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At least 973 records · Page 54Linked to original sources
PubMed2001

On multivariate spectral analysis of fMRI time series.

Most of functional magnetic resonance imaging (fMRI) time series analysis is based on single voxel data evaluation using parametric statistical tests. The result of such an analysis is a statistical parametric map. Voxels with a high significance value in the parametric test are interpreted as activation regions stimulated by the experimental task. However, for the investigation of functional connectivities it would be interesting to get some detailed information about the temporal dynamics of the blood oxygen level-dependent (BOLD) signal. For investigating that behavior, a method for fMRI data analysis has been developed that is based on Wiener theory of spectral analysis for multivariate time series. Spectral parameters such as coherence measure and phase lead can be estimated. The resulting maps give detailed information on brain regions that belong to a network structure and also show the temporal behavior of the BOLD response function. This paper describes the method and presents a visual fMRI experiment as an example to demonstrate the results.

Adult↗
PubMed1992

The pars tuberalis of the hypophysis: a modulator of the pars distalis?

The pineal hormone melatonin is known to influence circadian systems. Melatonin is also ascribed to mediate photoperiodic effects on the regulation of the hypothalamo-hypophyseal-gonadal axis. Other endocrine actions, especially a thyrotropic influence, have been postulated. Site and mechanism of action of melatonin, however, are still matters of speculation. In search of a functional cascade of (i) photoperiodic stimuli, (ii) their hormonal messenger melatonin, and (iii) endocrine targets, the pars tuberalis has gained a key position. The recent discovery and characterization of melatonin receptors located in the pars tuberalis of several species support such a functional significance. Earlier results point to a functional connection of the pars tuberalis with the pineal gland: the pars tuberalis is known for a pattern of differentiation distinctly different from other parts of the adenohypophysis. It contains a specific cell population with a morphology typical of peptide secreting cells. Like the hypothalamic nerve endings of the median eminence, they are in close contact with the primary plexus of the portal system. In contrast to secretory cells of the pars distalis, the specific cells of the pars tuberalis do not respond with morphological alterations to functional changes of peripheral endocrine glands. Yet, photoperiodic stimuli obviously influence morphology and functional activity of the pars tuberalis-specific cells. Investigations during recent years have led to the tentative conclusion that the pars tuberalis represents the hypophysial "receptor" for melatonin as the chemical messenger of photoperiodic stimuli. Depending on melatonin secretion pattern and melatonin receptivity, the pars tuberalis seems to modulate at least gonadotropic and thyrotropic activity of the pars distalis via a peptide hormone distributed in the pars distalis by the portal plexus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

[The connection of visual evoked potentials with the subjective differences between emotional expressions of the "schematic face"].

Human cortical visual potentials (VEP) were studied to obtain electrophysiological data concerning face discrimination and to compare them with the direct estimates of differences between faces obtained in the previous publications. The present schematic faces varied in curvature of a mouth and/or declination of eyebrows. These features determined the emotional expression of the schematic faces. We recorded the VEP as the response to the instant replacement of one schematic face (referent stimulus) by an other one (test stimulus) rather then to presentation of a single stimulus. Thus we recorded direct electrophysiological differences between schematic faces. A characteristic feature of this approach was the application of the set of functionally connected test stimuli with monotonously increasing values of differences between the referent and test stimuli. In a result of analysis the complex of components P120-N180-P230 in sites O1, O2, P3, P4, T5, T6 was described. Interpeaks amplitudes of the components shows high correlations with subjective differences between the same pairs of stimuli as well as with physical (configurative) differences between stimuli measured as the angles of lines, defining curvature of a mouth and a declination of eyebrows. The highest correlation with subjective estimates of emotional differences between faces was shown by interpeaks amplitudes N180-P230 in sites O1 and P3. In the some time the interpeaks amplitudes P120-N180 in sites O1 and T5 reflected highest correlation between configurative measures and subjective estimates of stimuli differences.

Electroencephalography↗
PubMed1995

A method for detecting the time course of correlation between single-unit activity and EMG during a behavioral task.

The chance that a change in excitability of one neuron leads to a change in excitability of another is likely to vary within a single volitional act. This temporal variability in functional connectivity is impossible to assess with standard analytical procedures to accurately that measure the correlation between such elements. This reports describes a technique designed to overcome this limitation by expressing a correlation measure calculated repeatedly in short epochs throughout a behavioral trial. The activity of two elements, a motor cortical neuron and a shoulder muscle, that might take place during a drawing task was first simulated so that the correlation could be manipulated. Various correlation algorithms (standard cross-correlation, spike-triggered average, impulse-response function, impulse-response surface) were tested with these data. Spike trains from a monkey's motor cortex and rectified EMG from its posterior deltoid muscle were compared using the same techniques and shown to have a correlation that changed in a characteristic manner throughout a task that required the monkey to draw a sinusoid.

Algorithms↗
PubMed2000

Autonomic reactivity of panic patients during a CO2 inhalation procedure.

The objectives of this study were to compare continuous subjective and physiological responses of panic disorder patients and normal controls during 5% CO2 inhalation. Psychophysiological responses of panic disorder patients (n = 42) and controls (n = 25) were monitored during baseline (20 min), 5% CO2 inhalation (20 min), and recovery (20 min). The data were compared at baseline and over periods of the experiment using analysis of variance. A subgroup of patients who experienced panic attacks during the CO2 inhalation (n = 12) were significantly different from the other subjects on baseline heart rate and on variability of systolic and diastolic blood pressure, skin conductance, and breathing variability (length and number of breathing pauses and length of breathing cycle variability). Inspection of the data showed that elevation in blood pressure and breathholding were present during some of the panic attacks, suggesting that some attacks may represent a complex psychophysiological response with elements of a "freezing" reaction, well described in animal experiments, which can quickly shift to a "fight/flight" reaction that is usually characterized by an increase in heart and breathing rate. However, some patients had only minimal changes in breathing and others had minimal psychophysiological changes during the time they indicated that they had a panic attack. Panic attacks are not homogeneous and may be characterized by a variety of physiological and cognitive responses. This may indicate that biological mechanisms of panic include abnormality in many functionally connected areas of the brain responsible for complex psychophysiological reactions to multiple threatening situations.

Administration, Inhalation↗
PubMed2003

Spontaneous initiation and termination of complex rhythms in cardiac cell culture.

INTRODUCTION: Complex cardiac arrhythmias often start and stop spontaneously. These poorly understood behaviors frequently are associated with pathologic modification of the structural heterogeneity and functional connectivity of the myocardium. To evaluate underlying mechanisms, we modify heterogeneity by varying the confluence of embryonic chick monolayer cultures that display complex bursting behaviors. A simple mathematical model was developed that reproduces the experimental behaviors and reveals possible generic mechanisms for bursting dynamics in heterogeneous excitable systems. METHODS AND RESULTS: Wave propagation was mapped in embryonic chick myocytes monolayers using calcium-sensitive dyes. Monolayer confluence was varied by plating cultures with different cell densities and by varying times in culture. At high plating densities, waves propagate without breaks, whereas monolayers plated at low densities display spirals with frequent breaks and irregular activation fronts. Monolayers at intermediate densities display bursting rhythms in which there is paroxysmal starting and stopping of spiral waves of activity. Similar spatiotemporal patterns of activity were also observed as a function of the time in culture; irregular activity dominates the first 30 hours, followed by repetitive bursting dynamics until 54 hours, after which periodic target patterns or stable spirals prevail. In some quiescent cultures derived from older embryos, it was possible to trigger pacemaker activity following a single activation. We are able to reproduce all of these behaviors by introducing spatial heterogeneity and varying neighborhood size, equivalent to cell connectivity, in a spontaneous cellular automaton model containing a rate-dependent fatigue term. CONCLUSION: We observe transitions from irregular propagating waves, to spiral waves that spontaneously start and stop, to target waves originating from localized pacemakers in cell culture and a simple theoretical model of heterogeneous excitable media. The results show how physiologic properties of spontaneous activity, heterogeneity, and fatigue can give rise to a wide range of different complex dynamic behaviors similar to clinically observed cardiac arrhythmias.

Algorithms↗
PubMed2005

The neurobiology of aging.

Basic principles of the neurobiology of aging were reviewed within selected topic areas chosen for their potential relevance to epileptogenesis in the aging brain. The availability of National Institute on Aging-supported aged mouse and rat strains and other biological resources for studies of aging and age-associated diseases was presented, and general principles of animal use in gerontological research were discussed. Neurobiological changes during normal brain aging were compared and contrasted with neuropathological events of Alzheimer's disease (AD) and age-associated memory impairment (AAMI). Major themes addressed were the loss of synaptic connections as vulnerable neurons die and circuits deteriorate in AD, the absence of significant neuron loss but potential synaptic alteration in the same circuits in AAMI, and the effects of decreased estrogen on normal aging. The "calcium hypothesis of brain aging" was examined by a review of calcium dyshomeostasis and synaptic communication in aged hippocampus, with particular emphasis on the role of L-type voltage-gated calcium channels during normal aging. Established and potential mechanisms of hippocampal plasticity during aging were discussed, including long-term potentiation, changes in functional connectivity, and increased gap junctions, the latter possibly being related to enhanced network excitability. Lastly, application of microarray gene chip technology to aging brain studies was presented and use of the hippocampal "zipper slice" preparation to study aged neurons was described.

Aging↗
PubMed2005

CRH stimulates POMC activity and corticosterone production in dermal fibroblasts.

It has been previously documented that human skin cells including epidermal keratinocytes and dermal fibroblasts produce and process proopiomelanocortin (POMC), corticotropin releasing hormone (CRH), and express functional CRH receptors type-1 (CRH-R1). The skin also has corticosteroidogenic activity, suggesting a functional connection between these elements. In the current study, we found that human dermal fibroblasts (but not normal epidermal keratinocytes) respond to CRH with stimulation of cAMP, with POMC gene and protein expression, and ACTH production and release. Furthermore, CRH and ACTH stimulate production of corticosterone in fibroblasts, with ACTH being more potent. Although cortisol-immunoreactivity accumulation/production in fibroblasts has been detected by ELISA, it appears to be constitutive (not affected by CRH or ACTH). These effects are absent in keratinocytes. Therefore, we propose that fibroblasts but not keratinocytes display a functional CRH-POMC-corticosteroid axis organized similarly to the hypothalamus-pituitary-adrenal (HPA) axis. However, it diverges from the HPA organization in its distal step, where CRH and ACTH stimulate production of corticosterone, instead of cortisol.

Adrenocorticotropic Hormone↗
PubMed2007

Functional neural circuits for mental timekeeping.

Theories of mental timekeeping suggest frontostriatal networks may mediate performance of tasks requiring precise timing. We assessed whether frontostriatal networks are functionally integrated during the performance of timing tasks. Functional magnetic resonance imaging (fMRI) data from 31 healthy adults were collected during performance of several different types of discrete interval timing tasks. Independent component analysis (ICA) was used to examine functional connectivity within frontostriatal circuits. ICA identifies groups of spatially discrete brain regions sharing similar patterns of hemodynamic signal change over time. The results confirm the existence of a frontostriatal neural timing circuit that includes anterior cingulate gyrus, supplementary motor area, bilateral anterior insula, bilateral putamen/globus pallidus, bilateral thalamus, and right superior temporal gyrus and supramarginal gyrus. Several other distinct neural circuits were identified that may represent the neurobiological substrates of different information processing stages of mental timekeeping. Small areas of right cerebellum were engaged in several of these circuits, suggesting that cerebellar function may be important in, but not the primary substrate of, the mental timing tasks used in this experiment. These findings are discussed within the context of current biological and information processing models of neural timekeeping.

Acoustic Stimulation↗
PubMed2004

Brain network interactions in auditory, visual and linguistic processing.

In the paper, we discuss the importance of network interactions between brain regions in mediating performance of sensorimotor and cognitive tasks, including those associated with language processing. Functional neuroimaging, especially PET and fMRI, provide data that are obtained essentially simultaneously from much of the brain, and thus are ideal for enabling one to assess interregional functional interactions. Two ways to use these types of data to assess network interactions are presented. First, using PET, we demonstrate that anterior and posterior perisylvian language areas have stronger functional connectivity during spontaneous narrative production than during other less linguistically demanding production tasks. Second, we show how one can use large-scale neural network modeling to relate neural activity to the hemodynamically-based data generated by fMRI and PET. We review two versions of a model of object processing - one for visual and one for auditory objects. The regions comprising the models include primary and secondary sensory cortex, association cortex in the temporal lobe, and prefrontal cortex. Each model incorporates specific assumptions about how neurons in each of these areas function, and how neurons in the different areas are interconnected with each other. Each model is able to perform a delayed match-to-sample task for simple objects (simple shapes for the visual model; tonal contours for the auditory model). We find that the simulated electrical activities in each region are similar to those observed in nonhuman primates performing analogous tasks, and the absolute values of the simulated integrated synaptic activity in each brain region match human fMRI/PET data. Thus, this type of modeling provides a way to understand the neural bases for the sensorimotor and cognitive tasks of interest.

Animals↗
PubMed2000

Postnatal synaptic potentiation: delivery of GluR4-containing AMPA receptors by spontaneous activity.

To examine how functional circuits are established in the brain, we studied excitatory transmission in early postnatal hippocampus. Spontaneous neural activity was sufficient to selectively deliver GluR4-containing AMPA receptors (AMPA-Rs) into synapses. This delivery allowed non-functional connections to transmit at resting potentials and required NMDA receptors (NMDA-Rs) but not CaMKII activation. Subsequently, these delivered receptors were exchanged with non-synaptic GluR2-containing AMPA-Rs in a manner requiring little neuronal activity. The enhanced transmission resulting from this delivery and subsequent exchange was maintained for at least several days and required an interaction between GluR2 and NSF. Thus, this sequence of subunit-specific trafficking events triggered by spontaneous activity in early postnatal development may be crucial for initial establishment of long-lasting functional circuitry.

Animals↗
PubMed2000

Position and behavioral modulation of synchronization of hippocampal and accumbens neuronal discharges in freely moving rats.

To understand how hippocampal signals are processed by downstream neurons, we analyzed the relative timing between neuronal discharges in simultaneous recordings in the hippocampus and nucleus accumbens of rats performing in a plus maze. In all, 154 pairs of cells (composed of 65 hippocampal and 56 accumbens neurons) were examined during the 1 s period prior to reward delivery. Cross-correlation analyses over a +/- 300-ms window with 10-ms bins revealed that 108 pairs had at least one significant histogram bin (P < 0.01). The most frequently occurring peaks of hippocampal firing prior to accumbens discharges appeared at latencies from -30-0 ms, corresponding to published values of the latency of the hippocampal pathway to the nucleus accumbens. Other peaks appeared most often at latencies multiples of about 110 ms prior to and after this, corresponding to theta rhythmicity. Since firing synchronization can result from several types of connectivity patterns (such as common inputs), a group of 18 hippocampus-accumbens pairs was selected as those most likely to have monosynaptic connections. The criterion was the presence of at least one highly significant peak (P < 0.001) at latencies corresponding to field potentials evoked in the accumbens by hippocampal stimulation. A significant peak occurred on all four maze arms for only one of these cell pairs, indicating positional modulation for the others. In addition, behavior dependence of the synchrony between these nucleus accumbens and hippocampus neurons was examined by studying data in relation to three different synchronization points: reward box arrival, box departure, and arrival at the center of the maze. This indicates that the functional connectivity between hippocampal and accumbens neurons was stronger when the rat was near reward areas. Ten of the hippocampal neurons in these 18 cell pairs showed 9-Hz (theta) rhythmic activity in autocorrelation analyses. Of these 10 cells, cross-correlograms from eight hippocampal-accumbens pairs also showed theta rhythmicity. Overall, these results indicate that the synchrony between hippocampus and nucleus accumbens neurons is modulated by spatial position and behavior, and theta rhythm may play an important role for this synchronization.

Animals↗
PubMed2001

The creatine kinase system is essential for optimal refill of the sarcoplasmic reticulum Ca2+ store in skeletal muscle.

Muscle function depends on an adequate ATP supply to sustain the energy consumption associated with Ca(2+) cycling and actomyosin sliding during contraction. In this regulation of energy homeostasis, the creatine kinase (CK) circuit for high energy phosphoryl transfer between ATP and phosphocreatine plays an important role. We earlier established a functional connection between the activity of the CK system and Ca(2+) homeostasis during depolarization and contractile activity of muscle. Here, we show how CK activity is coupled to the kinetics of spontaneous and electrically induced Ca(2+) transients in the sarcoplasm of myotubes. Using the UV ratiometric Ca(2+) probe Indo-1 and video-rate confocal microscopy in CK-proficient and -deficient cultured cells, we found that spontaneous and electrically induced transients were dependent on ryanodine-sensitive Ca(2+) release channels, sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase pumps, extracellular calcium, and functional mitochondria in both cell types. However, at increasing sarcoplasmic Ca(2+) load (induced by electrical stimulation at 0.1, 1, and 10 Hz), the Ca(2+) removal rate and the amount of Ca(2+) released per transient were gradually reduced in CK-deficient (but not wild-type) myotubes. We conclude that the CK/phosphocreatine circuit is essential for efficient delivery of ATP to the sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase pumps and thereby directly influences sarcoplasmic reticulum refilling and the kinetics of the sarcoplasmic Ca(2+) signals.

Adenosine Triphosphate↗
PubMed2003

[Modeling dynamics of gene net, regulating the cell cycle in mammalian cells].

The study of the molecular mechanisms determining cellular programs of proliferation, differentiation, and apoptosis is currently attracting much attention. Recent studies have demonstrated that the system of cell-cycle control based on the transcriptional regulation of the expression of specific genes is responsible for the transition between programs. These groups of functionally connected genes from so-called gene networks characterized by numerous feedbacks and a complex behavioral dynamics. Computer simulation methods have been applied to studying the dynamics of gene networks regulating the cell cycle of vertebrates. The data on the regulation of the key genes obtained from the CYCLE-TRRD database have been used as a basis to construct gene networks of different degrees of complexity controlling the G1/S transition, one of the most important stages of the cell cycle. The behavior dynamics of the model constructed has been analyzed. Two qualitatively different functional modes of the system has been obtained. It has also been shown that the transition between these modes depends on the duration of the proliferation signal. It has also been demonstrated that the additional feedback from factor E2F to genes c-fos and c-jun, which was predicted earlier based on the computer analysis of promoters, plays an important role in the transition of the cell to the S phase.

Animals↗
PubMed1998

Development of functional topography in the corticorubral projection: An in vivo assessment using synaptic potentials recorded from fetal and newborn cats.

In mammals, topographic maps emerge from initially diffuse projections during development. To gain insight into the mechanisms governing the transition from a diffuse projection to a topographic map, we studied topographic specificity of functional connections during development, using the cat corticorubral system as a model. In the adult cat, rubrospinal neurons in the dorsomedial part of the red nucleus (RN) receive input primarily from the forelimb area of the sensorimotor cortex, whereas those in the ventrolateral part receive input primarily from the hindlimb area. During development, axons from the sensorimotor cortex arrive in the RN at embryonic day 50 (E50) (Song et al., 1995a) and are diffusely distributed in the RN until postnatal day 13 (P13) (Higashi et al., 1990). Here, we studied the development of the pattern of functional cortical inputs to individual rubrospinal neurons, using synaptic potentials recorded in vivo. The functional topography in each rubrospinal neuron in developing cats was examined and classified either as adult-like or nonadult-like by comparison with the adult pattern. In preterm kittens from E61 to E65, only about half of the recorded neurons (41%; n = 22) showed adult-like functional topography. This percentage, however, increased to 82% (n = 56) in P1-P8 kittens and to 93% (n = 42) in P13-P28 kittens. These results, in conjunction with the above mentioned anatomical observations, suggest that corticorubral axons make functional synapses nonselectively with rubrospinal neurons before birth. Furthermore, the functional topographic map developed earlier than the anatomical map ( P13), suggesting that there is a developmental step of selective promotion of synapse formation and/or selective enhancement of synaptic efficacy in topographically appropriate regions in the RN, before the emergence of the mature anatomical map.

Age Factors↗
PubMed2005

Co-activation of the amygdala, hippocampus and inferior frontal gyrus during autobiographical memory retrieval.

Functional MRI was used to investigate the role of medial temporal lobe and inferior frontal lobe regions in autobiographical recall. Prior to scanning, participants generated cue words for 50 autobiographical memories and rated their phenomenological properties using our autobiographical memory questionnaire (AMQ). During scanning, the cue words were presented and participants pressed a button when they retrieved the associated memory. The autobiographical retrieval task was interleaved in an event-related design with a semantic retrieval task (category generation). Region-of-interest analyses showed greater activation of the amygdala, hippocampus, and right inferior frontal gyrus during autobiographical retrieval relative to semantic retrieval. In addition, the left inferior frontal gyrus showed a more prolonged duration of activation in the semantic retrieval condition. A targeted correlational analysis revealed pronounced functional connectivity among the amygdala, hippocampus, and right inferior frontal gyrus during autobiographical retrieval but not during semantic retrieval. These results support theories of autobiographical memory that hypothesize co-activation of frontotemporal areas during recollection of episodes from the personal past.

Adolescent↗
PubMed2002

The Caenorhabditis elegans EGL-26 protein mediates vulval cell morphogenesis.

In screens for Caenorhabditis elegans mutants defective in vulval morphogenesis, we isolated multiple mutants in which the uterus and the vulva fail to make a functional connection, resulting in an egg-laying defective phenotype. Two of these connection of gonad defective (Cog) mutants carry alleles of the egl-26 gene. We demonstrate that vulval lineages in egl-26 mutant animals are normal, but one vulval cell, vulF, adopts an abnormal morphology. This results in formation of an abnormally thick layer of vulval tissue at the apex of the vulva and a physical blockage of the exit to the vulva from the uterus. egl-26 was cloned and is predicted to encode a novel protein. Mosaic analysis indicates that egl-26 activity is required in the primary vulval lineage for vulF morphogenesis. Expression of a functional translational fusion of EGL-26 to GFP was observed within the primary vulval lineage only in vulE, which neighbors vulF. EGL-26 is localized at the apical edge of the vulE cell. It is thus possible that vulE acts to instruct morphological changes in the neighboring cell, vulF, in an interaction mediated by EGL-26.

Amino Acid Sequence↗
PubMed1998

High cancer susceptibility and embryonic lethality associated with mutation of the PTEN tumor suppressor gene in mice.

BACKGROUND: Germ-line and sporadic mutations in the tumor suppressor gene PTEN (also known as MMAC or TEP1), which encodes a dual-specificity phosphatase, cause a variety of cancers such as Cowden disease, glioblastoma, endometrial carcinoma and prostatic cancer. PTEN is widely expressed, and Cowden disease consistently affects various organ systems, suggesting that the PTEN protein must have an important, although as yet poorly understood, function in cellular physiology. RESULTS: Homozygous mutant mice lacking exons 3-5 of the PTEN gene (mPTEN3-5) had severely expanded and abnormally patterned cephalic and caudal regions at day 8.5 of gestation. Embryonic death occurred by day 9.5 and was associated with defective chorio-allantoic development. Heterozygous mPTEN3-5 mice had an increased incidence of tumors, especially T-cell lymphomas; gamma-irradiation reduced the time lapse of tumor formation. DNA analysis of these tumors revealed the deletion of the mPTEN gene due to loss of heterozygosity of the wild-type allele. Tumors associated with loss of heterozygosity in mPTEN showed elevated phosphorylation of protein kinase B (PKB, also known as Akt kinase), thus providing a functional connection between mPTEN and a murine proto-oncogene (c-Akt) involved in the development of lymphomas. CONCLUSIONS: The mPTEN gene is fundamental for embryonic development in mice, as mPTEN3-5 mutant embryos died by day 9.5 of gestation, with patterning defects in cephalic and caudal regions and defective placentation. Heterozygous mice developed lymphomas associated with loss of heterozygosity of the wild-type mPTEN allele, and tumor appearance was accelerated by gamma-irradiation. These lymphomas had high levels of activated Akt/PKB, the protein product of a murine proto-oncogene with anti-apoptotic function, associated with thymic lymphomas. This suggests that tumors associated with mPTEN loss of heterozygosity may arise as a consequence of an acquired survival advantage. We provide direct evidence of the role of mPTEN as a tumor suppressor gene in mice, and establish the mPTEN mutant mouse as an experimental model for investigating the role of PTEN in cancer progression.

Animals↗