Cheng En Lee1, Kay Laura Sindabizera1, Ruolin Li1,2, Wentao Wu1,2, Minhui Ouyang1,3, and Hao Huang1,3
1Department of Radiology, Children's Hospital of Philadelphia, Philadelphia, PA, United States, 2Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, United States, 3Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States
Synopsis
Keywords: Gray Matter, Brain, Screening, Infant, Early Development, Structural MRI
Motivation: Human brain development is suggested to rely on a complex interplay between biological and environmental factors. For the latter, socioeconomic status (SES) and parental stress can significantly impact the development of cognitive and social skills. However, their links to infant brain development are not well understood.
Goal(s): Our goal is to identify regional brain development critically affected by environmental influences.
Approach: High-resolution structural MRI of 95 infants aged 0-22 months, and the corresponding SES, and parental perceived stress scales (PSS) were utilized to investigate how they are associated.
Results: Higher SES is associated with larger volumes in prefrontal cortex and inferior frontal gyrus.
Impact: The significant,
positive correlations between socioeconomic status and prefrontal cortical,
inferior frontal gyral volume underscore environmental impact on brain
development during the critical period of infancy. Further investigation of brain
regions related to emotion, executive function, and memory is warranted.
Introduction
Infant brain
development is characterized by the most dynamic and rapid structural and
functional changes across the lifespan1,2. In addition to genetic
factors, the environmental contexts a person experiences also heavily
influences their cognitive development3,4. Previous studies showed
positive correlations between socioeconomic status (SES) and brain volume in
children5 and young adults6. Children from disadvantaged
socioeconomic backgrounds often have limited exposure to cognitive and
linguistic stimulation, impacting the development of prefrontal cortex and left
inferior frontal gyrus3,7. Additionally, increased stress in these households
also affects the development of hippocampus, amygdala, and thalamus which are
crucial for memory and social-emotional processing8. Hence, we hypothesized
that regional brain structural changes during infancy are affected by
environmental factors like SES and parental stress9,10. We measured
the amygdaloid, thalamic, hippocampal, left inferior fontal gyral, and
prefrontal cortical volumes of 95 infants using T1-weighted (T1w) MRI and
assessed their parental stress and SES through questionnaires. The goal of this
study is to investigate the association between specific brain structural
development and environmental factors in typical developing infants from 0 to 22
months.Methods
Participants and data
acquisition:
This study involved 95 typically developing infants comprising 53 females and
42 males, ranging from 0 to 22 months. Images were acquired using a 3.0T
Siemens Prisma scanner. T1w images were obtained using the MPRAGE sequence,
featuring a voxel size of 0.8mm isotropic. The T1w imaging parameters included TR/TE/TI
of 2400/2.24/1060ms, a field of view (FOV) of 256 × 240 mm², an acquisition
matrix of 320 x 300, and slice thickness of 0.8 mm. The acquisition of the T1w
images took 6.38 minutes.
Parental questionnaires: Parents of the infants
were asked to complete questionnaires on SES and perceived stress using the
Perceived Stress Scale (PSS). SES, based on parental education and occupation,
was quantified using the Amherst modification of the Hollingshead two-factor
index11. The PSS questionnaire contains 10 items measuring whether
caregivers perceive life as unpredictable, uncontrollable, or overloading in
the past month. Responses ranged from 0 (never) to 4 (very often). Total stress
was calculated by reverse-scoring and summing responses for questions 4, 5, 7,
8. Scores ranged from 0 to 40, with higher scores indicating greater perceived
stress12.
Data analysis: The T1w images of all
infants were segmented using Infant FreeSurfer13. The following regional
brain volumes were calculated based on the segmentation results: thalamus, amygdala,
hippocampus, left inferior frontal gyrus, and prefrontal cortex. The left inferior
frontal gyral volume was obtained by summing up the pars opercularis, pars
orbitalis and pars triangularis. As for the prefrontal cortex volume, 9 brain
regions were added together: frontal pole, lateral orbitofrontal, medial
orbitofrontal, rostral middle frontal, superior frontal, caudal middle frontal,
and the left inferior frontal gyrus.
Statistical analyses were
conducted using R to investigate the associations between brain volumetric
measurements and age, SES, PSS, and sex using linear models. For a better fit,
the amygdaloid volume did not utilize a log scale for the age parameter.
$$Volume (i.e.,
volumetric measure) ~ β1 log(Age) + β2 SES + β3 PSS + β4 Sex + β0$$Results
Figure 1 showcases a representative
T1w infant at 12 months age, highlighting segmented brain regions including
limbic sub-regions, the left inferior frontal gyrus, and the prefrontal cortex.
Logarithmic scales were used to fit brain regions with age, except for the
amygdala which used a linear scale (Fig. 2). It is evident that all brain
regions exhibited positive associations (β>0) with SES (Fig. 3). Notably, significant
positive correlations were observed between SES and the left inferior frontal
gyrus (β1 = 34.74, p = 0.004) as well as the prefrontal cortex (β1 = 334.0, p =
0.001) (Figure 3B and C). Conversely, no significant correlations were found
between regional brain volumes and PSS (Fig. 4). However, it's worth noting
that a negative association (β<0) emerged between PSS and the hippocampus,
the left inferior frontal gyrus, and the prefrontal cortex.Discussion and Conclusion
Our findings
demonstrated that environmental factors such as parental stress and family SES
can influence brain structural development as early as and throughout infancy. Consistent
with previous literatures14, 15, regional brain volumes increased
rapidly during this early developmental period. SES showed a significant impact
on the left inferior frontal gyral and prefrontal cortical volumes, but less so
on the thalamus and hippocampus with no impact on the amygdala. Despite the
lack of significant correlation, lower perceived parental stress tends to be
associated with higher inferior frontal gyral and prefrontal cortical volume. The
analysis of the relationship between environmental factors and infant’s
neurodevelopmental outcomes is under way.Acknowledgements
This study is funded by NIH R01MH092535, R01MH125333,
R01EB031284, R01MH129981, R21MH123930 and P50HD105354.References
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