bluuebunny/crossref_metadata_2025 huggingface dataset:
Synchronizing with Music: Intercultural Differences
Authors: DRAKE CAROLYN , EL HENI JAMEL BEN
Published: January 2004

Abstract: The way in which listeners perceive music changes throughout childhood, but little is known about the factors responsible for these changes. One factor, explicit music training, has received considerable attention, with studies indicating that musicians demonstrate a more complex hierarchical mental representation for music and superior temporal organizational skills. But does acculturation—the passive exposure to a particular type of music since birth—also influence the acquisition of these skills? We compared the music synchronization performance of Tunisian and French subjects with music from these two contrasting musical cultures. Twelve musical excerpts were selected from the two popular music cultures, matched for perceived tempo, complexity, and familiarity, and subjects were asked to tap in time with the music. Tapping mode (rate and hierarchical level) varied with subjects' familiarity with the musical idiom, as evidenced by an interaction between musical culture and type of music: participants synchronized at higher hierarchical levels (and over a wider range) with music from their own culture than with an unfamiliar type of music. Thus, passive acculturation as well as explicit music tuition influence our perception and cognition of music.
Music and Learning‐Induced Cortical Plasticity
Authors: PANTEV CHRISTO , ROSS BERNHARD , FUJIOKA TAKAKO , TRAINOR LAUREL J. , SCHULTE MICHAEL , SCHULZ MATTHIAS
Published: January 2004

Abstract: Auditory stimuli are encoded by frequency‐tuned neurons in the auditory cortex. There are a number of tonotopic maps, indicating that there are multiple representations, as in a mosaic. However, the cortical organization is not fixed due to the brain's capacity to adapt to current requirements of the environment. Several experiments on cerebral cortical organization in musicians demonstrate an astonishing plasticity. We used the MEG technique in a number of studies to investigate the changes that occur in the human auditory cortex when a skill is acquired, such as when learning to play a musical instrument. We found enlarged cortical representation of tones of the musical scale as compared to pure tones in skilled musicians. Enlargement was correlated with the age at which musicians began to practice. We also investigated cortical representations for notes of different timbre (violin and trumpet) and found that they are enhanced in violinists and trumpeters, preferentially for the timbre of the instrument on which the musician was trained. In recent studies we extended these findings in three ways. First, we show that we can use MEG to measure the effects of relatively short‐term laboratory training involving learning to perceive virtual instead of spectral pitch and that the switch to perceiving virtual pitch is manifested in the gamma band frequency. Second, we show that there is cross‐modal plasticity in that when the lips of trumpet players are stimulated (trumpet players assess their auditory performance by monitoring the position and pressure of their lips touching the mouthpiece of their instrument) at the same time as a trumpet tone, activation in the somatosensory cortex is increased more than it is during the sum of the separate lip and trumpet tone stimulation. Third, we show that musicians' automatic encoding and discrimination of pitch contour and interval information in melodies are specifically enhanced compared to those in nonmusicians in that musicians show larger functional mismatch negativity (MMNm) responses to occasional changes in melodic contour or interval, but that the two groups show similar MMNm responses to changes in the frequency of a pure tone.
Gray Matter Differences between Musicians and Nonmusicians
Authors: GASER CHRISTIAN , SCHLAUG GOTTFRIED
Published: January 2004

Abstract: Musicians learn complex motor and auditory skills at an early age and practice these specialized skills extensively from childhood through their entire careers. Using a voxel‐by‐voxel morphometric technique, we found gray matter volume differences in motor as well as auditory and visuospatial brain regions comparing professional musicians (keyboard players) with matched amateur musicians and nonmusicians. These multiregional differences might represent structural adaptations in response to long‐term skill learning and repetitive rehearsal of these skills. This is supported by finding a strong association between structural differences, musician status, and practice intensity as well as by a wealth of supporting animal data showing structural changes in response to long‐term motor training.
Toddlers' Musical Preferences
Authors: LAMONT ALEXANDRA
Published: January 2004

Abstract: The current paper reports a pilot study of the preferences of children aged 2‐3.5 years for different kinds of music. With the use of a novel interactive procedure to measure active preferences, preliminary results indicate general preferences for fast and loud music irrespective of style.
Long‐Term Memory for Pitch in Six‐Month‐Old Infants
Authors: PLANTINGA JUDY , TRAINOR LAUREL J.
Published: January 2004

Abstract: We examined 6‐month‐old infants' long‐term memory representations for the pitch of familiar melodies. Infants remembered the relative pitch of the melodies, but the absolute pitch was either not remembered or not a particularly salient attribute.
Interactions of Leptin, GH, and Cortisol in Normal Children
Authors: GHIZZONI LUCIA , MASTORAKOS GEORGE
Published: January 2004

Abstract: Leptin is the product of the ob gene located in humans on chromosome 7q31.3. It is a 16‐kDa protein named after the Greek “leptos,” meaning lean, to indicate the function that this adipocyte‐secreted protein was thought to have. Since its discovery, in fact, most of the research focused on the role of leptin in body‐weight regulation, aiming to elucidate the pathophysiology of human obesity. However, more and more data show that leptin is not only important in the regulation of food intake and energy balance, but it also functions as a neuroendocrine hormone. It is involved in glucose metabolism, as well as in normal sexual maturation and reproduction, and interacts with the hypothalamic‐pituitary‐adrenal (HPA) and the growth hormone (GH) axes.
The Role of Leptin in Female Adolescence
Authors: APTER DAN
Published: January 2004

Abstract: Leptin, the ob gene product, is related to the onset of puberty in animal models, but its role in human puberty is still rather undefined. In prepubertal girls and boys, leptin concentrations increase slowly with age and body‐fat mass. In boys, this increase is interrupted in early puberty, when testosterone and lean body mass increase. In girls, leptin, along with the body‐fat mass, continue to increase during puberty. Plasma leptin concentrations are significantly correlated with fat mass at all Tanner stages in males and females. The diurnal variation of leptin concentrations seen in adults is apparent for all age groups with no significant changes in the pattern across puberty. Leptin is bound in blood by a high‐affinity binding protein identical with the soluble leptin receptor (sOB‐R). In the first year of life, the concentration of sOB‐R is high, and then a continuous decline of sOB‐R follows until midpuberty. The therapeutic response to leptin treatment in a child with leptin deficiency confirms the importance of leptin in the regulation of body weight in humans, and establishes an important role for this hormone in the regulation of appetite. Still no evidence is available that would indicate leptin is a primary signal that initiates the onset of human puberty. Instead, it may act in a permissive way as one of several metabolic factors to allow pubertal maturation to proceed and later reproduction to occur.
Roles of Reproductive Corticotropin‐Releasing Hormone
Authors: KALANTARIDOU SOPHIA N. , MAKRIGIANNAKIS ANTONIS , MASTORAKOS GEORGE , CHROUSOS GEORGE P.
Published: January 2004

Abstract: Corticotropin‐releasing hormone (CRH), the principal regulator of the hypothalamic‐pituitary‐adrenal axis, as well as its receptors, have been identified in most female reproductive tissues, including the uterus, placenta, and ovary. Endometrial CRH may participate in decidualization, implantation, and early maternal tolerance; placental CRH may participate in the physiology of pregnancy and the onset of parturition, and ovarian CRH may participate in follicular maturation, ovulation, and luteolysis. The hypercortisolism of the latter half of pregnancy can be explained by increased levels of placental CRH in plasma. This hypercortisolism is followed by a transient suppression of hypothalamic CRH secretion in the postpartum period, which may explain the blues or depression and autoimmune phenomena frequently observed during this period.
Miniature, Low‐Dose, Intrauterine Drug‐Delivery Systems
Authors: WILDEMEERSCH D. , DHONT M. , WEYERS S. , TEMMERMAN M.
Published: January 2004

Abstract:The safety of systemically administered sex steroids continues to be a major focus of researchers. The negative results of the Women's Health Initiative study (WHI), and follow‐up reports published inJAMA, evaluating the safety of estro‐progestogen in postmenopausal women, elicited an unprecedented reaction in the press by women and doctors alike. From these publications, it is clear that research should focus on new progestogens and on alternative administration routes to minimize adverse drug effects. One approach to the improvement of safety, efficacy, and acceptability of steroid hormones, including patient compliance, is to develop long‐acting implantable methods that deliver the lowest possible dose to the key target tissues. This therapeutic concept of “minimal intervention” has been known for several decades, but the practical applications of the method were lacking. Intrauterine drug‐delivery systems can be developed to achieve minimal intervention fertility control without influencing normal ovarian function and/or causing adverse hormonal effects. With hormone replacement therapy in postmenopausal women, research suggests that progestogens delivered directly to the uterine mucosa could reduce side effects and minimize reversal of the beneficial effect of estrogens. Various “frameless” and “framed” intrauterine systems are currently being clinically evaluated. They are less troublesome than the available intrauterine systems and could therefore be suitable for use in the majority of women for contraception and treatment purposes (e.g., menorrhagia, hormone replacement). These systems require a single short office procedure, and have a low morbidity, which is undeniably linked with more invasive methods and systemic hormonal contraceptives. Due to the technological progress miniature, low‐dose, long‐term intrauterine drug‐delivery systems offer enhanced effectiveness, reduced side effects, and optimal user compliance. Although there is minimal absorption in the systemic circulation, they deserve the status of a locally acting method that should be regarded as fundamentally advantageous, if effective, to systemically applied medications that may have potentially inherent ill side effects.
Oral Contraceptives and Reproductive System Cancer
Authors: DELIGEOROGLOU E. , MICHAILIDIS E. , CREATSAS G.
Published: January 2004

Abstract: Extensive research during the last 20 years has shown that oral contraceptives are safe. Several recent epidemiological studies have confirmed that combined oral contraceptives (COCs) provide substantial protection against endometrial and ovarian cancer, and this protection is long‐lasting and may persist for 15 or more years after termination of OC use. In many studies COCs have been associated with an increased risk of cervical abnormalities and cervical cancer, but there might be alternative explanations for these epidemiological associations (COC users can start having sexual intercourse at an earlier age, they have more sexual partners, and they rarely use barrier methods of contraception), so OCs act as a promoter for HPV‐induced carcinogenesis. Finally, women who are currently using COCs or have used them in the past 10 years are at a slightly increased risk of having breast cancer during the next 10 years, although the additional cancers diagnosed tend to be localized to the breast and they are less advanced clinically than the cancers diagnosed in those who have never used COCs.
The Role of Selective Estrogen Receptor Modulators (SERMs) in Postmenopausal Health
Authors: DRAPER MICHAEL W.
Published: January 2004

Abstract: Concerns about long‐term therapy with HRT have recently highlighted interest in a class of compounds active in the estrogen receptor, but with selectivity in their actions, known as the selective estrogen receptor modulators (SERMs). Tamoxifen is recognized as the first widely marketed SERM, but its selectivity focuses interest on its approved indications: the treatment and prevention of breast cancer. Raloxifene has been approved in most countries of the world for the treatment and prevention of oseoporosis, and it displays a pattern of actions highly matched to the needs and concerns of many postmenopausal women. Further study of current and future SERMs promises to open new vistas in patient‐specific management of the field of postmenopausal health.
Endometrial Pinopodes and Uterine Receptivity
Authors: NIKAS GEORGE , MAKRIGIANNAKIS ANTONIS
Published: January 2004

Abstract: The human endometrium is an extremely sensitive target for steroid hormones. During the menstrual cycle, this tissue undergoes dynamic changes which are reflected on the surface morphology of the epithelium, and which can be followed by scanning electron microscopy. The morphological changes peak at the midsecretory phase, with the formation of the so‐called pinopodes. Increasing evidence suggests that these pinopodes are accurate markers for endometrial receptivity, and their detection may be of high clinical utility for the preparation of endometrium before embryo transfer.
In Vitro Fertilization: Angiogenic, Proliferative, and Apoptotic Factors in the Follicular Fluid
Authors: MALAMITSI‐PUCHNER ARIADNE , SARANDAKOU ANGELIKI , BAKA STAVROULA , HASIAKOS DEMETRIOS , KOUSKOUNI EVANGELIA , CREATSAS GEORGE
Published: January 2004

Abstract: The studies reported investigated the concentrations of angiogenic, proliferative, and apoptotic factors in the follicular fluid (FF) of individual follicles, aspirated from women undergoing controlled ovarian hyperstimulation using a long protocol for IVF treatment. Furthermore, the association of the concentrations of the preceding factors with oocyte maturity was studied. Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), angiogenin, tissue polypeptide specific antigen (TPS), and soluble Fas (sFas) were all found in the FF of all follicles examined. Moreover, from the angiogenic factors only angiogenin concentrations, and from the apoptotic factors sFas concentrations (the soluble form expressing rather an antiapoptotic function), were positively associated with oocyte maturity, possibly indicating angiogenin's biological role beyond neovascularization and a lower apoptotic rate allowing oocytes to mature. Last, the abundant expression of TPS in FF may be indicative of intense cell proliferation, in cases of ovarian stimulation.
Electrophysiological Interactions between Striatal Glutamatergic and Dopaminergic Systems
Authors: WEST ANTHONY R. , FLORESCO STAN B. , CHARARA ALI , ROSENKRANZ J. AMIEL , GRACE ANTHONY A.
Published: January 2004

Abstract: Glutamatergic and dopaminergic systems play a primary role in frontal‐subcortical circuits involved in motor and cognitive functions. Considerable evidence has emerged indicating that the complex interaction between these neurotransmitter systems within the dorsal striatum and nucleus accumbens is critically involved in the gating of information flow in these highly integrative brain regions. As a result, disruptions of the interaction between glutamate and dopamine has been proposed as a pathological basis for a number of disorders, including the pathophysiology of schizophrenia. In this chapter, we discuss recent studies that have significantly advanced our understanding of the reciprocal interactions between glutamatergic and dopaminergic systems within the striatal complex in the normal brain and in pathological states.
Glutamate Receptors and Transporters in the Hippocampus in Schizophrenia
Authors: HARRISON PAUL J. , LAW AMANDA J. , EASTWOOD SHARON L.
Published: January 2004

Abstract:Postmortem studies, using various methods and directed at several molecular targets, have provided increasing evidence that glutamatergic neurotransmission is affected in schizophrenia. The bulk of the data are in the hippocampus, wherein there is reduced expression of one or more subunits for all three ionotropic receptors (NMDA, AMPA, and kainate). Presynaptic glutamatergic markers, notably the vesicular glutamate transporter VGLUT1, may also be decreased in schizophrenia, especially in older subjects. CA1 appears less affected than other subfields, and the decrements may be greater in the left than in the right hippocampus. The recently described susceptibility genes for schizophrenia all act upon glutamatergic synaptic transmission, which may, therefore, be part of the core pathophysiology of the disorder.
Glutamate Transmission and Addiction to Cocaine
Authors: KALIVAS PETER W. , McFARLAND KRISTA , BOWERS SCOTT , SZUMLINSKI KAREN , XI ZHENG‐XIONG , BAKER DAVID
Published: January 2004

Abstract: A variety of data point to the possibility that neuroadaptations in glutamate transmission are produced by repeated exposure to cocaine that result in the expression of behaviors characteristic of addiction, such as craving and relapse. Using the reinstatement model of relapse in rats, glutamate release in the projection from the prefrontal cortex to the nucleus accumbens has been shown to underlie cocaine‐ and stress‐primed reinstatement. In this report, four adaptations produced by withdrawal from repeated cocaine are described that may regulate the release of glutamate underlying reinstatement of drug‐seeking resulted. (1) Neurons in the prefrontal cortex have increased levels of activator of G protein signaling 3 (AGS3) that causes reduced signaling through Gi coupled receptors, and normalization of AGS3 blocked cocaine‐primed reinstatement. (2) The activity of the cystine‐glutamate exchanger is reduced resulting in decreased extracellular glutamate in the nucleus accumbens, and normalization of exchanger activity prevented cocaine‐primed reinstatement. (3) Metobotropic glutamate receptor function is diminished after repeated cocaine administration that results in reduced regulation of glutamate release. (4) Homer1 protein is reduced in the nucleus accumbens, and Homer2 knockout mice show enhanced responsiveness to cocaine. Taken together, there appears to be both pre‐ and postsynaptic changes in glutamate transmission that dysregulates the glutamatergic projection from the prefrontal cortex to the nucleus accumbens. These adaptations are hypothesized to facilitate glutamate release in response to a cocaine injection or acute stress and lead to the reinstatement of drug‐seeking behavior.
NMDA Receptor Antagonism and the Ethanol Intoxication Signal
Authors: KRYSTAL JOHN H. , PETRAKIS ISMENE L. , KRUPITSKY EVGENY , SCHÜTZ CHRISTIAN , TREVISAN LOUIS , D'SOUZA D. CYRIL
Published: January 2004

Abstract:This paper reviews clinical evidence suggesting that antagonism of theN‐methyl‐d‐aspartate subtype of glutamate receptors by ethanol may convey an important component of the ethanol intoxication signal, that is, subjective and objective responses associated with the consumption of a large amount of ethanol. It will then review recent evidence that two phenotypes associated with increased risk for heavy alcohol consumption, recovering ethanol‐dependent patients, and healthy individuals with a family history of alcohol dependence, exhibit reduced sensitivity to the dysphoric consequences of administration of the NMDA receptor antagonist, ketamine. Each of these groups displays reduced sensitivity to a potentially important response that might normally trigger the cessation of ethanol consumption. These data raise the possibility that alterations in NMDA receptor function that reduce the response to the NMDA antagonist component of ethanol may increase the risk for heavy drinking. This hypothesis is consistent with growing evidence that NMDA receptor antagonists may play a role in the treatment of alcoholism by suppressing alcohol withdrawal, reducing the development or expression of alcohol tolerance, or preventing or reversing the sensitiziation to ethanol effects.
Glutamatergic Transmission in Opiate and Alcohol Dependence
Authors: SIGGINS GEORGE ROBERT , MARTIN GILLES , ROBERTO MARISA , NIE ZHIGUO , MADAMBA SAMUEL , DE LECEA LUIS
Published: January 2004

Abstract: Both the nucleus accumbens (NAcc) and central amygdala (CeA) are thought to play roles in tolerance to, and dependence on, abused drugs. Although our past studies in rat brain slices suggested a role for NMDA receptors (NMDARs) in NAcc neurons in the effects of acute and chronic opiate treatment, the cellular and molecular mechanisms remained unclear. Therefore, we examined the effects of morphine dependence on electrophysiological properties of NMDARs in freshly isolated NAcc neurons and on expression of mRNA coding for NR2A‐C subunits using single‐cell RT‐PCR. Chronic morphine did not alter the affinity for NMDAR agonists glutamate, homoquinolinate, or NMDA, but decreased the affinity of the coagonist glycine. Chronic morphine altered the NMDAR inhibition by two NMDAR antagonists, 7‐Cl‐kynurenate and ifenprodil, but not that by d‐APV or Mg2+. Chronic morphine accelerated the NMDA current desensitization rate in NAcc neurons. In single‐cell RT‐PCR, chronic morphine predominantly reduced the number of neurons expressing multiple NR2 subunits. Ethanol also alters NMDARs. We found that low ethanol concentrations (IC50= 13 mM) inhibited NMDA currents and NMDA‐EPSPs in most NAcc neurons in a slice preparation. NAcc neurons from ethanol‐dependent rats showed enhanced NMDA sensitivity. In CeA neurons, acute ethanol decreased (by 10–25%) non‐NMDA‐ and NMDA‐EPSPs in most neurons. In CeA neurons from ethanol‐dependent rats, acute ethanol decreased the non‐NMDA‐EPSPs to the same extent as in naïve rats, but inhibited (by 30–40%) NMDA‐EPSPs significantly more than in controls, suggesting sensitization to ethanol. Preliminary studies with microdialysis and real‐time PCR analysis support this idea: local ethanol administration in vivo had no effect on glutamate release, but chronic ethanol nearly tripled the expression of NR2B subunits (the most ethanol sensitive) in CeA. These combined findings suggest that changes in glutamatergic transmission in NAcc and CeA may underlie the neuroadaptions that lead to opiate and ethanol dependence.
Plastic Control of Striatal Glutamatergic Transmission by Ensemble Actions of Several Neurotransmitters and Targets for Drugs of Abuse
Authors: LOVINGER DAVID M. , PARTRIDGE JOHN G. , TANG KA‐CHOI
Published: January 2004

Abstract: Long‐lasting alterations in the efficacy of glutamatergic synapses, such as long‐term potentiation (LTP) and long‐term depression (LTD), are prominent models for mechanisms of information storage in the brain. It has been suggested that exposure to drugs of abuse produces synaptic plasticity at glutamatergic synapses that shares many features with LTP and LTD, and that these synaptic changes may play roles in addiction. We have examined the involvement of particular neurotransmitters in synaptic plasticity at glutamatergic synapses within the striatum, a brain region with prominent roles in initiation and sequencing of actions, as well as habit formation. Our studies indicate that multiple neurotransmitters interact to produce striatal synaptic plasticity, and that the relative strength and patterning of the afferent inputs that release the various neurotransmitters determines whether LTP or LTD is activated. Drugs of abuse interact with glutamatergic synaptic plasticity in multiple ways, including alterations in dopamine release and more direct effects on glutamate release and glutamate receptors. We hypothesize that these effects contribute to addiction by facilitating the formation of new, drug‐centered habits, and by disruption of more adaptive behaviors.
Regulation of Cellular Plasticity Cascades in the Pathophysiology and Treatment of Mood Disorders
Authors: ZARATE CARLOS A. , DU JING , QUIROZ JORGE , GRAY NEIL A. , DENICOFF KIRK D. , SINGH JASKARAN , CHARNEY DENNIS S. , MANJI HUSSEINI K.
Published: January 2004

Abstract: There is increasing evidence from a variety of sources that mood disorders are associated with regional reductions in brain volume, as well as reductions in the number, size, and density of glia and neurons in discrete brain areas. Although the precise pathophysiology underlying these morphometric changes remains to be fully elucidated, the data suggest that severe mood disorders are associated with impairments of structural plasticity and cellular resilience. In this context, it is noteworthy that a growing body of data suggests that the glutamatergic system—which is known to play a major role in neuronal plasticity and cellular resilience—may be involved in the pathophysiology and treatment of mood disorders. Preclinical studies have shown that the glutamatergic system represents targets (often indirect) for the actions of antidepressants and mood stabilizers. There are a number of glutamatergic “plasticity enhancing” strategies that may be of considerable utility in the treatment of mood disorders. Among the most immediate ones are NMDA antagonists, inhibitors of glutamate‐release agents, and AMPA potentiators; this research progress holds much promise for the development of novel therapeutics for the treatment of severe, refractory mood disorders.
Converging Evidence of NMDA Receptor Hypofunction in the Pathophysiology of Schizophrenia
Authors: COYLE JOSEPH T. , TSAI GUOCHUAN , GOFF DONALD
Published: January 2004

Abstract: Numerous clinical studies demonstrate that subanesthetic doses of dissociative anesthetics, which are noncompetitive antagonists at the NMDA receptor, replicate in normal subjects the cognitive impairments, negative symptoms, and brain functional abnormalities of schizophrenia. Postmortem and genetic studies have identified several abnormalities associated with schizophrenia that would interfere with the activation of the glycine modulatory site on the NMDA receptor. Placebo‐controlled clinical trials with agents that directly or indirectly activate the glycine modulatory site consistently reduce negative symptoms and frequently improve cognition in patients with chronic schizophrenia who are receiving concurrent typical antipsychotics. Thus, there is convincing evidence that hypofunction of a subset of NMDA receptors may contribute to the symptomatic features of schizophrenia.
Glutamate, Dopamine, and Schizophrenia
Authors: LARUELLE MARC , KEGELES LAWRENCE S. , ABI‐DARGHAM ANISSA
Published: January 2004

Abstract: The fundamental pathological process(es) associated with schizophrenia remain(s) uncertain, but multiple lines of evidence suggest that this condition is associated with (1) excessive stimulation of striatal dopamine (DA) D2 receptors, (2) deficient stimulation of prefrontal DA D1 receptors and, (3) alterations in prefrontal connectivity involving glutamate (GLU) transmission at N‐methyl‐d‐aspartate (NMDA) receptors. This chapter first briefly discusses the current knowledge status for these abnormalities, with emphasis on results derived from clinical molecular imaging studies. The evidence for hyperstimulation of striatal D2 receptors rests on strong pharmacological evidence and has recently received support from brain imaging studies. The hypothesis of deficient prefrontal cortex (PFC) D1 receptor stimulation is almost entirely derived from preclinical studies. Preliminary imaging data compatible with this hypothesis have recently emerged. The NMDA hypofunction hypothesis originates mainly from indirect pharmacological data. The interactions between DA and GLU systems relevant to schizophrenia are then reviewed. Animal and imaging data supporting the general model that the putative DA imbalance in schizophrenia (striatal excess and cortical deficiency) might be secondary to NMDA hypofunction in the PFC and its connections are presented. Equally important are the potential consequences of this DA imbalance for NMDA function in the striatum and the cortex, which are subsequently discussed. In conclusion, it is proposed that schizophrenia is associated with strongly interconnected abnormalities of GLU and DA transmission: NMDA hypofunction in the PFC and its connections might generate a pattern of dysregulation of DA systems that, in turn, further weakens NMDA‐mediated connectivity and plasticity.
Neural Control of Three‐Dimensional Eye and Head Posture
Authors: KLIER ELIANA M. , CRAWFORD J. DOUGLAS
Published: January 2004

The neural commands for gaze control include not only signals that drive the eyes and head from one point to the next, but also those that hold the eyes and head steady at the end of each movement. Studies using microstimulation and chemical inactivation techniques, in head‐fixed and head‐free macaques, were used to investigate the role of the interstitial nucleus of Cajal (INC) in the production of the latter, tonic signals. The right INC was found to control clockwise‐up and clockwise‐down components of both eye and head orientation, whereas the left INC was found to control the counterclockwise‐up and counterclockwise‐down components. Temporary inactivation of the INC left the eyes and head unable to hold their final torsional and vertical positions after each gaze shift. Thus, the INC is strongly implicated in the production of the tonic, step‐like commands that maintain eye and head orientations between gaze shifts. In addition, these studies also found that the INC represents the torsional and vertical commands for eye and head orientation using different coordinate coding strategies, optimally matched to the different three‐dimensional postural constraints observed in the eye and head.
Dynamic Modulation of Ocular Orientation during Visually Guided Saccades and Smooth‐Pursuit Eye Movements
Authors: HESS BERNHARD J.M. , ANGELAKI DORA E.
Published: January 2004

Rotational disturbances of the head about an off‐vertical yaw axis induce a complex vestibuloocular reflex pattern that reflects the brain's estimate of head angular velocity as well as its estimate of instantaneous head orientation (at a reduced scale) in space coordinates. We show that semicircular canal and otolith inputs modulate torsional and, to a certain extent, also vertical ocular orientation of visually guided saccades and smooth‐pursuit eye movements in a similar manner as during off‐vertical axis rotations in complete darkness. It is suggested that this graviceptive control of eye orientation facilitates rapid visual spatial orientation during motion.
Morphological Properties of Vestibulospinal Neurons in Primates
Authors: BOYLE RICHARD , JOHANSON CURT
Published: January 2004

The lateral and medial vestibulospinal tracts constitute the major descending pathways controlling extensor musculature of the body. We examined the axon morphology and synaptic input patterns and targets in the cervical spinal segments from these tract cells using intracellular recording and biocytin labeling in the squirrel monkey. Lumbosacral projecting cells represent a private, and mostly rapid, communication pathway between the dorsal Deiters' nucleus and the motor circuits controlling the lower limbs and tail. The cervical projecting cells provide both redundant and variable synaptic input to spinal cell groups, suggesting both general and specific control of the head and neck reflexes.
The Role of the Fastigial Nucleus in Saccadic Eye Oscillations
Authors: HELMCHEN CHRISTOPH , RAMBOLD HOLGER , ERDMANN CHRISTIAN , MOHR CHRISTIAN , SPRENGER ANDREAS , BINKOFSKI FERDINAND
Published: January 2004

For the first time, we provide functional magnetic resonance imaging evidence for a recent hypothesis that saccadic oscillations in opsoclonus may result from a disinhibition of the cerebellar fastigial nuclei. Two patients with severe opsoclonus were examined during fixation in the light and during eye closure and in darkness where opsoclonus disappeared. Their activation during opsoclonus was compared with 10 healthy subjects performing visually guided and self‐paced saccades in the light and darkness. In contrast to the control subjects, the patients showed a strong bilateral midline cerebellar activation that involved the deep cerebellar nuclei. This is probably not just a secondary finding in the fastigial nuclei due to the high frequent saccadic activity because there was, concomitantly, no oculomotor vermal activation, which is normally seen in healthy subjects. We propose that cerebellar activation of the fastigial nuclei may cause opsoclonus via their projections to the brainstem saccadic generator.
Vestibular Signals of Posterior Parietal Cortex Neurons during Active and Passive Head Movements in Macaque Monkeys
Authors: KLAM FRANÇOIS , GRAF WERNER
Published: January 2004

The posterior parietal cortex may function as an interface between sensory and motor cortices and thus could be involved in the formation of motor plans as well as abstract representations of space. We have recorded from neurons in the intraparietal sulcus, namely, the ventral and medial intraparietal areas (VIP and MIP, respectively), and analyzed their head‐movement‐related signals in relation to passive and active movements. To generate active head movements, we made the animals track a moving fixation spot in the horizontal plane under head‐free conditions. When under certain circumstances the animals were tracking the fixation spot almost exclusively via head movements, a clear correlation between neuronal firing rate and head movement could be established. Furthermore, a newly employed paradigm, the “replay method,” made available direct comparison of neuronal firing behavior under active and passive movement conditions. In such case, the animals were allowed to make spontaneous head movements in darkness. Subsequently, the heads were fixed and the previously recorded active head‐movement profile was reproduced by a turntable as passive stimulation. Neuronal responses ranged from total extinction of the vestibular signal during active movement to presence of activity only during active movement. Furthermore, in approximately one‐third of the neurons, a change of vestibular on‐direction depending on active versus passive movement mode was observed, that is, type I neurons became type II neurons, etc. We suggest that the role of parietal vestibular neurons has to be sought in sensory space representation rather than reflex behavior and motor control contexts.
Inhibitory Interhemispheric Visuovisual Interaction in Motion Perception
Authors: BRANDT THOMAS , MARX ESTHER , STEPHAN THOMAS , BENSE SANDRA , DIETERICH MARIANNE
Published: January 2004

Findings of an earlier functional magnetic resonance imaging (fMRI) study that coherent motion stimulation of the right or left visual hemifield exhibited negative signal changes (deactivations) in the primary visual cortex and the lateral geniculate nucleus contralateral to the stimulated hemisphere were evaluated to determine the functional significance of this contralateral inhibition of the visual system. Fourteen subjects participated in a psychophysical study on the perception of single object motion (0.4°/s) in one visual hemifield with or without concurrent coherent motion stimulation of the contralateral hemifield. Mean detection times for horizontal object motion (0.5 ± 0.19 vs. 0.61 ± 0.22 s) and vertical object motion (0.53 ± 0.19 vs. 0.72 ± 0.34 s) were significantly prolonged during concurrent motion pattern stimulation in the contralateral hemifield. These data support the interpretation that the deactivation of neuronal activity in the visual system found by fMRI is associated with a functional decrement in the sensitivity needed to perceive motion and may reflect transcallosal attentional shifts between the two hemispheres.
Spatial Memory Deficits in Patients with Chronic Bilateral Vestibular Failure
Authors: SCHAUTZER FRANZ , HAMILTON DEREK , KALLA ROGER , STRUPP MICHAEL , BRANDT THOMAS
Published: January 2004

The role of the vestibular system for navigation and spatial memory has been demonstrated in animals but not in humans. Vestibular signals are necessary for location‐specific “place cell” activity in the hippocampus which provides a putative neural substrate for the spatial representation involved in navigation. To investigate the spatial memory in patients with bilateral vestibular failure due to NF2 with bilateral neurectomy, a virtual variant (on a PC) of the Morris water task adapted to humans was used. Significant spatial learning and memory deficits were shown in 12 patients as compared to 10 healthy controls. These data suggest that functional hippocampal deficits manifest due to a chronic lack of vestibular input in these patients. These deficits can even be demonstrated with the subjects stationary, i.e., without any actual vestibular or somatosensory stimulation.
The Human Horizontal Vestibulo‐Ocular Reflex in Response to Active and Passive Head Impulses after Unilateral Vestibular Deafferentation
Authors: HALMAGYI G. M. , BLACK R. A. , THURTELL M. J. , CURTHOYS I. S.
Published: January 2004

We studied the compensatory eye movements made by subjects with unilateral vestibular deficits in response to passive (unpredictable, manually generated) and active (predictable, self‐generated) head impulses. A typical head impulse is a brief, low‐amplitude (15‐20°), high‐velocity (150‐350°/s), high‐acceleration (4000‐6000°/s2), yaw head‐on‐trunk rotation. In the initial 75 ms of the response, the vestibulo‐ocular reflex gain was significantly higher during active head impulses to both ipsilesional and contralesional sides, than during passive impulses. Mean gains were 0.15 (ipsilesional passive), 0.44 (ipsilesional active), 0.5 (contralesional passive), and 0.76 (contralesional active). Differences between active and passive head impulses were present from near the onset of head rotation. The mechanism for producing this behavior is unclear, but the findings could be related to enhanced sensitivity of second‐order neurons during active head impulses. However, even with active movements, there is still a large and statistically significant asymmetry in the eye‐movement responses for ipsilesional as opposed to contralesional head rotations. After 75 ms, rapid corrective eye movements often were generated to reduce any remaining gaze error.
Incomitance of Ocular Rotation Axes in Trochlear Nerve Palsy
Authors: WEBER KONRAD P. , PALLA ANTONELLA , LANDAU KLARA , HASLWANTER THOMAS , STRAUMANN DOMINIK
Published: January 2004

Strabismus due to palsy of a single muscle in one eye is always incomitant, which is a consequence of Hering's law of equal innervation. We asked whether this law had similar consequences on the orientation of ocular rotation axes. Patients with unilateral trochlear nerve palsy were oscillated about the nasooccipital (= roll) axis (±35°, 0.3 Hz), and monocularly fixed on targets on a head‐fixed Hess screen. Both the covered and uncovered eyes were measured with dual search coils. The rotation axis of the covered eye (paretic or healthy) tilted more nasally from the line of sight when gaze was directed toward the side of the healthy eye. The rotation axis of the viewing eye (paretic or healthy), however, remained roughly aligned with the line of sight. We conclude that incomitance due to eye muscle palsy extends to ocular rotation axes during vestibular stimulation.
The Critical Role of Velocity Storage in Production of Motion Sickness
Authors: COHEN BERNARD , DAI MINGJIA , RAPHAN THEODORE
Published: January 2004

We propose that motion sickness is mediated through the orientation properties of velocity storage in the vestibular system that tend to align eye velocity produced by the angular vestibulo‐ocular reflex (aVOR) with gravito‐inertial acceleration (GIA). (GIA is the sum of the linear accelerations acting on the head. In the absence of translational accelerations, gravity is the GIA.) We further postulate that motion sickness produced by cross‐coupled vestibular stimulation can be characterized by a metric composed of the disparity between the axis of eye rotation and the GIA, the strength of the response to angular motion, and the response duration, as determined by the central vestibular time constant, that is, by the time constant of velocity storage. The nodulus and uvula of the vestibulocerebellum are likely to be the central sites where the disparity is sensed, where the vestibular time constants are habituated, and where links are made to the autonomic system to produce the symptoms and signs.
Expression of CCAAT/enhancer-binding protein-beta (C/EBPβ) and CHOP in the murine growth plate
Authors: Martos-Rodríguez A. , Santos-Alvarez I. , Campo-Ruíz V. , González S. , García-Ruiz J. P. , Delgado-Baeza E.
Published: January 2004

Our aim was to evaluate the expression of transcription factors CCAAT/enhancer-binding protein-beta (C/EBPβ) and C/EBP-homologous protein (CHOP) in the growth plate. Proximal tibial epiphyseal growth plates from ten 15-day-old Wistar rats were used. Additionally, anti-proliferating cell nuclear antigen (PCNA), anti-5-bromo-2’-deoxyuridine (BrdU) immunostaining, terminal transferase dUTP nick end-labelling (TUNEL) and nucleolar organiser region-associated proteins (AgNOR) techniques were peformed. The histological morphology of the growth plate from C/EBPβknock-out mice was also analysed.

The normal growth plate showed that C/EBPβ and CHOP factors are expressed both in the germinative/ upper proliferative and in the lower proliferative zones. Furthermore, BdrU+ and PCNA+ cells were present exclusively in the germinative and proliferative zones, while TUNEL+ and AgNOR+ cells were seen in all three zones of the growth plate. Acellular areas, hypocellularity, the increase in cell death and anomalies in the architecture of the cell columns were observed in the growth plates of C/EBPβ (−/ −) knockout mice.

We suggest that C/EBPβ and CHOP transcription factors may be key modulators participating in the chondrocyte differentiation process in the growth plate.
The peroneus quartus muscle
Authors: Zammit J. , Singh D.
Published: January 2004

Whilst a few studies have associated various symptoms with the presence of a peroneus quartus muscle in the peroneal compartment of the leg, little is known of the clinical relevance of this muscle.

We dissected 102 cadaver legs and reviewed the magnetic resonance images of 80 patients with symptoms from the ankle. The peroneus quartus, with a number of different attachments, was present in 6.6% of the legs. It most commonly arose from the peroneus brevis muscle and inserted into the retrotrochlear eminence of the calcaneum. Associated pathology included a longitudinal tear in the tendon of peroneus brevis, possible peroneal tendon subluxation or dislocation, and a prominent retrotrochlear eminence. On the MR scans its presence was associated with pain and weakness of the ankle.

Orthopaedic surgeons and radiologists should be aware of the possible presence of the peroneus quartus muscle, not only because of possible associated pathology, but also for its potential use for surgical reconstruction.
A modified system of stress radiography for patellofemoral instability
Authors: Fukui N. , Nakagawa T. , Murakami S. , Hiraoka H. , Nakamura K.
Published: January 2004

Axial radiographs were obtained under valgus and external rotation stress at 45° of knee flexion with and without contraction of the quadriceps muscle in order to assess the dynamics of patellar subluxation or dislocation. The radiography was performed on 82 knees in 61 patients with patellofemoral instability, and on 44 normal knees. The lateral patellofemoral angle and the congruence angle were measured and compared with the conventional Merchant views. Both parameters showed greater differences between symptomatic and normal knees on the stress radiographs obtained without quadriceps contraction. There was a major difference in the lateral patellofemoral angles between the groups, which clearly distinguished symptomatic knees from normal controls. Congruence angles on stress radiography had a significant correlation with the functional scores obtained after a period of conservative treatment and a positive correlation with the frequency of patellar subluxation.

When the quadriceps contracted, two patterns of patellar shift were observed. While the patella reduced into the trochlear groove in all normal knees and about 70% of the symptomatic knees, contraction of the quadriceps caused further subluxation of the patella in the remaining symptomatic knees. All the knee joints which showed this displacement failed to respond to conservative treatment and eventually required surgical treatment. Thus, this technique of stress radiography is a simple, cost-effective and useful method of evaluating patellar instability and predicting the prognosis.
Fixation of a hydroxyapatite-tricalcium phosphate-coated cementless knee prosthesis
Authors: Akizuki S. , Takizawa T. , Horiuchi H.
Published: January 2004

Miller-Galante II total knee arthroplasty (MG II TKA) was performed on 32 knees in 30 patients. On both the femoral and tibial components, the fibre-metal area was plasma-sprayed with hydroxyapatite-tricalcium phosphate (HA-TCP). The clinical and radiographic outcome was evaluated. A mean pre-operative knee score of 26.0 ± 18.6 (SD) increased to 97.5 ± 3.5 and a mean pre-operative functional score of 21.7 ± 15.0 (SD) increased to 83.4 ± 12.4 at follow-up of seven years. Clear zones were common around the components at one month post-operatively but had completely disappeared after six months. An autopsy of a patient who underwent MG II TKA with HA-TCP two years previously, showed osteogenesis in all parts of the fibre-metal, and bone tissue comprised 77.7% of the interface. This coated prosthesis has good early fixation which is maintained at seven years with good clinical and radiographic outcomes.
Closed reduction of developmental dislocation of the hip by prolonged traction
Authors: Yamada N. , Maeda S. , Fujii G. , Kita A. , Funayama K. , Kokubun S.
Published: January 2004

The efficacy of traction before an attempted closed reduction for patients with developmental dislocation of the hip remains controversial. We treated 55 children (62 dislocations of the hip) by preliminary, prolonged traction for a mean of eight weeks. All were followed up for at least two years in order to observe the development of any avascular changes within the femoral head. Of the 55 children, 27 (31 dislocations) were followed up until they were over six years of age. Fifty-seven of the 62 hips (92%) showed a successful closed reduction. Only one had radiological evidence of avascular necrosis of the femoral head. Of the 31 hips which were followed up to over six years of age, 15 (48%) showed residual subluxation. Our method of prolonged preliminary traction leads to a high rate of successful closed reduction, a low incidence of avascular necrosis and a reduced need for secondary operations.
Outcome after later combined brachial plexus and shoulder surgery after birth trauma
Authors: Grossman J. A. I. , Price A. E. , Tidwell M. A. , Ramos L. E. , Alfonso I. , Yaylali I.
Published: January 2004

Of 22 infants aged between 11 and 29 months who underwent a combined reconstruction of the upper brachial plexus and shoulder for the sequelae of a birth injury, 19 were followed up for two or more years. The results were evaluated using a modified Gilbert scale. Three patients required a secondary procedure before follow-up. Three patients had a persistent minor internal rotation contracture. All improved by at least two grades on a modified Gilbert scale.