Memory Impairment In Schizophrenia Research Articles

Interaction between BDNF Val66Met polymorphism and mismatch negativity for working memory capacity in schizophrenia

Both the brain-derived neurotrophic factor (BDNF) valine (Val)/methionine (Met) polymorphism and mismatch negativity (MMN) amplitude are reportedly linked to working memory impairments in schizophrenia. However, there is evident scarcity of research aimed at exploring the relationships among the three factors. In this secondary analysis of a randomized, controlled, double-blind trial, we investigated these relationships. The trial assessed the efficacy of transcranial direct current stimulation for enhancing working memory in clinically stable schizophrenia patients, who were randomly divided into three groups: dorsolateral prefrontal cortex stimulation, posterior parietal cortex stimulation, and sham stimulation groups. Transcranial direct current stimulation was administered concurrently with a working memory task over five days. We assessed the BDNF genotype, MMN amplitude, working memory capacity, and interference control subdomains. These assessments were conducted at baseline with 54 patients and followed up post-intervention with 48 patients. Compared to BDNF Met-carriers, Val homozygotes exhibited fewer positive and general symptoms and increased working memory capacity at baseline. A correlation between MMN amplitude and working memory capacity was noted only in BDNF Val homozygotes. The correlations were significantly different in the two BDNF genotype groups. Furthermore, in the intervention group that showed significant improvement in MMN amplitude, BDNF Val homozygotes exhibited greater enhancement in working memory capacity than Met-carriers. This study provides in vivo evidence for the interaction between MMN and BDNF Val/Met polymorphism for working memory capacity. As MMN has been considered a biomarker of N-methyl-D-aspartate receptor (NMDAR) function, these data shed light on the complex interactions between BDNF and NMDAR in terms of working memory in schizophrenia.

Cross-modal associative memory impairment in schizophrenia

Impaired associative memory function in patients with schizophrenia has received considerable attention. However, previous studies have primarily concentrated on unisensory materials, which limits our understanding of the broader implications of this impairment. In this study, we sought to expand on this knowledge by examining two types of associative memory domains in individuals with schizophrenia, leveraging both visual (Vis) and auditory (Aud) materials. A total of 32 patients with schizophrenia and 29 healthy controls were recruited to participate in the study. Each participant participated in an experiment composed of three paradigms in which different abstract materials (Aud-Aud, Aud-Vis, and Vis-Vis) were presented. Subsequently, the discriminability scores of the two groups were calculated and compared in different modal tasks. Results from the study indicated that individuals with schizophrenia demonstrated varying degrees of associative memory dysfunction in both the same and cross-modalities, with the latter having a significantly lower score than healthy controls (t = 4.120, p < 0.001). Additionally, the cross-modal associative memory function was significantly and negatively correlated with the severity of negative symptoms among individuals diagnosed with schizophrenia (r = −0.362, p = 0.042). This study provides evidence of abnormalities in the processing and memorization of information that integrates multiple sensory modalities in individuals with schizophrenia. This is of great significance for further understanding the cognitive symptoms and pathological mechanisms of schizophrenia, potentially guiding the development of relevant interventions and treatment methods.

Neural substrates of verbal memory impairment in schizophrenia: A multimodal connectomics study.

While verbal memory is among the most compromised cognitive domains in schizophrenia (SZ), its neural substrates remain elusive. Here, we explored the structural and functional brain network correlates of verbal memory impairment in SZ. We acquired diffusion and resting-state functional MRI data of 49 SZ patients, classified as having preserved (VMP, n=22) or impaired (VMI, n=26) verbal memory based on the List Learning task, and 55 healthy controls (HC). Structural and functional connectivity matrices were obtained and analyzed to assess associations with disease status (SZ vs. HC) and verbal memory impairment (VMI vs. VMP) using two complementary data-driven approaches: threshold-free network-based statistics (TFNBS) and hybrid connectivity independent component analysis (connICA). TFNBS showed altered connectivity in SZ patients compared with HC (p < .05, FWER-corrected), with distributed structural changes and functional reorganization centered around sensorimotor areas. Specifically, functional connectivity was reduced within the visual and somatomotor networks and increased between visual areas and associative and subcortical regions. Only a tiny cluster of increased functional connectivity between visual and bilateral parietal attention-related areas correlated with verbal memory dysfunction. Hybrid connICA identified four robust traits, representing fundamental patterns of joint structural-functional connectivity. One of these, mainly capturing the functional connectivity profile of the visual network, was significantly associated with SZ (HC vs. SZ: Cohen's d=.828, p < .0001) and verbal memory impairment (VMP vs. VMI: Cohen's d=-.805, p=.01). We suggest that aberrant connectivity of sensorimotor networks may be a key connectomic signature of SZ and a putative biomarker of SZ-related verbal memory impairment, in consistency with bottom-up models of cognitive disruption.

Episodic Memory and Schizophrenia: From Characterization of Relational Memory Impairments to Neuroimaging Biomarkers.

Episodic memory research in schizophrenia has a long history already which has clearly established significant impairments and strong associations with brain measures and functional outcome. The purpose of this chapter is not to make an exhaustive review of the recent literature but to highlight some relatively recent developments in the cognitive neuroscience field of episodic memory and schizophrenia. Hence, we present a contemporary view focusing specifically of relational memory which represents a form of episodic memory that refers to associations or binding among items or elements presented together. We describe the major tasks used and illustrate how their combination with brain imaging has: (1) favored the use of experimental memory tasks to isolate specific processes with specific neural correlates, (2) led to a distributed view of the neural correlates of memory impairments in schizophrenia where multiple regions are contributing, and (3) made possible the identification of fMRI biomarkers specific to episodic memory. We then briefly propose what we see as the next steps for memory research in schizophrenia so that the impact of this work can be maximized.

Unraveling the role of retrieval deficits in autobiographical memory impairment in schizophrenia: A comparison of involuntary and voluntary autobiographical memories

Patients with schizophrenia show severe autobiographical memory impairment, thought to reflect retrieval deficits caused by executive dysfunction. However, prior research has focused exclusively on strategic (voluntary) retrieval, and ignored involuntary retrieval resulting from automatic and associative processes, involving minimal cognitive control. We report two studies with patients diagnosed with schizophrenia (Ns = 40 and 50 respectively) comparing their impairment in involuntary versus voluntary autobiographical memory. We use two different methodologies, not previously used in schizophrenia research: a naturalistic study involving real-life data and an experimental setup. Both studies consistently showed that involuntary and voluntary autobiographical memories were similarly impaired in schizophrenia. The absence of interaction effects between group and retrieval suggests that schizophrenic patients did not benefit from memory tasks involving little retrieval effort. These findings suggest that autobiographical memory impairment in schizophrenia are not caused by problems with self-initiated voluntary retrieval, but instead likely reflect encoding or binding deficits.

Habituation during encoding: A new approach to the evaluation of memory deficits in schizophrenia

BackgroundMemory is significantly impaired in schizophrenia. However, memory measures are often complex and confounded by additional impairments such as motivation and task comprehension, which can affect behavioral performance and obscure neural function during memory tasks. Neural signatures of memory encoding that are robust to potential confounds may shed additional light on neural deficits contributing to memory impairment in schizophrenia. MethodsHere, we investigate a potential neural signature of memory—habituation—and its relationship with healthy and impaired memory function. To limit potential confounds, we used a passive depth of encoding memory task designed to elicit neural responses associated with memory encoding while limiting other cognitive demands. To determine whether habituation during encoding was predictive of intact memory processing, we first compared neural habituation over repeated encoding exposures with subsequent explicit memory in healthy individuals. We then tested whether a similar relationship existed in patients with schizophrenia. ResultsExplicit memory performance was impaired in patients with schizophrenia relative to healthy control subjects. In healthy participants, more habituation over repeated exposures during encoding was associated with greater repetition-related increases in accuracy during testing. However, in patients with schizophrenia, better performance was associated with less habituation, or a more sustained neural response during encoding. ConclusionsThese results suggest that sustained neural activity is required for normal repetition-related improvements in memory performance in schizophrenia, in line with a neural inefficiency model. Habituation may serve as a valuable index of neural processes that underlie behavioral memory performance.

Altered levels of immune cell adhesion molecules are associated with memory impairment in schizophrenia and healthy controls

Increased cytokines and increased intercellular adhesion molecule-1 (ICAM1) found in the schizophrenia prefrontal cortex and in the blood may relate to cognitive deficits. Endothelial ICAM1 regulates immune cell trafficking into the brain by binding to integrins located on the surface of leukocytes. Whether the circulating levels of the main ICAM1 adhesion partners, lymphocyte-function associated antigen-1 (LFA1) and complement receptor 3 (CR3), both integrins, are altered in schizophrenia is unknown. Gene expressions of ICAM1, LFA1 and CR3 were measured in leukocytes from 86 schizophrenia patients and 77 controls. Participants were also administered cognitive testing to determine the extent to which cognitive ability was related to molecular measures of leukocyte adhesion. This cohort was previously stratified into inflammatory subgroups based on circulating cytokine mRNAs; thus, gene expressions were analysed by diagnosis and by inflammatory subgroups. Previously measured plasma ICAM1 protein was elevated in “high inflammation” schizophrenia compared to both “high” and “low inflammation” controls while ICAM1 mRNA was unchanged in leukocytes. LFA1 mRNA was decreased and CR3 mRNA was increased in leukocytes from people with schizophrenia compared to controls. LFA1 mRNA levels were positively correlated with working memory and elevated soluble ICAM1 was negatively correlated with verbal memory in schizophrenia. Altogether, some of the cognitive deficits in schizophrenia may be associated with altered expression of molecules that regulate immune cell trafficking.

Hippocampal glutamate and hippocampus subfield volumes in antipsychotic-naive first episode psychosis subjects and relationships to duration of untreated psychosis

Evidence points toward a relationship between longer duration of untreated psychosis (DUP) and worse long-term outcomes in patients with first episode psychosis (FEP), but the underlying neurobiology remains poorly understood. Proton magnetic resonance spectroscopy studies have reported altered hippocampus glutamatergic neurotransmission, and structural MRI as reported hippocampal atrophy that may be associated with memory impairment in schizophrenia. Here, we quantify left hippocampus glutamate (Glx) and left hippocampus subfield volumes in 54 antipsychotic-naive FEP and 41 healthy controls (HC), matched on age, sex, and parental occupation. While there were no significant group difference in Glx levels, hippocampal Glx levels were significantly higher in those who underwent a long DUP (>12 months) compared to those with a short DUP, and compared to HC. Compared to HC, FEP had significantly reduced whole hippocampus volume, as well as of CA1, CA4, granule cell layer, subiculum, and presubiculum subfields. Smaller whole hippocampal volume, as well as CA1, molecular layer, subiculum, presubiculum, and hippocampal tail volumes were significantly associated with longer DUP. However, we found no significant association between hippocampal Glx levels and hippocampal volume or subfields, suggesting that these alterations are not related, or their relationship does not follow a linear pattern. However, our results strongly suggest that one or several pathophysiological processes underlie the DUP. Importantly, our data highlight the critical need for reducing the DUP and for early pharmacological intervention with the hope to prevent structural deficits and, hopefully, improve clinical outcomes.

MK-801 impairs working memory on the Trial-Unique Nonmatch-to-Location test in mice, but this is not exclusively mediated by NMDA receptors on PV+ interneurons or forebrain pyramidal cells

NMDA receptors (NMDAr) are widely expressed throughout the brain on many cell types, and loss of function of these receptors (ie: NMDAr hypofunction) is a candidate mechanism explaining working memory impairment in schizophrenia. However, the cellular source driving the working memory deficits caused by NMDAr hypofunction has not been explored. The aim of this study was to assess the contribution of NMDAr on pyramidal cells and parvalbumin (PV+) interneurons to impairments in working memory induced by NMDAr hypofunction. We excised GluN1 - the gene encoding the obligatory subunit of the NMDAr - from PV + interneurons or CaMKIIα+ pyramidal cells using Cre-lox technology. Adult male PV GluN1 KO (n = 10) and CaMKIIα GluN1 KO mice (n = 9) and WT controls (n = 10 and n = 13) were trained to perform the Trial-Unique Nonmatching-to-Location (TUNL) task of working memory. Once trained, mice received the NMDAr antagonist MK-801 (0.1 and 0.3 mg/kg ip), and working memory assessed. Neither task acquisition nor working memory differed between the two transgenic lines and WT littermates. MK-801 dose-dependently decreased working memory accuracy in all strains (p < 0.001). PV GluN1 KO mice were sensitised to the impairing effects of MK-801 (p = 0.04), whereas CaMKIIα GluN1 KO mice showed equivalent working memory deficits as WT. Developmental NMDAr hypofunction at either PV+ interneurons or forebrain pyramidal cells is not sufficient to impair working memory, and neither of these cell types exclusively mediates working memory impairment caused by NMDAr antagonism. Reduced NMDAr signalling at PV+ interneurons could predispose circuits to NMDAr hypofunction magnifying deficits in working memory.

Brain insulin resistance and altered brain glucose are related to memory impairments in schizophrenia

Memory is robustly impaired in schizophrenia (SZ) and related to functional outcome. Memory dysfunction has been shown to be related to altered brain glucose metabolism and brain insulin resistance in animal models and human studies of Alzheimer's disease. In this study, differences in brain glucose using magnetic resonance spectroscopy (MRS) and blood Extracellular Vesicle (EV) biomarkers of neuronal insulin resistance (i.e. Akt and signaling effectors) between SZ and controls were investigated, as well as whether these measures were related to memory impairments. Neuronal insulin resistance biomarkers showed a trend for being lower in SZ compared to controls, and memory measures were lower in SZ compared to controls. Occipital cortex glucose was higher in SZ compared to controls indicating lower brain glucose utilization. Linear regression analyses revealed significant relationships between neuronal insulin resistance biomarkers, memory measures, and brain glucose. More specifically, p70S6K, an insulin signaling effector, was related to verbal learning and brain MRS glucose in the SZ group. For the first time, we show that memory impairments in SZ may be related to brain glucose and brain insulin resistance. These data suggest that brain insulin resistance may play a role in the pathophysiology of learning and memory dysfunction in SZ.

Prevalence of Working Memory Impairment in Drug Naive Schizophrenic Patients in a Tertiary Care Hospital

Schizophrenia is a mental disorder in which clear consciousness and the intellectual capacity are usually maintained, although certain cognitive deficits may evolve in the course of illness. Working memory impairment in schizophrenia affects the course, outcome, and quality of life of the patient significantly. The aim of the study was to find out the prevalence of working memory impairment in drug naive schizophrenic patients. This descriptive cross-sectional study was done in a tertiary care hospital, from June 2015 to December 2015 after taking ethical clearance from institutional review board registration number 38970/062/063. Convenience sampling was done. The samples of 30 schizophrenic patients between the ages of 15 to 45 years were enrolled from the inpatient and outpatient unit of department according to inclusion and exclusion criteria. Data was collected and entry was done in Epi Info, point estimate at 95% Confidence Interval was calculated along with frequency and proportion for binary data. The prevalence of working memory impairment was 26 (86.7%) in digit span forward test and 27 (90%) in digit span backward test. The mean age of patients was 27.5 years and the age of onset of schizophrenia was mainly in the age group between 16 to 25 years 16 (53.3%). These finding suggests high prevalence of working memory impairment in schizophrenic patients.

Memory and cognition in schizophrenia.

Episodic memory deficits are consistently documented as a core aspect of cognitive dysfunction in schizophrenia patients, present from the onset of the illness and strongly associated with functional disability. Over the past decade research using approaches from experimental cognitive neuroscience revealed disproportionate episodic memory impairments in schizophrenia (Sz) under high cognitive demand relational encoding conditions and relatively unimpaired performance under item-specific encoding conditions. These specific deficits in component processes of episodic memory reflect impaired activation and connectivity within specific elements of frontal-medial temporal lobe circuits, with a central role for the dorsolateral prefrontal cortex (DLPFC), relatively intact function of ventrolateral prefrontal cortex and variable results in the hippocampus. We propose that memory deficits can be understood within the broader context of cognitive deficits in Sz, where impaired DLPFC related cognitive control has a broad impact across multiple cognitive domains. The therapeutic implications of these findings are discussed.

An Exploratory Study of Exercise-related Effects on Memory and Hippocampal Connectivity in Schizophrenia.

Memory impairment in schizophrenia has been linked to abnormal functioning of fronto-temporal networks. In this pilot study, we investigated whether 12-weeks of exercise improved hippocampal-dependent memory functions and resting-state functional connectivity in middle-aged adults with schizophrenia. The exercise regimen was feasible, well-attended, and safe. There was a pre- to post-intervention increase in spatial memory accuracy that was correlated to an increase in hippocampal-prefrontal cortex connectivity. No increase was found in pattern separation performance or hippocampal volume. A controlled trial is needed to replicate these findings and elucidate the functional brain networks underlying exercise-induced cognitive improvement in schizophrenia.

P.2.049 - Fronto-parietal connectivity and its relation to frontal glutamate in patients suffering from schizophrenia

Cognitive deficits like working memory impairment in schizophrenia are of great importance for clinical outcome, but the underlying neurobiology is not fully understood. During working memory (WM) altered connectivity patterns in the fronto-parietal network are present in patients suffering from schizophrenia [1–3]. One candidate biochemical marker for the integrity of connectivity is glutamate [4]. Here we tested for group differences in fronto-parietal connectivity and it’s relation to possible glutamatergic influences. During a functional magnetic resonance imaging (fMRI) scan, a sample of 42 medicated patients (SZ) and 41 age and gender matched healthy controls (HC) were asked to perform a numeric n-back working memory task, which consisted of two conditions “2-back” and “0-back”. FMRI was conducted on a 3T Siemens Trio scanner with a 12 channel head coil using gradient-echo echo-planar imaging. Data were further preprocessed using the statistical parametric mapping (SPM 8; Welcome Department of Imaging Neuroscience, London, UK; htt://www.fil.ion.ucl.ac.uk/spm) in MATLAB 2009b. We performed dynamic causal modeling [5] (DCM) on a model space comprising regions of interest for a visual input, parietal (PC) and dorsolateral prefrontal cortex (DLPFC). We calculated Bayesian model averages to obtain weighted connectivity parameters. One-sample t-tests were calculated on parameters for PC->DLPFC and DLPFC->PC connectivity within each group in order to evaluate modulatory effects of working memory on the executive network. Glutamate levels were measured in left DLPFC using magnetic resonance spectroscopy. We used LCmodel (Linear Combination of Model spectra, a commercial spectral fitting package) to estimate local glutamate concentration. Absolute glutamate concentrations were adjusted for grey and white matter volume. We performed group comparisons (two-sample t-test) on connectivity parameters as well as on glutamate levels. Due to non-normality two-sided Spearman correlation analysis were calculated between connectivity parameters and glutamate levels. Working memory dependent connectivity effects (between PC and DLPFC) could be observed in the left hemisphere on backward connections (PC->DLPFC, HC: t=2.77, p=0.008; SZ: t=2.62, p=0.012), whereas no significant working memory effects were present on DLPFC->PC connectivity. We found no group difference in fronto-parietal connectivity parameters and no difference in glutamate levels. Nonetheless numerically controls show higher glutamate levels as compared to patients. To explore possible effects of local Glutamate levels on working memory dependent connectivity, we correlated parameters for PC->DLPFC connectivity (where we found significant working memory dependent effects) with glutamate levels. We found a significant negative association between parieto-frontal connectivity and glutamate in DLPFC in patients (rho=-0.47, p=0.0035). Controls did not show any significant association (rho=-0.12, p=0.53). Comparing correlation coefficients, we found a trend-wise significant difference between groups (z=1.55, p=0.06). Although our data neither showed a difference in connectivity nor in glutamate levels, our findings suggest that glutamate is differentially related to working memory dependent connectivity from parietal to frontal areas in patients as compared to controls.

Memory impairment and the mediating role of task difficulty in patients with schizophrenia.

Using meta-analytic methods, we sought to synthesize the research literature on memory impairment in schizophrenia. Additionally, we compared performances across memory measures to determine if task difficulty (e.g., effortful encoding and retrieval vs non-effortful encoding and retrieval) could account for variance across studies. Our primary measures of interest included the California Verbal Learning Test, Wechsler Memory Scale, Rey Auditory Verbal Learning Test, Hopkins Verbal Learning Test, Rey-Osterrieth Complex Figure Test, and the Benton Visual Retention Test. We searched for all studies that met inclusion criteria using PubMed, PsycINFO, Scholars Portal Search, and Google Scholar. Studies were included if: (i) they were published after 1980; (ii) healthy controls were compared to patients with schizophrenia; (iii) at least one of the noted measures of interest was employed in the primary study; and (iv) the primary study included data that could be transformed to point estimate effect sizes (i.e., Cohen's d). Cohen's d was calculated between patients and healthy controls, along with overall 95% confidence intervals. A two-tailed independent samples t-test was conducted to assess if performance differed on various paired subtests of the same domain. Large effect sizes were found for all memory tests. No significant differences were found between subtests. In conclusion, patients with schizophrenia experience significant verbal and visual memory impairments, which are not explained by task difficulty. Patients were unable to learn or retrieve more reliably despite repetition and cuing strategies, suggesting that memory impairment in the illness is not a function of task difficulty.

Memory and medial temporal lobe structures in patients with schizophrenia and their siblings

Episodic retrieval is characterized by the subjective experience of remembering. Semantic memory, on the other hand, is a more structured record of facts, meanings, concepts and knowledge about the external world that we have acquired. The medial temporal lobe (MTL), especially the hippocampus and parahippocampal cortex, plays a central role in both types of memory process. Published studies suggested that individuals with schizophrenia have deficits in episodic and semantic memory, as well as structural abnormalities of the medial temporal lobe. However, it is not clear whether reported correlations reflect the impact of the disease state or that of underlying genetic influences contributing to the risk. To understand better etiology and effects of psychosis on the global brain structure and cognitive processing, relatives of individuals with schizophrenia can be studied. The aim of our study was to examine the association between abnormalities of the MTL, psychopathology, and memory impairment in schizophrenia. Study sample (n = 60) consisted of first episode schizophrenia patients, their non-psychotic siblings and matching control subjects. We used high-resolution magnetic resonance imaging and probabilistic algorithms for image analysis. Episodic and semantic memory was measured with neuropsychological tests. Our results showed differences in memory performance between the groups. Neuropsychological data were correlated with MRI findings. The results may provide insight into etiology of schizophrenia and its effects on cognition and help to identify neuroanatomical and cognitive endophenotypes of psychotic disorders.Supported by the grant projects MH CR AZV 15-28998A, MEYS NPU4NUDZ: LO1611; Czech Science Foundation, grant No. 16-13093S; Institutional Support 00023001IKEM.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Prefrontal activity and impaired memory encoding strategies in schizophrenia

Schizophrenia patients have significant memory difficulties that have far-reaching implications in their daily life. These impairments are partly attributed to an inability to self-initiate effective memory encoding strategies, but its core neurobiological correlates remain unknown. The current study addresses this critical gap in our knowledge of episodic memory impairments in schizophrenia. Schizophrenia patients (n = 35) and healthy controls (n = 23) underwent a Semantic Encoding Memory Task (SEMT) during an fMRI scan. Brain activity was examined for conditions where participants were a) prompted to use semantic encoding strategies, or b) not prompted but required to self-initiate such strategies. When prompted to use semantic encoding strategies, schizophrenia patients exhibited similar recognition performance and brain activity as healthy controls. However, when required to self-initiate these strategies, patients had significant reduced recognition performance and brain activity in the left dorsolateral prefrontal cortex, as well as in the left temporal gyrus, left superior parietal lobule, and cerebellum. When patients were divided based on performance on the SEMT, the subgroup with more severe deficits in self-initiation also showed greater reduction in left dorsolateral prefrontal activity. These results suggest that impaired self-initiation of elaborative encoding strategies is a driving feature of memory deficits in schizophrenia. We also identified the neural correlates of impaired self-initiation of semantic encoding strategies, in which a failure to activate the left dorsolateral prefrontal cortex plays a key role. These findings provide important new targets in the development of novel treatments aiming to improve memory and ultimately patients' outcome.

Evidence for a differential contribution of early perceptual and late cognitive processes during encoding to episodic memory impairment in schizophrenia

Objectives: Schizophrenia is characterised by significant episodic memory impairment that is thought to be related to problems with encoding, however the neuro-functional mechanisms underlying these deficits are not well understood. The present study used a subsequent recognition memory paradigm and event-related potentials (ERPs) to investigate temporal aspects of episodic memory encoding deficits in schizophrenia. Methods: Electroencephalographic data was recorded in 24 patients and 19 healthy controls whilst participants categorised single words as pleasant/unpleasant. ERPs were generated to subsequently recognised versus unrecognised words on the basis of a forced-choice recognition memory task. Subsequent memory effects were examined with the late positive component (LPP). Group differences in N1, P2, N400 and LPP were examined for words correctly recognised.Results: Patients performed more poorly than controls on the recognition task. During encoding patients had significantly reduced N400 and LPP amplitudes than controls. LPP amplitude correlated with task performance however amplitudes did not differ between patients and controls as a function of subsequent memory. No significant differences in N1 or P2 amplitude or latency were observed.Conclusions: The present results indicate that early sensory processes are intact and dysfunctional higher order cognitive processes during encoding are contributing to episodic memory impairments in schizophrenia.

Memory deficit in patients with schizophrenia and posttraumatic stress disorder: relational vs item-specific memory.

It has been well established that patients with schizophrenia have impairments in cognitive functioning and also that patients who experienced traumatic events suffer from cognitive deficits. Of the cognitive deficits revealed in schizophrenia or posttraumatic stress disorder (PTSD) patients, the current article provides a brief review of deficit in episodic memory, which is highly predictive of patients’ quality of life and global functioning. In particular, we have focused on studies that compared relational and item-specific memory performance in schizophrenia and PTSD, because measures of relational and item-specific memory are considered the most promising constructs for immediate tangible development of clinical trial paradigm. The behavioral findings of schizophrenia are based on the tasks developed by the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative and the Cognitive Neuroscience Test Reliability and Clinical Applications for Schizophrenia (CNTRACS) Consortium. The findings we reviewed consistently showed that schizophrenia and PTSD are closely associated with more severe impairments in relational memory compared to item-specific memory. Candidate brain regions involved in relational memory impairment in schizophrenia and PTSD are also discussed.

Preliminary investigation of the effects of γ-tACS on working memory in schizophrenia.

Working memory impairment in schizophrenia has been strongly associated with abnormalities in gamma oscillations within the dorsolateral prefrontal cortex (DLFPC). We recently published the first ever study showing that anodal transcranial direct current stimulation (tDCS) to the left DLPFC was able to significantly improve working memory in schizophrenia and did so seemingly via restoring normal gamma oscillatory function. Transcranial alternating current stimulation (tACS) is a form of electrical brain stimulation that delivers stimulation at a specific frequency and has been shown to entrain endogenous cortical oscillations. Therefore, gamma (γ) tACS may be even more effective than tDCS in improving working memory in schizophrenia. In a randomized repeated-measures study we compared the effects of γ-tACS, tDCS and sham stimulation on the performance of the two back working memory tasks in ten patients with schizophrenia. There was a significant time by stimulation interaction, with tDCS and sham showing trend-level improvements in working memory, while γ-tACS, contrary to our hypothesis, showed no change. The results are discussed in light of posited divergent effects of tACS and tDCS on the pathophysiology of working memory impairment in schizophrenia.