Positive schizotypy and negative schizotypy are associated with differential patterns of episodic memory impairment.
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ABSTRACT:
SUBMITTER: Sahakyan L
PROVIDER: S-EPMC5514295 | biostudies-other | 2016 Sep
REPOSITORIES: biostudies-other
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Project description:BackgroundPatients with bipolar disorder (BD) engage in both negative and positive rumination, defined as maladaptive self-focused thinking, and this tendency predicts depressive and manic episodes, respectively. Prior research in patients with major depression implicates regions of the default mode network (DMN) consistent with the self-focused nature of rumination. Little is known about the neural correlates of rumination in bipolar disorder.MethodsFifteen euthymic patients with BD (twelve with Type I) and 17 healthy controls (HC) performed negative and positive rumination induction tasks, as well as a distraction task, followed by a self-related trait judgment task while undergoing functional magnetic resonance imaging (fMRI). Participants also underwent resting state scans. We examined functional connectivity at rest and during the induction tasks, as well as task-based activation during the trait judgment task, in core regions of the DMN.ResultsCompared to HC, patients with BD showed greater functional connectivity between the posterior cingulate cortex (PCC) and medial prefrontal cortex (MPFC) at rest and during positive rumination, compared to distraction. They also showed greater activity in the PCC and MPFC during processing of positive traits, following positive rumination. At rest and during negative rumination compared to distraction, patients with BD showed greater functional connectivity between the PCC and inferior parietal lobule than HC.ConclusionsThese findings demonstrate that negative and positive rumination are subserved by different patterns of connectivity within the DMN in BD. Additionally, the PCC and MPFC are key regions involved in the processing of positive self-relevant traits following positive rumination.
| S-EPMC9871916 | biostudies-literature
Project description:Schizotypy is a multidimensional construct conceptualized as the expression of the underlying vulnerability for schizophrenia. Certain traits of positive schizotypy, such as odd beliefs, unusual perceptual experiences, suspiciousness, and referential thinking show associations with aberrant salience. Positive schizotypy may involve hyper-attribution of salience toward insignificant events, whereas negative schizotypy may involve hypo-attribution of salience, even toward important events. Attribution of salience is thought to involve dopamine-mediated processes, a mechanism that is disrupted in schizotypy; however, little is known about the cognitive processes potentially underlying salience attribution. The present study assessed the relationship between aberrant salience and latent inhibition (LI), as well as their associations with positive and negative schizotypy. Salience was measured at various stages of processing, including visual salience, attributions of salience to contingency illusions, and self-reported experience of salience. Schizotypy traits were differentially associated with self-reported aberrant salience experiences: positive schizotypy showed positive associations (? = 0.67, f2 = 0.82, large effect) and negative schizotypy showed inverse associations (? = -0.20, f2 = 0.07, small effect). However, neither schizotypy dimension was associated with visual salience, contingency illusions, or LI. Salience processing across perceptual, cognitive, and experiential levels likely involves different mechanisms, some of which may not show major disruption in subclinical manifestations of schizotypy.
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Project description:ObjectiveParkinson's disease (PD) episodic memory impairments are common; however, it is not known whether these impairments are due to hippocampal pathology. Hippocampal Lewy-bodies emerge by Braak stage 4, but are not uniformly distributed. For instance, hippocampal CA1 Lewy-body pathology has been specifically associated with pre-mortem episodic memory performance in demented patients. By contrast, the dentate gyrus (DG) is relatively free of Lewy-body pathology. In this study, we used ultra-high field 7-Tesla to measure hippocampal subfields in vivo and determine if these measures predict episodic memory impairment in PD during life.MethodsWe studied 29 participants with PD (age 65.5 ± 7.8 years; disease duration 4.5 ± 3.0 years) and 8 matched-healthy controls (age 67.9 ± 6.8 years), who completed comprehensive neuropsychological testing and MRI. With 7-Tesla MRI, we used validated segmentation techniques to estimate CA1 stratum pyramidale (CA1-SP) and stratum radiatum lacunosum moleculare (CA1-SRLM) thickness, dentate gyrus/CA3 (DG/CA3) area, and whole hippocampus area. We used linear regression, which included imaging and clinical measures (age, duration, education, gender, and CSF), to determine the best predictors of episodic memory impairment in PD.ResultsIn our cohort, 62.1% of participants with PD had normal cognition, 27.6% had mild cognitive impairment, and 10.3% had dementia. Using 7-Tesla MRI, we found that smaller CA1-SP thickness was significantly associated with poorer immediate memory, delayed memory, and delayed cued memory; by contrast, whole hippocampus area, DG/CA3 area, and CA1-SRLM thickness did not significantly predict memory. Age-adjusted linear regression models revealed that CA1-SP predicted immediate memory (beta[standard error]10.895[4.215], p < .05), delayed memory (12.740[5.014], p < .05), and delayed cued memory (12.801[3.991], p < .05). In the fully-adjusted models, which included all five clinical measures as covariates, only CA1-SP remained a significant predictor of delayed cued memory (13.436[4.651], p < .05).ConclusionsIn PD, we found hippocampal CA1-SP subfield thickness estimated on 7-Tesla MRI scans was the best predictor of episodic memory impairment, even when controlling for confounding clinical measures. Our results imply that ultra-high field imaging could be a sensitive measure to identify changes in hippocampal subfields and thus probe the neuroanatomical underpinnings of episodic memory impairments in patients with PD.
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Project description:The notion that the brain is organized into two complementary networks, one that is task-positive and supports externally-oriented processing, and the other that is task-negative and supports internally-oriented processing, has recently attracted increasing attention. The goal of the present study was to investigate involvement of the task-positive and task-negative networks in overlapping activity between episodic memory encoding and retrieval. To this end, we performed a functional MRI study that included both encoding and retrieval tasks. We hypothesized that during the study phase, encoding success activity (remembered > forgotten) involves mainly the task-positive network, whereas encoding failure activity (forgotten > remembered) involves mainly the task-negative network. We also hypothesized that during the test phase, retrieval success activity (old > new) involves mainly the task-negative network, whereas novelty detection activity (new > old) involves mainly the task-positive network. Based on these hypotheses, we made 3 predictions regarding study-test overlap. First, there would be relatively high level of overlap between encoding success and novelty detection activity involving the task-positive network. Second, there would be relatively high level of overlap between encoding failure and retrieval success activity involving the task-negative network. Third, there would be relatively low level of overlap between encoding success and retrieval success activity as well as between encoding failure and novelty detection activity. The results fully confirmed our 3 predictions. Taken together, the present findings clarify roles of the task-positive and task-negative networks in encoding and retrieval and the function of overlapping brain activity between encoding and retrieval.
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Project description:ObjectiveSeveral genome-wide association studies (GWAS) have associated variants in late-onset Alzheimer disease (LOAD) susceptibility genes; however, these single nucleotide polymorphisms (SNPs) have very modest effects, suggesting that single SNP approaches may be inadequate to identify genetic risks. An alternative approach is the use of multilocus genotype patterns (MLGPs) that combine SNPs at different susceptibility genes.MethodsUsing data from 1,365 subjects in the National Institute on Aging Late-Onset Alzheimer's Disease Family Study, we conducted a family-based association study in which we tabulated MLGPs for SNPs at CR1, BIN1, CLU, PICALM, and APOE. We used generalized estimating equations to model episodic memory as the dependent endophenotype of LOAD and the MLGPs as predictors while adjusting for sex, age, and education.ResultsSeveral genotype patterns influenced episodic memory performance. A pattern that included PICALM and CLU was the strongest genotypic profile for lower memory performance (β = -0.32, SE = 0.19, p = 0.021). The effect was stronger after addition of APOE (p = 0.016). Two additional patterns involving PICALM, CR1, and APOE and another pattern involving PICALM, BIN1, and APOE were also associated with significantly poorer memory performance (β = -0.44, SE = 0.09, p = 0.009 and β = -0.29, SE = 0.07, p = 0.012) even after exclusion of patients with LOAD. We also identified genotype pattern involving variants in PICALM, CLU, and APOE as a predictor of better memory performance (β = 0.26, SE = 0.10, p = 0.010).ConclusionsMLGPs provide an alternative analytical approach to predict an individual's genetic risk for episodic memory performance, a surrogate indicator of LOAD. Identifying genotypic patterns contributing to the decline of an individual's cognitive performance may be a critical step along the road to preclinical detection of Alzheimer disease.
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Project description:Studies have demonstrated that episodic memory (EM) is often preferentially disrupted in schizophrenia. The neural substrates that mediate EM impairment in this illness are not fully understood. Several functional magnetic resonance imaging (fMRI) studies have employed EM probe tasks to elucidate the neural underpinnings of impairment, though results have been inconsistent. The majority of EM imaging studies have been conducted in chronic forms of schizophrenia with relatively few studies in early phase patients. Early phase schizophrenia studies are important because they may provide information regarding when EM deficits occur and address potential confounds more frequently observed in chronic populations. In this study, we assessed brain activation during the performance of visual scene encoding and recognition fMRI tasks in patients with earlyphase psychosis (n = 35) and age, sex, and race matched healthy control subjects (n = 20). Patients demonstrated significantly lower activation than controls in the right hippocampus and left fusiform gyrus during scene encoding and lower activation in the posterior cingulate, precuneus, and left middle temporal cortex during recognition of target scenes. Symptom levels were not related to the imaging findings, though better cognitive performance in patients was associated with greater right hippocampal activation during encoding. These results provide evidence of altered function in neuroanatomical circuitry subserving EM early in the course of psychotic illness, which may have implications for pathophysiological models of this illness.
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Project description:IntroductionWe aimed to assess episodic memory in genetic frontotemporal dementia (FTD) with the Free and Cued Selective Reminding Test (FCSRT).MethodsThe FCSRT was administered in 417 presymptomatic and symptomatic mutation carriers (181 chromosome 9 open reading frame 72 [C9orf72], 163 progranulin [GRN], and 73 microtubule-associated protein tau [MAPT]) and 290 controls. Group differences and correlations with other neuropsychological tests were examined. We performed voxel-based morphometry to investigate the underlying neural substrates of the FCSRT.ResultsAll symptomatic mutation carrier groups and presymptomatic MAPT mutation carriers performed significantly worse on all FCSRT scores compared to controls. In the presymptomatic C9orf72 group, deficits were found on all scores except for the delayed total recall task, while no deficits were found in presymptomatic GRN mutation carriers. Performance on the FCSRT correlated with executive function, particularly in C9orf72 mutation carriers, but also with memory and naming tasks in the MAPT group. FCSRT performance also correlated with gray matter volumes of frontal, temporal, and subcortical regions in C9orf72 and GRN, but mainly temporal areas in MAPT mutation carriers.DiscussionThe FCSRT detects presymptomatic deficits in C9orf72- and MAPT-associated FTD and provides important insight into the underlying cause of memory impairment in different forms of FTD.
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Project description:Normal ageing is associated with a decline in episodic memory, and neuroimaging studies in older adults have shown reduced activity in prefrontal cortex and other regions critical for memory function in the young. However, older adults also activate additional regions, suggesting a degree of functional reorganisation that has been attributed variously to detrimental and adaptive changes. Evaluation of these competing hypotheses depends critically upon inferences about the relative location and distribution of activity that are not well supported by current univariate or multivariate analyses. Here, we employed a recently developed model-based multivariate 'decoding' approach (Friston et al., 2008) to re-analyse a rich episodic encoding dataset and examine directly how the patterns of activity change in ageing. We assessed which spatial activity patterns, within lateral prefrontal cortex, best predict successful memory formation. Bayesian model comparison showed that the older adults had more distributed and bilateral (fragmented) predictive patterns of activity in anterior inferior frontal gyrus and middle frontal gyrus. With this direct multivariate test for changes in patterns of activity, we replicate and extend earlier findings of reduced prefrontal lateralisation in ageing. These findings extend conclusions based on conventional analyses, and support the notion that ageing alters the spatial deployment of neuronal activity, to render it less spatially coherent and regionally specific. This greater distribution of activity in older adults was also linked to poorer individual memory performance, suggesting that it reflects neural ageing, rather than adaptive compensatory responses.
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Project description:Cytoplasmic polyadenylation element-binding (CPEB) proteins are crucial for synaptic plasticity and memory in model organisms. A highly conserved, mammalian-specific short intronic sequence within CPEB3 has been identified as a ribozyme with self-cleavage properties. In humans, the ribozyme sequence is polymorphic and harbors a single nucleotide polymorphism that influences cleavage activity of the ribozyme. Here we show that this variation is related to performance in an episodic memory task and that the effect of the variation depends on the emotional valence of the presented material. Our data suggest a role for human CPEB3 in human episodic memory.
| S-EPMC2691156 | biostudies-literature
Project description:For over a century, stability of spatial context across related episodes has been considered a source of memory interference, impairing memory retrieval. However, contemporary memory integration theory generates a diametrically opposite prediction. Here, we aimed to resolve this discrepancy by manipulating local context similarity across temporally disparate but related episodes and testing the direction and underlying mechanisms of memory change. A series of experiments show that contextual stability produces memory integration and marked reciprocal strengthening. Variable context, conversely, seemed to result in competition such that new memories become enhanced at the expense of original memories. Interestingly, these patterns were virtually inverted in an additional experiment where context was reinstated during recall. These observations 1) identify contextual similarity across original and new memories as an important determinant in the volatility of memory, 2) present a challenge to classic and modern theories on episodic memory change, and 3) indicate that the sensitivity of context-induced memory changes to retrieval conditions may reconcile paradoxical predictions of interference and integration theory.
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