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Use the link below to share a full-text version of this article with your friends and colleagues. Learn more. Previous research indicates disruption of learning and memory in children who have experienced traumatic brain injury TBI. This research evaluates the impact of pediatric TBI on volumetric differences along the long axis of the hippocampus, a region of the brain that is critical for explicit memory.

Total hippocampal volume and hippocampal subregion volumes corresponding to hippocampal head, body, and tail were compared across groups and were examined in relation to verbal and visual memory. Analysis restricted to the TBI group indicated that hippocampal head volume was associated with severity of injury. Correlations between memory performance and hippocampal tail volume were not significant for the TBI or TDC groups, although for the EI group, a positive correlation was found between hippocampal tail volume and memory.

Together these results underscore an important relation between hippocampal structure and memory function during the subacute stage of recovery from pediatric TBI. Memory is one of several important cognitive aptitudes affected by pediatric traumatic brain injury TBI. TBI sustained during the childhood or adolescent years is particularly concerning because of the potential for disruption in the typical course of brain development and the cascading effects on other cognitive aptitudes.

The goal of the present research was to determine the impact of pediatric TBI on verbal and visual memory in relation to volume of the hippocampus, a region of the brain that is critical for explicit memory. Considering findings showing that the hippocampus continues to develop into adolescence with findings indicating that hippocampal development might be susceptible to common variation in environment, it is important to evaluate variation in hippocampal development in relation to neuropsychological outcomes related to memory. However, it remains unclear how TBI sustained during childhood disrupts the normal course of development of the hippocampus, and whether disruption of hippocampal development results in impaired memory aptitude.

Fetal Hippocampal Development: Analysis by Magnetic Resonance Imaging Volumetry

Taken together, these behavioral findings suggest that moderate to severe TBI often results in pervasive and chronic memory deficits. Taken together these findings indicate that rather than diffuse injury, which would impact the entire hippocampal formation, in the months following injury, TBI may selectively affect anterior regions of the hippocampus corresponding to the hippocampal head. However, cognitive performance in this study was operationalized as a linear composite of processing speed, working memory, verbal learning, and cognitive switching skills, rather than focusing specifically on memory performance.

The influence of age at the time of brain injury on specific structures and abilities is not well understood. However, to the best of our knowledge, the relation between volumetric variation along the long axis of the hippocampus and memory in children with TBI has not been investigated. Our investigation was guided by three hypotheses. Finally, we hypothesized that group differences in relations between hippocampal volume and performance on memory tests will be apparent. Specifically, we expect that the TBI group would show a positive relation between hippocampal volume, particularly in head regions, and memory performance.

The injury groups i. The TDC participants were recruited from the same community as TBI and EI participants by advertising with flyers in locations frequented by parents and attending local civic events. To account for these preinjury characteristics and postinjury factors, children with history of EI were included as a comparison injury group.

An additional benefit of including an EI patient group is the opportunity to differentiate effects specifically related to injury to the brain from the consequences of injury in general. Typically developing children were recruited from community notices and met inclusion criteria 2—7.

Baby’s Brain Begins Now: Conception to Age 3 | Urban Child Institute

We calculated a total ISS score and an ISS score excluding injury to the head which verified that the EI group did not have evidence of trauma to the head or concussion symptoms. Participants were recruited during or shortly following the initial hospital visit. Informed written consent was obtained from the child's guardian according to Institutional Review Board guidelines.

Written assent was obtained from all participants prior to data collection. For each participant, behavioral testing was conducted on the day of MRI data acquisition prior to scanning. Scaled scores corrected for age were used in all analyses. During the VSR task, participants were asked to learn a spatial dot pattern over the course of several trials. Participants were given reminders on missed sequences until the pattern was produced correctly, or after five unsuccessful attempts had elapsed.

During the WSR Immediate condition, participants were presented with a series of words and asked to repeat the list of words to the examiner. If a participant failed to report a word from the list, the experimenter would provide a reminder for the word and the participant was then asked to begin the list again. This was repeated for six trials or until the list was recalled correctly.

The scanning facility replaced the scanner with a Philips 3T Ingenia toward end of data collection and as a result 13 of our participants were collected after the upgrade. To account for differences in scanner, we included scanner change as a covariate in all analysis including MRI data. Cortical and subcortical volumes were first segmented with FreeSurfer version 5. Following pre and postprocessing in FreeSurfer, manual inspection of automated segmentation of the hippocampus was conducted and if required, corrections of hippocampal boundaries were made.

To further segment the hippocampal formation along the anterior to posterior axis, the hippocampi were manually parcellated into head, body, and tail regions using the Freesurfer tkmedit tool for visualization.

Introduction

Moving to posterior hippocampus, the body of the hippocampus is segmented from the tail of the hippocampus at the point where the fornix is visible indicating that the fornix is separating from hippocampus proper. In left and right hemispheres, intraclass coefficient above. To evaluate whether total and regional hippocampal volumes differed across groups, we first examined difference in volume of the hippocampal structure as a whole. As these are ordinal scales, Spearman Rank order correlations were used to assess injury severity in relation to memory scores as well as total and regional hippocampal volumes.

Finally, Pearson correlations were used to determine if hippocampal volume was related to memory scores for each group separately. However, there are no prior volumetric studies of the fetal hippocampus for comparison. Thus, our study provides initial data on fetal hippocampal volume during the second and third trimesters of gestation.

Interestingly, if we assume a continued linear increase in THV during the gestational period of weeks, then THV in our study is lower than hippocampal volumes reported in two neonatal hippocampal volumetric studies 30 , It is likely that this difference between fetal and neonatal hippocampal volumes is, in part, due to adaptations that were needed in order to deal with the unique features of the fetal brain and fetal MR images.

Thus, the hippocampal volumes in our study were obtained using different methodology. It also possible, however, that the growth of the hippocampus in the late third trimester may be more rapid than the growth that we observed between gestational weeks. Because of this, our results can only be applied to fetuses between 21 to 31 gestational weeks, and cannot be extrapolated beyond 31 gestational weeks. Further studies in older fetuses are needed to determine the growth rate of the hippocampus during later gestational ages.

In the current study, we did not observe a significant difference between THV and sex of the fetus. This is consistent with the findings of Thompson et al. Interestingly, several adult studies have shown that the volume of the hippocampus is larger in men than in women 27 , which suggests that these changes occur later. We also did not observe a significant difference between left and right hippocampal volumes, which differs from pediatric studies which have found larger hippocampal volumes on the right as early as term equivalent age 28 , 31 - It may be that in the fetal population the difference in right and left hippocampal volume is too small to be detected with the current technology or that this difference occurs at a later stage of development.

Although we were able to successfully segment the hippocampus and demonstrate an increase in hippocampal volume with increasing gestational age, our study has several technical limitations. These include limitations inherent to fetal MRI such as fetal movement, small size of imaged structures and the large distance between the fetus and the receiver coil Furthermore, we chose to segment the hippocampus based on reconstructed 3D images rather than based on 2D images.

Indeed, 2D images are variable in their slice orientation due to the effects of normal fetal motion, and segmentation of structures would be prone to significant errors. Using reconstructed 3D MR images, we were able to reformat the brain in the sagittal, axial and coronal planes, and use these planes to reliably segment the hippocampus in the same manner for all subjects.

Fetal Hippocampal Development: Analysis by Magnetic Resonance Imaging Volumetry

Our study was also limited by tissue contrast. At times segmentation and discrimination of two adjacent structures were limited by contrast resolution. This occurred, for example, when trying to segment the hippocampal formation from the germinal matrix, which is unique to the developing fetal brain. Involution of the germinal matrix begins late in the second trimester and is almost complete by term In the younger fetus the germinal matrix is present and appears hypointense on T2 images. Below 28 weeks gestation in most cases it was indistinguishable from the hippocampus on coronal sections, however it could be easily identified on sagittal sections and by following the wall of the ventricles.

However, in certain cases where differentiation was difficult, segmentation was achieved by changing the intensity of the image, which usually revealed a demarcation between the two structures with the germinal matrix being more hypointense than the hippocampal formation. When any ambiguity still persisted, we chose to include the entire area in the segmentation, which may have resulted in a slight overestimation in some cases. Using a different echo time may better distinguish the boundary of the germinal matrix and adjacent hippocampus depending on the gestational age, however, we were not able to vary echo times due to the inherent low signal to noise nature fetal MR as well as scan time considerations.

Although we focused on a limited 10 week gestational period between weeks , our study was limited by our small sample size which may have affected our ability to detect differences in hippocampal volume by gender or sidedness. Although right and left hippocampal segmentations were reviewed with a pediatric radiologist in a random order, our ability to detect differences in hippocampal volume by sidedness may have also been limited by the fact that we consistently segmented the right hippocampus first.

Additional studies, using a larger number of patients, with random order of hippocampal segmentation is needed to further explore where there are indeed no differences in hippocampal sidedness or gender volume during this gestational period. In summary, using 3D reconstructed fetal MR images, we were able to adapt previous hippocampal segmentation methodology to segment the fetal hippocampus.

We observed a progressive increase in the volume of the hippocampus during the second and third trimesters. This normative data can now be used for comparative studies of conditions suspected to affect in utero hippocampal development, such as intrauterine growth retardation and congenital brain malformations, and can be correlated with neurodevelopmental outcome measures such as learning and memory. We would like to thank Ms. Addison Cuneo for her logistical help, as well as the volunteers who participated in this study.

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Background

The hippocampal formation plays an important role in learning and memory; however, data on its development in utero in humans are limited. This study was performed to evaluate hippocampal development in healthy fetuses using 3D reconstructed MRI. Total hippocampal volume was calculated for each subject and compared against GA.


  1. Antennas for VHF and UHF (BP).
  2. 1. Introduction.
  3. Longitudinal development of hippocampal subregions from childhood to adulthood;

The snippet could not be located in the article text. This may be because the snippet appears in a figure legend, contains special characters or spans different sections of the article. Pediatr Res. Author manuscript; available in PMC May 1. PMID: Division of Pediatric Neurology [F.

Corresponding Author: Orit A. Glenn, M. Copyright notice. The publisher's final edited version of this article is available at Pediatr Res. See other articles in PMC that cite the published article. Abstract The hippocampal formation plays an important role in learning and memory, however data on its development in utero in humans is limited. Introduction The hippocampal formation plays an important role in the cognitive function of learning and memory 1. Methods Subjects A cohort of 20 healthy pregnant women underwent prenatal MRI without maternal or fetal sedation.

Data analysis Right and left hippocampal volumes were compared using a paired t-test, using a significance level of 0. Results Sagittal, coronal, and axial hippocampal images are shown in Figure 1 , illustrating segmentations of the left and right hippocampus of a fetus at 28 weeks gestation. Open in a separate window. Figure 1. Figure 2. Figure 3. Table 1 Estimated Total Hippocampal Volume based on gestational age.

Gestational Age weeks Average Volume mL 22 0.

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Figure 4. Discussion In vivo prenatal MRI is a non-invasive technique that enables us to study the development of the brain throughout gestation. Acknowledgments We would like to thank Ms. References 1. Memory deficits characterized by patterns of lesions to the hippocampus and parahippocampal cortex.

Ann N Y Acad Sci. Impact of intrauterine growth restriction and glucocorticoids on brain development: insights using advanced magnetic resonance imaging. Mol Cell Endocrinol. Kuchna I. Quantitative studies of human newborns' hippocampal pyramidal cells after perinatal hypoxia. Previous research indicates disruption of learning and memory in children who have experienced traumatic brain injury TBI. This research evaluates the impact of pediatric TBI on volumetric differences along the long axis of the hippocampus, a region of the brain that is critical for explicit memory.

Total hippocampal volume and hippocampal subregion volumes corresponding to hippocampal head, body, and tail were compared across groups and were examined in relation to verbal and visual memory. Analysis restricted to the TBI group indicated that hippocampal head volume was associated with severity of injury. Correlations between memory performance and hippocampal tail volume were not significant for the TBI or TDC groups, although for the EI group, a positive correlation was found between hippocampal tail volume and memory.

Together these results underscore an important relation between hippocampal structure and memory function during the subacute stage of recovery from pediatric TBI. Memory is one of several important cognitive aptitudes affected by pediatric traumatic brain injury TBI. TBI sustained during the childhood or adolescent years is particularly concerning because of the potential for disruption in the typical course of brain development and the cascading effects on other cognitive aptitudes. The goal of the present research was to determine the impact of pediatric TBI on verbal and visual memory in relation to volume of the hippocampus, a region of the brain that is critical for explicit memory.

Considering findings showing that the hippocampus continues to develop into adolescence with findings indicating that hippocampal development might be susceptible to common variation in environment, it is important to evaluate variation in hippocampal development in relation to neuropsychological outcomes related to memory. However, it remains unclear how TBI sustained during childhood disrupts the normal course of development of the hippocampus, and whether disruption of hippocampal development results in impaired memory aptitude.

Taken together, these behavioral findings suggest that moderate to severe TBI often results in pervasive and chronic memory deficits. Taken together these findings indicate that rather than diffuse injury, which would impact the entire hippocampal formation, in the months following injury, TBI may selectively affect anterior regions of the hippocampus corresponding to the hippocampal head. However, cognitive performance in this study was operationalized as a linear composite of processing speed, working memory, verbal learning, and cognitive switching skills, rather than focusing specifically on memory performance.

The influence of age at the time of brain injury on specific structures and abilities is not well understood. However, to the best of our knowledge, the relation between volumetric variation along the long axis of the hippocampus and memory in children with TBI has not been investigated. Our investigation was guided by three hypotheses. Finally, we hypothesized that group differences in relations between hippocampal volume and performance on memory tests will be apparent.

Specifically, we expect that the TBI group would show a positive relation between hippocampal volume, particularly in head regions, and memory performance. The injury groups i. The TDC participants were recruited from the same community as TBI and EI participants by advertising with flyers in locations frequented by parents and attending local civic events. To account for these preinjury characteristics and postinjury factors, children with history of EI were included as a comparison injury group.

An additional benefit of including an EI patient group is the opportunity to differentiate effects specifically related to injury to the brain from the consequences of injury in general. Typically developing children were recruited from community notices and met inclusion criteria 2—7. We calculated a total ISS score and an ISS score excluding injury to the head which verified that the EI group did not have evidence of trauma to the head or concussion symptoms. Participants were recruited during or shortly following the initial hospital visit.

Informed written consent was obtained from the child's guardian according to Institutional Review Board guidelines. Written assent was obtained from all participants prior to data collection. For each participant, behavioral testing was conducted on the day of MRI data acquisition prior to scanning. Scaled scores corrected for age were used in all analyses. During the VSR task, participants were asked to learn a spatial dot pattern over the course of several trials.

Participants were given reminders on missed sequences until the pattern was produced correctly, or after five unsuccessful attempts had elapsed. During the WSR Immediate condition, participants were presented with a series of words and asked to repeat the list of words to the examiner. If a participant failed to report a word from the list, the experimenter would provide a reminder for the word and the participant was then asked to begin the list again.

This was repeated for six trials or until the list was recalled correctly. The scanning facility replaced the scanner with a Philips 3T Ingenia toward end of data collection and as a result 13 of our participants were collected after the upgrade. To account for differences in scanner, we included scanner change as a covariate in all analysis including MRI data.

Cortical and subcortical volumes were first segmented with FreeSurfer version 5. Following pre and postprocessing in FreeSurfer, manual inspection of automated segmentation of the hippocampus was conducted and if required, corrections of hippocampal boundaries were made. To further segment the hippocampal formation along the anterior to posterior axis, the hippocampi were manually parcellated into head, body, and tail regions using the Freesurfer tkmedit tool for visualization. Moving to posterior hippocampus, the body of the hippocampus is segmented from the tail of the hippocampus at the point where the fornix is visible indicating that the fornix is separating from hippocampus proper.

In left and right hemispheres, intraclass coefficient above. To evaluate whether total and regional hippocampal volumes differed across groups, we first examined difference in volume of the hippocampal structure as a whole. As these are ordinal scales, Spearman Rank order correlations were used to assess injury severity in relation to memory scores as well as total and regional hippocampal volumes. Finally, Pearson correlations were used to determine if hippocampal volume was related to memory scores for each group separately.

For correlation analyses residual scores accounting for maternal education were calculated for each scaled TOMAL2 task score. For hippocampal volume scores, demographic and age effects were accounted for by calculating residual scores for hippocampus as a whole and hippocampal subregion volumes with the effects of maternal education, age, total brain volume, and scanner change removed.