Biology subjects

Fernandez, G.

Publications and source records attributed to Fernandez, G..

31 records · Page 2Linked to original sources

bioRxiv2020

Hippocampal-medial prefrontal event segmentation and integration contribute to episodic memory formation

How do we encode our continuous life experiences for later retrieval? Theories of event segmentation and integration suggest that the hippocampus binds separately represented events into an ordered narrative. Using a functional Magnetic Resonance Imaging (fMRI) movie watching-recall dataset, we quantified two types of neural similarities (i.e., activation pattern similarity and within-region voxel-based connectivity pattern similarity) between separate events during movie watching and related them to subsequent retrieval of events as well as retrieval of sequential order. We demonstrated that compared to forgotten events, successfully remembered events were associated with distinct activation patterns in the hippocampus and medial prefrontal cortex. By contrast, similar connectivity patterns between events were associated with memory formation and were also relevant for retaining events in the correct order. We applied the same approaches to an independent movie watching fMRI dataset as validation and highlighted again the role of hippocampal activation pattern and connectivity pattern in memory formation. We propose that distinct activation patterns represent neural segmentation of events while similar connectivity patterns encode context information, and therefore integrate events into a narrative. Our results provide novel evidence for the role of hippocampal-medial prefrontal event segmentation and integration in episodic memory formation of real-life experience.

neuroscience↗

bioRxiv2019

Probing the neural dynamics of mnemonic representations in humans

Memories are not stored as static engrams, but as dynamic representations affected by processes occurring after initial encoding. Previous studies revealed changes in activity and mnemonic representations in visual processing areas, parietal lobe, and hippocampus underlying repeated retrieval and suppression. However, these neural changes are usually induced by memory modulation immediately after memory formation. Here, we investigated 27 healthy participants with a two-day functional Magnetic Resonance Imaging design to probe how established memories are dynamically modulated by retrieval and suppression 24 hours after learning. Behaviorally, we demonstrated that established memories can still be strengthened by repeated retrieval. By contrast, repeated suppression had a modest negative effect, and suppression-induced forgetting was associated with individual suppression efficacy. Neurally, we demonstrated item-specific pattern reinstatements in visual processing areas, parietal lobe, and hippocampus. Then, we showed that repeated retrieval reduced activity amplitude in the ventral visual cortex and hippocampus, but enhanced the distinctiveness of activity patterns in the ventral visual cortex and parietal lobe. Critically, reduced activity was associated with enhanced representation of idiosyncratic memory traces in ventral visual cortex and precuneus. In contrast, repeated memory suppression was associated with the reduced lateral prefrontal activity, but relative intact mnemonic representations. Our results replicated most of the neural changes induced by memory retrieval and suppression immediately after learning and extended those findings to established memories after initial consolidation. Active retrieval seems to promote episode-unique mnemonic representations in the neocortex after initial encoding but also consolidation. HighlightsO_LIRepeated retrieval strengthened consolidated memories, while repeated suppression had a modest negative effect. C_LIO_LIPattern reinstatements of individual memories were detected in the visual area, parietal lobe, and hippocampus after 24 hours. C_LIO_LIAfter repeated retrieval, reduced activity amplitude was associated with increased distinctiveness of activity patterns in the ventral visual cortex and right precuneus. C_LIO_LIRepeated suppression was associated with the reduced lateral prefrontal activity, but unchanged mnemonic representations. C_LI

neuroscience↗

bioRxiv2019

Common neural and transcriptional correlates of inhibitory control across emotion, memory, and response inhibition

Inhibitory control is crucial for regulating emotions, and it may also enable memory control. However, evidence for their shared neurobiological correlates is limited. Here, we report meta-analyses of neuroimaging studies on emotion regulation, or memory control, and link neural commonalities to transcriptional commonalities using the Allen Human Brain Atlas (AHBA). Based on 95 fMRI studies, we reveal a role of the right inferior parietal lobule embedded in a frontal-parietal-insular network during emotion and memory control, which is similarly recruited during response inhibition. These co-activation patterns also overlap with the networks associated with "inhibition", "cognitive control", and "working memory" when consulting the Neurosynth. Using the AHBA, we demonstrate that emotion and memory control-related brain activity patterns are associated with transcriptional profiles of a specific set of "inhibition-related" genes. Gene ontology enrichment analysis of these "inhibition-related" genes reveal associations with the neuronal transmission and risk for major psychiatric disorders as well as seizures and alcoholic dependence. In summary, this study identified a neural network and a set of genes associated with inhibitory control across emotion regulation, memory control. These findings facilitate our understanding of the neurobiological correlates of inhibitory control and may contribute to the development of novel brain stimulation and pharmacological interventions.

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bioRxiv2019

Medial prefrontal decoupling from the default mode network benefits memory

In the last few years the involvement of the medial prefrontal cortex (mPFC) in memory processing has received increased attention. It is centrally involved when we use prior knowledge (schemas) to improve learning of new material. With the mPFC also being one of the core hubs of the default mode network (DMN) and the DMNs role in memory retrieval, we decided to investigate whether the mPFC in a schema paradigm acts independently of the DMN. We tested this with data from a cross-sectional developmental study. During retrieval of schema items, the mPFC decoupled from the DMN with the degree of decoupling predicting memory performance. This finding suggests that a demand specific reconfiguration of the DMN supports schema memory. Additionally, we found that in the control condition, which relied on episodic memory, activity in the parahippocampal gyrus was positively related to memory performance. We interpret these results as a demand specific network reconfiguration of the DMN: a decoupling of the mPFC to support schema memory and a decoupling of the parahippocampal gyrus facilitating episodic memory. This supports the notion of dynamic reconfiguration of brain networks in response to task demands in the sense of process specific alliances.

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bioRxiv2019

Differences in strategic abilities but not associative processes explain memory development

Childrens learning capabilities change while growing up. One framework that describes the cognitive and neural development of childrens growing learning abilities is the two-component model. It distinguishes processes that integrate separate features into a coherent memory representation (associative component) and executive abilities, such as elaboration, evaluation and monitoring, that support memory processing (strategic component). In an fMRI study using an object-location association paradigm, we investigated how the two components influence memory performance across development. We tested children (10-12 yrs., n=31), late adolescents (18 yrs., n=29) and adults (25+ yrs., n=30) of either sex. For studying the associative component, we also probed how the utilisation of prior knowledge (schemas) facilitates memory across age groups. Children had overall lower retrieval performance, while adolescents and adults did not differ from each other. All groups benefitted from schemas, but this effect did not differ between groups. Performance differences between groups were associated with deactivation of the dorsal medial prefrontal cortex (dmPFC), which in turn was linked to executive functioning. These patterns were stronger in adolescents and adults and seemed absent in children. This pattern of results suggests the childrens executive system, the strategic component, is not as mature and thus cannot facilitate memory performance in the same way as in adolescents/adults. In contrast, we did not find age-related differences in the associative component; with activity in the angular gyrus predicting memory performance systematically across groups. Overall our results suggest that differences of executive rather than associative abilities explain memory differences between children, adolescents and adults.

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bioRxiv2019

The influence of transcranial magnetic stimulation of the medial prefrontal cortex on emotional memory schemas

Memory bias for negative information is a critical characteristic of major depression, but the underlying neural mechanisms are largely unknown. The recently revived concept of memory schemas may shed new light on memory bias in depression: negative schemas might enhance the encoding and consolidation of negative experiences, thereby contributing to the genesis and perpetuation of depressive pathology. To investigate this relationship, we aimed to transiently perturb processing in the medial prefrontal cortex (mPFC), a core region involved in schema memory, using neuronavigated transcranial magnetic stimulation (TMS) targeting the mPFC. Forty healthy volunteers first underwent a negative mood induction to activate negative schema processing after which they received either active inhibitory (N = 20) or control (N = 20) stimulation to the mPFC. Then, all participants performed the encoding of an emotional false memory task. Recall and recognition performance was tested the following morning. Polysomnographic data was recorded continuously during the night before and after encoding. Secondary measures included sleep and mood questionnaires. We observed a significantly lower number of false recognition of negative critical lures following mPFC perturbation compared to the control group, whereas no differences in veridical memory performance were observed. These findings were supported by reaction time data. No relation between REM sleep and (false) emotional memory performance was observed. These findings support previous causal evidence for a role of the mPFC in schema memory processing and further suggest a role of the mPFC in memory bias.

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bioRxiv2019

The role of hippocampal spatial representations in contextualization and generalization of fear

Using contextual information to predict aversive events is a critical ability that protects from generalizing fear responses to safe contexts. Animal models have demonstrated the importance of spatial context representations within the hippocampal formation in contextualization of fear learning. The ventromedial prefrontal cortex (vmPFC) is known to play an important role in safety learning, possibly also through the incorporation of context information. However, if contextual representations are related to context-dependent expression of fear memory in humans remains unclear. Twenty-one healthy participants underwent functional MRI combined with a cue-context conditioning paradigm within a self-navigated virtual reality environment. The environment included two buildings (Threat and Safe context), which had distinct features outside but were identical inside. Within each context, participants saw two cues (CS+, CS-). The CS+ was consistently (100% reinforcement rate) paired with an electric shock in the Threat context, but never in the Safe context. The CS- was never paired with a shock. We found robust differential skin conductance responses (SCRs; CS+ > CS-) in the Threat context, but also within the Safe context, indicating fear generalization. Within the Safe context, vmPFC responses to the CS+ were larger than those in the Threat context. We furthermore found environment-specific representantions for the two contexts in the training paradigm (i.e., before conditioning took place) in the hippocampus to be related to fear expression and generalization. Namely, participants with a weak context representation (z-score < 1.65) showed stronger fear generalization compared to participants with a strong context representation (z-score > 1.65). Thus, a low neural representation of spatial context may explain overgeneralization of memory to safe contexts. In addition, our findings demonstrate that context-dependent regulation of fear expression engages ventromedial prefrontal pathways suggesting this involves a similar mechanism that is known to be involved in retrieval of extinction memory.

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bioRxiv2018

Neural dynamics of accumulating and updating linguistic knowledge structures

Knowledge is acquired by generalization and integration across learning experiences, which can then be applied to future instances. This study provides novel insights into how linguistic associative knowledge is acquired by systematically tracking schematic knowledge formation while participants were learning an abstract artificial language organized by higher-order associative regularity. During learning, we found activity in the left inferior frontal gyrus in response to knowledge updating during feedback presentation, as well as in response to available accumulated knowledge during retrieval. A complementary signal was found in the caudate nucleus, where activity correlated with the availability of recently acquired knowledge during retrieval, suggesting it initially supports the retrieval of knowledge. Furthermore, we find that activity in a set of regions, including the medial prefrontal cortex and hippocampus, scaled with accumulated knowledge during feedback presentation, which might be indicative of increased generalization of features of the hierarchical knowledge structure. Together, these results provide a mechanistic insight into how linguistic associative knowledge is acquired by generalization across repeated learning experiences.

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bioRxiv2018

The functional organisation of the hippocampus along its long axis is gradual and predicts recollection

Understanding the functional organisation of the hippocampus is crucial for understanding its role in cognition and disorders in which it is implicated. Different views have been proposed of how function is distributed along its long axis: one view suggests segregation, whereas the alternative view postulates a more gradual organisation. Here, we applied a novel connectopic mapping data-analysis approach to the resting-state fMRI data of participants of the Human Connectome Project, and demonstrate that the functional organisation of the hippocampal longitudinal axis is gradual rather than segregated into parcels. In addition, we show that inter-individual variations in this gradual organisation predicts variations in recollection memory better than a characterisation based on parcellation. These results present an important step forward in understanding the functional organisation of the human hippocampus and have important implications for translating between rodent and human research.

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bioRxiv2018

Brain scans from 21297 individuals reveal the genetic architecture of hippocampal subfield volumes

The hippocampus is a heterogeneous structure, comprising histologically distinguishable subfields. These subfields are differentially involved in memory consolidation, spatial navigation and pattern separation, complex functions often impaired in individuals with brain disorders characterized by reduced hippocampal volume, including Alzheimers disease (AD) and schizophrenia. Given the structural and functional heterogeneity of the hippocampal formation, we sought to characterize the subfields genetic architecture. T1-weighted brain scans (n=21297, 16 cohorts) were processed with the hippocampal subfields algorithm in FreeSurfer v6.0. We ran a genome-wide association analysis on each subfield, covarying for total hippocampal volume. We further calculated the single nucleotide polymorphism (SNP)-based heritability of twelve subfields, as well as their genetic correlation with each other, with other structural brain features, and with AD and schizophrenia. All outcome measures were corrected for age, sex, and intracranial volume. We found 15 unique genome-wide significant loci across six subfields, of which eight had not been previously linked to the hippocampus. Top SNPs were mapped to genes associated with neuronal differentiation, locomotor behaviour, schizophrenia and AD. The volumes of all the subfields were estimated to be heritable (h2 from .14 to .27, all p< 1x10-16) and clustered together based on their genetic correlations compared to other structural brain features. There was also evidence of genetic overlap of subicular subfield volumes with schizophrenia. We conclude that hippocampal subfields have partly distinct genetic determinants associated with specific biological processes and traits. Taking into account this specificity may increase our understanding of hippocampal neurobiology and associated pathologies.

genetics↗

bioRxiv2018

Eye-movement intervention enhances extinction via amygdala deactivation

Improving extinction learning is essential to optimize psychotherapy for persistent fear-related disorders. In two independent studies (both n=24), we found that goal-directed eye movements activate a dorsal fronto-parietal network and transiently deactivate the amygdala. Connectivity analyses revealed this down-regulation engages a ventromedial prefrontal pathway known to be involved in cognitive regulation of emotion. Critically, when eye movements followed memory reactivation during extinction learning, this reduced spontaneous fear recovery 24 hours later. Stronger amygdala deactivation furthermore predicted a stronger reduction in subsequent fear recovery after reinstatement. In conclusion, we show that extinction learning can be improved with a non-invasive eye-movement intervention that triggers a transient suppression of the amygdala. Our finding that another task which taxes working memory leads to a similar amygdala suppression furthermore indicates that this effect is likely not specific to eye movements, which is in line with a large body of behavioral studies. This study contributes to the understanding of a widely used treatment for traumatic symptoms by providing a parsimonious account for how working memory tasks and goal-directed eye movements can enhance extinction-based psychotherapy, namely through neural circuits similar to those that support cognitive control of emotion.\n\nSignificant statementFear-related disorders represent a significant burden on individual sufferers and society. There is a high need to optimize treatment, in particular via non-invasive means. One potentially effective intervention is execution of eye movements following trauma recall. However, a neurobiological understanding of how eye movements can reduce traumatic symptoms is lacking. We demonstrate that goal-directed eye-movements, like working memory tasks, deactivate the amygdala, the core neural substrate of fear learning. Effective connectivity analyses revealed amygdala deactivation engaged dorsolateral and ventromedial prefrontal pathways. When applied during safety learning, this deactivation predicts a reduction in later fear recovery. These findings provide a parsimonious and mechanistic account of how behavioral manipulations taxing working memory and suppress amygdala activity can alter retention of emotional memories.

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bioRxiv2017

2D:4D and spatial abilities: From rats to humans

Variance in spatial abilities are thought to be determined by in utero levels of testosterone and oestrogen, measurable in adults by the length ratio of the 2nd and 4th digit (2D:4D). We confirmed the relationship between 2D:4D and spatial performance using rats in two different tasks (paired-associate task and watermaze) and replicated this in humans. We further clarified anatomical and functional brain correlates of the association between 2D:4D and spatial performance in humans.

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bioRxiv2017

Cued reactivation during slow-wave sleep induces connectivity changes related to memory stabilization.

Memory reprocessing following acquisition enhances memory consolidation. Specifically, neural activity during encoding is thought to be replayed during subsequent slow-wave sleep (SWS). This natural tendency of memory replay can be induced by external cueing, known as \"targeted memory reactivation\". Here, we analyzed data from a published study (van Dongen, Takashima, et al. 2012), where auditory cues reactivated learned visual object-location memories during SWS. Memory replay during sleep presumably involves a shift in connectivity across the brain. Therefore, we characterized the effects of memory reactivation on brain network connectivity using graph-theory. We found that cue presentation during SWS introduced increased network integration of the occipital cortex, a visual region that was also active during the object retrieval task. Importantly, enhanced network integration of the occipital cortex showed a behavioural benefit and predicted overnight memory stabilization. Furthermore, occipital cortex displayed enhanced connectivity with mnemonic regions, namely the hippocampus, parahippocampal gyrus, thalamus and medial prefrontal cortex during cue versus control sound presentation. Finally, network integration of early occipital cortex during cueing in SWS was related to increased activation of the bilateral parahippocampal gyrus, a region involved in coding for spatial associative information, at the post-sleep test. Together, these results support a neural mechanism where cue-induced replay during sleep promotes memory consolidation by increased integration of task-relevant perceptual regions with mnemonic regions.

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