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.

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.

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.

Continuous theta burst stimulation over left supplementary motor area facilitates auditory-vocal integration in individuals with Parkinson's disease.

Accumulating evidence suggests that impairment in auditory-vocal integration characterized by abnormally enhanced vocal compensations for auditory feedback perturbations contributes to hypokinetic dysarthria in Parkinson's disease (PD). However, treatment of this abnormality remains a challenge. The present study examined whether abnormalities in auditory-motor integration for vocal pitch regulation in PD can be modulated by neuronavigated continuous theta burst stimulation (c-TBS) over the left supplementary motor area (SMA). After receiving active or sham c-TBS over left SMA, 16 individuals with PD vocalized vowel sounds while hearing their own voice unexpectedly pitch-shifted two semitones upward or downward. A group of pairwise-matched healthy participants was recruited as controls. Their vocal responses and event-related potentials (ERPs) were measured and compared across the conditions. The results showed that applying c-TBS over left SMA led to smaller vocal responses paralleled by smaller P1 and P2 responses and larger N1 responses in individuals with PD. Major neural generators of reduced P2 responses were located in the right inferior and medial frontal gyrus, pre- and post-central gyrus, and insula. Moreover, suppressed vocal compensations were predicted by reduced P2 amplitudes and enhanced N1 amplitudes. Notably, abnormally enhanced vocal and P2 responses in individuals with PD were normalized by c-TBS over left SMA when compared to healthy controls. Our results provide the first causal evidence that abnormalities in auditory-motor control of vocal pitch production in PD can be modulated by c-TBS over left SMA, suggesting that it may be a promising non-invasive treatment for speech motor disorders in PD.

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.

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 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.

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.

Spatially Refined Time-Varying Reproduction Numbers of COVID-19 by Health District in Georgia, USA, March-December 2020.

This study quantifies the transmission potential of SARS-CoV-2 across public health districts in Georgia, USA, and tests if per capita cumulative case count varies across counties. To estimate the time-varying reproduction number, Rt of SARS-CoV-2 in Georgia and its 18 public health districts, we apply the R package 'EpiEstim' to the time series of historical daily incidence of confirmed cases, 2 March-15 December 2020. The epidemic curve is shifted backward by nine days to account for the incubation period and delay to testing. Linear regression is performed between log10-transformed per capita cumulative case count and log10-transformed population size. We observe Rt fluctuations as state and countywide policies are implemented. Policy changes are associated with increases or decreases at different time points. Rt increases, following the reopening of schools for in-person instruction in August. Evidence suggests that counties with lower population size had a higher per capita cumulative case count on June 15 (slope = -0.10, p = 0.04) and October 15 (slope = -0.05, p = 0.03), but not on August 15 (slope = -0.04, p = 0.09), nor December 15 (slope = -0.02, p = 0.41). We found extensive community transmission of SARS-CoV-2 across all 18 health districts in Georgia with median 7-day-sliding window Rt estimates between 1 and 1.4 after March 2020.

Exploring the Relationship between Prosodic Control and Social Competence in Children with and without Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a developmental disorder characterized by persistent deficits in social communication and interaction. Speech is an important form of social communication. Prosody (e.g. vocal pitch, rhythm, etc.), one aspect of the speech signal, is crucial for ensuring information about the emotionality, excitability, and intent of the speaker, is accurately expressed. The objective of this study was to gain a better understanding of how auditory information is used to regulate speech prosody in autistic and non-autistic children, while exploring the relationship between the prosodic control of speech and social competence. Eighty autistic (M = 8.48 years, SD = 2.55) and non-autistic (M = 7.36 years, SD = 2.51) participants produced vocalizations while exposed to unaltered and frequency altered auditory feedback. The parent-report Multidimensional Social Competence Scale was used to assess social competence, while the Autism-Spectrum Quotient and the Autism Spectrum Rating Scales were used to assess autism characteristics. Results indicate that vocal response magnitudes and vocal variability were similar across autistic and non-autistic children. However, autistic children produced significantly faster responses to the auditory feedback manipulation. Hierarchical multiple regressions indicated that these faster responses were significantly associated with poorer parent-rated social competence and higher autism characteristics. These findings suggest that prosodic speech production differences are present in at least a subgroup of autistic children. These results represent a key step in understanding how atypicalities in the mechanisms supporting speech production may manifest in social-communication deficits, as well as broader social competence, and vice versa. Autism Res 2020, 13: 1880-1892. © 2020 International Society for Autism Research and Wiley Periodicals LLC LAY SUMMARY: In this study, autistic and non-autistic children produced vowel sounds while listening to themselves through headphones. When the children heard their vocal pitch shifted upward or downward, they compensated by shifting their vocal pitch in the opposite direction. Interestingly, autistic children were faster to correct for the perceived vowel sound changes than their typically developing peers. Faster responses in the children with ASD were linked to poorer ratings of their social abilities by their parent. These results suggest that autistic and non-autistic children show differences in how quickly they control their speech, and these differences may be related to the social challenges experienced by autistic children.

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.

Sensorimotor control of vocal production in early childhood.

Children maintain fluent speech despite dramatic changes to their articulators during development. Auditory feedback aids in the acquisition and maintenance of the sensorimotor mechanisms that underlie vocal motor control. MacDonald, Johnson, Forsythe, Plante, and Munhall (2012) reported that toddlers' speech motor control systems may "suppress" the influence of auditory feedback, since exposure to altered auditory feedback regarding their formant frequencies did not lead to modifications of their speech. This finding is not parsimonious with most theories of motor control. Here, we exposed toddlers to perturbations to the pitch of their auditory feedback as they vocalized. Toddlers compensated for the manipulations, producing significantly different responses to upward and downward perturbations. These data represent the first empirical demonstration that toddlers use auditory feedback for vocal motor control. Furthermore, our findings suggest toddlers are more sensitive to changes to the postural properties of their auditory feedback, such as fundamental frequency, relative to the phonemic properties, such as formant frequencies. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

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.

Decreased Gray-Matter Volume in Insular Cortex as a Correlate of Singers' Enhanced Sensorimotor Control of Vocal Production.

Accumulating evidence has shown enhanced sensorimotor control of vocal production as a consequence of extensive singing experience. The neural basis of this ability, however, is poorly understood. Given that the insula mediates motor aspects of vocal production, the present study investigated structural plasticity in insula induced by singing experience and its link to auditory feedback control of vocal production. Voxel-based morphometry (VBM) was used to examine the differences in gray matter (GM) volume in the insula of 21 singers and 21 non-singers. An auditory feedback perturbation paradigm was used to examine the differences in auditory-motor control of vocal production between singers and non-singers. Both groups vocalized sustained vowels while hearing their voice unexpectedly pitch-shifted -50 or -200 cents (200 ms duration). VBM analyses showed that singers exhibited significantly lower GM volumes in the bilateral insula than non-singers. When exposed to pitch perturbations in voice auditory feedback, singers involuntarily compensated for pitch perturbations in voice auditory feedback to a significantly lesser degree than non-singers. Moreover, across the two sizes of pitch perturbations, the magnitudes of vocal compensations were positively correlated with the total regional GM volumes in the bilateral insula. These results indicate that extensive singing training leads to decreased GM volumes in insula and suggest that morphometric plasticity in insula contributes to the enhanced sensorimotor control of vocal production observed in singers.

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.

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.