults.

Effects of foreign language learning on executive functions in healthy older adults: study protocol for a randomised controlled trial.

BACKGROUND: With age, most cognitive functions decline. As the number of people aged 60 years and older is expected to rise rapidly within the next decades, identifying interventions that promote healthy cognitive ageing is of utmost importance. Promising research on bilingualism has led to the notion that learning a foreign language could protect against cognitive decline. Foreign language learning likely promotes executive functions, which are higher-order cognitive abilities particularly affected by age-related cognitive decline. However, evidence is still sparse and has produced contradictory results. This study aims to investigate the effects of short and intensive foreign language learning on executive functions in healthy older adults. METHODS: In a randomised controlled trial, we will assign 60 native German-speaking monolingual healthy older adults, aged 65-80 years, to either a foreign language learning or a waiting list control group. Language learners will attend a face-to-face, group-based Spanish course for beginners for 1.5 h a day, 5 days a week, for a total of 3 weeks. Cognitive performance in executive functions will be assessed before and after the intervention or after a waiting period of 3 weeks (waiting list control group). Participants will be tested again after 3 months to evaluate longitudinal effects of foreign language learning. The waiting list control group will receive Spanish lessons only after the final assessment and will be invited to an additional voluntary evaluation after completion of the course. DISCUSSION: To the best of our knowledge, we are conducting the first randomised controlled trial on the effects of short and intensive foreign language learning in older adulthood on executive functions. Enhanced cognitive performance after foreign language learning would indicate that learning a foreign language could enlarge cognitive reserve and thus promote healthy cognitive ageing in older adults. TRIAL REGISTRATION: German Clinical Trials Register DRKS00016552 . Registered on 11 February 2019.

Usefulness of familiarity signals during recognition depends on test format: Neurocognitive evidence for a core assumption of the CLS framework.

Familiarity-based discrimination between studied items and similar foils in yes/no recognition memory tests is relatively poor. The complementary learning systems (CLS) framework explains this with the small difference in familiarity strength between targets and foils. The framework, however, also predicts that familiarity values of targets and corresponding similar foils are directly comparable - as long as they are presented side by side in a forced-choice corresponding (FCC) test. This is because in each trial, targets tend to be more familiar than their corresponding foils. In contrast, when forced-choice displays contain non-corresponding foils (FCNC) which are similar to other studied items, familiarity values are not directly comparable (as in yes/no-tasks). In a recognition memory task with pictures of objects, we found that the putative ERP correlate of familiarity, the mid-frontal old/new effect for targets vs. foils, was significantly larger in FCC compared to FCNC displays. Moreover, single-trial target-foil amplitude differences predicted the accuracy of the recognition judgment. This study supports the assumption of the CLS framework that the test format can influence the diagnostic reliability of familiarity. Moreover, it implies that the mid-frontal old/new effect does not reflect the difference in the familiarity signal between studied and non-studied items but the task-adequate assessment of this signal.

Hippocampus-Related Cognitive and Affective Impairments in Patients With Breast Cancer-A Systematic Review.

Background: Although improvements in medical treatment lead to a steadily rising survival rate of breast cancer patients (BCP), it is associated with a decrease in cognitive and affective function. The hippocampus, a brain region with a high influence on both cognitive and affective function, is increasingly becoming the focus of current research because of its high vulnerability to adverse direct (chemotherapeutic agents, endocrine therapeutic agents, and radiation) or indirect (stress and other psycho-social factors) treatment-related effects. Methods: This systematic review analyses current data from literature combining hippocampus-related brain changes due to breast cancer treatment with associated cancer-related cognitive and affective impairments (CRCI/CRAI). The seven studies that met the inclusion criteria consisted of six cross-sectional studies and one longitudinal study. Results: The study results indicate hippocampal differences across all types of treatment. Those differences include volume loss, deformation, and changes in functional connectivity. They are associated with CRCI, revealing executive function as well as working memory, episodic memory, and prospective memory as the most affected domains. Although an interaction between hippocampus-related brain changes, CRCI, and CRAI can be hypothesized, CRAI are less reflected in current research. Discussion: More research including longitudinal assessments with better overall methodology is needed to fully understand the interaction between hippocampal alterations and both CRCI and CRAI due to breast cancer treatment.

Evidence for fast mapping in adults - Moderating factors yet need to be identified.

Cooper, Greve, and Henson (this issue) discuss if fast mapping (FM) is dissociable from other learning procedures in adults. We strongly agree that drawing conclusions on cortical integration from recognition accuracy is questionable in healthy young adults. Additionally, we advise against interpreting explicit measures in patient studies if residual hippocampal functioning cannot be excluded or extra-hippocampal structures are also affected. Due to promising fMRI data patterns and confounds in studies reporting no evidence for implicitly measured semantic integration, we suggest that factors moderating FM learning success need to be systematically identified rather than doubting rapid cortical integration through FM.

Contingency awareness as a prerequisite for differential contextual fear conditioning.

Contingency awareness during conditioning describes the phenomenon of becoming consciously aware of the association between a conditioned stimulus (CS) and an unconditioned stimulus (US). Despite the fact that contingency awareness is necessary for associative learning in some conditioning paradigms, its role in contextual fear conditioning, a variant that uses a context-CS (CTX) instead of a cue, has not been characterized thus far. We investigated if contingency awareness is a prerequisite for contextual fear conditioning and if subjects classified as aware differ from unaware subjects on a hemodynamic, autonomic, and behavioral level. We used a computer-generated picture context as CTX and slightly painful electric stimulation as US while we recorded brain responses by functional magnetic resonance imaging (fMRI), and obtained skin conductance responses (SCR) and verbal ratings of emotional valence and arousal. SCR analyses revealed that only aware subjects became conditioned to the US-associated CTX (CTX+). Brain activity related to the CTX+ was more strongly pronounced in fear-associated areas like the insula in the aware relative to the unaware group. Finally, the hippocampus was functionally connected to the cingulate cortex and posterior medial frontal gyrus in aware subjects relative to unaware subjects. These task-related differential connectivity patterns suggest that information exchange between the hippocampus and regions involved in the expression of conditioned fear and decision uncertainty is crucial for the acquisition of contingency knowledge. This study demonstrates the importance of contingency awareness for contextual fear conditioning and points to the hippocampus as a potential mediator for contingency learning in contextual learning.

From Memory to Attitude: The Neurocognitive Process beyond Euthanasia Acceptance.

Numerous questionnaire studies on attitudes towards euthanasia produced conflicting results, precluding any general conclusion. This might be due to the fact that human behavior can be influenced by automatically triggered attitudes, which represent ingrained associations in memory and cannot be assessed by standard questionnaires, but require indirect measures such as reaction times (RT) or electroencephalographic recording (EEG). Event related potentials (ERPs) of the EEG and RT during an affective priming task were assessed to investigate the impact of automatically triggered attitudes and were compared to results of an explicit questionnaire. Explicit attitudes were ambivalent. Reaction time data showed neither positive nor negative associations towards euthanasia. ERP analyses revealed an N400 priming effect with lower mean amplitudes when euthanasia was associated with negative words. The euthanasia-related modulation of the N400 component shows an integration of the euthanasia object in negatively valenced associative neural networks. The integration of all measures suggests a bottom-up process of attitude activation, where automatically triggered negative euthanasia-relevant associations can become more ambiguous with increasing time in order to regulate the bias arising from automatic processes. These data suggest that implicit measures may make an important contribution to the understanding of euthanasia-related attitudes.

Impaired and preserved aspects of feedback learning in aMCI: contributions of structural connectivity.

Distinct lines of research demonstrated that patients with amnestic mild cognitive impairment (aMCI), a potential precursor of Alzheimer disease (AD), are particularly impaired in remembering relations between items and that the use of emotional targets can facilitate memory in patients with AD. We link these findings by examining learning through positive and negative feedback in patients with aMCI, and explore its anatomic underpinnings with diffusion tensor imaging and tractography. Compared to healthy controls, patients with single-domain aMCI were impaired in learning from positive feedback, while learning from negative outcomes was preserved. Among pathways within the brain circuit involved in feedback learning, abnormal white matter microstructure was observed in tracts, which connect left-hemispheric amygdala with hippocampus and entorhinal cortex. In all participants, reduced white matter integrity in this left fiber tract was specifically associated with learning from positive outcomes. Microstructure of right-hemispheric tracts between amygdala and entorhinal cortex was related to learning from negative feedback, and was not compromised in aMCI patients. Our results provide new insight into how anatomical connections might contribute to impaired and preserved aspects of learning behaviors in the early AD process and indicate potential compensatory mechanisms.

Simultaneous EEG-fMRI reveals brain networks underlying recognition memory ERP old/new effects.

The mapping of event-related potentials (ERP) on functional magnetic resonance imaging (fMRI) data remains difficult as scalp electroencephalography (EEG) is assumed to be largely insensitive to deep brain structures. Simultaneous recordings of EEG and fMRI might be helpful in reconciling surface ERPs with hemodynamic activations in medial temporal lobe structures related to recognition memory. EEG and imaging studies provide evidence for two independent processes underlying recognition memory, namely recollection and familiarity. Recollection reflects the conscious retrieval of contextual information about a specific episode, while familiarity refers to an acontextual feeling of knowing. Both processes were related to two spatiotemporally different ERP effects, namely the early mid-frontal old/new effect (familiarity) and the late parietal old new effect (recollection). We conducted an exploratory simultaneous EEG-fMRI study using a recognition memory paradigm to investigate which brain activations are modulated in relation to the ERP old/new effects. To this end we examined 17 participants in a yes/no recognition task with word stimuli. Single-trial amplitudes of ERP old/new effects were related to the hemodynamic signal in an EEG-informed fMRI analysis for a subset of 12 subjects. FMRI activation in the right dorsolateral prefrontal cortex and the right intraparietal sulcus was associated with the amplitude of the early frontal old/new effect (350-550ms), and activation in the right posterior hippocampus, parahippocampal cortex and retrosplenial cortex was associated with the amplitude of the late parietal old new effect (580-750ms). These results provide the first direct link between electrophysiological and hemodynamic correlates of familiarity and recollection. Moreover, these findings in healthy subjects complement data from intracranial ERP recordings in epilepsy patients and lesion studies in hypoxia patients.

Contextual fear conditioning in humans using feature-identical contexts.

Contextual fear conditioning studies in animals and humans found an involvement of the hippocampus and amygdala during fear learning. To exclude a focus on elements of the context we employed a paradigm, which uses two feature-identical contexts that only differ in the arrangement of the features and requires configural processing. We employed functional magnetic resonance imaging to determine the role of the hippocampus and neocortical areas during the acquisition of contextual fear in humans. For contextual fear acquisition, we paired one context (CS+) with an aversive electrical stimulus, whereas the other (CS-) was never followed by aversive stimulation. Blood oxygen level dependent activation to the CS+ was present in the insula, inferior frontal gyrus, inferior parietal lobule, superior medial gyrus and caudate nucleus. Furthermore, the amygdala and hippocampus were involved in a time-dependent manner. Psychophysiological interaction analyses revealed functional connectivity of a more posterior hippocampal seed region with the anterior hippocampus, posterior cingulate cortex and superior parietal lobule. The anterior hippocampus was functionally coupled with the amygdala and postcentral gyrus. This study complements previous findings in contextual fear conditioning in humans and provides a paradigm which might be useful for studying patients with hippocampal impairment.

Pain can produce systematic distortions of autobiographical memory.

OBJECTIVES: Cognitive-behavioral models highlight the role of learning and memory biases in the development and maintenance of chronic pain. However, the extent to which a memory bias is a consequence of the clinical state of being a chronic pain subject is unknown. This article presents a study which delineates the influence of chronic and acute pain on autobiographical memory retrieval. METHODS: 16 healthy controls and 16 individuals with chronic pain participated in an autobiographical memory task during two sessions (a current pain and a pain-free session for the chronic pain subjects) and received neutral words that served as a cue for the retrieval of past life events. RESULTS: The valence of remembered life events in individuals with chronic pain was more negative when they were in pain compared to pain-free states. Conversely, both groups did not differ in their ratings of the reported memories during the pain-free condition. In addition, no significant relationship between mood and the valence of retrieved memories was found. CONCLUSIONS: The present data demonstrate that current pain but not chronic pain per se can exert specific influences on remembering in participants with chronic pain. This memory bias could be a predisposition for the development of chronic pain but could also be a pain-maintaining consequence of painful experiences. This should be addressed in longitudinal studies.

Hippocampal-dorsolateral prefrontal coupling as a species-conserved cognitive mechanism: a human translational imaging study.

Hippocampal-prefrontal cortex (HC-PFC) interactions are implicated in working memory (WM) and altered in psychiatric conditions with cognitive impairment such as schizophrenia. While coupling between both structures is crucial for WM performance in rodents, evidence from human studies is conflicting and translation of findings is complicated by the use of differing paradigms across species. We therefore used functional magnetic resonance imaging together with a spatial WM paradigm adapted from rodent research to examine HC-PFC coupling in humans. A PFC-parietal network was functionally connected to hippocampus (HC) during task stages requiring high levels of executive control but not during a matched control condition. The magnitude of coupling in a network comprising HC, bilateral dorsolateral PFC (DLPFC), and right supramarginal gyrus explained one-fourth of the variability in an independent spatial WM task but was unrelated to visual WM performance. HC-DLPFC coupling may thus represent a systems-level mechanism specific to spatial WM that is conserved across species, suggesting its utility for modeling cognitive dysfunction in translational neuroscience.

Women are more strongly affected by dizziness in static magnetic fields of magnetic resonance imaging scanners.

Increasing field strengths in MRI necessitate the examination of potential side effects. Previously reported results have been contradictory, possibly caused by imbalanced samples. We aimed to examine whether special groups of people are more prone to develop side effects that might have led to contradictory results in previous studies. We examined the occurrence of sensory side effects in static magnetic fields of MRI scanners of 1.5, 3, and 7 T and a mock scanner in 41 healthy participants. The contribution of field strength, sex, age, and attention to bodily processes, and stress hormone levels to the sensation of dizziness was examined in separate univariate analyses and in a joint analysis that included all variables. Field strength and sex were significant factors in the joint analysis (P=0.001), with women being more strongly affected than men by dizziness in higher static magnetic fields. This effect was not mediated by the other variables such as attention to bodily symptoms or stress hormones. Further research needs to elucidate the underlying factors of increased dizziness in women in static magnetic fields in MRI. We hypothesize that imbalanced samples of earlier studies might be one reason for previous contradictory results on the side effects of static magnetic fields.

Bigger is better! Hippocampal volume and declarative memory performance in healthy young men.

The importance of the hippocampus for declarative memory processes is firmly established. Nevertheless, the issue of a correlation between declarative memory performance and hippocampal volume in healthy subjects still remains controversial. The aim of the present study was to investigate this relationship in more detail. For this purpose, 50 healthy young male participants performed the California Verbal Learning Test. Hippocampal volume was assessed by manual segmentation of high-resolution 3D magnetic resonance images. We found a significant positive correlation between putatively hippocampus-dependent memory measures like short-delay retention, long-delay retention and discriminability and percent hippocampal volume. No significant correlation with measures related to executive processes was found. In addition, percent amygdala volume was not related to any of these measures. Our data advance previous findings reported in studies of brain-damaged individuals in a large and homogeneous young healthy sample and are important for theories on the neural basis of episodic memory.

A combined electrophysiological and morphological examination of episodic memory decline in amnestic mild cognitive impairment.

Early stages of Alzheimer's disease (AD) are characterized by neuropathological changes within the medial temporal lobe cortex (MTLC), which lead to characteristic impairments in episodic memory, i.e., amnestic mild cognitive impairment (aMCI). Here, we tested the neural correlates of this memory impairment using event-related potentials (ERPs) and voxel-based morphometry. Twenty-four participants were instructed to encode lists of words and were tested in a yes/no recognition memory task. The dual-process model of recognition memory dissociates between acontextual familiarity and recollection of contextual details. The early frontal ERP old/new effect, which is thought to represent a neural correlate of familiarity-based memory, was absent in aMCI, whereas the control group showed a significant early old/new effect at frontal electrodes. This effect was positively correlated with behavioral episodic memory performance. Analyses of brain morphology revealed a focused gray matter loss in the inferior and medial temporal lobes in aMCI versus healthy controls. Moreover, the positive correlation between gray matter volume in the MTLC and the familiarity-related early frontal old/new effect supports the notion that this effect relies upon the integrity of the MTLC. Thus, the present findings might provide a further functional marker for prodromal AD.