In the central nervous system the brainstem links the brain to the spinal cord. This anatomical structure is usually divided into different portions, from top to bottom, these are the midbrain, pons (meaning bridge), and medulla. Though small, relative to the size of the brain, the brainstem provides a conduit to sensory and motor projections, and to the majority of cranial nerves. In terms of function, the brainstem serves to modulate vegetative aspects of the body such as breathing, sleeping, and heart rate.
Many core symptoms of autism involve the person’s ability to process thoughts (so-called higher cognitive functions) and probably stem from deficits of the cerebral cortex. However, other symptoms such as diminished facial expression, hypersensitivity to sound and touch, and sleep disturbances could have an origin within the brainstem. In effect, a rare birth defect caused by the underdevelopment or absence of cranial nerves, Moebius syndrome, is usually associated with autism in 30 to 40% of cases.
The late Patricia Rodier, a Professor within the Departments of Obstetrics and Gynecology at the University of Rochester, examined sections of the brainstem of a single autistic individual and reported a shortened distance between some anatomical landmarks (i.e., trapezoid body and the inferior olive). Both the superior olivary and facial nuclei were absent.
Although Rodier’s work has not been reproduced by others (Thevarkunnel et al., 2004), it did serve to broaden our thinking perspective in regards to autism. Most importantly, her work served to emphasize the possibility that autism starts before a child is born. According to her findings autism starts at around the 4th week of fetal development. She gave as supporting evidence the fact that some thalidomide babies that develop an autistic phenotype have an external ear malformation and an uncommon form of strabismus (Duane syndrome) but no malformations of their limbs. The timing of these malformations was early during the first 20-24th days of gestation.
It is interesting to note that Dr. Rodier’s arguments made their way to the Omnibus Proceedings for Vaccination Safety where she acted as a witness for the government. Her own work and data collected from thalidomide and valproic acid babies suggested an insult early during brain development not consistent with the idea of mercury toxicity by vaccines. Dr. Rodier also expanded her work to report a variant of a gene (HOXA1) as an autism susceptibility gene. Defects in the HOXA1 gene in humans give rise to difficulties in eye movement, poor ventilatory movements, deafness, swallowing difficulties, paralysis of the muscles of the face, mental retardation, and developmental delay.
Following the lead offered by Rodier, other investigators examined the structure of the medial superior olivary nucleus in 5 autistic individuals and 2 neurotypicals (Kulesza and Mangunay, 2008). Each of the 5 autistic individuals showed significant differences in the morphology of the superior olivary nucleus (cell body area, cell body shape, and orientation). Unfortunately, the study had many weaknesses. Among the weaknesses in study design, both autistics and neurotypicals were not matched for age and one of the so-called autistic individuals appears with a diagnosis of Fragile X syndrome in the Autism Tissue Program database. I was also able to examine many of the brainstem sections used in the study and they were of poor quality and ultimately unreliable for the purpose of quantitation.
Another anatomical element of the brainstem that has been paid close attention is the locus coeruleus. The cluster of cells in this nucleus control, among many things, body temperature. A few years ago, based primarily on speculation, a theory arose that abnormalities in the regulation of the body’s thermostat by the locus coeruleus would lead to either improvements or exacerbations of autistic behaviors (see http://www.sciencedaily.com/releases/2009/04/090401145312.htm).
Two of the reported cases by Bailey et al. (1998) had abnormally dispersed cells in their locus coeruleus. A few years after the study by Bailey and colleagues, Martchek et al. (2006) used stereology to examine several neuronal parameters of this nucleus. No significant findings were reported.
Studies of the brainstem in autism have been few and far between. The presence of autonomic abnormalities in autism could easily have its genesis within the brainstem of affected individuals. Data derived from animal models, genetics, and neuroimaging (e.g., Hashimoto et a. 1995) suggests abnormalities of the brainstem in autism. However, initial results from postmortem series have used a handful of patients with faulty research designs. It is a pity that research into this area of the central nervous system has not attracted the attention it deserves.
Bailey, A., Luthert, P., Dean, A., Harding, B., Janota, I., Montgomery, M., Rutter, M., & Lantos, P. (1998). A clinicopathological study of autism. Brain, 121, 889–905.
Hashimoto T, Tayama M, Murakawa K, Yoshimoto T, Miyazaki M, Harada M, Kuroda Y.(1995) Development of the brainstem and cerebellum in autistic patients.J Autism Dev Disord,25(1):1-18.
Kulesza, R. J., & Mangunay, K. (2008). Morphological features of the medial superior olive in autism. Brain Research, 1200, 132–137.
Martchek, M., Thevarkunnel, S., Bauman, M., Blatt, G., & Kemper, T. (2006). Lack of evidence of neuropathology in the locus coeruleus in autism. Acta Neuropathologica, 111, 497–499.
Rodier, P. M., Ingram, J. L., Tisdale, B., Nelson, S., & Romano, J. (1996). Embryological origins for autism: Developmental abnormalities of the cranial nerve motor nuclei. Journal of Comparative Neurology, 370, 247–261.
Thevarkunnel, S., Martchek, M. A., Kemper, T. L., Bauman, M. L., & Blatt, G. J. (2004). A neuroanatomical study of the brainstem nuclei in autism. Abstracts: Society for Neuroscience, 1028.10.