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Temporal memory about when in the past something happened is suggested to be reconstructed rather than recalled. Participants usually show a degree of mismatch between remembered and actual temporal position of an event. However, recent studies showed markedly different results, including both relatively low temporal precision, for visual objects presented earlier in a series, and relatively high temporal precision, for movie scenes shown at the start of a movie. One explanation could be the use of different stimulus materials, for which participants would employ different cognitive encoding or mnemonic strategies. However, a more parsimonious explanation would be that temporal judgments arise from a common mechanism, regardless of stimulus material or context. In the current manuscript, we reanalysed the results of two previously published experiments and investigated the effect of boundary segmentation and semantic relatedness during encoding in two new experiments. We found that participants showed more temporal uncertainty when the encoded visual objects and contexts were unrelated. Further, we found that increasing the semantic associations during encoding diminished temporal uncertainty but increased temporal underestimation bias, which we interpret as an indication of temporal compression. A simple computational model in which temporal judgment is based on a Gaussian process defined by temporal uncertainty (dispersion) and temporal bias (location) replicated the empirical data of all four experiments, suggesting that patterns of temporal errors observed in different experiments arise from a common mechanism. The model further underscores that semantic relatedness between items decreases temporal uncertainty but enhances temporal compression. These findings have important ramifications for how we memorize the temporal structure of events.

We tend to mentally segment a series of events according to perceptual contextual changes, such that items from a shared context are more strongly associated in memory than items from different contexts. It is also known that timing context provides a scaffold to structure experiences in memory, but its role in event segmentation has not been investigated. We adapted a previous paradigm, which was used to investigate event segmentation using visual contexts, to study the effects of changes in timing contexts on event segmentation in associative memory. In two experiments, we presented lists of 36 items in which the interstimulus intervals (ISIs) changed after a series of six items ranging between 0.5 and 4 s in 0.5 s steps. After each list, participants judged which one of two test items were shown first (temporal order judgment) for items that were either drawn from the same context (within an ISI) or from consecutive contexts (across ISIs). Further, participants judged from memory whether the ISI associated to an item lasted longer than a standard interval (2.25 s) that was not previously shown (temporal source memory). Experiment 2 further included a time-item encoding task. Results revealed an effect of timing context changes in temporal order judgments, with faster responses (Experiment 1) or higher accuracy (Experiment 2) when items were drawn from the same context, as opposed to items drawn from across contexts. Further, in both experiments, we found that participants were well able to provide temporal source memory judgments based on recalled durations. Finally, replicated across experiments, we found subjective duration bias, as estimated by psychometric curve fitting parameters of the recalled durations, correlated negatively with within-context temporal order judgments. These findings show that changes in timing context support event segmentation in associative memory.

We memorize our daily life experiences, which are often multisensory in nature, by segmenting them into distinct event models, in accordance with perceived contextual or situational changes. However, very little is known about how multisensory boundaries affect segmentation, as most studies have focused on unisensory (visual or audio) segmentation. In three experiments, we investigated the effect of multisensory boundaries on segmentation in memory and perception. In Experiment 1, participants encoded lists of pictures while audio and visual contexts changed synchronously or asynchronously. After each list, we tested recognition and temporal associative memory for pictures that were encoded in the same audio-visual context or that crossed a synchronous or an asynchronous multisensory change. We found no effect of multisensory synchrony for recognition memory: synchronous and asynchronous changes similarly impaired recognition for pictures encoded at those changes, compared to pictures encoded further away from those changes. Multisensory synchrony did affect temporal associative memory, which was worse for pictures encoded at synchronous than at asynchronous changes. Follow up experiments showed that this effect was not due to the higher dimensionality of multisensory over unisensory contexts (Experiment 2), nor that it was due to the temporal unpredictability of contextual changes inherent to Experiment 1 (Experiment 3). We argue that participants formed situational expectations through multisensory synchronicity, such that synchronous multisensory changes deviated more strongly from those expectations than asynchronous changes. We discuss our findings in light of supportive and conflicting findings of uni- and multi-sensory segmentation.

Segmentation of a narrative stimulus, such as a movie, into discrete events affects and shapes temporal memory of that narrative. One consequence is that segmentation causes temporal memory compression, such that participants believe a recollected event to have lasted shorter than it did during encoding of the event. The mechanism underlying this effect is not clear, but there is growing evidence that boundaries play an important role. In this study, we investigated how boundary differences affected temporal memory and temporal compression of two sitcom episodes. In a pilot study, participants segmented each episode while watching. Results showed more boundaries and a stronger inter-subject agreement about those boundaries for episode 1 compared to episode 2, suggesting a systematic difference in segmentation between the two episodes. In the first main experiment, new participants watched the two episodes and, after each episode, judged when movie frames occurred in the episode’s timeline. Results showed more temporal compression for the episode with larger boundary agreement, irrespective of the visual or semantic knowledge of participants about the episodes. In the second experiment, participants watched one of the episodes twice, on different days. Results showed that repeated watching increased boundary agreement and temporal expectations about when those boundaries would occur, but also increased temporal compression. Further, temporal compression correlated moderately with increased boundary expectation, suggesting a relation between boundary perception and updating of temporal memory. We discuss our findings in light of current theories about event segmentation and temporal memory updating.

BACKGROUND AND PURPOSE: Dynamic contrast-enhanced MRI (DCE-MRI) can be employed to assess the blood-brain barrier (BBB) integrity. Detection of BBB leakage at lower field strengths (≤3T) is cumbersome as the signal is noisy, while leakage can be subtle. Utilizing the increased signal-to-noise ratio at higher field strengths, we explored the application of 7T DCE-MRI for assessing BBB leakage.METHODS: A dual-time resolution DCE-MRI method was implemented at 7T and a slow injection rate (0.3 ml/s) and low dose (3 mmol) served to obtain signal changes linearly related to the gadolinium concentration, that is, minimized for T2 * degradation effects. With the Patlak graphical approach, the leakage rate (Ki ) and blood plasma volume fraction (vp ) were calculated. The method was evaluated in 10 controls, an ischemic stroke patient, and a patient with a transient ischemic attack.RESULTS: Ki and vp were significantly higher in gray matter compared to white matter of all participants. These Ki values were higher in both patients compared to the control subjects. Finally, for the lesion identified in the ischemic stroke patient, higher leakage values were observed compared to normal-appearing tissue.CONCLUSION: We demonstrate how a dual-time resolution DCE-MRI protocol at 7T, with administration of half the clinically used contrast agent dose, can be used for assessing subtle BBB leakage. Although the feasibility of DCE-MRI for assessing the BBB integrity at 3T is well known, we showed that a continuous sampling DCE-MRI method tailored for 7T is also capable of assessing leakage with a high sensitivity over a range of Ki values.

BackgroundA subset of patients with chronic pain who receive exposure in vivo (EXP) treatment experience clinically relevant relief of pain intensity. Although pain relief is not an explicit therapeutic target, it is important to understand how and why this concomitant effect occurs in some patients but not others. This longitudinal study therefore aimed to characterize brain plasticity as well as to explore pretreatment factors related to pain relief.MethodsResting-state functional magnetic resonance imaging data were acquired in 30 patients with chronic pain. Twenty-three patients completed EXP, and 6-month follow-up data were available in 20 patients (magnetic resonance imaging data in 17 patients). Pain-free control data were acquired at two time points (n = 29, n = 21). Seed-based resting-state functional connectivity (rsFC) analyses were performed, with seeds in the amygdala, hippocampus, and nucleus accumbens.ResultsPain relief after EXP was highly variable, with 60% of patients reporting a clinically relevant improvement. Amygdala rsFC with the middle frontal gyrus decreased significantly over time in patients but was not associated with pain relief. In contrast, greater pain relief was associated with greater decreases over time in hippocampus rsFC with the precuneus, which was related to reductions in catastrophizing (EXP therapeutic target) as well. Greater pain relief was also associated with lower pretreatment rsFC between nucleus accumbens and postcentral gyrus.ConclusionsWhile changes in hippocampus rsFC were associated with pain relief after EXP, pretreatment nucleus accumbens rsFC showed potential prognostic value. Our findings further support the importance of corticolimbic circuitry in chronic pain, emphasizing its relation to pain relief and identifying potential underlying mechanisms and prognostic factors, warranting further testing in independent samples.

The hippocampus and dorsal striatum are both associated with temporal processing, but they are thought to play distinct roles. The hippocampus has been reported to contribute to storing temporal structure of events in memory, whereas the striatum contributes to temporal motor preparation and reward anticipation. Here, we asked whether the striatum cooperates with the hippocampus in processing the temporal context of memorized visual associations. In our task, participants were trained to implicitly form temporal expectations for one of two possible time intervals associated to specific cue-target associations, and subsequently were scanned using 7T functional magnetic resonance imaging. During scanning, learned temporal expectations could be violated when the pairs were presented at either the learned or not-learned time intervals. When temporal expectations were not met during testing trials, activity in hippocampal subfields CA3/CA2 and CA1 decreased while right putamen activity increased, compared to when temporal expectations were met. Further, psycho-physiological interactions showed that functional connectivity between left CA1 and caudate, as well as between putamen and caudate, decreased when temporal expectations were not met. Our results indicate that the hippocampus and striatum cooperate to process implicit temporal expectation from mnemonic associations, with different but complementary contributions from caudate and putamen. Our findings provide further support for a hippocampal-striatal network in temporal associative processing.

BACKGROUND: The cerebral default mode network (DMN) can be mapped onto specific regions in the cerebellum, which are specifically vulnerable to atrophy in Alzheimer's disease (AD) patients.OBJECTIVE: We set out to determine whether there are specific differences in the interaction between the cerebral and cerebellar DMN in amnestic mild cognitive impairment (aMCI) patients compared to healthy controls using resting-state functional MRI and whether these differences are relevant for memory performance.METHODS: Eighteen patients with aMCI were age and education-matched to eighteen older adults and underwent 3T MR-imaging. We performed seed-based functional connectivity analysis between the cerebellar DMN seeds and the cerebral DMN.RESULTS: Our results showed that compared to healthy older adults, aMCI patients showed lower anti-correlation between the cerebellar DMN and several cerebral DMN regions. Additionally, we showed that degradation of the anti-correlation between the cerebellar DMN and the medial frontal cortex is correlated with worse memory performance in aMCI patients.CONCLUSION: These findings provide evidence that the cerebellar DMN and cerebral DMN are negatively correlated during rest in older individuals, and suggest that the reduced anti-correlated impacts the modulatory role of the cerebellum on cognitive functioning, in particular on the executive component of memory functions in neurodegenerative diseases.

Temporally structured sequences of experiences, such as narratives or life events, are segmented in memory into discrete situational models. In segmentation, contextual shifts are processed as situational boundaries that temporally cluster items according to the perceived contexts. As such, segmentation enhances associative binding of items within a situational model. One side effect of enhanced associative processing is increased risk of false recollections for not-presented, semantically related items. If so, do boundaries facilitate false recollections, or does segmentation protect against them? In two experiments, we introduced situational shifts in word sequences in the form of semantic and perceptual boundaries, with semantic relatedness between words or the frame color around a word changing on a regular basis. After encoding, we tested participants’ associative memory performance and false recollection rates. In Experiment 1, color boundaries occurred synchronously or asynchronously to semantic boundaries. We found better associative recognition, but also more false recollections, for synchronous than asynchronous boundaries. In Experiment 2, color boundaries occurred synchronous to semantic boundaries or were absent entirely. We found that false recollection rates elicited by semantic boundaries increased when color boundaries were absent. We also tested associative memory performance using a non-semantic, temporal memory task. We found better temporal memory performance for semantic boundaries, as well as a negative correlation between increased false recollection rates and better temporal memory performance for semantic lists, but not for random lists. We discuss implications for false memory theories and segmentation of narrative materials in false memory research.

Neural oscillations in the theta range (4–8 Hz) are thought to underlie associative memory function in the hippocampal-cortical network. While there is ample evidence supporting a role of theta oscillations in animal and human memory, most evidence is correlational. Non-invasive brain stimulation (NIBS) can be employed to modulate cortical oscillatory activity to influence brain activity, and possibly modulate deeper brain regions, such as hippocampus, through strong and reliable cortico-hippocampal functional connections. We applied focal transcranial alternating current stimulation (tACS) at 6 Hz over left parietal cortex to modulate brain activity in the putative cortico-hippocampal network to influence associative memory encoding. After encoding and brain stimulation, participants completed an associative memory and a perceptual recognition task. Results showed that theta tACS significantly decreased associative memory performance but did not affect perceptual memory performance. These results show that parietal theta tACS modulates associative processing separately from perceptual processing, and further substantiate the hypothesis that theta oscillations are implicated in the cortico-hippocampal network and associative encoding.

There is increasing evidence that the hippocampus is involved in language production and verbal communication, although little is known about its possible role. According to one view, hippocampus contributes semantic memory to spoken language. Alternatively, hippocampus is involved in the processing the (mis)match between expected sensory consequences of speaking and the perceived speech feedback. In the current study, we re-analysed functional magnetic resonance (fMRI) data of two overt picture-naming studies to test whether hippocampus is involved in speech production and, if so, whether the results can distinguish between a “pure memory” versus an “expectation” account of hippocampal involvement. In both studies, participants overtly named pictures during scanning while hearing their own speech feedback unimpededly or impaired by a superimposed noise mask. Results showed decreased hippocampal activity when speech feedback was impaired, compared to when feedback was unimpeded. Further, we found increased functional coupling between auditory cortex and hippocampus during unimpeded speech feedback, compared to impaired feedback. Finally, we found significant functional coupling between a hippocampal/supplementary motor area (SMA) interaction term and auditory cortex, anterior cingulate cortex and cerebellum during overt picture naming, but not during listening to one’s own pre-recorded voice. These findings indicate that hippocampus plays a role in speech production that is in accordance with an “expectation” view of hippocampal functioning.

Neural oscillations in the theta range (4-6 Hz) are thought to underlie associative memory function in the hippocampal-cortical network. While there is ample evidence supporting a role of theta oscillations in animal and human memory, most evidence is correlational. Non-invasive brain stimulation (NIBS) can be employed to modulate cortical oscillatory activity to influence brain activity, and possibly modulate deeper brain regions, such as hippocampus, through strong and reliable cortico-hippocampal functional connections. We applied high-definition transcranial alternating current stimulation (HD-tACS) at 6 Hz over left parietal cortex to modulate brain activity in the putative cortico-hippocampal network to influence associative memory encoding. After encoding and brain stimulation, participants completed an associative memory and a perceptual recognition task. Results showed that theta tACS significantly decreased associative memory performance but did not affect perceptual memory performance. These results show that parietal theta tACS modulates associative processing separately from perceptual processing, and further substantiate the hypothesis that theta oscillations are implicated in the cortico-hippocampal network and associative encoding.

Associative memory has been increasingly investigated in immersive virtual reality (VR) environments, but conditions that enable physical exploration remain heavily under-investigated. To address this issue, we designed two museum rooms in VR throughout which participants could physically walk (i.e., high immersive and interactive fidelity). Participants were instructed to memorize all room details, which each contained nine paintings and two stone sculptures. On a subsequent old/new recognition task, we examined to what extent shared associated context (i.e., spatial boundaries, ordinal proximity) and physically travelled distance between paintings facilitated recognition of paintings from the museum rooms. Participants more often correctly recognized a sequentially probed old painting when the directly preceding painting was encoded within the same room or in a proximal position, relative to those encoded across rooms or in a distal position. A novel finding was that sequentially probed paintings from the same room were also recognized better when the physically travelled spatial or temporal distance between the probed paintings was shorter, as compared with longer distances. Taken together, our results in highly immersive VR support the notion that spatiotemporal context facilitates recognition of associated event content. ispartof: MEMORY & COGNITION vol:48 issue:5 pages:691-703 ispartof: location:United States status: published

We tend to mentally segment a series of events according to perceptual contextual changes, such that items from a shared context are more strongly associated in memory than items from different contexts. It is also known that temporal context provides a scaffold to structure experiences in memory, but its role in event segmentation has not been investigated. We adapted a previous paradigm, which was used to investigate event segmentation using visual contexts, to study the effects of changes in temporal contexts on event segmentation in associative memory. We presented lists of items in which the inter-stimulus intervals (ISIs) ranged across lists between 0.5 and 4 s in 0.5 s steps. After each set of six lists, participants judged which one of two test items were shown first (temporal order judgment) for items that were either drawn from the same list or from consecutive lists. Further, participants judged from memory whether the ISI associated to an item lasted longer than a standard interval (2.25s) that was not previously shown. Results showed faster responses for temporal order judgments when items were drawn from the same context, as opposed to items drawn from different contexts. Further, we found that participants were well able to provide temporal duration judgments based on recalled durations. Finally, we found temporal acuity, as estimated by psychometric curve fitting parameters of the recalled durations, correlated inversely with within-list temporal order judgments. These findings show that changes in temporal context support event segmentation in associative memory.

The appropriate definition and scaling of the magnitude of EEG oscillations is an underdeveloped area. The aim of this study was to optimize the analysis of resting EEG alpha magnitude, focusing on alpha peak frequency and non-linear transformation of alpha power. A family of non-linear transforms, Box-Cox transforms, were applied to find the transform that (a) maximized a non-disputed effect: the increase in alpha magnitude when the eyes are closed (Berger effect), and (b) made the distribution of alpha magnitude closest to normal across epochs-within each participant, or across participants. The transformations were done either at the single epoch level, or at the epoch-average level. Alpha peak frequency showed large individual differences, yet good correspondence between various ways to estimate it in two minutes of eyes-closed and two minutes of eyes-open resting EEG data. Both alpha magnitude and the Berger effect were larger for individual alpha than for a generic (8-12 Hz) alpha band. The log transform on single epochs (a) maximized the t-value of the contrast between the eyes-open and eyes-closed condition when tested within each participant, and (b) rendered near-normally distributed alpha power across epochs and participants, thereby making further transformation of epoch-averages superfluous. The results suggest that the log-normal distribution is a fundamental property of variations in alpha power across time in the order of seconds. Moreover, effects on alpha power appear to be multiplicative rather than additive. These findings support the use of the log transform on single epochs to achieve appropriate scaling of alpha magnitude. This article is protected by copyright. All rights reserved.

Contains fulltext : 207240.pdf (Publisher’s version ) (Open Access) Neurobiological models propose reactive aggression as a failure in emotion regulation, caused by an imbalance between prefrontal cortical control and excessive bottom-up signals of negative affect by limbic regions, including the amygdala. Therefore, we hypothesize a negative correlation between PFC and amygdala activity (pre/post resting-state scans) in violent offenders. In this study resting-state fMRI was administered before and after an emotion (anger and happiness) provocation or engagement task within 18 male violent offenders scoring high on reactive aggression, and 18 male non-offender controls. Research in emotional pre/post resting-state showed altered connectivity by task performance. Therefore, bilateral amygdala region of interest (ROI) whole brain functional connectivity analysis tested dynamic change differences between pre and post resting-state connectivity between groups. Self-reported anger showed a positive significant relationship with medial prefrontal cortex activity in the pre-task scan and significantly increased during the emotion task in both the violent and control group. Imaging results showed a significant decrease in amygdala - medial prefrontal functional connectivity in the violent offenders and an increase in the non-offender controls after the emotion task. The opposite pattern was found for amygdala connectivity with the (para) limbic regions: violent offenders showed increased connectivity and non-offender controls showed decreased connectivity. The present results indicate that reactive aggression might stem from a focus on emotion processing, as indicated by an increase in limbic functional connectivity. The combination of a focus on emotion, along with a lack of medial prefrontal cortex regulation, has the potential to grow out of control e.g. in reactive aggression. 13 p.

In recent years, there has been increasing interest in the potential for alterations to the brain's resting-state networks (RSNs) to explain various kinds of psychopathology. RSNs provide an intriguing new explanatory framework for hallucinations, which can occur in different modalities and population groups, but which remain poorly understood. This collaboration from the International Consortium on Hallucination Research (ICHR) reports on the evidence linking resting-state alterations to auditory hallucinations (AH) and provides a critical appraisal of the methodological approaches used in this area. In the report, we describe findings from resting connectivity fMRI in AH (in schizophrenia and nonclinical individuals) and compare them with findings from neurophysiological research, structural MRI, and research on visual hallucinations (VH). In AH, various studies show resting connectivity differences in left-hemisphere auditory and language regions, as well as atypical interaction of the default mode network and RSNs linked to cognitive control and salience. As the latter are also evident in studies of VH, this points to a domain-general mechanism for hallucinations alongside modality-specific changes to RSNs in different sensory regions. However, we also observed high methodological heterogeneity in the current literature, affecting the ability to make clear comparisons between studies. To address this, we provide some methodological recommendations and options for future research on the resting state and hallucinations.

Generalization on the basis of prior experience is a central feature of human and non-human behavior, and anomalies in generalization can give rise to a wide array of problems. For instance, elevated levels of generalization have been shown in individuals suffering from an anxiety disorder. Identifying the individual difference variables that influence the extent to which behavior generalizes to novel stimuli may help our understanding of generalization and its potential maladaptive consequences. In this study, we first present an index of generalization that captures individual differences in generalization in a single continuous measure, thereby surpassing problems associated with traditional analyzing techniques. Further, we investigate whether generalization is predicted by working memory capacity. More precisely, it is hypothesized that generalization is a function of individual differences in the capacity to compare the current situation with previous learning experiences in working memory, and to adjust subsequent behavior accordingly. In a community sample, we found higher levels of generalization in individuals who were less efficient at filtering out irrelevant information from access to working memory. These results suggest that working memory impairments may contribute to elevated and potentially maladaptive levels of generalization. ispartof: Behavior Therapy vol:47 issue:1 pages:130-140 ispartof: location:England status: published

The dorsal attention network (DAN) is known to be involved in shifts of spatial attention or in orienting. However, the involvement of each hemisphere in shifts to either hemifield is still a matter of debate. In this study, interindividual hemifield-specific attentional benefits in RTs were correlated with cue-related BOLD responses specific to directive cues in the left and right frontal and posterior nodes of the DAN, measured in a Spatial Orienting Paradigm. The pattern of correlations was analyzed with respect to its fit with three existing hypotheses of spatial attention control: the contralateral, right dominance, and hybrid hypotheses. Results showed that activation in frontal and parietal nodes of the DAN could explain a significant proportion of the interindividual variance in attentional benefits. Although we found that benefits in the right hemifield correlated with cue-related activity in the left, as well as the right, DAN and that the pattern of correlations fit best with the right dominance hypothesis, there were no significant correlations between left benefits and activation in the right (as well as left) DAN, which precludes the conclusion that our data support the right dominance hypothesis and might instead point toward a potential qualitative difference between leftward and rightward shifts of attention. In conclusion, this study demonstrates that behavioral effects of orienting can be linked to activation changes in the DAN, and it raises new questions with respect to the involvement of the frontal and parietal nodes in each hemisphere in hemifield-specific orienting.

Altered frontoparietal network functional connectivity (FPN-fc) has been associated with neurocognitive dysfunction in individuals with (risk for) psychotic disorder. Cannabis use is associated with cognitive and FPN-fc alterations in healthy individuals, but it is not known whether cannabis exposure moderates the FPN-fc-cognition association. We studied FPN-fc in relation to psychosis risk, as well as the moderating effects of psychosis risk and cannabis use on the association between FPN-fc and (social) cognition. This was done by collecting resting-state fMRI scans and (social) cognitive test results from 63 patients with psychotic disorder, 73 unaffected siblings and 59 controls. Dorsolateral prefrontal cortex (DLPFC) seed-based correlation analyses were used to estimate FPN-fc group differences. Additionally, group x FPN-fc and cannabis x FPN-fc interactions in models of cognition were assessed with regression models. Results showed that DLPFC-fc with the left precuneus, right inferior parietal lobule, right middle temporal gyrus (MTG), inferior frontal gyrus (IFG) regions and right insula was decreased in patients compared to controls. Siblings had reduced DLPFC-fc with the right MTG, left middle frontal gyrus, right superior frontal gyrus, IFG regions, and right insula compared to controls, with an intermediate position between patients and controls for DLPFC-IFG/MTG and insula-fc. There were no significant FPN-fc x group or FPN-fc x cannabis interactions in models of cognition. Reduced DLPFC-insula-fc was associated with worse social cognition in the total sample. In conclusion, besides patient- and sibling-specific FPN-fc alterations, there was evidence for trait-related alterations. FPN-fc-cognition associations were not conditional on familial liability or cannabis use. Lower FPN-fc was associated with lower emotion processing in the total group. (C) 2015 Elsevier B.V. and ECNP. All rights reserved

Neuropathology suggests an important role for the locus coeruleus (LC) in Alzheimer's disease (AD) pathophysiology. Neuropathology and structural damage in the LC appears to be one of the earliest changes. We hypothesize that reduced functional integration of the LC reflected by lower brain functional connectivity contributes to early memory dysfunction. To test this, we examined resting-state functional connectivity from the LC in 18 healthy older individuals and 18 mildly cognitively impaired patients with possible AD. Connectivity measures were correlated with memory scores. The left LC showed strong connectivity to the left parahippocampal gyrus that correlated with memory performance in healthy persons. This connectivity was reduced in aMCI patients. Lateralization of connectivity-memory correlations was altered in less impaired aMCI patients: greater right LC-left parahippocampal gyrus connectivity was associated with better memory performance, in particular for encoding. Our results provide new evidence that the LC, in interaction with the parahippocampal gyrus, may contribute to episodic memory formation. They suggest functional impairment and the possibility that associated compensatory changes contribute to preserved memory functions in early AD. Structural and functional LC-related measures may provide early AD markers.

This chapter discusses human functional neuroimaging findings about how the brain creates true and false memories. These studies have shown that different brain systems contribute to the creation and retrieval of false memories, including systems for sensory perception, executive functioning and cognitive control, and the medial temporal lobe, which has long been associated with episodic and autobiographical memory formation. Many neuroimaging findings provide support for an associative account of false memories, which proposes that false memories arise from associating unrelated mental experiences in memory. At the same time, other neuroimaging findings suggest that false memory creation may depend on states of brain activity during memory encoding. Finally, the chapter briefly provides cautionary notes about using functional neuroimaging as a tool to assess private mental states in individual cases in the courtroom.

Emotion instability in borderline personality disorder (BPD) has been associated with an impaired fronto-limbic inhibitory network. However, functional connectivity (FC) underlying altered emotion regulation in BPD has yet to be established. Here, we used resting-state fMRI to investigate enduring effects of effortful emotion regulation on the amygdala intrinsic FC in BPD. In this multicenter study, resting-state fMRI was acquired before and after an emotion regulation task in 48 BPD patients and 39 non-patient comparison individuals. The bilateral amygdalae were used as a seed in the whole-brain FC analysis and two-way mixed ANOVA to test whether BPD patients exhibited weaker post-task increase in the amygdala intrinsic FC with the prefrontal cortex (PFC), compared to non-patients. Subsequently, we explored whether the results are common for personality disorders characterized by emotional problems, using additional data of 21 cluster-C personality disorder patients. In contrast to non-patients, BPD patients failed to show increased post-task amygdala resting-state FC with the medial, dorsolateral, ventrolateral PFC, and superior temporal gyrus, but surprisingly exhibited decreased FC with the posterior cingulate cortex and increased FC with the superior parietal lobule. In BPD patients, the emotion regulation task failed to increase resting-state amygdala FC with brain regions essential for effortful emotion regulation, which suggests: (a) altered cognitive control typically used to indirectly alleviate distress by reinterpreting the meaning of emotional stimuli; (b) impaired direct regulation of emotional responses, which might be common for personality disorders; (c) avoidance of self-related appraisals induced by social emotional stimuli. Electronic supplementary material The online version of this article (doi:10.1007/s00406-016-0760-z) contains supplementary material, which is available to authorized users.

Neuroimaging studies have demonstrated that activity patterns in early visual areas predict stimulus properties actively maintained in visual working memory. Yet, the mechanisms by which such information is represented remain largely unknown. In this study, observers remembered the orientations of 4 briefly presented gratings, one in each quadrant of the visual field. A 10Hz Transcranial Magnetic Stimulation (TMS) triplet was applied directly at stimulus offset, or midway through a 2-second delay, targeting early visual cortex corresponding retinotopically to a sample item in the lower hemifield. Memory for one of the four gratings was probed at random, and participants reported this orientation via method of adjustment. Recall errors were smaller when the visual field location targeted by TMS over-lapped with that of the cued memory item, compared to errors for stimuli probed diagonally to TMS. This implied topographic storage of orientation information, and a memory-enhancing effect at the targeted location. Furthermore, early pulses impaired performance at all four locations, compared to late pulses. Next, response errors were fit empirically using a mixture model to characterize memory precision and guess rates. Memory was more precise for items proximal to the pulse location, irrespective of pulse timing. Guesses were more probable with early TMS pulses, regardless of stimulus location. Thus, while TMS administered at the offset of the stimulus array might disrupt early-phase consolidation in a non-topographic manner, TMS also boosts the precise representation of an item at its targeted retinotopic location, possibly by increasing attentional resources or by injecting a beneficial amount of noise.

Sensory perceptual processing deficits, such as impaired visual object identification and perceptual closure, have been reported in schizophrenia. These perceptual impairments may be associated with neural deficits in visual association areas, including lateral occipital cortex and inferior temporal areas. However, it remains unknown if such deficits can be found in the intrinsic architecture of the visual system. In the current study, we measured perceptual closure performance and resting-state functional connectivity using functional magnetic resonance imaging (FMRI) in 16 schizophrenia patients and 16 matched healthy controls. We estimated intrinsic functional connectivity using self-organized grouping spatial ICA, which clusters component maps in the subject space according to spatial similarity. Patients performed worse than controls in the perceptual closure task. This impaired closure performance of patients was correlated with increased severity of psychotic symptoms. We also found that intrinsic connectivity of the visual processing system was diminished in patients compared to controls. Lower perceptual closure performance was correlated to lower visual cortical intrinsic connectivity overall. We suggest that schizophrenia is associated with impaired intrinsic connectivity of the visual system, and that it is a potential mechanism leading to impaired visual object perception. These findings contribute to increasing evidence for impairments of higher visual functions in schizophrenia., Highlights • We found reduced visual resting-state network connectivity in schizophrenia. • Reduced connectivity correlated with impaired perceptual closure performance • Schizophrenia is associated with impaired intrinsic connectivity of the visual system.

We have previously reported altered functional asymmetry of the primary auditory cortex (Heschl's gyrus) of patients with schizophrenia (SZ) and their relatives during auditory processing. In this study, we investigated whether schizophrenia patients have altered intrinsic functional organization of Heschl's gyrus (HG) during rest. Using functional magnetic resonance imaging (fMRI), we measured functional connectivity between bilateral HG and the whole brain in 24 SZ patients, 22 unaffected first-degree relatives and 24 matched healthy controls. SZ patients and relatives showed altered functional asymmetry in HG and altered connectivity between temporal and limbic areas in the auditory network during resting-state in comparison with healthy controls. These changes in functional connectivity correlated with predisposition towards hallucinations in patients and relatives and with acute positive symptoms in patients. The results are in line with the results from task-related and symptom-mapping studies that investigated the neural correlates of positive symptoms, and suggest that individual psychopathology is associated with aberrant intrinsic organization of auditory regions in schizophrenia. This might be evidence that reduced hemispheric lateralization and reduced functional connectivity of the auditory network are trait markers of schizophrenia.

The apolipoprotein E epsilon 4 (ApoE epsilon 4) allele not only represents the strongest single genetic risk factor for sporadic Alzheimer's disease, but also imposes independent effects on brain function in healthy individuals where it has been shown to promote subtle memory deficits and altered intrinsic functional brain network connectivity. Based on previous work showing a potential relevance of the default mode network (DMN) functional connectivity for episodic memory function, we hypothesized that the ApoE epsilon 4 genotype would affect memory performance via modulation of the DMN. We assessed 63 healthy individuals (50-80years old), of which 20 carried the epsilon 4 allele. All participants underwent resting-state functional magnetic resonance imaging (fMRI), high-resolution 3D anatomical MRI imaging and neuropsychological assessment. Functional connectivity analysis of resting-state activity was performed with a predefined seed region located in the left posterior cingulate cortex (PCC), a core region of the DMN. ApoE epsilon 4 carriers performed significantly poorer than non-carriers in wordlist recognition and cued recall. Furthermore, epsilon 4 carriers showed increased connectivity relative to epsilon 4 non-carriers between the PCC seed region and left-hemispheric middle temporal gyrus (MTG). There was a positive correlation between recognition memory scores and resting-state connectivity in the left MTG in epsilon 4 carriers. These results can be interpreted as compensatory mechanisms strengthening the cross-links between DMN core areas and cortical areas involved in memory processing.

The planum temporale (PT) is a highly lateralized brain area associated with auditory and language processing. In schizophrenia, reduced structural and functional laterality of the PT has been suggested, which is of clinical interest because of its potential role in the generation of auditory verbal hallucinations. We investigated whether resting-state functional imaging (fMRI) of the PT reveals aberrant functional connectivity and laterality in patients with schizophrenia (SZ) and unaffected relatives, and examined possible associations between altered intrinsic functional organization of auditory networks and hallucinations. We estimated functional connectivity between bilateral PT and whole-brain in 24 SZ patients, 22 unaffected first-degree relatives and 24 matched healthy controls. The results indicated reduced functional connectivity between PT and temporal, parietal, limbic and subcortical regions in SZ patients and relatives in comparison with controls. Altered functional connectivity correlated with predisposition towards hallucinations (measured with the Revised Hallucination Scale [RHS]) in both patients and relatives. We also observed reduced functional asymmetry of the superior temporal gyrus in patients and relatives, which correlated significantly with acute severity of hallucinations in the patient group. To conclude, SZ patients and relatives showed abnormal asymmetry and aberrant connectivity in the planum temporale during resting-state, which was related to psychopathology. These results are in line with results from auditory processing and symptom-mapping studies that suggest that the PT is a central node in the generation of hallucinations. Our findings support reduced intrinsic functional hemispheric asymmetry of the auditory network as a possible trait marker in schizophrenia. (C) 2013 Elsevier B. V. All rights reserved.

Tactile perceptual learning has been shown to improve performance on tactile tasks, but there is no agreement about the extent of transfer to untrained skin locations. The lack of such transfer is often seen as a behavioral index of the contribution of early somatosensory brain regions. Moreover, the time course of improvements has never been described explicitly. Sixteen subjects were trained on the Ludvigh task (a tactile vernier task) on four subsequent days. On the fifth day, transfer of learning to the non-trained contralateral hand was tested. In five subjects, we explored to what extent training effects were retained approximately 1.5 years after the final training session, expecting to find long-term retention of learning effects after training. Results showed that tactile perceptual learning mainly occurred offline, between sessions. Training effects did not transfer initially, but became fully available to the untrained contralateral hand after a few additional training runs. After 1.5 years, training effects were not fully washed out and could be recuperated within a single training session. Interpreted in the light of theories of visual perceptual learning, these results suggest that tactile perceptual learning is not fundamentally different from visual perceptual learning, but might proceed at a slower pace due to procedural and task differences, thus explaining the apparent divergence in the amount of transfer and long-term retention.

Neuroimaging studies have demonstrated that activity patterns in early visual areas predict stimulus properties actively maintained in visual short-term memory. Yet, the mechanisms by which such information is represented remain largely unknown. In this study, observers remembered the orientations of 4 briefly presented gratings, one in each quadrant of the visual field. A 10Hz Transcranial Magnetic Stimulation (TMS) triplet was applied directly at stimulus offset, or midway through a 2-second delay, targeting early visual cortex corresponding retinotopically to a sample item in the lower hemifield. Memory for one of the four gratings was probed at random, and participants reported this orientation via method of adjustment. Replication errors were smaller when the visual field location targeted by TMS overlapped with that of the cued memory item, compared to errors for stimuli probed diagonally to TMS. This implied topographic storage of orientation information, and a memory-enhancing effect at the targeted location. Furthermore, early pulses impaired performance at all four locations, compared to late pulses. Next, response errors were fit empirically using a mixture model analysis to characterize memory precision and guess rates. Memory was more precise for items proximal to the pulse location, irrespective of pulse timing. Guesses were more probable with early TMS pulses, regardless of stimulus location. Thus, whereas TMS administered at the offset of the stimulus array might disrupt early-phase consolidation in a topographically unspecific manner, TMS also boosts the precise representation of an item at its targeted retinotopic location, perhaps by increasing attentional resources or by injecting a beneficial amount of noise.

Practice-induced improvements in skilled performance reflect “offline ” consolidation processes extending beyond daily training sessions. According to visual learning theories, an early, fast learning phase driven by high-level areas is followed by a late, asymptotic learning phase driven by low-level, retinotopic areas when higher resolution is required. Thus, low-level areas would not contribute to learning and offline consolidation until late learning. Recent studies have challenged this notion, demonstrating modified responses to trained stimuli in primary visual cortex (V1) and offline activity after very limited training. However, the behavioral relevance of modified V1 activity for offline consolidation of visual skill memory in V1 after early training sessions remains unclear. Here, we used neuronavigated transcranial magnetic stimulation (TMS) directed to a trained retinotopic V1 location to test for behaviorally relevant consolidation in human low-level visual cortex. Applying TMS to the trained V1 location within 45 min of the first or second training session strongly interfered with learning, as measured by impaired performance the next day. The interference was conditional on task context and occurred only when training in the location targeted by TMS was followed by training in a second location before TMS. In this condition, high-level areas may become coupled to the second location and uncoupled from the previously trained low-level representation, thereby rendering consolidation vulnerable to interference. Our data show that, during the earliest phases of skill learning in the lowest-level visual areas, a behaviorally relevant form of consolidation exists of which the robustness is controlled by high-level, contextual factors.

A number of mental disorders comprise aberrant perceptions that are often described as possessing a perceptual quality approaching real-life sensory experience, while at the same time lacking a sensory correlate in the real world. Healthy individuals can also have perceptual experience without an external correlate when they engage in mental imagery. Aberrant perceptions differ from mental imagery in their lack of voluntary control and the sense of reality. Early theories suggested that increased imagery vividness could lead to aberrant perceptions in a number of clinical disorders. However, cognitive and neuroimaging studies do not endorse this view, and instead suggest that mental imagery comprises a functional architecture that is at least partly shared with memory and perception. Miscommunication or disconnection between brain areas or functional modules within this architecture may give rise to aberrant perceptions and their sense of reality. We describe the evidence for this view in relation to psychotic hallucinations in schizophrenia, hallucinations in neurodegenerative disorders and flashbacks of traumatic events in post-traumatic stress disorder. We suggest that an impaired neural architecture of imagery, rather than merely increased intensity or vividness of imagery, underlies aberrant perceptions. This view fits with neurobiological models of mental disorders that suggest that psychopathological symptoms arise from disrupted communication between brain areas.

Computational neuromodeling may help to further our understanding of how empirical neuroimaging findings are generated by underlying neural mechanisms. Here, we used a simple computational model that simulates early visual processing of brightness changes in a dynamic, illusory display. The model accurately predicted illusory brightness changes in a grey area of constant luminance induced by (and in anti-phase to) luminance changes in its surroundings. Moreover, we were able to directly compare these predictions with recently observed fMRI results on the same brightness illusion by projecting predicted activity from our model onto empirically investigated brain regions. This new approach in which generated network activity and measured neuroimaging data are interfaced in a common representational "brain space" can contribute to the integration of computational and experimental neuroscience.

The processing of visual and haptic inputs, occurring either separately or jointly, is crucial for everyday-life object recognition, and has been a focus of recent neuroimaging research. Previously, visuohaptic convergence has been mostly investigated with matching-task paradigms. However, much less is known about visuohaptic convergence in the absence of additional task demands. We conducted two functional magnetic resonance imaging experiments in which subjects actively touched and/or viewed unfamiliar object stimuli without any additional task demands. In addition, we performed two control experiments with audiovisual and audiohaptic stimulation to examine the specificity of the observed visuohaptic convergence effects. We found robust visuohaptic convergence in bilateral lateral occipital cortex and anterior cerebellum. In contrast, neither the anterior cerebellum nor the lateral occipital cortex showed any involvement in audiovisual or audiohaptic convergence, indicating that multisensory convergence in these regions is specifically geared to visual and haptic inputs. These data suggest that in humans the lateral occipital cortex and the anterior cerebellum play an important role in visuohaptic processing even in the absence of additional task demands.