Glutamatergic modulation of auditory cortex connectivity with attentional brain networks in unpredictable perceptual environment.

In a stable environment the brain can minimize processing required for sensory input by forming a predictive model of the surrounding world and suppressing neural response to predicted stimuli. Unpredicted stimuli lead to a prediction error signal propagation through the perceptual network, and resulting adjustment to the predictive model. The inter-regional plasticity which enables the model-building and model-adjustment is hypothesized to be mediated via glutamatergic receptors. While pharmacological challenge studies with glutamate receptor ligands have demonstrated impact on prediction-error indices, it is not clear how inter-individual differences in the glutamate system affect the prediction-error processing in non-medicated state. In the present study we examined 20 healthy young subjects with resting-state proton MRS spectroscopy to characterize glutamate + glutamine (rs-Glx) levels in their Heschl's gyrus (HG), and related this to HG functional connectivity during a roving auditory oddball protocol. No rs-Glx effects were found within the frontotemporal prediction-error network. Larger rs-Glx signal was related to stronger connectivity between HG and bilateral inferior parietal lobule during unpredictable auditory stimulation. We also found effects of rs-Glx on the coherence of default mode network and frontoparietal network during unpredictable auditory stimulation. Our results demonstrate the importance of Glx in modulating long-range connections and wider networks in the brain during perceptual inference.

Resting-state glutamatergic neurotransmission is related to the peak latency of the auditory mismatch negativity (MMN) for duration deviants: An (1)H-MRS-EEG study.

Mismatch negativity (MMN), an ERP elicited by a deviant stimulus in a train of standard stimuli, has been suggested to be associated to glutamatergic neurotransmission, mediated by glutamatergic NMDA receptors. In this study, we examined the relationship between interindividual variation of (1)H-MRS-measured glutamate+glutamine (Glx) in the superior temporal gyrus and MMN for duration and frequency deviants in 19 healthy young adults (9 male). We found a significant relationship between the peak latency of the duration-MMN peak and creatine-scaled Glx (p = .0003, η(2) = .43), with increased Glx level being associated to earlier peak of the duration-MMN (r = -.63). In contrast, the amplitude of the duration-MMN was not related to Glx. There was no significant relationship between Glx and the frequency-MMN. The present study is the first to demonstrate that interindividual variation in the glutamatergic neurotransmission affects the MMN response in healthy individuals.

Reliability of radiologic measures of hip displacement in a cohort of preschool-aged children with cerebral palsy.

BACKGROUND: Radiologic hip surveillance is recommended for children with cerebral palsy (CP) at risk of hip displacement. Young children with abnormal proximal femoral geometry (Hilgenreiner epiphyseal angle, HEA) may be more likely to develop hip displacement, less likely to respond to nonsurgical intervention, and may benefit from earlier surgical referral. The reliability of radiographic measures of migration percentage (MP) in the immature pelvis of young children has been reported in smaller retrospective studies; HEA has not been examined in this population. This prospective study describes the reliability of MP and HEA in very young children with CP. METHODS: Participants were entered from tertiary referral center CP clinics into a prospectively recruited population-based cohort for hip surveillance with pelvic radiography using standardized patient position, at 18, 24, 30, 36, and 48 months. All Gross Motor Function Classification System (GMFCS) levels were included. Two independent raters assessed radiographs for HEA and MP. The intraclass correlation coefficient (ICC) was computed as a measure of interrater and intrarater reliability. The correlation coefficient between HEA and femoral position was computed. RESULTS: Ninety-eight children less than 25 months (spasticity=83, 85%; GMFCS IV-V=38, 39%), and 114 children 25 to 48 months (spasticity=96, 85%; GMFCS IV-V=37, 32%) were included from 133 unique participants (spasticity=111, 84%; GMFCS IV-V=42, 32%). Of these 79 children were studied in both age groups. Overall interrater and intrarater reliability of MP was high [ICC=0.93; 95% confidence interval (CI), 0.91-0.95]; SEM was 3.9% (single) and 5.5% (sequential). Perfect concordance for classification of marked hip displacement (MP>30%) occurred in 217 cases (95.2%); nonweighted κ=0.80; 95% CI, 0.68-0.91. For HEA, overall reliability was high (ICC=0.89; 95% CI, 0.85-0.93); SEM=4.8% (single) and 6.7% (sequential). Correlation between changes in HEA and femoral abduction was poor (coefficient=-0.27, P=0.244). CONCLUSIONS: MP and HEA can be reliably applied to very young children with CP, with high reliability for both measures. Measured HEA values appear to be independent of patient position, and may reflect genuine changes in proximal femoral geometry. A longitudinal study should be performed to determine the relationship between HEA and later hip outcomes. LEVEL OF EVIDENCE: Level I/II--testing and development of diagnostic tests.

Australian Cerebral Palsy Child Study: protocol of a prospective population based study of motor and brain development of preschool aged children with cerebral palsy.

BACKGROUND: Cerebral palsy (CP) results from a static brain lesion during pregnancy or early life and remains the most common cause of physical disability in children (1 in 500). While the brain lesion is static, the physical manifestations and medical issues may progress resulting in altered motor patterns. To date, there are no prospective longitudinal studies of CP that follow a birth cohort to track early gross and fine motor development and use Magnetic Resonance Imaging (MRI) to determine the anatomical pattern and likely timing of the brain lesion. Existing studies do not consider treatment costs and outcomes. This study aims to determine the pathway(s) to motor outcome from diagnosis at 18 months corrected age (c.a.) to outcome at 5 years in relation to the nature of the brain lesion (using structural MRI). METHODS: This prospective cohort study aims to recruit a total of 240 children diagnosed with CP born in Victoria (birth years 2004 and 2005) and Queensland (birth years 2006-2009). Children can enter the study at any time between 18 months to 5 years of age and will be assessed at 18, 24, 30, 36, 48 and 60 months c.a. Outcomes include gross motor function (GMFM-66 & GMFM-88), Gross Motor Function Classification System (GMFCS); musculoskeletal development (hip displacement, spasticity, muscle contracture), upper limb function (Manual Ability Classification System), communication difficulties using Communication and Symbolic Behaviour Scales-Developmental Profile (CSBS-DP), participation using the Paediatric Evaluation of Disability Inventory (PEDI), parent reported quality of life and classification of medical and allied health resource use and determination of the aetiology of CP using clinical evaluation combined with MRI. The relationship between the pathways to motor outcome and the nature of the brain lesion will be analysed using multiple methods including non-linear modelling, multilevel mixed-effects models and generalised estimating equations. DISCUSSION: This protocol describes a large population-based study of early motor development and brain structure in a representative sample of preschool aged children with CP, using direct clinical assessment. The results of this study will be published in peer reviewed journals and presented at relevant international conferences. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ACTRN1261200169820).