Anomalous morphology in left hemisphere motor and premotor cortex of children who stutter

Stuttering is a neurodevelopmental disorder that affects the smooth flow of speech production. Stuttering onset occurs during a dynamic period of development when children first start learning to formulate sentences. Although most children grow out of stuttering naturally, ∼1% of all children develop persistent stuttering that can lead to significant psychosocial consequences throughout one’s life. To date, few studies have examined neural bases of stuttering in children who stutter, and even fewer have examined the basis for natural recovery versus persistence of stuttering. Here we report the first study to conduct surface-based analysis of the brain morphometric measures in children who stutter. We used FreeSurfer to extract cortical size and shape measures from structural MRI scans collected from the initial year of a longitudinal study involving 70 children (36 stuttering, 34 controls) in the 3–10-year range. The stuttering group was further divided into two groups: persistent and recovered, based on their later longitudinal visits that allowed determination of their eventual clinical outcome. A region of interest analysis that focused on the left hemisphere speech network and a whole-brain exploratory analysis were conducted to examine group differences and group × age interaction effects. We found that the persistent group could be differentiated from the control and recovered groups by reduced cortical thickness in left motor and lateral premotor cortical regions. The recovered group showed an age-related decrease in local gyrification in the left medial premotor cortex (supplementary motor area and and pre-supplementary motor area). These results provide strong evidence of a primary deficit in the left hemisphere speech network, specifically involving lateral premotor cortex and primary motor cortex, in persistent developmental stuttering. Results further point to a possible compensatory mechanism involving left medial premotor cortex in those who recover from childhood stuttering.This study was supported by Award Numbers R01DC011277 (SC) and R01DC007683 (FG) from the National Institute on Deafness and other Communication Disorders (NIDCD). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIDCD or the National Institutes of Health. (R01DC011277 - National Institute on Deafness and other Communication Disorders (NIDCD); R01DC007683 - National Institute on Deafness and other Communication Disorders (NIDCD))Accepted manuscrip

Neural activity during solo and choral reading: A functional magnetic resonance imaging study of overt continuous speech production in adults who stutter

Previous neuroimaging investigations of overt speech production in adults who stutter (AWS) found increased motor and decreased auditory activity compared to controls. Activity in the auditory cortex is heightened, however, under fluency-inducing conditions in which AWS temporarily become fluent while synchronizing their speech with an external rhythm, such as a metronome or another speaker. These findings suggest that stuttering is associated with disrupted auditory motor integration. Technical challenges in acquiring neuroimaging data during continuous overt speech production have limited experimental paradigms to short or covert speech tasks. Such paradigms are not ideal, as stuttering primarily occurs during longer speaking tasks. To address this gap, we used a validated spatial ICA technique designed to address speech movement artifacts during functional magnetic resonance imaging (fMRI) scanning. We compared brain activity and functional connectivity of the left auditory cortex during continuous speech production in two conditions: solo (stutter-prone) and choral (fluency-inducing) reading tasks. Overall, brain activity differences in AWS relative to controls in the two conditions were similar, showing expected patterns of hyperactivity in premotor/motor regions but underactivity in auditory regions. Functional connectivity of the left auditory cortex (STG) showed that within the AWS group there was increased correlated activity with the right insula and inferior frontal area during choral speech. The AWS also exhibited heightened connectivity between left STG and key regions of the default mode network (DMN) during solo speech. These findings indicate possible interference by the DMN during natural, stuttering-prone speech in AWS, and that enhanced coordination between auditory and motor regions may support fluent speech

Delayed diagnosis of 22q11.2 deletion syndrome in an adult Chinese lady

We report a 32 year-old Chinese lady with history of tetralogy of Fallot, presented to us with chest pain due to hypocalcemia secondary to hypoparathyroidism. With her dysmorphic facial features and intellectual disability 22q11.2 deletion was suspected and confirmed by genetic study. Clinicians should consider the diagnosis of DiGeorge syndrome in adult patient with past medical history of congenital heart disease, facial dysmorphism, intellectual disability and primary hypoparathyroidism.published_or_final_versio

Neurofilament-lysosomal genetic intersections in the cortical network of stuttering

The neurobiological underpinnings of stuttering, a speech disorder characterized by disrupted speech fluency, remain unclear. While recent developments in the field have afforded researchers the ability to pinpoint several genetic profiles associated with stuttering, how these specific genetic backgrounds impact neuronal circuits and how they generate or facilitate the emergence of stuttered speech remains unknown. In this study, we identified the large-scale cortical network that characterizes stuttering using functional connectivity MRI and graph theory. We performed a spatial similarity analysis that examines whether the topology of the stuttering cortical network intersects with genetic expression levels of previously reported genes for stuttering from the protein-coding transcriptome data of the Allen Human Brain Atlas. We found that GNPTG – a gene involved in the mannose-6-phosphate lysosomal targeting pathways – was significantly co-localized with the stuttering cortical network. An enrichment analysis demonstrated that the genes identified with the stuttering cortical network shared a significantly overrepresented biological functionality of Neurofilament Cytoskeleton Organization (NEFH, NEFL and INA). The relationship between lysosomal pathways, cytoskeleton organization, and stuttering, was investigated by comparing the genetic interactome between GNPTG and the neurofilament genes implicated in the current study. We found that genes of the interactome network, including CDK5, SNCA, and ACTB, act as functional links between lysosomal and neurofilament genes. These findings support the notion that stuttering is due to a lysosomal dysfunction, which has deleterious effects on the neurofilament organization of the speech neuronal circuits. They help to elucidate the intriguing, unsolved link between lysosomal mutations and the presence of stuttering

Association of anticardiolipin, antiphosphatidylserine, anti-β2 glycoprotein I, and antiphosphatidylcholine autoantibodies with canine immune thrombocytopenia

β2GPI expression and identification. (PDF 159 kb

First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signalto- noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far

Lupus nephritis in Chinese children--a territory-wide cohort study in Hong Kong

We report a multicenter study of Chinese children in Hong Kong with systemic lupus erythematosus (SLE) nephritis. Children were included if: they fulfilled the ACR criteria, had significant proteinuria or casturia, were Chinese and younger than 19 years and had been diagnosed with SLE between January 1990 and December 2003. Investigators in each center retrieved data on clinical features, biopsy reports, treatment and outcome of these patients. There were 128 patients (eight boys, 120 girls; mean age: 11.9+/-2.8 years). About 50% presented with multisystem illness and 40% with nephritic/nephrotic symptoms. Negative anti-dsDNA antibodies were found in 6% of the patients. Renal biopsy revealed WHO Class II, III, IV and V nephritis in 13 (10%), 22 (17%), 69 (54%) and 13 (10%) patients, respectively. The clinical severity of the nephritis did not accurately predict renal biopsy findings. The follow-up period ranged from 1 to 16.5 years (mean+/-SD: 5.76+/-3.61 years). During the study five patients died (two from lupus flare, one from cardiomyopathy, two from infections). Four patients had endstage renal failure (ESRF) (one died during a lupus flare). All deaths and end-stage renal failure occurred in the Class IV nephritis group. Chronic organ damage was infrequent in the survivors. The actuarial patient survival rates at 5, 10 and 15 years of age were 95.3, 91.8, and 91.8%, respectively. For Class IV nephritis patients, the survival rates without ESRF at 5, 10, and 15 years were 91.5, 82.3 and 76%, respectively. The survival and chronic morbidity rates of the Chinese SLE children in the present study are comparable to those of other published studies.postprin

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT