Cognitive flexibility (CF) is the ability to adapt cognitive strategies according to the changing environment. The deficit in CF has often been linked to various neurological and psychiatric disorders including schizophrenia. However, the operationalization and assessment of CF have not been unified and the current research suggests that the available instruments measure different aspects of CF. The main objective of the present study was to compare three frequently used neuropsychological measures of CF-Wisconsin Card Sorting Test (WCST), Trail Making Test (TMT) and Stroop Color and Word Test (SCWT) in a population of patients (N = 220) with first-episode schizophrenia spectrum disorders in order to evaluate their convergent validity. The hypothesis of an underlying latent construct was tested via a confirmatory factor analysis. We used a one-factor CF model with scores from WCST, SCWT and TMT as observed variables. The established model showed a good fit to the data (χ2 = 1.67, p = 0.43, SRMR = 0.02, RMSEA = 0.0, CFI = 1.00). The highest factor loading was found in WCST as CF explained most of the variance in this neuropsychological measure compared to the other instruments. On the other hand, a TMT ratio index and a SCWT interference demonstrated lowest loadings in the model. The findings suggest that not all the frequently used measures share an underlying factor of CF or may capture different aspects of this construct.
- MeSH
- Adult MeSH
- Executive Function * physiology MeSH
- Factor Analysis, Statistical MeSH
- Cognitive Dysfunction * etiology diagnosis physiopathology MeSH
- Cognitive Flexibility MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Neuropsychological Tests * standards MeSH
- Psychometrics MeSH
- Schizophrenic Psychology * MeSH
- Schizophrenia * complications physiopathology MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Semantic and short-term episodic memory are impaired in some brain disorders including Alzheimer's disease. OBJECTIVE: Development and validation of an almost self-administered, but cognitively demanding four-minute test identifying very mild cognitive impairment (vMCI). METHODS: The innovative hedgehog PICture Naming and Immediate Recall (PICNIR) consisted of two parts. The first task was to write down the names of 20 black-and-white pictures to evaluate long-term semantic memory and language. The second task involves immediate recall and writing the names of as many previously named pictures as possible in one minute. The PICNIR is assessed using the number of naming errors (NE) and correctly recalled picture names (PICR). The PICNIR and a neuropsychological battery were administered to 190 elderly individuals living independently in the community. They were divided into those with vMCI (n = 43 with Montreal Cognitive Assessment (MoCA) 24 ± 3 points) and sociodemographically matched cognitively normal (CN) individuals (n = 147 with MoCA 26 ± 3). Both subgroups had predicted mean Mini-Mental State Examination scores of 28-29 points. RESULTS: Compared to CN, vMCI participants made more NE (0.3 ± 0.6 versus 0.6 ± 0.9; p = 0.02) and recalled fewer PICR (8.9 ± 2.2 versus 6.8 ± 2.2; p < 0.000001). Discriminative validity was satisfactory using the area under the ROC curve (AUC): 0.76 for PICR, 0.74 for MoCA, 0.67 for MoCA-five-word recall, and 0.59 for NE. The AUCs of PICR and MoCA were comparable and larger than those of MoCA five-point recall or NE. Logical Memory scores, RAVLT scores, Digit symbol, and animal fluency correlated with PICR. CONCLUSIONS: The picture-based PICNIR is an ultra-brief, sensitive cognitive test valid for assessing very mild cognitive impairment. Its effectiveness should be validated for other languages and cultures.
- MeSH
- Memory, Episodic * MeSH
- Cognitive Dysfunction * diagnosis psychology MeSH
- Memory, Short-Term physiology MeSH
- Humans MeSH
- Neuropsychological Tests * statistics & numerical data MeSH
- Reproducibility of Results MeSH
- Mental Recall * physiology MeSH
- Semantics MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Mental Status and Dementia Tests statistics & numerical data MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: The hippocampal representation of space, formed by the collective activity of populations of place cells, is considered as a substrate of spatial memory. Alzheimer's disease (AD), a widespread severe neurodegenerative condition of multifactorial origin, typically exhibits spatial memory deficits among its early clinical signs before more severe cognitive impacts develop. OBJECTIVE: To investigate mechanisms of spatial memory impairment in a double transgenic rat model of AD. METHODS: In this study, we utilized 9-12-month-old double-transgenic TgF344-AD rats and age-matched controls to analyze the spatial coding properties of CA1 place cells. We characterized the spatial memory representation, assessed cells' spatial information content and direction-specific activity, and compared their population coding in familiar and novel conditions. RESULTS: Our findings revealed that TgF344-AD animals exhibited lower precision in coding, as evidenced by reduced spatial information and larger receptive zones. This impairment was evident in maps representing novel environments. While controls instantly encoded directional context during their initial exposure to a novel environment, transgenics struggled to incorporate this information into the newly developed hippocampal spatial representation. This resulted in impairment in orthogonalization of stored activity patterns, an important feature directly related to episodic memory encoding capacity. CONCLUSIONS: Overall, the results shed light on the nature of impairment at both the single-cell and population levels in the transgenic AD model. In addition to the observed spatial coding inaccuracy, the findings reveal a significantly impaired ability to adaptively modify and refine newly stored hippocampal memory patterns.
- MeSH
- Alzheimer Disease * physiopathology MeSH
- Amyloid beta-Protein Precursor genetics MeSH
- CA1 Region, Hippocampal physiopathology MeSH
- Hippocampus physiopathology MeSH
- Rats MeSH
- Humans MeSH
- Disease Models, Animal * MeSH
- Memory Disorders etiology physiopathology MeSH
- Rats, Inbred F344 MeSH
- Rats, Transgenic * MeSH
- Spatial Memory physiology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
INTRODUCTION: Loneliness has a rising public health impact, but research involving neuropathology and representative cohorts has been limited. METHODS: Inverse odds of selection weights were generalized from the autopsy sample of Rush Alzheimer's Disease Center cohorts (N = 680; 89 ± 9 years old; 25% dementia) to the US-representative Health and Retirement Study (N = 8469; 76 ± 7 years old; 5% dementia) to extend external validity. Regressions tested cross-sectional associations between loneliness and (1) Alzheimer's disease (AD) and cerebrovascular pathology; (2) five cognitive domains; and (3) relationships between pathology and cognition, adjusting for depression. RESULTS: In weighted models, greater loneliness was associated with microinfarcts, lower episodic and working memory in the absence of AD pathology, lower working memory in the absence of infarcts, a stronger association of infarcts with lower episodic memory, and a stronger association of microinfarcts with lower working and semantic memory. DISCUSSION: Loneliness may relate to AD through multiple pathways involving cerebrovascular pathology and cognitive reserve. HIGHLIGHTS: Loneliness was associated with worse cognition in five domains. Loneliness was associated with the presence of microinfarcts. Loneliness moderated cognition-neuropathology associations. Transportability methods can provide insight into selection bias.
- MeSH
- Alzheimer Disease * psychology pathology MeSH
- Cerebrovascular Disorders * psychology pathology MeSH
- Cognition * physiology MeSH
- Humans MeSH
- Neuropsychological Tests statistics & numerical data MeSH
- Loneliness * psychology MeSH
- Cross-Sectional Studies MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Despite advances in understanding the cellular and molecular processes underlying memory and cognition, and recent successful modulation of cognitive performance in brain disorders, the neurophysiological mechanisms remain underexplored. High frequency oscillations beyond the classic electroencephalogram spectrum have emerged as a potential neural correlate of fundamental cognitive processes. High frequency oscillations are detected in the human mesial temporal lobe and neocortical intracranial recordings spanning gamma/epsilon (60-150 Hz), ripple (80-250 Hz) and higher frequency ranges. Separate from other non-oscillatory activities, these brief electrophysiological oscillations of distinct duration, frequency and amplitude are thought to be generated by coordinated spiking of neuronal ensembles within volumes as small as a single cortical column. Although the exact origins, mechanisms and physiological roles in health and disease remain elusive, they have been associated with human memory consolidation and cognitive processing. Recent studies suggest their involvement in encoding and recall of episodic memory with a possible role in the formation and reactivation of memory traces. High frequency oscillations are detected during encoding, throughout maintenance, and right before recall of remembered items, meeting a basic definition for an engram activity. The temporal coordination of high frequency oscillations reactivated across cortical and subcortical neural networks is ideally suited for integrating multimodal memory representations, which can be replayed and consolidated during states of wakefulness and sleep. High frequency oscillations have been shown to reflect coordinated bursts of neuronal assembly firing and offer a promising substrate for tracking and modulation of the hypothetical electrophysiological engram.
- MeSH
- Electroencephalography MeSH
- Cognition * physiology MeSH
- Humans MeSH
- Brain physiology MeSH
- Brain Waves physiology MeSH
- Memory physiology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Episodic memory, the ability to recall specific events and experiences, is a cornerstone of human cognition with profound clinical implications. While animal studies have provided valuable insights into the neuronal underpinnings of episodic memory, research has largely relied on a limited subset of tasks that model only some aspects of episodic memory. In this narrative review, we provide an overview of rodent episodic-like memory tasks that expand the methodological repertoire and diversify the approaches used in episodic-like memory research. These tasks assess various aspects of human episodic memory, such as integrated what-where-when or what-where memory, source memory, free recall, temporal binding, and threshold retrieval dynamics. We review each task's general principle and consider whether alternative non-episodic mechanisms can account for the observed behavior. While our list of tasks is not exhaustive, we hope it will guide researchers in selecting models that align with their specific research objectives, leading to novel advancements and a more comprehensive understanding of mechanisms underlying specific aspects of episodic memory.
- MeSH
- Memory, Episodic * MeSH
- Humans MeSH
- Neurosciences methods MeSH
- Mental Recall physiology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Elektrokonvulzívna terapia (ECT) má v psychiatrii svoje stále miesto a nezastupiteľnú úlohu v liečbe závažných psychických porúch. Výskyt vážnejších nežiaducich účinkov je zriedkavý, mortalita ECT je nižšia, v porovnaní s inými lekárskymi zákrokmi realizovanými v celkovej anestéze. V súvislosti s ECT sa popisujú rôzne poruchy kognitívnych funkcií, ktoré predstavujú riziko z hľadiska negatívneho vplyvu na kvalitu života pacienta. Obavy z ich výskytu a údajnej vysokej závažnosti dlhodobo pretrvávajú v laickej verejnosti. Jedná sa o tzv. nesystematický prehľad. Literárne zdroje boli čerpané najmä z databázy PubMed (metaanalýzy, systematické prehľadové práce a klinické štúdie, publikované na danú tématiku v priebehu posledných 10 rokov). Podľa nedávnej a pomerne rozsiahlej metaanalýzy bol výskyt subjektívnych kognitívnych nežiaducich účinkov u pacientov po ECT zaznamenaný v 48 % prípadov. Podľa aktuálne dostupných údajov sú však väčšinou prechodné, krátkodobé a týkajú sa len určitých kognitívnych domén (rýchlosť spracovania informácií, exekutívne funkcie, pozornosť, pracovná a verbálna pamäť, autobiografická pamäť). Napriek tomu porucha autobiografickej pamäti môže pretrvávať v niektorých prípadoch aj viac ako 1 rok s parciálnou ireverzibilitou. Na výskyt kognitívnych nežiaducich účinkov má vplyv viacero modifikovateľných faktorov, ktoré je potrebné poznať a rešpektovať. Podstatným z nich je individualizácia množstva aplikovaného elektrického náboja počas ECT prostredníctvom jeho postupnej titrácie, za účelom nájdenia individuálneho záchvatového prahu. Jednoznačne by mali byť uprednostňované ultrakrátke impulzy (0,3ms) pred dlhšími. Ak to klinický stav umožní, je vhodné použiť unilaterálne umiestnenie elektród (nad nedominantnou hemisférou). Neodporúča sa podávanie viac ako 12 aplikácií v jednej sérii v akútnej fáze liečby (pri bitemporálnom umiestnení elektród). Individuálne faktory pacienta, ku ktorým sa radia vyšší vek, ženské pohlavie, prítomnosť organického poškodenia mozgu a nižší intelekt, predstavujú vyššie riziko rozvoja kognitívnych nežiaducich účinkov po ECT, rovnako aj súbežná liečba lítiom počas ECT. Súčasné národné a medzinárodné odporúčania ponúkajú rôzne psychometrické inštrumenty na monitorovanie kognitívnych nežiaducich účinkov ECT. V niektorých krajinách, napríklad v nemecky hovoriacich regiónoch, ale ani na Slovensku, konkrétne odporúčania neboli vypracované. V dnešnej dobe existujú batérie testov hodnotiace relevantné kognitívne domény, ktoré je možné pri ECT použiť v klinickej praxi, pretože nie sú časovo ani odborne náročné na administráciu. Jedná sa napr. o ECCA test (ElectroConvulsive therapy Cognitive Assessment), prípadne o batériu B4ECT-ReCoDe (Battery for ECT Related Cognitive Deficits). Komplikáciou ich využitia v podmienkach Slovenskej i Českej republiky je, že tam nie sú štandardizované. Alternatívou je použitie jednotlivých testov na spomenuté domény. Významné je najmä hodnotenie dĺžky dezorientácie pacienta po ECT zákrokoch, vyhodnocovanie autobiografickej pamäti, schopnosti verbálneho učenia, exekutívnych funkcií a rýchlosti spracovania informácií a pozornosti, resp. pracovnej pamäti. Hodnotenie výskytu a závažnosti kognitívnych nežiaducich účinkov u pacientov podstupujúcich ECT je v praxi potrebné, zníži riziko rozvoja ich závažnejšieho stupňa, prispeje k optimalizácii liečby, ako aj k zlepšeniu spolupráce pacientov pri tejto terapii.
Electroconvulsive therapy (ECT) has a solid place in psychiatry and an irreplaceable role in the treatment of serious mental disorders. The occurrence of serious side effects is rare, the mortality rate of ECT is lower, compared to other medical interventions performed under general anesthesia. In connection with ECT, various disorders of cognitive functions are described, which pose a risk in terms of a negative impact on the patient ́s quality of life. Concerns about their occurrence and alleged high severity persist for a long time in the public. This is the so-called unsystematic review. Literary sources were mainly drawn from the PubMed database (meta-analyses, systematic review works and clinical studies published on the given topic during the last 10 years). According to a recent and fairly extensive meta-analysis, the occurrence of subjective cognitive side effects in patients after ECT was recorded in 48% of cases. However, according to the currently available data, they are mostly transitory, short-term and affect only certain cognitive domains (information processing speed, executive functions, attention, working and verbal memory, autobiographical memory). Nevertheless, the autobiographical memory disorder can persist in some cases for more than 1 year with partial irreversibility. The occurrence of cognitive side effects is influenced by several modifiable factors that need to be known and respected. An essential one is the individualization of the amount of applied electric charge during ECT through its gradual titration, in order to find the individual seizure threshold. Ultrabrief pulses (0.3ms) should clearly be preferred over longer ones. If the clinical condition allows it, it is advisable to use unilateral electrode placement (over the non-dominant hemisphere). It is not recommended to administer more than 12 applications in one series in the acute phase of treatment (with bitemporal placement of electrodes). Individual patient factors such as older age, female gender, presence of organic brain damage, and lower intellect pose a higher risk of developing cognitive adverse effects after ECT. So does concurrent lithium treatment during ECT. Current national and international guidelines offer various psychometric instruments to monitor the cognitive side effects of ECT. In some countries, for example in German-speaking regions, but also in Slovakia, specific recommendations have not been developed. Nowadays, there are batteries of tests evaluating relevant cognitive domains that can be used in clinical practice during ECT, because they are neither time nor expertly hard to administer. It is, for example, the ECCA test (ElectroConvulsive therapy Cognitive Assessment), or the B4ECT-ReCoDe battery (Battery for ECT Related Cognitive Deficits). The complication of their use in the conditions of Slovakia and the Czech Republic is that they are not standardized there. An alternative is to use individual tests for the mentioned domains. It is particularly important to assess the length of the patient ́s disorientation after ECT procedures, the evaluation of autobiographical memory, verbal learning ability, executive functions and information processing speed and attention, or working memory. Assessment of the occurrence and severity of cognitive side effects in patients undergoing ECT is necessary in practice, it will reduce the risk of developing their more severe degree, contribute to the optimization of treatment, as well as to the improvement of patient cooperation in this therapy.
Výjimečné kognitivní stárnutí neboli superaging je novou oblastí výzkumu. SuperAgers jsou definováni jako osoby ve věku nejméně 80 let, které mají mladistvou epizodickou paměť. Studií je dosud poskrovnu a velmi málo se ví o jejich životním stylu a volnočasových aktivitách, včetně zapojení do fyzické aktivity, která bývá spojována s lepším zdravím. Cílem projektu je zjistit souvislosti celoživotně fyzicky aktivního životního stylu, objektivní zdatnosti a kognitivního superstárnutí u žen. Jedná se o průřezovou ex-post-facto studii. Tímto představujeme její protokol. Testováno bylo 225 žen ve věku 80–96 let, které uvedly, že jejich zapojení do fyzické aktivity v období mezi 30. a 60. rokem života bylo alespoň na úrovni doporučené Světovou zdravotnickou organizací pro dospělé, tj. alespoň 150 minut aerobní fyzické aktivity střední intenzity týdně. Epizodická paměť byla testována Reyovým testem auditorně verbálního učení, nepaměťovými testy byly Test cesty, Verbální fluence – zvířata a Bostonský test pojmenování – 30položková verze. Ke zmapování předchozích a současných volnočasových aktivit bylo použito několik dotazníků. Objektivní údaje byly získány pomocí Senior Fitness Testu. Uvádíme také srovnávací data z předchozí české studie kognitivně normálních starších osob, NANOK, se kterými budeme náš soubor porovnávat. Konkrétně použijeme dílčí výběr 70 žen ve věku 80–94 let, které byly vybrány ze souboru NANOK na základě stejných kritérií pro zařazení jako do studie COSACTIW. Z nich bylo 23 (32,9 %) SuperAgers. Naše zjištění mohou nabídnout podněty k preventivním strategiím pro úspěšné stárnutí a kognitivní odolnost.
Exceptional cognitive aging, or superaging is a recent area of research. SuperAgers are defined as persons aged at least 80 years who have youthful episodic memory. Studies are scarce and very little is known about their lifestyle and leisure activities including their engagement in physical activity, which is otherwise known to be associated with better health. The project aims to identify associations between a lifelong physically active lifestyle, objective fitness and cognitive superaging in old-old women. COSACTIW is a cross-sectional ex-post-facto study. Herewith, we present its protocol. There were 225 women aged 80-96 years tested who reported that their engagement in physical activity between the ages of 30 to 60 years was at least on the level recommended for adults by the World Health Organization, i.e. at least 150 minutes of moderate-intensity aerobic physical activity per week. Episodic memory was tested with Rey Auditory Verbal Learning Test, non-memory tests were Trail Making Test, Verbal fluency – animals, and Boston Naming Test – 30 item version. Several questionnaires were used to map previous and current leisure activities. Objective data were obtained with the Senior Fitness Test. We also present benchmark data from a previous Czech study of cognitively normal older persons, NANOK, to whom we will compare our sample. Specifically, we are going to use a subsample of 70 women, aged 80-94 years, who were selected from the NANOK sample using the same inclusion criteria as in COSACTIW. There were 23 (32.9%) SuperAgers among them. Our findings may offer insights into preventive strategies for successful aging and cognitive resilience.
OBJECTIVES: "SuperAgers" are generally defined as people 80+ years old with episodic memory performance comparable to those 20 years younger. Limited knowledge exists to describe characteristics of SuperAgers, with even less known about Hispanic SuperAgers. METHODS: We examined indicators of cognitive, physical, and psychological resilience in relation to the likelihood of being a SuperAger using data from 2 population-based studies of Hispanic older adults (Puerto Rican Elderly: Health Conditions [PREHCO] Study; Health and Retirement Study [HRS]). SuperAgers were defined as (1) ≥80 years old, (2) recall scores ≥ the median for Hispanic respondents aged 55-64, and (3) no cognitive impairment during the observation period. Overall, 640 PREHCO participants and 180 HRS participants were eligible, of whom 45 (7%) and 31 (17%) met SuperAging criteria. RESULTS: Logistic regressions controlling for age and sex demonstrated that higher education (PREHCO: odds ratio [OR] = 1.20, p < .001; HRS: OR = 1.14, p = .044) and fewer instrumental activities of daily living limitations (PREHCO: OR = 0.79, p = .019; HRS: OR = 0.58, p = .077; cognitive resilience), fewer activities of daily living limitations (PREHCO: OR = 0.72, p = .031; HRS: OR = 0.67, p = .068; physical resilience), and fewer depressive symptoms (PREHCO: OR = 0.84, p = .015; HRS: OR = 0.69, p = .007; psychological resilience) were associated with SuperAging, although not all results reached threshold for statistical significance, presumably due to low statistical power. Additionally, known indicators of physical health (e.g., chronic conditions and self-rated health) did not relate to SuperAging. DISCUSSION: Increasing access to education and recognizing/treating depressive symptoms represent potential pathways to preserve episodic memory among older Hispanic adults.
- MeSH
- Activities of Daily Living psychology MeSH
- Memory, Episodic MeSH
- Hispanic or Latino * statistics & numerical data psychology MeSH
- Middle Aged MeSH
- Humans MeSH
- Resilience, Psychological * MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Aging psychology ethnology MeSH
- Educational Status MeSH
- Health Status MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, N.I.H., Extramural MeSH
- Geographicals
- United States MeSH
The duration of slow-wave sleep (SWS) is related to the reported sleep quality and to the important variables of mental and physical health. The internal cues to end an episode of SWS are poorly understood. One such internal cue is the initiation of a body movement, which is detectable as electromyographic (EMG) activity in sleep-electroencephalography (EEG). In the present study, we characterized the termination of SWS episodes by movement to explore its potential as a biomarker. To this end, we characterized the relation between the occurrence of SWS termination by movement and individual characteristics (age, sex), SWS duration and spectral content, chronotype, depression, medication, overnight memory performance, and, as a potential neurological application, epilepsy. We analyzed 94 full-night EEG-EMG recordings (75/94 had confirmed epilepsy) in the video-EEG monitoring unit of the EpiCARE Centre Salzburg, Austria. Segments of SWS were counted and rated for their termination by movement or not through the visual inspection of continuous EEG and EMG recordings. Multiple linear regression was used to predict the number of SWS episodes that ended with movement by depression, chronotype, type of epilepsy (focal, generalized, no epilepsy, unclear), medication, gender, total duration of SWS, occurrence of seizures during the night, occurrence of tonic-clonic seizures during the night, and SWS frequency spectra. Furthermore, we assessed whether SWS movement termination was related to overnight memory retention. According to multiple linear regression, patients with overall longer SWS experienced more SWS episodes that ended with movement (t = 5.64; p = 0.001). No other variable was related to the proportion of SWS that ended with movement, including no epilepsy-related variable. A small sample (n = 4) of patients taking Sertraline experienced no SWS that ended with movement, which was significant compared to all other patients (t = 8.00; p < 0.001) and to n = 35 patients who did not take any medication (t = 4.22; p < 0.001). While this result was based on a small subsample and must be interpreted with caution, it warrants replication in a larger sample with and without seizures to further elucidate the role of the movement termination of SWS and its potential to serve as a biomarker for sleep continuity and for medication effects on sleep.
- Publication type
- Journal Article MeSH