CD44 Expression in Renal Tissue Is Associated with an Increase in Urinary Levels of Complement Components in Chronic Glomerulopathies.

It is suggested that activated CD44+ cells play a profibrogenic role in the pathogenesis of active glomerulopathies. Complement activation is also involved in renal fibrogenesis. The aim of the study was to evaluate the role of the activation of CD44+ cells in the kidney tissue and complement components' filtration to the urine as factors of renal tissue fibrosis in patients with glomerulopathies. In total, 60 patients with active glomerulopathies were included in our study: 29 patients with focal segmental glomerulosclerosis (FSGS), 10 patients with minimal change disease (MCD), 10 patients with membranous nephropathy (MN), and 11 patients with IgA nephropathy. The immunohistochemical peroxidase method was used to study the expression of CD44+ in kidney biopsies. Components of complement were analyzed in urine by the multiple reaction monitoring (MRM) approach using liquid chromatography. Strong CD44 expression was noted predominantly in PEC and mesangial cells (MC) in patients with FSGS, and to a lesser extent, in patients with MN and IgA nephropathy, and it was absent in patients with MCD. Expression of profibrogenic CD44+ in glomeruli correlated with the levels of proteinuria and complement C2, C3, and C9 components, and CFB and CFI in urine. The CD44+ expression scores in the renal interstitium correlated with the level of C3 and C9 components of complement in the urine and the area of tubulo-interstitial fibrosis. The strongest expression of CD44+ was found in the glomeruli (MC, PEC, and podocytes) of patients with FSGS compared with other glomerulopathies. The CD44 expression score in the glomeruli and interstitium is associated with high levels of complement components in the urine and renal fibrosis.

Neural and functional validation of fMRI-informed EEG model of right inferior frontal gyrus activity.

The right inferior frontal gyrus (rIFG) is a region involved in the neural underpinning of cognitive control across several domains such as inhibitory control and attentional allocation process. Therefore, it constitutes a desirable neural target for brain-guided interventions such as neurofeedback (NF). To date, rIFG-NF has shown beneficial ability to rehabilitate or enhance cognitive functions using functional Magnetic Resonance Imaging (fMRI-NF). However, the utilization of fMRI-NF for clinical purposes is severely limited, due to its poor scalability. The present study aimed to overcome the limited applicability of fMRI-NF by developing and validating an EEG model of fMRI-defined rIFG activity (hereby termed "Electrical FingerPrint of rIFG"; rIFG-EFP). To validate the computational model, we employed two experiments in healthy individuals. The first study (n = 14) aimed to test the target engagement of the model by employing rIFG-EFP-NF training while simultaneously acquiring fMRI. The second study (n = 41) aimed to test the functional outcome of two sessions of rIFG-EFP-NF using a risk preference task (known to depict cognitive control processes), employed before and after the training. Results from the first study demonstrated neural target engagement as expected, showing associated rIFG-BOLD signal changing during simultaneous rIFG-EFP-NF training. Target anatomical specificity was verified by showing a more precise prediction of the rIFG-BOLD by the rIFG-EFP model compared to other EFP models. Results of the second study suggested that successful learning to up-regulate the rIFG-EFP signal through NF can reduce one's tendency for risk taking, indicating improved cognitive control after two sessions of rIFG-EFP-NF. Overall, our results confirm the validity of a scalable NF method for targeting rIFG activity by using an EEG probe.

A Novel and Less Traumatic Needle for Kidney Puncture: Development and Preclinical Study Results.

Abstract Introduction: A considerable proportion of percutaneous nephrolithotomy complications occurs during renal puncture. An option to decrease the complications rate is needle modification to make the procedure less traumatic. We aimed to evaluate the effectiveness of the novel MG needle in a preclinical study. Materials and Methods: We developed an original MG needle based on the Veress needle concept containing an atraumatic (blunt) mandrin connected through a spring to the cannula. The MG needle's properties were compared with those of the conventional Chiba and Trocar needles in two experiments. In the first experiment, we assessed the force required to puncture the model. In the second experiment, we punctured a porcine kidney and analyzed histology report after the puncture. Results: We performed a series of 30 punctures of polypropylene block by each needle. The force required to make a puncture with the Chiba needle (6.53 ± 0.87 N) was significantly lower compared with the MG needle (7.1 ± 1.07 N), p = 0.027. However, the MG needle turned out to be superior to the Trocar needle (8.71 ± 1.08 N), p = 0.001. A total of 15 specimens were obtained after three renal punctures were made with each needle. A microscopy of the specimen after puncture with the Chiba and Trocar needles showed small fragments of epithelium and erythrocytes inside the canal with uneven margins where the needle passed. A microscopy of the specimen after puncture with a novel MG needle showed a canal with even margins. No tissue fragments inside the canal were observed. Conclusion: The force required to puncture with the novel MG needle is comparable with conventional needles. According to preclinical experiments, histology report of porcine kidney indicates that renal puncture with an MG needle is less traumatic. It may reduce the risk of bleeding, and this should be proved during clinical trials.

Neural Synchrony During Naturalistic Information Processing Is Associated With Aerobically Active Lifestyle and Cardiorespiratory Fitness in Cognitively Intact Older Adults.

The functional neural mechanisms underlying the cognitive benefits of aerobic exercise have been a subject of ongoing research in recent years. However, while most neuroimaging studies to date which examined functional neural correlates of aerobic exercise have used simple stimuli in highly controlled and artificial experimental conditions, our everyday life experiences require a much more complex and dynamic neurocognitive processing. Therefore, we have used a naturalistic complex information processing fMRI paradigm of story comprehension to investigate the role of an aerobically active lifestyle in the processing of real-life cognitive-demanding situations. By employing the inter-subject correlation (inter-SC) approach, we have identified differences in reliable stimulus-induced neural responses between groups of aerobically active (n = 27) and non-active (n = 22) cognitively intact older adults (age 65-80). Since cardiorespiratory fitness has previously been suggested to play a key role in the neuroprotective potential of aerobic exercise, we have investigated its dose-response relationship with regional inter-subject neural responses. We found that aerobically active lifestyle and cardiorespiratory fitness were associated with more synchronized inter-subject neural responses during story comprehension in higher order cognitive and linguistic brain regions in the prefrontal and temporo-parietal cortices. In addition, while higher regional inter-SC values were associated with higher performance on a post-listening memory task, this was not translated to a significant between-group difference in task performance. We, therefore, suggest that the modulatory potential of aerobic exercise and cardiorespiratory fitness on cognitive processing may extend beyond simple and highly controlled stimuli to situations in which the brain faces continuous real-life complex information. Additional studies incorporating other aspects of real-life situations such as naturalistic visual stimuli, everyday life decision making, and motor responses in these situations are desired to further validate the observed relationship between aerobic exercise, cardiorespiratory fitness, and complex naturalistic information processing.

Hippocampal and non-hippocampal correlates of physically active lifestyle and their relation to episodic memory in older adults.

Aging is associated with compromised neurocognition. While aerobic exercise has been linked with cognitive resilience, findings regarding its relationship with brain morphology are inconsistent. Furthermore, the biological underpinnings of the relationship between aerobic activity and memory in the aging human brain are unclear. To investigate these issues, we examined hippocampal and non-hippocampal structural correlates of aerobically active lifestyle and cardiorespiratory fitness in older adults. We then examined structural pathways which may potentially mediate the association between active lifestyle and memory. Fifty participants (aged 65-80) underwent structural and diffusion MRI, memory evaluation, were examined for active lifestyle and cardiorespiratory fitness. Morphological features of the hippocampus and fornix, white matter lesions, and brain atrophy were assessed. Active lifestyle and cardiorespiratory fitness correlated with all neurocognitive measures. An exploratory mediation analysis revealed hippocampal and white matter lesions pathways linking active lifestyle and cardiorespiratory fitness with memory. Our results support a neuroprotective role of aerobic exercise on the aging brain and suggest plausible morphological pathways that may underlie the relationship between aerobic exercise and memory.

Physically Active Lifestyle Is Associated With Attenuation of Hippocampal Dysfunction in Cognitively Intact Older Adults.

Alterations in hippocampal function have been shown in older adults, which are expressed as changes in hippocampal activity and connectivity. While hippocampal activation during memory demands has been demonstrated to decrease with age, some older individuals present increased activity, or hyperactivity, of the hippocampus which is associated with increased neuropathology and poor memory function. In addition, lower functional coherence between the hippocampus and core hubs of the default mode network (DMN), namely, the posteromedial and medial prefrontal cortices, as well as increased local intrahippocampal connectivity, were also demonstrated in cognitively intact older adults. Aerobic exercise has been shown to elicit neuroprotective effects on hippocampal structure and vasculature in aging, and improvements in cardiorespiratory fitness have been suggested to mediate these exercise-related effects. However, how these lifestyle factors relate to hippocampal function is not clear. Fifty-two cognitively intact older adults (aged 65-80 years) have been recruited and divided into physically active (n = 29) or non-active (n = 23) groups based on their aerobic activity lifestyle habits. Participants underwent resting-state and task-based fMRI experiments which included an associative memory encoding paradigm followed by a post-scan memory recognition test. In addition, 44 participants also performed cardiopulmonary exercise tests to evaluate cardiorespiratory fitness by measuring peak oxygen consumption (Vo2peak). While both groups demonstrated increased anterior hippocampal activation during memory encoding, a physically active lifestyle was associated with significantly lower activity level and higher memory performance in the recognition task. In addition, the physically active group also demonstrated higher functional connectivity of the anterior and posterior hippocampi with the core hubs of the DMN and lower local intra-hippocampal connectivity within and between hemispheres. Vo2peak was negatively associated with the hippocampal activation level and demonstrated a positive correlation with hippocampal-DMN connectivity. According to these findings, an aerobically active lifestyle may be associated with attenuation of hippocampal dysfunction in cognitively intact older adults.

Changes in Cortical Coherence Supporting Complex Visual and Social Processing in Adolescence.

Despite our differences, there is much about the natural visual world that most observers perceive in common. Across adults, approximately 30% of the brain is activated in a consistent fashion while viewing naturalistic input. At what stage of development is this consistency of neural profile across individuals present? Here, we focused specifically on whether this mature profile is present in adolescence, a key developmental period that bridges childhood and adulthood, and in which new cognitive and social challenges are at play. We acquired fMRI data evoked by a movie shown twice to younger (9-14 years old) and older adolescents (15-19 years old) and to adults, and conducted three key analyses. First, we characterized the consistency of the neural response within individuals (across separate runs of the movie), then within individuals of the same age group, and, last, between age groups. The neural consistency within individuals was similar across age groups with reliable activation in largely overlapping but slightly different cortical regions. In contrast, somewhat differing regions exhibited higher within-age correlations in both groups of adolescents than in the adults. Last, across the whole cortex, we identified regions evincing different patterns of maturation across age. Together, these findings provide a fine-grained characterization of functional neural development in adolescence and uncover signatures of widespread change in cortical coherence that supports the emerging mature stereotypical responses to naturalistic stimuli. These results also offer a more nuanced account of development that obeys neither a rigid linear progression nor a large qualitative change over time.

Neurocognitive Plasticity Is Associated with Cardiorespiratory Fitness Following Physical Exercise in Older Adults with Amnestic Mild Cognitive Impairment.

BACKGROUND: Aerobic training has been shown to promote structural and functional neurocognitive plasticity in cognitively intact older adults. However, little is known about the neuroplastic potential of aerobic exercise in individuals at risk of Alzheimer's disease (AD) and dementia. OBJECTIVE: We aimed to explore the effect of aerobic exercise intervention and cardiorespiratory fitness improvement on brain and cognitive functions in older adults with amnestic mild cognitive impairment (aMCI). METHODS: 27 participants with aMCI were randomized to either aerobic training (n = 13) or balance and toning (BAT) control group (n = 14) for a 16-week intervention. Pre- and post-assessments included functional MRI experiments of brain activation during associative memory encoding and neural synchronization during complex information processing, cognitive evaluation using neuropsychological tests, and cardiorespiratory fitness assessment. RESULTS: The aerobic group demonstrated increased frontal activity during memory encoding and increased neural synchronization in higher-order cognitive regions such as the frontal cortex and temporo-parietal junction (TPJ) following the intervention. In contrast, the BAT control group demonstrated decreased brain activity during memory encoding, primarily in occipital, temporal, and parietal areas. Increases in cardiorespiratory fitness were associated with increases in brain activationin both the left inferior frontal and precentral gyri. Furthermore, changes in cardiorespiratory fitness were also correlated with changes in performance on several neuropsychological tests. CONCLUSION: Aerobic exercise training may result in functional plasticity of high-order cognitive areas, especially, frontal regions, among older adults at risk of AD and dementia. Furthermore, cardiorespiratory fitness may be an important mediating factor of the observed changes in neurocognitive functions.

Maximal aerobic capacity is associated with hippocampal cognitive reserve in older adults with amnestic mild cognitive impairment.

Maximal aerobic capacity (MAC) has been associated with preserved neural tissue or brain maintenance (BM) in healthy older adults, including the hippocampus. Amnestic mild cognitive impairment (aMCI) is considered a prodromal stage of Alzheimer's disease. While aMCI is characterized by hippocampal deterioration, the MAC-hippocampal relationship in these patients is not well understood. In contrast to healthy individuals, neurocognitive protective effects in neurodegenerative populations have been associated with mechanisms of cognitive reserve (CR) altering the neuropathology-cognition relationship. We investigated the MAC-hippocampal relationship in aMCI (n = 29) from the perspectives of BM and CR mechanistic models with structural MRI and a memory fMRI paradigm using both group-level (higher-fit patients vs. lower-fit patients) and individual level (continuous correlation) approaches. While MAC was associated with smaller hippocampal volume, contradicting the BM model, higher-fit patients demonstrated statistically significant lower correlation between hippocampal volume and memory performance compared with the lower-fit patients, supporting the model of CR. In addition, while there was no difference in brain activity between the groups during low cognitive demand (encoding of familiar stimuli), higher MAC level was associated with increased cortical and sub-cortical activation during increased cognitive demand (encoding of novel stimuli) and also with bilateral hippocampal activity even when controlling for hippocampal volume, suggesting for an independent effect of MAC. Our results suggest that MAC may be associated with hippocampal-related cognitive reserve in aMCI through altering the relationship between hippocampal-related structural deterioration and cognitive function. In addition, MAC was found to be associated with increased capacity to recruit neural resources during increased cognitive demands.

Plasma metabolomic profile in prostatic intraepithelial neoplasia and prostate cancer and associations with the prostate-specific antigen and the Gleason score.

INTRODUCTION: The metabolic alterations reflecting the influence of prostate cancer cells can be captured through metabolomic profiling. OBJECTIVE: To characterize the plasma metabolomic profile in prostatic intraepithelial neoplasia (PIN) and prostate cancer (PCa). METHODS: Metabolomics analyses were performed in plasma samples from individuals classified as non-cancerous control (n = 36), with PIN (n = 16), or PCa (n = 27). Untargeted [26 moieties identified after pre-processing by gas chromatography/mass spectrometry (GC/MS)] and targeted [46 amino acids, carbohydrates, organic acids and fatty acids by GC/MS, and 16 nucleosides and amino acids by ultra performance liquid chromatography-triple quadrupole/mass spectrometry (UPLC-TQ/MS)] analyses were performed. Prostate specific antigen (PSA) concentrations were measured in all samples. In PCa patients, the Gleason scores were determined. RESULTS: The metabolites that were best discriminated (p < 0.05, FDR < 0.2) for the Kruskal-Wallis test with Dunn's post-hoc comparing the control versus the PIN and PCa groups included isoleucine, serine, threonine, cysteine, sarcosine, glyceric acid, among several others. PIN was mainly characterized by alterations on steroidogenesis, glycine and serine metabolism, methionine metabolism and arachidonic acid metabolism, among others. In the case of PCa, the most predominant metabolic alterations were ubiquinone biosynthesis, catecholamine biosynthesis, thyroid hormone synthesis, porphyrin and purine metabolism. In addition, we identified metabolites that were correlated to the PSA [i.e. hypoxanthine (r = - 0.60, p < 0.05; r = - 0.54, p < 0.01) and uridine (r = - 0.58, p < 0.05; r = - 0.50, p < 0.01) in PIN and PCa groups, respectively] and metabolites that were significantly different in PCa patients with Gleason score < 7 and ≥ 7 [i.e. arachidonic acid, median (P25-P75) = 883.0 (619.8-956.4) versus 570.8 (505.6-651.8), respectively (p < 0.01)]. CONCLUSIONS: This human plasma metabolomic assessment contributes to the understanding of the unique metabolic features exhibited in PIN and PCa and provides a list of metabolites that can have the potential to be used as biomarkers for early detection of disease progression and management.

Plasma Sarcosine Measured by Gas Chromatography-Mass Spectrometry Distinguishes Prostatic Intraepithelial Neoplasia and Prostate Cancer from Benign Prostate Hyperplasia.

OBJECTIVE: Sarcosine was postulated in 2009 as a biomarker for prostate cancer (PCa). Here, we assess plasma sarcosine as a biomarker that is complementary to prostate-specific antigen (PSA). METHODS: Plasma sarcosine was measured using gas chromatography-mass spectrometry (GC-MS) in adults classified as noncancerous controls (with benign prostate hyperplasia [BPH], n = 36), with prostatic intraepithelial neoplasia (PIN, n = 16), or with PCa (n = 27). Diagnostic accuracy was assessed using receiver operating characteristic curve analysis. RESULTS: Plasma sarcosine levels were higher in the PCa (2.0 µM [1.3-3.3 µM], P <.01) and the PIN (1.9 µM [1.2-6.5 µM], P <.001) groups than in the BPH (0.9 µM [0.6-1.4 µM]) group. Plasma sarcosine had "good" and "very good" discriminative capability to detect PIN (area under the curve [AUC], 0.734) and PCa (AUC, 0.833) versus BPH, respectively. The use of PSA and sarcosine together improved the overall diagnostic accuracy to detect PIN and PCa versus BPH. CONCLUSION: Plasma sarcosine measured by GC-MS had "good" and "very good" classification performance for distinguishing PIN and PCa, respectively, relative to noncancerous patients diagnosed with BPH.

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.

Transient subcortical functional connectivity upon emergence from propofol sedation in human male volunteers: evidence for active emergence.

BACKGROUND: Emergence from sedation entails rapid increase in the levels of both awareness and wakefulness, the two axes of consciousness. Functional MRI (fMRI) studies of emergence from sedation often focus on the recovery period, with no description of the moment of emergence. We hypothesised that by focusing on the moment of emergence, novel insights, primarily about subcortical activity and increased wakefulness, will be gained. METHODS: We conducted a resting state fMRI analysis of 17 male subjects (20-40 yr old) gradually entering into and emerging from deep sedation (average computed propofol concentrations of 2.41 and 1.11 µg ml-1, respectively), using target-controlled infusion of propofol. RESULTS: Functional connectivity analysis revealed a robust spatiotemporal signature of return of consciousness, in which subcortical seeds showed transient positive correlations that rapidly turned negative shortly after emergence. Elements of this signature included four components of the ascending reticular activating system: the ventral tegmentum area, the locus coeruleus, median raphe, and the mammillary body. The involvement of the rostral dorsolateral pontine tegmentum, which is specifically impaired in comatose patients with pontine lesions, in emergence was previously unknown. CONCLUSIONS: Emergence from propofol sedation is characterised, and possibly driven, by a transient activation of brainstem loci. Some of these loci are known components of the ascending reticular activating system, whereas an additional locus was found that is also impaired in comatose patients.

Chain free association, creativity, and the default mode network.

Research on creativity shows that creative thinking entails both executive (controlled) and associative (spontaneous) processes. Yet standard creativity tasks cannot reliably isolate these two types of cognitive processes, making it difficult to understand the relation between the two and the roles of their corresponding brain networks in creative cognition. In this study we used a behavioral and neuroimaging approach in an effort to establish chain free association (FA) tasks as a relevant method for directly investigating spontaneous associative thinking and its role in creative cognition. We further examined the relation between performance on such tasks and intelligence. Participants completed common creativity tasks and then underwent fMRI scanning while producing FA chains. Instructions to participants that emphasized the spontaneous nature of the task, coupled with proper control conditions that were balanced for difficulty, enabled us to uncover spontaneous (as opposed to controlled) processes. To examine whether behavioral measures that can be derived from FA chains (associative fluency, associative flexibility and semantic remoteness between associations) are indicative of unconstrained spontaneous associative processing and are related to different aspects of verbal creativity and intelligence, scores on these measures were correlated with scores on creativity tasks and on an intelligence task, and with brain activity. We found that: (1) the Default Mode Network (DMN), a network involved in self-generated and internally-directed thought, was more involved in chain FA than in other tasks expected to reflect more controlled forms of internally-directed thought, suggesting that the DMN involvement might be related to the unconstrained spontaneous nature of chain FA. Higher involvement of the left IFG, SFG, MFG under chain FA was also revealed; (2) higher scores on different behavioral measures from FA chains were related to higher activation of the DMN and to reduced activation of the left IFG, a major node in the executive function network; (3) behavioral measures from FA chains were correlated with different aspects of creative performance but not with intelligence. Taken together, these findings lend support to the hypothesis that chain FA involves associative spontaneous thinking. They further suggest that behavioral measures derived from chain FA could indicate patterns of unconstrained associative thinking, related to reduced cognitive control, that are relevant for creative ideation, and might be able to serve as a measure of these patterns.

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.

Abnormal neural hierarchy in processing of verbal information in patients with schizophrenia.

Previous research indicates abnormal comprehension of verbal information in patients with schizophrenia. Yet the neural mechanism underlying the breakdown of verbal information processing in schizophrenia is poorly understood. Imaging studies in healthy populations have shown a network of brain areas involved in hierarchical processing of verbal information over time. Here, we identified critical aspects of this hierarchy, examining patients with schizophrenia. Using functional magnetic resonance imaging, we examined various levels of information comprehension elicited by naturally presented verbal stimuli; from a set of randomly shuffled words to an intact story. Specifically, patients with first episode schizophrenia (N = 15), their non-manifesting siblings (N = 14) and healthy controls (N = 15) listened to a narrated story and randomly scrambled versions of it. To quantify the degree of dissimilarity between the groups, we adopted an inter-subject correlation (inter-SC) approach, which estimates differences in synchronization of neural responses within and between groups. The temporal topography found in healthy and siblings groups were consistent with our previous findings - high synchronization in responses from early sensory toward high order perceptual and cognitive areas. In patients with schizophrenia, stimuli with short and intermediate temporal scales evoked a typical pattern of reliable responses, whereas story condition (long temporal scale) revealed robust and widespread disruption of the inter-SCs. In addition, the more similar the neural activity of patients with schizophrenia was to the average response in the healthy group, the less severe the positive symptoms of the patients. Our findings suggest that system-level neural indication of abnormal verbal information processing in schizophrenia reflects disease manifestations.

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.

Neural dynamics underlying emotional transmissions between individuals.

Emotional experiences are frequently shaped by the emotional responses of co-present others. Research has shown that people constantly monitor and adapt to the incoming social-emotional signals, even without face-to-face interaction. And yet, the neural processes underlying such emotional transmissions have not been directly studied. Here, we investigated how the human brain processes emotional cues which arrive from another, co-attending individual. We presented continuous emotional feedback to participants who viewed a movie in the scanner. Participants in the social group (but not in the control group) believed that the feedback was coming from another person who was co-viewing the same movie. We found that social-emotional feedback significantly affected the neural dynamics both in the core affect and in the medial pre-frontal regions. Specifically, the response time-courses in those regions exhibited increased similarity across recipients and increased neural alignment with the timeline of the feedback in the social compared with control group. Taken in conjunction with previous research, this study suggests that emotional cues from others shape the neural dynamics across the whole neural continuum of emotional processing in the brain. Moreover, it demonstrates that interpersonal neural alignment can serve as a neural mechanism through which affective information is conveyed between individuals.

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.

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.