Localized standing waves induced by spatiotemporal forcing.

Particle-type solutions are observed in out-of-equilibrium systems. These states can be motionless, oscillatory, or propagative depending on the injection and dissipation of energy. We investigate a family of localized standing waves based on a liquid-crystal light valve with spatiotemporal modulated optical feedback. These states are nonlinear waves in which energy concentrates in a localized and oscillatory manner. The organization of the family of solutions is characterized as a function of the applied voltage. Close to the reorientation transition, an amplitude equation allows us to elucidate the origin of these localized states and establish their bifurcation diagram. Theoretical findings are in qualitative agreement with experimental observations. Our results open the possibility of manipulating localized states induced by light, which can be used to expand and improve the storage and manipulation of information.

[Enhanced Recovery After Surgery (ERAS®) after radical cystectomy-current data]. / Aktuelle Studienlage der Enhanced Recovery After Surgery (ERAS®) nach radikaler Zystektomie.

BACKGROUND: Radical cystectomy is associated with considerable morbidity and mortality. Based on the solid evidence in colorectal surgery, fast-track/ERAS® (Enhanced Recovery After Surgery) protocols have been developed to improve the perioperative management of patients undergoing radical cystectomy. OBJECTIVES: To review the literature and guidelines and evaluate the evidence regarding the different components of ERAS® protocols. MATERIALS AND METHODS: Systemic literature search and evaluation of relevant guidelines. RESULTS: The majority of ERAS® recommendations for radical cystectomy are based on extrapolations of abdominal surgery studies. Four randomized, controlled trials and one ERAS® guideline were published for radical cystectomy. ERAS® seems to shorten length of stay without increasing the complication rate. Key elements are no bowel preparation, no nasogastric tube, optimized fluid substitution, multimodal pain management, early mobilization, and oral diet. CONCLUSIONS: Implementation of ERAS® requires multidisciplinary collaboration. Individualization of an ERAS® program, identification of the most important components and adaption to the specific needs of radical cystectomy patients are future goals.

Front propagation steered by a high-wavenumber modulation: Theory and experiments.

Homogeneously driven dynamical systems exhibit multistability. Depending on the initial conditions, fronts present a rich dynamical behavior between equilibria. Qualitatively, this phenomenology is persistent under spatially modulated forcing. However, the understanding of equilibria and front dynamics organization is not fully established. Here, we investigate these phenomena in the high-wavenumber limit. Based on a model that describes the reorientation transition of a liquid crystal light valve with spatially modulated optical forcing and the homogenization method, equilibria and fronts as a function of forcing parameters are studied. The forcing induces patterns coexisting with the uniform state in regions where the system without forcing is monostable. The front dynamics is characterized theoretically and numerically. Experimental results verify these phenomena and the law describing bistability, showing quite good agreement.

Prospective evaluation of 4-D contrast-enhanced-ultrasound (CEUS) imaging in bladder tumors.

PURPOSE: The evaluation of the potential clinical benefit of four-dimensional ultrasound (4D-US) in the assessment of bladder cancer (BC). MATERIAL AND METHODS: 20 patients with indication for cystoscopy for suspicion of bladder cancer were prospectively included in this study. All patients underwent two-dimensional ultrasound (2D-US), contrast enhanced ultrasound (CEUS) and real-time four-dimensional ultrasound (4D-US). All acquisitions were compared to each other in regard to image quality. This assessment was done using a 6 point scale (1 = best). All patients underwent subsequently cystoscopy with resection of the tumor (TURB), due a histopathological analysis was possible. RESULTS: All examinations were performed successfully and no patient had to be excluded from the study. Patients acceptance of 4D-US was consistently good. No adverse events occurred. Image quality of real time 4D-US (score: 1.27±0.46) was significantly superior (p < 0.001) to both, conventional 2D-US (score: 2.33±0.62) and also to 2D-CEUS (score: 2.00±0.53). In terms of tumor detection no superiority was evident for 4D-US compared to 2D-US or in utilization of CEUS (sensitivity = 0.89; specificity = 1.00; positive predictive value = 1.00; negative predictive value = 0.50; AUC = 0.944; (95% CI: 07.43-0.998)). CONCLUSION: The assessment of bladder cancer using real time 4D-US is feasible and improves the image quality and therefore also the precise anatomical consistency of intravesical tumor masses.

[Follow-up surveillance of muscle-invasive urinary bladder cancer after curative treatment]. / Nachsorge des muskelinvasiven Harnblasenkarzinoms nach kurativer Therapie.

Follow-up care of patients with muscle-invasive bladder cancer is subdivided into oncological and functional surveillance. More than 80% of local relapses and distant metastases occur within the first 2 years. Recurrences in the remnant urothelium also occur several years after radical cystectomy. Urinary cytology and a computed tomography (CT) scan of the abdomen and thorax including a urography phase are the standard diagnostics for tumor follow-up. There is no clear evidence for a survival benefit for the detection of asymptomatic vs. symptomatic recurrences. After partial cystectomy or trimodal treatment, there is no established follow-up schedule; however, the relatively high incidence of intravesical recurrences should be considered as there are curative treatment approaches including salvage cystectomy. Functional surveillance, which should be carried out lifelong, encompasses prevention and diagnostics of metabolic complications, urethral/ureteral strictures, problems with the urinary stoma, urinary incontinence, sexual dysfunction and urinary tract infections.

[Aftercare of non-muscle invasive bladder cancer]. / Nachsorge des nicht muskelinvasiven Harnblasenkarzinoms.

Tumor follow-up in patients with non-muscle invasive bladder cancer (NMIBC) is a weighing up between the morbidity associated with invasive diagnostics and the risk of tumor recurrence and especially progression. The risk stratification into low, intermediate, and high-risk tumors enables a risk-adapted follow-up. For individual estimation of the risk of progression and recurrence, risk calculators should be used. Follow-up is still based on cystoscopy, which is recommended lifelong for high and intermediate-risk tumors and for up to 5 tumor-free years for low-risk tumors. Urine cytology has a high sensitivity and specificity for high-risk tumors and is recommended in the follow-up care. There is currently no recommendation for any commercially available urinary marker due to inadequate evidence. For the clarification of synchronous and metachronous tumors of the upper urinary tract computed tomography (CT) urography or alternatively magnetic resonance (MR) urography is recommended.

[Deployment of the in-hospital emergency team in a tertiary care university hospital : Data analysis for the time period 2013-2016 in North-Rhine/Westphalia]. / Einsätze des innerklinischen Notfallteams eines überregionalen Maximalversorgers : Datenanalyse für den Zeitraum 2013­2016 im nordrhein-westfälischen Raum.

BACKGROUND: Recent studies demonstrated that in-hospital emergencies are linked to a higher patient mortality. In approximately 10% of patients an unexpected incident occurs during the hospital stay. Therefore, the establishment of in-hospital medical emergency teams (MET) is becoming more important in the interdisciplinary emergency treatment. The aim of this study was an analysis of medical documentation, operational tactics and procedures taken by MET of the University Hospital of Cologne in a 4-year period ranging from 2013 to 2016. MATERIAL AND METHODS: A retrospective analysis of 1664 emergency forms from MET activities at the University Hospital of Cologne from 1 January 2013 to 31 December 2016 was carried out. Every MET activation call via the emergency telephone number (5555) and subsequent emergency treatment was recorded using a standardized documentation form. The registry number on ClinicalTrials.gov is NCT03786445. RESULTS: There were 1664 emergency team calls in the whole study period. Between 2013 (404 calls) and 2016 (461 calls) the number of calls increased by 11.4%. The total mission time of the MET increased in the study period from 8342 min (2013) to 10,800 min (2016, +29.5%) and the average mission time increased from 2013 (35 min) to 2016 (40 min) by 14.3%. The primary reason for activation was collapse or syncope and was the underlying cause for 29% of calls. The number of deployments for emergencies at weekends was 50% of those during weekdays and 6.5% of the calls were for cardiopulmonary resuscitation (CPR). CONCLUSION: Analysis of data revealed that the number of MET calls, total operating time and average deployment time increased from 2013 to 2016. The primary reason for MET activations was collapse or syncope and every 17th deployment was for cardiopulmonary resuscitation. The incidence of in-hospital cardiac arrests decreased during the study period.

[Value of imaging in upper urinary tract tumors]. / Wertigkeit der Bildgebung bei Tumoren des oberen Harntraktes.

BACKGROUND: Staging of bladder cancer, hematuria as well as the evaluation of unclear findings of the kidneys and ureters are the most frequent indications for imaging of the upper urinary tract (UUT). Endourological assessment of the UUT is much more invasive compared to imaging of the bladder, raising the question of the optimal imaging technique. Several technical improvements regarding computed tomography (CT) as well as magnetic resonance imaging (MRI) were implemented in recent years. OBJECTIVES: To compare the efficacy and limitations of the most important imaging techniques regarding the UUT. MATERIALS AND METHODS: Systematic review of the literature and current German, European, and American guidelines regarding bladder cancer, urothelial carcinoma of the UUT and hematuria. RESULTS: The CT-based urography has superseded excretory urography and is the first choice for imaging of the UUT. In case of contraindications, MRI is a feasible alternative. In all cases, a urography phase is indispensable. CONCLUSIONS: Imaging of the UUT has to be used in a reasonable combination together with endourological methods and cytology. Optical coherence tomography, confocal laser endomicroscopy and scientific innovations such as radiomics might improve UUT imaging and differential diagnosis of UUT lesions in the future.

[Follow-up of renal cell carcinoma in a nonmetastatic stage]. / Nachsorge beim Nierenzellkarzinom im nicht fernmetastasierten Stadium.

Postoperative follow-up care after curative surgery or ablative treatment is the standard of care in patients with nonmetastatic renal cell carcinoma. The goal is to identify and treat postoperative complications and local recurrences early on. Follow-up investigations and their relevance are widely acknowledged and validated and patients undergoing follow-up seem to benefit from a longer survival in nonmetastatic renal cell carcinoma. Hence there is no consensus on a standardized follow-up strategy. The most disputed question is around the frequency of the investigations and the duration of the follow-up. Without an evidence-based follow-up protocol, urologists should carry out an individualized, potentially lifelong follow-up regimen, which also includes the patients' needs and perspectives.

Encefalopatía asociada a enfermedad tiroídea, un diagnóstico a tener en mente / Encephalopathy associated with thyroid disease, a diagnosis to take into account

Mujer de 54 años con antecedentes de Hipertensión arterial e Hipotiroidismo. Historia de aproximadamente 3 meses de evolución caracterizado al inicio por ánimo bajo, cambios en el comportamiento con aparición progresiva de conductas extraña, ideas delirantes y alucinaciones visuales y auditivas, junto con disminución en requerimientos de hormonas tiroídeas hasta la suspensión. Consulta en varios centros donde se cataloga como Trastorno depresivo severo con síntomas psicóticos, Síndrome confusional, Síndrome Psicótico. En este contexto se pesquisa Hipertiroidismo con títulos elevados de Anticuerpos Antitiroídeos e inicia tratamiento con Metimazol y Betabloqueo. Tras extenso estudio que descartan causas infecciosas, neoplásicas y autoinmunes; se inicia tratamiento con pulsos de Metilprednisolona con excelente y rápida respuesta clínica, la cual mantiene durante el curso del seguimiento con dosis decrecientes de corticoides.

A 54-year-old woman with a history of arterial hypertension and hypothyroidism. History of approximately 3 months of evolution characterized at the beginning by low mood, changes in behavior with progressive appearance of bizarre behaviors, delusional ideas and visual and auditory hallucinations. Consultation in several centers where it is classified as severe Depressive disorder with psychotic symptoms, Confusional syndrome, Psychotic syndrome. Hyperthyroidism is investigated with high titers of Antithyroid Antibodies and initiates treatment with Methimazole and Betablock. After extensive study that ruled out infectious, neoplastic and autoimmune causes; Treatment with Methylprednisolone pulses is initiated with excellent and rapid clinical response, which is maintained during the course of follow-up with decreasing doses of corticosteroid.

Risks and benefits of pelvic lymphadenectomy in octogenarians undergoing radical cystectomy due to urothelial carcinoma of the bladder.

OBJECTIVES: According to current guidelines, radical cystectomy (RC) should be combined with an extended pelvic lymphadenectomy (PLND) as therapeutic and staging instrument. Objective of this study was to analyze the influence of PLND on survival rates and complication rates in a selected group of elderly patients with a minimum age of 80 years. MATERIALS AND METHODS: In this single-center retrospective analysis, we evaluated 102 patients who underwent RC due to UCB from 2004 to 2015 at our institution. In 74 patients (73%), RC was combined with PLND; in 28 cases (27%), RC was performed without PLND. Impact of PLND on cancer specific survival (CSS), overall survival (OS) and progression-free survival (PFS) was analyzed using log-rank test and COX regression model. RESULTS: In univariate analysis of the data, we were not able to show a significant impact of PLND on CSS (p = 0.606), OS (p = 0.979) or PFS (p = 0.883). Also in multivariate analysis of the data, we were not able to identify PLND as an independent prognostic parameter on survival rates of patients undergoing RC, neither for CSS (p = 0.912) nor OS (p = 0.618) or PFS (p = 0.900). CONCLUSIONS: Our small and single-center study was not able to demonstrate a significant independent influence of PLND on CSS, OS and PFS in octogenarians undergoing RC due to UCB. There is no doubt that RC should usually be combined with PLND, but the results of this small data set with a selected patient cohort indicate that RC without PLND might be an option in selected cases of elderly patients.

Multiple cytokines for the detection of Mycobacterium tuberculosis infection in children with tuberculosis.

SETTING: Interferon-gamma (IFN-γ) release assays (IGRAs) play an important role in the diagnosis of Mycobacterium tuberculosis infection. However, in children with tuberculosis (TB), some studies have shown increased frequencies of false-negative or indeterminate IGRA results. OBJECTIVE: To analyse the spectrum of different cytokines to improve the diagnostic accuracy of IGRAs in latent tuberculous infection (LTBI) and active TB. DESIGN: We performed multiplex cytokine expression analysis of QuantiFERON® Gold In-Tube supernatants in children with active TB (n = 21) and disease-free contacts with (n = 15) and without LTBI (n = 12), to determine the sensitivity and specificity of the modified tests. RESULTS: Of 21 initial cytokines analysed, IFN-γ and six other candidates (interleukin [IL] 2, inducible protein 10 [IP-10], IL-13, IL-1α, tumour necrosis factor alpha [TNF-α] and granulocyte-macrophage colony-stimulating factor [GM-CSF]) were significantly more elevated in children with TB and those with LTBI than in the non-infected controls. Sensitivity and specificity were similar for IFN-γ and IL-2, but lower for the remaining candidates. Notably, a subset of candidates, including IP-10, showed M. tuberculosis antigen-induced specific expression in non-infected children. None of the candidates showed differences in expression between children with TB and those with LTBI. CONCLUSIONS: Our results did not suggest that alternative IGRA cytokines can distinguish between children with active TB and those with LTBI. IFN-γ and IL-2 showed comparable capacity in diagnosing M. tuberculosis infection in our study groups.

Mice with heterozygous deficiency of manganese superoxide dismutase (SOD2) have a skin immune system with features of "inflamm-aging".

Dendritic cells (DC) are central in regulating skin immunity. Immunosenescence is associated with a chronic inflammatory state. Little is known about the contribution of DC to "inflamm-aging". When determining langerhans cell (LC) numbers, we found a 60 % reduction of LC in aged epidermis. Reactive oxygen species(ROS) are linked with aging. The mitochondrial manganese superoxide dismutase (SOD2) is in the first line of antioxidant defense. We investigated the function of DC from SOD2 heterozygous mice (SOD2+/-) and found that at 4 months of age LC numbers are not altered, but activated LC have impaired expression of MHC-II and CD44. Immature SOD2+/- DC produced increased proinflammatory IL-6 and chemokines CXCL1 and CXCL2. Upon challenge SOD2+/- DC accumulated ROS. When activating SOD2+/- DC by LPS they less efficiently upregulated MHC-II, CD86 and CD44. Surprisingly, in vivo contact hypersensitivity (CHS) was enhanced in SOD2+/- mice although SOD2+/- DC were less potent in stimulating wt T cells. However, SOD2+/- T cells showed increased proliferation, even when stimulated with SOD2+/- DC, possibly explaining the increased CHS. Our findings suggest that SOD2 is a molecular candidate in the regulation of "inflamm-aging" conveying both immunosuppressive and proinflammatory signals through alteration of DC and T cell functions.

Individual cow's milk allergens as prognostic markers for tolerance development?

BACKGROUND: Cow's milk allergy (CMA) is one of the most common causes of food allergy in the first years of life. Fortunately, the majority of children with CMA develop clinical tolerance with time. However, no good individual markers exist to predict whether this will occur. Therefore, a prognosis to identify children with persistent CMA at diagnosis would be helpful. OBJECTIVE: In this study, we sought to assess whether measurement of IgE to individual allergens of cow's milk (CM) would separate patients with persistent CMA from those who became clinically tolerant to CM over time. METHODS: A total of 52 patients ranging from 3 months to 114 months of age with proven CMA by DBPCFC were followed over time. From these 52 patients, 32 (61.5%) patients became tolerant in the analysed time period. All patients were rechallenged at least once, some were rechallenged two or three times. Serum was analysed prior to each challenge for specific IgE, IgG and IgG4 binding to crude CM protein as well as to individual allergens of CM. RESULTS: The individual likelihood of outgrowing CMA significantly correlates with a low level of CM-specific IgE as well as a low level of specific IgE to α-lactalbumin, ß-lactoglobulin (Bos d5.0102), κ-casein and α(s1) -casein. No significant correlation was found for IgE levels to total casein, lactoferrin, ß-casein and ß-lactoglobulin (Bos d5.0101) as well as IgG and IgG4 levels to α-lactalbumin, ß-lactoglobulin and total casein. CONCLUSIONS: CM-specific IgE is a good prognostic marker for persistence of CMA. In addition, component-resolved diagnostic showed similar results. However, in our view, the rising laboratory costs do not justify a measurement on a daily basis. Additional determination of specific IgG or IgG4 levels was not useful in predicting tolerance development in our study population.

The role of hen's egg-specific IgE, IgG and IgG4 in the diagnostic procedure of hen's egg allergy.

BACKGROUND: Hen's egg (HE) allergy is a common disease in childhood. HE-specific serum IgE has been correlated with the outcome of oral food challenge tests, and diagnostic decision points have been described as helpful but still not sufficient to reduce the requirement for oral food challenges. The aim of the study was to correlate HE-specific IgE, IgG and IgG4 levels with the outcome of double-blind, placebo-controlled food challenges (DBPCFC) in patients with suspected HE allergy to improve diagnostic procedures. METHODS: HE-specific IgE, IgG, and IgG4 levels were compared between 150 children with suspected HE allergy based on sensitization and/or patient's history who underwent DBPCFC. Sixty-six patients were HE-allergic (HE-sensitized with a positive DBPCFC), 48 HE-sensitized but tolerant (negative DBPCFC), and 36 patients were nonsensitized and tolerant (negative DBPCFC). Prior to food challenge HE-specific serum IgE, IgG, and IgG4 were measured with the Phadia CAP-system. RESULTS: HE-specific IgE was significantly higher in HE-allergic patients than in clinically tolerant ones. However, there was no difference in HE-specific IgG and IgG4 concentrations between the patient groups. CONCLUSION: A proposed cut-off level of 12 kU/l IgE would identify children above this level correctly as HE-allergic. The level of HE-specific IgG or IgG4 in serum of children with suspected HE allergy does not add any additional information in the diagnostic procedure of HE allergy. For diagnostic purposes, specific IgG or IgG4 should not routinely be tested.

Electrophysiological evidence of functional integration between the language and motor systems in the brain: a study of the speech Bereitschaftspotential.

OBJECTIVE: We investigated whether the Bereitschaftspotential (BP), an event related potential believed to reflect motor planning, would be modulated by language-related parameters prior to speech. We anticipated that articulatory complexity would produce effects on the BP distribution similar to those demonstrated for complex limb movements. We also hypothesized that lexical semantic operations would independently impact the BP. METHODS: Eighteen participants performed 3 speech tasks designed to differentiate lexical semantic and articulatory contributions to the BP. EEG epochs were time-locked to the earliest source of speech movement per trial. Lip movements were assessed using EMG recordings. Doppler imaging was used to determine the onset of tongue movement during speech, providing a means of identification and elimination of potential artifact. RESULTS: Compared to simple repetition, complex articulations produced an anterior shift in the maximum midline BP. Tasks requiring lexical search and selection augmented these effects and independently elicited a left lateralized asymmetry in the frontal distribution. CONCLUSIONS: The findings indicate that the BP is significantly modulated by linguistic processing, suggesting that the premotor system might play a role in lexical access. SIGNIFICANCE: These novel findings support the notion that the motor systems may play a significant role in the formulation of language.

Structural and biological aspects of carotenoid cleavage.

Apo-carotenoid compounds such as retinol (vitamin A) are involved in a variety of cellular processes and are found in all kingdoms of life. Instead of being synthesized from small precursors, they are commonly produced by oxidative cleavage and subsequent modification of larger carotenoid compounds. The cleavage reaction is catalyzed by a family of related enzymes, which convert specific substrate double bonds to the corresponding aldehydes or ketones. The individual family members differ in their substrate preference and the position of the cleaved double bond, giving rise to a remarkable number of products starting from a limited number of carotenoid substrate molecules. The recent determination of the structure of a member of this family has provided insight into the reaction mechanism, showing how substrate specificity is achieved. This review will focus on the biochemistry of carotenoid oxygenases and the structural determinants of the cleavage reaction.

Transiliac bone biopsy in osteoporosis: frequency, indications, consequences and complications. An evaluation of 99 consecutive cases over a period of 14 years.

Bone biopsy is a diagnostic procedure restricted to untypical, unclear and complicated cases in evidence-based guidelines on diagnosis and treatment of osteoporosis. Its relevance has been a topic of recent controversial discussion. This study was performed to evaluate its role and relevance in routine use. A total of 99 horizontal transiliac bone biopsies performed over a time period of 14 years because of an osteological indication in one single centre were analysed, which reflects that bone biopsy followed about 0.003% of patients' consultations. Bone biopsies were indicated for osteoporotic males (n = 63) and premenopausal osteoporotic females (n = 18) without endocrine abnormality and normal immunofixation (serum and urine), suspected systemic/malignant disease such as mastocytosis, osteogenesis imperfecta, non-secreting plasmocytoma, metastatic infiltration (n = 16) and decreasing bone mineral density under anti-osteoporotic treatment (n = 2). The most frequent diagnoses besides osteoporosis were normal histology, borderline finding towards mild osteoporosis, and osteoporomalacia with relevant osteoidosis. In some cases, pathological findings in bone marrow were detected. In most cases (82/99), bone biopsy led to consequences in medical treatment. Following histopathological diagnosis, 16 patients did not receive any anti-osteoporotic treatment. In six patients, further diagnostic procedures were initiated because of bone histology. Bone biopsy was well tolerated and complications were rare and mild. In conclusion, despite all progress in non-invasive diagnostic procedures for metabolic bone diseases such as osteoporosis, there remains a small but significant subset of patients who may benefit from inclusion of bone biopsy into the diagnostic procedure.

Phenylalanine ammonia-lyase modified with polyethylene glycol: potential therapeutic agent for phenylketonuria.

Phenylketonuria (PKU) is an autosomal recessive genetic disease caused by the defects in the phenylalanine hydroxylase (PAH) gene. Individuals homozygous for defective PAH alleles show elevated levels of systemic phenylalanine and should be under strict dietary control to reduce the risk of neuronal damage associated with high levels of plasma phenylalanine. Researchers predict that plant phenylalanine ammonia-lyase (PAL), which converts phenylalanine to nontoxic t-cinnamic acid, will be an effective therapeutic enzyme for the treatment of PKU. The problems of this potential enzyme therapy have been the low stability in the circulation and the antigenicity of the plant enzyme. Recombinant PAL originated from parsley (Petroselinum crispum) chemically conjugated with activated PEG2 [2,4-bis(O-methoxypolyethyleneglycol)-6-chloro-s-triazine] showed greatly enhanced stability in the circulation and was effective in reducing the plasma concentration of phenylalanine in the circulation of mice. PEG-PAL conjugate will be an effective therapeutic enzyme for the treatment of PKU.

Functional neuroanatomy of human vocalization: an H215O PET study.

Vocalization in lower animals is associated with a well-described visceromotor call system centered on the mesencephalic periacqueductal grey matter (PAG), which is itself regulated by paramedian cortical structures. To determine the role this phylogenetically older system plays in human phonation, we contrasted voiced and unvoiced speech using positron emission tomography and then evaluated functional connectivity of regions that significantly differentiated these conditions. Vocalization was associated with increased and highly correlated activity within the midline structures--PAG and paramedian cortices--described in lower mammalian species. Concurrent activation and connectivity of neocortical and subcortical motor regions--medial and lateral premotor structures and elements of basal ganglia thalamocortical circuitry--suggest a mechanism by which this system may have come under an increasing degree of voluntary control in humans. Additionally, areas in the temporal lobe and cerebellum were selectively activated during voiced but not unvoiced speech. These regions are functionally coupled to both visceromotor and neocortical motor areas during production of voiced speech, suggesting they may play a central role in self-monitoring and feedback regulation of human phonation.