Elsevier

NeuroImage

Volume 22, Issue 4, August 2004, Pages 1543-1553
NeuroImage

Age-associated changes of cerebral glucose metabolic activity in both male and female deaf children: parametric analysis using objective volume of interest and voxel-based mapping

https://doi.org/10.1016/j.neuroimage.2004.04.010Get rights and content

Abstract

Quantitative analysis of brain activity in the brains of children requires the establishment of age-associated norms. We investigated regional differences in age-associated changes in fluorodeoxyglucose (FDG) uptake in the developmental brains. From 87 (44 male and 43 female) deaf children from the age of 1 to 15, brain FDG positron emission tomography (PET) images were examined after spatial normalization, smoothing, and global normalization to identify brain regions showing a correlation between FDG uptake and age. Using population-based probabilistic volume of interests (VOIs), an objective VOI analysis was performed where normalized relative FDG uptake was measured and their correlations with age were examined in both genders. For the voxel-based analyses, the correlations with age were examined in a general linear model using statistical parametric mapping (SPM99). Both methods revealed that FDG uptake linearly increases with age both in the bilateral inferior prefrontal/orbitofrontal gyri and the right dorsomedial frontal gyrus and decreases in the inferior temporal gyrus and internal capsule white matter. Male children showed age-associated increases of FDG uptake in the right dorsomedial frontal gyrus, and female children in the left dorsolateral prefrontal cortex and thalamus. These changes in FDG uptake in various brain regions may suggest changes in synaptic density or regional activity resulting from normal maturation or deaf-induced adaptation. Caution should be exercised in interpreting the differences in the brain of child patients when compared with adult control's or with a different gender. Further research will be needed to examine if gender difference is manifested in the development rate of behavioral/cognitive functions in association with the age-associated changes of the right medial frontal (male) or the left dorsolateral prefrontal cortices.

Introduction

When we want to find abnormalities in brain perfusion or metabolism specific to a disease in children, brain positron emission tomography (PET) or single photon emission computed tomography (SPECT) images are visually interpreted by experts or analyzed in a voxel-wise fashion using statistical parametric mapping (SPM) Juhasz et al., 2001, Kim et al., 2001, Kim et al., 2002, Vandermeeren et al., 2002, Villemagne et al., 2002. However, developmental changes in terms of brain perfusion or metabolism of children are not well understood because PET or SPECT studies cannot be performed in ‘normal’ children due to radiation exposure risk. Only volume changes or myelinization patterns have been easily reported Caviness et al., 1996, Giedd et al., 1996, Kanemura et al., 2003, Mukherjee et al., 2001, Steen et al., 1997.

Instead of relying on reports from brain perfusion or metabolism studies in children, we often have to use adult normal images or images of the probably normal or close-to-normal children as controls for statistical parametric mapping studies (Juengling et al., 2002, Juhasz et al., 2001, Kang et al., 2003, Lee et al., 2002; Vendermeeren et al., 2001; Villemagne et al., 2002). While we know what changes occur during development in children in terms of volumes and displacements of brain structures Paus et al., 1999, Thompson et al., 2000, we do not know exactly what changes take place in the children's brain in terms of metabolism or perfusion. In rare early reports Chugani, 1998, Chugani et al., 1987, brain glucose metabolism was found to increase until the age of 2–4 years and then to decrease slowly again to the adult level. Regional differences have been noted but have not been examined in detail (Chugani and Phelps, 1986). The reason is partly due to the poorer resolution of earlier scanners and partly because of the lack of objective means of analytical comparison.

When we use voxel-wise comparison such as statistical parametrical mapping (SPM) method to analyze brain metabolism, brain images are usually normalized in counts and only the relative differences between different regions can be determined. For example, child patients' brain images have been compared on a voxel-to-voxel manner with adult control brains Juhasz et al., 2001, Juengling et al., 2002, Kang et al., 2003, Lee et al., 2002. PET or SPECT images of epileptic (Vendermeeren et al., 2001) or transient ischemic attack patients (Villemagne et al., 2002) have often been used as age-matched disease controls due to lack of normal healthy children control data. It is important to delineate developmental or age-related changes as much as possible even in deaf children since it still could provide valuable information in understanding normal development of brain function.

The brain glucose metabolism of profoundly deaf children has been reported to have prognostic significance for cochlear implant patients (Lee et al., 2001). Younger age and the hypometabolism in temporal regions were associated with better outcome following implantation (Oh et al., 2003). There seemed to be a relationship between the age and the glucose metabolism in deaf children. The goal of this study is to examine the developmental metabolic changes in deaf brain to understand the relationship between these two factors. Meanwhile, we would like to know which changes were part of normal development and which were part of deaf-induced changes. Fluorodeoxyglucose (FDG) PET studies are routinely performed on deaf children in our center before cochlear implantation. This is a part of an on-going effort to understand the brain plasticity of deaf children and to evaluate the relationship between the regional brain metabolic activity of deaf patients and the implantation outcome (e.g., speech hearing) (Kang et al., in press). Being interested in examining individual differences in functional brain activity at rest, we became aware of the importance of identifying the time course of regional glucose metabolic activity changes with increasing age during the development period, whether or not it is affected by the fact that these children have been deprived of auditory sensory input. Since it has been well known that sex steroid hormones influence brain developments both in function and structure (Cameron, 2001), we also examined if there was a sex difference in the rate of changes in FDG uptake with increasing age during developmental years in these children.

In this study, we examined age-associated changes in FDG uptake using a large size of the deaf children cohort (N = 87). Linear or nonlinear age-associated changes in glucose metabolism in children's brain during developmental years (1–15 years) were studied both with voxel-based analysis and with volume of interests (VOI) analyses using objective and probabilistic VOIs. We modeled a sex difference between a group of male (N = 44) and a group of female (N = 43) children as well as ages in those analyses.

Since it is practically difficult to have PET data from group of normal children, we would not be able to compare the deaf developmental changes with the normal developmental changes.

In summary, the goal of this study is to understand general changes of the brain metabolic activity with increasing ages and sex difference in these changes in the deaf children of developmental ages (from 1 to 15 years old).

Section snippets

Materials and methods

FDG PET was performed on deaf patients as a clinical presurgical evaluation in the Seoul National University Hospital. Informed consent was obtained from the parents or guardians after explaining the procedure, risk, and purpose/benefit of the FDG PET study, which was performed as a preoperative evaluation to predict postsurgical outcome. A total of 87 children with early onset deaf were included. Early deaf are those who were born deaf or became deaf early in life (before or around the time of

Objective VOI analysis results

Of the 98 regions of interests, five gray matter regions showed linear relation between FDG uptake and age (Table 2). Inferior frontal gyrus both in left (Fig. 1A) and right hemisphere and right medial frontal region were found to be positively correlated with age.

Counts of right inferior temporal gyrus (Fig. 1B) and bilateral parahippocampal gyri were negatively correlated with age. Five white matter regions in both hemispheres showed linear relations with age, including corpus callosum, left

Discussion

Our findings reveal that some areas show increased FDG uptake during developmental ageing in deaf children using two different objective methods, namely, objective VOI analysis and voxel-based analysis. Both analyses suggested that relative FDG uptake in the inferior frontal gyri in both hemispheres and in the right dorsomedial frontal gyrus increased as the children got older. Additional analyses modeling sex difference revealed that the age-associated changes in the right dorsomedial frontal

Acknowledgements

This study was supported by the Basic Atomic Energy Research Institute Project of the Ministry of Science and Technology and KOSEF project (R01-2002-000-00346-0).

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