bluuebunny/crossref_metadata_2025 huggingface dataset:
Rhythm in Language and Music
Authors: PATEL ANIRUDDH D.
Published: January 2004

Abstract:Rhythm is widely acknowledged to be an important feature of both speech and music, yet there is little empirical work comparing rhythmic organization in the two domains. One approach to the empirical comparison of rhythm in language and music is to break rhythm down into subcomponents and compare each component across domains. This approach reveals empirical evidence that rhythmic grouping is an area of overlap between language and music, but no empirical support for the long‐held notion that language has periodic structure comparable to that of music. Focusing on the statistical patterning of event duration, new evidence suggests that the linguistic rhythm of a culture leaves an imprint on its musical rhythm. The latter finding suggests that one effective strategy for comparing rhythm in language and music is to determine if differences in linguistic rhythm between cultures are reflected in differences in musical rhythm.
Recognition of Interleaved Melodies
Authors: BEY CAROLINE , ZATORRE ROBERT J.
Published: January 2004

Abstract: An fMRI study of interleaved melody recognition was conducted to examine the neural basis of the bottom‐up and top‐down mechanisms involved in auditory stream segregation. Hemodynamic activity generated by a mixed sequence was recorded in eight listeners who were asked to recognize a target melody interleaved with distractor tones when the target was presented either before or after the composite sequence. fMRI results suggest that similar cortical networks were involved in both conditions, including bilaterally the auditory cortices within the superior temporal gyrus as well as the thalamus and the inferior frontal gyrus. However, when listeners heard the melody before they had to extract it from the mixture, neural activation in the inferior frontal operculum was significantly enhanced bilaterally; no change in auditory cortical activity was detected.
Electrical Brain Responses to Descriptive versus Evaluative Judgments of Music
Authors: BRATTICO ELVIRA , JACOBSEN THOMAS , DE BAENE WOUTER , NAKAI NOA , TERVANIEMI MARI
Published: January 2004

Abstract: The present study was aimed at finding neural correlates of aesthetic versus descriptive listening of the same musical cadences. Results showed that aesthetic listening generated greater right frontocentral negativities than did descriptive listening, indicating distinct cortical mechanisms for aesthetic versus descriptive processing of music.
Estimating Internal Drift and Just Noticeable Difference in the Perception of Continuous Tempo Drift
Authors: DAHL SOFIA , GRANQVIST SVANTE
Published: January 2004

Abstract: Is there such a thing as an internal representation of a “steady tempo” and is this representation itself free from tempo drift? To investigate this question, we propose a new method for studying detection of continuous tempo drift.
Congenital Amusia Interferes with the Ability to Synchronize with Music
Authors: BELLA SIMONE DALLA , PERETZ ISABELLE
Published: January 2004

Abstract: Eight adults with a music‐specific learning disability (i.e., tone deafness, but we prefer the term “congenital amusia”) were asked to tap along with music (e.g., Ravel's Bolero) and with nonmusical isochronous sequences (i.e., noise bursts). The amusic persons' tapping performance was poorly synchronized with music compared to that of nine matched control participants. By contrast, synchronization with the noise bursts was normal, suggesting that amusic persons' timing difficulty is limited to music.
Exploration of Roughness by Means of the Mismatch Negativity Paradigm
Authors: DE BAENE WOUTER , VANDIERENDONCK ANDRÉ , LEMAN MARC , WIDMANN ANDREAS , TERVANIEMI MARI
Published: January 2004

Abstract: A mismatch negativity study was set up to find the neural correlates of roughness perception. The results suggest that when the sounds are not attended to, roughness is reflected by the mismatch positivity as evidenced at the mastoid electrodes.
“Out‐of‐Pitch” but Still “In‐Time”
Authors: HYDE KRISTA L. , PERETZ ISABELLE
Published: January 2004

Abstract: Congenital amusia is a lifelong disability, commonly known as tone deafness, that prevents afflicted individuals from developing basic musical skills despite normal audiometry and above‐average intellectual, memory, and language skills. Although it is estimated that 4% of the general population would be born with such a musical handicap, the underlying cause is presently unknown. Recently, we proposed that this disorder could be traced to a deficit in pitch perception on the basis of a single case.4 Here we provide psychophysical evidence for the existence of a generalized defect that is both fine grained and specific to pitch because time is unaffected.
Evoked Potentials to Test Rhythm Perception Theories
Authors: JONGSMA MARIJTJE L.A. , DESAIN PETER , HONING HENKJAN , VAN RIJN CLEMENTINA M.
Published: January 2004

Abstract: The general aim of this study was to investigate how rhythmic information is processed by the brain and how a mental representation of a rhythm leads to expectancies about events in the near future. We investigate this by means of EEG recordings from which evoked potentials (EPs), resulting from sensory and cognitive neural activity, are extracted.
Perceiving Musical Scale Structures
Authors: NEUHAUS CHRISTIANE
Published: January 2004

Abstract: In this study, event‐related brain potentials (ERPs) are used to investigate the processing of musical scale structures from a cross‐cultural perspective. ERP reactions reveal that universal listening strategies per se are modified by culture.
Singing: A Selective Deficit in the Retrieval of Musical Intervals
Authors: SCHÖN DANIELE , LORBER BOGDAN , SPACAL MARTIN , SEMENZA CARLO
Published: January 2004

Abstract: A case of dissociation between discrimination and retrieval of musical information in a patient with a lesion of the right hemisphere is described. This patient has lost the ability to correctly retrieve a musical interval when required to sing. This occurs in the presence of unimpaired interval discrimination and correct retrieval of temporal patterns and melodic contour (direction).
Audiovisual Interactions in Music Reading
Authors: SCHÖNA DANIELE , BESSON MIREILLE
Published: January 2004

Abstract: The general aim of this experiment was to investigate the processes involved in reading musical notation and to study the relationship between written music and its auditory representation. Our main interest was to determine if musicians can develop expectancies for plausible or implausible auditory events on the sole basis of the visual score. Results showed that musicians can clearly expect auditory endings on the basis of visual information. These findings enliven the discussion on the question of whether music reading is actually music perception.
Preattentive Processing of Lexical Tone Perception by the Human Brain as Indexed by the Mismatch Negativity Paradigm
Authors: SITTIPRAPAPORN WICHIAN , CHINDADUANGRATN CHITTIN , TERVANIEMI MARI , KHOTCHABHAKDI NAIPHINICH
Published: January 2004

Abstract: Mismatch negativity (MMN) was used to investigate the processing of the discrimination between native and non‐native CV syllables in tonal languages. MMN elicited by the native word was greater than that elicited by the non‐native word. Hearing a native‐language deviant significantly altered the elicited MMN in both amplitude and scalp voltage field distribution, reflecting the presence of a long‐term memory trace for spoken words in tonal languages.
Becoming a Pianist
Authors: STEWART LAUREN , HENSON RIK , KAMPE KNUT , WALSH VINCENT , TURNER ROBERT , FRITH UTA
Published: January 2004

Abstract: Musically naïve subjects were scanned using functional magnetic resonance imaging (fMRI) before and after they had been taught to read music and play keyboard. When subjects played melodies from musical notation after training, activation was seen in a cluster of voxels within the right superior parietal cortex consistent with the view that music reading involves spatial sensorimotor mapping.
Activation of the Inferior Frontal Cortex in Musical Priming
Authors: TILLMANN BARBARA , JANATA PETR , BHARUCHA JAMSHED J.
Published: January 2004

Abstract: Musical contexts influence the processing of target events. Our study investigated the neural correlates of processing related and unrelated musical events presented as the last chord of eight‐chord sequences.
Analyzing Pitch Chroma and Pitch Height in the Human Brain
Authors: WARREN JASON D. , UPPENKAMP STEFAN , PATTERSON ROY D. , GRIFFITHS TIMOTHY D.
Published: January 2004

Abstract: The perceptual pitch dimensions of chroma and height have distinct representations in the human brain: chroma is represented in cortical areas anterior to primary auditory cortex, whereas height is represented posterior to primary auditory cortex.
The Perception of Microsound and its Musical Implications
Authors: ROADS CURTIS
Published: January 2004

Abstract:Sound particles or microsounds last only a few milliseconds, near the threshold of auditory perception. We can easily analyze the physical properties of sound particles either individually or in masses. However, correlating these properties with human perception remains complicated. One cannot speak of a single time frame, or a “time constant” for the auditory system. The hearing mechanism involves many different agents, each of which operates on its own timescale. The signals being sent by diverse hearing agents are integrated by the brain into a coherent auditory picture. The pioneer of “sound quanta,” Dennis Gabor (1900‐1979), suggested that at least two mechanisms are at work in microevent detection: one that isolates events, and another that ascertains their pitch. Human hearing imposes a certain minimum duration in order to establish a firm sense of pitch, amplitude, and timbre. This paper traces disparate strands of literature on the topic and summarizes their meaning. Specifically, we examine the perception of intensity and pitch of microsounds, the phenomena of tone fusion and fission, temporal auditory acuity, and preattentive perception. The final section examines the musical implications of microsonic analysis, synthesis, and transformation.
More About the Musical Expertise of Musically Untrained Listeners
Authors: BIGAND EMMANUEL
Published: January 2004

Abstract: Several behavioral experiments that were designed to compare the abilities of musicians and nonmusicians to process subtle changes in musical structures are surveyed. These experiments deal with different aspects of music perception including the processing of melodic and harmonic structures, the processing of large‐scale structures, and implicit learning. In all these experiments, the so‐called nonmusician listeners behaved in a very similar way as did highly trained students from music conservatories and music departments. This outcome suggests that when the experimental setting requires participants to process musical structures (in contrast to musical tones), the large audience of untrained listeners exhibits sophisticated musical abilities that are similar to those of musical experts. It has been suggested that musically untrained listeners are “experienced listeners” who use the same principles as musical experts in organizing their hearing of music.
Neurobiology of Rhythmic Motor Entrainment
Authors: MOLINARI MARCO , LEGGIO MARIA G. , DE MARTIN MARTINA , CERASA ANTONIO , THAUT MICHAEL
Published: January 2004

Abstract: Timing is extremely important for movement, and understanding the neurobiological basis of rhythm perception and reproduction can be helpful in addressing motor recovery after brain lesions. In this quest, the science of music might provide interesting hints for better understanding the brain timing mechanism. The report focuses on the neurobiological substrate of sensorimotor transformation of time data, highlighting the power of auditory rhythmic stimuli in guiding motor acts. The cerebellar role of timing is addressed in subjects with cerebellar damage; subsequently, cerebellar timing processing is highlighted through an fMRI study of professional musicians. The two approaches converge to demonstrate that different levels of time processing exist, one conscious and one not, and to support the idea that timing is a distributed function. The hypothesis that unconscious motor responses to auditory rhythmic stimuli can be relevant in guiding motor recovery and modulating music perception is advanced and discussed.
Neural Basis of Rhythmic Timing Networks in the Human Brain
Authors: THAUT MICHAEL H.
Published: January 2004

Abstract: The study of rhythmicity provides insights into the understanding of temporal coding of music and temporal information processing in the human brain. Auditory rhythms rapidly entrain motor responses into stable steady synchronization states below and above conscious perception thresholds. Studying the neural dynamics of entrainment by measuring brain wave responses (MEG) we found nonlinear scaling of M100 amplitudes generated in primary auditory cortex relative to changes in the period of the rhythmic interval during subliminal and supraliminal tempo modulations. In recent brain imaging studies we have described the neural networks involved in motor synchronization to auditory rhythm. Activated regions include primary sensorimotor and cingulate areas, bilateral opercular premotor areas, bilateral SII, ventral prefrontal cortex, and, subcortically, anterior insula, putamen, and thalamus. Within the cerebellum, vermal regions and anterior hemispheres ipsilateral to the movement became significantly activated. Tracking temporal modulations additionally activated predominantly right prefrontal, anterior cingulate, and intraparietal regions as well as posterior cerebellar hemispheres. Furthermore, strong evidence exists for the substantial benefits of rhythmic stimuli in rehabilitation training with motor disorders.
Effect of Unilateral Temporal Lobe Resection on Short‐Term Memory for Auditory Object and Sound Location
Authors: LANCELOT CÉLINE , SAMSON SÉVERINE , AHAD PIERRE , BAULAC MICHEL
Published: January 2004

Abstract: To investigate auditory spatial and nonspatial short‐term memory, a sound location discrimination task and an auditory object discrimination task were used in patients with medial temporal lobe resection. The results showed a double dissociation between the side of the medial temporal lobe lesion and the nature of the auditory discrimination deficits, suggesting that right and left temporal lobe structures are differently involved in auditory spatial and nonspatial short‐term memory.
Implicit and Explicit Emotional Memory for Melodies in Alzheimer's Disease and Depression
Authors: QUONIAM NOLWENN , ERGIS ANNE‐MARIE , FOSSATI PHILIPPE , PERETZ ISABELLE , SAMSON SÉVERINE , SARAZIN MARIE , ALLILAIRE JEAN‐FRANÇOIS
Published: January 2004

Abstract: The present study investigates the impact of emotional deficits on implicit and explicit memory for musical stimuli in patients with Alzheimer's disease and elderly depressed patients. Results showed that unlike Alzheimer's patients, depressed patients were unable to develop a positive affective bias of judgment for previously heard melodies.
Musicians Differ from Nonmusicians in Brain Activation despite Performance Matching
Authors: GAAB NADINE , SCHLAUG GOTTFRIED
Published: January 2004

Abstract: Brain activation patterns in a group of musicians and a group of nonmusicians (matched in performance score to the musician group) were compared during a pitch memory task using a sparse‐temporal sampling functional magnetic resonance imaging experiment. Both groups showed bilateral activaton (left more than right) of the superior temporal gyrus, supramarginal gyrus, posterior middle and inferior frontal gyrus, and superior parietal lobe. Musicians showed greater right posterior temporal and supramarginal activation, whereas nonmusicians had greater activation of the left secondary auditory cortex.
Experimental Strategies for Understanding the Role of Experience in Music Cognition
Authors: KRUMHANSL CAROL L.
Published: January 2004

Abstract: Research in music cognition has assessed the role of experience by investigating the effects of development, training, and cross‐cultural differences. A fourth approach is to apply statistical techniques to identify patterns that are relatively frequent in the listeners' musical experience. As an example of this approach, a functional magnetic resonance imaging (fMRI) study was conducted on melodic expectancy. Two patterns that frequently began musical themes in classical and folk music were identified. A final continuation tone was added to these opening patterns. Some of the continuation tones were frequent in the musical styles; others were infrequent. Listeners judged how well the continuation tones fit with their expectations. A sparse‐sampling (event‐related) design was used in the fMRI study, with image acquisition at varying delays after the sequence. Early acquisitions showed activation in the auditory cortex, and late acquisitions showed effects of the motor response. These results suggest the timing of the image acquisitions was appropriate. Contrasting melodies and monotonic controls showed right inferior frontal activation, similar to that found in other studies. However, no differences were found as a function of whether or not the continuation tone was frequent or infrequent in the statistical style analysis. Methodological differences of this study from other recent fMRI studies on harmonic expectations are discussed.
Biological and Psychological Correlates of Exceptional Performance in Development
Authors: OERTER ROLF
Published: January 2004

Abstract: The issue of exceptional performance is discussed from four perspectives: genetic distribution of high giftedness, gene‐environment interaction, neurobiological findings, and the role of deliberate practice as well as environment in general. The genetic perspective is illustrated mainly by the emergenic and epigenetic model of Simonton, followed by the three types of gene‐environment interaction (Scarr and McCartney). The neurological perspective focuses on the role of early practice for neurological representation and on hormonal changes during development. The perspective of deliberate practice summarizes the present state of affairs within this field of research. Finally, a distinction between different levels of excellent performance is proposed, arguing against the neglect of genius as a specific phenomenon among excellent performance.
Prosodic and Melodic Processing in Adults and Children
Authors: MAGNE CYRILLE , SCHÖN DANIELE , BESSON MIREILLE
Published: January 2004

Abstract:The results of a series of experiments aimed at directly comparing the prosodic level of processing in language with the melodic level of processing in music are reported. The first series of experiments was conducted on adults, musicians and nonmusicians, and the second one on 7‐ to 9‐year‐old musician and nonmusician children. However, as this last study is still in progress, only preliminary results will be presented. The theoretic framework within which these experiments are taking place is described. The first problem concerns the specificity of the perceptive and cognitive computations necessary to perceive and understand language. We argue that comparing language with music can provide interesting insights into this complex issue. The second problem is linked to the relationship between different types of learning. Does early musical training influence the way in which musicians process some aspects of language as prosody? These two problems are considered and the results of the experiments are described.
Young Children's Harmonic Perception
Authors: COSTA‐GIOMI EUGENIA
Published: January 2004

Abstract: Harmony and tonality are two of the most difficult elements for young children to perceive and manipulate and are seldom taught in the schools until the end of early childhood. Children's gradual harmonic and tonal development has been attributed to their cumulative exposure to Western tonal music and their increasing experiential knowledge of its rules and principles. Two questions that are relevant to this problem are: (1) Can focused and systematic teaching accelerate the learning of the harmonic/tonal principles that seem to occur in an implicit way throughout childhood? (2) Are there cognitive constraints that make it difficult for young children to perceive and/or manipulate certain harmonic and tonal principles? A series of studies specifically addressed the first question and suggested some possible answers to the second one. Results showed that harmonic instruction has limited effects on children's perception of harmony and indicated that the drastic improvement in the perception of implied harmony noted approximately at age 9 is due to development rather than instruction. I propose that young children's difficulty in perceiving implied harmony stems from their attention behaviors. Older children have less memory constraints and more strategies to direct their attention to the relevant cues of the stimulus. Younger children focus their attention on the melody, if present in the stimulus, and specifically on its concrete elements such as rhythm, pitch, and contour rather than its abstract elements such as harmony and key. The inference of the abstract harmonic organization of a melody required in the perception of implied harmony is thus an elusive task for the young child.
Do Mental Speed and Musical Abilities Interact?
Authors: GRUHN WILFRIED , GALLEY NIELS , KLUTH CHRISTINE
Published: January 2004

Abstract: The relation between mental speed and musical ability was investigated. Seventeen subjects aged 3‐7 years were divided into two subgroups: one (G1; n= 9) consisted of children who participated in an early childhood music program and who received informal musical guidance, but no special training; the other (G2; n= 8) consisted of highly talented young violin players who received intensive parental support and special training by daily deliberate practice. Mental and musical abilities of both groups were controlled by standardized tests (Kaufman's ABC and Gordon's PMMA) and compared with data taken from recordings of saccadic eye movement using online identification from an electrooculogram (EOG). Results of EOG measurement are referred to as “mental speed,” which correlates highly with general mental abilities (intelligence). These results were compared with EOG scores taken from a larger sample of children of the same age range (n= 82) who received no music instruction. The grand average of their scores served as a reference line for mental speed, which is normally expected to be performed by an equivalent age group. Data in the two experimental groups did not differ statistically; however, all musically experienced children had a highly significant advantage in mental age (P <0.01) compared to the reference line of the normal population who did not exhibit any effect of training and practice. This indicates strong interaction between mental speed and music ability, which can be interpreted in terms of the expertise model and cognitive transfer effects.
Dyslexia and Music
Authors: OVERY KATIE
Published: January 2004

Abstract: The underlying causes of the language and literacy difficulties experienced by dyslexic children are not yet fully understood, but current theories suggest that timing deficits may be a key factor. Dyslexic children have been found to exhibit timing difficulties in the domains of language, music, perception and cognition, as well as motor control. The author has previously suggested that group music lessons, based on singing and rhythm games, might provide a valuable multisensory support tool for dyslexic children by encouraging the development of important auditory and motor timing skills and subsequently language skills. In order to examine this hypothesis, a research program was designed that involved the development of group music lessons and musical tests for dyslexic children in addition to three experimental studies. It was found that classroom music lessons had a positive effect on both phonologic and spelling skills, but not reading skills. Results also indicated that dyslexic children showed difficulties with musical timing skills while showing no difficulties with pitch skills. These apparent disassociations between spelling and reading ability and musical timing and pitch ability are discussed. The results of the research program are placed in the context of a more general model of the potential relationship between musical training and improved language and literacy skills.
Effects of Musical Training on the Auditory Cortex in Children
Authors: TRAINOR LAUREL J. , SHAHIN ANTOINE , ROBERTS LARRY E.
Published: January 2004

Abstract:Several studies of the effects of musical experience on sound representations in the auditory cortex are reviewed. Auditory evoked potentials are compared in response to pure tones, violin tones, and piano tones in adult musicians versus nonmusicians as well as in 4‐ to 5‐year‐old children who have either had or not had extensive musical experience. In addition, the effects of auditory frequency discrimination training in adult nonmusicians on auditory evoked potentials are examined. It was found that the P2‐evoked response is larger in both adult and child musicians than in nonmusicians and that auditory training enhances this component in nonmusician adults. The results suggest that the P2 is particularly neuroplastic and that the effects of musical experience can be seen early in development. They also suggest that although the effects of musical training on cortical representations may be greater if training begins in childhood, the adult brain is also open to change. These results are discussed with respect to potential benefits of early musical training as well as potential benefits of musical experience in aging.
Absolute Pitch Does Not Depend on Early Musical Training
Authors: ROSS DAVID A. , OLSON INGRID R. , GORE JOHN C.
Published: January 2004

Abstract: The etiology and defining characteristics of absolute pitch (AP) have been controversial. To test the importance of musical training in the development of this skill, we developed a new paradigm for identifying AP that is independent of a subject's musical experience. We confirm the efficacy of the paradigm using classically defined AP and non‐AP musicians. We then present data from a nonmusician who nevertheless appears to possess AP. We conclude that musical training is not necessary for the development of AP.
Investigating the Musical Qualities of Early Infant Sounds
Authors: RUZZA BARBARA , ROCCA FRANCESCA , BOERO DANIELA LENTI , LENTI CARLO
Published: January 2004

Abstract: Early vocalizations in Italian and Moroccan infants are examined and the results presented.
Perceiving Prosody in Speech
Authors: THOMPSON WILLIAM FORDE , SCHELLENBERG E. GLENN , HUSAIN GABRIELA
Published: January 2004

Abstract:In two experiments, musically trained and untrained adults were tested on their ability to match spoken utterances with their tonal analogues (tone sequences that retained the pitch and temporal patterns of the utterances). In both cases, musical training was associated with superior performance, indicating an enhanced ability to extract prosodic information from spoken phrases.
Reproductive Health and Obstetricians and Gynecologists
Authors: SHETH SHIRISH S.
Published: January 2004

Abstract: The art of medicine provides a rare opportunity to understand human values and to contribute toward the well‐being of one's fellow humans—women in the case of ob‐gyn—a contribution that fits in with the mission of the International Federation of Gynaecology & Obstetrics (FIGO). Obstetricians and gynecologists should indeed take it upon themselves to improve conditions for women, since the bond and respect between the two is a significant one. It is obstetricians‐gynecologists who can provide the much needed technical information to throw light on justifying services that deal with devastating, debilitating, degenerating, and devaluating situations, such as neglected pregnancy, disregard toward cancer detection, and humiliating genital mutilation. Indeed, this can be termed as “terrorism in ob‐gyn,” neglected by those who should deal with it. Those in ob‐gyn and other medical professions clearly witness gender inequality and its ugly aftermath, a degradation of women's reproductive rights. Ob‐gyn must look a little beyond just the lucrative practice of the plain science of obstetrics and gynecology and undertake the responsibility to help and protect the health and life of women around the world. A conscientious doctor cannot practice medicine on women's bodies alone, but must also “practice” against several social evils, the prevention of which is crucial to women's health. Obstetricians and gynecologists can utilize their access to policymakers and health “builders” to carry this brief for women's health, and can urge governments to take a second look at women's rights to ensure that they are on par with the accepted norms of human rights, to be protected and propagated.
Molecular Abnormalities of FSH and LH Action
Authors: McDONOUGH PAUL G.
Published: January 2004

Abstract: The identification of naturally occurring genetic mutations in individuals with disorders of reproductive function is the first logical step to therapy. To date, diagnostic investigations have been assisted by polymerase chain reaction and the development of an increasing number of effective screening techniques to scan genomic DNA (deoxyribonucleic acid) for causative mutations. The continued expansion of these technologies, coupled with high throughput gene sequencing, will ultimately result in automated DNA diagnosis for the practicing clinician at the point of care. At that time, the direct examination of a patient's DNA will be the definitive means of establishing the presence of specific genetic changes that cause or increase one's susceptability to disease. This presentation selects important candidate genes in the human hypothalamic‐pituitary‐ovarian axis (HPG), reviews our knowledge of the spontaneously occurring human mutations that affect these genes, and reviews the biological implications of this information. To date, causative mutations in candidate genes have provided important insights into the transcription factors, receptors, and hormones that regulate the HPG axis at many levels. A major challenge in this field is that mutations in many of these genes and others remaining to be identified lead to infertility. The reduction in reproductive fitness due to these mutations limits the ability of investigators to use traditional genetic linkage and association studies to identify and clone important unidentified reproductive genes. Fortunately analysis of human gametes and new strategies that are being developed for the identification and mapping of complex human diseases will become increasingly important in continuing studies of idiopathic human infertility. At this time, it is helpful for the reader to become acquainted with some of the prototype mutations in candidate genes, their phenotypic consequences, and their prevalence. This presentation is designed to describe the known mutations in the gonadotropin genes and the genes encoding their respective receptors. The phenotypic effects of these mutations is compared, and evidence for causation is reviewed.
Modulatory Effect of the Ovary on LH Secretion
Authors: MESSINIS IOANNIS E.
Published: January 2004

Abstract: Ovarian steroids are important regulators of gonadotropin secretion during the normal menstrual cycle. Estradiol is the predominant factor in the follicular phase, while progesterone plays an important role in the luteal phase. Gonadotropin surge attenuating factor (GnSAF) is a nonsteroidal ovarian substance that attenuates the endogenous LH surge in superovulated women. Attempts to purify GnSAF from various sources have provided several sequences. In human follicular fluid, GnSAF is shown to be the carboxyl terminal fragment of human serum albumin (HSA) and a molecular mass of 12.5 kDa. Preliminary data have shown the expression of the carboxyl terminal fragment of HSA in human granulosa cells. In vivo studies have provided evidence that GnSAF may participate in the control of LH response to GnRH in the context of a mechanism that facilitates the full expression of the midcycle LH surge. Further research is expected to clarify the role of GnSAF in women's physiology.
Some New Thoughts on the Pathophysiology and Genetics of Polycystic Ovary Syndrome
Authors: STRAUSS JEROME F.
Published: January 2004

Abstract: Polycystic ovary syndrome (PCOS) is a common disorder of unknown etiology, but several lines of evidence suggest that there is an underlying genetic cause for PCOS. Studies of first‐degree relatives of women diagnosed with PCOS reveal familial clustering of the disease, particularly hyperandrogenemia. A prospective study of first‐degree female relatives of PCOS women found that 46% of ascertainable sisters of PCOS women were hyperandrogenemic. The serum bioavailable testosterone in the cohort of sisters showed a bimodal distribution. These observations suggest a dominantly inherited trait controlling androgen levels. Studies on cultures of human theca cells derived from follicles isolated from the ovaries of PCOS and normal women demonstrated that PCOS theca cells produce greater amounts of testosterone, 17α‐hydroxyprogesterone, and progesterone than normal theca cells, despite the fact that cells were cultured under identical conditions for multiple population doublings. Examination of the metabolism of radiolabeled steroid hormone precursors and steady‐state levels of mRNAs encoding steroidogenic enzymes revealed that there are multiple alterations in the steroidogenic machinery of PCOS theca cells, including elevated expression of the CYP11A, 3BHSD2, and CYP17 genes. The increased mRNA levels are the result, in least in part, of increased gene transcription. Interestingly, the STAR gene is not expressed at a higher level in PCOS theca cells. The stable up‐regulation of steroidogenesis in PCOS thecal cells indicates either a genetic abnormality in these cells or a persistent metabolic imprint established in vivo. Linkage and association studies conducted by the National Cooperative Program in Infertility Research using affected sib‐pair analysis and the transmission/disequilibrium test to explore candidate genes point a finger at a region on chromosome 19p13.3. The putative PCOS gene lying in this region has yet to be identified. However, existing data suggest that it is probably involved in signal transduction mechanisms leading to altered expression of a suite of genes that affect theca cell steroidogenic activity as well as the metabolic phenotype of other cell types, including muscle and fat.
Polycystic Ovary Syndrome in Adolescence
Authors: DRISCOLL DEBORAH A.
Published: January 2004

Abstract: Polycystic ovary syndrome (PCOS) is a common disorder among reproductive‐age women, yet the diagnosis may be overlooked during adolescence. Although the clinical and metabolic features are similar to those found in adult women, it can be difficult to distinguish the young woman with PCOS from a normal adolescent. Irregular menses, anovulatory cycles, and acne are not uncommon in adolescent women. Adolescents with a history of premature pubarche, a family history of PCOS, Caribbean‐Hispanic and African‐American ancestry, and/or obesity are at risk for PCOS and deserve close surveillance. The laboratory evaluation of the adolescent with suspected PCOS or hyperandrogenism should be individualized based on the history, symptoms, and examination findings. The cornerstone of management of PCOS in adolescence includes either a combination oral contraceptive or progestin. Consideration of insulin‐sensitizing agents, antiandrogens, topical treatments for acne, and various treatments for hair removal are dependent on the patient's symptoms and concerns. Healthy eating, regular exercise, and for the overweight adolescent, weight reduction, are encouraged to reduce the risk of cardiovascular disease and type II diabetes mellitus. Numerous studies have shown that weight loss and exercise decrease androgen levels, improve insulin sensitivity, and lead to the resumption of ovulation. Although initial studies suggest that Metformin may be particularly useful for treating the PCOS adolescent with insulin resistance and obesity, additional studies are needed to determine the efficacy and long‐term outcome. Management of the adolescent with PCOS is challenging and requires a supportive, multidisciplinary team approach for optimal results.
Growth Hormone Insufficiency and Its Impact on Ovarian Function
Authors: SPILIOTIS BESSIE E.
Published: January 2004

Abstract: Growth hormone (GH) and the insulin‐like growth factor‐I (IGF‐I) play significant roles in pubertal development, menarche, the menstrual cycle, fertility, and reproduction. Growth hormone deficiency or insufficiency causes a delay in the onset of puberty and in its normal course unless treated with synthetic GH. It seems that GH affects the ovary during puberty both indirectly through the gonadotropins and IGF‐I, and directly through its effect on steroidogenesis. The GH axis is activated by small increases in circulating estrogens, which initiate large increases in GH during puberty. The reproductive function of the female is also affected by GH. GH acts on the ovary affecting gametogenesis and steroidogenesis. GH receptor mRNA and protein have been found in ovarian cells, and this suggests that the direct action of GH provides an important modulatory effect on gonadotropin‐dependent and ‐independent functions. It also affects the maturation of the follicle and gamete, and thereby plays a facilitatory role in fertility. The majority of women with GH‐deficiency, but not all, require assisted reproductive technologies to induce ovulation. Many women with polycystic ovary syndrome (PCOS) have an impaired GH response to stimulation with Levo‐Dopa and GH releasing hormone (GHRH). Hyperandrogenism in PCOS may contribute to the reduced GH secretion because testosterone directly stimulates somatostatin release. Reduction of the excessive androgens facilitates the dopaminergic control of GH. In conclusion, GH‐insufficient states disrupt ovarian function, causing problems in sexual maturation, the menstrual cycle, and the reproductive ability of the female.
Uterine and Embryonic Trophoblast CRH Promotes Implantation and Maintenance of Early Pregnancy
Authors: MAKRIGIANNAKIS ANTONIS , ZOUMAKIS EMMANOUIL , KALANTARIDOU SOFIA , CHROUSOS GEORGE , GRAVANIS ACHILLEAS
Published: January 2004

Abstract: Epithelial cells of human endometrium and differentiated endometrial stromal cells express the corticotropin‐releasing hormone (CRH) gene. CRH is also produced by the human placental cytotrophoblast. Endometrial and placental CRH is under the endocrine control of gonadal steroids as well as under an autocrine/paracrine regulation by prostanoids and interleukins. Human endometrium, myometrium and placenta also express the relevant receptors. Invasive trophoblasts promote apoptosis of activated Fas‐expressing human T lymphocytes, an effect potentiated by CRH and inhibited by the CRH type 1 antagonist, antalarmin. Female rats treated with antalarmin during the first 6 days of gestation had a dose‐dependent decrease of implantation sites and live embryos, and significantly decreased endometrial FasL expression. Our data suggest important physiological roles of endometrial and placental CRH in the regulation of decidualization, blastocyst implantation, and early maternal tolerance.
Perimenopausal Conception
Authors: TARLATZIS BASIL C. , ZEPIRIDIS LEONIDAS
Published: January 2004

Abstract: Fertility, defined as the ability to achieve a pregnancy, declines gradually over the woman's lifespan. Although this decline seems to begin from the age of 30 years, it is more obvious between 35 and 40 and increases dramatically thereafter. The age of 41 is considered to be the point when fertility stops and sterility starts. The actual menopause occurs approximately 10 years after the substantial loss of conception potential. Thus, the biological rather than the chronological age of the woman can predict more accurately her fertility potential. This decline in female reproductive potential correlates with ovarian factors, although a slight contribution from the uterus itself and from the neuroendocrine axis cannot be excluded. The ovarian reserve decreases with advancing age, while a parallel decrease in the quality of the oocytes is present, as indicated by the increased incidence of oocyte aneuploidy. The endocrine function of the ovary also declines with age, the later becoming unable to sustain its normal function in the neuroendocrine axis. Additionally, the role of the various endometrial factors remains controversial. On the other hand, exposure to toxic factors and the increased prevalence of infertility‐related diseases like endometriosis and PID, may also contribute. Spontaneous conception rates are minimal in perimenopausal women, mainly due to a qualitative and quantitative loss of female gametes. In the rare case of spontaneous conception achievement, complications are more likely. The application of classic ovulation induction and IVF may serve some selected cases, where the woman's ovarian biological age does not correspond to her chronological one. However, the implantation, clinical pregnancy, and live birth rates in women of advanced age undergoing IVF treatment, show very poor results. On the other hand, preimplantation genetic diagnosis is an accurate diagnostic tool for exclusion of genetically deficient embryos prior to embryo transfer. Oocyte donation seems to be the most reliable option of the perimenopausal woman, since the cumulative birth rates after four treatment cycles is approximately 80%. Cryopreservation of ovarian tissue may be an alternative in nulliparas women <40 years of age who want to have children in the future or women with the same desire who, unfortunately, have had pelvic radiotherapy, chemotherapy, oophorectomy, or premature menopause. This technique has given encouraging results in animals, but has not achieved pregnancies in humans. In the future, the use of drugs to block oocyte depletion as well as recent techniques, such as cytoplasmic or germinal vesicle transfer, will be more widely tested and may offer an option to the perimenopausal woman who wishes to conceive.
Mild Stimulation in In Vitro Fertilization
Authors: MACKLON N. S. , FAUSER B.C. J.M.
Published: January 2004

Abstract: Current approaches to ovarian stimulation for in vitro fertilization (IVF) are aimed at optimizing the number of oocytes retrieved in a treatment cycle. This approach is not without risks. Moreover, as the true costs of multiple pregnancy become clearer, the need to produce multiple embryos for transfer is increasingly questioned. Increasing knowledge of the physiological mechanisms involved in follicular development and dominance has led to new strategies in ovarian stimulation for IVF. The clinical availability of GnRH antagonists allows the normal cycle to be harnessed and manipulated by mild interventions to produce sufficient oocytes for successful IVF treatment. Recent evidence suggests that oocyte quality after mild stimulation may be superior to that after conventional stimulation regimens.
Alternative Approaches in the Management of Poor Response in Controlled Ovarian Hyperstimulation (COH)
Authors: LOUTRADIS DIMITRIS , DRAKAKIS PETER , MILINGOS SPYROS , STEFANIDIS KONSTANTINE , MICHALAS STYLIANOS
Published: January 2004

Abstract: Improving pregnancy rates in patients with many failed attempts remains a challenge during IVF‐ET or ICSI‐ET programs. The availability of good‐quality oocytes is a prerequisite for good results in such programs. The use of a personalized protocol for controlled ovarian hyperstimulation (COH) that gives the best possible results for the specific patient is a main factor for the success in IVF or ICSI. The response of many patients to the ovarian stimulation used is very poor, giving fewer oocytes than expected, resulting in much lower, if any, pregnancy rates. The definition of a poor responder is not clear and differs among researchers. A variety of strategies have been used to improve response in these patients, regardless of the definition used. These include various ovulation induction protocols that we believe might assist these patients achieve a pregnancy. The difficulty is greater due to the fact that poor responders are not a homogeneous group and each patient may have a different cause. More studies with large numbers of patients are needed in order to find those protocols that could provide these couples with an acceptable pregnancy rate.
Ethical Aspects of Advanced Reproductive Technologies
Authors: SCHENKER JOSEPH G.
Published: January 2004

Abstract: The progress achieved during the last 25 years in the assisted reproductive technology field has been phenomenal. Many countries currently practice genetic material donation, human embryo cryopreservation, selective embryo reduction, preimplantation genetic diagnosis, and surrogacy. While embryo research and therapeutic cloning are carried out only in a few centers, thus far human cloning has been universally condemned. Nonetheless, the rapid evolution and progress of these various techniques of assisted reproduction has opened a Pandora's box of ethical issues that must be urgently addressed.
Endocrine‐Related Causes and Consequences of Intrauterine Growth Retardation
Authors: KANAKA‐GANTENBEIN CHRISTINA , MASTORAKOS GEORGE , CHROUSOS GEORGE P.
Published: January 2004

Abstract: The term intrauterine growth retardation (IUGR) is assigned to newborns born with a birth weight and/or birth length below the tenth percentile for their gestational age. Intrauterine growth retardation is usually due to maternal, fetal factors, or placental insufficiency, while endocrine factors represent just a small minority in its etiology. Main endocrine‐related causes of IUGR are disorders in insulin or insulin‐like growth factor‐I (IGF‐I) secretion or action. Newborns with IUGR are at increased risk to develop a metabolic syndrome later in life, namely obesity, arterial hypertension, hypercholesterolemia, cardiovascular disease, impaired glucose tolerance, or diabetes mellitus type 2. This association is the result of the adaptational changes of the fetal endocrine‐metabolic mechanisms to the impaired intrauterine milieu to assure survival in the short term. The persistence of these changes after birth can be detrimental in adult life. Furthermore, premature adrenarche, as well as ovarian hyperandrogenism, seem to be associated with IUGR in girls, demonstrating that IUGR may have long‐lasting effects on both somatic health and reproductive function. Finally, the intrauterine exposure of the fetus to stressors may affect the individual's ability to face stress in postnatal life. Therefore, if optimization of somatic and psychosocial well‐being of the individual is the golden goal of medicine, special attention should be paid to maintain an optimal intrauterine milieu devoid of any stressors with adequate nutrient supply and to reserve ideal psychosocial support to the pregnant woman.
How Low Can You Get?
Authors: BRINCAT M. , BARON Y. MUSCAT , GALEA R.
Published: January 2004

Abstract: Since the early 1960s the side effects of oral contraceptives have been known to be related to the high doses (50 μg) of ethinyl estradiol used. Research has focused on reducing the dose of both the estrogen and progestin components to reduce these side effects. While reducing the dose of both components, the contraceptive efficacy has to be maintained so as to retain a satisfactory Pearl index. These requirements appear to have been attained with 24‐day regimen of a low‐dose pill (15 μg of ethinyl estradiol and 60 μg of gestedone) as one part of an open‐label noncomparative multicenter study. This paper reports our unit's results, which indicate that the low‐dose pill promises to reduce contraceptive‐related side effects, to encourage better compliance, and as corollary, to retain a satisfactory Pearl index