bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional and effective connectivity in neuroimaging: A synthesis
Authors: Friston Karl J. 
Published: January 2005

AbstractThe brain appears to adhere to two principles of functional organization; functional segregation and functional integration. The integration within and between functionally specialized areas is mediated by functional or effective connectivity. The characterization of this sort of connectivity is an important theme in many areas of neuroscience. This article presents one approach that has been used in functional imaging.This article reviews the basic distinction between functional and effective connectivity (as the terms are used in neuroimaging) and their role in addressing several aspects of functional organization (e.g. the topography of distributed system, integration between cortical areas, time‐dependent changes in connectivity and nonlinear interactions). Emphasis is placed on the points of contact between the apparently diverse applications of these concepts and in particular the central role of eigenimages or spatial modes. Although the framework that has been developed is inherently linear, it has been extended to assess nonlinear interactions among cortical areas. ©1994 Wiley‐Liss, Inc.
Permanently altered hippocampal structure, excitability, and inhibition after experimental status epilepticus in the rat: The “dormant basket cell” hypothesis and its possible relevance to temporal lobe epilepsy
Authors: Sloviter Robert S. 
Published: January 2005

AbstractThe relationship between an episode of status epilepticus, the resulting hippocampal pathology, and the subsequent development of pathophysiological changes possibly relevant to human cpilepsy was explored using the experimental epilepsy model of perforant path stimulation in the rat. Granule cell hyperexcitability and decreased feedforward and feedback inhibition were evident immediately after 24 hours of intermittent perforant path stimulation and persisted relatively unchanged for more than 1 year. All of the pathophysiological changes induced by perforant path stimulation were replicated in normal animals by a subconvulsive dose of bicuculline, suggesting that the permanent “epileptiform” abnormalities produced by sustained perforant path stimulation may be due to decreased GABA‐mediated inhibition. Granule cell pathophysiology was seen only in animals that exhibited a loss of adjacent dentate hilar mossy cells and hilar somatostatin/neuropeptide Y‐immunoreactive neurons. GABA‐immunoreactive dentate basket cells survived despite the extensive loss of adjacent hilar neurons. However, Parvalbumin immunoreactivity, present normally in a subpopulation of GABA‐immunoreactive dentate basket cells, was absent on the stimulated side. Whether this represents decreased parvalbumin synthesis in surviving basket cells or a loss of a specific subset of inhibitory cells is unclear.Hyperexcitability and decreased paired‐pulse inhibition in response to ipsilateral perforant path stimulation were also present in the CA1 pyramidal cell layer on the previously stimulated side, despite minimal damage to CA1 pyramidal cells or interneurons. The possibility that CA1 inhibitory neurons were hypofunctional or “dormant” due to a loss of excitatory input to inhibitory cells from damaged CA3 pyramidal cells was tested by stimulating the contralateral perforant path in order to activate the same CA1 basket cells via different inputs. Contralateral stimulation evoked CA1 pyramidal cell paired‐pulse inhibition immediately in the previously stimulated hippocampus. Thus, we propose the “dormant basket cell” hypothesis, which implies that despite malfunction, inhibitory systems remain intact in “epileptic” tissue and are capable of functioning if appropriately activated.
Target cell specificity of synaptic connections in the hippocampus
Authors: Frotscher M. 
Published: January 2005

AbstractA major question of neurobiological research is how precise connections between neurons are formed and maintained. In the hippocampus, afferent fiber systems are known to terminate in a laminated fashion. Previous studies have indicated that this lamination is largely due to spatiotemporal constraints during ontogenetic development. In this commentary, recent fine structural studies on the target cell specificity of the various hippocampal afferents are discussed. It becomes obvious that some afferent fibers establish synapses with all available target cells, whereas other afferents are restricted to distinct types of neurons. A high degree of neuronal specificity is found in the hippocampal and dentate axo‐axonic cells, which are restricted not only to specific types of target cells (pyramidal neurons and granule cells, respectively) but also to distinct portions of the target cell's membrane (the axon initial segment). Altogether, these data indicate that there are different levels of target cell specificity in the hippocampus. It is suggested that specific molecular interactions between pre‐ and postsynaptic elements, in addition to spatial and temporal factors, play a role in the formation and stabilization of the various synaptic connections of the hippocampal formation.
Mossy cells of the rat fascia dentata are glutamate‐immunoreactive
Authors: Soriano Eduardo , Frotscher Michael 
Published: January 2005

AbstractThe mossy cells represent a prominent cell type of the hilar region. Whereas the morphology of these neurons, their synaptic connections, and physiological characteristics have been described in some detail, information about their neurotransmitter is still lacking. Using immunocytochemistry in combination with Golgi impregnation, the authors demonstrate that identified mossy cells are GABA‐immunonegative but stain for glutamate. These results do not prove that these cells use glutamate as a transmitter, since glutamate is a ubiquitous metabolite. However, together with the lack of GABA staining and a recent report on asymmetric spine synapses formed by identified mossy cell axons, the present results support an excitatory nature of these neurons.
Brain temperature and hippocampal function
Authors: Andersen Per , Moser Edvard I. 
Published: January 2005

AbstractEven though homeothermic animals regulate the body temperature, fluctuations up to 2–3°C may occur during physiological conditions. In many species, including the rat, a similar variation can be measured in the brain temperature. Such changes are expressed throughout the brain with a preserved gradient between the warmer basal and cooler dorsal parts. In spite of these recordable physiological changes, spatial learning is quite robust, in that it occurs at brain temperatures between 30 and 39°C. Even drastic cooling (to below 15°C) fails to affect consolidation or storage of information when the animal is tested after rewarming. The physiological temperature fluctuations have significant consequences for electrophysiological responses in the brain. Various bioelectrical signals are more sensitive during warming, axonal conduction is speeded up, and stimulus‐elicited transmitter release becomes faster and more synchronized. Action potentials have shorter rise and decay times in warm conditions, and the amplitude becomes slightly smaller. Population responses are differently affected by these changes. Dentate field potentials in response to stimulation of perforant‐path fibers appear with shorter latency in warm conditions, and the rate of rise in the field EPSP is increased. Paradoxically, the amplitude of the population spike is reduced. This is due to a combination of reduced amplitude of individual action potentials and reduced efficiency of the summation of groups of action potentials. Due to the large effects of temperature on hippocampal field potentials, it is mandatory that brain temperature changes are monitored and/or controlled whenever such responses are recorded in freely moving and anesthetized animals. © 1995 Wiley‐Liss, Inc.
Place cells recorded in the parasubiculum of freely moving rats
Authors: Taube Jeffrey S. 
Published: January 2005

AbstractPrevious studies have identified neurons in the hippocampus, subiculum, and entorhinal cortex which discharge as a function of the animal's location in the environment. In contrast, neurons in the postsubiculum and anterior thalamic nucleus discharge as a function of the animal's head direction in the horizontal plane, independent of its behavior and location in the environment. Because the parasubiculum (PaS) has extensive connections, either directly or indirectly, with these structures, it is centrally located to influence the neuronal activity in these areas. This study was therefore designed to determine the types of behavioral and spatial correlates in neurons from the PaS. Single unit recordings were conducted in the PaS of freely moving rats trained to retrieve food pellets thrown randomly into a cylindrical apparatus. A total of 10.3% of the cells were classified as place cells because they discharged in relation to the animal's location in the cylinder. A large percentage of cells (41.4%) were classified as theta cells. The remaining cells had nondiscernable behavioral correlates.Quantitative analysis of the firing rate maps for the place cells showed they had higher levels of background activity and contained larger firing fields than values reported previously for hippocampal place cells. Directional analysis showed that only three out of 16 cells contained a secondary directional correlate; the firing rate for the remaining cells was not affected by the animal's directional heading within the firing field. A time shift analysis, which shifted the spike time series relative to the animal location series, was conducted to determine whether the quality of the location‐specific firing could be improved. The time shifts for three different spatial parameters were optimal when cell discharge led the animal's position. Furthermore, the optimal time shifts for two of these parameters (firing area and information content) were less than the optimal shift reported for hippocampal place cells and suggested that PaS cell discharge lagged behind hippocampal place cell activity. Rotation of the cue card with the animal out of view led to near equal rotation of the firing field when the animal was returned to the apparatus. These results indicate that a small population of cells in the PaS encode the animal's location in its environment, although the representation of space encoded by these cells is different from the type of representation encoded by hippocampal place cells. © 1995 Wiley‐Liss, Inc.
The long‐term use of psychotropic drugs: A follow‐up study in italian general practice
Authors: Fiorio R. , Bellantuono C. , Leoncini M. , Montemezzi G. , Micciolo R. , Williams P. 
Published: January 2005

AbstractFour general practitioners (GPs) of Verona, a town in northern Italy of about 300,000 inhabitants, recruited in 1986 a cohort of 75 adult patients to whom they prescribed benzodiazepines or antidepressants for the “first time”. The patients, new users of psychotropic drugs, were 51 women (68 per cent) and 24 men (32 per cent). They were followed up during the 26 weeks after the first psychotropic drug prescription. At the end of the study 20 patients (26·7 per cent of the original cohort‐–“long‐term” users) were still consuming psychotropic drugs (mainly benzodiazepines with or without an antidepressant). Severity of psychiatric symptoms (only for patients over 45 years), prescriptions of an antidepressant (but only for women under 45 years) and low educational level (only in males over 45 years) were identified as factors associated with long‐term psychotropic drug consumption.
Increased anticholinergic levels, memory and judgement
Authors: Walkup J. 
Published: January 2005

AbstractClinicians who have contact with patients taking medications which produce cholinergic blockade may need to consider possible links between increased anticholinergic levels and problems in judgement. Although it appears that there has as yet been no direct experimental test of the impact of anticholinergic agents on the judgement of normals or psychiatric patients, a review is offered of two types of basic cognitive findings which strongly suggest that the risk of such a link should figure in clinical cost—benefit analysis. It is then argued that, in the absence of definitive findings, several clinical considerations suggest that the clinician should consider the possible impact of anticholinergics on judgement in his or her practice.
Study of effects of clobazam and lorazepam on memory and cognitive functions in healthy subjects
Authors: Patat A. , Klein M. J. , Surjus A. , Rostand A. , Granier J. 
Published: January 2005

AbstractThis was a double‐blind, placebo‐controlled crossover study in 15 healthy female volunteers. It consisted of five sessions, separated by 1 week wash‐out between sessions. The purpose of the trial was to study the potential amnesic and sedative activity of clobazam and lorazepam, and the potential antagonism between these effects under the joint influence of a high noise level and intense intermittent light stimulation (ILS), aimed at increasing the level of alertness. The study drugs were administered as a single daily oral dose. The amnesic and sedative effects were evaluated by objective measurements (digit span, Buschke selective reminding test, critical flicker fusion, reaction time, tapping, mental arithmetic test) and subjective measurements (visual analogue scale and adverse effect questionnaire) before each administration, then 1 h, 2 h, 2·5 h, 3 h, 4 h and 7 h post‐dosing. An analysis of variance according to a balanced Latin square design was performed. Clobazam, at a dosage of 10 mg, was devoided of sedative and amnesic effects; at a dosage of 30 mg it induced only moderate memory disturbances. In contrast, lorazepam, administered at doses of 1 and 3 mg, produced marked and dose‐dependent disturbances of memory, alertness and cognitive functions. The use of visual and sound stimuli, designed to increase the level of alertness, did not counteract the sedative effects induced by lorazepam.
A commentary: Measuring the health economics of depression
Authors: Eckett Simon 
Published: January 2005

AbstractThe perspective of a health economic analysis is vital and this is particularly true in the current debate on the economic analysis of Selective Serotonin Reuptake Inhibitors (SSRIs) and Tricyclic Antidepressants (TCAs). The perspective can be institutional, from central government, region, health commission to GP fundholder, and it can be by cost type: including drug costs alone in the analysis; other direct costs such as GPs' and counselling time; and indirect costs such as loss of earnings due to depression. Economic analysts, who focus on drug costs alone tend to favour TCAs over SSRIs. Those who cast their cost net wider tend to favour SSRIs over TCAs. Future research should concentrate on the ‘invisible costs’ that exist in the prescribing process; and on quality of life and health outcomes to establish treatment cost/successful outcome. This could form an intergral part in the development of future cost effective guidelines for depression.
The Remarkable Structure of Lithium Cyanide/Isocyanide
Authors: Von Ragué Schleyer Paul , Sawaryn Andrzej , Reed Alan E. , Hobza Pavel 
Published: January 2005

AbstractElectron correlation corrections have a considerable influence on the relative stabilities of lithium isocyanide (1), lithium cyanide (2), and the bridged form, 3. While Hartree‐Fock theory finds 1 to be most stable and 3 not to be a minimum, MP2/6‐31G* optimization indicates 3 to be the global minimum. At higher levels employing full fourth‐order Møller‐Plesset theory and a quadruply split valence and polarized basis set (MP4STDQ/6‐311+G*), 2 is only about 2 kcal/mol less stable than 1 and 3, which are indicated to have nearly the same energy. LiNC thus is similar to C(Na)N and C(K)N, both of which are known to prefer T‐shaped (bridged) structures in the gas phase. However, to an even greater extent than formerly realized, rotation of the lithium cation around the cyanide anion nucleus should be practically free. ΔH (LiCN) = 32.8 kcal/mol is estimated from the calculated lithium cation affinity of 151.2 kcal/mol. In addition, we find at the MP4SDTQ/6‐31+G*//MP2/6‐31G* level that the bridged form of NaCN is favored by 2–3 kcal/mol over the corresponding linear forms, which have nearly the same energy.
Free energy perturbation calculations on models of active sites: Applications to adenosine deaminase inhibitors
Authors: Hansen Lillian M. , Kollman Peter A. 
Published: January 2005

AbstractFree energy perturbation calculations were performed to determine the free energy of binding associated with the presence of perhaps an unusual hydroxyl group in the transition state analog of nebularine, an inhibitor of the enzyme adenosine deaminase. The presence of a single hydroxyl group in this inhibitor has been found to contribute −9.8 kcal/mol to the free energy of binding, with a 108‐fold increase in the binding affinity by the enzyme. In this work, we calculate the difference in solvation free energy for the 1,6‐dihydropurine complex versus that of the 6‐hydroxyl‐1,6‐dihydropurine complex to determine if this marked increase in binding affinity is attributed to an unusually hydrophobic hydroxyl group. The calculated ΔG associated for the solvation free energy is −11.8 kcal/mol. This large change in the solvation free energy suggests that this hydroxyl is instead unusually hydrophilic and that the difference in free energy of interaction for the two inhibitors to the enzyme must be at least ca. 20 kcal/mol. Although the crystal structure for adenosine deaminase is currently not known, we attempt to mimic the nature of the active site by constructing models which simulate the enzyme‐inhibitor complex. We present a first attempt at determining the change in free energy of binding for a system in which structural data for the enzyme is incomplete. To do this, we construct what we believe is a minimal model of the binding between adenosine deaminase and an inhibitor. The active site is simulated as a single charged carboxyl group which can form a hydrogen bond with the hydroxyl group of the analog. Two different carboxyl anion models are used. In the first model, the association is modeled between an acetic acid anion and the modified inhibitor. The second model consists of a hydrophobic amino acid pocket with an interior Glu residue in the active site. From these models we calculate the change in free energy of association and the overall change in free energy of binding. We calculate the free energies of interaction both in the absence and presence of water. We conclude from this that the presence of a single suitably placed‐CO−2 group probably cannot explain the binding effect of the‐OH group and that additional interactions will be found in the adenosine deaminase active site.
A hybrid compartmental model for the alligator Purkinje cell. I: Preferred somatopetal conduction of dendritic spikes and soma‐axon interaction
Authors: Pottala Erik W. , Mortimer James A. 
Published: January 2005

AbstractA compartmental hardware model of an alligator Purkinje cell is described, consisting of a branched dendritic tree with four zones of spike generation and electrically excitable soma and initial‐segment regions. Passive properties of the model compartments are represented by a cable analog circuit. Simulated action potentials, generated by a combination of depolarizing and hyperpolarizing conductance changes, are triggered in active compartments when the simulated membrane potential passes through preset thresholds. These were set at values corresponding to 28mV depolarization in the dendrites, 22 mV in the soma, and 7 mV in the initial‐segment compartment. Synaptic inputs consisting of brief (0.35 msec) rectangular conductance changes give rise to exponentially decaying postsynaptic potentials in the input compartment which are electrotonically spread to other compartments. Orthodromic activation of the model neuron by computer‐generated random pulse trains generates a simple discharge in the initial‐segment compartment without evoking complex spikes. Synchronized excitatory input to the same compartments, however, does evoke a complex spike response in the soma and initial segment, coupled with dendritic spikes, Following antidromic activation of the model neuron, dendritic spikes are not generated, demonstrating a tendency in the dendritic tree for preferential conduction of spikes toward the soma. Investigation of some of the factors underlying this tendency suggests that variations in voltage attenuation due to dendritic geometry, convergence of electrotonically spread dendritic spikes, and the relative durations of dendritic and somatic action potentials may contribute to it. The presence of a threshold gradient in the dendritic tree, proposed by Llinás and his coworkers, was not found to be necessary to explain this tendency toward somatopetal conduction, although it cannot be excluded by the model. Examination of the role of the conically shaped initial‐segment region suggests that this zone may provide a low‐pass filter for signals conducted electrotonically from the axon to the soma, blocking repolarization of the soma during the complex spike burst generated in the axon.
An adrenergic mechanism for visual neuroregulation
Authors: Coppola Robert J. , Rolek Dennis F. , Kramer Stanley Z. 
Published: January 2005

AbstractStudies of the diffuse electroretinogram (ERG) and evoked responses in the optic lobe in the baby chick have shown that epinephrine produces changes in both. Epinephrine produces enhancement of the a‐wave and depression of the b‐ and d‐waves in both intact and isolated eyes. In the optic lobe it produces enhancement of both components of the evoked response. The presence of epinephrine in the vertebrate retina and the optic lobe of chicks suggests that these changes may reflect the involvement of epinephrine in synaptic transmission.
Spontaneous and flash‐induced multiple unit activity in the hypothalamic gonadotropic areas: Effects of photoperiod and of optic nerve section in quail
Authors: Oliver J. , Baylé J. D. 
Published: January 2005

AbstractThe present study was devoted to recording of spontaneous and flash‐evoked multiple unit discharges in the gonadotropic areas of the quail hypothalamus and to investigate the influence of the length of the day and of bilateral optic nerve section.Blinding resulted in a marked decrease of MUA in the tuberal region which was much less important in the dorsal part of the nuclear infundibular complex. Burst and continuous patterns of discharges subsisted in tuberal and dorsal areas of blinded quail but responses to flash were completely suppressed.Lengthening the photofraction led to a very strong reduction of firing rates in both tuberal and dorsal hypothalamic regions. Furthermore, flash stimulation was no longer effective in intact photostimulated quail (18L‐6D).Flash‐evoked modification of MUA in gonadotropic regions were differentiated in a clear‐cut fashion from specific responses which were obtained in the visual system.