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PubMed1979

Effects of 1-desamo-8-D-arginine vasopressin on behaviour and cognition in primary affective disorder.

DDAVP (1-desamino-8-d-arginine vasopressin), a synthetic analogue of vasopressin with prolonged half-life and high antidiuretic and low pressor activity, was given in a double-blind placebo-controlled trial to four patients with major affective illness. Three of four patients showed highly significant and consistent improvements in tests designed to measure the formation, encoding, and organisation of long-term trace events in memory. Two patients also showed a significant but less consistent amelioration of other depressive symptoms during DDAVP treatment. These findings implicate central vasopressin function in the processing of information and possibly other aspects of affective illness.

Affective Symptoms↗
PubMed2024

The effect of fampridine on working memory: a randomized controlled trial based on a genome-guided repurposing approach.

Working memory (WM), a key component of cognitive functions, is often impaired in psychiatric disorders such as schizophrenia. Through a genome-guided drug repurposing approach, we identified fampridine, a potassium channel blocker used to improve walking in multiple sclerosis, as a candidate for modulating WM. In a subsequent double-blind, randomized, placebo-controlled, crossover trial in 43 healthy young adults (ClinicalTrials.gov, NCT04652557), we assessed fampridine's impact on WM (3-back d-prime, primary outcome) after 3.5 days of repeated administration (10 mg twice daily). Independently of baseline cognitive performance, no significant main effect was observed (Wilcoxon P = 0.87, r = 0.026). However, lower baseline performance was associated with higher working memory performance after repeated intake of fampridine compared to placebo (rs = -0.37, P = 0.014, n = 43). Additionally, repeated intake of fampridine lowered resting motor threshold (F(1,37) = 5.31, P = 0.027, R2β = 0.01), the non-behavioral secondary outcome, indicating increased cortical excitability linked to cognitive function. Fampridine's capacity to enhance WM in low-performing individuals and to increase brain excitability points to its potential value for treating WM deficits.

Adult↗
PubMed2026

Distinct contributions of schizophrenia and neurotransmitter pathway genetic liability to neurocognition and antipsychotic efficacy in drug-naïve first-episode schizophrenia.

The genetic mechanisms underlying heterogeneity in symptom presentation and antipsychotic response in schizophrenia remain unclear, limiting the development of personalized treatment. We integrated genome-wide schizophrenia polygenic risk scores (SZ-PRS) and pathway-specific PRSs (pPRSs) for four major neurotransmitter systems to examine their associations with clinical phenotypes across the course of illness. Primary analyses were conducted in 394 drug-naïve, first-episode patients from the Chinese First-Episode Schizophrenia Trial (CNFEST) to investigate associations with baseline symptom severity, neurocognitive impairment, and longitudinal treatment response. The CNFEST cohort included 52-week longitudinal assessments of symptoms and neurocognition using the Positive and Negative Syndrome Scale and a modified version of the MATRICS Consensus Cognitive Battery. An independent case-control cohort evaluated associations with schizophrenia diagnosis, while a cohort of 514 healthy adults assessed whether PRS-cognition associations are specific to schizophrenia. Higher SZ-PRS predicted schizophrenia diagnosis (OR = 2.28, Pfdr = 0.003) and poorer baseline executive function (β = -0.44, Pfdr = 0.006) and working memory (β = -0.49, Pfdr = 0.018), but these associations were absent in healthy adults. In contrast, pPRSs showed weaker associations with diagnosis and baseline cognition but were more informative for treatment outcomes: higher serotonin-pPRS predicted greater improvement in depressive symptoms (Pfdr = 0.023-0.032), and higher GABA-pPRS predicted greater improvement in overall symptoms (Pfdr = 0.038-0.043) during weeks 4-24. Exploratory drug-specific analyses further suggested that treatment response varied across antipsychotics and was differentially associated with pPRSs. These findings demonstrate that genome-wide and pathway-specific PRSs contribute distinctly to schizophrenia phenotypes, supporting their integration for personalized stratification and treatment.

Humans↗
PubMed1975

EEG sleep studies of insomniacs under flunitrazepam treatment.

This study investigates the effect of flunitrazepam, a new benzodiazepine, on the sleep of insomniac patients under chronic treatment. Polygraphic recordings have shown that this drug decreases not only the activity of the wakefulness system, but also the activity of the synchronizing system of slow-wave sleep. The subjective feeling of improved and sounder sleep seems to be related to a decrease of wakefulness pressure as well as to a decrease of body motoricity, but not with the modification of sleep stages themselves. Flunitrazepam appears to possess some regulatory properties on REM sleep, since this stage is enhanced in patients with an initial low amount of REM sleep and decreased in those having a higher initial REM sleep. Flunitrazepam possesses potent and useful hypnogenic properties in man but does not induce physiological sleep.

Adult↗
PubMed1979

Effects on learning and memory of 2-week treatments with chlordiazepoxide lactam, N-desmethyldiazepam, oxazepam and methyloxazepam, alone or in combination with alcohol.

A double-blind study with 40 healthy students was done in order to measure the effects of a 2-week treatment with chloridiazepoxide lactam (5 mg), nordiazepam (10 mg), oxazepam (15 mg) and methyloxazepam (20 mg) on immediate memory and associative learning. The drugs were administered t.i.d. and the tests were done after the very last capsule was given. It was ingested with a placebo drink and 0.5 g alcohol/kg body weight. Oxazepam and methyloxazepam alone behaved similar to the placebo. Immediate memory was significantly impaired following the treatment with nordiazepam, chlordiazepoxide lactam, alcohol, and after the simultaneous administration of nordiazepam and chlordiazepoxide lactam with alcohol. Chlordiazepoxide lactam was the only drug which alone impaired associative learning. Also alcohol alone, and all the drugs in combination with alcohol retarded learning acquisition.

Adult↗
PubMed1978

[Assessment of vigilance].

Two aspects of vigilance are to be distinguished: the quantitative one refers to sleep-wakefulness dimension and the qualitative one refers to focusing of attention. Their combination leads to a curvilinear relationship between activation and performances. After describing the psychometric characteristics of vigilance tests, some examples are given of simple paper-pencil or more sophisticated methods. Physiological indices are also approached. The sources of variation influencing vigilance measurement are presented and also some useful experimental designs. At last some remarks are made on statistical exploitation and interpretation of results.

Attention↗
PubMed1977

A psychometric evaluation of the acute tremulous state.

The acute alcohol withdrawal state (tremulous state), with mainly vegetative symptoms and without evident loss of conciousness or confusion, was evaluated as to functional psychopathological disturbances aiming to present a complete and objective record of the clinical findings and to establish a control of the course and drug treatment. We tried to meet the inherent inability to cooperate by using proven and also new test devices (flicker fusion, simple reaction time on light and tone, reaction on multiple serial stimuli, visual motor coordination, tachistoscopic perception and memory test, test of concentration and sustained performance with simple arithmetical calculation by analogy with the Pauli test) to circumvent the difficulties arising when patients have to answer long questionnaires. The tests enabled a measurement of the disturbances as objective as possible and proved to have a discriminating sensitivity for different functions. The correlations between the results were found to be similar for alcoholics and controls. tthe degree of the established functional cerebral and cerebellar defects which was revealed was more severe than expected in this mild stage of withdrawal.

Adult↗
PubMedDate not supplied

Use of concanavalin A to analyse the mechanism of memory cell differentiation into killer cells.

The renewing by ConA of the cytolytic activity evaluated in a short-term chromium release assay in a population of memory cells obtained in a long-term mixed lymphocyte culture is shown to be largely dependent upon the dose of ConA used; a three staged phenomenon in terms of dose response and kinetics is analysed and suggests that at least for low concentration of ConA (0.5 micrograms/ml) the lectin acts on the same subpopulation and through the same mechanism as the specific antigen, as shown by DNA-synthesis inhibition experiments. Preincubation with ConA at doses giving the best secondary-like response strongly inhibits further response to the primary alloantigen. Experiments using mixtures of ConA and alloantigens as stimulators show that both agents can compete in differentiating memory cells into killer cells. All these data suggest an important overlap of the structures on memory cells which are triggered by ConA or specific antigen.

Animals↗
PubMed2026

Electromagnetic Radiation Stimulated Learning in Perovskite Nickelates.

Biological plasticity refers to the ability of synapses to strengthen or weaken over time. These adaptive properties play a fundamental role in learning and memory, spanning many orders of magnitude in timescales. Short-term plasticity (STP) arises from rapid correlative activity, while long-term plasticity (LTP) is governed by slower biochemical processes. Here, we investigate electromagnetically driven relaxation dynamics in perovskite nickelate thin films as an analogue of biological learning behaviors. By comparing radio frequency (RF), infrared (IR), visible, and ultraviolet (UV) radiation as stimuli, we find that RF excitation primarily induces STP, while visible and IR illumination lead to reversible relaxation on behavioral timescales. In contrast, UV illumination results in persistent, non-thermal changes in conductivity over extended timescales. Notably, UV-exposed nickelate films exhibit glass-like dynamics, characterized by stretched exponential relaxation and aging phenomena. The films display habituation to repeated stimuli, along with sensitization and spontaneous recovery under controlled environments. A minimal dynamical systems model captures key qualitative features of the UV-induced resistance changes. Our results demonstrate that electromagnetic frequency enables multi-timescale relaxation spanning nearly nine orders of magnitude, suggesting perovskite nickelates as promising platforms for adaptive optoelectronic hardware and for linking computational neuroscience with emerging quantum technologies.

electromagnetic radiation↗
PubMed2025

Impact of Chewing Behavior Change on Cognition and Cerebral Hemodynamics.

BACKGROUND: Impaired chewing ability is a recognized risk factor for cognitive decline in older adults, potentially due to reduced neural stimulation in cognition-related brain regions. While short-term studies have demonstrated transient increases in neural activity from chewing, the sustained cognitive and neurophysiological effects of encouraging thorough chewing habits in daily life remain unclear. OBJECTIVE: This randomized controlled trial investigated whether promoting thorough chewing during meals could improve cognitive function and cerebral hemodynamics in older adults. METHODS: Fifty participants aged 65 y or older were randomly assigned to either a 1-mo intervention group, which used a wearable device to monitor and increase chewing strokes during meals, or a control group that maintained usual chewing habits. Chewing behavior, cognitive performance (including memory and executive function via the color Stroop test), and cerebral hemodynamics in the dorsolateral prefrontal cortex (DLPFC) were measured at baseline and after 1 mo. Statistical analyses included t tests, chi-square tests, 2-way analysis of variance with post hoc tests, Pearson correlations, and generalized linear models to evaluate group differences and associations between chewing and cognitive outcomes. RESULTS: Significant time-by-group interactions were observed for memory, F(1, 48) = 6.24, P = 0.043, and hemodynamic responses in the left DLPFC, F(1, 48) = 6.19, P = 0.013. The intervention group showed increased chewing frequency (P = 0.017), improved memory performance, and reduced left DLPFC responses compared with controls. Chewing frequency was positively correlated with Stroop test scores (r = 0.53, P = 0.010) and negatively with hemodynamic changes in the left DLPFC (r = -0.30, P = 0.040). Although improvements in other cognitive outcomes and hemodynamic measures favored the intervention group, these differences did not reach statistical significance. CONCLUSIONS: Promoting intentional chewing habits for 1 mo may enhance memory-related cognitive performance and neural efficiency in the DLPFC during working memory tasks in older adults. This nonpharmacologic, low-burden strategy warrants further research with longer interventions to support cognitive health and dementia prevention. TRIAL REGISTRATION ID: UMIN000044280Knowledge Transfer Statement:This study demonstrates that promoting thorough chewing habits in older adults can improve memory and enhance neural efficiency in the brain. Encouraging intentional mastication is a simple, nonpharmacologic approach that may help maintain cognitive health and prevent dementia, providing a practical strategy for clinicians and policymakers to support healthy aging.

Humans↗
PubMed2026

Comparing trajectories of cognitive functioning in treatment-resistant and non-resistant depression: a multicentre linear mixed-effects analysis.

BACKGROUND: Impaired cognitive functioning is a severe symptom in major depressive disorder (MDD). Recent evidence suggests it may be a central characteristic in its treatment resistant form (TRD), potentially constituting a clinical marker for treatment resistance and a target amenable to intervention. To date, cognitive functioning in TRD remains poorly understood and longitudinal investigations are scarce. METHODS: This observational prospective cohort study, including 320 patients diagnosed with MDD from the multicentre PROMPT study, examined differences in cognitive functioning between 118 TRD and 202 non-TRD patients over a period of twelve weeks in a real-world setting, using linear mixed modelling. Patients that failed to respond to at least two prior antidepressants trials at baseline were classified as TRD. RESULTS: TRD patients showed significantly poorer baseline performances than non-TRD patients in attention/processing speed (β = -0.45; 95%CI[-0.70, -0.19]; FDR-p = 0.003) and verbal memory (β = -0.45; 95%CI[-0.72, -0.18]; FDR-p = 0.003). Significant time × group interactions were observed in motor speed and verbal fluency tasks. Post-hoc-analyses revealed stagnation in TRD patients and significant improvement in non-TRD patients. Across all other tasks improvement was observed in both groups, and random effects showed large heterogeneity between patients, indicating notable individual differences in cognitive performances. CONCLUSIONS: The results suggest distinct recovery patters between non-TRD and TRD patients, and diminished functioning in TRD patients at the domain level. However, intact and diminished performances likely occur in both groups, warranting further investigation of cognitive heterogeneity. These short-term findings highlight the need for more comprehensive longitudinal research on cognition in TRD.

Humans↗
PubMed1979

Generation of cytolytic T lymphocytes in vitro. X. Induction of primary and secondary CTL responses by the mitogen sodium periodate.

Short-term (15 min) sodium periodate (NaIO4) treatment of mouse spleen cells previously primed in vivo or in vitro against alloantigens induced the formation of secondary (2 degree) cytolytic T lymphocytes (CTL) specific for the priming antigens. CTL formation was readily demonstrable within 24 hr after treatment. This early CTL response occurred equally well in the presence or absence of cytosine arabinoside (Ara C), indicating that NaIO4 could induce CTL independently of DNA synthesis. Forty-eight hours after periodate treatment, the lytic activity was similar to that observed in parallel cultures stimulated with irradiated allogeneic spleen cells, although the peak activity was reached earlier (day 4) and was somewhat lower than that induced by alloantigen. The addition of irradiated NaIO4-treated unprimed syngeneic spleen cells to cultures of untreated alloimmune spleen cells also led to CTL formation, which suggests an indirect mechanism of activation. In contrast to alloimmune spleen cells, normal spleen cells treated with NaIO4 developed only very low levels of cytotoxicity after 4 days of incubation. However, in the presence of PHA, such cells were capable of lysing syngeneic and allogeneic target cells.

Animals↗