Neural evidence for advantaged representation of first items in memory.

Visual areas activated during perception can retain specific information held in memory without the presence of physical stimuli via distributed activity patterns. Neuroimaging studies have shown that the delay-period representation of information in visual areas is modulated by factors such as memory load and task demands, raising the possibility of serial position as another potential modulator. Specifically, enhanced representation of first items during the post-encoding delay period may serve as a mechanism underlying the well-established but not well-understood primacy effect - the mnemonic advantage of first items. To test this hypothesis, 13 males and 16 females performed a human fMRI task, wherein each trial consisted of the sequential encoding of two stimuli (a famous face and landscape, order counterbalanced), followed by a distracting task, a delay period, and then a cued recall of one of the items. Participants exhibited the expected behavioral primacy effect, manifested as faster recall of the first items. In order to elucidate the still debated neural underpinnings of this effect, using multivariate decoding, a classifier was trained on data collected during encoding to differentiate stimulus categories (i.e., faces vs. landscapes) and tested on data collected during the post-encoding period. Greater reactivation of first versus second items was observed in the ventral occipito-temporal cortex during the entire post-encoding period but not during encoding. Moreover, trial-level analyses revealed that the degree of first-item neural advantage during the post-encoding delay predicted the behavioral primacy effect. These findings highlight the role of item reinstatement in ventral occipito-temporal cortex in the primacy effect and are discussed in the context of the uniqueness of the very first item and event boundaries, illuminating putative neural mechanisms underlying the effect.

A new perspective on the role of the frontoparietal regions in Stroop-like conflicts.

Humans are goal-directed; however, goal-unrelated information still affects us, but how? The Stroop task is often used to answer this question, relying on conflict (incongruency) between attributes, one targeted by the task and another irrelevant to the task. The frontal regions of the brain are known to play a crucial role in processing such conflict, as they show increased activity when we encounter incongruent stimuli. Notably, the Stroop stimuli also consist of conceptual dimensions, such as semantic or emotional content, that are independent of the attributes that define the conflict. Since the non-targeted attribute usually refers to the same conceptual dimension as the targeted-attribute, it is relevant to the task at hand. For example, when naming the emotion of an emotional face superimposed by an emotional word, both the targeted-attribute and the non-targeted attribute refer to the conceptual dimension "emotion". We designed an fMRI paradigm to investigate how conflicts between different conceptual dimensions impact us. Even though the conflict was task-irrelevant, incongruent stimuli resulted in longer reaction times, indicating a behavioral congruency effect. When examining the neural mechanisms that underlie this effect, we found that the frontal regions exhibited repetition suppression, while the bilateral intraparietal sulcus (IPS) showed a congruency effect linked to the behavioral effect. Taken together, these findings suggest that individuals are unable to completely ignore task-irrelevant information, and that the IPS plays a crucial role in processing such information.

Monkeypox DNA levels correlate with virus infectivity in clinical samples, Israel, 2022.

The current monkeypox virus global spread and lack of data regarding clinical specimens' infectivity call for examining virus infectivity, and whether this correlates with results from PCR, the available diagnostic tool. We show strong correlation between viral DNA amount in clinical specimens and virus infectivity toward BSC-1 cell line. Moreover, we define a PCR threshold value (Cq ≥ 35, ≤ 4,300 DNA copies/mL), corresponding to negative viral cultures, which may assist risk-assessment and decision-making regarding protective-measures and guidelines for patients with monkeypox.

Is the Cutoff of the MoCA too High? Longitudinal Data From Highly Educated Older Adults.

BACKGROUND: The Montreal Cognitive Assessment (MoCA) is widely used to evaluate cognitive decline in older individuals. Although, age and education-related norms have been published, the vast majority of diagnostic clinicians use the MoCA cutoff score to identify patients with cognitive impairment. AIM: To identify whether the MoCA cutoff is too stringent for cognitively normal older adults. METHODS: Twenty-seven participants aged 68 to 83 (mean = 75.07, standard deviation [SD] = 4.62), with high education level (mean = 17.14 years, SD = 3.21) underwent cognitive assessment once a year for 5 consecutive years. The cognitive assessment included MoCA; Rey Auditory Verbal Learning Test; Rey Osterrieth Complex Figure test; Wechsler Adult Intelligence Scale Information and Digit Span Subtest; Trail Making Test; Verbal Fluency Test; and Beck Depression Inventory questionnaire. Repeated measures analysis of variance (ANOVA) was used to analyze all standardized scores as well as MoCA standardized and raw scores across all years. RESULTS: Repeated-measures ANOVA for MoCA raw scores yielded significant decline across the years (P < .05). From the second year and forward, the average MoCA total score was below the cutoff of 26/30. However, in substantial contrast, all other neuropsychological scores and the MoCA standardized scores were within the normal range and even above in all years. CONCLUSION: Our study demonstrates that the currently used MoCA cutoff is too high even for highly educated, cognitively normal older adults. Therefore, it is crucial to use the age- and education-related norms for the MoCA in order to avoid misdiagnosis of cognitive decline.

Conflict monitoring mechanism at the single-neuron level in the human ventral anterior cingulate cortex.

Life requires monitoring and adjusting behavior in the face of conflicts. The conflict monitoring theory implicates the anterior cingulate cortex (ACC) in these processes; its ventral aspect (vACC) specializes in emotional conflict. To elucidate the underpinning neural mechanism, we recorded vACC extracellular activity from 12 patients with mood disorders or epilepsy who performed the face-emotional Stroop task. Behaviorally, both conflict detection and adaptation to conflict were evident. The firing rate of neurons in the vACC represented current conflict, i.e., current-congruency. The late onset of the effect is compatible with a role in monitoring. Additionally, early responses of some neurons represented the immediate history of conflicts, i.e., previous-trial-congruency. Finally, in some neurons the response to the current-trial was modulated by previous-trial-congruency, laying the ground for adjusting-to-conflicts. Our results uncover a single neuron level mechanism in the vACC that encodes and integrates past and present emotional conflicts, allowing humans to accommodate their responses accordingly.

Schema benefit vs. proactive interference: Contradicting behavioral outcomes and coexisting neural patterns.

Prior knowledge can either assist or hinder the ability to learn new information. These contradicting behavioral outcomes, referred to as schema benefit and proactive interference respectively, have been studied separately. Here we examined whether the known neural correlates of each process coexist, and how they are influenced by attentional loading and aging. To this end we used an fMRI task that affected both processes simultaneously by presenting pairs of related short movies in succession. The first movie of each pair provided context for the second movie, which could evoke schema benefit and/or proactive interference. Inclusion of an easy or hard secondary task performed during encoding of the movies, as well as testing both younger (22-35y) and older (65-79y) adults, allowed examining the effect of attentional load and older age on the neural patterns associated with context. Analyses focused on three predefined regions and examined how their inter-subject correlation (inter-SC) and functional connectivity (FC) with the hippocampi changed between the first and second movie. The results in the medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC) matched and expanded previous findings: higher inter-SC and lower FC were observed during the second compared to the first movie; yet the differentiation between the first and second movies in these regions was attenuated under high attentional load, pointing to dependency on attentional resources. Instead, at high load there was a significant context effect in the FC of the left ventrolateral prefrontal cortex (vlPFC), and greater FC in the second movie was related to greater proactive interference. Further, older adults showed context effect in the PCC and vlPFC. Intriguingly, older adults with inter-SC mPFC patterns similar to younger adults exhibited schema benefit in our task, while those with inter-SC PCC patterns similar to younger adults showed proactive interference in an independent task. The brain-behavior relationships corroborate the functional significance of these regions and indicate that the mPFC mainly contributes to schema benefit, while the left vlPFC and PCC contribute to proactive interference. Importantly, our findings show that the functions of the regions are retained throughout the lifespan and may predict the predominant behavioral outcome.

Losing Neutrality: The Neural Basis of Impaired Emotional Control without Sleep.

Sleep deprivation has been shown recently to alter emotional processing possibly associated with reduced frontal regulation. Such impairments can ultimately fail adaptive attempts to regulate emotional processing (also known as cognitive control of emotion), although this hypothesis has not been examined directly. Therefore, we explored the influence of sleep deprivation on the human brain using two different cognitive-emotional tasks, recorded using fMRI and EEG. Both tasks involved irrelevant emotional and neutral distractors presented during a competing cognitive challenge, thus creating a continuous demand for regulating emotional processing. Results reveal that, although participants showed enhanced limbic and electrophysiological reactions to emotional distractors regardless of their sleep state, they were specifically unable to ignore neutral distracting information after sleep deprivation. As a consequence, sleep deprivation resulted in similar processing of neutral and negative distractors, thus disabling accurate emotional discrimination. As expected, these findings were further associated with a decrease in prefrontal connectivity patterns in both EEG and fMRI signals, reflecting a profound decline in cognitive control of emotion. Notably, such a decline was associated with lower REM sleep amounts, supporting a role for REM sleep in overnight emotional processing. Altogether, our findings suggest that losing sleep alters emotional reactivity by lowering the threshold for emotional activation, leading to a maladaptive loss of emotional neutrality. Significance statement: Sleep loss is known as a robust modulator of emotional reactivity, leading to increased anxiety and stress elicited by seemingly minor triggers. In this work, we aimed to portray the neural basis of these emotional impairments and their possible association with frontal regulation of emotional processing, also known as cognitive control of emotion. Using specifically suited EEG and fMRI tasks, we were able to show that sleep deprivation alters emotional reactivity by triggering enhanced processing of stimuli regarded previously as neutral. These changes were further accompanied by diminished frontal connectivity, reduced REM sleep, and poorer performance. Therefore, we suggest that sleep loss alters emotional reactivity by lowering the threshold for emotional activation, leading to a maladaptive loss of emotional neutrality.

Task-specific Aspects of Goal-directed Word Generation Identified via Simultaneous EEG-fMRI.

Generating words according to a given rule relies on retrieval-related search and postretrieval control processes. Using fMRI, we recently characterized neural patterns of word generation in response to episodic, semantic, and phonemic cues by comparing free recall of wordlists, category fluency, and letter fluency [Shapira-Lichter, I., Oren, N., Jacob, Y., Gruberger, M., & Hendler, T. Portraying the unique contribution of the default mode network to internally driven mnemonic processes. Proceedings of the National Academy of Sciences, U.S.A., 110, 4950-4955, 2013]. Distinct selectivity for each condition was evident, representing discrete aspects of word generation-related memory retrieval. For example, the precuneus, implicated in processing spatiotemporal information, emerged as a key contributor to the episodic condition, which uniquely requires this information. Gamma band is known to play a central role in memory, and increased gamma power has been observed before word generation. Yet, gamma modulation in response to task demands has not been investigated. To capture the task-specific modulation of gamma power, we analyzed the EEG data recorded simultaneously with the aforementioned fMRI, focusing on the activity locked to and immediately preceding word articulation. Transient increases in gamma power were identified in a parietal electrode immediately before episodic and semantic word generation, however, within a different time frame relative to articulation. Gamma increases were followed by an alpha-theta decrease in the episodic condition, a gamma decrease in the semantic condition. This pattern indicates a task-specific modulation of the gamma signal corresponding to the specific demands of each word generation task. The gamma power and fMRI signal from the precuneus were correlated during the episodic condition, implying the existence of a common cognitive construct uniquely required for this task, possibly the reactivation or processing of spatiotemporal information.

Portraying the unique contribution of the default mode network to internally driven mnemonic processes.

Numerous neuroimaging studies have implicated default mode network (DMN) involvement in both internally driven processes and memory. Nevertheless, it is unclear whether memory operations reflect a particular case of internally driven processing or alternatively involve the DMN in a distinct manner, possibly depending on memory type. This question is critical for refining neurocognitive memory theorem in the context of other endogenic processes and elucidating the functional significance of this key network. We used functional MRI to examine DMN activity and connectivity patterns while participants overtly generated words according to nonmnemonic (phonemic) or mnemonic (semantic or episodic) cues. Overall, mnemonic word fluency was found to elicit greater DMN activity and stronger within-network functional connectivity compared with nonmnemonic fluency. Furthermore, two levels of functional organization of memory retrieval were shown. First, across both mnemonic tasks, activity was greater mainly in the posterior cingulate cortex, implying selective contribution to generic aspects of memory beyond its general involvement in endogenous processes. Second, parts of the DMN showed distinct selectivity for each of the mnemonic conditions; greater recruitment of the anterior prefrontal cortex, retroesplenial cortex, and hippocampi and elevated connectivity between anterior and posterior medial DMN nodes characterized the semantic condition, whereas increased recruitment of posterior DMN components and elevated connectivity between them characterized the episodic condition. This finding emphasizes the involvement of DMN elements in discrete aspects of memory retrieval. Altogether, our results show a specific contribution of the DMN to memory processes, corresponding to the specific type of memory retrieval.

An international multicenter study comparing COVID-19 omicron outcomes in patients with hematological malignancies treated with obinutuzumab versus rituximab.

OBJECTIVES: Hematological malignancy (HM) patients treated with anti-CD20 monoclonal antibodies are at higher risk for severe COVID-19. A previous single-center study showed worse outcomes in patients treated with obinutuzumab compared to rituximab. We examined this hypothesis in a large international multicenter cohort. METHODS: We included HM patients from 15 centers, from five countries treated with anti-CD20, comparing those treated with obinutuzumab (O-G) to rituximab (R-G) between December 2021 and June 2022, when Omicron lineage was dominant. RESULTS: We collected data on 1048 patients. Within the R-G (n = 762, 73%), 191 (25%) contracted COVID-19 compared to 103 (36%) in the O-G. COVID-19 patients in the O-G were younger (61 ± 11.7 vs. 64 ± 14.5, p = 0.039), had more indolent HM diagnosis (aggressive lymphoma: 3.9% vs. 67.0%, p < 0.001), and most were on maintenance therapy at COVID-19 diagnosis (63.0% vs. 16.8%, p < 0.001). Severe-critical COVID-19 occurred in 31.1% of patients in the O-G and 22.5% in the R-G. In multivariable analysis, O-G had a 2.08-fold increased risk for severe-critical COVID-19 compared to R-G (95% CI 1.13-3.84), adjusted for Charlson comorbidity index, sex, and tixagevimab/cilgavimab (T-C) prophylaxis. Further analysis comparing O-G to R-G demonstrated increased hospitalizations (51.5% vs. 35.6% p = 0.008), ICU admissions (12.6% vs. 5.8%, p = 0.042), but the nonsignificant difference in COVID-19-related mortality (n = 10, 9.7% vs. n = 12, 6.3%, p = 0.293). CONCLUSIONS: Despite younger age and a more indolent HM diagnosis, patients receiving obinutuzumab had more severe COVID-19 outcomes than those receiving rituximab. Our findings underscore the need to evaluate the risk-benefit balance when considering obinutuzumab therapy for HM patients during respiratory viral outbreaks.

Learning and memory-related brain activity dynamics are altered in systemic lupus erythematosus: a functional magnetic resonance imaging study.

BACKGROUND: Memory impairment is prevalent in systemic lupus erythematosus (SLE); however, the pathogenesis is unknown. METHODS: We studied 12 patients with SLE without clinically overt neuropsychiatric manifestations and 11 matched healthy controls, aiming to characterize neural correlates of memory impairment, using structural and functional magnetic resonance imaging (MRI). The paradigm consisted of three encoding and free-recall cycles, allowing characterization of dynamics along consecutive retrieval attempts. RESULTS: During learning, patients with SLE and healthy controls showed brain activity changes in two principal networks, the default mode network (DMN) and the task-positive network (TPN). Patients with SLE demonstrated significantly less deactivation in the DMN and greater activation in the TPN, reflecting greater recruitment of both networks. The anterior medial prefrontal cortex (amPFC) of the DMN emerged as the only region where brain activity dynamics were altered both over the learning process (p < 0.006), and within free-recall period attempts (p < 0.034). Patients showed significant positive correlations between learning efficiency and hippocampal activity, and greater hippocampal functional connectivity, with pronounced connectivity to DMN structures. CONCLUSIONS: Increased brain activation in patients with SLE during learning may reflect compensatory mechanisms to overcome memory impairment. Our findings localize this impairment to the amPFC, consistent with the behavioral pattern seen in SLE. Altered networking of the hippocampal subsystem of the DMN is consistent with hippocampal neuronal damage seen in SLE, and may reflect compensatory cortical reorganization to cope with dysfunction in these regions pivotal to mnemonic functions.

Spinal epidural abscess: in search of reasons for an increased incidence.

BACKGROUND: Spinal epidural abscess (SEA) is a rare disease with a potentially devastating outcome, and a reported incidence traditionally estimated at 0.2-2 cases/10,000 hospital admissions. Since the implementation in October 2007 of a program to increase medical personnel's awareness of SEA, we have documented a sharp increase in the incidence of SEA at our medical center OBJECTIVES: To investigate the cause of the increased incidence of SEA. METHODS: All cases diagnosed with SEA during the period 1998-2010 were retrospectively reviewed. Cases diagnosed before 2007 were compared with those diagnosed thereafter. RESULTS: From January 1998 to October 2007 SEA was diagnosed in 22 patients (group A), giving an annual incidence of 0.14-0.6 cases per 10,000 admissions. During the period November 2007 to April 2010, 26 additional patients were diagnosed (group B), yielding an incidence of 0.81-1.7 cases per 10,000 admissions (P < 0.01). The two groups did not differ significantly in epidemiological, clinical or laboratory characteristics, or in the causative bacteria isolated. CONCLUSIONS: The threefold rise in the incidence of SEA observed at a tertiary medical center in Tel Aviv since November 2007 was not explained by different host characteristics or by more virulent bacterial isolates. We suggest that heightened awareness of the clinical presentation and timely utilization of MR imaging has resulted in more cases being identified.

The First Word Recalled Measure - A Potential Addition to Clinical Exams.

Characterizing episodic memory abilities is highly important in the diagnosis of Alzheimer's disease (AD) and mild cognitive impairment (MCI), and usually includes wordlist learning and recall tasks. Clinical evaluations typically focus on the number of words recalled, ignoring additional information, like serial position. Here, we tested the potential value of two serial positioning measures for clinical diagnosis - how retrieval is initiated, as measured by the first word recalled, and how it proceeds - using data from patients with AD and MCI that completed a wordlist learning and recall task. Our results show that during the early stages of learning, patients with AD are less prone to retrieve the first word from the wordlist, manifested as lower primacy effect in the first word recalled, compared with MCI patients. The first word recalled measure adds to the differentiation between the groups over and above the total number of words learned. Thus, the first word recalled during word list learning and recall tasks may be used as a simple complementary measure to distinguish between MCI and AD during standard neuropsychological evaluations.

WAIS Information Subtest as an indicator of crystallized cognitive abilities and brain reserve among highly educated older adults: A three-year longitudinal study.

The Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) Information Subtest (IS) is known as a neuropsychological "Hold" test that is relatively resistant to decline with aging. We administered neuropsychological tests among highly educated healthy older adults once a year for three subsequent years. Results showed highly stable performances on the IS across years (Mean Z score: T0 = 1.39, SD = 0.60; T1 = 1.37, SD = 0.77; T2 = 1.50, SD = 0.66; T3 = 1.48, SD = 0.66), that were significantly higher than zero (T0: t = 12.08; T1: t = 9.29; T2: t = 11.71; T3: t = 11.68; for all, p < 0.0001). In contrast, other neuropsychological tests showed differences in performance across time; some performances significantly declined (Rey Osterrieth Complex Figure test-copy, Rey-Auditory Verbal Learning Test, and Montreal Cognitive Assessment test [MoCA]), whereas others were improved, possibly due to practice effects (Rey Osterrieth Complex Figure test- delayed, Rey-Auditory Verbal Learning Test- delayed, and Trail Making Test- part A). Correlation with whole brain volumetric analysis revealed a positive correlation between gray matter volumes and IS scores (r = 0.46, p < 0.05) even when controlling for age and education (partial correlations: r = 0.43; r = 0.45, for both p < 0.05). No significant correlations were found between gray matter and other test scores. Therefore, the WAIS-III Information subtest appears to be an adequate neuropsychological measurement of crystallized ability in highly educated older adults and may be considered as a proxy measure of brain reserve.

Changes in Resting-State Functional Connectivity of the Hippocampus Following Cognitive Effort Predict Memory Decline at Older Age-A Longitudinal fMRI Study.

Memory decline is a feature of some, but not all, healthy older adults. The neural patterns of this variability are still largely unknown. We examined the resting-state functional connectivity (RSFC) of older and younger adults before and after cognitive effort as an underlying feature for subsequent memory changes, focusing on the RSFC between the left anterior hippocampus (laHC) and the posterior hippocampi (pHC). Results showed that for younger adults, post-effort increases in laHC-pHC RSFC were related to increases in RSFC between the laHC and the hubs of the default mode network (DMN). However, for older adults, post-effort increases in the RSFC of laHC-pHC were related to decreases in the RSFC of the laHC and right precentral gyrus. Thus, the correlation between intra-HC and inter-HC RSFC was altered with cognitive effort and aging. Importantly, older adults who had lower post-effort RSFC between the laHC and the pHC demonstrated a decline in episodic memory 2 years later. Hence, the change in intra-HC RSFC following cognitive effort was able to predict subsequent memory function with aging in our sample.

How attention modulates encoding of dynamic stimuli in older adults.

Aging is marked by memory decline that is exacerbated with attentional loading. Portraying older adults' neural functions when encoding information in conditions of high and low attentional load is a necessary step toward understanding this phenomenon. Furthermore, the information gained may be used to devise strategies aimed to prevent age-related decline in memory. To address this issue, a group of older adults underwent fMRI scanning while encoding short movies under two levels of attentional loading. High attentional load was associated with increased inter-subject correlation (inter-SC) in only a subset of prefrontal regions that were previously identified in younger adults. It was also associated with lower inter-SC in task-relevant visual regions, suggesting that as load increased, visual processing became less synchronized across participants. Critically, while we have shown that inter-SC in the dorsal posterior cingulate cortex (dPCC) was increased for younger adults at high load, older adults did not generally show this effect. However, those older adults who did display this pattern also displayed a 'younger-like' memory profile. These results point to a pivotal role of the dPCC in the interplay between attention and memory across the lifespan.

Neural patterns underlying the effect of negative distractors on working memory in older adults.

Working memory (WM) declines with age. Older adults, however, perform similar to younger adults in WM tasks with negative distractors at low WM load. To clarify the neural basis of this phenomenon, older (n = 28) and younger (n = 24) adults performed an emotional n-back task during an fMRI scan, and activity in task-related regions was examined. Comparing negative with neutral distraction at low WM load, older adults demonstrated shorter reaction times (RT) and reduced activation in frontoparietal regions: bilateral middle frontal gyrus (MFG) and left parietal cortex. They also had greater coherence within the frontoparietal network, as well as greater deactivation of the ventromedial prefrontal cortex and the amygdala. These patterns probably contributed to the older adults' diminished distractibility by negative task-irrelevant stimuli. Since recruitment of control mechanisms was less required, the frontoparietal network was less activated and performance was improved. Faster RT during the negative condition was related to lesser activation of the MFG in both age groups, corroborating the functional significance of this region to WM across the lifespan.

Sensitivity of Neuropsychological Tests to Identify Cognitive Decline in Highly Educated Elderly Individuals: 12 Months Follow up.

Highly educated individuals have a lower risk of developing dementia and Alzheimer's disease (AD). A common assumption is that their "cognitive reserve" protects them from cognitive decline and postpones the clinical manifestation of dementia. These highly educated individuals usually obtain normal scores on cognitive screening tests, although at the same time they can experience subjective cognitive decline and difficulty in multiple cognitive domains. Although comprehensive neuropsychological evaluations usually identify subtle changes in cognition, they demand extensive resources and thus are expensive and difficult to obtain. Therefore, lack of sensitivity of screening tests on the one hand, along with difficulty to acquire a comprehensive neuropsychological evaluation on the other hand, impede identification of cognitive decline at its earliest stages in this special population. Accordingly, this study aims to identify which neuropsychological tests have the highest sensitivity to detect the earliest stages of cognitive decline among highly educated elderly [n = 27, ages 66-80 (mean = 72.6 SD = 4.54), mean education level = 17.14 (SD = 3.21 range: 12-24 years)]. Baseline scores and scores at one-year follow up were obtained. We also conducted MRI scans to characterize the relation between brain volume and cognitive performance. Results show significant reductions in RVALT, Semantic verbal Fluency, ROCF copy, and MoCA scores whereas PF, TMT, ROCF delay, digit span, and knowledge tests were not significant. The study stresses the importance of using sensitive neuropsychological tests to examine this special population and the need to create norms that combine an individual's education with age.

Altered Topology in Information Processing of a Narrated Story in Older Adults with Mild Cognitive Impairment.

The ability to store, integrate, and manipulate information declines with aging. These changes occur earlier, faster, and to a greater degree as a result of neurodegeneration. One of the most common and early characteristics of cognitive decline is difficulty with comprehension of information. The neural mechanisms underlying this breakdown of information processing are poorly understood. Using functional MRI and natural stimuli (e.g., stories), we mapped the neural mechanisms by which the human brain accumulates and processes information with increasing duration and complexity in participants with amnestic mild cognitive impairment (aMCI) and healthy older adults. To explore the mechanisms of information processing, we measured the reliability of brain responses elicited by listening to different versions of a narrated story created by segmenting the story into words, sentences, and paragraphs and then scrambling the segments. Comparing healthy older adults and participants with aMCI revealed that in both groups, all types of stimuli similarly recruited primary auditory areas. However, prominent differences between groups were found at the level of processing long and complex stimuli. In healthy older adults, parietal and frontal regions demonstrated highly synchronized responses in both the paragraph and full story conditions, as has been previously reported in young adults. Participants with aMCI, however, exhibited a robust functional shift of long time scale processing to the pre- and post-central sulci. Our results suggest that participants with aMCI experienced a functional shift of higher order auditory information processing, possibly reflecting a functional response to concurrent or impending neuronal or synaptic loss. This observation might assist in understanding mechanisms of cognitive decline in aMCI.

How Attention Modulates Encoding of Dynamic Stimuli.

When encoding a real-life, continuous stimulus, the same neural circuits support processing and integration of prior as well as new incoming information. This ongoing interplay is modulated by attention, and is evident in regions such as the prefrontal cortex section of the task positive network (TPN), and in the posterior cingulate cortex (PCC), a hub of the default mode network (DMN). Yet the exact nature of such modulation is still unclear. To investigate this issue, we utilized an fMRI task that employed movies as the encoded stimuli and manipulated attentional load via an easy or hard secondary task that was performed simultaneously with encoding. Results showed increased intersubject correlation (inter-SC) levels when encoding movies in a condition of high, as compared to low attentional load. This was evident in bilateral ventrolateral and dorsomedial prefrontal cortices and the dorsal PCC (dPCC). These regions became more attuned to the combination of the movie and the secondary task as the attentional demand of the latter increased. Activation analyses revealed that at higher load the prefrontal TPN regions were more activated, whereas the dPCC was more deactivated. Attentional load also influenced connectivity within and between the networks. At high load the dPCC was anti-correlated to the prefrontal regions, which were more functionally coherent amongst themselves. Finally and critically, greater inter-SC in the dPCC at high load during encoding predicted lower memory strength when that information was retrieved. This association between inter-SC levels and memory strength suggest that as attentional demands increased, the dPCC was more attuned to the secondary task at the expense of the encoded stimulus, thus weakening memory for the encoded stimulus. Together, our findings show that attentional load modulated the function of core TPN and DMN regions. Furthermore, the observed relationship between memory strength and the modulation of the dPCC points to this region as a key area involved in the manipulation of attentional load on memory function.