Factors Associated with Medical Students' Attitudes About Cost-Conscious Care: A Mixed-Methods Multi-school Study.

BACKGROUND: Because physician practices contribute to national healthcare expenditures, initiatives aimed at educating physicians about high-value cost-conscious care (HVCCC) are important. Prior studies suggest that the training environment influences physician attitudes and behaviors towards HVCCC. OBJECTIVE: To explore the relationship between medical student experiences and HVCCC attitudes. DESIGN: Quantitative and qualitative analysis of a multi-institutional survey. PARTICIPANTS: Medical students from nine US medical schools. APPROACH: A 44-item survey that included the Maastricht HVCCC Attitudes Questionnaire, a validated tool for assessing HVCCC attitudes, was administered electronically. Attitudinal domains of high-value care (HVC), cost incorporation (CI), and perceived drawbacks (PD) were compared using one-way ANOVA among students with a range of exposures. Open text responses inviting participants to reflect on their attitudes were analyzed using classical content analysis. KEY RESULTS: A total of 740 students completed the survey (response rate 15%). Students pursuing a "continuity-oriented" specialty held more favorable attitudes towards HVCCC than those pursuing "technique-oriented" specialties (HVC sub-score = 3.20 vs. 3.06; p = 0.005, CI sub-score = 2.83 vs. 2.74; p < 0.001). Qualitative analyses revealed personal, educational, and professional experiences shape students' HVCCC attitudes, with similar experiences interpreted differently leading to both more and less favorable attitudes. CONCLUSION: Students pursuing specialties with longitudinal patient contact may be more enthusiastic about practicing high-value care. Life experiences before and during medical school shape these attitudes, and complex interactions between these forces drive student perceptions of HVCCC.

Differences in vocal brain areas and astrocytes between the house wren and the rufous-tailed hummingbird.

The house wren shows complex song, and the rufous-tailed hummingbird has a simple song. The location of vocal brain areas supports the song's complexity; however, these still need to be studied. The astrocytic population in songbirds appears to be associated with change in vocal control nuclei; however, astrocytic distribution and morphology have not been described in these species. Consequently, we compared the distribution and volume of the vocal brain areas: HVC, RA, Area X, and LMAN, cell density, and the morphology of astrocytes in the house wren and the rufous-tailed hummingbird. Individuals of the two species were collected, and their brains were analyzed using serial Nissl- NeuN- and MAP2-stained tissue scanner imaging, followed by 3D reconstructions of the vocal areas; and GFAP and S100ß astrocytes were analyzed in both species. We found that vocal areas were located close to the cerebral midline in the house wren and a more lateralized position in the rufous-tailed hummingbird. The LMAN occupied a larger volume in the rufous-tailed hummingbird, while the RA and HVC were larger in the house wren. While Area X showed higher cell density in the house wren than the rufous-tailed hummingbird, the LMAN showed a higher density in the rufous-tailed hummingbird. In the house wren, GFAP astrocytes in the same bregma where the vocal areas were located were observed at the laminar edge of the pallium (LEP) and in the vascular region, as well as in vocal motor relay regions in the pallidum and mesencephalon. In contrast, GFAP astrocytes were found in LEP, but not in the pallidum and mesencephalon in hummingbirds. Finally, when comparing GFAP astrocytes in the LEP region of both species, house wren astrocytes exhibited significantly more complex morphology than those of the rufous-tailed hummingbird. These findings suggest a difference in the location and cellular density of vocal circuits, as well as morphology of GFAP astrocytes between the house wren and the rufous-tailed hummingbird.

Steroid-dependent plasticity in the song control system: Perineuronal nets and HVC neurogenesis.

The vocal control nucleus HVC in songbirds has emerged as a widespread model system to study adult brain plasticity in response to changes in the hormonal and social environment. I review here studies completed in my laboratory during the last decade that concern two aspects of this plasticity: changes in aggregations of extracellular matrix components surrounding the soma of inhibitory parvalbumin-positive neurons called perineuronal nets (PNN) and the production/incorporation of new neurons. Both features are modulated by the season, age, sex and endocrine status of the birds in correlation with changes in song structure and stability. Causal studies have also investigated the role of PNN and of new neurons in the control of song. Dissolving PNN with chondroitinase sulfate, a specific enzyme applied directly on HVC or depletion of new neurons by focalized X-ray irradiation both affected song structure but the amplitude of changes was limited and deserves further investigations.

Notch1 is involved in cell proliferation and neuronal differentiation in the HVC of zebra finch (Taeniopygia guttata).

Significant sex differences are found in songbirds' song control nuclei and their controlled song behaviors. To elucidate the underlying mechanisms, we explored the role of Notch1 during the development of the high vocal centre (HVC) and song learning in zebra finch. Our study first found that Notch1 positive cells were distributed in HVC with female-biased densities at posthatching day (PHD) 15, but male-biased at PHD 45 and adult. There were about 60 putative oestrogen-responsive elements within 2.5 kb upstream of Notch1, and Notch1 mRNA in the explants that contained the developing male HVC was significantly increased after estrogen addition into the cultured medium for 48 h. After injecting Notch1-interfering lentivirus into the male or female HVC at PHD 15, cell proliferation was significantly promoted in the ventricle zone overlying the HVC at PHD 23. In addition, neuronal differentiation towards Hu+ /BrdU+ at PHD 31, mature neurons (NeuN+/BrdU+) including those projecting to RA in HVC and the sizes of HVC and RA at adult increased significantly after Notch1-interfering lentiviruses were injected into the male HVC at PHD 15. However, the above measurements decreased, following the injection of the lentiviruses expressing Notch intracellular domain (NICD). Finally, the repeat numbers of syllables 'b' or 'c' of learned songs changed after the injection of Notch1-interfering or NICD-expressing lentiviruses into the HVC at PHD15. Our study suggests that Notch1 is related to the development of HVC and song learning in the zebra finch.

The effects of Wnt, BMP, and Notch signaling pathways on cell proliferation and neural differentiation in a song control nucleus (HVC) of Lonchura striata.

There is obvious sexual dimorphism in the song control system of songbirds. In the higher vocal center (HVC), cell proliferation and neuronal differentiation contribute to the net addition of neurons. However, the mechanism underlying these changes is unclear. Given that Wnt, Bmp, and Notch pathways are involved in cell proliferation and neuronal differentiation, no reports are available to study the role of the three pathways in the song control system. To address the issue, we studied cell proliferation in the ventricle zone overlying the developing HVC and neural differentiation within the HVC of Bengalese finches (Lonchura striata) at posthatching day 15 when HVC progenitor cells are generated on a large scale and differentiate into neurons, after Wnt and Bmp pathways were activated by using a pharmacological agonist (LiCl) or Bmp4, respectively, and the Notch pathway was inhibited by an inhibitor (N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester), DAPT). The results indicated that both cell proliferation and neural differentiation toward HVC neurons increased significantly after activation of the Wnt signaling pathway or inhibition of the Notch signaling pathway. Although cell proliferation was increased, neural differentiation was inhibited after treatment with Bmp4. There was obvious synergetic enhancement in the number of proliferating cells after the coregulation of two or three signaling pathways. In addition, synergetic enhancement was also found in the Wnt and Notch pathways in neural differentiation toward neurons within HVC. These results suggest that the three signaling pathways are involved in cell proliferation and neural differentiation of HVC.

A neural hub for holistic courtship displays.

Courtship displays often involve the concerted production of several distinct courtship behaviors. The neural circuits that enable the concerted production of the component behaviors of a courtship display are not well understood. Here, we identify a midbrain cell group (A11) that enables male zebra finches to produce their learned songs in concert with various other behaviors, including female-directed orientation, pursuit, and calling. Anatomical mapping reveals that A11 is at the center of a complex network including the song premotor nucleus HVC as well as brainstem regions crucial to calling and locomotion. Notably, lesioning A11 terminals in HVC blocked female-directed singing but did not interfere with female-directed calling, orientation, or pursuit. In contrast, lesioning A11 cell bodies strongly reduced and often abolished all female-directed courtship behaviors. However, males with either type of lesion still produced songs when in social isolation. Lastly, imaging calcium-related activity in A11 terminals in HVC showed that during courtship, A11 signals HVC about female-directed calls and during female-directed singing, about the transition from simpler introductory notes to the acoustically more complex syllables that depend intimately on HVC for their production. These results show how a brain region important to reproduction in both birds and mammals enables holistic courtship displays in male zebra finches, which include learning songs, calls, and other non-vocal behaviors.

Sex differences in myelination of the zebra finch vocal control system emerge relatively late in development.

The role of myelination in the development of motor control is widely known, but its role in the development of cognitive abilities is less understood. Here, we examined sex differences in the development of myelination of structures and tracts that support song learning and production in songbirds. We collected brains from 63 young male and female zebra finches (Taeniopygia guttata) over four stages of development that correspond to different stages of song learning. Using a myelination marker (myelin basic protein), we measured the development of myelination in three different nuclei of the vocal control system (HVC, RA, and lateral magnocellular nucleus of the anterior nidopallium [LMAN]) and two tracts (HVC-RA and lamina mesopallium ventralis [LMV]). We found that the myelination of the vocal control nuclei and tracts is sex related and male biased. In males, the patterns of myelination were age-dependent, asynchronous in rate and progression and associated with the development of song learning and production. In females, myelination of vocal control nuclei was low or absent and did not significantly change with age. Sex differences in myelination of the HVC-RA tract were large and emerged late in development well after sex differences in the size of vocal control brain regions are established. Myelination of this tract in males coincides with the age of song crystallization. Overall, the changes in myelination in the vocal control areas and tracts measured are region-, age-, and sex-specific and are consistent with sex differences in song development.

Hepatitis Virus C-associated Nephropathy: A Review and Update.

Hepatitis C virus (HCV) infection causes hepatic and extrahepatic organ involvement. Chronic kidney disease (CKD) is a prevalent non-communicable disorder, accounting for significant morbidity and mortality worldwide. Acute kidney injury and CKD are not uncommon sequels of acute or chronic HCV infection. The pathogenesis of HCV-associated kidney injuries is not well explored. Excess cryoglobulin production occurs in HCV infection. The cryoglobulin may initiate immune complex-mediated vasculitis, inducing vascular thrombosis and inflammation due to cryoglobulin deposits. Furthermore, direct damage to nephron parts also occurs in HCV patients. Other contributory causes such as hypertension, diabetes, and genetic polymorphism enhance the risk of kidney damage in HCV-infected individuals. Implementing CKD prevention, regular evaluation, and therapy may improve the HCV burden of kidney damage and its related outcomes. Therefore, in this review, we discuss and update the possible mechanism(s) of kidney injury pathogenesis with HCV infection. We searched for related published articles in EMBASE, Google Scholar, Google, PubMed, and Scopus. We used various texts and phrases, including hepatitis virus and kidney, HCV and CKD, kidney pathology in viral hepatitis, kidney transplantation in HCV-infected patients, kidney allograft survival in viral hepatitis patients, mechanism of kidney pathology in viral hepatitis, dialysis and viral hepatitis, HCV infection and kidney injuries, and viral hepatitis and CKD progression, etc. to identify relevant articles.

A feedforward inhibitory premotor circuit for auditory-vocal interactions in zebra finches.

During vocal exchanges, hearing specific auditory signals can provoke vocal responses or suppress vocalizations to avoid interference. These abilities result in the widespread phenomenon of vocal turn taking, yet little is known about the neural circuitry that regulates the input-dependent timing of vocal replies. Previous work in vocally interacting zebra finches has highlighted the importance of premotor inhibition for precisely timed vocal output. By developing physiologically constrained mathematical models, we derived circuit mechanisms based on feedforward inhibition that enable both the temporal modulation of vocal premotor drive as well as auditory suppression of vocalization during listening. Extracellular recordings in HVC during the listening phase confirmed the presence of auditory-evoked response patterns in putative inhibitory interneurons, along with corresponding signatures of auditory-evoked activity suppression. Further, intracellular recordings of identified neurons projecting to HVC from the upstream sensorimotor nucleus, nucleus interfacialis (NIf), shed light on the timing of auditory inputs to this network. The analysis of incrementally time-lagged interactions between auditory and premotor activity in the model resulted in the prediction of a window of auditory suppression, which could be, in turn, verified in behavioral data. A phasic feedforward inhibition model consistently explained the experimental results. This mechanism highlights a parsimonious and generalizable principle for how different driving inputs (vocal and auditory related) can be integrated in a single sensorimotor circuit to regulate two opposing vocal behavioral outcomes: the controlled timing of vocal output or the suppression of overlapping vocalizations.

DARPP-32 distinguishes a subset of adult-born neurons in zebra finch HVC.

Adult male zebra finches (Taeniopygia guttata) continually incorporate adult-born neurons into HVC, a telencephalic brain region necessary for the production of learned song. These neurons express activity-dependent immediate early genes (e.g., zenk and c-fos) following song production, suggesting that these neurons are active during song production. Half of these adult-born HVC neurons (HVC NNs) can be backfilled from the robust nucleus of the arcopallium (RA) and are a part of the vocal motor pathway underlying learned song production, but the other half do not backfill from RA, and they remain to be characterized. Here, we used cell birth-dating, retrograde tract tracing, and immunofluorescence to demonstrate that half of all HVC NNs express the phosphoprotein DARPP-32, a protein associated with dopamine receptor expression. We also demonstrate that DARPP-32+ HVC NNs are contacted by tyrosine hydroxylase immunoreactive fibers, suggesting that they receive catecholaminergic input, have transiently larger nuclei than DARPP-32-neg HVC NNs, and do not backfill from RA. Taken together, these findings help characterize a group of HVC NNs that have no apparent projections to RA and so far have eluded positive identification other than HVC NN status.

Extensive GJD2 Expression in the Song Motor Pathway Reveals the Extent of Electrical Synapses in the Songbird Brain.

Birdsong is a precisely timed animal behavior. The connectivity of song premotor neural networks has been proposed to underlie the temporal patterns of neuronal activity that control vocal muscle movements during singing. Although the connectivity of premotor nuclei via chemical synapses has been characterized, electrical synapses and their molecular identity remain unexplored. We show with in situ hybridizations that GJD2 mRNA, coding for the major channel-forming electrical synapse protein in mammals, connexin 36, is expressed in the two nuclei that control song production, HVC and RA from canaries and zebra finches. In canaries' HVC, GJD2 mRNA is extensively expressed in GABAergic and only a fraction of glutamatergic cells. By contrast, in RA, GJD2 mRNA expression is widespread in glutamatergic and GABAergic neurons. Remarkably, GJD2 expression is similar in song nuclei and their respective embedding brain regions, revealing the widespread expression of GJD2 in the avian brain. Inspection of a single-cell sequencing database from zebra and Bengalese finches generalizes the distributions of electrical synapses across cell types and song nuclei that we found in HVC and RA from canaries, reveals a differential GJD2 mRNA expression in HVC glutamatergic subtypes and its transient increase along the neurogenic lineage. We propose that songbirds are a suitable model to investigate the contribution of electrical synapses to motor skill learning and production.

The Gene Expression Profile of the Song Control Nucleus HVC Shows Sex Specificity, Hormone Responsiveness, and Species Specificity Among Songbirds.

Singing occurs in songbirds of both sexes, but some species show typical degrees of sex-specific performance. We studied the transcriptional sex differences in the HVC, a brain nucleus critical for song pattern generation, of the forest weaver (Ploceus bicolor), the blue-capped cordon-bleu (Uraeginthus cyanocephalus), and the canary (Serinus canaria), which are species that show low, medium, and high levels of sex-specific singing, respectively. We observed persistent sex differences in gene expression levels regardless of the species-specific sexual singing phenotypes. We further studied the HVC transcriptomes of defined phenotypes of canary, known for its testosterone-sensitive seasonal singing. By studying both sexes of canaries during both breeding and non-breeding seasons, non-breeding canaries treated with testosterone, and spontaneously singing females, we found that the circulating androgen levels and sex were the predominant variables associated with the variations in the HVC transcriptomes. The comparison of natural singing with testosterone-induced singing in canaries of the same sex revealed considerable differences in the HVC transcriptomes. Strong transcriptional changes in the HVC were detected during the transition from non-singing to singing in canaries of both sexes. Although the sex-specific genes of singing females shared little resemblance with those of males, our analysis showed potential functional convergences. Thus, male and female songbirds achieve comparable singing behaviours with sex-specific transcriptomes.

A review on high velocity compaction mechanism of powder metallurgy.

High Velocity Compaction (HVC) is a key technology to realize the performance of powder metallurgy parts "three high and one low" (high density, high precision, high performance, and low cost). The main purpose of this paper is to summarize the research results at home and abroad on the forming mechanism, forming influencing factors and theoretical basis of high velocity compaction. This paper analyzes and summarizes the literature and monographs at home and abroad through literature research methods to obtain the research results of high velocity powder metallurgy compaction, so as to fully and correctly understand the research progress, development trends and application prospects of high velocity compaction. This paper expounds the technical characteristics, advantages and limitations of high velocity compaction, and analyzes and looks forward to its development trend, application prospect and expansion field, So as to provide reference and reference for the future research and application direction of high velocity compaction technology.

Neurogenesis and the development of neural sex differences in vocal control regions of songbirds.

The brain regions that control the learning and production of song and other learned vocalizations in songbirds exhibit some of the largest sex differences in the brain known in vertebrates and are associated with sex differences in singing behavior. Song learning takes place through multiple stages: an early sensory phase when song models are memorized, followed by a sensorimotor phase in which auditory feedback is used to modify song output through subsong, plastic song, to adult crystalized song. However, how patterns of neurogenesis in these brain regions change through these learning stages, and differ between the sexes, is little explored. We collected brains from 63 young male and female zebra finches (Taeniopygia guttata) over four stages of song learning. Using neurogenesis markers for cell division (proliferating cell nuclear antigen), neuron migration (doublecortin), and mature neurons (neuron-specific nuclear protein), we demonstrate that there are sex-specific changes in neurogenesis over song development that differ between the caudal motor pathway and anterior forebrain pathway of the vocal control circuit. In many of these regions, sex differences emerged very early in development, by 25 days post hatch, at the beginning of song learning. The emergence of sex differences in other components of the system was more gradual and had specific trajectories depending on the brain region and its function. In conclusion, we found that sex differences occurred early and continued during song learning. Moreover, transitions from the different phases of song development do not seem to depend on large changes in neurogenesis in the vocal control areas measured.

Dynamic transcriptome landscape in the song nucleus HVC between juvenile and adult zebra finches.

Male juvenile zebra finches learn to sing by imitating songs of adult males early in life. The development of the song control circuit and song learning and maturation are highly intertwined processes, involving gene expression, neurogenesis, circuit formation, synaptic modification, and sensory-motor learning. To better understand the genetic and genomic mechanisms underlying these events, we used RNA-Seq to examine genome-wide transcriptomes in the song control nucleus HVC of male juvenile (45 d) and adult (100 d) zebra finches. We report that gene groups related to axon guidance, RNA processing, lipid metabolism, and mitochondrial functions show enriched expression in juvenile HVC compared to the rest of the brain. As juveniles mature into adulthood, massive gene expression changes occur. Expression of genes related to amino acid metabolism, cell cycle, and mitochondrial function is reduced, accompanied by increased and enriched expression of genes with synaptic functions, including genes related to G-protein signaling, neurotransmitter receptors, transport of small molecules, and potassium channels. Unexpectedly, a group of genes with immune system functions is also developmentally regulated, suggesting potential roles in the development and functions of HVC. These data will serve as a rich resource for investigations into the development and function of a neural circuit that controls vocal behavior.

Readmission following extracranial-intracranial bypass surgery in the United States: nationwide rates, causes, risk factors, and volume-driven outcomes.

OBJECTIVE: Extracranial-intracranial (EC-IC) bypass surgery remains an important treatment option for patients with moyamoya disease (MMD), intracranial arteriosclerotic disease (ICAD) with symptomatic stenosis despite the best medical management, and complex aneurysms. The therapeutic benefit of cerebral bypass surgery depends on optimal patient selection and the minimization of periprocedural complications. The nationwide burden of readmissions and associated complications following EC-IC bypass surgery has not been previously described. Therefore, the authors sought to analyze a nationwide database to describe the national rates, causes, risk factors, complications, and morbidity associated with readmission following EC-IC bypass surgery for MMD, ICAD, and aneurysms. METHODS: The Nationwide Readmissions Database (NRD) was queried for the years 2010-2014 to identify patients who had undergone EC-IC bypass for MMD, medically failed symptomatic ICAD, or unruptured aneurysms. Predictor variables included demographics, preexisting comorbidities, indication for surgery, and hospital bypass case volume. A high-volume center (HVC) was defined as one that performed 10 or more cases/year. Outcome variables included perioperative stroke, discharge disposition, length of stay, total hospital costs, and readmission (30 days, 90 days). Multivariable analysis was used to identify predictors of readmission and to study the effect of treatment at HVCs on quality outcomes. RESULTS: In total, 2500 patients with a mean age of 41 years were treated with EC-IC bypass surgery for MMD (63.1%), ICAD (24.5%), or unruptured aneurysms (12.4%). The 30- and 90-day readmission rates were 7.5% and 14.0%, respectively. Causes of readmission included new stroke (2.5%), wound complications (2.5%), graft failure (1.5%), and other infection (1.3%). In the multivariable analysis, risk factors for readmission included Medicaid/self-pay (OR 1.6, 95% CI 1.1-2.4, vs private insurance), comorbidity score (OR 1.2, 95% CI 1.1-1.4, per additional comorbidity), and treatment at a non-HVC (OR 1.9, 95% CI 1.1-3.0). Treatment at an HVC (17% of patients) was associated with significantly lower rates of nonroutine discharge dispositions (13.4% vs 26.7%, p = 0.004), ischemic stroke within 90 days (0.8% vs 2.9%, p = 0.03), 30-day readmission (3.9% vs 8.2%, p = 0.03), and 90-day readmission (8.6% vs 15.2%, p = 0.01). These findings were confirmed in a multivariable analysis. The authors estimate that centralization to HVCs may result in 333 fewer nonroutine discharges (50% reduction), 12,000 fewer hospital days (44% reduction), 165 fewer readmissions (43%), and a cost savings of $15.3 million (11% reduction). CONCLUSIONS: Readmission rates for patients after EC-IC bypass are comparable with those after other common cranial procedures and are primarily driven by preexisting comorbidities, socioeconomic status, and treatment at low-volume centers. Periprocedural complications, including stroke, graft failure, and wound complications, occurred at the expected rates, consistent with those in prior clinical series. The centralization of care may significantly reduce perioperative complications, readmissions, and hospital resource utilization.

Sex differences and similarities in the neural circuit regulating song and other reproductive behaviors in songbirds.

In the 1970s, Nottebohm and Arnold reported marked male-biased sex differences in the volume of three song control nuclei in songbirds. Subsequently a series of studies on several songbird species suggested that there is a positive correlation between the degree to which there is a sex difference in the volume of these song control nuclei and in song behavior. This correlation has been questioned in recent years. Furthermore, it has become clear that the song circuit is fully integrated into a more comprehensive neural circuit that regulates multiple courtship and reproductive behaviors including song. Sex differences in songbirds should be evaluated in the context of the full complement of behaviors produced by both sexes in relation to reproduction and based on the entire circuit in order to understand the functional significance of variation between males and females in brain and behavior. Variation in brain and behavior exhibited among living songbird species provides an excellent opportunity to understand the functional significance of sex differences related to social behaviors.

Acetylcholine in action.

The neurotransmitter acetylcholine influences how male finches perform courtship songs by acting on a region of the premotor cortex called HVC.

Acetylcholine acts on songbird premotor circuitry to invigorate vocal output.

Acetylcholine is well-understood to enhance cortical sensory responses and perceptual sensitivity in aroused or attentive states. Yet little is known about cholinergic influences on motor cortical regions. Here we use the quantifiable nature of birdsong to investigate how acetylcholine modulates the cortical (pallial) premotor nucleus HVC and shapes vocal output. We found that dialyzing the cholinergic agonist carbachol into HVC increased the pitch, amplitude, tempo and stereotypy of song, similar to the natural invigoration of song that occurs when males direct their songs to females. These carbachol-induced effects were associated with increased neural activity in HVC and occurred independently of basal ganglia circuitry. Moreover, we discovered that the normal invigoration of female-directed song was also accompanied by increased HVC activity and was attenuated by blocking muscarinic acetylcholine receptors. These results indicate that, analogous to its influence on sensory systems, acetylcholine can act directly on cortical premotor circuitry to adaptively shape behavior.

Manipulations of inhibition in cortical circuitry differentially affect spectral and temporal features of Bengalese finch song.

The interplay between inhibition and excitation can regulate behavioral expression and control, including the expression of communicative behaviors like birdsong. Computational models postulate varying degrees to which inhibition within vocal motor circuitry influences birdsong, but few studies have tested these models by manipulating inhibition. Here we enhanced and attenuated inhibition in the cortical nucleus HVC (used as proper name) of Bengalese finches (Lonchura striata var. domestica). Enhancement of inhibition (with muscimol) in HVC dose-dependently reduced the amount of song produced. Infusions of higher concentrations of muscimol caused some birds to produce spectrally degraded songs, whereas infusions of lower doses of muscimol led to the production of relatively normal (nondegraded) songs. However, the spectral and temporal structures of these nondegraded songs were significantly different from songs produced under control conditions. In particular, muscimol infusions decreased the frequency and amplitude of syllables, increased various measures of acoustic entropy, and increased the variability of syllable structure. Muscimol also increased sequence durations and the variability of syllable timing and syllable sequencing. Attenuation of inhibition (with bicuculline) in HVC led to changes to song distinct from and often opposite to enhancing inhibition. For example, in contrast to muscimol, bicuculline infusions increased syllable amplitude, frequency, and duration and decreased the variability of acoustic features. However, like muscimol, bicuculline increased the variability of syllable sequencing. These data highlight the importance of inhibition to the production of stereotyped vocalizations and demonstrate that changes to neural dynamics within cortical circuitry can differentially affect spectral and temporal features of song.NEW & NOTEWORTHY We reveal that manipulations of inhibition in the cortical nucleus HVC affect the structure, timing, and sequencing of syllables in Bengalese finch song. Enhancing and blocking inhibition led to opposite changes to the acoustic structure and timing of vocalizations, but both caused similar changes to vocal sequencing. These data provide support for computational models of song control but also motivate refinement of existing models to account for differential effects on syllable structure, timing, and sequencing.