Subsequent memory paradigms allow to identify neural correlates of successful encoding by separating brain responses as a function of memory performance during later retrieval. In functional magnetic ...resonance imaging (fMRI), the paradigm typically elicits activations of medial temporal lobe, prefrontal and parietal cortical structures in young, healthy participants. This categorical approach is, however, limited by insufficient memory performance in older and particularly memory-impaired individuals. A parametric modulation of encoding-related activations with memory confidence could overcome this limitation. Here, we applied cross-validated Bayesian model selection (cvBMS) for first-level fMRI models to a visual subsequent memory paradigm in young (18–35 years) and older (51–80 years) adults. Nested cvBMS revealed that parametric models, especially with non-linear transformations of memory confidence ratings, outperformed categorical models in explaining the fMRI signal variance during encoding. We thereby provide a framework for improving the modeling of encoding-related activations and for applying subsequent memory paradigms to memory-impaired individuals.
Experiencing insight when solving problems can improve memory formation for both the problem and its solution. The underlying neural processes involved in this kind of learning are, however, thus far ...insufficiently understood. Here, we conceptualized insight as the sudden understanding of a novel relationship between known stimuli that fits into existing knowledge and is accompanied by a positive emotional response. Hence, insight is thought to comprise associative novelty, schema congruency, and intrinsic reward, all of which are separately known to enhance memory performance. We examined the neural correlates of learning from induced insight with functional magnetic resonance imaging (fMRI) using our own version of the compound-remote-associates-task (CRAT) in which each item consists of three clue words and a solution word. (Pseudo-)Solution words were presented after a brief period of problem-solving attempts to induce either sudden comprehension (CRA items) or continued incomprehension (control items) at a specific time point. By comparing processing of the solution words of CRA with control items, we found induced insight to elicit activation of the rostral anterior cingulate cortex/medial prefrontal cortex (rACC/mPFC) and left hippocampus. This pattern of results lends support to the role of schema congruency (rACC/mPFC) and associative novelty (hippocampus) in the processing of induced insight. We propose that (1) the mPFC not only responds to schema-congruent information, but also to the detection of novel schemata, and (2) that the hippocampus responds to a form of associative novelty that is not just a novel constellation of familiar items, but rather comprises a novel meaningful relationship between the items-which was the only difference between our insight and no insight conditions. To investigate episodic long-term memory encoding, we compared CRA items whose solution word was recognized 24 h after encoding to those with forgotten solutions. We found activation in the left striatum and parts of the left amygdala, pointing to a potential role of brain reward circuitry in the encoding of the solution words. We propose that learning from induced insight mainly relies on the amygdala evaluating the internal value (as an affective evaluation) of the suddenly comprehended information, and striatum-dependent reward-based learning.
We report a human electrophysiological brain state that predicts successful memory for events before they occur. Using magnetoencephalographic recordings of brain activity during episodic memory ...encoding, we show that amplitudes of theta oscillations shortly preceding the onsets of words were higher for later-recalled than for later-forgotten words. Furthermore, single-trial analyses revealed that recall rate in all 24 participants tested increased as a function of increasing prestimulus theta amplitude. This positive correlation was independent of whether participants were preparing for semantic or phonemic stimulus processing, thus likely signifying a memory-related theta state rather than a preparatory task set. Source analysis located this theta state to the medial temporal lobe, a region known to be critical for encoding and recall. These findings provide insight into state-related aspects of memory formation in humans, and open a perspective for improving memory through theta-related brain states.
Episodic memory performance declines with increasing age, and older adults typically show reduced activation of inferior temporo-parietal cortices in functional magnetic resonance imaging (fMRI) ...studies of episodic memory formation. Given the age-related cortical volume loss, it is conceivable that age-related reduction of memory-related fMRI activity may be partially attributable to reduced grey matter volume (GMV). We performed a voxel-wise multimodal neuroimaging analysis of fMRI correlates of successful memory encoding, using regional GMV as covariate. In a large cohort of healthy adults (106 young, 111 older), older adults showed reduced GMV across the entire neocortex and reduced encoding-related activation of inferior temporal and parieto-occipital cortices compared to young adults. Importantly, these reduced fMRI activations during successful encoding could in part be attributed to lower regional GMV. Our results highlight the importance of controlling for structural MRI differences in fMRI studies in older adults but also demonstrate that age-related differences in memory-related fMRI activity cannot be attributed to structural variability alone.
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•Structural differences in distinct age groups may in part explain fMRI differences.•We included voxel-wise GMV into models of the fMRI subsequent memory effect.•Reduced encoding-related activations could in part be attributed to lower local GMV.•Care is advised when modelling fMRI effects for groups with structural differences.•Structural modalities may in part explain alleged differences in function.
Schizophrenia is a complex, heterogeneous psychiatric disorder that affects about 1% of the global population. Hippocampal dysfunction has been linked to both cognitive deficits and positive symptoms ...in schizophrenia. Here, we briefly review current findings on disrupted hippocampal processing from a clinical perspective before concentrating on preclinical studies of aberrant hippocampal synaptic plasticity using the N-methyl-D-aspartate receptor hypofunction model of psychosis and related findings from genetic models. Taken together, the results put the case for maladaptive hippocampal synaptic plasticity and its extrinsic connections as mechanistic underpinnings of cognitive impairments in schizophrenia.
Chronic infection with the neurotropic parasite Toxoplasma gondii has been implicated in the risk for several neuropsychiatric disorders. The mechanisms, by which the parasite may alter neural ...function and behavior of the host, are not yet understood completely.
Here, a novel proteomic approach using mass spectrometry was employed to investigate the alterations in synaptic protein composition in a murine model of chronic toxoplasmosis. In a candidate-based strategy, immunoblot analysis and immunohistochemistry were applied to investigate the expression levels of key synaptic proteins in glutamatergic signaling.
A comparison of the synaptosomal protein composition revealed distinct changes upon infection, with multiple proteins such as EAAT2, Shank3, AMPA receptor, and NMDA receptor subunits being downregulated, whereas inflammation-related proteins showed an upregulation. Treatment with the antiparasitic agent sulfadiazine strongly reduced tachyzoite levels and diminished neuroinflammatory mediators. However, in both conditions, a significant number of latent cysts persisted in the brain. Conversely, infection-related alterations of key synaptic protein levels could be partly reversed by the treatment.
These results provide evidence for profound changes especially in synaptic protein composition in T. gondii-infected mice with a downregulation of pivotal components of glutamatergic neurotransmission. Our results suggest that the detected synaptic alterations are a consequence of the distinct neuroinflammatory milieu caused by the neurotropic parasite.
Abstract
Age-related decline in episodic memory performance is a well-replicated finding across numerous studies. Recent studies focusing on aging and individual differences found that the Big Five ...personality trait Openness to Experience (hereafter: Openness) is associated with better episodic memory performance in older adults, but the associated neural mechanisms are largely unclear. Here, we investigated the relationship between Openness and memory network function in a sample of 352 participants (143 older adults, 50–80 years; 209 young adults, 18–35 years). Participants underwent functional magnetic resonance imaging (fMRI) during a visual memory encoding task. Functional memory brain–network integrity was assessed using the similarity of activations during memory encoding (SAME) scores, which reflect the similarity of a participant’s memory network activity compared to prototypical fMRI activity patterns of young adults. Openness was assessed using the NEO Five-Factor Inventory. Older vs young adults showed lower memory performance and higher deviation of fMRI activity patterns (i.e. lower SAME scores). Specifically in older adults, high Openness was associated with better memory performance, and mediation analysis showed that this relationship was partially mediated by higher SAME scores. Our results suggest that trait Openness may constitute a protective factor in cognitive aging by better preservation of the brain’s memory network.
We hypothesized that novel stimuli represent salient learning signals that can motivate ‘exploration’ in search for potential rewards. In computational theories of reinforcement learning, this is ...referred to as the novelty ‘exploration bonus’ for rewards. If true, stimulus novelty should enhance the reward anticipation signals in brain areas that are part of dopaminergic circuitry and thereby reduce responses to reward outcomes. We investigated this hypothesis in two fMRI experiments. Images of complex natural scenes predicted monetary reward or a neutral outcome by virtue of depicting either indoor or outdoor scenes. Half of the reward-predicting and neutral images had been familiarized the day before, the other half were novel. In experiment 1, subjects indicated whether images were novel or familiar, whereas in experiment 2, they explicitly decided whether or not images predicted reward by depicting indoor or outdoor scenes. Novelty led to the hypothesized enhancement of mesolimbic reward prediction responses and concomitant reduction of mesolimbic responses to reward outcomes. However, this effect was strongly task-dependent and occurred only in experiment 2, when the reward-predicting property of each image was attended. Recognition memory for the novel and familiar stimuli (after 24
h) was enhanced by reward anticipation in both tasks. These findings are compatible with the proposition that novelty can act as a bonus for rewards under conditions when rewards are explicitly attended, thus biasing the organism towards reward anticipation and providing a motivational signal for exploration.
The Met allele of the Val66Met SNP of the BDNF gene (rs6265) is associated with impaired activity-dependent release of brain-derived neurotrophic factor (BDNF), resulting in reduced synaptic ...plasticity, impaired glutamatergic neurotransmission, and morphological changes. While previous work has demonstrated Val66Met effects on magnetic resonance spectroscopy (MRS) markers of either glutamatergic metabolism (Glx) or neuronal integrity (NAA), no study has investigated Val66Met effects on these related processes simultaneously. As these metabolites share a metabolic pathway, the Glx/NAA ratio may be a more sensitive marker of changes associated with the Val66Met SNP. This ratio is increased in psychiatric disorders linked to decreased functioning in the anterior cingulate cortex (ACC). In this study, we investigated the correlation of the Val66Met polymorphism of the BDNF gene with Glx/NAA in the pregenual anterior cingulate cortex (pgACC) using MRS at 3 Tesla (T) (n = 30, all males) and 7 T (n = 98, 40 females). In both cohorts, Met carriers had lower Glx/NAA compared to Val homozygotes. Follow-up analyses using absolute quantification revealed that the Met carriers do not show decreased pgACC glutamate or glutamine levels, but instead show increased NAA compared to the Val homozygotes. This finding may in part explain conflicting evidence for Val66Met as a risk factor for developing psychiatric illnesses.
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