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1.
Psychophysiology ; : e13545, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32052868

RESUMO

Prospective evidence indicates that functional biomechanics and brain connectivity may predispose an athlete to an anterior cruciate ligament injury, revealing novel neural linkages for targeted neuromuscular training interventions. The purpose of this study was to determine the efficacy of a real-time biofeedback system for altering knee biomechanics and brain functional connectivity. Seventeen healthy, young, physically active female athletes completed 6 weeks of augmented neuromuscular training (aNMT) utilizing real-time, interactive visual biofeedback and 13 served as untrained controls. A drop vertical jump and resting state functional magnetic resonance imaging were separately completed at pre- and posttest time points to assess sensorimotor adaptation. The aNMT group had a significant reduction in peak knee abduction moment (pKAM) compared to controls (p = .03, d = 0.71). The aNMT group also exhibited a significant increase in functional connectivity between the right supplementary motor area and the left thalamus (p = .0473 after false discovery rate correction). Greater percent change in pKAM was also related to increased connectivity between the right cerebellum and right thalamus for the aNMT group (p = .0292 after false discovery rate correction, r2  = .62). No significant changes were observed for the controls (ps > .05). Our data provide preliminary evidence of potential neural mechanisms for aNMT-induced motor adaptations that reduce injury risk. Future research is warranted to understand the role of neuromuscular training alone and how each component of aNMT influences biomechanics and functional connectivity.

2.
Acta Paediatr ; 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31854046

RESUMO

AIM: Caregiver-child reading is advocated by health organisations, citing cognitive and neurobiological benefits. The influence of home literacy environment (HLE) on brain structure prior to kindergarten has not previously been studied. METHODS: Preschool-age children completed assessments of language (EVT-2, CTOPP-2 Rapid Object Naming) and emergent literacy skills (Get Ready to Read!, The Reading House) followed by diffusion tensor imaging (DTI). Parents completed a survey of HLE (StimQ-P2 READ), which has four subscales. DTI measures included axial diffusivity (AD), radial diffusivity (RD), mean diffusivity (MD) and fractional anisotropy (FA). RESULTS: Forty-seven children completed DTI (54 ± 7 months, range 36-63; 27 girls). StimQ-P2 READ scores correlated with higher EVT-2, GRTR and TRH scores, controlling for age and gender (P < .01), and also with lower AD, RD and MD in tracts supporting language and literacy skills, controlling for age, gender and income (P < .05, family-wise error corrected). Correlations were strongest for the Bookreading Quantity subscale, including with higher scores on all cognitive measures including CTOPP-2, and also with higher FA in left-lateralised literacy-supporting tracts, controlling for age, gender and income. CONCLUSION: More nurturing home reading environment prior to kindergarten may stimulate brain development supporting language and literacy skills, reinforcing the need for further study.

3.
JAMA Pediatr ; : e193869, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31682712

RESUMO

Importance: The American Academy of Pediatrics (AAP) recommends limits on screen-based media use, citing its cognitive-behavioral risks. Screen use by young children is prevalent and increasing, although its implications for brain development are unknown. Objective: To explore the associations between screen-based media use and integrity of brain white matter tracts supporting language and literacy skills in preschool-aged children. Design, Setting, and Participants: This cross-sectional study of healthy children aged 3 to 5 years (n = 47) was conducted from August 2017 to November 2018. Participants were recruited at a US children's hospital and community primary care clinics. Exposures: Children completed cognitive testing followed by diffusion tensor imaging (DTI), and their parent completed a ScreenQ survey. Main Outcomes and Measures: ScreenQ is a 15-item measure of screen-based media use reflecting the domains in the AAP recommendations: access to screens, frequency of use, content viewed, and coviewing. Higher scores reflect greater use. ScreenQ scores were applied as the independent variable in 3 multiple linear regression models, with scores in 3 standardized assessments as the dependent variable, controlling for child age and household income: Comprehensive Test of Phonological Processing, Second Edition (CTOPP-2; Rapid Object Naming subtest); Expressive Vocabulary Test, Second Edition (EVT-2; expressive language); and Get Ready to Read! (GRTR; emergent literacy skills). The DTI measures included fractional anisotropy (FA) and radial diffusivity (RD), which estimated microstructural organization and myelination of white matter tracts. ScreenQ was applied as a factor associated with FA and RD in whole-brain regression analyses, which were then narrowed to 3 left-sided tracts supporting language and emergent literacy abilities. Results: Of the 69 children recruited, 47 (among whom 27 [57%] were girls, and the mean [SD] age was 54.3 [7.5] months) completed DTI. Mean (SD; range) ScreenQ score was 8.6 (4.8; 1-19) points. Mean (SD; range) CTOPP-2 score was 9.4 (3.3; 2-15) points, EVT-2 score was 113.1 (16.6; 88-144) points, and GRTR score was 19.0 (5.9; 5-25) points. ScreenQ scores were negatively correlated with EVT-2 (F2,43 = 5.14; R2 = 0.19; P < .01), CTOPP-2 (F2,35 = 6.64; R2 = 0.28; P < .01), and GRTR (F2,44 = 17.08; R2 = 0.44; P < .01) scores, controlling for child age. Higher ScreenQ scores were correlated with lower FA and higher RD in tracts involved with language, executive function, and emergent literacy abilities (P < .05, familywise error-corrected), controlling for child age and household income. Conclusions and Relevance: This study found an association between increased screen-based media use, compared with the AAP guidelines, and lower microstructural integrity of brain white matter tracts supporting language and emergent literacy skills in prekindergarten children. The findings suggest further study is needed, particularly during the rapid early stages of brain development.

4.
Epilepsy Behav ; 99: 106395, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31422309

RESUMO

OBJECTIVE: We prospectively validated stereo-electroencephalography (EEG) electrical stimulation mapping (ESM) of language against a reference standard of meta-analytic functional magnetic resonance imaging (fMRI) framework (Neurosynth). METHODS: Language ESM was performed using 50 Hz, biphasic, bipolar, stimulation at 1-8 mA, with a picture naming task. Electrode contacts (ECs) were scored as ESM+ if ESM interfered with speech/language function. For each patient, presurgical MRI was transformed to a standard space and coregistered with computed tomographic (CT) scan to obtain EC locations. After whole-brain parcellation, this fused image data were intersected with three-dimensional language fMRI (Neurosynth), and each EC was classified as lying within/outside the fMRI language parcel. Diagnostic odds ratio (DOR) and other indices were estimated. Current thresholds for language inhibition and after-discharges (ADs) were analyzed using multivariable linear mixed models. RESULTS: In 10 patients (5 females), aged 5.4-21.2 years, speech/language inhibition was noted with ESM on 87/304 (29%) ECs. Stereo-EEG language ESM was a valid classifier of fMRI (Neurosynth) language sites (DOR: 9.02, p < 0.0001), with high specificity (0.87) but poor sensitivity (0.57). Similar diagnostic indices were seen for ECs in frontal or posterior regions, and gray or white matter. Language threshold (3.1 ±â€¯1.5 mA) was lower than AD threshold (4.0 ±â€¯2.0 mA, p = 0.0001). Language and AD thresholds decreased with age and intelligence quotient. Electrical stimulation mapping triggered seizures/auras represented patients' habitual semiology with 1 Hz stimulation. CONCLUSIONS: Stereo-EEG ESM can reliably identify cerebral parcels with/without language function but may under detect all language sites. We suggest a 50-Hz stimulation protocol for language ESM with stereo-EEG.

5.
Braz J Phys Ther ; 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31377125

RESUMO

OBJECTIVE: This study's purpose was to utilize a prospective dataset to examine differences in functional brain connectivity in male high school athletes who suffered an ACL anterior cruciate ligament injury relative to their non-injured peers. METHODS: Sixty-two male high school football players were evaluated using functional magnetic resonance imaging prior to their competitive season to evaluate resting-state functional brain connectivity. Three athletes later experienced an ACL injury and were matched to 12 teammates who did not go on to sustain an ACL injury (controls) based on school, age, height, weight, and year in school. Twenty-five knee-motor regions of interest (ROIs) were created to identify differences in connectivity between the two groups. Between-subject F and t tests were used to identify significant ROI differences using a false discovery rate correction for multiple comparisons. RESULTS: There was significantly less connectivity between the left secondary somatosensory cortex and the left supplementary motor area (p = 0.025), right pre-motor cortex (p = 0.026), right supplementary motor area (p = 0.026), left primary somatosensory cortex (superior division; p = 0.026), left primary somatosensory cortex (inferior division; p = 0.026), and left primary motor cortex (p = 0.048) for the ACL-injured compared to the control subjects. No other ROI-to-ROI comparisons were significantly different between the groups (all p > 0.05). CONCLUSION: Our preliminary data indicate a potential sensorimotor disruption for male football players who go on to experience an ACL injury. Future studies with larger sample sizes and complimentary measures of neuromuscular control are needed to support these findings.

6.
J Neuroimaging ; 29(5): 580-588, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31270890

RESUMO

BACKGROUND AND PURPOSE: The purpose of this study was to assess the consistency of a novel MR safe lower extremity motor control neuroimaging paradigm to elicit reliable sensorimotor region brain activity. METHODS: Participants completed multiple sets of unilateral leg presses combining ankle, knee, and hip extension and flexion movements against resistance at a pace of 1.2 Hz while lying supine in a 3T MRI scanner. Regions of Interest (ROI) consisted of regions primarily involved in lower extremity motor control (right and left primary motor cortex, primary somatosensory cortex, premotor cortex, secondary somatosensory cortex, basal ganglia, and the cerebellum). RESULTS: The group analysis based on mixed effects paired samples t-test revealed no differences for brain activity between sessions (P > .05). Intraclass correlation coefficients in the sensorimotor regions were good to excellent for average percent signal change (.621 to .918) and Z-score (.697 to .883), with the exception of the left secondary somatosensory cortex percent signal change (.165). CONCLUSIONS: These results indicate that a loaded lower extremity force production and attenuation task that simulates the range of motion of squatting, stepping, and landing from a jump is reliable for longitudinal neuroimaging applications and support the use of this paradigm in further studies examining therapeutic interventions and changes in dynamic lower extremity motor function.

7.
AJR Am J Roentgenol ; 213(3): 592-601, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31120779

RESUMO

OBJECTIVE. The purpose of this study is to develop a machine learning model to categorically classify MR elastography (MRE)-derived liver stiffness using clinical and nonelastographic MRI radiomic features in pediatric and young adult patients with known or suspected liver disease. MATERIALS AND METHODS. Clinical data (27 demographic, anthropomorphic, medical history, and laboratory features), MRI presence of liver fat and chemical shift-encoded fat fraction, and MRE mean liver stiffness measurements were retrieved from electronic medical records. MRI radiomic data (105 features) were extracted from T2-weighted fast spin-echo images. Patients were categorized by mean liver stiffness (< 3 vs ≥ 3 kPa). Support vector machine (SVM) models were used to perform two-class classification using clinical features, radiomic features, and both clinical and radiomic features. Our proposed model was internally evaluated in 225 patients (mean age, 14.1 years) and externally evaluated in an independent cohort of 84 patients (mean age, 13.7 years). Diagnostic performance was assessed using ROC AUC values. RESULTS. In our internal cross-validation model, the combination of clinical and radiomic features produced the best performance (AUC = 0.84), compared with clinical (AUC = 0.77) or radiomic (AUC = 0.70) features alone. Using both clinical and radiomic features, the SVM model was able to correctly classify patients with accuracy of 81.8%, sensitivity of 72.2%, and specificity of 87.0%. In our external validation experiment, this SVM model achieved an accuracy of 75.0%, sensitivity of 63.6%, specificity of 82.4%, and AUC of 0.80. CONCLUSION. An SVM learning model incorporating clinical and T2-weighted radiomic features has fair-to-good diagnostic performance for categorically classifying liver stiffness.


Assuntos
Técnicas de Imagem por Elasticidade , Hepatopatias/diagnóstico por imagem , Hepatopatias/patologia , Aprendizado de Máquina , Imagem por Ressonância Magnética/métodos , Adolescente , Criança , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Adulto Jovem
8.
Brain Connect ; 9(7): 580-592, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31144523

RESUMO

The American Academy of Pediatrics recommends that parents read with their children early and often and limits on screen-based media. While book sharing may benefit attention in children, effects of animated content are controversial, and the influence of either on attention networks has not previously been studied. This study involved functional magnetic resonance imaging (fMRI) of three separate active-task scans composed of similar 5-min stories presented in the same order for each child (audio → illustrated → animated), followed by assessment of comprehension. Five functional brain networks were defined a priori through literature review: dorsal attention network (DAN), ventral attention network (VAN), language (L), visual imagery (VI), and visual perception (VP). Analyses involved comparison of functional connectivity (FC) within- and between networks across formats, applying false discovery rate correction. Twenty-seven of 33 children completed fMRI (82%; 15 boys, 12 girls; mean 58 ± 8 months old). Comprehension of audio and illustrated stories was equivalent and lower for animation (p < 0.05). For illustration relative to audio, FC within DAN and VAN and between each of these and all other networks was similar, lower within-L, and higher between VI-VP, suggesting reduced strain on the language network using illustrations and imagery. For animation relative to illustration, FC was lower between DAN-L, VAN-VP, VAN-VI, L-VI, and L-VP, suggesting less focus on narrative, reorienting to imagery, and visual-language integration. These findings suggest that illustrated storybooks may be optimal at this age to encourage integration of attention, visual, and language networks, while animation may bias attention toward VP.

9.
Clin Imaging ; 57: 77-82, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31136882

RESUMO

BACKGROUND: MRI brain segmentation and volume estimation of gray matter (GM), white matter (WM) and cerebrospinal fluid (CSF) are important for many neurological applications. Signal intensity based measurements, such as the current statistical parametric mapping (SPM) based volume estimation techniques rely on T1W images that involve a series of pre-processing steps, making it impractical for clinical use. PURPOSE: In this study, we compared Synthetic MRI (SyMRI) generated relaxometry maps based brain segmentation and estimation of brain volumes with SPM image intensity based segmentation and volume estimation in children and young adults. SUBJECTS: 176 studies were included for analysis with mean age of 10.9 ±â€¯5.5 years. METHODS: Included studies were quantitatively analyzed and segmented using SyMRI® software. In SPM, the segmentation routine segments brain T1W images into GM, WM, and CSF based on image intensity values. SPM and SyMRI segmentation based volume estimates were plotted. Scatter plots comparing the two methods were generated and agreement was assessed using correlation coefficients. RESULTS: Correlation coefficient, r, of agreement between the 2 methods was 0.85 for GM, 0.91 for WM, and 0.38 for CSF (P < 0.0001 for all three volumes). CONCLUSION: Brain imaging in children using SyMRI can identify and calculate estimates of GM, WM, CSF volumes. With our work, we have shown high similarity of volume estimates in GM and WM using SyMRI with a systematic bias for CSF values. The ease of use of this software can make this quantitative data to be used clinically along with the routine anatomical images.


Assuntos
Encéfalo/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Imagem por Ressonância Magnética/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Substância Cinzenta/diagnóstico por imagem , Humanos , Masculino , Doenças do Sistema Nervoso/diagnóstico por imagem , Estudos Retrospectivos , Software , Substância Branca/diagnóstico por imagem , Adulto Jovem
10.
Mol Diagn Ther ; 23(3): 311-331, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30941670

RESUMO

Circulating tumor DNA (ctDNA) is a component of cell-free DNA that is shed by malignant tumors into the bloodstream and other bodily fluids. Levels of ctDNA are typically low, particularly in patients with localized disease, requiring highly sophisticated methods for detection and quantification. Multiple liquid biopsy methods have been developed for ctDNA analysis in solid tumor malignancies and are now enabling detection and assessment of earlier stages of disease, post-treatment molecular residual disease (MRD), resistance to targeted systemic therapy, and tumor mutational burden. Understanding ctDNA biology, mechanisms of release, and clearance and size characteristics, in conjunction with the application of molecular barcoding and targeted error correction, have increased the sensitivity and specificity of ctDNA detection techniques. Combinatorial approaches including integration of ctDNA data with circulating protein biomarkers may further improve assay sensitivity and broaden the scope of ctDNA applications. Circulating viral DNA may be utilized to monitor disease in some virally induced malignancies. In spite of increasingly accurate methods of ctDNA detection, results need to be interpreted with caution given that somatic mosaicisms such as clonal hematopoiesis of indeterminate potential (CHIP) may give rise to genetic variants in the bloodstream unrelated to solid tumors, and the limited concordance observed between different commercial platforms. Overall, highly precise ctDNA detection and quantification methods have the potential to transform clinical practice via non-invasive monitoring of solid tumor malignancies, residual disease detection at earlier timepoints than standard clinical and/or imaging surveillance, and treatment personalization based on real-time assessment of the tumor genomic landscape.

11.
Cancer Discov ; 9(4): 500-509, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30578357

RESUMO

Current regimens for the detection and surveillance of bladder cancer are invasive and have suboptimal sensitivity. Here, we present a novel high-throughput sequencing (HTS) method for detection of urine tumor DNA (utDNA) called utDNA CAPP-Seq (uCAPP-Seq) and apply it to 67 healthy adults and 118 patients with early-stage bladder cancer who had urine collected either prior to treatment or during surveillance. Using this targeted sequencing approach, we detected a median of 6 mutations per patient with bladder cancer and observed surprisingly frequent mutations of the PLEKHS1 promoter (46%), suggesting these mutations represent a useful biomarker for detection of bladder cancer. We detected utDNA pretreatment in 93% of cases using a tumor mutation-informed approach and in 84% when blinded to tumor mutation status, with 96% to 100% specificity. In the surveillance setting, we detected utDNA in 91% of patients who ultimately recurred, with utDNA detection preceding clinical progression in 92% of cases. uCAPP-Seq outperformed a commonly used ancillary test (UroVysion, P = 0.02) and cytology and cystoscopy combined (P ≤ 0.006), detecting 100% of bladder cancer cases detected by cytology and 82% that cytology missed. Our results indicate that uCAPP-Seq is a promising approach for early detection and surveillance of bladder cancer. SIGNIFICANCE: This study shows that utDNA can be detected using HTS with high sensitivity and specificity in patients with early-stage bladder cancer and during post-treatment surveillance, significantly outperforming standard diagnostic modalities and facilitating noninvasive detection, genotyping, and monitoring.This article is highlighted in the In This Issue feature, p. 453.

12.
Br J Sports Med ; 53(24): 1539-1551, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30323056

RESUMO

PURPOSE: To (1) quantify white matter (WM) alterations in female high school athletes during a soccer season and characterise the potential for normalisation during the off-season rest period, (2) determine the association between WM alterations and exposure to repetitive subconcussive head impacts, and (3) evaluate the efficacy of a jugular vein compression collar to prevent WM alterations associated with head impact exposure. METHODS: Diffusion tensor imaging (DTI) data were prospectively collected from high school female soccer participants (14-18 years) at up to three time points over 9 months. Head impacts were monitored using accelerometers during all practices and games. Participants were assigned to a collar (n=24) or non-collar group (n=22). The Tract-Based Spatial Statistics approach was used in the analysis of within-group longitudinal change and between-group comparisons. RESULTS: DTI analyses revealed significant pre-season to post-season WM changes in the non-collar group in mean diffusivity (2.83%±2.46%), axial diffusivity (2.58%±2.34%) and radial diffusivity (3.52%±2.60%), but there was no significant change in the collar group despite similar head impact exposure. Significant correlation was found between head impact exposure and pre-season to post-season DTI changes in the non-collar group. WM changes in the non-collar group partially resolved at 3 months off-season follow-up. DISCUSSION: Microstructural changes in WM occurred during a season of female high school soccer among athletes who did not wear the collar device. In comparison, there were no changes in players who wore the collar, suggesting a potential prophylactic effect of the collar device in preventing changes associated with repetitive head impacts. In those without collar use, the microstructural changes showed a reversal towards normal over time in the off-season follow-up period.


Assuntos
Bandagens Compressivas , Traumatismos Craniocerebrais/patologia , Traumatismos Craniocerebrais/prevenção & controle , Veias Jugulares/fisiologia , Futebol/lesões , Substância Branca/patologia , Adolescente , Comportamento Competitivo/fisiologia , Traumatismos Craniocerebrais/diagnóstico por imagem , Imagem de Tensor de Difusão , Feminino , Humanos , Estudos Longitudinais , Estudos Prospectivos , Recidiva , Ultrassonografia , Substância Branca/diagnóstico por imagem
13.
J Sci Med Sport ; 22(2): 169-174, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30017465

RESUMO

OBJECTIVES: We aimed to present a unique prospective neurological dataset for participants who experienced an ACL injury. DESIGN: Prospective longitudinal case-control. METHODS: High school female soccer athletes were evaluated using functional magnetic resonance imaging to capture resting-state brain connectivity prior to their competitive season. Two of these athletes later experienced an ACL injury (ACLI). We matched these ACLI participants with eight teammates who did not go on to sustain an ACL injury (uninjured controls, Con) based on age, grade, sex, height, and weight to examine differences in preseason connectivity. Knee-motor regions of interest (ROIs) were created based on previously published data from which five specific areas were selected as seeds for analysis. Independent-samples t-tests with a false discovery rate correction for multiple comparisons determined differences in connectivity between the ACLI and Con. RESULTS: There was significantly greater connectivity between the left primary sensory cortex (a brain region responsible for proprioception) and the right posterior lobe of the cerebellum (a brain region responsible for balance and coordination) for the Con relative to ACLI, t (8)=4.53, p=0.03 (false discovery rate corrected). CONCLUSIONS: These preliminary data indicate that those who do not later sustain an ACL injury exhibit a stronger functional connection between a cortical sensory-motor region and a cerebellar region responsible for balance and coordination. These findings may help to guide development of brain-driven biofeedback training that optimizes and promotes adaptive neuroplasticity to reduce motor coordination errors and injury risk.


Assuntos
Lesões do Ligamento Cruzado Anterior/fisiopatologia , Traumatismos em Atletas/fisiopatologia , Encéfalo/fisiologia , Futebol/lesões , Adolescente , Atletas , Biomarcadores , Estudos de Casos e Controles , Feminino , Neuroimagem Funcional , Humanos , Estudos Longitudinais , Imagem por Ressonância Magnética , Estudos Prospectivos , Fatores de Risco
14.
J Neurotrauma ; 36(5): 721-734, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30136637

RESUMO

Special Weapons and Tactics (SWAT) personnel who conduct breacher exercises are at risk for blast-related head trauma. We aimed to investigate the potential impact of low-level blast exposure during breacher training on the neural functioning of working memory and auditory network connectivity. We also aimed to evaluate the effects of a jugular vein compression collar, designed to internally mitigate slosh energy absorption, preserving neural functioning and connectivity, following blast exposure. A total of 23 SWAT personnel were recruited and randomly assigned to a non-collar (n = 11) and collar group (n = 12). All participants completed a 1-day breacher training with multiple blast exposure. Prior to and following training, 18 participants (non-collar, n = 8; collar, n = 10) completed functional magnetic resonance imaging (fMRI) of working memory using N-Back task; 20 participants (non-collar, n = 10; collar, n = 12) completed resting-state fMRI. Key findings from the working memory analysis include significantly increased fMRI brain activation in the right insular, right superior temporal pole, right inferior frontal gyrus, and pars orbitalis post-training for the non-collar group (p < 0.05, threshold-free cluster enhancement corrected), but no changes were noted for the collar group. The elevation in fMRI activation in the non-collar group was found to correlate significantly (n = 7, r = 0.943, p = 0.001) with average peak impulse amplitude experienced during the training. In the resting-state fMRI analysis, significant pre- to post-training increase in connectivity between the auditory network and two discrete regions (left middle frontal gyrus and left superior lateral occipital/angular gyri) was found in the non-collar group, while no change was observed in the collar group. These data provided initial evidence of the impact of low-level blast on working memory and auditory network connectivity as well as the protective effect of collar on brain function following blast exposure, and is congruent with previous collar findings in sport-related traumatic brain injury.

15.
Brain Imaging Behav ; 2018 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-30377932

RESUMO

The American Academy of Pediatrics (AAP) recommends that parents begin reading to their children soon after birth, and limits on screen-based media. Benefits of traditional book-sharing are well documented in children, while cited deleterious effects of animated content on narrative processing are controversial. The influence of story format on underlying functional brain networks has not previously been studied. Thirty-three healthy children were recruited for this study via advertisement at an academic medical center, which involved functional magnetic resonance imaging (fMRI) at a single visit. Twenty-seven of them completed fMRI (82%; 15 boys, 12 girls; mean 58 ± 8 months old). The fMRI protocol involved the presentation of 3 similar, unrhymed stories by the same author lasting 5 min each in audio, illustrated, and animated format during separate runs, followed by a test of factual recall. Within- and between-network functional connectivity (FC) was compared across formats involving five functional networks, which were defined via literature review and refined via a data-driven parcellation method: visual perception, visual imagery, language, Default Mode (DMN), and cerebellar association. For illustration relative to audio, FC was decreased within the language network and increased between visual, DMN, and cerebellar networks, suggesting decreased strain on the language network afforded by pictures and visual imagery. Between-network connectivity was decreased for all networks for animation relative to the other formats, particularly illustration, suggesting a bias towards visual perception at the expense of network integration. These findings suggest substantial differences in functional brain network connectivity for animated and more traditional story formats in preschool-age children, reinforcing the appeal of illustrated storybooks at this age to provide efficient scaffolding for language, and suggesting novel neurobiological correlates of how functional networks may contribute to this process.

16.
Exp Brain Res ; 236(10): 2691-2701, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29987537

RESUMO

Exposure to explosive blasts places one at risk for traumatic brain injury, especially for special weapons and tactics (SWAT) and military personnel, who may be repeatedly exposed to blasts. In the current study, the effectiveness of a jugular vein compression collar to prevent alterations in resting-state electrocortical activity following a single-SWAT breacher training session was investigated. SWAT team personnel were randomly assigned to wear a compression collar during breacher training and resting state electroencephalography (EEG) was measured within 2 days prior to and two after breacher training. It was hypothesized that significant changes in brain dynamics-indicative of possible underlying neurodegenerative processes-would follow blast exposure for those who did not wear the collar, with ameliorated changes for the collar-wearing group. Using recurrence quantification analysis (RQA) it was found that participants who did not wear the collar displayed longer periods of laminar electrocortical behavior (as indexed by RQA's vertical max line measure) after breacher training. It is proposed that the blast wave exposure for the no-collar group may have reduced the number of pathways, via axonal disruption-for electrical transmission-resulting in the EEG signals becoming trapped in laminar states for longer periods of time. Longer laminar states have been associated with other electrocortical pathologies, such as seizure, and may be important for understanding head trauma and recovery.


Assuntos
Lesões Encefálicas/cirurgia , Traumatismos Craniocerebrais/prevenção & controle , Veias Jugulares/cirurgia , Pressão , Armas , Adulto , Idoso , Encéfalo/patologia , Lesões Encefálicas/prevenção & controle , Lesões Encefálicas Traumáticas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
17.
J Neurotrauma ; 35(11): 1248-1259, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29334834

RESUMO

Recent neuroimaging studies have suggested that repetitive subconcussive head impacts, even after only one sport season, may lead to pre- to post-season structural and functional alterations in male high school football athletes. However, data on female athletes are limited. In the current investigation, we aimed to (1) assess the longitudinal pre- to post-season changes in functional MRI (fMRI) of working memory and working memory performance, (2) quantify the association between the pre- to post-season change in fMRI of working memory and the exposure to head impact and working memory performance, and (3) assess whether wearing a neck collar designed to reduce intracranial slosh via mild compression of the jugular veins can ameliorate the changes in fMRI brain activation observed in the female high school athletes who did not wear collars after a full soccer season. A total of 48 female high school soccer athletes (age range: 14.00-17.97 years) were included in the study. These athletes were assigned to the non-collar group (n = 21) or to the collar group (n = 27). All athletes undewent MRI at both pre-season and post-season. In each session, a fMRI verbal N-Back task was used to engage working memory. A significant pre- to post-season increase in fMRI blood oxygen level dependent (BOLD) signal was demonstrated when performing the N-back working memory task in the non-collar group but not in the collar group, despite the comparable exposure to head impacts during the season between the two groups. The collar group demonstrated significantly smaller pre- to post-season change in fMRI BOLD signal than the non-collar group, suggesting a potential protective effect from the collar device. Significant correlations were also found between the pre- to post-season increase in fMRI brain activation and the decrease in task accuracy in the non-collar group, indicating an association between the compensatory mechanism in underlying neurophysiology and the alteration in the behavioral outcomes.


Assuntos
Traumatismos em Atletas/prevenção & controle , Lesões Encefálicas Traumáticas/prevenção & controle , Memória de Curto Prazo , Equipamento de Proteção Individual , Futebol/lesões , Adolescente , Feminino , Humanos , Veias Jugulares , Estudos Longitudinais , Imagem por Ressonância Magnética , Estudos Prospectivos
18.
Clin Chem ; 64(2): 307-316, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29038154

RESUMO

BACKGROUND: Cell-free DNA (cfDNA) diagnostics are emerging as a new paradigm of disease monitoring and therapy management. The clinical utility of these diagnostics is relatively limited by a low signal-to-noise ratio, such as with low allele frequency (AF) mutations in cancer. While enriching for rare alleles to increase their AF before sample analysis is one strategy that can greatly improve detection capability, current methods are limited in their generalizability, ease of use, and applicability to point mutations. METHODS: Leveraging the robust single-base-pair specificity and generalizability of the CRISPR associated protein 9 (Cas9) system, we developed a deactivated Cas9 (dCas9)-based method of minor-allele enrichment capable of efficient single-target and multiplexed enrichment. The dCas9 protein was complexed with single guide RNAs targeted to mutations of interest and incubated with cfDNA samples containing mutant strands at low abundance. Mutation-bound dCas9 complexes were isolated, dissociated, and the captured DNA purified for downstream use. RESULTS: Targeting the 3 most common epidermal growth factor receptor mutations (exon 19 deletion, T790M, L858R) found in non-small cell lung cancer (NSCLC), we achieved >20-fold increases in AF and detected mutations by use of qPCR at an AF of 0.1%. In a cohort of 18 NSCLC patient-derived cfDNA samples, our method enabled detection of 8 out of 13 mutations that were otherwise undetected by qPCR. CONCLUSIONS: The dCas9 method provides an important application of the CRISPR/Cas9 system outside the realm of genome editing and can provide a step forward for the detection capability of cfDNA diagnostics.


Assuntos
Proteína 9 Associada à CRISPR/genética , Ácidos Nucleicos Livres/genética , Frequência do Gene , Humanos , Limite de Detecção , Mutação Puntual , Reação em Cadeia da Polimerase em Tempo Real/métodos , Deleção de Sequência
19.
Nutr Neurosci ; 21(4): 297-305, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-28221821

RESUMO

OBJECTIVES: Preclinical studies have shown that blueberry supplementation can improve cognitive performance and neural function in aged animals and have identified associations between anthocyanins and such benefits. Preliminary human trials also suggest cognitive improvement in older adults, although direct evidence of enhancement of brain function has not been demonstrated. In this study, we investigated the effect of blueberry supplementation on regional brain activation in older adults at risk for dementia. METHODS: In a randomized, double-blind, placebo-controlled trial we performed pre- and post-intervention functional magnetic resonance imaging during a working memory (WM) task to assess the effect of blueberry supplementation on blood oxygen level-dependent (BOLD) signal in older adults with mild cognitive impairment, a risk condition for dementia. RESULTS: Following daily supplementation for 16 weeks, blueberry-treated participants exhibited increased BOLD activation in the left pre-central gyrus, left middle frontal gyrus, and left inferior parietal lobe during WM load conditions (corrected P < 0.01). There was no clear indication of WM enhancement associated with blueberry supplementation. Diet records indicated no between-group difference in anthocyanin consumption external to the intervention. DISCUSSION: These data demonstrate, for the first time, enhanced neural response during WM challenge in blueberry-treated older adults with cognitive decline and are consistent with prior trials showing neurocognitive benefit with blueberry supplementation in this at-risk population.


Assuntos
Mirtilos Azuis (Planta)/química , Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/dietoterapia , Idoso , Idoso de 80 Anos ou mais , Antocianinas/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/fisiologia , Disfunção Cognitiva/diagnóstico por imagem , Demência , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/efeitos dos fármacos , Frutas , Humanos , Imagem por Ressonância Magnética , Masculino , Memória de Curto Prazo , Lobo Parietal/diagnóstico por imagem , Lobo Parietal/efeitos dos fármacos , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/efeitos dos fármacos
20.
Hum Brain Mapp ; 39(1): 491-508, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29080230

RESUMO

The cumulative effects of repetitive subclinical head impacts during sports may result in chronic white matter (WM) changes and possibly, neurodegenerative sequelae. In this pilot study, we investigated the longitudinal WM changes over the course of two consecutive high-school football seasons and explored the long-term effects of a jugular vein compression collar on these WM alterations. Diffusion tensor imaging data were prospectively collected both pre- and postseason in the two consecutive seasons. Participants were assigned into either collar or noncollar groups. Tract-based spatial statistics (TBSS) approach and region of interest-based approach were used to quantify changes in WM diffusion properties. Despite comparable exposure to repetitive head impacts, significant reductions in mean, axial, and/or radial diffusivity were identified in Season 1 in multiple WM regions in the noncollar group but not in the collar group. After an 8- to 9-month long off-season, these changes observed in the noncollar group partially and significantly reversed but also remained significantly different from the baseline. In Season 2, trend level WM alterations in the noncollar group were found but located in spatially different regions than Season 1. Last, the WM integrity in the collar group remained unchanged throughout the four time points. In conclusion, we quantitatively assessed the WM structural changes and partial reversal over the course of two consecutive high-school football seasons. In addition, the mitigated WM alterations in athletes in the collar group might indicate potential effect of the collar in ameliorating the changes against repetitive head impacts. Hum Brain Mapp 39:491-508, 2018. © 2017 Wiley Periodicals, Inc.


Assuntos
Traumatismos em Atletas/diagnóstico por imagem , Traumatismos em Atletas/prevenção & controle , Futebol Americano/lesões , Equipamento de Proteção Individual , Substância Branca/diagnóstico por imagem , Adolescente , Atletas , Concussão Encefálica/diagnóstico por imagem , Concussão Encefálica/prevenção & controle , Imagem de Tensor de Difusão , Seguimentos , Humanos , Veias Jugulares , Estudos Longitudinais , Imagem por Ressonância Magnética , Masculino , Projetos Piloto , Estudos Prospectivos , Estudantes , Resultado do Tratamento
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