bluuebunny/crossref_metadata_2025 huggingface dataset:
Synaptic Mechanisms for Auditory‐Vocal Integration and the Correction of Vocal Errors
Authors: MOONEY RICHARD
Published: August 2004

Abstract: A central goal of neuroscience is to understand the cellular mechanisms enabling the cultural transmission of behaviors, such as speech and music. Birdsong is a rare non‐human instance of a culturally transmitted vocal behavior. The songbird's brain provides a powerful system in which to study the cellular mechanisms underlying auditory‐guided vocal learning. Identifying those mechanisms requires an analysis of synaptic function, because the synapse is the fundamental organizational unit of the neuronal networks that mediate behavior. Intracellular recordings provide a powerful method for simultaneously probing the activities of a single neuron and the synaptic networks in which that cell is embedded. This chapter details initial steps in the in vivo intracellular analysis of the synaptic connectivity of neurons important to singing and song learning. Our analysis is focused upon HVC and involves studies of interneurons as well as projection neurons of the two major output pathways of HVC. We test predictions derived from several models of how such learning may take place, including contributions from “comparator” and “corollary discharge” auditory feedback cancellation mechanisms. Our studies in anesthetized animals and brain slices provide insight into the synaptic properties of HVC that might be well suited for these mechanisms, although extrapolation to synaptic behavior in the awake, singing bird must be made with caution. We suggest that future work must extend the analysis of synaptic properties into the intact brain of the songbird, preferably as the bird learns to sing.
Song Function and the Evolution of Female Preferences: Why Birds Sing, Why Brains Matter
Authors: NOWICKI STEPHEN , SEARCY WILLIAM A.
Published: August 2004

Abstract:Analyzing the function of song and its evolution as a communication signal provides an essential backdrop for understanding the physiological and neural mechanisms responsible for song learning, perception, and production. The reverse also is true—understanding the mechanisms underlying song learning provides insight into how song has evolved as a communication signal. Song has two primary functions: to repel other males from a defended space and to attract females and stimulate their courtship. The developmental stress hypothesis we present here builds on studies of the development of the song system to suggest how learned features of song, including complexity and local dialect structure, can serve as indicators of male quality useful to females in mate choice. The link between song and male quality depends on the fact that brain structures underlying song learning largely develop during the first few months post‐hatching and that during this same period, songbirds are likely to be subject to nutritional and other developmental stresses. Individuals faring well in the face of stress are able to invest more resources to brain development and are expected to be correspondingly better at song learning. Learned features of song thus become reliable indicators of male quality, with reliability maintained by the developmental costs of song. Data from both field and laboratory studies are now beginning to provide broad support for the developmental stress hypothesis, illustrating the utility of connecting mechanistic and evolutionary analyses of song learning.
Functional Neuroanatomy of the Sensorimotor Control of Singing
Authors: WILD J MARTIN
Published: August 2004

Abstract: Reviews of the songbird vocal control system frequently begin by describing the forebrain nuclei and pathways that form anterior and posterior circuits involved in song learning and song production, respectively. They then describe extratelencephalic projections upon the brainstem respiratory‐vocal system in a manner suggesting, quite erroneously, that this system is itself well understood. One aim of this chapter is to demonstrate how limited is our understanding of that system. I begin with an overview of the neural network for the motor control of song production, with a particular emphasis on brainstem structures, including the tracheosyringeal motor nucleus (XIIts), which innervates the syrinx, and nucleus retroambigualis (RAm), which projects upon XIIts and upon spinal motor neurons innervating expiratory muscles. I describe the sources of afferent projections to XIIts and RAm and discuss their probable role in coordinating the bilateral activity of respiratory and syringeal muscles during singing. I then consider the routes by which sensory feedback, which could arise from numerous structures involved in singing, might access the song system to guide song learning, maintain accurate song production, and inform the song system of the requirements for air. I describe possible routes of access of auditory feedback, which is known to be necessary for song learning and maintenance, and identify potential sites of interaction with somatosensory and visceral feedback that could arise from the syrinx, the lungs and air sacs, and the upper vocal tract, including the jaw. I conclude that the incorporation of brainstem‐based respiratory‐vocal variables is likely to be a necessary next step in the construction of more sophisticated models of the control of vocalization.
Auditory Experience and Adult Song Plasticity
Authors: WOOLLEY SARAH M. N.
Published: August 2004

Abstract: Adults Bengalese finches normally sing stereotyped songs, which do not change under the influence of auditory experience. If deafened, however, adult birds sing significantly degraded songs that are characterized by a lack of stereotypy of syllable order and the deterioration of syllable structure. We studied the importance of auditory feedback for maintenance of normal adult song. Auditory feedback can be partially or completely removed by eliminating auditory hair cells, the sensory receptor cells for hearing. The effects are reversible because birds regenerate new hair cells when original cells are lost. Limiting the frequency range of auditory feedback available to birds using partial hair cell lesions indicated that low‐frequency information (1500 Hz) is necessary and sufficient for the maintenance of normal adult song. Reversible deafening experiments using hair cell loss and regeneration indicated that adult Bengalese finches store memories of their own songs, which can be used to guide vocal behavior. Additionally, destabilizing song behavior by removing auditory feedback leads to renewed song plasticity, and some adults can be induced to learn new song. These studies suggest that Bengalese finches maintain normal song by comparing ongoing vocal output to stored models of their own stable songs and that neural circuitry for song learning persists beyond the sensitive period for song learning.
Song and the Limbic Brain: A New Function for the Bird's Own Song
Authors: CHENG MEI‐FANG , DURAND SARAH E.
Published: August 2004

Abstract: The neurobiological investigation of the avian song system has largely focused on the unique neural features of vocal control systems that contribute to learned motor patterns in songbirds. The role of emotion has been disregarded in developing a theory of song learning and performance. Here we review emerging evidence in support of Darwin's observation that vocal communication is emotional expression. We propose that neural pathways mediating emotional state remained integrated with the vocal control system as forebrain vocal control pathways evolved to support learned communication patterns. Vocalizations are therefore both a motor component of an emotional state and can influence emotional state via sensory feedback during vocal production. By acknowledging the importance of emotion in vocal communication, we are proposing that the song system and limbic brain are functionally linked in the production and reception of song.
Methods for the Analysis of Auditory Processing in the Brain
Authors: THEUNISSEN FRÉDÉRIC E. , WOOLLEY SARAH M.N. , HSU ANNE , FREMOUW THANE
Published: August 2004

Abstract: Understanding song perception and singing behavior in birds requires the study of auditory processing of complex sounds throughout the avian brain. We can divide the basics of auditory perception into two general processes: (1) encoding, the process whereby sound is transformed into neural activity and (2) decoding, the process whereby patterns of neural activity take on perceptual meaning and therefore guide behavioral responses to sounds. In birdsong research, most studies have focused on the decoding process: What are the responses of the specialized auditory neurons in the song control system? and What do they mean for the bird? Recently, new techniques addressing both encoding and decoding have been developed for use in songbirds. Here, we first describe some powerful methods for analyzing what acoustical aspects of complex sounds like songs are encoded by auditory processing neurons in songbird brain. These methods include the estimation and analysis of spectro‐temporal receptive fields (STRFs) for auditory neurons. Then we discuss the decoding methods that have been used to understand how songbird neurons may discriminate among different songs and other sounds based on mean spike‐count rates.
Song‐Induced Gene Expression: A Window on Song Auditory Processing and Perception
Authors: MELLO CLAUDIO V. , VELHO TARCISO A.F. , PINAUD RAPHAEL
Published: August 2004

Abstract:We review here evidence that a large portion of the caudomedial telencephalon of songbirds, distinct from the song control circuit, is involved in the perceptual processing of birdsong. When songbirds hear song, a number of caudomedial pallial areas are activated, as revealed by expression of the activity‐dependent genezenk. These areas, which include field L subfields L1 and L3, as well as the adjacent caudomedial nidopallium (NCM) and caudomedial mesopallium (CMM), are part of the central auditory pathway and constitute a lobule in the caudomedial aspect of the telencephalon. Several lines of evidence indicate that the neural circuits integrating this lobule are capable of performing the auditory processing of song based on fine acoustic features. Thus, this lobule is well positioned to mediate song perceptual processing and discrimination, which are required for vocal communication and vocal learning. Importantly, thezenkgene encodes a transcription factor linked to synaptic plasticity, and it regulates the expression of target genes associated with specific neuronal cell functions. The induction ofzenklikely represents a key regulatory event in a gene cascade triggered by song and leading to neuronal plasticity. Thus,zenkmay be linked to molecular and cellular mechanisms underlying experience‐dependent modification of song‐responsive circuits. In summary, songbirds possess an elaborate system for song perceptual processing and discrimination that potentially also subserves song‐induced neuronal plasticity and song memory formation. The continued use of a multidisciplinary approach that integrates molecular, anatomical, physiological and behavioral methodologies has the potential to provide further significant insights into the underlying neurobiology of the perceptual aspects of vocal communication and learning.
Neural Mechanisms of Vocal Sequence Generation in the Songbird
Authors: FEE MICHALE S. , KOZHEVNIKOV ALEXAY A. , HAHNLOSER RICHARD H.R.
Published: August 2004

Abstract: Little is known about the biophysical and neuronal circuit mechanisms underlying the generation and learning of behavioral sequences. Songbirds provide a marvelous animal model in which to study these phenomena. By use of a motorized microdrive to record the activity of single neurons in the singing bird, we are beginning to understand the circuits that generate complex vocal sequences. We describe recent experiments elucidating the role of premotor song‐control nucleus HVC in the production of song. We find that HVC neurons projecting to premotor nucleus RA each generate a single burst of spikes at a particular time in the song and may form a sparse representation of temporal order. We incorporate this observation into a working hypothesis for the generation of vocal sequences in the songbird, and examine some implications for song learning.
Song Selectivity in the Song System and in the Auditory Forebrain
Authors: THEUNISSEN FRÉDÉRIC E. , AMIN NOOPUR , SHAEVITZ SARITA S. , WOOLLEY SARAH M. N. , FREMOUW THANE , HAUBER MARK E.
Published: August 2004

Abstract: The sensorimotor neurons found in the song‐system nuclei are responsive to the sounds of the bird's own song. This selectivity emerges during vocal learning and appears to follow the development of the bird's song vocalization in two ways: at each stage, the neurons are most selective for the bird's current vocalizations and this selectivity increases as the bird learns to produce a stable adult song. Also, because of their location in the sensori‐vocal pathway and because their physiological properties are correlated with the motor program, it is postulated that these neurons play a crucial role in interpreting the auditory feedback during song to preserve a desirable vocal output. The neurons found in presynaptic auditory areas lack this selectivity for the bird's own song. Auditory neurons in the secondary auditory areas caudal nidopallium and caudal mesopallium show specific responses to familiar songs or behaviorally relevant songs. These auditory areas might therefore be involved in perceptual tasks. Neurons in the primary forebrain auditory area are selective for the spectrotemporal modulations that are common in song, yielding an efficient neural representation of those sounds. Neurons that are particularly selective for the tutor song at the end of the sensory period have not yet been described in any areas. Although these three levels of selectivity found in the primary auditory forebrain areas, the secondary auditory forebrain areas, and the song system suggest a form of hierarchical sensory processing, the functional connectivity between these areas and the mechanisms generating the specific selectivity for songs that are behaviorally relevant or crucial in song learning and production have yet to be revealed.
The Bengalese Finch: A Window on the Behavioral Neurobiology of Birdsong Syntax
Authors: OKANOYA KAZUO
Published: August 2004

Abstract:The Bengalese finchLonchura striatavar.domesticais a domesticated strain of a wild species, the white‐rumped muniaLonchura striataof Southeast Asia. Bengalese finches have been domesticated in Japan for 240 years. Comparing their song syntax with that of their wild ancestors, we found that the domesticated strain has highly complex, conspicuous songs with finite‐state syntax, while the wild ancestor sang very stereotyped linear songs. To examine the functional utility of the song complexity, we compared serum levels of estradiol and measured the amount of nesting materials carried into the nest by female birds that were stimulated with either the complex “domesticated” song or the simple wild‐type song. In the females stimulated with complex songs the estradiol levels were significantly higher and the amount of nesting material carried was significantly greater. We then performed brain lesions in the song system to identify the neural substrates that are responsible for these differences in song behavior. In Bengalese finches lesions of NIf, a higher order song control nucleus, resulted in simplification of the complex song syntax. That is, the complex “domesticated” syntax changed into the simple wild‐type syntax. Based on these data, we hypothesize that mutations in the song control nuclei have occurred that enabled complex song syntax and became fixed into the population of domesticated Bengalese finches through a process of indirect sexual selection.
Songbird Genomics: Methods, Mechanisms, Opportunities, and Pitfalls
Authors: CLAYTON DAVID F.
Published: August 2004

Abstract:The biology of songbirds poses fundamental questions about the interplay between gene, brain, and behavior. New tools of genomic analysis will be invaluable in pursuing answers to these questions. This review begins with a summary of the broad properties of the songbird genome and how songbird brain gene expression has been measured in past studies. Four key problems in songbird biology are then considered from a genomics perspective: What role does differential gene expression play in the development, maintenance, and functional organization of the song control circuit? Does gene regulation set boundaries on the process of juvenile song learning? What is the purpose of song‐induced gene activity in the adult brain? How does the genome underlie the profound sexual differentiation of the song control circuit? Finally, the range of genomic technologies currently or soon to be available to songbird researchers is briefly reviewed. These technologies include online databases of expressed genes (“expressed sequence tags” or ESTs); a complete library of the zebra finch genome maintained as a bacterial artificial chromosome (BAC) library; DNA microarrays for simultaneous measurement of many genes in a single experiment; and techniques for gene manipulation in the organism. Collectively, these questions and techniques define the field of songbird neurogenomics.
Studying the Song Development Process: Rationale and Methods
Authors: TCHERNICHOVSKI O , LINTS T J , DERÉGNAUCOURT S , CIMENSER A , MITRA P P
Published: August 2004

Abstract:Current technology makes it possible to measure song development continuously throughout a vocal ontogeny. Here we briefly review some of the problems involved and describe experimental and analytic methods for automatic tracing of vocal changes. These techniques make it possible to characterize the specific methods the bird uses to imitate sounds: an automated song recognition procedure allows continuous song recording, followed by automated sound analysis that partition the song to syllables, extract acoustic features of each syllable, and summarize the entire song development process over time into a single database. The entire song development is then presentable in the form of images or movie clips. These Dynamic Vocal Development (DVD) maps show how each syllable type emerges, and how the bird manipulates syllable features to eventually approximate the model song. Most of the experimental and analytic methods described here have been organized into a software package, which also allows combined neural and sound recording to monitor changes in brain activity as vocal learning occurs. The software is available athttp://ofer.sci.ccny.cuny.edu.
Genetic Components of Vocal Learning
Authors: SCHARFF CONSTANCE , WHITE STEPHANIE A.
Published: August 2004

Abstract: Vocal learning is a rare trait. Humans depend on vocal learning to acquire spoken language, but most species that communicate acoustically have an innate repertoire of sounds that they use for information exchange. Among the few non‐human species that also rely on vocal learning, songbirds have provided by far the most information for understanding this process. This article concentrates on the genetic components of vocal learning in humans and birds. We summarize the existing evidence for a genetic predisposition towards acquiring the species‐specific human and avian vocal repertoires. We describe the approaches used for finding genes involved in shaping the neural circuitry required for vocal learning or in mediating the learning process itself. Special attention is given to a particular gene, FOXP2, which has been implicated in a human speech and language disorder. We have studied FoxP2 in avian vocal learners and non‐learners and review evidence that links both the molecule and its close homologue FoxP1 to the development of brain regions implicated in vocal learning and to their function. FoxP2 has a characteristic expression pattern in a brain structure uniquely associated with learned vocal communication, Area X in songbirds, or its analogue in parrots and hummingbirds. In both avian song learners and non‐learners FoxP2 expression predominates in sensory and sensory‐motor circuits. These latter regions also express FoxP2 in mammals and reptiles. We conclude that FoxP2 is important for the building and function of brain pathways including, but not limited to, those essential for learned vocal communication.
Cellular, Circuit, and Synaptic Mechanisms in Song Learning
Authors: DOUPE ALLISON J. , SOLIS MICHELE M. , KIMPO RHEA , BOETTIGER CHARLOTTE A.
Published: August 2004

Abstract: Songbirds, much like humans, learn their vocal behavior, and must be able to hear both themselves and others to do so. Studies of the brain areas involved in singing and song learning could reveal the underlying neural mechanisms. Here we describe experiments that explore the properties of the songbird anterior forebrain pathway (AFP), a basal ganglia‐forebrain circuit known to be critical for song learning and for adult modification of vocal output. First, neural recordings in anesthetized, juvenile birds show that auditory AFP neurons become selectively responsive to the song stimuli that are compared during sensorimotor learning. Individual AFP neurons develop tuning to the bird's own song (BOS), and in many cases to the tutor song as well, even when these stimuli are manipulated to be very different from each other. Such dual selectivity could be useful in the BOS‐tutor song comparison critical to song learning. Second, simultaneous neural recordings from the AFP and its target nucleus in the song motor pathway in anesthetized adult birds reveal correlated activity that is preserved through multiple steps of the circuits for song, including the AFP. This suggests that the AFP contains highly functionally interconnected neurons, an architecture that can preserve information about the timing of firing of groups of neurons. Finally, in vitro studies show that recurrent synapses between neurons in the AFP outflow nucleus, which are expected to contribute importantly to AFP correlation, can undergo activity‐dependent and timing‐sensitive strengthening. This synaptic enhancement appears to be restricted to birds in the sensory critical and early sensorimotor phases of learning. Together, these studies show that the AFP contains cells that reflect learning of both BOS and tutor song, as well as developmentally regulated synaptic and circuit mechanisms well‐suited to create temporally organized assemblies of such cells. Such experience‐dependent sensorimotor assemblies are likely to be critical to the AFP's role in song learning. Moreover, studies of such mechanisms in this basal ganglia circuit specialized for song may shed light more generally on how basal ganglia circuits function in guiding motor learning using sensory feedback signals.
Song Development: In Search of the Error‐Signal
Authors: DERÉGNAUCOURT S , MITRA P P , FEHÉR O , MAUL K K , LINTS T J , TCHERNICHOVSKI O
Published: August 2004

Abstract: Song development provides an opportunity to study the mechanisms of vocal learning dynamically at molecular, cellular and systems levels, and across time scales ranging from minutes to months. To exploit these opportunities one needs to identify appropriate units, types and time scales of vocal change in nearly real time. The previous chapter by Tchernikovski et al. in this volume described techniques that make this research strategy feasible by allowing us to observe the song learning process through a “temporal microscope” with variable degrees of resolution. In this chapter we summarize some of the new observations and raise hypotheses about the learning strategy of the bird. We focus on inferences that can be drawn from behavioral observations to the nature and complexity of the instructive signal that guides the vocal change (error‐signal). We examine two effects: i) the emergence of syllable types and ii) changes in features within a syllable type. We found that different features of the same syllable change during different and sometimes disjointed developmental windows. We discuss the possibility that song imitation is achieved by correcting partial errors, and that features of those partial errors change adaptively during development, perhaps concurrently with changes in perception and in motor proficiency. Those hypotheses can be best examined by across levels investigation, starting from identifying critical moments in song development and recording of articulatory dynamics and neural patterns when only a few features of specific syllables undergo rapid changes. Such investigation could relate behavioral events to brain mechanisms that guide song learning from moment‐to‐moment and across extended periods.
Developmental Regulation of Basal Ganglia Circuitry during the Sensitive Period for Vocal Learning in Songbirds
Authors: BOTTJER SARAH W.
Published: August 2004

Abstract: A hallmark of sensitive periods of development is an enhanced capacity for learning, such that experience exerts a profound effect on the brain resulting in the establishment of behaviors and underlying neural circuitry that can last a lifetime. Songbirds, like humans, have a sensitive period for vocal learning: they acquire the sounds used for vocal communication during a restricted period of development. In principle, any organism that undertakes vocal learning is faced with the same challenge: to form some representation of target vocal sounds based on auditory experience, and then to translate that auditory target into a motor program that reproduces the sound. Both birds and humans achieve this translation by using auditory (and other) feedback resulting from incipient vocalizations (“babbling” in humans, “subsong” in birds) to adjust motor commands until vocal output produces a good copy of the target sounds. Similarities between vocal learning in birds and humans suggest that many aspects of the learning process have evolved to meet demands imposed by vocal communication. Thus songbirds provide a valuable animal model in which to study the physiological basis of learned vocal communication and the nature of sensitive periods in general. In this article, I describe aspects of both behavioral and neural frameworks that currently inform our thinking about mechanisms underlying vocal learning and behavior in songbirds, and highlight ideas that may need re‐examination.
Learned Birdsong and the Neurobiology of Human Language
Authors: JARVIS ERICH D.
Published: August 2004

Abstract:Vocal learning, the substrate for human language, is a rare trait found to date in only three distantly related groups of mammals (humans, bats, and cetaceans) and three distantly related groups of birds (parrots, hummingbirds, and songbirds). Brain pathways for vocal learning have been studied in the three bird groups and in humans. Here I present a hypothesis on the relationships and evolution of brain pathways for vocal learning among birds and humans. The three vocal learning bird groups each appear to have seven similar but not identical cerebral vocal nuclei distributed into two vocal pathways, one posterior and one anterior. Humans also appear to have a posterior vocal pathway, which includes projections from the face motor cortex to brainstem vocal lower motor neurons, and an anterior vocal pathway, which includes a strip of premotor cortex, the anterior basal ganglia, and the anterior thalamus. These vocal pathways are not found in vocal non‐learning birds or mammals, but are similar to brain pathways used for other types of learning. Thus, I argue that if vocal learning evolved independently among birds and humans, then it did so under strong genetic constraints of a pre‐existing basic neural network of the vertebrate brain.
Origin of the Anterior Forebrain Pathway
Authors: PERKEL DAVID J.
Published: August 2004

Abstract: The brain nuclei and pathways comprising the song system of oscine songbirds bear many similarities with circuits in other bird species and in mammals. This suggests that the song system evolved as a specialization of pre‐existing circuits and may retain fundamental properties in common with those of other taxa. Here we review evidence for these similarities, including electrophysiological, morphological, and neurochemical data for identifying specific cell types. In addition, we discuss connectional data, addressing similarities in axonal projections among nuclei across taxa. We focus primarily on the anterior forebrain pathway, a circuit essential for song learning and vocal plasticity, because the evidence is strongest that this circuit is homologous to mammalian circuits. These fundamental similarities highlight the importance of comparative approaches; for example, understanding the role the anterior forebrain pathway plays in song plasticity may shed light on general principles of basal ganglia function. In addition, understanding specializations of such circuits in songbirds may illuminate specific innovations critical for vocal learning.
Producing Song: The Vocal Apparatus
Authors: SUTHERS RODERICK A. , ZOLLINGER SUE ANNE
Published: August 2004

Abstract:In order to achieve the goal of understanding the neurobiology of birdsong, it is necessary to understand the peripheral mechanisms by which song is produced. This paper reviews recent advances in the understanding of syringeal and respiratory motor control and how birds utilize these systems to create their species‐typical sounds. Songbirds have a relatively homogeneous duplex vocal organ in which sound is generated by oscillation of a pair of thickened labia on either side of the syrinx. Multiple pairs of syringeal muscles provide flexible, independent control of sound frequency and amplitude, and each side of the syrinx exhibits a degree of acoustic specialization. This is in contrast to many non‐songbirds, including vocal learners such as parrots, which have fewer syringeal muscles and use syringeal membranes to generate sound. In doves, at least, these membranes generate a harmonic signal in which the fundamental frequency is regulated by respiratory pressure in the air sac surrounding the syrinx and the overtones are filtered out by the vocal tract. The songs of adult songbirds are generally accompanied by precisely coordinated respiratory and syringeal motor patterns that, despite their relative stereotypy, are modulated in real time by somatosensory feedback. Comparative studies indicate songbirds have evolved species‐specific motor patterns that utilize the two sides of the syrinx in specific ways and enhance the particular acoustic effects characterizing the species song. A vocal mimic tutored with heterospecific song uses the same motor pattern as the tutor species when he accurately copies the song, suggesting that physical or physiological constraints on sound production have had a prominent role in the evolution of species‐specific motor patterns. An understanding of the relationship between the central processing and peripheral performance of song motor programs is essential for an understanding of the development, function, and evolution of these complex vocal signals.
Contributions of the Anterior Forebrain Pathway to Vocal Plasticity
Authors: BRAINARD MICHAEL S.
Published: August 2004

Abstract: The anterior forebrain pathway (AFP) is a basal ganglia‐dorsal forebrain circuit that is prominent specifically in birds that learn to sing. This circuit is interconnected with the song motor pathway, is active during song production, and contains neurons that are selective for the sound of the bird's own song, suggesting an important role for the AFP in vocal behavior. However, interruption of the AFP by lesions in adult birds has little overt effect on the production of learned song. In contrast, lesions in juvenile birds prevent the normal progression of song learning. Moreover, lesions in adults, while not disrupting production, can prevent experience‐dependent plasticity of song. Such data implicate the AFP specifically in song learning and vocal plasticity. This chapter reviews some of the experimental evidence supporting a role for the AFP in these processes and discusses potential instructive and permissive functions of the AFP in vocal plasticity.
Seasonal Plasticity in the Song Control System: Multiple Brain Sites of Steroid Hormone Action and the Importance of Variation in Song Behavior
Authors: BALL GREGORY F. , AUGER CATHERINE J. , BERNARD DANIEL J. , CHARLIER THIERRY D. , SARTOR JENNIFER J. , RITERS LAUREN V. , BALTHAZART JACQUES
Published: August 2004

Abstract:Birdsong, in non‐tropical species, is generally more common in spring and summer when males sing to attract mates and/or defend territories. Changes in the volumes of song control nuclei, such as HVC and the robust nucleus of the arcopallium (RA), are observed seasonally. Long photoperiods in spring stimulate the recrudescence of the testes and the release of testosterone. Androgen receptors, and at times estrogen receptors, are present in HVC and RA as are co‐factors that facilitate the transcriptional activity of these receptors. Thus testosterone can act directly to induce changes in nucleus volume. However, dissociations have been identified at times among long photoperiods, maximal concentrations of testosterone, large song control nuclei, and high rates of song. One explanation of these dissociations is that song behavior itself can influence neural plasticity in the song system. Testosterone can act via brain‐derived neurotrophic factor (BDNF) that is also released in HVC as a result of song activity. Testosterone could enhance song nucleus volume indirectly by acting in the preoptic area, a region regulating sexual behaviors, including song, that connects to the song system through catecholaminergic cells. Seasonal neuroplasticity in the song system involves an interplay among seasonal state, testosterone action, and behavioral activity.
Allogeneic Lymphocytes Induce Tumor Regression of Advanced Metastatic Breast Cancer
Authors: Bishop Michael R. , Fowler Daniel H. , Marchigiani Donna , Castro Kathleen , Kasten-Sportes Claude , Steinberg Seth M. , Gea-Banacloche Juan C. , Dean Robert , Chow Catherine K. , Carter Charles , Read Elizabeth J. , Leitman Susan , Gress Ronald
Published: August 2004

Purpose

Allogeneic T lymphocytes can induce regression of metastatic breast cancer through an immune-mediated graft-versus-tumor (GVT) effect in murine models. To determine if a clinical GVT effect exists against metastatic breast cancer, allogeneic lymphocytes were used as adoptive cellular therapy after a reduced-intensity chemotherapy conditioning regimen and allogeneic hematopoietic stem-cell transplantation (HSCT) from human leukocyte antigen–matched siblings.

Patients and Methods

Sixteen patients with metastatic breast cancer that had progressed after treatment with anthracyclines, taxanes, hormonal agents, and trastuzumab, received allogeneic HSCT. The reduced-intensity transplant conditioning regimen consisted of cyclophosphamide and fludarabine. To distinguish an immunological GVT effect from any antitumor effect of cytotoxic chemotherapy in the transplant-conditioning regimen, allogeneic T lymphocytes were removed from the stem-cell graft and were subsequently administered late postallogeneic HSCT. Allogeneic lymphocytes containing 1 × 106, 5 × 106, and 10 × 106 CD3+ cells/kg were infused on days +42, +70, and +98 post–allogeneic HSCT, respectively.

Results

Objective tumor regressions occurred after day +28 post–allogeneic HSCT in six patients and were attributed to allogeneic lymphocyte infusions. Two of these responding patients had disease progression post–allogeneic HSCT before subsequent tumor regression. Tumor regressions occurred concomitantly with the establishment of complete donor T-lymphoid engraftment, were associated with the development of graft-versus-host disease (GVHD), and were abrogated by subsequent systemic immunosuppression for GVHD.

Conclusion

Allogeneic lymphocytes can induce regression of advanced metastatic breast cancer. These results indicate that an immunological GVT effect from allogeneic lymphocytes exists against metastatic breast cancer and provide rationale for further development of allogeneic cellular therapy for this largely incurable disease.
Gamma Knife Radiosurgery for Pituitary Adenoma: Early Results
Authors: Petrovich Zbigniew , Yu Cheng , Giannotta Steven L. , Zee Chi-Shing , Apuzzo Michael L.J.
Published: August 2004

OBJECTIVE

In recent years, gamma knife radiosurgery (GKRS) has emerged as an important treatment modality in the management of pituitary adenomas. Treatment results after performing GKRS and the complications of this procedure are reviewed.

METHODS

Between 1994 and 2002, a total of 78 patients with pituitary adenomas underwent a total of 84 GKRS procedures in our medical center. This patient group comprised 46 men (59%) and 32 women (41%). All patients were treated for recurrent or residual disease after surgery or radiotherapy, with 83% presenting with extensive tumor involvement. The cavernous sinus was involved in 75 patients (96%), and 22 patients (28%) had hormone-secreting adenomas. This latter subset of patients included 12 prolactinomas (15%), 6 growth-hormone secreting tumors (8%), and 4 adrenocorticotropic hormone-secreting tumors (5%). The median tumor volume was 2.3 cm3, and the median radiation dose was 15 Gy defined to the 50% isodose line. The mean and median follow-up periods were 41 and 36 months, respectively.

RESULTS

GKRS was tolerated well in these patients; acute toxicity was uncommon and of no clinical significance. Late toxicity was noted in three patients (4%) and consisted of VIth cranial nerve palsy. In two patients, there was spontaneous resolution of this palsy, and in one patient, it persisted for the entire 3-year duration of follow-up. Of the 15 patients who presented with cranial nerve dysfunction, 8 (53%) experienced complete recovery and 3 (20%) showed major improvement within 12 months of therapy. Tumor volume reduction was slow, with 30% of patients showing decreased tumor volume more than 3 years after undergoing GKRS. None of the 56 patients with nonfunctioning tumors showed progression in the treated volume, and 4 (18%) of the 22 hormone-secreting tumors relapsed (P = 0.008). Of the four patients with adrenocorticotropic hormone-secreting adenomas, therapy failed in two of them. All six patients with growth hormone-producing tumors responded well to therapy. Of the 12 patients with prolactinomas 10 (83%) had normalization of hormone level and 2 patients experienced increasing prolactin level. Two patients with prolactinomas had three normal pregnancies after undergoing GKRS.

CONCLUSION

GKRS is a safe and effective therapy in selected patients with pituitary adenomas. None of the patients in our study experienced injury to the optic apparatus. A radiation dose higher than 15 Gy is probably needed to improve control of hormone-secreting adenomas. Longer follow-up is required for a more complete assessment of late toxicity and treatment efficacy.
Limited Benefit of Intraoperative Low-field Magnetic Resonance Imaging in Craniopharyngioma Surgery
Authors: Nimsky Christopher , Ganslandt Oliver , Hofmann Bernd , Fahlbusch Rudolf
Published: August 2004

OBJECTIVE

To investigate the benefit of intraoperative low-field magnetic resonance imaging (MRI) in craniopharyngioma surgery.

METHODS

We used a 0.2-T Magnetom Open scanner (Siemens Medical Solutions, Erlangen, Germany) that was located in a radiofrequency-shielded operating theater for intraoperative MRI. The head of the patient was placed in the fringe field of the scanner, so that standard microinstruments could be used. In transsphenoidal surgery, T1-weighted coronal and sagittal images were acquired. In transcranial surgery, a three-dimensional, gradient echo, T1-weighted, fast low-angle shot sequence was measured, thus allowing multiplanar reformatting.

RESULTS

A total of 21 surgical procedures in craniopharyngioma patients were investigated. In 10 patients, a bifrontal-translaminar approach was used; in 6 patients, the craniopharyngioma was removed via a transsphenoidal approach; and in 5 patients, intraoperative MRI was used to monitor cyst puncture and aspiration. In the craniotomy group, intraoperative imaging depicted a clear tumor remnant in one patient, which was subsequently removed. In another patient, an area of contrast enhancement was interpreted as artifact; however, postoperative follow-up at 3 months was suspicious for a minor remnant. Two of the eight patients with complete removal developed a recurrence during the follow-up period. In the group of patients who underwent primary transsphenoidal surgery (n = 4), complete removal was estimated by the surgeon in three cases. Intraoperative imaging depicted a remaining tumor in one case, leading to further tumor removal; however, follow-up revealed recurrent cysts.

CONCLUSION

Intraoperative low-field MRI allows an ultraearly evaluation of the extent of tumor removal in craniopharyngioma surgery in most cases. Imaging showing an incomplete resection offers the chance for further tumor removal during the same operation. However, intraoperative low-field MRI depicting a complete resection does not exclude craniopharyngioma recurrence.
The Natural History of Incidental Meningiomas
Authors: Nakamura Makoto , Roser Florian , Michel Julia , Jacobs Cornelius , Samii Madjid
Published: August 2004

OBJECTIVE

Little information about the natural history of incidental meningiomas exists in the literature. The aim of this study was to determine the natural history of asymptomatic meningiomas by comparing different methods of growth rate calculation to establish a strategy for dealing with these tumors.

METHODS

In 47 asymptomatic patients, hospital charts, follow-up records, and imaging studies were reviewed. Of these patients, 6 underwent surgery. Tumor growth rates were determined by calculating the absolute and relative growth rates and the tumor volume doubling times.

RESULTS

In 41 patients with conservative management, the average tumor size was 9 cm3, and the majority (66%) of growth rates were less than 1 cm3/yr. The absolute growth rate ranged from 0.03 to 2.62 cm3/yr (mean, 0.796 cm3/yr). Relative annual growth rates ranged from 0.48 to 72.8% (mean, 14.6%). The tumor doubling time ranged from 1.27 to 143.5 years (mean, 21.6 yr). A moderate correlation between the age and growth rates was found. In young patients, annual growth rates tended to be higher and tumor doubling times shorter. There was no clear correlation between the initial tumor size and tumor doubling time. The mean annual growth rate of meningiomas with calcification was lower than in tumors without calcification. Also, tumors with hypointense or isointense T2 signals on magnetic resonance imaging had a lower growth rate. In the group of six patients with surgical excision, tumor growth rates were higher and tumor doubling times shorter than in the nonsurgical group.

CONCLUSION

The majority of incidental meningiomas show minimal growth; thus, they may be observed without surgical intervention unless specific symptoms appear. Tumor growth is associated with patient age. The initial tumor size is not considered a predictive factor for tumor growth. Radiological features, such as calcification or T2 signal intensity, may provide useful information to predict the growth potential of meningiomas.
Recombinant Activated Factor VII for the Rapid Correction of Coagulopathy in Nonhemophilic Neurosurgical Patients
Authors: Park Paul , Fewel Matthew E. , Garton Hugh J. , Thompson B. Gregory , Hoff Julian T.
Published: August 2004

OBJECTIVE

Coagulopathy is a significant contraindication for neurosurgery. Unfortunately, many coagulopathic patients require urgent neurosurgical intervention. Standard use of blood products, including fresh-frozen plasma or prothrombin complexes, to correct the coagulopathy often leads to significant delays in treatment. Recombinant activated factor VII (rFVIIa) is a medication originally designed to treat bleeding in hemophiliacs but also seems to correct a wide variety of coagulopathies rapidly and safely in nonhemophilic patients.

METHODS

The medical records of nine patients with coagulopathy requiring urgent neurosurgical intervention were reviewed retrospectively. Each patient was given a dose ranging from 40 to 90 μg/kg of rFVIIa before undergoing surgery. Pre-rFVIIa coagulation and post-rFVIIa coagulation parameters were obtained. Once correction of the coagulopathy was verified, each patient underwent the appropriate neurosurgical procedure.

RESULTS

The average age of the patients was 40.9 years; six were women. The causes of the coagulopathy included anticoagulant medication, liver dysfunction, and dilutional coagulopathy after traumatic hemorrhage. Neurosurgical indications included intraparenchymal/intraventricular hemorrhage, hydrocephalus, diffuse cerebral edema, and epidural hematoma. Post-rFVIIa coagulation parameters obtained as early as 20 minutes after infusion of the medication showed normalization of values. There were no procedural or operative complications and no postoperative hemorrhagic complications. No associated thromboembolic or other complications with the use of rFVIIa were observed.

CONCLUSION

The use of rFVIIa for the urgent surgical treatment of coagulopathic patients is quite promising. Further studies, including randomized, prospective trials using rFVIIa to address issues such as optimal dosing, efficacy, surgical indications, cost-effectiveness, morbidity, and mortality are needed.
Routine Placement of a Ventricular Reservoir at Endoscopic Third Ventriculostomy
Authors: Aquilina Kristian , Edwards Richard J. , Pople Ian K.
Published: August 2004

OBJECTIVE

Endoscopic third ventriculostomy (ETV) failure may be abrupt in onset, causing a potentially life-threatening increase in intracranial pressure. ETV failure may also have a more insidious onset, and in these cases, diagnosis on clinical and radiological grounds can be difficult. This study evaluates the usefulness of routine ventricular reservoir placement at the time of ETV for subsequent emergency ventricular access or the diagnosis of ETV failure.

METHODS

A retrospective review of 84 consecutive patients undergoing ETV with routine insertion of a ventricular reservoir during a 4-year period (1996–2000) was undertaken. The mean follow-up period was 14.8 months. End points for ETV failure were shunt insertion or revision of ETV. The diagnostic and therapeutic use of the reservoir was quantified.

RESULTS

The reservoir was used in 32% of patients (n = 27). The reservoir allowed life-saving emergency ventricular access in two cases of acute recurrent hydrocephalus. In patients with symptoms but equivocal radiological evidence of recurrent hydrocephalus, the reservoir allowed for assessment of intracranial pressure (n = 19) and/or a therapeutic trial of cerebrospinal fluid aspiration (n = 5). Seven of these patients subsequently required revision ETV or shunt insertion. In the 14 patients who had normal intracranial pressure, conservative management was successful. The reservoir also facilitated intrathecal drug administration for postoperative ventriculitis (n = 2). No patients requested reservoir removal.

CONCLUSION

Routine insertion of a ventricular reservoir allows life-saving emergency therapeutic cerebrospinal fluid aspiration to be performed for sudden neurological deterioration caused by ventriculostomy failure. It also assists in the diagnosis of ETV failure and allows intrathecal drug administration.