A two-year longitudinal pilot MRI study of the brainstem in autism.
Child Neuroscience Laboratory, Child Study Center, Yale School of Medicine
Research has demonstrated the potential role of the brainstem in the pathobiology of autism.
Previous studies have suggested reductions in brainstem volume and a relationship between this structure and sensory abnormalities. However, little is known regarding the developmental aspects of the brainstem across childhood and adolescence.
The goal of this pilot study was to examine brainstem development via MRI volumetry using a longitudinal research design.
Participants included 23 boys with autism and 23 matched controls (age range=7-17 years), all without intellectual disability. Participants underwent structural MRI scans once at baseline and again at two-year follow-up. Brainstem volumetric measurements were performed using the BRAINS2 software package.
There were no significant group differences in age, gender, handedness, and total brain volume; however, full-scale IQ was higher in controls.
Autism and control groups showed different patterns of growth in brainstem volume.
While whole brainstem volume remained stable in controls over the two-year period, the autism group showed increases with age reaching volumes comparable to controls by age 15 years.
This increase of whole brainstem volume was primarily driven by bilateral increases in gray matter volume.
Findings from this preliminary study are suggestive of developmental brainstem abnormalities in autism primarily involving gray matter structures.
These findings are consistent with autism being conceptualized as a neurodevelopmental disorder with alterations in brain-growth trajectories.
More longitudinal MRI studies are needed integrating longitudinal cognitive/behavioral data to confirm and elucidate the clinical significance of these atypical growth patterns.
Further Readings of Interest
Grey matter is made up of neuronal cell bodies. The grey matter includes regions of the brain involved in muscle control, sensory perception such as seeing and hearing, memory, emotions, and speech.
Brain enlargement and increased behavioral and cytokine reactivity in infant monkeys following acute prenatal endotoxemia.
Harlow Primate Laboratory, University of Wisconsin
Infections and inflammatory conditions during pregnancy can dysregulate neural development and increase the risk for developing autism and schizophrenia.
The following research utilized a nonhuman primate model to investigate the potential impact of a mild endotoxemia during pregnancy on brain maturation and behavioral reactivity as well as the infants’ hormone and immune physiology.
Nine pregnant female rhesus monkeys (Macaca mulatta) were administered nanogram concentrations of lipopolysaccharide (LPS) on two consecutive days, 6 weeks before term, and their offspring were compared to nine control animals.
When tested under arousing challenge conditions, infants from the LPS pregnancies were more behaviorally disturbed, including a failure to show a normal attenuation of startle responses on tests of prepulse inhibition.
Examination of their brains at 1 year of age with magnetic resonance imaging (MRI) revealed the unexpected finding of a significant 8.8% increase in global white matter volume distributed across many cortical regions compared to controls.
More selective changes in regional gray matter volume and cortical thickness were noted in parietal, medial temporal, and frontal areas.
While inhibited neural growth has been described previously after prenatal infection and LPS administration at higher doses in rodents, this low dose endotoxemia in the monkey is the first paradigm to produce a neural phenotype associated with augmented gray and white matter growth.