The left inferior frontal gyrus is causally linked to vocal feedback control: evidence from high-definition transcranial alternating current stimulation.

Current models of speech motor control propose a role for the left inferior frontal gyrus (IFG) in feedforward control of speech production. There is evidence, however, that has implicated the functional relevance of the left IFG for the neuromotor processing of vocal feedback errors. The present event-related potential (ERP) study examined whether the left IFG is causally linked to auditory feedback control of vocal production with high-definition transcranial alternating current stimulation (HD-tACS). After receiving active or sham HD-tACS over the left IFG at 6 or 70 Hz, 20 healthy adults vocalized the vowel sounds while hearing their voice unexpectedly pitch-shifted by ±200 cents. The results showed that 6 or 70 Hz HD-tACS over the left IFG led to larger magnitudes and longer latencies of vocal compensations for pitch perturbations paralleled by larger ERP P2 responses than sham HD-tACS. Moreover, there was a lack of frequency specificity that showed no significant differences between 6 and 70 Hz HD-tACS. These findings provide first causal evidence linking the left IFG to vocal pitch regulation, suggesting that the left IFG is an important part of the feedback control network that mediates vocal compensations for auditory feedback errors.

Right, but not left, posterior superior temporal gyrus is causally involved in vocal feedback control.

The posterior superior temporal gyrus (pSTG) has been implicated in the integration of auditory feedback and motor system for controlling vocal production. However, the question as to whether and how the pSTG is causally involved in vocal feedback control is currently unclear. To this end, the present study selectively stimulated the left or right pSTG with continuous theta burst stimulation (c-TBS) in healthy participants, then used event-related potentials to investigate neurobehavioral changes in response to altered auditory feedback during vocal pitch regulation. The results showed that, compared to control (vertex) stimulation, c-TBS over the right pSTG led to smaller vocal compensations for pitch perturbations accompanied by smaller cortical N1 and larger P2 responses. Enhanced P2 responses received contributions from the right-lateralized temporal and parietal regions as well as the insula, and were significantly correlated with suppressed vocal compensations. Surprisingly, these effects were not found when comparing c-TBS over the left pSTG with control stimulation. Our findings provide evidence, for the first time, that supports a causal relationship between right, but not left, pSTG and auditory-motor integration for vocal pitch regulation. This lends support to a right-lateralized contribution of the pSTG in not only the bottom-up detection of vocal feedback errors but also the involvement of driving motor commands for error correction in a top-down manner.

Continuous theta burst stimulation over left and right supramarginal gyri demonstrates their involvement in auditory feedback control of vocal production.

The supramarginal gyrus (SMG) has been implicated in auditory-motor integration for vocal production. However, whether the SMG is bilaterally or unilaterally involved in auditory feedback control of vocal production in a causal manner remains unclear. The present event-related potential (ERP) study investigated the causal roles of the left and right SMG to auditory-vocal integration using neuronavigated continuous theta burst stimulation (c-TBS). Twenty-four young adults produced sustained vowel phonations and heard their voice unexpectedly pitch-shifted by ±200 cents after receiving active or sham c-TBS over the left or right SMG. As compared to sham stimulation, c-TBS over the left or right SMG led to significantly smaller vocal compensations for pitch perturbations that were accompanied by smaller cortical P2 responses. Moreover, no significant differences were found in the vocal and ERP responses when comparing active c-TBS over the left vs. right SMG. These findings provide neurobehavioral evidence for a causal influence of both the left and right SMG on auditory feedback control of vocal production. Decreased vocal compensations paralleled by reduced P2 responses following c-TBS over the bilateral SMG support their roles for auditory-motor transformation in a bottom-up manner: receiving auditory feedback information and mediating vocal compensations for feedback errors.

Cerebellar Continuous Theta Burst Stimulation Facilitates Auditory-Vocal Integration in Spinocerebellar Ataxia.

Clinical studies have shown the efficacy of transcranial magnetic stimulation in treating movement disorders in patients with spinocerebellar ataxia (SCA). However, whether similar effects occur for their speech motor disorders remains largely unknown. The present event-related potential study investigated whether and how abnormalities in auditory-vocal integration associated with SCA can be modulated by neuronavigated continuous theta burst stimulation (c-TBS) over the right cerebellum. After receiving active or sham cerebellar c-TBS, 19 patients with SCA were instructed to produce sustained vowels while hearing their voice unexpectedly pitch-shifted by ±200 cents. Behaviorally, active cerebellar c-TBS led to smaller magnitudes of vocal compensations for pitch perturbations than sham stimulation. Parallel modulatory effects were also observed at the cortical level, as reflected by increased P1 and P2 responses but decreased N1 responses elicited by active cerebellar c-TBS. Moreover, smaller magnitudes of vocal compensations were predicted by larger amplitudes of cortical P1 and P2 responses. These findings provide the first neurobehavioral evidence that c-TBS over the right cerebellum produces modulatory effects on abnormal auditory-motor integration for vocal pitch regulation in patients with SCA, offering a starting point for the treatment of speech motor disorders associated with SCA with cerebellar c-TBS.

A causal link between left supplementary motor area and auditory-motor control of vocal production: Evidence by continuous theta burst stimulation.

The supplementary motor area (SMA) has been implicated in the feedforward control of speech production. Whether this region is involved in speech motor control through auditory feedback, however, remains uncertain. The present event-related potential (ERP) study examined the role of the left SMA in vocal pitch regulation in a causal manner by combining auditory feedback manipulations and neuronavigated continuous theta bust stimulation (c-TBS). After receiving c-TBS over the left SMA or the control site (vertex), twenty young adults vocalized the vowel sound /u/ while hearing their voice unexpectedly pitch-shifted -50 or -200 cents. Compared to the control stimulation, c-TBS over the left SMA led to decreased vocal compensations for pitch perturbations of -50 and -200 cents. A significant decrease of N1 and P2 responses to -200 cents perturbations was also found when comparing active and control stimulation. Major neural generators of decreased P2 responses included the right-lateralized superior and middle temporal gyrus and angular gyrus. Notably, a significant correlation was found between active-control differences in the vocal compensation and P2 responses for the -200 cents perturbations. These findings provide neurobehavioral evidence for a causal link between the left SMA and auditory-motor integration for vocal pitch regulation, suggesting that the left SMA receives auditory feedback information and mediates vocal compensations for feedback errors in a bottom-up manner.

Linking Cortical Morphology to Interindividual Variability in Auditory Feedback Control of Vocal Production.

Speakers regulate vocal motor behaviors in a compensatory manner when perceiving errors in auditory feedback. Little is known, however, about the source of interindividual variability that exists in the degree to which speakers compensate for perceived errors. The present study included 40 young adults to investigate whether individual differences in auditory integration for vocal pitch regulation, as indexed by vocal compensations for pitch perturbations in auditory feedback, can be predicted by cortical morphology as assessed by gray-matter volume, cortical thickness, and surface area in a whole-brain manner. The results showed that greater gray-matter volume in the left inferior parietal lobule and greater cortical thickness and surface area in the left superior/middle temporal gyrus, temporal pole, inferior/superior parietal lobule, and precuneus predicted larger vocal responses. Greater cortical thickness in the right inferior frontal gyrus and superior parietal lobule and surface area in the left precuneus and cuneus were significantly correlated with smaller magnitudes of vocal responses. These findings provide the first evidence that vocal compensations for feedback errors are predicted by the structural morphology of the frontal and tempo-parietal regions, and further our understanding of the neural basis that underlies interindividual variability in auditory-motor control of vocal production.

Adolescence exposure to China's great famine period and the association of metabolic syndrome in adulthood: a retrospective study.

BACKGROUND: Exposure to famine during early life is related to several adverse health outcomes in adulthood, but the effect of famine exposure during adolescence is unclear. This study aims to examine whether exposure to famine in adolescence is associated with metabolic syndrome (MetS) in adulthood. METHODS: This study included 4130 Chinese adults (2059 males and 2071 females) aged 59-71 from the 2011 China Health and Retirement Longitudinal Study (CHARLS). All the selected participants were exposed to the three-year time period (1959-1961) of China's Great Famine. Participants were categorized into an adolescent-exposed group (born 01/01/1944-12/31/1948) and a non-adolescent-exposed group (born 01/01/1940-12/31/1941 and 01/01/1951-12/31/1952). Sex-stratified multiple logistic regression models were used to estimate the association between exposure to famine in adolescence and MetS. RESULTS: Participants exposed to famine during adolescence were more likely to report MetS (aOR = 1.35; 95%CI 1.01-1.78) compared to the non-adolescent-exposed group. Further, males were 45% less likely to report MetS than females (aOR = 0.55; 95%CI 0.36-0.83). After stratification by sex, the effects of famine exposure during adolescence on MetS were detected among males only (aOR = 1.97; 95%CI 1.20-3.24). Additionally, males with a history of drinking were more likely to report MetS compared to those with no history of drinking (aOR = 2.63; 95%CI 1.41-4.90). CONCLUSIONS: Our findings reveal that exposure to famine during adolescence is associated with higher odds of MetS in adulthood overall, and this association is only pronounced among males. This study emphasizes that undernutrition in early life, including adolescence, may have a long-term effect and be associated with adverse health events in middle-to-late life. Targeting those elderly people who suffered famine during adolescence may help prevent the development of MetS in later life.

A Causal Role of the Cerebellum in Auditory Feedback Control of Vocal Production.

Accumulating evidence demonstrates that the cerebellum is involved in a variety of cognitive functions. Recently, impaired auditory-motor integration for vocal control has been identified in patients with cerebellar degeneration, characterized by abnormally enhanced vocal compensations for pitch perturbations. However, the causal relationship between the cerebellum and auditory feedback during vocal production remains unclear. By applying anodal transcranial direct current stimulation (a-tDCS) over right cerebellum, the present study investigated cerebellar contributions to auditory-motor processing of feedback errors during vocal pitch regulation. Twenty young adults participated in a frequency-altered-feedback (FAF) task, in which they vocalized vowel sounds and heard their voice unexpectedly pitch-shifted by ± 50 or ± 200 cents. Active or sham cerebellar a-tDCS was applied either prior to or during the FAF task. Compensatory vocal responses to pitch perturbations were measured and compared across the conditions. Active cerebellar a-tDCS led to significantly larger and slower vocal compensations for pitch perturbations than sham stimulation. Moreover, this modulatory effect was observed regardless of the timing of cerebellar a-tDCS as well as the size and direction of the pitch perturbation. These findings provide the first causal evidence that the cerebellum is essentially involved in auditory feedback control of vocal production. Enhanced and slowed vocal compensations caused by cerebellar a-tDCS may be related to its inhibition on the prefrontal cortex that exerts inhibitory control over vocal compensation behavior, suggesting the importance of the cerebrocerebellar connections in this feedback control process.

Top-Down Inhibitory Mechanisms Underlying Auditory-Motor Integration for Voice Control: Evidence by TMS.

The dorsolateral prefrontal cortex (DLPFC) has been implicated in auditory-motor integration for accurate control of vocal production, but its precise role in this feedback-based process remains largely unknown. To this end, the present event-related potential study applied a transcranial magnetic stimulation (TMS) protocol, continuous theta-burst stimulation (c-TBS), to disrupt cortical activity in the left DLPFC as young adults vocalized vowel sounds while hearing their voice unexpectedly shifted upwards in pitch. The results showed that, as compared to the sham condition, c-TBS over left DLPFC led to significantly larger vocal compensations for pitch perturbations that were accompanied by significantly smaller cortical P2 responses. Source localization analyses revealed that this brain activity pattern was the result of reduced activation in the left superior frontal gyrus and right inferior parietal lobule (supramarginal gyrus). These findings demonstrate c-TBS-induced modulatory effects of DLPFC on the neurobehavioral processing of vocal pitch regulation, suggesting that disrupting prefrontal function may impair top-down inhibitory control mechanisms that prevent speech production from being excessively influenced by auditory feedback, resulting in enhanced vocal compensations for feedback perturbations. This is the first study that provides direct evidence for a causal role of the left DLPFC in auditory feedback control of vocal production.

Cerebellar contribution to auditory feedback control of speech production: Evidence from patients with spinocerebellar ataxia.

The cerebellum has been implicated in the feedforward control of speech production. However, the role of the cerebellum in the feedback control of speech production remains unclear. To address this question, the present event-related potential study examined the behavioral and neural correlates of auditory feedback control of vocal production in patients with spinocerebellar ataxia (SCA) and healthy controls. All participants were instructed to produce sustained vowels while hearing their voice unexpectedly pitch-shifted -200 or -500 cents. The behavioral results revealed significantly larger vocal compensations for pitch perturbations in patients with SCA relative to healthy controls. At the cortical level, patients with SCA exhibited significantly smaller cortical P2 responses that were source localized in the right superior temporal gyrus, primary auditory cortex, and supramarginal gyrus than healthy controls. These findings indicate that reduced brain activity in the right temporal and parietal regions are significant neural contributors to abnormal auditory-motor processing of vocal pitch regulation as a consequence of cerebellar degeneration, which may be related to disrupted reciprocal interactions between the cerebellum and cortical regions that support the top-down modulation of auditory-vocal integration. These differences in behavior and cortical activity between healthy controls and patients with SCA demonstrate that the cerebellum is not only essential for feedforward control but also plays a crucial role in the feedback-based control of speech production.

Clinicopathological and molecular characteristics of extramedullary acute myeloid leukaemia.

AIMS: Myeloid sarcoma (MS) is a rare extramedullary neoplasm composed of immature myeloid precursor cells thought to be a unique clinical presentation of acute myeloid leukaemia (AML). Like AML, MS has a poor prognosis, but due to the rare nature of MS there are limited studies examining potential prognostic factors. We report our institutional experience, with the aim of investigating and establishing salient clinicopathological and molecular features of MS. METHODS AND RESULTS: We retrospectively examined all clinicopathological and molecular data on MS patients between 2001 and 2017 from the University of Alabama at Birmingham (UAB) electronic medical records. The UAB electronic medical records were also reviewed and compared with the literature for other potential prognostic factors. Sixty-three patients were included in the study. The median overall survival was 24 months in the group with normal karyotype and 12 months in patients with an abnormal karyotype. CONCLUSIONS: We found that an abnormal karyotype was associated with a statistically significant worse prognosis.

Diffusion modeling of interference and decay in auditory short-term memory.

Decay and interference are two leading proposals for the cause of forgetting from working and/or short-term memory, and mathematical models of both processes exist. In the present study, we apply a computational model to data from a simple short-term memory task and demonstrate that decay and interference can co-occur in the same experimental paradigm, and that neither decay nor interference alone can account for all cases of forgetting.

Factors Associated With Continuous Improvement by Local Boards of Health.

BACKGROUND: The continuous improvement function, 1 of the 6 public health governance functions, can be usefully applied in the context of local boards of health (LBoHs) operations to target self-improvements. PURPOSE: The purpose of this study was to determine the engagement level of LBoHs in continuous improvement efforts and to identify factors associated with this function. METHODS: Negative binomial regression was performed to analyze data from the 2015 Local Board of Health National Profile. The LBoH taxonomy was used as the guiding model. The taxonomy includes 6 governance functions as structural domains and LBoHs' characteristics and strengths as the central or seventh domain. RESULTS: For the 17 items that comprise the continuous improvement domain, the mean of the dichotomous responses was 4.97 (SD = 3.41). The negative binomial regression analysis showed that the overall summary scale for the other 5 governance domains and the LBoHs' other strengths domain had a significant positive association with the governance domain continuous improvement domain (incidence rate ratio [IRR] = 1.05, P < .001). The 5 individual scales for the governance domains also had significant positive associations with the continuous improvement domain, which included the governance functions of policy development (IRR = 1.13, P < .001), resource stewardship (IRR = 1.18, P < .001), legal authorization (IRR = 1.09, P < .001, partnership engagement (IRR = 1.12, P < .001), and oversight (IRR = 1.29, P < .001). The scale for other characteristics and strengths also showed positive association with continuous improvement (IRR = 1.14, P < .001). CONCLUSION: The findings of this study revealed that there was room for improvement in LBoHs' engagement in the continuous improvement governance function. The results also identified other governance functions and LBoHs' characteristics as factors associated with their continuous improvement.

Top-Down Modulation of Auditory-Motor Integration during Speech Production: The Role of Working Memory.

Although working memory (WM) is considered as an emergent property of the speech perception and production systems, the role of WM in sensorimotor integration during speech processing is largely unknown. We conducted two event-related potential experiments with female and male young adults to investigate the contribution of WM to the neurobehavioural processing of altered auditory feedback during vocal production. A delayed match-to-sample task that required participants to indicate whether the pitch feedback perturbations they heard during vocalizations in test and sample sequences matched, elicited significantly larger vocal compensations, larger N1 responses in the left middle and superior temporal gyrus, and smaller P2 responses in the left middle and superior temporal gyrus, inferior parietal lobule, somatosensory cortex, right inferior frontal gyrus, and insula compared with a control task that did not require memory retention of the sequence of pitch perturbations. On the other hand, participants who underwent extensive auditory WM training produced suppressed vocal compensations that were correlated with improved auditory WM capacity, and enhanced P2 responses in the left middle frontal gyrus, inferior parietal lobule, right inferior frontal gyrus, and insula that were predicted by pretraining auditory WM capacity. These findings indicate that WM can enhance the perception of voice auditory feedback errors while inhibiting compensatory vocal behavior to prevent voice control from being excessively influenced by auditory feedback. This study provides the first evidence that auditory-motor integration for voice control can be modulated by top-down influences arising from WM, rather than modulated exclusively by bottom-up and automatic processes.SIGNIFICANCE STATEMENT One outstanding question that remains unsolved in speech motor control is how the mismatch between predicted and actual voice auditory feedback is detected and corrected. The present study provides two lines of converging evidence, for the first time, that working memory cannot only enhance the perception of vocal feedback errors but also exert inhibitory control over vocal motor behavior. These findings represent a major advance in our understanding of the top-down modulatory mechanisms that support the detection and correction of prediction-feedback mismatches during sensorimotor control of speech production driven by working memory. Rather than being an exclusively bottom-up and automatic process, auditory-motor integration for voice control can be modulated by top-down influences arising from working memory.

Predicting auditory feedback control of speech production from subregional shape of subcortical structures.

Although a growing body of research has focused on the cortical sensorimotor mechanisms that support auditory feedback control of speech production, much less is known about the subcortical contributions to this control process. This study examined whether subregional anatomy of subcortical structures assessed by statistical shape analysis is associated with vocal compensations and cortical event-related potentials in response to pitch feedback errors. The results revealed significant negative correlations between the magnitudes of vocal compensations and subregional shape of the right thalamus, between the latencies of vocal compensations and subregional shape of the left caudate and pallidum, and between the latencies of cortical N1 responses and subregional shape of the left putamen. These associations indicate that smaller local volumes of the basal ganglia and thalamus are predictive of slower and larger neurobehavioral responses to vocal pitch errors. Furthermore, increased local volumes of the left hippocampus and right amygdala were predictive of larger vocal compensations, suggesting that there is an interplay between the memory-related subcortical structures and auditory-vocal integration. These results, for the first time, provide evidence for differential associations of subregional morphology of the basal ganglia, thalamus, hippocampus, and amygdala with neurobehavioral processing of vocal pitch errors, suggesting that subregional shape measures of subcortical structures can predict behavioral outcome of auditory-vocal integration and associated neural features. Hum Brain Mapp 39:459-471, 2018. © 2017 Wiley Periodicals, Inc.

Elevated Wall Tension Initiates Interleukin-6 Expression and Abdominal Aortic Dilation.

BACKGROUND: Hypertension (HTN) has long been associated with abdominal aortic aneurysm (AAA) development, and these cardiovascular pathologies are biochemically characterized by elevated plasma levels of angiotensin II (AngII) as well as interleukin-6 (IL-6). A biologic relationship between HTN and AAA has not been established, however. Accordingly, the objective of this study was to evaluate whether elevated tension may initiate IL-6 production to accumulate monocyte/macrophages and promote dilation of the abdominal aorta (AA). METHODS: An IL-6 infusion model (4.36 µg/kg/day) was created utilizing an osmotic infusion pump, and after 4 weeks, AA diameter was measured by digital microscopy. The AA was then excised for CD68 immunostaining and flow cytometric analysis with CD11b and F4/80 to identify macrophages. Aortic segments from wild-type mice were suspended on parallel wires in an ex vivo tissue myograph at experimentally derived optimal tension (1.2 g) and in the presence of elevated tension (ET, 1.7 g) for 3 hr, and expression of IL-6 and monocyte chemoattractant protein-1 (MCP-1) was evaluated by quantitative polymerase chain reaction (QPCR). Isolated aortic vascular smooth muscle cells (VSMCs) were subjected to 12% biaxial cyclic stretch or held static (control) for 3 hr (n = 7), and IL-6 and MCP-1 expressions were evaluated by QPCR. RESULTS: Four-week IL-6 infusion resulted in an AA outer diameter that was 72.5 ± 5.6% (P < 0.05) greater than that of control mice, and aortic dilation was accompanied by an accumulation of macrophages in the AA medial layer as defined by an increase in CD68 + staining as well as an increase by flow cytometric quantification of CD11b+/F4/80+ cells. Wild-type AA segments did not respond to ex vivo application of ET but cyclic stretch of isolated VSMCs increased IL-6 (2.03 ± 0.3 fold) and MCP-1 (1.51 ± 0.11 fold) expression compared to static control (P < 0.05). Pretreatment with the selective STAT3 inhibitor WP1066 blunted the response in both cases. Interestingly, AngII did not stimulate expression of IL-6 and MCP-1 above that initiated by tension and again, the response was inhibited by WP1066, supporting an integral role of STAT3 in this pathway. CONCLUSIONS: An IL-6 infusion model can initiate macrophage accumulation as well as aortic dilation, and under conditions of elevated tension, this proinflammatory cytokine can be produced by aortic VSMCs. By activation of STAT3, MCP-1 is expressed to increase media macrophage abundance and create an environment susceptible to dilation. This biomechanical association between HTN and aortic dilation may allow for the identification of novel therapeutic strategies.

A phase 1/1b study of rituximab, bendamustine, and ibrutinib in patients with untreated and relapsed/refractory non-Hodgkin lymphoma.

Ibrutinib has single agent activity of 22% to 68% in relapsed B-cell non-Hodgkin lymphoma(NHL). This study evaluated the safety and efficacy of ibrutinib combined with rituximab (R) and bendamustine. Patients received R (375 mg/m(2)) on day 1, bendamustine (90 mg/m(2)) on days 1 and 2, and ibrutinib (280 or 560 mg) on days 1 to 28 every 28 days for 6 cycles followed by ibrutinib alone until progression. Forty-eight patients enrolled, including 12 patients with follicular lymphoma (FL), 16 with diffuse large B-cell lymphoma (DLCL), and 17 with mantle cell lymphoma (MCL). No dose-limiting toxicities were observed. Patients received a median of 8 cycles, with 26 completing 6 cycles and continuing ibrutinib alone in cycles 7 to 34. The overall response (OR) rate was 72%, with 52% complete responses (CRs). By histology, the OR rate was 94% (76% CR) in MCL, 37% (31% CR) in DLCL, and 90% (50% CR) in FL. Grade 3 to 4 toxicities included lymphopenia (77%), neutropenia (33%), thrombocytopenia (19%), and rash (25%). Median progression-free survival has not been reached (95% CI, 8.7 months to not reached). The recommended phase 2 dose of ibrutinib in combination with R-bendamustine in patients with NHL is 560 mg. The combination has promising efficacy, particularly in MCL and FL. This trial was registered at www.clinicaltrials.gov as #NCT01479842.

Multidisciplinary team learning in the management of the morbidly adherent placenta: outcome improvements over time.

BACKGROUND: Morbidly adherent placenta (MAP) is a serious obstetric complication causing mortality and morbidity. OBJECTIVE: To evaluate whether outcomes of patients with MAP improve with increasing experience within a well-established multidisciplinary team at a single referral center. STUDY DESIGN: All singleton pregnancies with pathology-confirmed MAP (including placenta accreta, increta, or percreta) managed by a multidisciplinary team between January 2011 and August 2016 were included in this retrospective study. Turnover of team members was minimal, and cases were divided into 2 time periods so as to compare 2 similarly sized groups: T1 = January 2011 to April 2014 and T2 = May 2014 to August 2016. Outcome variables were estimated blood loss, units of red blood cell transfused, volume of crystalloid transfused, massive transfusion protocol activation, ureter and bowel injury, and neonatal birth weight. Comparisons and adjustments were made by use of the Student t test, Mann-Whitney U test, χ2 test, analysis of covariance, and multinomial logistic regression. RESULTS: A total of 118 singleton pregnancies, 59 in T1 and 59 in T2, were managed during the study period. Baseline patient characteristics were not statistically significant. Forty-eight of 59 (81.4%) patients in T1 and 42 of 59 (71.2%) patients in T2 were diagnosed with placenta increta/percreta. The median [interquartile range] estimated blood loss (T1: 2000 [1475-3000] vs T2: 1500 [1000-2700], P = .04), median red blood cell transfusion units (T1: 2.5 [0-7] vs T2: 1 [0-4], P = .02), and median crystalloid transfusion volume (T1: 4200 [3600-5000] vs T2: 3400 [3000-4000], P < .01) were significantly less in T2. Also, a massive transfusion protocol was instituted more frequently in T1: 15/59 (25.4%) vs 3/59 (5.1%); P < .01. Neonatal outcomes and surgical complications were similar between the 2 groups. CONCLUSION: Our study shows that patient outcomes are improved over time with increasing experience within a well-established multidisciplinary team performing 2-3 cases per month. This suggests that small, collective changes in team dynamics lead to continuous improvement of clinical outcomes. These findings support the development of centers of excellence for MAP staffed by stable, core multidisciplinary teams, which should perform a significant number of these procedures on an ongoing basis.

Regional homogeneity of intrinsic brain activity correlates with auditory-motor processing of vocal pitch errors.

It has been well documented that speakers produce rapid compensatory vocal adjustments for errors they perceive in their auditory feedback. The fact that they differ greatly in the degree to which they compensate for perceived errors, however, has received much less attention. The present study investigated whether intrinsic brain activity during resting can predict an individual's behavioral and cortical responses in compensating for pitch-shifted auditory feedback during vocalization. This relationship was investigated by correlating the regional homogeneity (ReHo) of resting-state fMRI signals with the vocal compensation and event-related potentials (N1 and P2) in response to pitch shifts of -200 and -500 cents. Behaviorally, the magnitudes of vocal compensation were significantly correlated with the ReHo values in the right supplementary motor area (SMA) for both -200 and -500 cents, the right primary motor cortex (M1) for -200 cents, and the left premotor cortex (PMC) for -500 cents. For both pitch shift sizes, there were significant correlations between ReHo and N1 amplitude in the left inferior frontal gyrus (IFG), right superior temporal gyrus (STG), bilateral M1, and left SMA. Significant correlations between ReHo and P2 amplitude were observed in the bilateral IFG, right STG, left SMA and M1 for -200 and -500 cents, the left PMC for -200 cents, and the right SMA for -500 cents. These findings provide the first evidence that regional homogeneity of intrinsic brain activity can predict behavioral and cortical responses in compensating for pitch errors in voice auditory feedback.

Attentional demands modulate sensorimotor learning induced by persistent exposure to changes in auditory feedback.

Hearing one's own voice is important for regulating ongoing speech and for mapping speech sounds onto articulator movements. However, it is currently unknown whether attention mediates changes in the relationship between motor commands and their acoustic output, which are necessary as growth and aging inevitably cause changes to the vocal tract. In this study, participants produced vocalizations while they heard their vocal pitch persistently shifted downward one semitone in both single- and dual-task conditions. During the single-task condition, participants vocalized while passively viewing a visual stream. During the dual-task condition, participants vocalized while also monitoring a visual stream for target letters, forcing participants to divide their attention. Participants' vocal pitch was measured across each vocalization, to index the extent to which their ongoing vocalization was modified as a result of the deviant auditory feedback. Smaller compensatory responses were recorded during the dual-task condition, suggesting that divided attention interfered with the use of auditory feedback for the regulation of ongoing vocalizations. Participants' vocal pitch was also measured at the beginning of each vocalization, before auditory feedback was available, to assess the extent to which the deviant auditory feedback was used to modify subsequent speech motor commands. Smaller changes in vocal pitch at vocalization onset were recorded during the dual-task condition, suggesting that divided attention diminished sensorimotor learning. Together, the results of this study suggest that attention is required for the speech motor control system to make optimal use of auditory feedback for the regulation and planning of speech motor commands.