Differential rates of perinatal maturation of human primary and nonprimary auditory cortex

Abstract Primary and nonprimary cerebral cortex mature along different timescales; however, the differences between the rates of maturation of primary and nonprimary cortex are unclear. Cortical maturation can be measured through changes in tissue microstructure detectable by diffusion magnetic resonance imaging (MRI). In this study, diffusion tensor imaging (DTI) was used to characterize the maturation of Heschl’s gyrus (HG), which contains both primary auditory cortex (pAC) and nonprimary auditory cortex (nAC), in 90 preterm infants between 26 and 42 weeks postmenstrual age (PMA). The preterm infants were in different acoustical environments during their hospitalization: 46 in open ward beds and 44 in single rooms. A control group consisted of 15 term-born infants. Diffusion parameters revealed that (1) changes in cortical microstructure that accompany cortical maturation had largely already occurred in pAC by 28 weeks PMA, and (2) rapid changes were taking place in nAC between 26 and 42 weeks PMA. At term equivalent PMA, diffusion parameters for auditory cortex were different between preterm infants and term control infants, reflecting either delayed maturation or injury. No effect of room type was observed. For the preterm group, disturbed maturation of nonprimary (but not primary) auditory cortex was associated with poorer language performance at age two years

Cerebrospinal fluid levels of amyloid precursor protein are associated with ventricular size in post-hemorrhagic hydrocephalus of prematurity.

Neurological outcomes of preterm infants with post-hemorrhagic hydrocephalus (PHH) remain among the worst in infancy, yet there remain few instruments to inform the treatment of PHH. We previously observed PHH-associated elevations in cerebrospinal fluid (CSF) amyloid precursor protein (APP), neural cell adhesion molecule-L1 (L1CAM), neural cell adhesion molecule-1 (NCAM-1), and other protein mediators of neurodevelopment.The objective of this study was to examine the association of CSF APP, L1CAM, and NCAM-1 with ventricular size as an early step toward developing CSF markers of PHH.CSF levels of APP, L1CAM, NCAM-1, and total protein (TP) were measured in 12 preterm infants undergoing PHH treatment. Ventricular size was determined using cranial ultrasounds. The relationships between CSF APP, L1CAM, and NCAM-1, occipitofrontal circumference (OFC), volume of CSF removed, and ventricular size were examined using correlation and regression analyses.CSF levels of APP, L1CAM, and NCAM-1 but not TP paralleled treatment-related changes in ventricular size. CSF APP demonstrated the strongest association with ventricular size, estimated by frontal-occipital horn ratio (FOR) (Pearson R = 0.76, p = 0.004), followed by NCAM-1 (R = 0.66, p = 0.02) and L1CAM (R = 0.57,p = 0.055). TP was not correlated with FOR (R = 0.02, p = 0.95).Herein, we report the novel observation that CSF APP shows a robust association with ventricular size in preterm infants treated for PHH. The results from this study suggest that CSF APP and related proteins at once hold promise as biomarkers of PHH and provide insight into the neurological consequences of PHH in the preterm infant

FOR, L1CAM, and NCAM-1 levels.

<p><b>A</b>.FOR measurements (red left y-axis) and absolute L1CAM concentrations (blue right y-axis) plotted versus relative time of reservoir surgery in selected timepoints of patients #7 (left) and #8 (right). <b>B</b>. FOR measurements (left y-axis) and absolute NCAM-1 concentrations plotted versus relative time of reservoir surgery in selected timepoints of patients #7 (left) and #8 (right).</p

Total protein.

<p>Total protein measurements (μg/ml) for all 12 PHH subjects analyzed throughout the duration of the study.</p

FOR, L1CAM, and NCAM-1 levels.

<p><b>A</b>.FOR measurements (red left y-axis) and absolute L1CAM concentrations (blue right y-axis) plotted versus relative time of reservoir surgery in selected timepoints of patients #7 (left) and #8 (right). <b>B</b>. FOR measurements (left y-axis) and absolute NCAM-1 concentrations plotted versus relative time of reservoir surgery in selected timepoints of patients #7 (left) and #8 (right).</p

Characteristics of the 12 subjects with post-hemorrhagic hydrocephalus enrolled in the study.

<p>Characteristics of the 12 subjects with post-hemorrhagic hydrocephalus enrolled in the study.</p

FOR and APP levels.

<p><b>A</b>.FOR measurements (red left y-axis) and absolute APP concentrations (blue right y-axis) and total protein (black right y-axis) plotted versus relative time of reservoir surgery in selected timepoints of patients #7 (left) and #8 (right). Each FOR data point is accompanied by an US image for the selected patient at that particular timepoint. The image shown is a coronal slice taken at the foramen of Monro. <b>B</b>. FOR measurements (left y-axis) and normalized APP levels (right y-axis) plotted versus relative time of reservoir surgery in selected timepoints of patients #7 (left) and #8 (right).</p

The Pearson Correlation Coefficients (and p-value) for normalized proteins and their correlation with the ventricular size metrics Ventricular Index (VI) and Frontal-Occipital Horn Ratio (FOR).

<p>* All levels normalized by total protein.</p><p>The Pearson Correlation Coefficients (and p-value) for normalized proteins and their correlation with the ventricular size metrics Ventricular Index (VI) and Frontal-Occipital Horn Ratio (FOR).</p

Correlation of FOR with normalized proteins.

<p>A linear regression analysis showing the correlation of normalized APP (A), normalized L1CAM (B), and normalized NCAM-1 (C) with FOR measurements for all 12 subjects used.</p