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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↗
PubMed1979

The monkey's prefrontal cortex functions in motor programming.

A new experimental approach is presented which resulted in clarification of the specific functions of the monkey’s prefrontal cortex. Monkeys with chronically implanted transcortical nonpolarizable electrodes were trained on delayed response (DR) and visual delayed matching-to-sample (DMS) tasks. The onset of the trial for each group depended upon on-line computer detection of one of the specified events: FN – surface-negative steady potential shifts (SPS) from principalis cortex; MN – a similar SPS from precentral cortex; FB – near baseline SP from principalis cortex; LEM – rightward eye deviations; and YC – controls, with intertrial intervals yoked to those of other monkeys. Monkeys were trained with 1-s cue presentations. on successive delays of 2 to 12 s. The DR acquisition rate by the FN group was substantially faster than that of any other group, as indicated by its mean error that was only 17.24 percent the YC group’s error. The MN and LEM monkeys acquired the task at the same rates as the YCs, while the FB monkeys were the slowest learners. The correct DR performance transferred to testing with constant intertrial intervals (without preconditions). Subsequent on-line tests with brief (0.1 s) cue duration showed high DR performance by the FN, but not by other groups. No similar rapid learning was found with the DMS task. The findings from this, and other experiments, suggest that the major function of principalis cortex is the selection, or programming of delayed spatial choice responses. The view seems consonant with interpretations for the role of the human prefrontal cortex.

Animals↗
PubMed1975

Recognition and reproduction of words by Down's syndrome and non-Down's syndrome retarded children.

Children with Down's syndrome were compared with other severely retarded children on tests of recognition and reproduction of real and nonsense words after 0-, 15-, and 30-seconds delay. The results indicated that Down's syndrome children performed better on the recognition task, but worse on the reproduction task after delay, as compared with the other retarded children. It was hypothesized that the articulatory deficit in the Down's syndrome group is part of a general motor disability due to a difficulty in preprogramming sequences of movements.

Auditory Perception↗
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↗
PubMedDate not supplied

Behavioral role of the mammillary efferent system.

The present study examined the effects of lesions of the mammillary system on spatial memory and arousal. Destruction of the medial mammillary nucleus or the mammillotegmental tract produces impairments on a delayed alternation task and greatly increases activity in the open-field. Lesions of the mammillothalamic tract produce a differential effect in that the spatial alternation deficit is accompanied by a general lethargy and unresponsiveness. It is suggested that the mammillary system plays a crucial role in the short-term storage of proprioceptive information necessary for the successive execution of maze choices. It also appears to play a role in the arousal state of the animal.

Animals↗
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↗