The importance of chest CT severity score and lung CT patterns in risk assessment in COVID-19-associated pneumonia: a comparative study.

Introduction: Chest computed tomography (CT) is suitable to assess morphological changes in the lungs. Chest CT scoring systems (CCTS) have been developed and use in order to quantify the severity of pulmonary involvement in COVID-19. CCTS has also been correlated with clinical outcomes. Here we wished to use a validated, relatively simple CTSS to assess chest CT patterns and to correlate CTSS with clinical outcomes in COVID-19. Patients and methods: Altogether 227 COVID-19 cases underwent chest CT scanning using a 128 multi-detector CT scanner (SOMATOM Go Top, Siemens Healthineers, Germany). Specific pathological features, such as ground-glass opacity (GGO), crazy-paving pattern, consolidation, fibrosis, subpleural lines, pleural effusion, lymphadenopathy and pulmonary embolism were evaluated. CTSS developed by Pan et al. (CTSS-Pan) was applied. CTSS and specific pathologies were correlated with demographic, clinical and laboratory data, A-DROP scores, as well as outcome measures. We compared CTSS-Pan to two other CT scoring systems. Results: The mean CTSS-Pan in the 227 COVID-19 patients was 14.6 ± 6.7. The need for ICU admission (p < 0.001) and death (p < 0.001) were significantly associated with higher CTSS. With respect to chest CT patterns, crazy-paving pattern was significantly associated with ICU admission. Subpleural lines exerted significant inverse associations with ICU admission and ventilation. Lymphadenopathy was associated with all three outcome parameters. Pulmonary embolism led to ICU admission. In the ROC analysis, CTSS>18.5 significantly predicted admission to ICU (p = 0.026) and CTSS>19.5 was the cutoff for increased mortality (p < 0.001). CTSS-Pan and the two other CTSS systems exerted similar performance. With respect to clinical outcomes, CTSS-Pan might have the best performance. Conclusion: CTSS may be suitable to assess severity and prognosis of COVID-19-associated pneumonia. CTSS and specific chest CT patterns may predict the need for ventilation, as well as mortality in COVID-19. This can help the physician to guide treatment strategies in COVID-19, as well as other pulmonary infections.

The Alterations of Serum N-glycome in Response to SARS-CoV-2 Vaccination.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused a global concern since its outbreak in 2019, with one of the main solutions being vaccination. Altered glycosylation has been described in patients after SARS-CoV-2 infection, while the effect of vaccination on serum glycoproteins remained unexplored. In this study, total serum glycosylation was analyzed in patients after SARS-CoV-2 infection and/or mRNA vaccination in order to identify potential glycosylation-based alterations. Enzyme-linked immunosorbent assay was applied to identify post-COVID-19 and post-Vaccinated patients and rule out potential outliers. Serum samples were deglycosylated by PNGase F digestion, and the released glycans were fluorescently derivatized using procainamide labeling. Solid-phase extraction was used to purify the labeled glycans followed by the analysis of hydrophilic-interaction liquid chromatography with fluorescence and mass-spectrometric detection. Alterations of serum N-glycome in response to SARS-CoV-2 infection and mRNA vaccination were revealed by linear discriminant analysis.

Tocilizumab in Combination with Corticosteroids in COVID-19 Pneumonia: A Single-Centre Retrospective Controlled Study.

Introduction: Interleukin 6 receptor inhibition by tocilizumab (TCZ) has been effectively used worldwide for the treatment of multisystem inflammatory syndrome (MIS) associated with COVID-19. In this single centre study, we compared the outcome of COVID-19 pneumonia in TCZ-treated vs. untreated (control) patients. We wished to compare TCZ administration in the general ward vs. in the intensive care unit (ICU). We also studied the role of a consulting rheumatologist in the management of severe COVID-19 pneumonia. Patients and methods: In our patients, COVID-19 pneumonia was confirmed by SARS-CoV-2 PCR, chest X-ray, and CT. We compared patients selected for TCZ treatment with TCZ-untreated age- and sex-matched controls. All patients received corticosteroids. In the TCZ-treated group, patients received one or two doses of TCZ 8 mg/kg IV in combination with corticosteroids. We recorded age, sex, symptom duration, oxygen saturation (SaO2), partial arterial oxygen pressure (PaO2), total white blood cell (WBC), absolute neutrophil, absolute lymphocyte and platelet counts, CRP, ferritin, IL-6, LDH, procalcitonin (PCT), and D-dimer. The primary outcome parameters were the need for ICU, ventilation, death, and time of hospitalisation. Results: Altogether, 104 patients, 52 TCZ-treated and 52 TCZ-untreated, were included in this study. At baseline, the TCZ-treated patient group indeed had more pronounced COVID-19-related MIS compared to controls. Consultation with a rheumatologist was performed in 60% vs. 40% of cases. Nineteen patients (37%) received one, while 33 (63%) received two TCZ doses. TCZ was administered to 28 patients (54%) in the general ward and to 24 (46%) in the ICU. TCZ treatment was found to be safe in our COVID-19 pneumonia patients. TCZ treatment favourably influenced MIS biomarkers, and was associated with better clinical outcomes compared to controls. Patients receiving TCZ treatment in combination with corticosteroids already in the general ward exerted much better outcomes than those treated in the ICU. Consultation with a rheumatologist also improved outcome. Conclusions: We successfully used TCZ in combination with corticosteroids in Hungarian COVID-19 pneumonia patients. We pointed out the importance of early treatment already in the general ward, and the involvement of a rheumatologist in making treatment decisions.

Deterministic and probabilistic regularities underlying risky choices are acquired in a changing decision context.

Predictions supporting risky decisions could become unreliable when outcome probabilities temporarily change, making adaptation more challenging. Therefore, this study investigated whether sensitivity to the temporal structure in outcome probabilities can develop and remain persistent in a changing decision environment. In a variant of the Balloon Analogue Risk Task with 90 balloons, outcomes (rewards or balloon bursts) were predictable in the task's first and final 30 balloons and unpredictable in the middle 30 balloons. The temporal regularity underlying the predictable outcomes differed across three experimental conditions. In the deterministic condition, a repeating three-element sequence dictated the maximum number of pumps before a balloon burst. In the probabilistic condition, a single probabilistic regularity ensured that burst probability increased as a function of pumps. In the hybrid condition, a repeating sequence of three different probabilistic regularities increased burst probabilities. In every condition, the regularity was absent in the middle 30 balloons. Participants were not informed about the presence or absence of the regularity. Sensitivity to both the deterministic and hybrid regularities emerged and influenced risk taking. Unpredictable outcomes of the middle phase did not deteriorate this sensitivity. In conclusion, humans can adapt their risky choices in a changing decision environment by exploiting the statistical structure that controls how the environment changes.

Severity and prognostic factors of SARS-CoV-2-induced pneumonia: The value of clinical and laboratory biomarkers and the A-DROP score.

Introduction: Numerous clinical and laboratory scores that include C-reactive protein (CRP), D-dimer, ferritin, lactate dehydrogenase (LDH), interleukin 6 (IL-6), procalcitonin (PCT), blood urea nitrogen (BUN), creatinine levels and oxygenation (PaO2 and SaO2) have been used for the prognosis of COVID-19. In addition, composite scores have been developed for the assessment of general state and risk in community-acquired pneumonia (CAP) that may be applied for COVID-19 as well. In this study, we assessed severity and potential prognostic risk factors for unfavorable outcome among hospitalized COVID-19 patients. We also applied the A-DROP general scoring system used in CAP to COVID-19. Patients and methods: Altogether 233 patients admitted to our center with COVID-19 were included in the study. Clinical status, several laboratory biomarkers described above, indicators of oxygenation were determined at hospital admission. We also applied the A-DROP composite scoring system that includes Age (≥ 70 years in males and ≥ 75 years in females), Dehydration (BUN ≥ 7.5 mmol/l), Respiratory failure (SaO2 ≤ 90% or PaO2 ≤ 60 mmHg), Orientation disturbance (confusion) and low blood Pressure (systolic BP ≤ 90 mmHg) to COVID-19. Results: At the time of admission, most patients had elevated CRP, LDH, ferritin, D-dimer, and IL-6 levels indicating multisystemic inflammatory syndrome (MIS). Altogether 49 patients (21.2%) required admission to ICU, 46 (19.7%) needed ventilation and 40 patients (17.2%) died. In the binary analysis, admission to ICU, the need for ventilation and death were all significantly associated with the duration of hospitalization, history of hypertension or obesity, confusion/dizziness, as well as higher absolute leukocyte and neutrophil and lower lymphocyte counts, elevated CRP, PCT, LDH, ferritin, IL-6, BUN, and creatinine levels, low PaO2 and SaO2 and higher A-DROP score at the time of admission (p < 0.05). Conclusion: Numerous laboratory biomarkers in addition to obesity, dizziness at the time of admission and the history of hypertension may predict the need for ICU admission and ventilation, as well as mortality in COVID-19. Moreover, A-DROP may be a suitable scoring system for the assessment of general health and disease outcome in COVID-19.

Introduction of a Capillary Gel Electrophoresis-Based Workflow for Biotherapeutics Characterization: Size, Charge, and N-Glycosylation Variant Analysis of Bamlanivimab, an Anti-SARS-CoV-2 Product.

Coronavirus Disease 2019 (COVID-19) is a major public health problem worldwide with 5-10% hospitalization and 2-3% global mortality rates at the time of this publication. The disease is caused by a betacoronavirus called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The receptor-binding domain (RBD) of the Spike protein expressed on the surface of the virus plays a key role in the viral entry into the host cell via the angiotensin-converting enzyme 2 receptor. Neutralizing monoclonal antibodies having the RBD as a target have the ability to inhibit angiotensin-converting enzyme 2 (ACE2) receptor binding, therefore, prevent SARS-CoV-2 infection, represent a promising pharmacological strategy. Bamlanivimab is the first anti-spike neutralizing monoclonal antibody, which got an emergency use authorization from the FDA for COVID-19 treatment. Albeit, bamlanivimab is primarily a neutralizing mAb, some of its effector function related activity was also emphasized. The effector function of antibody therapeutics is greatly affected by their N-linked carbohydrates at the conserved Fc region, possibly influenced by the manufacturing process. Various capillary gel electrophoresis methods are widely accepted in the biopharmaceutical industry for the characterization of therapeutic antibodies. In this paper we introduce a capillary gel electrophoresis based workflow for 1) size heterogeneity analysis to determine the presence/absence of the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE); 2) capillary gel isoelectric focusing for possible N-glycosylation mediated charge heterogeneity determination, e.g., for excess sialylation and finally, 3) capillary gel electrophoresis for N-glycosylation profiling and sequencing. Our results have shown the presence of negligible amount of non-glycosylated heavy chain (NGHC) while 25% acidic charge variants were detected. Comprehensive N-glycosylation characterization revealed the occurrence of approximately 8.2% core-afucosylated complex and 17% galactosylated N-linked oligosaccharides, suggesting the possible existence of antibody dependent cell mediated cytotoxicity (ADCC) effector function in addition to the generally considered neutralizing effect of this particular therapeutic antibody molecule.

Adaptation to recent outcomes attenuates the lasting effect of initial experience on risky decisions.

Both primarily and recently encountered information have been shown to influence experience-based risky decision making. The primacy effect predicts that initial experience will influence later choices even if outcome probabilities change and reward is ultimately more or less sparse than primarily experienced. However, it has not been investigated whether extended initial experience would induce a more profound primacy effect upon risky choices than brief experience. Therefore, the present study tested in two experiments whether young adults adjusted their risk-taking behavior in the Balloon Analogue Risk Task after an unsignaled and unexpected change point. The change point separated early "good luck" or "bad luck" trials from subsequent ones. While mostly positive (more reward) or mostly negative (no reward) events characterized the early trials, subsequent trials were unbiased. In Experiment 1, the change point occurred after one-sixth or one-third of the trials (brief vs. extended experience) without intermittence, whereas in Experiment 2, it occurred between separate task phases. In Experiment 1, if negative events characterized the early trials, after the change point, risk-taking behavior increased as compared with the early trials. Conversely, if positive events characterized the early trials, risk-taking behavior decreased after the change point. Although the adjustment of risk-taking behavior occurred due to integrating recent experiences, the impact of initial experience was simultaneously observed. The length of initial experience did not reliably influence the adjustment of behavior. In Experiment 2, participants became more prone to take risks as the task progressed, indicating that the impact of initial experience could be overcome. Altogether, we suggest that initial beliefs about outcome probabilities can be updated by recent experiences to adapt to the continuously changing decision environment.

Neurophysiological and functional neuroanatomical coding of statistical and deterministic rule information during sequence learning.

Humans are capable of acquiring multiple types of information presented in the same information stream. It has been suggested that at least two parallel learning processes are important during learning of sequential patterns-statistical learning and rule-based learning. Yet, the neurophysiological underpinnings of these parallel learning processes are not fully understood. To differentiate between the simultaneous mechanisms at the single trial level, we apply a temporal EEG signal decomposition approach together with sLORETA source localization method to delineate whether distinct statistical and rule-based learning codes can be distinguished in EEG data and can be related to distinct functional neuroanatomical structures. We demonstrate that concomitant but distinct aspects of information coded in the N2 time window play a role in these mechanisms: mismatch detection and response control underlie statistical learning and rule-based learning, respectively, albeit with different levels of time-sensitivity. Moreover, the effects of the two learning mechanisms in the different temporally decomposed clusters of neural activity also differed from each other in neural sources. Importantly, the right inferior frontal cortex (BA44) was specifically implicated in visuomotor statistical learning, confirming its role in the acquisition of transitional probabilities. In contrast, visuomotor rule-based learning was associated with the prefrontal gyrus (BA6). The results show how simultaneous learning mechanisms operate at the neurophysiological level and are orchestrated by distinct prefrontal cortical areas. The current findings deepen our understanding on the mechanisms of how humans are capable of learning multiple types of information from the same stimulus stream in a parallel fashion.

Implicit anticipation of probabilistic regularities: Larger CNV emerges for unpredictable events.

Anticipation of upcoming events plays a crucial role in automatic behaviors. It is, however, still unclear whether the event-related brain potential (ERP) markers of anticipation could track the implicit acquisition of probabilistic regularities that can be considered as building blocks of automatic behaviors. Therefore, in a four-choice reaction time (RT) task performed by young adults (N = 36), the contingent negative variation (CNV) as an ERP marker of anticipation was measured from the onset of a cue stimulus until the presentation of a target stimulus. Due to the probability structure of the task, target stimuli were either predictable or unpredictable, but this was unknown to participants. The cue did not contain predictive information on the upcoming target. Results showed that the CNV amplitude during response preparation was larger before the unpredictable than before the predictable target stimuli. In addition, although RTs increased, the P3 amplitude decreased for the unpredictable as compared with the predictable target stimuli, possibly due to the stronger response preparation that preceded stimulus presentation. These results suggest that enhanced attentional resources are allocated to the implicit anticipation and processing of unpredictable events. This might originate from the formation of internal models on the probabilistic regularities of the stimulus stream, which primarily facilitates the processing of predictable events. Overall, we provide ERP evidence that supports the role of implicit anticipation and predictive processes in the acquisition of probabilistic regularities.

Accurate response selection and inhibition in healthy aging: An event-related potential study.

Inhibitory control is thought to be critical for appropriate response selection in an ever-changing environment and to decline with age. However, experimental paradigms (e.g., go/no-go) confound stimulus frequency with demands to respond or inhibit responding. The present study eliminated that confound by using a modified go/no-go task controlling for stimulus frequency differences (using frequent-go, infrequent-go, and infrequent no-go types of stimuli) in healthy older and young adults. Event-related potential (ERP) components related to detection of response conflict (N2) and response evaluation (P3) were also examined. Behaviorally, older and young adults were sensitive to stimulus frequencies indicated by significant slowing for the infrequent-go compared with the frequent-go stimuli observed in both groups. Furthermore, older adults were characterized by reduced commission errors and overall slowing, suggesting that they could take advantage of their slower performance. Increase of N2 amplitude was evident for correctly inhibited no-go stimuli in both groups. In contrast, no-go stimulus-related increase in P3 amplitude could be observed only in the young. Stimulus frequency-related ERP amplitude differences were not significant either in the young or in the older adults. These results suggest preserved behavioral control over inappropriate responses in older adults and indicate that efficient response inhibition is related to compensatory mechanisms. The age-related decrease in the P3 amplitude suggests that the evaluation of response inhibition (a) could be independent of the detection of response conflict and (b) supports the notion of strategic differences in performance with age. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Perceiving structure in unstructured stimuli: Implicitly acquired prior knowledge impacts the processing of unpredictable transitional probabilities.

It is unclear how implicit prior knowledge is involved and remains persistent in the extraction of the statistical structure underlying sensory input. Therefore, this study investigated whether the implicit knowledge of second-order transitional probabilities characterizing a stream of visual stimuli impacts the processing of unpredictable transitional probabilities embedded in a similar input stream. Young adults (N = 50) performed a four-choice reaction time (RT) task that consisted of structured and unstructured blocks. In the structured blocks, more probable and less probable short-range nonadjacent transitional probabilities were present. In the unstructured blocks, the unique combinations of the short-range transitional probabilities occurred with equal probability; therefore, they were unpredictable. All task blocks were visually identical at the surface level. While one-half of the participants completed the structured blocks first followed by the unstructured blocks, this was reversed in the other half of them. The change in the structure was not explicitly denoted, and no feedback was provided on the correctness of each response. Participants completing the structured blocks first showed faster RTs to more probable than to less probable short-range transitional probabilities in both the structured and unstructured blocks, indicating the persistent effect of prior knowledge. However, after extended exposure to the unstructured blocks, they updated this prior knowledge. Participants completing the unstructured blocks first showed the RT difference only in the structured blocks, which was not constrained by the preceding exposure to unpredictable stimuli. The results altogether suggest that implicitly acquired prior knowledge of predictable stimuli influences the processing of subsequent unpredictable stimuli. Updating this prior knowledge seems to require a longer stretch of time than its initial acquisition.

Cognitive dysfunction in autoimmune rheumatic diseases.

For people with chronic autoimmune rheumatic diseases (AIRD), such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) or systemic sclerosis (SSc), normal cognitive functions are essential for performing daily activities. These diseases may be associated with cognitive dysfunction (CD). In RA, CD has been associated with age, lower education and disease duration and activity. Great advances have been achieved in neuropsychiatric SLE in the identification of pathogenic pathways, assessment and possible treatment strategies. SSc rarely exerts direct effects on the brain and cognitive function. However, the psychological burden that includes depression, anxiety and social impact may be high. AIRD patients with sustained disease activity, organ damage or lower education should be evaluated for CD. The control of systemic inflammation together with tailored behavioural cognitive therapies may benefit these patients.

Correction to: Assessment of cervical spine involvement in rheumatoid arthritis patients in the era of biologics: a real-life, cross-sectional MRI study.

In the original article, the first author's given name and family name were interchanged as provided by the authors in the original manuscript.

Assessment of cervical spine involvement in rheumatoid arthritis patients in the era of biologics: a real-life, cross-sectional MRI study.

Cervical spine involvement may lead to severe complications in rheumatoid arthritis (RA). In the era of modern therapies, atlantoaxial subluxation (AAS) may be rare; however, it may still be detected in asymptomatic patients. The onset of myelopathy can occur at any time. Altogether 49 female RA patients were included. Among them, 15 were methotrexate treated, biologic free, while 34 patients received biologics. The patients had no cervical pain or any neurological symptoms. We assessed the first (C1) and second (C2) cervical vertebrae by 3 T magnetic resonance imaging (MRI). In addition to AAS, we also determined odontoid erosion or periodontal soft tissue thickening. We associated our MRI findings with clinical, laboratory parameters, and hand radiography. We detected anterior AAS and soft tissue thickening in one-quarter, while odontoid erosions in eight (16%) of RA patients. There were no significant differences among the therapeutic subgroups. No posterior or vertical AAS was seen. Anterior AAS was associated with higher degree of inflammation, soft tissue thickening was seen at younger age, while odontoid erosions were associated with van der Heijde-Sharp scores of the hand. None of the patients had any lesions requiring surgery. The presence of cervical involvement in RA patients with 10-11 years of disease duration is still an important and frequent phenomenon. Higher disease activity and erosive disease are associated with atlantoaxial involvement. 3 T MRI is a sensitive method to assess AAS, as well as soft tissue lesions and odontoid erosions.

Assessment of cognitive function in female rheumatoid arthritis patients: associations with cerebrovascular pathology, depression and anxiety.

We assessed cognitive function of female rheumatoid arthritis (RA) patients and analyze the determinants, with special focus on cerebrovascular morphology. Sixty methotrexate (MTX-) or biologic-treated RA patients and 39 healthy controls were included in a cross-sectional study. Smoking habits, alcohol intake and time spent in education were recorded. Standard measures were performed to assess cognitive function (Montreal Cognitive Assessment, MOCA; Trail Making Test, TMT; Victoria Stroop Test, VST; Wechsler Adult Intelligence Scale, WAIS; Benton Visual Retention test, BVRT), depression (Beck Depression Inventory, BDI), anxiety (State-Trait Anxiety Inventory, STAIT/S) and general health status (Short Form 36, SF-36). Mean disease activity (28-joint Disease Activity Score, mDAS28; erythrocyte sedimentation rate, mESR; C-reactive protein, mCRP) of the past 12 months was calculated; anti-cyclic citrullinated peptide (CCP) and rheumatoid factor (RF) were assessed. Cerebral vascular lesions and atrophy, carotid intima-media thickness (cIMT) and plaques, as well as median cerebral artery (MCA) circulatory reserve capacity (CRC) were assessed by brain magnetic resonance imaging (MRI), carotid ultrasound and transcranial Doppler, respectively. Cognitive function tests showed impairment in RA vs controls. Biologic- vs MTX-treated subgroups differed in TMT-A. Correlations were identified between cognitive function and depression/anxiety tests. WAIS, STAIS, STAIT and BDI correlated with most SF-36 domains. Numerous cognitive tests correlated with age and lower education. Some also correlated with disease duration, mESR and mDAS28. Regarding vascular pathophysiology, cerebral vascular lesions were associated with VST-A, carotid plaques with multiple cognitive parameters, while MCA and CRC with MOCA, BVRT and BDI. RA patients have significant cognitive impairment. Cognitive dysfunction may occur together with or independently of depression/anxiety. Older patients and those with lower education are at higher risk to develop cognitive impairment. Cognitive screening might be a useful tool to identify subgroups to be further investigated for cerebrovascular pathologies.

Reorganization of Large-Scale Functional Networks During Low-Frequency Electrical Stimulation of the Cortical Surface.

We investigated the functional network reorganization caused by low-frequency electrical stimulation (LFES) of human brain cortical surface. Intracranial EEG data from subdural grid positions were analyzed in 16 pre-surgery epileptic patients. LFES was performed by injecting current pulses (10mA, 0.2ms pulse width, 0.5Hz, 25 trials) into all adjacent electrode contacts. Dynamic functional connectivity analysis was carried out on two frequency bands (low: 1-4Hz; high: 10-40Hz) to investigate the early, high frequency and late, low frequency responses elicited by the stimulation. The centralization increased in early compared to late responses, suggesting a more prominent role of direct neural links between primarily activated areas and distant brain regions. Injecting the current into the seizure onset zone (SOZ) evoked a more integrated functional topology during the early (N1) period of the response, whereas during the late (N2) period - regardless of the stimulation site - the connectedness of the SOZ was elevated compared to the non-SOZ tissue. The abnormal behavior of the epileptic sub-network during both part of the responses supports the idea of the pathogenic role of impaired inhibition and excitation mechanisms in epilepsy.

[Musculoskeletal relevance of obesity: a new approach to an old topic]. / Az elhízás mozgásszervi vonatkozásai: egy régi téma új megközelítésben.

Authors discuss the musculoskeletal aspects of obesity by applying a novel approach. Biochemical changes associated with obesity and especially metabolic syndrome, may have a great impact on the function of bones, joints and muscles. Therefore we need a new view and new strategies in rheumatic diseases. Obesity-associated metabolic changes should be considered during the progress of as well as the selection of treatment in inflammatory rheumatic diseases. Individualised treatment is necessary due to associated comorbidities as well. Orv Hetil. 2019; 160(44): 1727-1734.

Tracking the implicit acquisition of nonadjacent transitional probabilities by ERPs.

The implicit acquisition of complex probabilistic regularities has been found to be crucial in numerous automatized cognitive abilities, including language processing and associative learning. However, it has not been completely elucidated how the implicit extraction of second-order nonadjacent transitional probabilities is reflected by neurophysiological processes. Therefore, this study investigated the sensitivity of event-related brain potentials (ERPs) to these probabilistic regularities embedded in a sequence of visual stimuli without providing explicit information on the structure of the stimulus stream. Healthy young adults (N = 32) performed a four-choice RT task that included a sequential regularity between nonadjacent trials yielding a complex transitional probability structure. ERPs were measured relative to both stimulus and response onset. RTs indicated the rapid acquisition of the sequential regularity and the transitional probabilities. The acquisition process was also tracked by the stimulus-locked and response-locked P3 component: The P3 peak was larger for the sequence than for the random stimuli, while the late P3 was larger for less probable than for more probable short-range relations among the random stimuli. According to the RT and P3 effects, sensitivity to the sequential regularity is assumed to be supported by the initial sensitivity to the transitional probabilities. These results suggest that stimulus-response contingencies on the probabilistic regularities of the ongoing stimulus context are implicitly mapped and constantly revised. Overall, this study (1) highlights the role of predictive processes during implicit memory formation, and (2) delineates a potential to gain further insight into the dynamics of implicit acquisition processes.

ERPs differentiate the sensitivity to statistical probabilities and the learning of sequential structures during procedural learning.

Procedural learning facilitates the efficient processing of complex environmental stimuli and contributes to the acquisition of automatic behaviors. Although earlier findings suggest different temporal trajectories of the multiple learning processes within procedural learning, this has not been clarified at the level of neurocognitive correlates. Therefore, we investigated whether two prominent learning processes - statistical learning and sequence learning - can be distinguished using event-related brain potentials (ERPs) within the same experimental setting. Healthy young adults (N = 40) performed the Alternating Serial Reaction Time task while RTs and ERPs were measured time-locked to the onset of the task's stimuli. Both RT and N2 effects reflected the rapid acquisition of statistical probabilities. At the same time, these effects reflected the gradual learning of sequential structures. The amplitude change of the P3 reflected only gradual sequence learning. The P1 component was sensitive to both learning processes, which did not change as the task progressed. Our results altogether indicate that statistical learning and sequence learning develop differently at the level of both ERPs and overt responses. These findings could provide insight to the dynamic change of multiple parallel learning processes that occur during procedural memory formation.

Increased frequency of temporal acoustic window failure in rheumatoid arthritis: a manifestation of altered bone metabolism?

Assessment of intracranial vessels includes transcranial Doppler (TCD). TCD performance requires intact temporal acoustic windows (TAW). Failure of TAW (TAWF) is present in 8-20% of people. There have been no reports on TAWF in rheumatoid arthritis (RA). Altogether, 62 female RA patients were included. Among them, 20 were MTX-treated and biologic-free, 20 received infliximab, and 22 tocilizumab. The controls included 60 non-RA women. TAWF, temporal bone thickness, and texture were determined by ultrasound and CT. BMD and T-scores of multiple bones were determined by DEXA. Several bone biomarkers were assessed by ELISA. In RA, 54.8% of the patients had TAWF on at least one side. Neither TAW could be identified in 34% of RA subjects. In contrast, only 20.0% of control subjects had TAWF on either or both sides (p < 0.001). In RA vs controls, 53.0 vs 2.9% of subjects exerted the trilayer, "sandwich-like" structure of TAW (p < 0.001). Finally, in RA vs controls, the mean temporal bone thickness values of the right TAW were 3.58 ± 1.43 vs 2.92 ± 1.22 mm (p = NS), while those of the left TAW were 4.16 ± 1.56 vs 2.90 ± 1.16 mm (p = 0.001). There was close association between TAWF, bone thickness, and texture (p < 0.05). These TAW parameters all correlated with age; however, TAW failure and texture also correlated with serum osteoprotegerin. TAW bone thickness inversely correlated with hip BMD (p < 0.05). TAWF, thicker, and heterogeneous temporal bones were associated with RA. These features have been associated with bone loss and OPG production. Bone loss seen in RA may result in OPG release and stimulation of bone formation around TAW.