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A behavioral teratogenic model of the impact of prenatal cocaine exposure on arousal regulatory systems.

Studies of both preclinical and human models of prenatal cocaine exposure suggest that one mechanism for the impact of cocaine on developing neural systems may be through functional alterations in monoaminergically regulated arousal systems. Conceptually, arousal regulation refers to a set of multimodal central nervous system mechanisms underlying cortical activation in response to internal and/or external stimulation. The emerging capacity for moment-to-moment regulation of states of arousal influences attentional states (e.g., posterior cortex) and executive functions (prefontal cortex) and thus information processing and learning as well as socialization. Furthermore, as a gating mechanism for response to novel and/or stressful conditions, arousal regulation is also a central construct for understanding stress reactivity and response to acute chronic trauma. In this paper, we review the findings of prenatal cocaine exposure in both preclinical and human studies with a particular focus on studies of neurobehavioral, neurocognitive functioning. A theoretical model of interactive arousal systems is presented as one possibility for integrating the profile of apparent cocaine-related neurobehavioral impairments in infants and young children prenatally exposed to cocaine.

Animals↗

Women but not men exhibit a positive correlation between complex partial epileptic-like signs and tactile-visual cross-modal matching: implications for hemispheric intercalation.

16 right-handed men and 19 women were asked to feel various sized wooden cubes with the dominant hand for 2 sec. (without visual feedback) and then to select this cube from a random visual arrangement of cubes (tactile-visual matching) after a brief delay. The accuracy for men and women for this task did not differ significantly; however, the accuracy was significantly correlated (rho = 0.61) with a history of complex partial epileptic-like signs for the women but not for the men. The results support the hypothesis that elevated scores for complex partial epileptic-like signs in right-handed women enhance their capacity to associate different perceptual domains of the same stimuli because there is elevated activity within the (multimodal) hippocampal-amygdaloid system (sensory-limbic hyperconnectionism) and the correlative enhanced intercalation between the right and left temporoparietal lobes.

Adolescent↗

Integration of information-seeking skills and activities into a problem-based curriculum.

Recent trends in medical education include a shift from the traditional, didactic, lecture-oriented approach to a more student-driven, problem-based approach to learning. This trend provides librarians with an opportunity to develop programs to teach information-gathering skills that support and are integrated into problem-based learning (PBL). In 1992, the University of Pittsburgh School of Medicine implemented the initial phase of a curriculum revision that emphasizes PBL. Since that time, Falk Library of the Health Sciences has provided a large-scale, intensive program integrating information-seeking skills and activities into the first-year Patient-Doctor Relationship course, a sequence that initiates medical school. A multimodal approach to information seeking and sources is emphasized, utilizing print and audiovisual materials, computerized resources, and subject experts. The Falk Library program emphasizes the gathering and use of information as central to both PBL and student skills development. An informal, post-course evaluation was conducted to gauge which information resources were used and valued most by students. This article presents evaluation results, including data on the use of information sources and services, and student perceptions of the librarian's role in the PBL sessions.

Curriculum↗

Auditory cues support place navigation in rats when associated with a visual cue.

Rats, like other crepuscular animals, have excellent auditory capacities and they discriminate well between different sounds [Heffner HE, Heffner RS, Hearing in two cricetid rodents: wood rats (Neotoma floridana) and grasshopper mouse (Onychomys leucogaster). J Comp Psychol 1985;99(3):275-88]. However, most experimental literature concerning spatial orientation almost exclusively emphasizes the use of visual landmarks [Cressant A, Muller RU, Poucet B. Failure of centrally placed objects to control the firing fields of hippocampal place cells. J Neurosci 1997;17(7):2531-42; and Goodridge JP, Taube JS. Preferential use of the landmark navigational system by head direction cells in rats. Behav Neurosci 1995;109(1):49-61]. To address the important issue of whether rats are able to achieve a place navigation task relative to auditory beacons, we designed a place learning task in the water maze. We controlled cue availability by conducting the experiment in total darkness. Three auditory cues did not allow place navigation whereas three visual cues in the same positions did support place navigation. One auditory beacon directly associated with the goal location did not support taxon navigation (a beacon strategy allowing the animal to find the goal just by swimming toward the cue). Replacing the auditory beacons by one single visual beacon did support taxon navigation. A multimodal configuration of two auditory cues and one visual cue allowed correct place navigation. The deletion of the two auditory or of the one visual cue did disrupt the spatial performance. Thus rats can combine information from different sensory modalities to achieve a place navigation task. In particular, auditory cues support place navigation when associated with a visual one.

Animals↗

Verbal memory and learning in unilateral posterior cerebral infarction. A report on 30 cases.

Unilateral posterior cerebral infarction, sparing memory-related structures in the diencephalon, may represent a means of investigating the role of hippocampal afferents and the parahippocampal areas in memory processing. Among 30 patients with unilateral posterior cerebral infarction a group of 12 subjects with left-sided lesions suffered from marked verbal memory and learning dysfunction, whereas the remaining subjects with left or right-sided lesions showed no obvious memory deficit. The impairment was most prominent for verbal learning tasks, while recall of isolated and complex verbal information appeared to be less affected. In some cases the memory disturbance could be detected up to one year after the causative event. Analysis by CT scanning revealed a coincidence of mnestic disturbances with lesions around the left collateral sulcus affecting the posterior parahippocampal gyrus and the collateral isthmus. The latter term refers to the fibre stem of the medial temporal lobe limited by the floor of the lateral ventricle and the depth of the collateral sulcus. Through this bottle-neck, bidirectional fibres run between the posterior parahippocampal gyrus and different sensory-specific and multimodal association areas. A lesion within the collateral isthmus or, more particularly, a combined lesion of the collateral isthmus and the posterior parahippocampal gyrus, deprives the hippocampus itself of its main afferent projection source and, on the other hand, prevents dissemination of the hippocampal output to widespread neocortical areas. It cannot be excluded, at least in some cases, that small lesions in the fimbria-fornix route, in the retrosplenial cortex or in the hippocampal formation itself also contribute to the memory and learning dysfunction. However, these small lesions, so far as they could be detected by CT scanning, were present in patients with and without memory disturbances.

Adult↗

A quantitative coordinate system for developmental dynamics.

Quantitative comparison of morphogenesis across individuals remains a fundamental challenge, as developing embryos vary in shape, orientation and developmental tempo. Moreover, real-time three-dimensional imaging generates large, heterogeneous four-dimensional datasets that are difficult to directly align. As a result, developmental variability is typically described qualitatively rather than measured. Here we introduce STERN, a quantitative framework that learns continuous spatiotemporal representations of morphogenesis directly from in vivo 4D imaging data. By embedding embryos into a shared spatiotemporal space, STERN defines a quantitative developmental coordinate system that enables direct comparison of developmental trajectories across individuals without requiring explicit registration or staging. Applied to mouse embryogenesis, STERN reveals that embryos follow conserved developmental trajectories while progressing at distinct temporal rates, providing a quantitative measure of developmental heterochrony. Extending this framework to zebrafish neural crest light-sheet timelapse imaging, we further show that developmental order is preserved across distinct imaging views even with altered anatomical coverage, supporting the generality of the learned representation across vertebrate imaging contexts. Finally, in developing mouse hearts, where morphogenesis proceeds through subtle and continuously evolving structural changes, STERN resolves fine-scale developmental dynamics at minute-scale temporal resolution that are difficult to localize reproducibly using human experts or general-purpose multimodal AI. Together, these results establish a shared quantitative coordinate system for morphogenesis, in which developmental trajectories become directly comparable across individuals and developmental variability becomes a measurable property.

Journal Article↗

Attention-deficit/hyperactivity disorder.

In this chapter we have reviewed the diagnosis and management of attention deficit disorder, focusing particularly on the role of stimulant therapy in ADHD. Hisorical review suggests that ADHD has roots that extend back almost a century. The definition of ADHD is based on inclusion and exclusion criteria that are established by history and reflect behavioral concerns. Attention-deficit/hyperactivity disorder is a chronic disorder affecting the child's home, school, and community life. The primary symptoms of the disorder manifest a developmental pattern: activity diminishes while attentional deficits persist. Major sources of concern are the secondary and often more resistant problems of learning difficulties, behavioral problems, lack of peer acceptance, and low self-esteem. An often frustrating and perplexing characteristic of the disorder is its marked variability-over time, across situations, and within the same child and similar situations. Educational management represents an important priority and often forms the cornerstone of all other therapies, nonpharmacologic or pharmacologic. Cognitive-behavioral therapies represent the most widely used alternative to pharmacotherapy. Although the effects of CBT alone are disappointing, recent studies suggest that such therapies may provide a useful adjunct to pharmacotherapy and may be helpful when children are tapered off medication. Psychotherapy, or a combination of psychotherapy and medication (termed multimodality therapy), may also be useful. Pharmacotherapy for ADHD originated almost 60 years ago, and at this time the ameliorative effects of medications in ADHD are well established. The general skepticism of experienced clinicians, coupled with a climate where parents are reluctant to medicare children, serves to limit their use except where indicated. Although the effects of stimulants on attention and activity seem well established, effects on cognition, conduct, and social behavior are more controversial. Within recent years, a great deal has been learned about the pharmacokinetics of stimulants in children with ADHD, providing a rational basis for administration. It is also clear that side effects are minimal, the most serious being the possibility of the emergence of tics. Whereas stimulants are clearly the most effective agents, other agents, including antidepressants, may also be effective. Recent advances may now provide an opportunity to better understand the neural and molecular basis for ADHD. Recent advances in imaging technology, particularly fMRI, offer an opportunity to examine the neural basis of ADHD, and advances in genetics may provide clues to its etiology.

Attention Deficit Disorder with Hyperactivity↗

The Israel Center for Medical Simulation: a paradigm for cultural change in medical education.

Simulation-based medical education (SBME) is a rapidly growing field, as is illustrated by the increased development of simulation centers worldwide. SBME is becoming a powerful force in addressing the need to increase patient safety through quality-care training. Recognizing the benefits of SBME, increasing numbers of bodies involved in medical and health care education and training are establishing simulation centers worldwide. The general model of most facilities focuses on a single simulation modality or a specific branch of medicine or health care, limiting their overall impact on patient safety and quality of care across the health care systems. MSR, the Israel Center for Medical Simulation, is a comprehensive, national, multimodality, multidisciplinary medical simulation center dedicated to enhancing hands-on medical education, performance assessment, patient safety, and quality of care by improving clinical and communication skills. The center uses an "error-driven" educational approach, which recognizes that errors provide an opportunity to create a unique beneficial learning experience. The authors present the Israeli experience as an alternative model, and describe the impact of the MSR model on the Israeli medical community during four years of activity. They also describe the opportunities this model has opened towards changing the culture of medical education and patient safety within Israel Although this model may require modification when implemented in other medical systems, it highlights important lessons regarding the power of SBME in triggering and bringing about cultural changes in traditional medical education.

Computer Simulation↗

Subfrontal transbasal approach and technique for resection of craniopharyngioma.

A multimodality approach to craniopharyngioma, including minimally invasive stereotactic techniques, microsurgery, conventional radiotherapy, and radiosurgery has been recommended to tackle craniopharyngioma aggressively while minimizing harm to the patient. With all approaches, there are varying levels of risk for endocrinological morbidity, vascular complications, neuropsychological and behavioral disorders, neurocognitive disorders, and learning disabilities. Although many treatment options are available, total tumor resection remains the most commonly performed procedure for treatment of craniopharyngioma, and it is still believed to give the patient the greatest chance of having an independent and productive life with low risk of recurrences. The authors prefer the subfrontal transbasal approach for resection of these tumors, and they describe this approach and illustrate it with the accompanying figures.

Brain Neoplasms↗

Evidence for training-induced crossmodal reorganization of cortical functions in trumpet players.

The aim of this study was to compare multimodal information processing in the somatosensory and auditory cortices and related multimodal areas in musicians (trumpet players) and non-musicians. Magnetoencephalographic activity (MEG) was recorded in response to five stimulus conditions from 10 professional trumpet players and nine musically untrained control subjects. Somatosensory and auditory stimuli were presented alone or in combination. Our data suggest that musicians, in general, process multisensory stimuli differently to the control group. When stimulating the lip in professional trumpet players, a multimodal interaction (expressed as difference between the multimodal response and the sum of unimodal responses) in the corresponding somatosensory cortex showed a positive peak at 33 ms, which was not found in the control group. Conversely, the control group shows a significant interaction of opposite polarity around 60-80 ms. We suggest that training-induced reorganization in musicians leads to a qualitatively different way to process multisensory information. It favors an early stage of cortical processing, which is modified by the connections between multimodal and auditory neurons from thalamus to primary somatosensory area.

Acoustic Stimulation↗

Spectral-Proteomic Integration Analysis (SPIA) Deciphers Molecular Trajectories of Breast Cancer and Enables Multitarget Therapeutic Assessment.

Raman spectroscopy and mass spectrometry-based proteomics offer deeply complementary yet largely disconnected views of cancer biology: the former provides a label-free, real-time biochemical phenotype, while the latter delivers a quantitative inventory of specific protein effectors. Bridging this gap remains a fundamental challenge in analytical biomedicine. Here, we introduce Spectral-Proteomic Integration Analysis (SPIA)─a novel, data-driven integrative framework that systematically links Raman spectroscopic phenotypes with quantitative proteomic profiles through machine learning and statistical correlation. Using a DMBA-induced rat breast cancer model with and without Toremifene (TOR) intervention, SPIA dynamically maps tumor microenvironment remodeling, capturing progressive collagen deposition and lipid metabolic reprogramming. An SVM classifier trained on Raman spectra achieves exceptional diagnostic accuracy (AUC ≥ 99.0%) and successfully predicts TOR therapeutic response. Proteomic analysis identifies 1,350 differentially expressed proteins, with convergent machine learning feature selection (LASSO, Random Forest, XGBoost) pinpointing core regulators including Luc7l2, Nucb1, Cbx3, and Csnk2a1. Crucially, Spearman correlation analysis between key Raman bands and core DEPs reveals strong, statistically robust associations (median ρ ∼ 0.75 in the 1533-1669 cm-1 region), empirically validating SPIA's core integrative logic. Leveraging this multimodal map, we elucidate a multitarget mechanism for TOR involving concurrent suppression of collagen deposition and correction of aberrant lipid metabolism. SPIA establishes a powerful, generalizable paradigm for integrating phenotypic and molecular data, with broad implications for biomarker discovery, drug mechanism elucidation, and precision oncology.

Animals↗

Subdivisions of hymenopteran mushroom body calyces by their afferent supply.

The mushroom bodies are regions in the insect brain involved in processing complex multimodal information. They are composed of many parallel sets of intrinsic neurons that receive input from and transfer output to extrinsic neurons that connect the mushroom bodies with the surrounding neuropils. Mushroom bodies are particularly large in social Hymenoptera and are thought to be involved in the control of conspicuous orientation, learning, and memory capabilities of these insects. The present account compares the organization of sensory input to the mushroom body's calyx in different Hymenoptera. Tracer and conventional neuronal staining procedures reveal the following anatomic characteristics: The calyx comprises three subdivisions, the lip, collar, and basal ring. The lip receives antennal lobe afferents, and these olfactory input neurons can terminate in two or more segregated zones within the lip. The collar receives visual afferents that are bilateral with equal representation of both eyes in each calyx. Visual inputs provide two to three layers of processes in the collar subdivision. The basal ring is subdivided into two modality-specific zones, one receiving visual, the other antennal lobe input. Some overlap of modality exists between calycal subdivisions and within the basal ring, and the degree of segregation of sensory input within the calyx is species-specific. The data suggest that the many parallel channels of intrinsic neurons may each process different aspects of sensory input information.

Afferent Pathways↗

Event based self-supervised temporal integration for multimodal sensor data.

A method for synergistic integration of multimodal sensor data is proposed in this paper. This method is based on two aspects of the integration process: (1) achieving synergistic integration of two or more sensory modalities, and (2) fusing the various information streams at particular moments during processing. Inspired by psychophysical experiments, we propose a self-supervised learning method for achieving synergy with combined representations. Evidence from temporal registration and binding experiments indicates that different cues are processed individually at specific time intervals. Therefore, an event-based temporal co-occurrence principle is proposed for the integration process. This integration method was applied to a mobile robot exploring unfamiliar environments. Simulations showed that integration enhanced route recognition with many perceptual similarities; moreover, they indicate that a perceptual hierarchy of knowledge about instant movement contributes significantly to short-term navigation, but that visual perceptions have bigger impact over longer intervals.

Animals↗

Topographic distribution of modality-specific amygdalar neurons in alert monkey.

Neuronal activity in the amygdala (AM) was recorded from alert monkeys during performance of tasks that led to presentation of rewarding or aversive stimuli. The tasks had 3 phases: (1) discrimination (visual, auditory), (2) operant response (bar pressing), and (3) ingestion (reward) or avoidance (aversion). Neuronal activity was analyzed and compared during each of these phases. Of 585 AM neurons tested, 312 (53.3%) responded to at least one stimulus in one or more of 5 major groups: vision related, audition related, ingestion related, multimodal, and selective. Forty neurons (6.8%) in the anterior dorsolateral capsule of the basolateral nuclei responded exclusively to visual stimuli (vision related). Twenty-six neurons (4.4%) further posterior in the basolateral group responded only to auditory stimuli (audition related). During ingestion an additional 41 neurons (7.0%) increased their activity (ingestion related). These were in the corticomedial group and at the boundaries between the nuclei of the basolateral group. Of these, 27 responded only in the ingestion phase, 11 during ingestion and at the sight of food, and 3 during ingestion and to certain sounds. Throughout the AM other neurons (n = 117, 20.0%) responded to visual, auditory, and somesthetic stimuli and, when tested, to involuntary ingestion of liquid (multimodal). Of these, 40 responded transiently (phasic; 36 excited, 4 inhibited). The remaining 77 maintained their altered activity into the subsequent phases of the task (tonic; 69 excited, 8 inhibited). In each of these 4 categories, most cells were activated primarily by novel or unfamiliar stimuli, and their responses habituated during repeated stimulation. A small number of cells in the basolateral and the basomedial nuclei (n = 14, 2.4%) were highly selective in that they responded specifically to one biologically significant object or sound more than to any other stimuli (selective). Some of these neurons responded to both sight and ingestion of a specific food. In summary, most AM neurons responded vigorously to novel stimuli, and some of the neurons had multimodal responsiveness. These results suggest the AM is related to processing of new environmental stimuli and to those cross-modal association.

Acoustic Stimulation↗

[A network capable of reading the temporal codes in the olfactory discrimination of insects].

Recent work on the insect olfactory system has shown that its mushroom bodies (one of its major components) are involved in the fine discrimination of odours and that the temporal organisation of spike discharges plays a fundamental role. We propose here a model of a network that is able to decode the temporal patterns which characterise an odour. This model has three fundamental properties that seem to exist in all mushroom bodies of insects studied so far: a) long lasting inhibitions with rebounds, able to facilitate delayed spike generation; b) synaptic plasticity, which allows the network to learn to recognise temporal patterns; c) above all a large interconnection, which allows this network to recognise intervals of various duration. This model thus appears suited to identify combinations of temporal patterns in the dendrites of Kenyon cells (the principal cells in the calyces of the mushroom bodies). Moreover, the mushroom bodies integrate multimodal inputs, suggesting that the detection of temporal patterns may be extended to the detection of a complex environment, combining in particular olfactive and visual inputs.

Animal Structures↗

Children with ADHD treated with long-term methylphenidate and multimodal psychosocial treatment: impact on parental practices.

OBJECTIVE: To test the hypothesis that multimodal psychosocial intervention, which includes parent training, combined with methylphenidate significantly enhances the behavior of parents of children with attention-deficit/hyperactivity disorder (ADHD), compared with methylphenidate alone and compared with methylphenidate and nonspecific psychosocial treatment (attention control). METHOD: One hundred three children with ADHD (ages 7-9), free of conduct and learning disorders, who responded to short-term methylphenidate therapy were randomized for 2 years to receive either (1) methylphenidate treatment alone; (2) methylphenidate plus psychosocial treatment that included parent training and counseling, social skills training, academic assistance, and psychotherapy; or (3) methylphenidate plus attention control treatment. Parents rated their knowledge of parenting principles and negative and positive parenting behavior. Children rated their parents' behavior. RESULTS: Psychosocial treatment led to significantly better knowledge of parenting principles but did not enhance parenting practices, as rated by parents and children. Significant improvement in mothers' negative parenting occurred across all treatments and was maintained. CONCLUSIONS: In nonconduct-disordered, stimulant-treated children with ADHD, parent training does not improve self-rated parental behavior. The benefits of brief stimulant treatment for negative parental behavior are sustained with extended treatment.

Attention Deficit Disorder with Hyperactivity↗

Automated CEAP Classification of Venous Duplex Reports Using Multimodal Artificial Intelligence.

OBJECTIVE: To develop and internally validate a prototype multimodal artificial intelligence system for automated CEAP (Clinical, Etiological, Anatomical and Pathophysiological) classification of venous duplex ultrasound (VDUS) reports, integrating natural language processing of free-text components with computer vision analysis of hand-drawn anatomical diagrams. METHODS: Single centre retrospective observational study using routinely collected clinical data. One thousand consecutive venous duplex ultrasound reports from Cambridge University Hospitals NHS Foundation Trust, UK (July 2024 - May 2025) were labelled according to the CEAP classification, excluding the Etiological component, which could not be reliably determined from duplex reports alone. Transfer learning was applied using ClinicalBERT for text and MobileNetV3 for diagrammatic data. Clinical classes were predicted from request line text. Text- and image-based pathophysiological models were developed for four anatomical territories (Great Saphenous Vein, Small Saphenous Vein, Deep system, Perforators), combined using late fusion with probability averaging. RESULTS: The clinical CEAP model achieved accuracy of 0.91, macro-F1 of 0.82, and macro-AUC of 0.98. Pathophysiological prediction varied, with text models broadly outperforming image models. Fusion yielded heterogeneous benefits, improving SSV performance but reducing Deep system accuracy. The performance of the final pathophysiological CEAP fusion models varied across anatomical territories: accuracy ranged from 0.70-0.92 and macro-AUC from 0.80-0.92. CONCLUSION: This study demonstrates the feasibility of automated CEAP classification from VDUS reports. Despite class imbalance affecting minority class predictions, the strong discriminatory performance validates this multimodal ML model for extracting clinically meaningful information from real-world data. This approach offers potential, pending external validation, to streamline vascular services through automated triage and guideline-compliant decision making.

Artificial intelligence↗

DeepPlaque: a scalable multimodal platform for Aβ pathology and cell analysis in Alzheimer's disease.

Histological analysis is essential for understanding disease pathology and the microenvironment, particularly in Alzheimer's disease (AD), characterized by beta-amyloid (Aβ) plaques that exist as diffuse, fibrillar, and core species, with distinct toxicity levels. However, accurate classification of Aβ plaque types in postmortem brain tissues and profiling of surrounding cells present significant challenges. To address these challenges, we developed "DeepPlaque", an integrated system featuring "PlaqueNet", a deep learning model for automated classification of Aβ plaque species from diverse imaging platforms. DeepPlaque includes automated workflows for cellular phenotyping and proteomic profiling through targeted laser microdissection. PlaqueNet achieves expert-level accuracy (AUC > 90%) in classifying the 3 major Aβ plaque species, supporting consistent and large-scale annotation. By integrating spatial cellular phenotyping with laser microdissection, DeepPlaque enables high-throughput proteomic analysis of Aβ plaque niches, revealing that microglia are more abundant around core and fibrillar Aβ plaques, with increased expression of apolipoprotein E and amyloid precursor protein in core Aβ plaques. This customizable platform enhances the molecular and cellular characterization of Aβ plaque-associated environments, providing critical insights into AD pathology.

Alzheimer Disease↗