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Interactions between the dorsal and the ventral pathways in mental rotation: an fMRI study.

In this fMRI study, we examined the relationship between activations in the inferotemporal region (ventral pathway) and the parietal region (dorsal pathway), as well as in the prefrontal cortex (associated with working memory), in a modified mental rotation task. We manipulated figural complexity (simple vs. complex) to affect the figure recognition process (associated with the ventral pathway) and the amount of rotation (0 degrees vs. 90 degrees), typically associated with the dorsal pathway. The pattern of activation not only showed that both streams are affected by both manipulations, but also showed an overadditive interaction. The effect of figural complexity was greater for 90 degrees rotation than for 0 degrees in multiple regions, including the ventral, dorsal, and prefrontal regions. In addition, functional connectivity analyses on the correlations across the time courses of activation between regions of interest showed increased synchronization among multiple brain areas as task demand increased. The results indicate that both the dorsal and the ventral pathways show interactive effects of object and spatial processing, and they suggest that multiple regions interact to perform mental rotation.

Adult↗

Initiation and spread of epileptiform discharges in the methylazoxymethanol acetate rat model of cortical dysplasia: functional and structural connectivity between CA1 heterotopia and hippocampus/neocortex.

Neuronal migration disorders (NMDs) are often associated with medically intractable epilepsy. In utero injection of methylazoxymethanol acetate into pregnant rats gives rise to dysplastic cell clusters ("heterotopia") in hippocampus (and nearby regions), providing an animal model of NMD. In the present study, we have examined the structural and functional integration of hippocampal heterotopic cells into circuits that link the heterotopia with surrounding "normal" brain. Bi-directional morphological connectivity between the heterotopia and hippocampus/neocortex was demonstrated using the neurotracer, biotinylated dextran amine. Single cell recordings in hippocampal slices showed that heterotopia neurons form functional connections with the surrounding hippocampus and neocortex. However, simultaneous field recordings from the CA1 heterotopia, normotopic hippocampus, and neocortex indicated that epileptiform discharges (spontaneous events seen in slices bathed with high [K+]o and bicuculline) were rarely initiated in the heterotopia (although the heterotopia was capable of generating epileptiform discharges independently of normal brain regions). Further, in most of the experiments, the aberrant connectivity provided by CA1 heterotopia failed to function as a "bridge" for epileptiform discharges to propagate directly from low-threshold hippocampus to neocortex. These data do not support the hypothesis that NMDs (heterotopic cell populations) serve as a focus and/or trigger for epileptiform activity, and/or facilitate propagation of epileptiform events.

Abnormalities, Drug-Induced↗

Cerebral mechanisms involved in word reading in dyslexic children: a magnetic source imaging approach.

The purpose of the present investigation was to describe spatiotemporal brain activation profiles during word reading using magnetic source imaging (MSI). Ten right-handed dyslexic children with severe phonological decoding problems and eight age-matched non-impaired readers were tested in two recognition tasks, one involving spoken and the other printed words. Dyslexic children's activation profiles during the printed word recognition task consistently featured activation of the left basal temporal cortices followed by activation of the right temporoparietal areas (including the angular gyrus). Non-impaired readers showed predominant activation of left basal followed by left temporoparietal activation. In addition, we were able to rule out the hypothesis that hypoactivation of left temporoparietal areas in dyslexics was due to a more general cerebral dysfunction in these areas. Rather, it seems likely that reading difficulties in developmental dyslexia are associated with an aberrant pattern of functional connectivity between brain areas normally involved in reading, namely ventral visual association cortex and temporoparietal areas in the left hemisphere. The interindividual consistency of activation profiles characteristic of children with dyslexia underlines the potential utility of this technique for examining neurophysiological changes in response to specific educational intervention approaches.

Adolescent↗

An integrative model of developing tinnitus based on recent neurobiological findings.

Brain imaging studies suggest that the functional connectivity of various limbic, prefrontal, and temporal brain structures can be understood as the basis for particularly intense experiences of impairment and many secondary symptoms of decompensated tinnitus. Results to date suggest cortical plasticity as a likely mechanism to be involved in the chronic progression of tinnitus. Relationships between the processing of auditory signals and neural networks associated with somatosensory, attentional, cognitive and emotional processes are relevant for the genesis of the pathology. However, the neural bases of subjective impairment in tinnitus patients are unknown. An integrative model of developing tinnitus is presented here, based on the most recent neurophysiological data in current discussion. We assume the involvement of altered brain functions in the development and maintenance of perceptions of tinnitus and outline various possibilities which could contribute to decompensation and chronic progression. The discussions surrounding present models of the generation of tinnitus and its reinforcement to the point of decompensation make it clear that a unidimensional approach in clinical interventions is insufficient. Patients with decompensated tinnitus suffer from a complex somatic and psychological disorder. The interactive processes involving emotions, behaviour and symptoms, as well as the high co-morbidity with affective and psychosomatic illnesses and the important influence of psychosocial factors (distress), make the use of stage-appropriate interdisciplinary treatments necessary.

Brain↗

Denervation-induced sprouting of intact peripheral afferents into the cuneate nucleus of adult rats.

In adult monkeys with dorsal rhizotomies extending from the second cervical (C2) to the fifth thoracic (T5) vertebrae, cortex deprived of its normal inputs regained responsiveness to inputs conveyed by intact peripheral afferents from the face [T.P. Pons, P.E. Garraghty, A.K. Ommaya, J.H. Kaas, E. Taub, M. Mishkin, Massive reorganization of the primary somatosensory cortex after peripheral sensory deafferentation, Science 252 (1991) 1857-1860]. It has been suggested that the extent of this massive topographic reorganization may be due to the establishment of novel connections between intact afferents and neurons denervated after dorsal rhizotomy [P.E. Garraghty, D.P. Hanes, S.L. Florence, J.H. Kaas, Pattern of peripheral deafferentation predicts reorganizational limits in adult primate somatosensory cortex, Somatosens. Motor Res. 11 (1994) 109-117]. Using adult rats with comparably extensive dorsal rhizotomies, we employed anatomical tracing techniques to address this possibility. Subcutaneous hindpaw injections of horseradish peroxidase conjugated to either wheat germ agglutinin or cholera toxin subunit B revealed aberrant expansions of gracile projections into the cuneate and, in one case, external cuneate nucleus within three months of the deafferentation. It seems plausible that such modest sprouting of ascending projections at the level of the brainstem may form functional connections which, through divergence, ultimately drive a larger population of neurons in cortex. This new growth may well account for both the substantial cortical reorganization observed in the 'Silver Spring monkeys' [T.P. Pons, P.E. Garraghty, A.K. Ommaya, J.H. Kaas, E. Taub, M. Mishkin, Massive reorganization of the primary somatosensory cortex after peripheral sensory deafferentation, Science 252 (1991) 1857-1860] and the 'referred sensation' phenomena (see J.P. Donoghue, Plasticity of adult sensorimotor representations, Curr. Opin. Neurobiol., 5 (1995) 749-754 for review) reported to follow proximal limb amputations in humans.

Afferent Pathways↗

Calcineurin phosphatase in signal transduction: lessons from fission yeast.

Calcineurin (protein phosphatase 2B), the only serine/threonine phosphatase under the control of Ca2+/calmodulin, is an important mediator in signal transmission, connecting the Ca2+-dependent signalling to a wide variety of cellular responses. Furthermore, calcineurin is specifically inhibited by the immunosuppressant drugs cyclosporin A and tacrolimus (FK506), and these drugs have been a powerful tool for identifying many of the roles of calcineurin. Calcineurin is enriched in the neural tissues, and also distributes broadly in other tissues. The structure of the protein is highly conserved from yeast to man. The combined use of powerful genetics and of specific calcineurin inhibitors in fission yeast Schizosaccharomyces pombe (S. pombe) identified new components of the calcineurin pathway, and defined new roles of calcineurin in the regulation of the many cellular processes. Recent data has revealed functional interactions in which calcineurin phosphatase is involved, such as the cross-talk between the Pmk1 MAP kinase signalling, or the PI signalling. Calcineurin also participates in membrane traffic and cytokinesis of fission yeast through its functional connection with members of the small GTPase Rab/Ypt family, and Type II myosin, respectively. These findings highlight the potential of fission yeast genetic studies to elucidate conserved elements of signal transduction cascades.

Calcineurin↗

Correlations of neuronal spike discharges of VL neurons during spontaneous firing and during the activity evoked by peripheral stimulation.

The temporal relations between simultaneously recorded neurons of the nucleus ventralis lateralis (VL) of cat thalamus were studied. The interaction and the functional connections between individual VL neurons are described. This was achieved with an application of cross correlation techniques. The response patterns of different individual neurons to somatic sensory and photic stimuli were also analyzed. For the purpose of classifying neurons as thalamocortical relay cells (T-C) and non relay cells (N-C) which do not project to the motor sensory cortex antidromic cortical stimulation was used. This stimulation was also used as conditioning one when proceeded peripheral stimuli. To analyze the nonspecific specific interactions upon single neurons conditioning photic stimuli were applied. The results show that T-C neurons are antidromically excited from a wide cortical areas and that the functional interaction between T-C neurons is mediated by a shared input from common sources. It is further postulated that N-C cells interposed between relay neurons subserve the functions of gating units modifying the neuronal network of lateral ventral nucleus of the thalamus.

Action Potentials↗

Does intranasal application of zinc sulfate produce anosmia in the mouse? An olfactometric and anatomical study.

Mice pre-trained in an olfactometer were tested daily on odor detection and discrimination tasks after irrigation of their olfactory epithelium in each naris with 50 microl of 5% zinc sulfate or saline. Anterograde transport of a wheatgerm agglutinin-horseradish peroxidase (WGA-HRP) conjugate from the epithelium to the olfactory bulb was used to assess anatomical connectivity in these and in mice that were used only for histological analyses. One day after treatment, saline controls performed at high levels of accuracy in detecting vapor from solutions of 5-0.01% ethyl acetate and in an odor discrimination task but most ZnSO4-treated mice performed at chance for 5-30 days before showing recovery. Although dense WGA-HRP reaction product was found in the accessory olfactory bulb, there was little or no evidence for axonal transport to glomeruli of the main olfactory bulb in the first 4-8 days after treatment. These results demonstrate that intranasal application of ZnSO4 to mice produces a brief but essentially total disruption of functional connections from the olfactory epithelium to the main olfactory bulb and a corresponding transient anosmia.

Acetates↗

Age-dependent modulation of PKC isoforms and NOS activity and expression in rat cortex, striatum, and hippocampus.

Recently, PKC has been shown to play a pivotal role in physiological brain functions, connected with the memorizing processes and their correspondent progressive decline with brain aging. We have studied the age-dependent changes of PKC isoforms activity in connection with NOS expression and activity in specific brain areas such as hippocampus, cortex and striatum. Starting from middle aged rats, a significant inactivation of c-PKC isoforms occurred, with respect to young animals, in all the brain areas analysed. However, in middle aged animals, no significant changes in the protein level of the main PKC isoforms expressed in brain were demonstrated. Moreover, in the hippocampus and in the cortex of middle aged rats, an increased level of NOS activity--a substrate of PKC whose phosphorylation by the kinase inhibits NOS activity--has been demonstrated, reaching the same level that occurs in striatum. However, only in the hippocampus, deeply implicated in learning and memory functions, an increase of nuclear c-PKC activity and of i- and n-NOS mRNA levels was shown. Taken together, these results indicate that down-regulation of c-PKC activity occurring in middle aged rats, leads to higher levels of NO that may contribute to cell damage and to alter the neuronal physiological functions as described in older animals. Moreover, in the hippocampus, our results suggest a relationship between the translocation of c-PKC to the nucleus and the enhancement of the expression of i- and n-NOS.

Aging↗

Functional structure in lymphoepithelial cooperation.

With the help of electron microscopic investigations the morphological and functional connection of the epithelialial and lymphoid elements was examined in the lymphoepithelial organs (thymus, bursa of Fabricius, tonsils, Peyer's patches, gland of Harder). In all these organs special receptor cells were demonstrated, which may play a role in the uptake and transfer of the antigen. In the cytoplasm they all contain characteristic flattened vacuoles, with walls similar to the structure of the cell membrane. Formation of these bodies is identified with the striated bodies of micropinocytosis vermiformis and it was observed that the endocytosis start with a disintegration of the cell membrane which enters with the absorbed antigen in characteristic form into the cytoplasm of the epithel cell and induces the process of cellular immunity. Besides the function of lacrimal secretion the Harder's gland, as a lymphoepithelial organ is full of plasma cells, which constitutes the main lymphoid elements of this organ.

Animals↗

Neural connectivity in hand sensorimotor brain areas: an evaluation by evoked field morphology.

The connectivity pattern of the neural network devoted to sensory processing depends on the timing of relay recruitment from receptors to cortical areas. The aim of the present work was to uncover and quantify the way the cortical relay recruitment is reflected in the shape of the brain-evoked responses. We recorded the magnetic somatosensory evoked fields (SEF) generated in 36 volunteers by separate bilateral electrical stimulation of median nerve, thumb, and little fingers. After defining an index that quantifies the shape similarity of two SEF traces, we studied the morphologic characteristics of the recorded SEFs within the 20-ms time window that followed the impulse arrival at the primary sensory cortex. Based on our similarity criterion, the shape of the SEFs obtained stimulating the median nerve was observed to be more similar to the one obtained from the thumb (same median nerve innervation) than to the one obtained from the little finger (ulnar nerve innervation). In addition, SEF shapes associated with different brain regions were more similar within an individual than between subjects. Because the SEF morphologic characteristics turned out to be quite diverse among subjects, we defined similarity levels that allowed us to identify three main classes of SEF shapes in normalcy. We show evidence that the morphology of the evoked response describes the anatomo-functional connectivity pattern in the primary sensory areas. Our findings suggest the possible existence of a thalamo-cortico-thalamic responsiveness loop related to the different classes.

Adult↗

Frontal lobe networks for effective processing of ambiguously expressed emotions in humans.

This study examines the neural substrates involved in the recognition of ambiguous facial expressions using functional magnetic resonance imaging. Subjects performed two tasks, one in which they judged facial expressions and another in which they identified gender. Subtraction between ambiguous expression and clear expression conditions revealed the activation of anterior cingulate (ACC), medial frontal (MeFG) and bilateral inferior frontal gyrus (IFG). Structural equation modeling showed that the functional connectivity between these areas was greater with the ambiguous expressions than with the clear ones. The activation of the ACC, MeFG, and right IFG was greater with ambiguous expressions than with ambiguous gender. These results suggest that the neural network involving these frontal regions plays a crucial role in the processing of the ambiguously expressed facial emotions.

Adult↗

Can regenerating axons recapitulate developmental guidance during recovery from spinal cord injury?

The precise wiring of the adult mammalian CNS originates during a period of stunning growth, guidance and plasticity that occurs during and shortly after development. When injured in adults, this intricate system fails to regenerate. Even when the obstacles to regeneration are cleared, growing adult CNS fibres usually remain misdirected and fail to reform functional connections. Here, we attempt to fill an important niche related to the topics of nervous system development and regeneration. We specifically contrast the difficulties faced by growing fibres within the adult context to the precise circuit-forming capabilities of developing fibres. In addition to focusing on methods to stimulate growth in the adult, we also expand on approaches to recapitulate development itself.

Animals↗

Functional magnetic resonance imaging evidence for disrupted basal ganglia function in schizophrenia.

OBJECTIVE: This study was an examination of basal ganglia dysfunction in schizophrenia using functional magnetic resonance imaging (fMRI). METHOD: The authors used a motor sequencing task to investigate activation of the caudate, anterior putamen plus globus pallidus, and posterior putamen plus globus pallidus in eight subjects with schizophrenia and 12 group-matched comparison subjects. Differences in activation of the thalamus, the target of direct output from the globus pallidus, were also examined. RESULTS: The schizophrenia subjects showed significant bilateral deficits in the posterior putamen, globus pallidus, and thalamus but not the anterior putamen plus globus pallidus or caudate. Functional connectivity analysis revealed that the deficits in thalamic activation were related to deficits in posterior putamen and globus pallidus activation. CONCLUSIONS: These results provide fMRI evidence for basal ganglia dysfunction in subjects with schizophrenia and suggest that this deficit results in disrupted outflow to the thalamus. These deficits may underlie the behavioral impairments in goal-directed action observed in schizophrenia.

Adult↗

Neurocorrelates of nocturnal enuresis in pre-adolescent children.

INTRODUCTION: Nocturnal enuresis (NE) is a common neurodevelopmental condition, yet its underlying neural mechanisms remain unclear. This study leverages the large-scale Adolescent Brain Cognitive Development (ABCD) dataset to identify structural and functional brain correlates associated with active symptoms and the resolution of bedwetting. METHODS: Using cross-sectional data from 3472 participants aged 9-10 years, children were categorized into three groups: active nocturnal enuresis (ANE, n = 225), history of nocturnal enuresis (HNE, n = 1171), and healthy control groups (CG, n = 2076). Multimodal neuroimaging protocol evaluated macrostructural properties via structural MRI (sMRI), microstructural white matter integrity via diffusion MRI (dMRI), and functional connectivity via resting-state fMRI (fMRI). Group differences were evaluated using linear models within an ANCOVA framework, adjusting for intracranial volume and handedness with False Discovery Rate (FDR) correction. RESULTS: Compared to controls, the ANE group exhibited a significant volume deficit in the right caudate, decreased sulcal depth in the left insula, and lower internal correlation within the Cingulo-Opercular Network (CON). Conversely, the dry HNE group demonstrated significant structural adaptations, including bilaterally larger putamen volumes and increased right caudate volume compared to the ANE group. The HNE group also showed increased microstructural density (decreased mean diffusivity) in the bilateral hippocampus and an increased cortical surface area in the left insula. Both NE groups demonstrated persistently reduced functional coupling within the CON. CONCLUSIONS: Nocturnal enuresis appears to be associated with a potential complex central signaling deficits. Reduced internal correlation within the CON across both active and former bedwetters indicates a potential for impairment in processing internal homeostatic bladder signals during sleep.

Humans↗

From grid cells to place cells: a mathematical model.

Anatomical connectivity and recent neurophysiological results imply that grid cells in the medial entorhinal cortex are the principal cortical inputs to place cells in the hippocampus. The authors propose a model in which place fields of hippocampal pyramidal cells are formed by linear summation of appropriately weighted inputs from entorhinal grid cells. Single confined place fields could be formed by summing input from a modest number (10-50) of grid cells with relatively similar grid phases, diverse grid orientations, and a biologically plausible range of grid spacings. When the spatial phase variation in the grid-cell input was higher, multiple, and irregularly spaced firing fields were formed. These observations point to a number of possible constraints in the organization of functional connections between grid cells and place cells.

Animals↗

[Pelvic inflammatory disease--prophylactic trends].

On the basis of his own observations and experience, compared with literary data from recent years, the author think that the most proper planning of prophylactic measures in connection with pelvic inflammatory disease (PID) could be carried out after thorough study and good knowledge of risk factors and groups. Some with special medico-social significance are outlined among them: age groups up to 20,20--24 and 25--29 years; sexual education and behaviour, delivery and postpartal period, intrauterine diagnostic and therapeutic manipulations, intrauterine contraceptive devices, abdominal operative interventions with special significance of the operations for acute appendicitis and ectopic pregnancy; latent, clinically unsuspected, or accompanying other diseases PID. The necessity of effective cooperation between a gynecologist and physicians from other specialties (surgeons, internists, urologists, etc.) for timely establishment of a latent disease, examination of a sexual partner, ect. Important condition for effective work is improvement of the functional connections and bilateral information between polyclinic obstetric-gynecological sector gynecological ward.

Adolescent↗

Vagal influences over mast cells.

The established microanatomical association of rat intestinal mucosal mast cells (IMMC) and mucosal nerves raises the possibility that there is crosstalk between mast cells and extrinsic nerves that connect to the CNS. The idea of mast cell-CNS interactions is supported by the demonstration that rat mast cell protease II (RMCPII), found predominantly in IMMC, can be conditionally released by pairing an audio-visual cue with antigen challenge. That the vagus nerve is involved in the IMMC-nerve axis was further demonstrated in a series of our studies showing that: (a) vagal afferents penetrate the small intestinal mucosa and contact IMMC; (b) vagotomy causes a reduction in IMMC density, suggesting a trophic relationship (typical of nerve-target interactions); and (c) stimulation of the cervical vagus causes an increase in histamine and serotonin in IMMC. To further investigate the IMMC-nerve axis in a model of post-inflammatory bowel disorders, infection with Nippostrongylus brasiliensis (Nb) was used to demonstrate an increase in mast cell numbers in the intestinal mucosa and mucosal nerve remodelling with hyperinnervation. Administration of Nb antigen resulted in dramatic increases in mesenteric afferent nerve firing in Nb infected rats, that was absent in sham animals. Moreover, challenge of post-Nb rats with 2-methyl-5HT caused increased mesenteric afferent firing, indicating that vagal afferent innervation remains intact in the post-infection state. These data suggest a functional connection between mast cells and extrinsic afferent nerves. Nb infection provides a useful model of altered communication between IMMCs, peripheral nerves and the CNS, as may occur in post-inflammatory disease states. Since a close anatomical relationship has also previously been demonstrated between nerves and IMMC in humans, further understanding the mast cell-nerve axis may be of critical importance in the development of treatments for various human disease states, including functional bowel disorders.

Animals↗