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PubMed2005

Integration of hydrodynamic and odorant inputs by local interneurons of the crayfish deutocerebrum.

Intracellular electrodes were used to record from local interneurons in the olfactory lobes of the midbrain in the crayfish Procambarus clarkii. Cells that resembled previously studied central targets of olfactory receptor neurons on the lateral antennular flagellum were specifically examined for their responses to hydrodynamic stimuli. Initiation of water movement past the antennular flagellum, confined within an olfactometer, evoked a triphasic excitatory-inhibitory-excitatory postsynaptic potential lasting up to 2 s that generated spikes on depolarizing phases of the response sequence. Odorant pulses seamlessly imbedded in the water pulse past the antennule evoked purely excitatory, dose-dependent postsynaptic responses and associated spike trains. The latency of the initial phase of the response to water was approximately half as long as the latency of the response to odorant, suggesting that different afferent pathways are involved in responses to hydrodynamic and odorant stimuli, respectively. In some olfactory lobe interneurons that resembled previously described cells classified as Type I, conjoint stimulation of fluid onset and odorant evoked responses that were twice the amplitude of the summed response to either hydrodynamic or odorant stimulation alone, suggesting that the olfactory responses were potentiated by hydrodynamic input. Individuals of at least one other class of first-order interneuron that responded to both hydrodynamic and odorant stimulation were occasionally recorded from. These results indicate that multimodal integration of chemical and mechanical information occurs at the level of first-order sensory interneurons in the crayfish brain.

Animals↗
PubMed1997

A three-dimensional multimodality brain map of the nemestrina monkey.

A three-dimensional multimodality computerized map of the nemestrina monkey brain was created with serial sectioning and digital imaging techniques. An adult female Macaca nemestrina (pigtail macaque) weighing 7.2 kg was used in constructing this atlas. CT, PET, and MRI were performed on the monkey before the specimen's head was frozen and cryoplaned. Closely spaced (50 microns) images of the specimen blockface were then digitally acquired and modified to produce whole head and brain-only 3D image sets. The resulting data sets were organized into a digital volume and repositioned into a stereotaxic coordinate system defined by Horsley and Clark in 1908 [7]. Orthogonal images were obtained by digitally resampling the volume in order to produce a full set of coronal, sagittal, and horizontal images. Stereotaxic reference grids were applied to each image indicating the A/P, M/L, or Ho position within the digital volume. Specific anatomic structures were outlined from the cryosection data set and 3D surface models reconstructed. Structural labels indicating nuclei, tracts, and other neuroanatomical features were incorporated into coronally sliced cryosection images spaced at 500 microns. The CT, PET, and MRI data sets were reconstructed into a digital volume and coregistered to the cryosection volume. All images constructed from this 3D map are available for public access via the internet using an anonymous file transfer protocol (FTP) and the World Wide Web (http:@www.loni.ucla.edu). The foremost advantage of this digital map is an integrated multimodality three-dimensional representation of the Macaca nemestrina brain, which is not possible with traditional atlases.

Animals↗
PubMed1999

A psychodynamically informed, integrated psychotherapy for anorexia nervosa.

Anorexia nervosa is a multiply determined syndrome, thought to require integrated, multimodal treatment. In this article, we discuss the place of psychodynamically inspired psychotherapy techniques in the treatment of Anorexia Nervosa, and attempt to provide a practical heuristic for the application of such techniques with anorexic clients. Our recommendations for therapy emphasize confrontation of interpersonal patterns arising within the therapeutic dyad and linkage of these patterns to parallel adaptations that structure the client's generalized patterns of coping and eating symptoms. Case vignettes, drawn from different clinical contexts, are used to illustrate dynamic themes that frequently emerge in psychotherapeutic work with anorexic clients, and techniques that use interactions that occur in the therapeutic relationship to (i) expose implicit metaphors between interpersonal adaptations and eating symptoms, and (ii) balance against the intensity of anorexic preoccupations.

Adaptation, Psychological↗
PubMed2002

Development of cricket mushroom bodies.

Mushroom bodies are recognized as a multimodal integrator for sensorial stimuli. The present study analyzes cricket mushroom body development from embryogenesis to adulthood. In the house cricket, Kenyon cells were born from a group of neuroblasts located at the apex of mushroom bodies. Our results demonstrate the sequential generation of Kenyon cells: The more external they are, the earlier they were produced. BrdU treatment on day 8 (57% stage) of embryonic life results, at the adult stage, in the labelling of the large Kenyon cells at the periphery of the mushroom body cortex. These cells have specific projections into the posterior calyx, the gamma lobe, and an enlargement at the inner part of the vertical lobe; they represent a part of mushroom bodies of strictly embryonic origin. The small Kenyon cells were formed from day 9 (65% stage) of the embryonic stage onward, and new interneurons are produced throughout the entire life of the insect. They send their projections into the anterior calyx and into the vertical and medial lobes. Mushroom body development of Acheta should be considered as a primitive template, and cross-taxonomic comparisons of the mushroom body development underscore the precocious origin of the gamma lobe. As a result of continuous neurogenesis, cricket mushroom bodies undergo remodeling throughout life, laying the foundation for future studies of the functional role of this developmental plasticity.

Animals↗
PubMed2006

Convergence of spinal trigeminal and cochlear nucleus projections in the inferior colliculus of the guinea pig.

In addition to ascending auditory inputs, the external cortex of the inferior colliculus (ICX) receives prominent somatosensory inputs. To elucidate the extent of interaction between auditory and somatosensory representations at the level of IC, we explored the dual projections from the cochlear nucleus (CN) and the spinal trigeminal nucleus (Sp5) to the inferior colliculus (IC) in the guinea pig, using both retrograde and anterograde tracing techniques. Injections of retrograde tracers into ICX resulted in cell-labeling primarily in the contralateral DCN and pars interpolaris and caudalis of Sp5. Labeled cells in DCN were either fusiform or multipolar cells, whereas those in Sp5 varied in size and shape. Injections of anterograde tracers into either CN or Sp5 resulted in terminal labeling in ICX primarily on the contralateral side. Most projection fibers from Sp5 terminated in a laminar pattern from ventromedial to dorsolateral within the ventrolateral ICX, the ventral border of IC, and the ventromedial edge of IC (collectively termed "the ventrolateral border region of IC," ICXV). Less dense anterograde labeling was observed in lateral and rostral ICX. Injecting different tracers into both Sp5 and CN confirmed the overlapping areas of convergent projections from Sp5 and CN in IC: The most intense dual labeling was seen in the ICXV, and less intense dual labeling was also observed in the rostral part of ICX. This convergence of projection fibers from CN and Sp5 provides an anatomical substrate for multimodal integration in the IC.

Afferent Pathways↗
PubMed2004

Simple and complex movement-associated functional MRI changes in patients at presentation with clinically isolated syndromes suggestive of multiple sclerosis.

Using functional magnetic resonance imaging (fMRI), we investigated whether movement-associated functional changes of the brain are present in patients who are, most likely, at the earliest stage of multiple sclerosis (MS). Functional MRI exams were obtained from 16 patients at presentation with clinically isolated syndromes (CIS) suggestive of MS and 15 sex- and age-matched healthy volunteers during the performance of three simple and one more complex motor tasks with fully normal functioning extremities. fMRI analysis was performed using statistical parametric mapping (SPM99). Compared to healthy volunteers, CIS patients had increased activations of the contralateral primary sensorimotor cortex (SMC), secondary somatosensory cortex (SII), and inferior frontal gyrus (IFG), when performing a simple motor task with the dominant hand. The increased recruitment of the contralateral primary SMC was also found during the performance of the same motor task with the non-dominant hand and with the dominant foot. In this latter case, an anterior shift of the center of activation of this region was detected. During the performance of a complex motor task with the dominant upper and lower limbs, CIS patients had an increased recruitment of a widespread network (including the frontal lobe, the insula, the thalamus), usually considered to function in motor, sensory, and multimodal integration processing. The comparison of brain activations during the performance of simple vs. complex motor tasks showed that the movement-associated somatotopic organization of the cerebral and cerebellar cortices was retained in patients with CIS. Cortical reorganization occurs in patients at presentation with CIS highly suggestive of MS. Local synaptic reorganization, recruitment of parallel existing pathways, and reorganization of distant sites are all likely to contribute to the observed functional changes. Hum. Brain Mapping 21:106-115, 2004.

Adult↗
PubMed2007

Influence of body segment position during in-phase and antiphase hand and foot movements: a kinematic and functional MRI study.

Behavioral studies have provided important insights into the mechanisms governing interlimb coordination. In this study, we combined kinematic and functional magnetic resonance imaging (fMRI) analysis to investigate the brain cortical and subcortical areas involved in interlimb coordination and the influence of direction of movement and of body segment position on the activity of those areas. Fifteen right-handed healthy subjects were studied while performing cyclic in-phase and antiphase hand and foot movements with the dominant, right limbs, with the upper limb positioned either prone or supine, and in front or behind with respect to the trunk. When contrasting antiphase to in-phase movements, fMRI analysis demonstrated an increased recruitment of a widespread sensorimotor network (including regions in the frontal and parietal lobes, bilaterally, the cingulated motor area, the thalami, the visual cortex, and the cerebellum) considered to function in motor, sensory, and multimodal integration processing. When contrasting the anterior to the posterior position of the upper limb with respect to the trunk, we found different recruitment patterns in the frontal and parietal regions as well as the preferential recruitment of the basal ganglia, the insula, and the cerebellum during the first condition and of regions located in the temporal lobes during the second one. Different brain areas are engaged at a different extent during interlimb coordination. In addition to the relative difficulty of the movement, the different cognitive and sensorial loads needed to control and perform the motor act might be responsible for these findings.

Adult↗
PubMed2004

Ewing sarcoma: the pediatrician's point of view.

BACKGROUND: Integrated multimodal care is needed for patients with Ewing sarcoma, which is the second most common primary bone malignancy in children and adolescence. Chemotherapy increases survival from less than 5% to 65-70% for patients with localized tumors and to 25-30% for those with metastases at diagnosis. Surgery is a major tool, whereas advances in imaging techniques have improved the indications for and the optimization of treatment. Radiotherapy remains useful, either alone or in addition to surgery, and new techniques (conformational RT and IMRT) will reduce short-term toxic effects. Pediatric oncologists do not outweigh surgeons or radiation therapists, but they are the ones who coordinate the medical team, which also includes pathologists and imaging specialists. METHODS: The point of view of the pediatric oncologist was assessed as follows: the place of chemotherapy in Ewing tumor treatment, the place of radiotherapy in Ewing tumor treatment (including why avoid radiotherapy when technically possible in children), and how to proceed into the future? The place of surgery as local treatment for Ewing tumors was also evaluated. RESULTS: These reviews show a dynamic and kaleidoscopic panorama of intense activity at the laboratory and clinical levels. CONCLUSIONS: Though good survival rates have been achieved, improvements using entirely new approaches are needed.

Algorithms↗
PubMed1993

Theoretical considerations on the formation of secretory granules in the rat pancreas.

Rat pancreatic zymogen granule sizes were determined by analysis of electron micrographs of the pancreas from adult and newborn rats. Areas of granule profiles were measured and converted to equivalent volumes. Histograms of the equivalent volumes showed integral multimodal distributions which were evaluated for goodness of fit with two models, unit addition and random fusion. Previous analyses of zymogen granule size distributions have failed to recognize the multimodality we have observed. Distributions of equivalent volumes for the two models were developed using Monte Carlo simulation. In the case of the granules from the newborn rats, the distribution of granule sizes gave a better fit with the random fusion model, whereas the granules from the adult rats had distributions with a better fit to the unit granule addition model. The estimated unit granule sizes for the two different ages were the same. Both unit addition and random fusion models propose that following formation of secretory granules from Golgi-derived material, the granules fuse with one another to create a wide dispersion of granule sizes. The present results extend the evidence for fusional growth of secretory granules, originally developed for the mast cell, to the zymogen granules of pancreas. All normal cells previously studied have yielded secretory granule distributions most consistent with unit addition. The basis for the expression of random fusion in the newborn rather than the more usual unit addition is not known.

Aging↗
PubMed2002

Correlations between structural CNS damage and functional MRI changes in primary progressive MS.

In patients with primary progressive multiple sclerosis (PPMS), we investigated whether brain and cervical cord structural changes in lesions and normal-appearing brain tissue (NABT), measured using conventional, magnetization transfer (MT), and diffusion tensor (DT) MRI, are correlated with movement-associated cortical activations measured using functional magnetic resonance imaging (fMRI). From 26 right-handed PPMS patients and 15 right-handed, sex- and age-matched healthy controls, we obtained: (a) brain and cervical cord dual-echo scans and MT ratio (MTR) maps; (b) brain mean diffusivity (D(-)) maps, and (c) f-MRI (flexion-extension of the last four fingers of the right hand). All PPMS patients had no previous symptoms affecting their right upper limbs, which were functionally normal. Healthy volunteers showed more significant activation in the ipsilateral cerebellar hemisphere than PPMS patients. PPMS patients showed greater activation bilaterally in the superior temporal gyrus, ipsilaterally in the middle frontal gyrus, and, contralaterally in the insula/claustrum. In PPMS patients, moderate to strong correlations (r values ranging from 0.59 to 0.68) were found between relative activations of cortical areas located in a widespread network for sensory-motor and multimodal integration and the severity of structural changes of the NABT (as measured using MT and DT MRI) and the severity of cervical cord damage (as measured using MT MRI). This study shows that the pattern of cortical activation of PPMS patients is different from that of normal controls even when performing a motor task with clinically unaffected limbs. It also suggests that cortical reorganization might be able to limit the consequences of MS injury in the brain and cervical cord.

Adult↗
PubMed1995

Effects of eye position on saccadic eye movements and on the neuronal responses to auditory and visual stimuli in cat superior colliculus.

Many neurons in the deeper layers of the superior colliculus (SC) respond to multiple sensory inputs--visual, auditory, and somatic--as well as provide signals essential for saccadic eye movements to targets in different modalities. When the eyes and pinnae are in primary position, the neural map of auditory space is in rough topographic alignment with the map of visual space, and if the auditory map is based solely on headpinna coordinates, any changes in eye position in the orbit will cause misalignment of the maps. We investigated the effects of eye position on the response of sound-sensitive neurons in the SC of cats because previous work on cats and on monkeys had suggested the possibility of species differences in the representation of auditory signals in the SC. We also investigated the effects of eye position on the accuracy of saccades to auditory, visual, and bimodal stimuli. All studies were conducted in alert, trained cats with the head restrained in a fixed position. Neuronal and behavioral responses were studied during periods when the eyes were steadily directed to different positions relative to the position of the sound. Cats showed partial compensation for eye position in making saccades, regardless of the modality of the target, and they showed similar patterns of error in saccades to auditory and visual targets. These behavioral data are consistent with coding the location of visual and auditory targets in the same coordinate system. In the vast majority of intermediate-layer neurons, eye position significantly affected the number of spikes evoked by sound stimuli. For most of these neurons, changes in eye position produced significant shifts in the speaker location producing maximal response. In some neurons, eye position significantly facilitated the magnitude of neuronal response evoked by sounds from a variety of speaker locations. Because few pinna movements could be detected, in is unlikely that these changes in neuronal response could be due to changes in the position of the pinnae. Our results indicate that the deep layers of the SC contain an eye-centered representation of sound location. Because eye position did not affect the percentage of neurons exhibiting multimodal integration, visual and auditory maps appear to remain integrated in the SC even when the eyes are directed eccentrically.(ABSTRACT TRUNCATED AT 400 WORDS)

Acoustic Stimulation↗
PubMed1991

Parallel evolution in mammalian and avian brains: comparative cytoarchitectonic and cytochemical analysis.

Comparative morphology, which is based on the selection theory of evolution, analyses the impact of function upon structure and, therefore, emphasizes the adaptive events and biological advantage during the evolution of organs. A comparison based on analogies is described here as an adequate method. The hypothesis is proposed that the evolution of the brain follows the same trends in birds as in mammals. This hypothesis is proved by (1) allometric studies of brain weight and brain structure volume in relation to body weight in mammals and birds; (2) architectonic studies using image analysis on cell and fibre stains as well as on histochemical preparations and receptor autoradiography; and (3) hodological studies with injections of [3H]leucin, HRP and WGA-HRP. The results reveal a vast amount of structural and functional similarities in avian and mammalian brain organization, especially an expansion of structures that permit multimodal integration capacity in the telencephalon. Thus, a parallel evolution occurred in these two groups of vertebrates. It is argued that this may be a general phenomenon in evolution. A cladistic approach, which is based on the concept of homologies (plesio-, apomorphies), pushes aside the existence of analogies. For this reason, cladism does not seem to be a method to answer questions of evolutionary morphology adequately.

Animals↗
PubMed2005

Motor-maps, navigation and implicit space representation in the hippocampus.

Multiple sensory-motor maps located in the brainstem and the cortex are involved in spatial orientation. Guiding movements of eyes, head, neck and arms they provide an approximately linear relation between target distance and motor response. This involves especially the superior colliculus in the brainstem and the parietal cortex. There, the natural frame of reference follows from the retinal representation of the environment. A model of navigation is presented that is based on the modulation of activity in those sensory-motor maps. The actual mechanism chosen was gain-field modulation, a process of multimodal integration that has been demonstrated in the parietal cortex and superior colliculus, and was implemented as attraction to visual cues (colour). Dependent on the metric of the sensory-motor map, the relative attraction to these cues implemented as gain field modulation and their position define a fixed point attractor on the plane for locomotive behaviour. The actual implementation used Kohonen-networks in a variant of reinforcement learning that are well suited to generate such topographically organized sensory-motor maps with roughly linear visuo-motor response characteristics. In the following, it was investigated how such an implicit coding of target positions by gain-field parameters might be represented in the hippocampus formation and under what conditions a direction-invariant space representation can arise from such retinotopic representations of multiple cues. Information about the orientation in the plane--as could be provided by head direction cells--appeared to be necessary for unambiguous space representation in our model in agreement with physiological experiments. With this information, Gauss-shaped "place-cells" could be generated, however, the representation of the spatial environment was repetitive and clustered and single cells were always tuned to the gain-field parameters as well.

Algorithms↗
PubMed2005

Testing models of thalamic dysfunction in schizophrenia using neuroimaging.

Neural models of schizophrenia have implicated the thalamus in deficits of early sensory processing and multimodal integration. We have reviewed the existing neuroimaging literature for evidence in support of models that propose abnormalities of thalamic relay nuclei, the mediodorsal thalamic nucleus, and large-scale cortico-thalamic networks. Thalamic volume reduction was found in some but not all studies. Studies of the early stages of schizophrenia suggest that thalamic volume reduction is present early in the course of the illness. Functional imaging studies have revealed task related abnormalities in several cortical and subcortical areas including the thalamus, suggesting a disruption of distributed thalamocortical networks. Chemical imaging studies have provided evidence for a loss of thalamic neuronal integrity in schizophrenia. There is, at present, inadequate data to support the hypothesis that schizophrenia is associated with abnormalities of sensory relay or association nuclei. There is evidence for a perturbation of cortico-thalamic networks, but further research is needed to elucidate the underlying mechanisms at the cellular and systems levels. The challenges ahead include better delineation of thalamic structure and function in vivo, the combination of genetic and imaging techniques to elucidate the genetic contributions to a thalamic phenotype of schizophrenia, and longitudinal studies of thalamic structure and function.

Animals↗
PubMed2006

LONI visualization environment.

Over the past decade, the use of informatics to solve complex neuroscientific problems has increased dramatically. Many of these research endeavors involve examining large amounts of imaging, behavioral, genetic, neurobiological, and neuropsychiatric data. Superimposing, processing, visualizing, or interpreting such a complex cohort of datasets frequently becomes a challenge. We developed a new software environment that allows investigators to integrate multimodal imaging data, hierarchical brain ontology systems, on-line genetic and phylogenic databases, and 3D virtual data reconstruction models. The Laboratory of Neuro Imaging visualization environment (LONI Viz) consists of the following components: a sectional viewer for imaging data, an interactive 3D display for surface and volume rendering of imaging data, a brain ontology viewer, and an external database query system. The synchronization of all components according to stereotaxic coordinates, region name, hierarchical ontology, and genetic labels is achieved via a comprehensive BrainMapper functionality, which directly maps between position, structure name, database, and functional connectivity information. This environment is freely available, portable, and extensible, and may prove very useful for neurobiologists, neurogenetisists, brain mappers, and for other clinical, pedagogical, and research endeavors.

Brain Mapping↗
PubMed2005

Enhanced recovery after surgery: a consensus review of clinical care for patients undergoing colonic resection.

BACKGROUND & AIMS: Clinical care of patients undergoing colonic surgery differs between hospitals and countries. In addition, there is considerable variation in rates of recovery and length of hospital stay following major abdominal surgery. There is a need to develop a consensus on key elements of perioperative care for inclusion in enhanced recovery programmes so that these can be widely adopted and refined further in future clinical trials. METHODS: Medline database was searched for all clinical studies/trials relating to enhanced recovery after colorectal resection. Relevant papers from the reference lists of these articles and from the authors' personal collections were also reviewed. A combination of evidence-based and consensus methodology was used to develop the resulting enhanced recovery after surgery (ERAS) clinical care protocol. RESULTS AND CONCLUSIONS: Within traditional perioperative practice there is considerable evidence supporting a range of manoeuvres which, in isolation, may improve individual aspects of recovery after colonic surgery. The present manuscript reviews these issues in detail. There is also growing evidence that an integrated multimodal approach to perioperative care can result in an overall enhancement of recovery. However, effects on major morbidity and mortality remain to be determined. A protocol is presented which is in current use by the ERAS Group and may provide a standard of care against which either current or future novel elements of an enhanced recovery approach can be tested for their effect on outcome.

Colon↗
PubMed2005

Prenatal hypoxia impairs memory function but does not result in overt structural alterations in the postnatal chick brain.

We showed previously that hypoxia in ovo impairs memory consolidation in the chick tested 2 days after hatching. Our present aim was to investigate whether we could detect any morphological effects of the same prenatal hypoxia. Hypoxia was induced by half-wrapping the egg with an impermeable membrane from either days 10-18 (W10-18 chicks) or days 14-18 (W14-18 chicks) of incubation (hatching approximately 21 days). Measurement of blood gases showed that reducing the surface area of the egg for gas exchange resulted in reduced pO2 and increased pCO2 2 days after wrapping. Although this hypoxia was sufficient to impair cognitive processing in the postnatal chick, our data suggest that it did not produce overt structural alterations or changes in the number of neurons, glutamine synthetase-immunoreactive cells or immunoreactivity to synaptophysin in the presynaptic vesicles in the multimodal integration (cortical) area compared to controls. Hence, we found no differences in the astrocyte to neuron ratio, synaptic density and/or vesicle number. Analysis of the ontogeny of astrocytes during the prenatal period of hypoxia showed them to be present at embryonic day 12, but not at the earlier ages examined. Although we found cognitive deficits in chicks from embryos made hypoxic during incubation, our regimen of prenatal hypoxia did not alter any of the parameters measured in the brains. This does not preclude the possibility that changes have occurred at the cellular or molecular levels or in specific neurotransmitter systems.

Animals↗
PubMed2026

Artificial intelligence agents and agentic artificial intelligence applied to precision medicine.

Precision medicine seeks to individualise care by integrating multimodal biomedical data, yet most deployed clinical artificial intelligence (AI) remains assistive, providing predictions without managing workflows or adapting autonomously. Agentic AI, built on large language models (LLMs), has emerged as a paradigm characterised by autonomy, goal-directed reasoning, memory, planning and tool use. This review synthesises evidence on agentic AI and LLMs applied to precision medicine, encompassing drug discovery, genomics, oncology, rare disease diagnostics and clinical pharmacology. This review also examines architectural components, recent validation milestones and emerging challenges, including hallucination, sociodemographic bias and evolving regulatory frameworks across the FDA, the EU AI Act and the WHO.

agentic AI↗