Risk of conversion to mild cognitive impairment or dementia among subjects with amyloid and tau pathology: a systematic review and meta-analysis.

BACKGROUND: Measurement of beta-amyloid (Aß) and phosphorylated tau (p-tau) levels offers the potential for early detection of neurocognitive impairment. Still, the probability of developing a clinical syndrome in the presence of these protein changes (A+ and T+) remains unclear. By performing a systematic review and meta-analysis, we investigated the risk of mild cognitive impairment (MCI) or dementia in the non-demented population with A+ and A- alone and in combination with T+ and T- as confirmed by PET or cerebrospinal fluid examination. METHODS: A systematic search of prospective and retrospective studies investigating the association of Aß and p-tau with cognitive decline was performed in three databases (MEDLINE via PubMed, EMBASE, and CENTRAL) on January 9, 2024. The risk of bias was assessed using the Cochrane QUIPS tool. Odds ratios (OR) and Hazard Ratios (HR) were pooled using a random-effects model. The effect of neurodegeneration was not studied due to its non-specific nature. RESULTS: A total of 18,162 records were found, and at the end of the selection process, data from 36 cohorts were pooled (n= 7,793). Compared to the unexposed group, the odds ratio (OR) for conversion to dementia in A+ MCI patients was 5.18 [95% CI 3.93; 6.81]. In A+ CU subjects, the OR for conversion to MCI or dementia was 5.79 [95% CI 2.88; 11.64]. Cerebrospinal fluid Aß42 or Aß42/40 analysis and amyloid PET imaging showed consistent results. The OR for conversion in A+T+ MCI subjects (11.60 [95% CI 7.96; 16.91]) was significantly higher than in A+T- subjects (2.73 [95% CI 1.65; 4.52]). The OR for A-T+ MCI subjects was non-significant (1.47 [95% CI 0.55; 3.92]). CU subjects with A+T+ status had a significantly higher OR for conversion (13.46 [95% CI 3.69; 49.11]) than A+T- subjects (2.04 [95% CI 0.70; 5.97]). Meta-regression showed that the ORs for Aß exposure decreased with age in MCI. (beta = -0.04 [95% CI -0.03 to -0.083]). CONCLUSIONS: Identifying Aß-positive individuals, irrespective of the measurement technique employed (CSF or PET), enables the detection of the most at-risk population before disease onset, or at least at a mild stage. The inclusion of tau status in addition to Aß, especially in A+T+ cases, further refines the risk assessment. Notably, the higher odds ratio associated with Aß decreases with age. TRIAL REGISTRATION: The study was registered in PROSPERO (ID: CRD42021288100).

Theta-burst rTMS in schizophrenia to ameliorate negative and cognitive symptoms: study protocol for a double-blind, sham-controlled, randomized clinical trial.

BACKGROUND: Treatment effects of conventional approaches with antipsychotics or psychosocial interventions are limited when it comes to reducing negative and cognitive symptoms in schizophrenia. While there is emerging clinical evidence that new, augmented protocols based on theta-burst stimulation can increase rTMS efficacy dramatically in depression, data on similar augmented therapies are limited in schizophrenia. The different patterns of network impairments in subjects may underlie that some but not all patients responded to given stimulation locations. METHODS: Therefore, we propose an augmented theta-burst stimulation protocol in schizophrenia by stimulating both locations connected to negative symptoms: (1) the left dorsolateral prefrontal cortex (DLPFC), and (2) the vermis of the cerebellum. Ninety subjects with schizophrenia presenting negative symptoms and aging between 18 and 55 years will be randomized to active and sham stimulation in a 1:1 ratio. The TBS parameters we adopted follow the standard TBS protocols, with 3-pulse 50-Hz bursts given every 200 ms (at 5 Hz) and an intensity of 100% active motor threshold. We plan to deliver 1800 stimuli to the left DLPFC and 1800 stimuli to the vermis daily in two 9.5-min blocks for 4 weeks. The primary endpoint is the change in negative symptom severity measured by the Positive and Negative Syndrome Scale (PANSS). Secondary efficacy endpoints are changes in cognitive flexibility, executive functioning, short-term memory, social cognition, and facial emotion recognition. The difference between study groups will be analyzed by a linear mixed model analysis with the difference relative to baseline in efficacy variables as the dependent variable and treatment group, visit, and treatment-by-visit interaction as independent variables. The safety outcome is the number of serious adverse events. DISCUSSION: This is a double-blind, sham-controlled, randomized medical device study to assess the efficacy and safety of an augmented theta-burst rTMS treatment in schizophrenia. We hypothesize that social cognition and negative symptoms of patients on active therapy will improve significantly compared to patients on sham treatment. TRIAL REGISTRATION: The study protocol is registered at "ClinicalTrials.gov" with the following ID: NCT05100888. All items from the World Health Organization Trial Registration Data Set are registered. Initial release: 10/19/2021.

Low Functional network integrity in cognitively unimpaired and MCI subjects with depressive symptoms: results from a multi-center fMRI study.

Evidence suggests that depressive symptomatology is a consequence of network dysfunction rather than lesion pathology. We studied whole-brain functional connectivity using a Minimum Spanning Tree as a graph-theoretical approach. Furthermore, we examined functional connectivity in the Default Mode Network, the Frontolimbic Network (FLN), the Salience Network, and the Cognitive Control Network. All 183 elderly subjects underwent a comprehensive neuropsychological evaluation and a 3 Tesla brain MRI scan. To assess the potential presence of depressive symptoms, the 13-item version of the Beck Depression Inventory (BDI) or the Geriatric Depression Scale (GDS) was utilized. Participants were assigned into three groups based on their cognitive status: amnestic mild cognitive impairment (MCI), non-amnestic MCI, and healthy controls. Regarding affective symptoms, subjects were categorized into depressed and non-depressed groups. An increased mean eccentricity and network diameter were found in patients with depressive symptoms relative to non-depressed ones, and both measures showed correlations with depressive symptom severity. In patients with depressive symptoms, a functional hypoconnectivity was detected between the Anterior Cingulate Cortex (ACC) and the right amygdala in the FLN, which impairment correlated with depressive symptom severity. While no structural difference was found in subjects with depressive symptoms, the volume of the hippocampus and the thickness of the precuneus and the entorhinal cortex were decreased in subjects with MCI, especially in amnestic MCI. The increase in eccentricity and diameter indicates a more path-like functional network configuration that may lead to an impaired functional integration in depression, a possible cause of depressive symptomatology in the elderly.

Lifestyle and behavioural changes in older adults during the Covid-19 pandemic are associated with subjective cognitive complaints.

Subjective cognitive complaints (SCC) is a self-reported experience of persistently impaired cognitive functions which could be the earliest red flag of neurocognitive disorders. The COVID-19 pandemic and related restriction measures changed the lifestyle and behaviour of older adults. The aim of this study was to assess the relation of these changes and SCC status in Hungary. This cross-sectional study analysed the data of 359 elderly Hungarians who filled out the WW-FINGERS-SARS-CoV2 survey. A quarter of the respondents (n:88) reported SCC in connection with the pandemic. We compared sociodemographic features, health status, lifestyle, and social life parameters between subjects with reported SCC and without. To eliminate the potential interrelation across group differences, stepwise logistic regression was applied. Participants with SCC showed the following characteristics, compared to individuals without: (1) they were older; (2) they were more likely to be women; (3) they had a higher number of chronic disorders; (4) showed more prominent impairment in physical mobility; (5) had worse sleep quality; (6) spent less time with family; and (7) used internet more frequently during the pandemic (all p's < 0.001). Logistic regression highlighted that only two parameters were related to SCC status independently, the physical mobility (ability to walk 500 m without difficulties; OR = 1.186; p < 0.001; 95%CI = 1.101, 1.270) and changes in time spent with grandchildren (OR = 1.04; p = 0.015; 95%CI = 1.008, 1.073). Our study draws attention to the importance of physical mobility and quality time with family as key factors in the cognitive well-being of elderly people.

Domain-specific cognitive impairment in multiple sclerosis: A systematic review and meta-analysis.

OBJECTIVE: Methods of cognitive measurements in multiple sclerosis (MS) are not standardized. We aimed to identify the prevalence of cognitive domain-specific impairment (DSI) in MS by using subtests of the Brief Repeatable Battery of Neuropsychological Tests (BRB-N) with analyzing different cutoff values. METHODS: The systematic review and meta-analysis were registered on PROSPERO (ID: CRD42021287004). The systematic literature search was performed via PubMed, Embase, and CENTRAL on 24 October 2021. Inclusion criteria were adults of different MS subtypes (CIS, RRMS, PPMS, and SPMS) with the condition of distinct DSI measured by BRB-N. Pediatric MS, computerized versions of BRB-N, and patients receiving steroids were excluded. Primary outcome was pooled prevalence rates of impaired patients within each cutoff and MS subtype, with 95% confidence interval, I-squared statistics for heterogeneity, and chi-squared test for subgroup differences. Risk of bias was assessed using the "JBI Quality Assessment Tool for Prevalence Studies." RESULTS: In 48 eligible observational studies (n = 3431 patients), the three most prevalent thresholds were the 2.0 SD and 1.5 SD below the mean of normative values, and the score below the fifth percentile of the normative values. A progressively increasing worsening of the overall DSI was observed from CIS, moving toward RRMS, PPMS, and SPMS. INTERPRETATION: Cognitive impairment is observed in all MS phenotypes, with varying degrees. Due to several potential influencing factors, our comprehensive literature review has not revealed consistent findings, and we, therefore, recommend considering a more sophisticated, "individual referencing" approach, acknowledging the diverse clinical and sociodemographic characteristics among populations and disparities in cognitive testing.

A comparison of visual and acoustic mismatch negativity as potential biomarkers in schizophrenia.

Mismatch negativity (MMN) is an event-related potential (ERP) component generated when an unexpected deviant stimulus occurs in a pattern of standard stimuli. Several studies showed that the MMN response to both auditory and visual stimuli is attenuated in schizophrenia. While previous studies investigated auditory and visual MMN in different cohorts, here we examined the potential clinical utility of MMN responses to auditory and visual stimuli within the same group of patients. Altogether 39 patients with schizophrenia and 39 healthy controls matched in age, gender, and education were enrolled. We recorded EEG using 64 channels in eight experimental blocks where we presented auditory and visual stimulus sequences. Mismatch responses were obtained by subtracting responses to standard from the physically identical deviant stimuli. We found a significant MMN response to the acoustic stimuli in the control group, whereas no significant mismatch response was observed in the patient group. The group difference was significant for the acoustic stimuli. The 12 vane windmill pattern evoked a significant MMN response in the early time window in the control group but not in the patient group. The 6 vane windmill pattern evoked MMN only in the patient group. However, we found no significant difference between the groups. Furthermore, we found no correlation between the clinical variables and the MMN amplitudes. Our results suggest that predictive processes underlying mismatch generation in patients with schizophrenia may be more affected in the acoustic compared to the visual domain. Acoustic MMN tends to be a more promising biomarker in schizophrenia.

Comparison of the diagnostic accuracy of resting-state fMRI driven machine learning algorithms in the detection of mild cognitive impairment.

Mild cognitive impairment (MCI) is a potential therapeutic window in the prevention of dementia; however, automated detection of early cognitive deterioration is an unresolved issue. The aim of our study was to compare various classification approaches to differentiate MCI patients from healthy controls, based on rs-fMRI data, using machine learning (ML) algorithms. Own dataset (from two centers) and ADNI database were used during the analysis. Three fMRI parameters were applied in five feature selection algorithms: local correlation, intrinsic connectivity, and fractional amplitude of low frequency fluctuations. Support vector machine (SVM) and random forest (RF) methods were applied for classification. We achieved a relatively wide range of 78-87% accuracy for the various feature selection methods with SVM combining the three rs-fMRI parameters. In the ADNI datasets case we can also see even 90% accuracy scores. RF provided a more harmonized result among the feature selection algorithms in both datasets with 80-84% accuracy for our local and 74-82% for the ADNI database. Despite some lower performance metrics of some algorithms, most of the results were positive and could be seen in two unrelated datasets which increase the validity of our methods. Our results highlight the potential of ML-based fMRI applications for automated diagnostic techniques to recognize MCI patients.

Plasma Exchange versus Intravenous Immunoglobulin in Worsening Myasthenia Gravis: A Systematic Review and Meta-Analysis with Special Attention to Faster Relapse Control.

Currently used rescue interventions to prevent rapid myasthenic deterioration are plasma exchange (PLEX) and intravenous immunoglobulin (IVIG). We investigated the evidence to determine whether the two methods were interchangeable or whether one was superior to the other. This review was registered on PROSPERO (CRD42021285985). Only randomized controlled trials (RCTs) comparing the efficacy and safety of PLEX and IVIG in patients with moderate-to-severe myasthenia gravis (MG) were included. Five major databases were systematically searched (PubMed, CENTRAL, Embase, Scopus, and Web of Science). Odds ratios (OR) with 95% confidence intervals (CI) were calculated for adverse events and mean differences (MD) for changes in quantitative myasthenia gravis scores (QMG). Three RCTs met the inclusion criteria. Two investigating 114 patients in total were eligible for meta-analysis to analyze efficacy and safety. For the change in QMG score, the MD was -2.8 (95% CI: -5.614-0.113), with PLEX performing better. For adverse events, an OR of 1.04 was found (95% CI: 0.25-4.27). This study demonstrated a low risk of bias in evaluating treatment efficacy but indicated a high risk of bias in assessing procedural safety outcomes. Although the results did not show any significant difference, there was a tendency indicating faster efficacy of PLEX in the first two weeks of treatment. In such a critical clinical condition, this tendency may be clinically meaningful, but further studies should clarify this benefit.

Hemoadsorption as Adjuvant Therapy in Acute Respiratory Distress Syndrome (ARDS): A Systematic Review and Meta-Analysis.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is often a consequence of a dysregulated immune response; therefore, immunomodulation by extracorporeal cytokine removal has been increasingly used as an adjuvant therapy, but convincing data are still missing. The aim of this study was to investigate the effects of adjunctive hemoadsorption (HA) on clinical and laboratory outcomes in patients with ARDS. METHODS: We performed a systematic literature search in PubMed, Embase, CENTRAL, Scopus, and Web of Science (PROSPERO: CRD42022292176). The population was patients receiving HA therapy for ARDS. The primary outcome was the change in PaO2/FiO2 before and after HA therapy. Secondary outcomes included the before and after values for C-reactive protein (CRP), lactate, interleukin-6 (IL-6), and norepinephrine (NE) doses. RESULTS: We included 26 publications, with 243 patients (198 undergoing HA therapy and 45 controls). There was a significant improvement in PaO2/FiO2 ratio following HA therapy (MD = 68.93 [95%-CI: 28.79 to 109.06] mmHg, p = 0.005) and a reduction in CRP levels (MD = -45.02 [95%-CI: -82.64; -7.39] mg/dL, p = 0.026) and NE dose (MD = -0.24 [95%-CI: -0.44 to -0.04] µg/kg/min, p = 0.028). CONCLUSIONS: Based on our findings, HA resulted in a significant improvement in oxygenation and a reduction in NE dose and CRP levels in patients treated with ARDS. Properly designed RCTs are still needed.

CYP1A2 expression rather than genotype is associated with olanzapine concentration in psychiatric patients.

Olanzapine is a commonly prescribed atypical antipsychotic agent for treatment of patients with schizophrenia and bipolar disorders. Previous in vitro studies using human liver microsomes identified CYP1A2 and CYP2D6 enzymes being responsible for CYP-mediated metabolism of olanzapine. The present work focused on the impact of CYP1A2 and CYP2D6 genetic polymorphisms as well as of CYP1A2 metabolizing capacity influenced by non-genetic factors (sex, age, smoking) on olanzapine blood concentration in patients with psychiatric disorders (N = 139). CYP2D6 genotype-based phenotype appeared to have negligible contribution to olanzapine metabolism, whereas a dominant role of CYP1A2 in olanzapine exposure was confirmed. However, CYP1A2 expression rather than CYP1A2 genetic variability was demonstrated to be associated with olanzapine concentration in patients. Significant contribution of - 163C > A (rs762551), the most common SNP (single nucleotide polymorphism) in CYP1A2 gene, to enhanced inducibility was confirmed by an increase in CYP1A2 mRNA expression in smokers carrying - 163A, and smoking was found to have appreciable impact on olanzapine concentration normalized by the dose/bodyweight. Furthermore, patients' olanzapine exposure was in strong association with CYP1A2 expression; therefore, assaying CYP1A2 mRNA level in leukocytes can be an appropriate tool for the estimation of patients' olanzapine metabolizing capacity and may be relevant in optimizing olanzapine dosage.

[Care of dementia in the general practice]. / A dementia ellátása a háziorvosi gyakorlatban.

Treating and caring for people with dementia is a complex task, which can be achieved through cooperation between primary and specialist healthcare, social care and specialist care services. General practitioners are key players in the prevention, screening, treatment and care of dementia. Our aim was to present the general practitioner's aspects of modern dementia care through different levels of prevention. Educating patients to lead a healthy lifestyle and optimising their cardiovascular status reduces the risk of developing dementia. Emphasis was placed on early screening and referral to a specialist, and the importance of timely, individualised therapy for modern care. General practitioner's care of patients with dementia includes monitoring the progression of the disease as well as co-morbidities so that the quality of life of both the patients and their family can be improved by reducing complications. Family doctors also have an important role to support family members who care for the patient. In addition to presenting the current possibilities in Hungary, we reviewed the international literature and national guidelines, which must be followed continuously to ensure quality patient care. Orv Hetil. 2023; 164(32): 1263-1270.

Stronger coupling of emotional instability with reward processing in borderline personality disorder is predicted by schema modes.

BACKGROUND: Mood instability and risk-taking are hallmarks of borderline personality disorder (BPD). Schema modes are combinations of self-reflective evaluations, negative emotional states, and destructive coping strategies common in BPD. When activated, they can push patients with BPD into emotional turmoil and a dissociative state of mind. Our knowledge of the underlying neurocognitive mechanisms driving these changes is incomplete. We hypothesized that in patients with BPD, affective instability is more influenced by reward expectation, outcomes, and reward prediction errors (RPEs) during risky decision-making than in healthy controls. Additionally, we expected that these alterations would be related to schema modes. METHODS: Thirty-two patients with BPD and thirty-one healthy controls were recruited. We used an established behavioral paradigm to measure mood fluctuations during risky decision-making. The impact of expectations and RPEs on momentary mood was quantified by a computational model, and its parameters were estimated with hierarchical Bayesian analysis. Model parameters were compared using High-Density Intervals. RESULTS: We found that model parameters capturing the influence of RPE and Certain Rewards on mood were significantly higher in patients with BPD than in controls. These model parameters correlated significantly with schema modes, but not with depression severity. CONCLUSIONS: BPD is coupled with altered associations between mood fluctuation and reward processing under uncertainty. Our findings seem to be BPD-specific, as they stand in contrast with the correlates of depressive symptoms. Future studies should establish the clinical utility of these alterations, such as predicting or assessing therapeutic response in BPD.

The complexity of theory of mind deficit in schizophrenia: A cross-sectional analysis of baseline data from a longitudinal schizophrenia study.

A large number of trials have supported the functional significance of Theory of Mind (ToM) impairment in schizophrenia. However, the nature and the extent of the impairment are still unclear. Reviews on the topic suggest that, in many cases, studies use only one tool to assess the levels of difficulty in the field, limiting the validity of the measurement to one aspect of ToM. On the other hand, the divergence of the used assessment tools makes it hard to compare the result of these studies. Thus, we decided to use additional assessment tools to evaluate the extent of ToM in order to describe several aspects of the phenomenon. A hierarchical cluster analysis of variables was used on a sample of 68 participants with schizophrenia or schizoaffective disorder, to determine the similarity between variances of the assessed ToM subcomponents. Further cross-sectional correlational analysis was then performed to investigate the association between the identified clusters and other used measures (e.g.: neurocognition). The statistical analysis supported a five-cluster model. Identified clusters illustrate the difference between Hypo and HyperToM as well as the degree of ToM task complexity, allowing for a more accurate description of the nature of ToM deficit in schizophrenia.

Differentiation of patients with mild cognitive impairment and healthy controls based on computer assisted hand movement analysis: a proof-of-concept study.

Mild cognitive impairment (MCI) is the prodromal phase of dementia, and it is highly underdiagnosed in the community. We aimed to develop an automated, rapid (< 5 min), electronic screening tool for the recognition of MCI based on hand movement analysis. Sixty-eight individuals participated in our study, 46 healthy controls and 22 patients with clinically defined MCI. All participants underwent a detailed medical assessment including neuropsychology and brain MRI. Significant differences were found between controls and MCI groups in mouse movement characteristics. Patients showed higher level of entropy for both the left (F = 5.24; p = 0.001) and the right hand (F = 8.46; p < 0.001). Longer time was required in MCI to perform the fine motor task (p < 0.005). Furthermore, we also found significant correlations between mouse movement parameters and neuropsychological test scores. Correlation was the strongest between motor parameters and Clinical Dementia Rating scale (CDR) score (average r: - 0.36, all p's < 0.001). Importantly, motor parameters were not influenced by age, gender, or anxiety effect (all p's > 0.05). Our study draws attention to the utility of hand movement analysis, especially to the estimation of entropy in the early recognition of MCI. It also suggests that our system might provide a promising tool for the cognitive screening of large populations.

Virtual reality-based theory of mind intervention in schizophrenia: Preliminary efficacy results.

BACKGROUND: In recent years, a growing body of literature has supported the core nature and functional significance of Theory of Mind (ToM) deficit in schizophrenia. These findings have made ToM impairment a promising treatment target. However, despite the encouraging results, its complexity makes it difficult to develop new interventions and even to understand the exact nature and scope of the deficit. Yet, further investigation has suggested that using modern technology and multilevel assessment may help solve the problem. METHODS: Virtual Reality-based Theory of Mind Intervention (VR-ToMIS) is a recently developed structured method using the combination of cognitive and behavioral therapeutic techniques and the advantages of Virtual Reality (VR) technology. A controlled study with a three-month follow-up was conducted with 42 patients (suffering from schizophrenia or schizo-affective disorder) randomly assigned to either an experimental (VR-ToMIS) or control group (passive-VR). Repeated two-way factorial analysis of covariance was used to evaluate the effects of VR-ToMIS on symptoms, neuro- and social cognition, pragmatic skills, and quality of life when the effect of IQ was controlled. RESULTS: Patients participating in VR-ToMIS showed significant improvements in all types of ToM tasks (except for hyper-ToM task, based on the results of Cartoon test, Faux pas test and and Baron-Cohen Minds in the Eyes Test) compared to the control group with moderate to large effect sizes. In the case of negative and cognitive symptoms, significant between-group differences were also supported. Improvement was moderated by IQ in the case of higher-order ToM, manner, and relevance implicatures. Results were proved to be sustainable three months after the treatment. CONCLUSION: Although the presented results are considered preliminary, they support the potential of the integration of modern technology and traditional methods for future interventions.

Impact of the third wave of the COVID-19 pandemic on the lifestyle, mental and physical health of the Hungarian population over 60 / A COVID-19-pandémia harmadik hullámának hatása a 60 év feletti magyar lakosság életmódjára, mentális és fizikai egészségére

Introduction: Elderly population is the most vulnerable group of the COVID-19 pandemic, since they often live with chronic diseases. Objective: The goal of our research is to analyze the direct and indirect effects of the pandemic on the Hungarian population over 60 years of age. Method: We collected data using the authentic Hungarian translation of the,World-Wide FINGERS SARS-CoV-2 Survey between 1st of February and 1st of June 2021. Results: Our study included 431 people with a low rate of COVID infection (6%). The most marked changes were the increase in the use of digital services in 71%, increased feeling of loneliness in 46%, decrease in subjective sleep quality in 47%, and reduced contact with friends and relatives in 80% of the respondents. Eight-six percent of participants had at least one chronic illness and 23% missed an illness-related medical visit during the pandemic. In 45%, the subjective quality of life deteriorated and 25% reported impairment of memory functions. Discussion: Participants became socially isolated during the pandemic having a significant negative impact on their way of life. The changes in physical and mental health are likely to be reflected in an increased incidence and accelerated progression of age-related diseases in the elderly. Conclusion: In order to reduce the direct and indirect harmful effects of the COVID-19 pandemic, it is of paramount importance to know how the pandemic and the following restrictions affect the behavior and lifestyle of the elderly as well as the care of patients living with chronic diseases.

Alteration of Visuospatial System as an Early Marker of Cognitive Decline: A Double-Center Neuroimaging Study.

Amnestic-type mild cognitive impairment (a-MCI) represents the prodromal phase of Alzheimer's disease associated with a high conversion rate to dementia and serves as a potential golden period for interventions. In our study, we analyzed the role of visuospatial (VS) functions and networks in the recognition of a-MCI. We examined 78 participants (32 patients and 46 controls) in a double-center arrangement using neuropsychology, structural, and resting-state functional MRI. We found that imaging of the lateral temporal areas showed strong discriminating power since in patients only the temporal pole (F = 5.26, p = 0.034) and superior temporal gyrus (F = 8.04, p < 0.001) showed reduced cortical thickness. We demonstrated significant differences between controls and patients in various neuropsychological results; however, analysis of cognitive subdomains revealed that the largest difference was presented in VS skills (F = 8.32, p < 0.001). Functional connectivity analysis of VS network showed that patients had weaker connectivity between the left and right frontotemporal areas, while stronger local connectivity was presented between the left frontotemporal structures (FWE corrected p < 0.05). Our results highlight the remarkable potential of examining the VS system in the early detection of cognitive decline. Since resting-state setting of functional MRI simplifies the possible automatization of data analysis, detection of VS system alterations might provide a non-invasive biomarker of a-MCI.

Prolongation of cortical sleep spindles during hippocampal interictal epileptiform discharges in epilepsy patients.

OBJECTIVE: Memory deficits are frequent among patients with epilepsies affecting the temporal lobe. Hippocampal interictal epileptic discharges (hIEDs), the presumed epileptic exaggeration of sharp wave-ripples (SWRs), are known to contribute to memory dysfunction, but the potential underlying mechanism is unknown. The precise temporal coordination between hippocampal SWRs and corticothalamic spindles during sleep is critical for memory consolidation. Moreover, previous investigation indicated that hIEDs induce neocortical spindlelike oscillation. In the present study, we aimed to assess the influence of hIEDs on neocortical spindles. METHODS: We analyzed the spindle characteristics (duration, amplitude, frequency) of 21 epilepsy patients implanted with foramen ovale (FO) electrodes during a whole night sleep. Scalp sleep spindles were categorized based on their temporal relationship to hIEDs detected on the FO electrodes. Three groups were created: (1) spindles coinciding with hIEDs, (2) spindles "induced" by hIEDs, and (3) spindles without hIED co-occurrence. RESULTS: We found that spindles co-occurring with hIEDs had altered characteristics in all measured properties, lasted longer by 126 ± 48 ms (mean ± SD), and had higher amplitude by 3.4 ± 3.2 µV, and their frequency range shifted toward the higher frequencies within the 13-15-Hz range. Also, hIED-induced spindles had identical oscillatory properties to spindles without any temporal relationships with hIEDs. In more than half of our subjects, clear temporal coherence was revealed between hIEDs and spindles, but the direction of the coupling was patient-specific. SIGNIFICANCE: We investigated the effect of hippocampal IEDs on neocortical spindle activity and found spindle alterations in cases of spindle-hIED co-occurrence, but not in cases of hIED-initiated spindles. We propose that this is a marker of a pathologic process, where IEDs may have direct effect on spindle generation. It could mark a potential mechanism whereby IEDs disrupt memory processes, and also provide a potential therapeutic target to treat memory disturbances in epilepsy.

[What makes someone a troll? The psychology of trolling: Systematic literature review].

BACKGROUND: The World Wide Web along with online social media has significantly changed the dynamics of communication. Information is easier and faster to access, but at the same time the relevance of the content often remains questionable, often confronting users with half-truths and untruths. Information consumption patterns have also changed a lot, allowing more room for the emergence of deviant, provocative behaviors through anonymity. The latter form of behavior can have different effects depending on its intensity and content, including, the polarization of opinions or the negative influence on users 'psychological wellbeing'. In our current article the literature on the pheno menon known as trolling in Internet slang was reviewed in order to better understand its nature and its possible effects. METHOD: Our systematic literature review was based on a computer search of the PubMed and ScienceDirect databases framed by the PRISMA guideline. The following keywords were used: "Internet" OR "Facebook" OR "Twitter" OR "Instagram" AND "troll" OR "trolling". RESULT: Based on the mentioned methon, a total number of 4575 articles were identified. Based on the inclusion and exclusion criteria 24 articles were included in the final sample. The results and experiences of the published papers were presented according to the subgroups formed on the basis of the purpose of the studies. CONCLUSION: Included articles focused primarily on understanding the motivation of trolling behavior and their impact on online behavior. However, the possible impact of trolls on individuals was left out of focus, leaving many open questions behind.

Distractor filtering and its electrophysiological correlates in schizophrenia.

OBJECTIVE: Patients with schizophrenia are characterized by compromised working memory (WM) performance and increased distractibility. Theta synchronization (especially over the frontal midline areas) is related to cognitive control and executive processes during WM encoding and retention. Alpha event-related desynchronization (ERD) is associated with information processing and attention. METHODS: Participants (35 patients and 39 matched controls) performed a modified Sternberg WM task, containing salient and non-salient distractor items in the retention period. A high-density 128 channel EEG was recorded during the task. Theta (4-7 Hz) and fast alpha (10-13 Hz) event-related spectral perturbation (ERSP) were analyzed during the retention and encoding period. RESULTS: Patients with schizophrenia showed worse WM performance and increased attentional distractibility in terms of lower hit rates and increased distractor-related commission errors compared to healthy controls. Theta synchronization was modulated by condition (learning vs. distractor) in both groups but it was modulated by salience only in controls. Furthermore, salience of distractors modulated less the fast alpha ERD in patients. CONCLUSIONS: Our results suggest that patients with schizophrenia process salient and non-salient distracting information less efficiently and show weaker cognitive control compared to controls. SIGNIFICANCE: These differences may partly account for diminished WM performance and increased distractibility in schizophrenia.