Effects of temporal grouping on unimodal and multimodal sequential information processing in nonretarded and retarded subjects.
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Adolescent↗
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Results for “Multimodal learning”
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Pyrazine odour makes visually conspicuous prey aversive.
Unpalatable insects frequently adopt multimodal signals to ward off predators, incorporating sounds and odours into their colourful displays. Pyrazine is an odour commonly used in insect warning displays, and has previously been shown to elicit unlearned biases against common warning colours, e.g. yellow and red in naive predators. We designed two experiments to test for similar effects of pyrazine on the conspicuousness of prey, perhaps the most ubiquitous aspect of aposematic coloration. In the first experiment, we offered predators (Gallus gallus domesticus) a choice between conspicuous crumbs and cryptic crumbs in the presence or absence of pyrazine. In the second experiment, we manipulated the birds' experience of conspicuous prey during an initial training phase. Only in the presence of pyrazine did birds show a bias against conspicuously coloured food, and this occurred whether or not they had previously experienced food that contrasted with the background. This emergent behaviour relied upon the visual and odorous signal components being presented together. These unlearned, yet hidden, responses against conspicuousness demonstrate that there are initial benefits to prey being conspicuous when the multimodal nature of warning signals is accounted for.
Animals↗
A process for developing community consensus regarding the diagnosis and management of attention-deficit/hyperactivity disorder.
There remain large discrepancies between pediatricians' practice patterns and the American Academy of Pediatrics (AAP) guidelines for the assessment and treatment of children with attention-deficit/hyperactivity disorder (ADHD). Several studies raise additional concerns about access to ADHD treatment for girls, blacks, and poorer individuals. Barriers may occur at multiple levels, including identification and referral by school personnel, parents' help-seeking behavior, diagnosis by the medical provider, treatment decisions, and acceptance of treatment. Such findings confirm the importance of establishing appropriate mechanisms to ensure that children of both genders and all socioeconomic, racial, and ethnic groups receive appropriate assessment and treatment. Publication of the AAP ADHD toolkit provides resources to assist with implementing the ADHD guidelines in clinical practice. These resources address a number of the barriers to office implementation, including unfamiliarity with Diagnostic and Statistical Manual of Mental Disorders criteria, difficulty identifying comorbidities, and inadequate knowledge of effective coding practices. Also crucial to the success of improved processes within clinical practice is community collaboration in care, particularly collaboration with the educational system. Such collaboration addresses other barriers to good care, such as pressures from parents and schools to prescribe stimulants, cultural biases that may prevent schools from assessing children for ADHD or may prevent families from seeking health care, and inconsistencies in recognition and referral among schools in the same system. Collaboration may also create efficiencies in collection of data and school-physician communications, thereby decreasing physicians' non-face-to-face (and thus nonreimbursable) elements of care. This article describes a process used in Guilford County, North Carolina, to develop a consensus among health care providers, educators, and child advocates regarding the assessment and treatment of children with symptoms of ADHD. The outcome, ie, a community protocol followed by school personnel and community physicians for >10 years, ensures communication and collaboration between educators and physicians in the assessment and treatment of children with symptoms of ADHD. This protocol has the potential to increase practice efficiency, improve practice standards for children with ADHD, and enhance identification of children in schools. Perhaps most importantly, the community process through which the protocol was developed and implemented has an educational component that increases the knowledge of school personnel about ADHD and its treatment, increasing the likelihood that referrals will be appropriate and increasing the likelihood that children will benefit from coordination of interventions among school personnel, physicians, and parents. The protocol reflects a consensus of school personnel and community health care providers regarding the following: (1) ideal ADHD assessment and management principles; (2) a common entry point (a team) at schools for children needing assessment because of inattention and classroom behavior problems, whether the problems present first to a medical provider, the behavioral health system, or the school; (3) a protocol followed by the school system, recognizing the schools' resource limitations but meeting the needs of community health care providers for classroom observations, psychoeducational testing, parent and teacher behavior rating scales, and functional assessment; (4) a packet of information about each child who is determined to need medical assessment; (5) a contact person or team at each physician's office to receive the packet from the school and direct it to the appropriate clinician; (6) an assessment process that investigates comorbidities and applies appropriate diagnostic criteria; (7) evidence-based interventions; (8) processes for follow-up monitoring of children after establishment of a treatment plan; (9) roles for central participants (school personnel, physicians, school nurses, and mental health professionals) in assessment, management, and follow-up monitoring of children with attention problems; (10) forms for collecting and exchanging information at every step; (11) processes and key contacts for flow of communication at every step; and (12) a plan for educating school and health care professionals about the new processes. A replication of the community process, initiated in Forsyth County, North Carolina, in 2001, offers insights into the role of the AAP ADHD guidelines in facilitating development of a community consensus protocol. This replication also draws attention to identification and referral barriers at the school level. The following recommendations, drawn from the 2 community processes, describe a role for physicians in the collaborative community care of children with symptoms of ADHD. (1) Achieve consensus with the school system regarding the role of school personnel in collecting data for children with learning and behavior problems; components to consider include (a) vision and hearing screening, (b) school/academic histories, (c) classroom observation by a counselor, (d) parent and teacher behavior rating scales (eg, Vanderbilt, Conner, or Achenbach scales), (e) consideration of speech/language evaluation, (f) screening intelligence testing, (g) screening achievement testing, (h) full intelligence and achievement testing if discrepancies are apparent in abbreviated tests, and (i) trials of classroom interventions. (2) Use pediatric office visits to identify children with academic or behavior problems and symptoms of inattention (history or questionnaire). (3) Refer identified children to the contact person at each child's school, requesting information in accordance with community consensus. (4) Designate a contact person to receive school materials for the practice. (5) Review the packet from the school and incorporate school data into the clinical assessment. (6) Reinforce with the parents and the school the need for multimodal intervention, including academic and study strategies for the classroom and home, in-depth psychologic testing of children whose discrepancies between cognitive level and achievement suggest learning or language disabilities and the need for an individualized educational plan (special education), consideration of the "other health impaired" designation as an alternate route to an individualized educational plan or 504 plan (classroom accommodations), behavior-modification techniques for targeted behavior problems, and medication trials, as indicated. (7) Refer the patient to a mental health professional if the assessment suggests coexisting conditions. (8) Use communication forms to share diagnostic and medication information, recommended interventions, and follow-up plans with the school and the family. (9) Receive requested teacher and parent follow-up reports and make adjustments in therapy as indicated by the child's functioning in targeted areas. (10) Maintain communication with the school and the parents, especially at times of transition (eg, beginning and end of the school year, change of schools, times of family stress, times of change in management, adolescence, and entry into college or the workforce).
Adolescent↗
Future directions in lung cancer research and therapeutics.
Although immune and genetic approaches do not yet have substantial clinical exposure in NSCLC, it is hoped that the future will bring less toxic, more specific, and more effective methods to prevent the development of end-stage NSCLC. The principles of multitargeted and multimodality therapy to overcome tumor heterogeneity and resistance, and drug delivery issues have been developed over years of effort using chemotherapy. The lessons learned should not be forgotten, because they will remain applicable to newer biologic and genetic modalities.
Antineoplastic Agents↗
Beyond antibiotics: artificial intelligence-enabled anti-infective ecosystems for next-generation precision therapeutics against antimicrobial resistance.
The rapid global expansion of antimicrobial resistance (AMR) threatens to undermine decades of progress in infectious disease management and highlights the limitations of conventional antibiotic-centered therapeutic strategies. Although emerging technologies-including antimicrobial peptides, bacteriophage therapy, CRISPR-based antimicrobials, microbiome therapeutics, anti-virulence approaches, nanotechnology-enabled drug delivery, and artificial intelligence (AI)-have individually demonstrated considerable promise, they are predominantly being developed as independent interventions rather than as coordinated components of an integrated therapeutic strategy. This Perspective proposes the Intelligent Anti-Infective Ecosystem (IAIE) as a conceptual systems-level framework that computationally integrates multimodal diagnostics, pathogen genomics, microbiome profiling, AI-assisted decision support, programmable precision therapeutics, ecological monitoring, and longitudinal clinical feedback within a continuously learning dynamically optimized workflow. Unlike existing paradigms that primarily optimize individual technologies or therapeutic decisions, IAIE emphasizes closed-loop coordination among complementary antimicrobial approaches to support precision-guided infection management while preserving microbiome integrity and mitigating resistance selection pressure. We further outline the core components, operational principles, translational challenges, and technology readiness of the major therapeutic platforms that could contribute to such an ecosystem, while distinguishing clinically established interventions from emerging experimental strategies. Importantly, IAIE should be interpreted as a prospective conceptual architecture rather than an existing clinical platform. Its proposed clinical value remains to be established through sequential computational, preclinical, and prospective clinical investigations using standardized microbiological, ecological, and patient-centered outcome measures. By framing antimicrobial innovation within an responsive systems perspective, IAIE provides a roadmap for future multidisciplinary research aimed at integrating artificial intelligence and systems microbiology to enable sustainable management of antimicrobial resistance.
Humans↗
Evaluation of coma and vegetative states.
The Coma/Near-Coma (CNC) scale was designed to measure small clinical changes in patients with severe traumatic and nontraumatic brain injuries who were functioning at very low levels characteristic of near-vegetative and vegetative states. In 20 patients followed for 16 weeks the scale identified 25% who ultimately showed modest improvement. Interrater reliability was high (r = .95); validity was supported by significant correlations between CNC- and brain-multimodality evoked potential abnormality scores as well as between scores on the CNC and the Disability Rating Scale. The CNC scale was easily learned and it could be completed quickly and cost effectively. Staff found it useful in recognizing among relatively homogeneous low-level patients those most likely to respond to further rehabilitation care. The CNC appears to be useful for justifying ongoing intensive rehabilitation and for preventing premature transfer to lower levels of care.
Adolescent↗
Biological Foundation Models for Complex Disease Research and Clinical Translation.
Complex diseases, including cancer, rare genetic disorders, neurodevelopmental and psychiatric conditions, and neurodegenerative diseases, arise from interactions among genetic variation, gene regulation, and cellular states that are difficult to capture using a single data type or biological scale. Biological foundation models address this challenge by treating nucleotides and genes as tokens and learning representations that can be transferred to downstream biomedical and clinical tasks. In this review, we examine two major model classes, genomic sequence foundation models and cell foundation models, and compare their tokenization strategies, model architectures, pretraining objectives, and adaptation methods. We summarize their emerging applications in regulatory variant interpretation, disease-associated cell-state analysis, drug-response prediction, and therapeutic target discovery across complex diseases. We distinguish applications supported by experimental or retrospective validation from those that remain primarily computational or conceptual. We further discuss key challenges to clinical translation, including multimodal data integration, model interpretability, benchmarking, patient-specific prediction, and privacy protection. We highlight future opportunities to integrate biological foundation models with emerging frameworks of medical digital twins, agentic AI, and federated learning. By linking model design to translational goals, this review provides a practical framework for evaluating biological foundation models and their readiness for complex disease research and clinical use.
biological foundation model↗
Physiological and morphological development of the rat cerebellar Purkinje cell.
Cerebellar Purkinje cells integrate multimodal afferent inputs and, as the only projection neurones of the cerebellar cortex, are key to the coordination of a variety of motor- and learning-related behaviours. In the neonatal rat the cerebellum is undeveloped, but over the first few postnatal weeks both the structure of the cerebellum and cerebellar-dependent behaviours mature rapidly. Maturation of Purkinje cell physiology is expected to contribute significantly to the development of cerebellar output. However, the ontogeny of the electrophysiological properties of the Purkinje cell and its relationship to maturation of cell morphology is incompletely understood. To address this problem we performed a detailed in vitro electrophysiological analysis of the spontaneous and intracellularly evoked intrinsic properties of Purkinje cells obtained from postnatal rats (P0 to P90) using whole-cell patch clamp recordings. Cells were filled with neurobiotin to enable subsequent morphological comparisons. Three stages of physiological and structural development were identified. During the early postnatal period (P0 to approximately P9) Purkinje cells were characterized by an immature pattern of Na(+)-spike discharge, and possessed only short multipolar dendrites. This was followed by a period of rapid maturation (from approximately P12 to approximately P18), consisting of changes in Na(+)-spike discharge, emergence of repetitive bursts of Na(+) spikes terminated by Ca(2+) spikes (Ca(2+)-Na(+) bursts), generation of the trimodal pattern, and a significant expansion of the dendritic tree. During the final stage (> P18 to P90) there were minor refinements of cell output and a plateau in dendritic area. Our results reveal a rapid transition of the Purkinje cell from morphological and physiological immaturity to adult characteristics over a short developmental window, with a close correspondence between changes in cell output and dendritic growth. The development of Purkinje cell intrinsic electrophysiological properties further matches the time course of other measures of cerebellar structural and functional maturation.
Action Potentials↗
AI-Supported, Integrative Prediction of Postoperative Delirium: Protocol for the CONFUSED Study.
BACKGROUND: Postoperative delirium (POD) is a frequent and serious complication in older surgical patients, characterized by acute cognitive dysfunction and fluctuating levels of consciousness. POD is associated with prolonged hospitalization, long-term cognitive decline, reduced quality of life, and increased mortality. Despite its clinical relevance, the underlying pathophysiological mechanisms remain poorly understood, and reliable biomarkers for early prediction and prevention are lacking. OBJECTIVE: The CONFUSED study aims to identify molecular and clinical predictors of POD by integrating clinical data with proteomic, transcriptomic, and epigenetic analyses. The primary objective is to develop predictive models for POD using multimodal data. Secondary objectives include the identification of delirium-associated genes, proteins, and epigenetic signatures, as well as the exploration of patient subgroups at increased risk for POD. METHODS: CONFUSED is a prospective observational cohort study conducted at a German university hospital. Adult patients undergoing major surgery under general anesthesia will be enrolled until 100 cases of POD have been observed, which is expected to require a total sample size of approximately 200 to 300 patients. Blood samples are collected at 4 predefined time points: before premedication, immediately after surgery, and on postoperative days 2 and 5. Samples undergo comprehensive proteomic profiling, transcriptomic analysis using RNA microarrays, DNA methylation analysis, and genotyping of selected polymorphisms. Clinical data, including demographics, comorbidities, perioperative variables, medications, and delirium assessments using the Confusion Assessment Method (CAM) and CAM for the intensive care unit, are systematically recorded. Statistical analyses include univariate and multivariate methods, as well as machine learning approaches such as random forests and support vector machines, to identify relevant biomarkers and develop predictive models. The study protocol follows STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) and TRIPOD (Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis) guidelines and was approved by the responsible ethics committees. RESULTS: The study was registered in the German Clinical Trials Register (DRKS00033854) on March 18, 2024. Recruitment started in January 2024 and is ongoing at the time of manuscript submission. As of now, 135 patients have been enrolled. Sample collection and laboratory analyses are ongoing. Data analysis began in January 2026, with first results anticipated in July 2026. Final data lock is anticipated after the completion of recruitment. CONCLUSIONS: By integrating multimodal molecular data with clinical parameters and applying advanced machine learning techniques, the CONFUSED study aims to improve the prediction and understanding of POD. The results are expected to support the development of personalized preventive strategies and contribute to improved perioperative care for patients at risk of POD.
Humans↗
Amygdala role in conditioned associative learning.
Amygdala role in emotion was reviewed in reference to recent amygdala lesion studies and neuronal responses in the rat amygdala to conditioned stimuli. Extensive lesion studies suggest that the amygdala is crucial in various kinds of motivated and emotional behavior, and related autonomic responses. These amygdala functions critically depend on learning and memory. Amygdala lesions, both before and after training of conditioned associative learning, impaired emotional expression without simple sensory-motor deficits. Pharmacological experiments indicated neurotransmission in the amygdala is mediated through NMDA and AMPA receptors. These results strongly suggest the amygdala involvement in acquiring and storing associative memory (i.e. stimulus-affect association), by which animals recognize and evaluate the biological significance of a stimulus. This information is then transferred to the brainstem executing system. In the neurophysiological experiments, there were topographic distributions of sensory-responsive neurons within the amygdala, which were well correlated to anatomical data. The responses of rat amygdala neurons changed plastically during learning. Furthermore, more sensory-responsive neurons were encountered in the amygdala of rats trained to associate the sensory stimuli with a reinforcement than in the amygdala of rats that were not trained. In trained rats, multimodal neurons that responded to conditioned and unconditioned stimuli were frequently found in the basolateral and central nuclei of the amygdala. The results suggest that basolateral and central nuclei are foci where various sensory modalities converge, and which might perform critical functions in acquiring and storing long-term associative memory to link between sensory information and affective significance.
Amygdala↗
Dreaming and episodic memory: a functional dissociation?
The activity that takes place in memory systems during sleep is likely to be related to the role of sleep in memory consolidation and learning, as well as to the generation of dream hallucinations. This study addressed the often-stated hypothesis that replay of whole episodic memories contributes to the multimodal hallucinations of sleep. Over a period of 14 days, 29 subjects kept a log of daytime activities, events, and concerns, wrote down any recalled dreams, and scored the dreams for incorporation of any waking experiences. While 65% of a total of 299 sleep mentation reports were judged to reflect aspects of recent waking life experiences, the episodic replay of waking events was found in no more than 1-2% of the dream reports. This finding has implications for understanding the unique memory processing that takes place during the night and is consistent with evidence that sleep has no role in episodic memory consolidation.
Consciousness↗
The psychology of polio as prelude to post-polio sequelae: behavior modification and psychotherapy.
Even as the physical causes and treatments for post-polio sequelae (PPS) are being identified, psychological symptoms--chronic stress, anxiety, depression, and compulsive, Type A behavior--are becoming evident in polio survivors. Importantly, these symptoms are not only causing marked distress but are preventing patients from making the lifestyle changes necessary to treat their PPS. Neither clinicians nor polio survivors have paid sufficient attention to the acute polio experience, its conditioning of life-long patterns of behavior, its relationship to the development of PPS, and its effect on the ability of individuals to cope with and treat their new symptoms. We describe the acute polio and post-polio experiences on the basis of patient histories, relate the experience of polio to the development of compulsive, Type A behavior, link these behaviors to the physical and psychological symptoms reported in the National Post-Polio Surveys, and present a multimodal behavioral approach to treatment.
Activities of Daily Living↗
Behavioural and neurohistological changes in aging Sepia.
The life cycle of the cuttlefish in the English Channel is characterized by a succession of homogeneous population cohorts. These conditions provide an excellent opportunity for the study of aging in this cephalopod. In a first longitudinal study, we considered the oldest animals and compared their success rates at the first capture attempt. During the first weeks of the study, the results remained constant and then, during the weeks immediately preceding the natural death, a dramatic drop was observed. This deterioration may be due to defects of visuomotor coordination. In a second study, we used an associative learning protocol with negative reinforcement and the performances of young and old animals were compared. The most striking results showed that the performances of the oldest animals during the retention test were very mediocre. Such results suggest that the long-term memory process is affected. Finally, a modification of the Fink-Heimer silver stain enabled us to draw a map of spontaneous terminal degeneration in the central nervous system of the oldest animals. The structures which are characterized by the presence of multimodal inputs (the spine of the peduncle lobe and the basal lobes) present the most obvious signs of degeneration.
Aging↗
Traces of learning in the auditory localization pathway.
One of the fascinating properties of the central nervous system is its ability to learn: the ability to alter its functional properties adaptively as a consequence of the interactions of an animal with the environment. The auditory localization pathway provides an opportunity to observe such adaptive changes and to study the cellular mechanisms that underlie them. The midbrain localization pathway creates a multimodal map of space that represents the nervous system's associations of auditory cues with locations in visual space. Various manipulations of auditory or visual experience, especially during early life, that change the relationship between auditory cues and locations in space lead to adaptive changes in auditory localization behavior and to corresponding changes in the functional and anatomical properties of this pathway. Traces of this early learning persist into adulthood, enabling adults to reacquire patterns of connectivity that were learned initially during the juvenile period.
Animals↗
From brainstem to cortex: computational models of saccade generation circuitry.
The brain circuitry of saccadic eye movements, from brainstem to cortex, has been extensively studied during the last 30 years. The wealth of data gathered allowed the conception of numerous computational models. These models proposed descriptions of the putative mechanisms generating this data, and, in turn, made predictions and helped to plan new experiments. In this article, we review the computational models of the five main brain regions involved in saccade generation: reticular formation saccadic burst generators, superior colliculus, cerebellum, basal ganglia and premotor cortical areas. We present the various topics these models are concerned with: location of the feedback loop, multimodal saccades, long-term adaptation, on the fly trajectory correction, strategy and metrics selection, short-term spatial memory, transformations between retinocentric and craniocentric reference frames, sequence learning, to name the principle ones. Our objective is to provide a global view of the whole system. Indeed, narrowing too much the modelled areas while trying to explain too much data is a recurrent problem that should be avoided. Moreover, beyond the multiple research topics remaining to be solved locally, questions regarding the operation of the whole structure can now be addressed by building on the existing models.
Animals↗
Nonlinear autoassociation is not equivalent to PCA.
A common misperception within the neural network community is that even with nonlinearities in their hidden layer, autoassociators trained with backpropagation are equivalent to linear methods such as principal component analysis (PCA). Our purpose is to demonstrate that nonlinear autoassociators actually behave differently from linear methods and that they can outperform these methods when used for latent extraction, projection, and classification. While linear autoassociators emulate PCA, and thus exhibit a flat or unimodal reconstruction error surface, autoassociators with nonlinearities in their hidden layer learn domains by building error reconstruction surfaces that, depending on the task, contain multiple local valleys. This interpolation bias allows nonlinear autoassociators to represent appropriate classifications of nonlinear multimodal domains, in contrast to linear autoassociators, which are inappropriate for such tasks. In fact, autoassociators with hidden unit nonlinearities can be shown to perform nonlinear classification and nonlinear recognition.
Linear Models↗
Concepts of a Web-based open distributed textbook for the multimodal diagnostics of gastrointestinal tumours with MRI, CT and video-endoscopy addressing students of medicine and students of medical informatics as two different target groups.
Multimodal diagnostics of gastrointestinal tumours with MRI, CT and video-endoscopy is a rapidly changing domain. The education at our universities should overcome the obstacles of traditional learning based on paper media and oral lectures with retention rates of 10-30% only. The paper presents the objectives and the results of the design phase of the project ODITEB1-Open Distributed TExt Book, for Computer-Assisted Instruction in the domain mentioned above. The main objective is to produce an electronic interactive textbook in order to shift education to more efficient learning settings with higher retention rates. The main concepts are 1) three-layer architecture (dynamic case layer, intermediate query layer, static instruction layer) 2) case pool distribution 3) active learners experience (interactive exploration of original image data).
Computer-Assisted Instruction↗
Predicting fear of heights, snakes, and public speaking from multimodal classical conditioning events.
BACKGROUND: Two hundred fifty one men and women participated in a study of the prediction of fear of heights, snakes, and public speaking by providing retrospective accounts of multimodal classical conditioning events involving those stimuli. The fears selected for study represent those believed by some to be innate (i.e., heights), prepared (i.e., snakes), and purely experientially learned (i.e., public speaking). This study evaluated the extent to which classical conditioning experiences in direct, observational, and verbal modes contributed to the prediction of the current level of fear severity. MATERIAL/METHODS: Subjects were asked to describe their current level of fear and to estimate their experience with fear response-augmenting events (first- and higher-order aversive pairings) and fear response-moderating events (first- and higher-order appetitive pairings, and pre- and post-conditioning neutral presentations) in direct, observational, and verbal modes. RESULTS: For each stimulus, fear was predictable from direct response-augmenting events and prediction was enhanced by the inclusion of response-moderating events. Furthermore, for each fear, maximum prediction was attained by the addition of variables tapping experiences in the observational and/or verbal modes. CONCLUSIONS: Conclusions are offered regarding the importance of including response-augmenting and response-moderating events in all three modes in both research and clinical applications of classical conditioning.
Adolescent↗