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Despite a near 1⁄3 comorbidity rate between ASD and pediatric epilepsy, a cause or direct correlation remains an enigma. Because neither disease is fully understood, it is impossible to track how and where epilepsy overlaps with Autism. However, in the past several decades, researchers have begun to map the impossible through the advances of various imaging studies.
Several of these studies have identified the amygdala as a potential source of overlap. Supporting the amygdala theory of autism, that abnormalities in this nuclei cluster responsible for the emotional-memory association, cause some of the behavioral deficiencies typical of autism is that many ASD patients who suffer from spontaneous seizures originate from the amygdala region (Gaigg). Additionally, Amygdala fulsifum cortex “showed inefficient performance by patients suffering from epilepsy and amygdala damage” on patients asked to identify objects by name, indicating a potential link between individuals with ASD and epilepsy (Khetrapai). Any deformation of this area can lead to a series of seizures, as a neuron’s failure to reach a synapse causes inefficient neural connections, thus instigating the wrong signals to be sent, causing a seizure (LeBlanc). Over time, these seizures change both the chemistry and structure of the brain, which alter the formation of regions such as the amygdala, making seizures increasingly likely.
Hippocampal abnormalities, in combination with the interconnectivity with the amygdala, are also accredited with relations to the coexistence of ASD and epilepsy. Thought to be the center of information consolidation, the hippocampus controls the autonomic nervous system. The hippocampus projects many neurons into the neocortex to dictate spatial awareness and fine motor control. When this region is “inwardly deformed”, neurons inherently fail to synapse, thus instigating a similar cycle of seizure and damage (Desrosiers). Interestingly, hippocampal and amygdalar damage in epileptic patients with autism often presents itself
through seizures originating in the prefrontal cortex (Khetrapai). This would have to be due to the neural pathways, potentially damaged by the inflammation caused by this sort of deformity and the duration of synapses during this travel, resulting in a failure in the prefrontal cortex region (Mazarati).
Not surprisingly, several studies have revealed that certain regions of the brain are underactive, while others are over. While inward damage to the amygdala and hippocampus suggests underactivity, MRI scans and other tests have identified over-zealous occipital and parietal cortex activation (DeRamus). The overactivation of any region, especially major parts involved with the production and release of excitatory neurotransmitters such as lobes, can contribute to unexplained seizures. As excessive neurons are fired and send messages throughout the nervous system, those that fire too quickly or too slowly or are affected by external membrane changes fail to synapse, sending misinformation throughout the brain, instigating a seizure.
Other topics of interest within the realm of the comorbidity of ASD and pediatric epilepsy include genes, neurotransmitters, and even cannabinoid receptors (Rosenburg). While these three topics warrant their own intersectional research study and are far too complex to ascertain through a brief summary, they pose interesting questions for the future of neuro abnormalities, specifically these two enigmatic disorders. The way in which cannabinoid receptors are more susceptible to damage and chemical changes involves the processes by which neurotransmitters, specifically GABA and glutamate, are processed and fused. Genetics plays a chief role in this process, thus denoting yet another perpetuating cycle of the unknown (Varcin).
Sources Consulted
Baird, G., Cass, H., & Slonims, V. (2003). Diagnosis Of Autism. BMJ: British Medical Journal,
327(7413), 488-493. Retrieved February 9, 2021, from
http://www.jstor.org/stable/25455385
Chaddad, A., Desrosiers, C., Hassan, L. et al. Hippocampus and amygdala radiomic biomarkers for the study of autism spectrum disorder. BMC Neurosci 18, 52 (2017). https://doi.org/10.1186/s12868-017-0373-0
Cui, W., Kobau, R., Zack, M., Helmers, S., & Yeargin-Allsopp, M. (2015). Seizures in Children and Adolescents Aged 6–17 Years — United States, 2010–2014. Morbidity and Mortality Weekly Report,64(43), 1209-1214. Retrieved February 9, 2021, from https://www.jstor.org/stable/24856867
DeRamus, T. P., Black, B. S., Pennick, M. R., & Kana, R. K. (2014). Enhanced parietal cortex activation during location detection in children with autism. Journal of neurodevelopmental disorders, 6(1), 37. https://doi.org/10.1186/1866-1955-6-37
Gaigg, Sebastian B. Differential fear conditioning in Asperger's syndrome: Implications for an amygdala theory of autism, Neuropsychologia, Volume 45, Issue 9, 2007, Pages 2125-2134, ISSN 0028-3932, https://doi.org/10.1016/j.neuropsychologia.2007.01.012.
Guo, B., Chen, J., Chen, Q. et al. Anterior cingulate cortex dysfunction underlies social deficits in Shank3 mutant mice. Nat Neurosci 22, 1223–1234 (2019).
https://doi.org/10.1038/s41593-019-0445-9
Khetrapal N. (2010). Overlap of autism and seizures: understanding cognitive comorbidity. Mens sana monographs, 8(1), 122–128. https://doi.org/10.4103/0973-1229.58823
LeBlanc JJ, Fagiolini M. Autism: a "critical period" disorder? Neural Plast. 2011;2011:921680. doi: 10.1155/2011/921680. Epub 2011 Aug 3. PMID: 21826280; PMCID: PMC3150222.
Margari, L., De Giacomo, A., Craig, F., Palumbi, R., Peschechera, A., Margari, M., Picardi, F., Caldarola, M., Maghenzani, M. A., & Dicuonzo, F. (2018). Frontal lobe metabolic alterations in autism spectrum disorder: a 1H-magnetic resonance spectroscopy study. Neuropsychiatric disease and treatment, 14, 1871–1876.https://doi.org/10.2147/NDT.S165375
Mazarati, A.M., Lewis, M.L. and Pittman, Q.J. (2017), Neurobehavioral comorbidities of epilepsy: Role of inflammation. Epilepsia, 58: 48-56.
https://doi.org/10.1111/epi.13786
Minshew, N. J., & Williams, D. L. (2007). The new neurobiology of autism: cortex, connectivity, and neuronal organization. Archives of neurology, 64(7), 945–950. https://doi.org/10.1001/archneur.64.7.945
Rosenberg, A., Patterson, J., & Angelaki, D. (2015). A computational perspective on autism.
Proceedings of the National Academy of Sciences of the United States of America, 112(30), 9158-9165. Retrieved February 9, 2021, from https://www.jstor.org/stable/26464161
Subramanian K, Brandenburg C, Orsati F, Soghomonian JJ, Hussman JP, Blatt GJ. Basal ganglia and autism - a translational perspective. Autism Res. 2017
Nov;10(11):1751-1775. doi: 10.1002/aur.1837. Epub 2017 Jul 21. PMID:
28730641
Varcin, K. J., & Nelson, C. A., 3rd (2016). A developmental neuroscience approach to the search for biomarkers in autism spectrum disorder. Current opinion in neurology, 29(2), 123–129. https://doi.org/10.1097/WCO.0000000000000298
Wakefield, J. (2002). New Centers to Focus on Autism and Other Developmental Disorders. Environmental Health Perspectives, 110(1), A20-A21. Retrieved February 9, 2021, from http://www.jstor.org/stable/3455285
Zhou, Y., Shi, L., Cui, X., Wang, S., & Luo, X. (2016). Functional Connectivity of the Caudal Anterior Cingulate Cortex Is Decreased in Autism. PloS one, 11(3), e0151879. https://doi.org/10.1371/journal.pone.0151879
Several of these studies have identified the amygdala as a potential source of overlap. Supporting the amygdala theory of autism, that abnormalities in this nuclei cluster responsible for the emotional-memory association, cause some of the behavioral deficiencies typical of autism is that many ASD patients who suffer from spontaneous seizures originate from the amygdala region (Gaigg). Additionally, Amygdala fulsifum cortex “showed inefficient performance by patients suffering from epilepsy and amygdala damage” on patients asked to identify objects by name, indicating a potential link between individuals with ASD and epilepsy (Khetrapai). Any deformation of this area can lead to a series of seizures, as a neuron’s failure to reach a synapse causes inefficient neural connections, thus instigating the wrong signals to be sent, causing a seizure (LeBlanc). Over time, these seizures change both the chemistry and structure of the brain, which alter the formation of regions such as the amygdala, making seizures increasingly likely.
Hippocampal abnormalities, in combination with the interconnectivity with the amygdala, are also accredited with relations to the coexistence of ASD and epilepsy. Thought to be the center of information consolidation, the hippocampus controls the autonomic nervous system. The hippocampus projects many neurons into the neocortex to dictate spatial awareness and fine motor control. When this region is “inwardly deformed”, neurons inherently fail to synapse, thus instigating a similar cycle of seizure and damage (Desrosiers). Interestingly, hippocampal and amygdalar damage in epileptic patients with autism often presents itself
through seizures originating in the prefrontal cortex (Khetrapai). This would have to be due to the neural pathways, potentially damaged by the inflammation caused by this sort of deformity and the duration of synapses during this travel, resulting in a failure in the prefrontal cortex region (Mazarati).
Not surprisingly, several studies have revealed that certain regions of the brain are underactive, while others are over. While inward damage to the amygdala and hippocampus suggests underactivity, MRI scans and other tests have identified over-zealous occipital and parietal cortex activation (DeRamus). The overactivation of any region, especially major parts involved with the production and release of excitatory neurotransmitters such as lobes, can contribute to unexplained seizures. As excessive neurons are fired and send messages throughout the nervous system, those that fire too quickly or too slowly or are affected by external membrane changes fail to synapse, sending misinformation throughout the brain, instigating a seizure.
Other topics of interest within the realm of the comorbidity of ASD and pediatric epilepsy include genes, neurotransmitters, and even cannabinoid receptors (Rosenburg). While these three topics warrant their own intersectional research study and are far too complex to ascertain through a brief summary, they pose interesting questions for the future of neuro abnormalities, specifically these two enigmatic disorders. The way in which cannabinoid receptors are more susceptible to damage and chemical changes involves the processes by which neurotransmitters, specifically GABA and glutamate, are processed and fused. Genetics plays a chief role in this process, thus denoting yet another perpetuating cycle of the unknown (Varcin).
Sources Consulted
Baird, G., Cass, H., & Slonims, V. (2003). Diagnosis Of Autism. BMJ: British Medical Journal,
327(7413), 488-493. Retrieved February 9, 2021, from
http://www.jstor.org/stable/25455385
Chaddad, A., Desrosiers, C., Hassan, L. et al. Hippocampus and amygdala radiomic biomarkers for the study of autism spectrum disorder. BMC Neurosci 18, 52 (2017). https://doi.org/10.1186/s12868-017-0373-0
Cui, W., Kobau, R., Zack, M., Helmers, S., & Yeargin-Allsopp, M. (2015). Seizures in Children and Adolescents Aged 6–17 Years — United States, 2010–2014. Morbidity and Mortality Weekly Report,64(43), 1209-1214. Retrieved February 9, 2021, from https://www.jstor.org/stable/24856867
DeRamus, T. P., Black, B. S., Pennick, M. R., & Kana, R. K. (2014). Enhanced parietal cortex activation during location detection in children with autism. Journal of neurodevelopmental disorders, 6(1), 37. https://doi.org/10.1186/1866-1955-6-37
Gaigg, Sebastian B. Differential fear conditioning in Asperger's syndrome: Implications for an amygdala theory of autism, Neuropsychologia, Volume 45, Issue 9, 2007, Pages 2125-2134, ISSN 0028-3932, https://doi.org/10.1016/j.neuropsychologia.2007.01.012.
Guo, B., Chen, J., Chen, Q. et al. Anterior cingulate cortex dysfunction underlies social deficits in Shank3 mutant mice. Nat Neurosci 22, 1223–1234 (2019).
https://doi.org/10.1038/s41593-019-0445-9
Khetrapal N. (2010). Overlap of autism and seizures: understanding cognitive comorbidity. Mens sana monographs, 8(1), 122–128. https://doi.org/10.4103/0973-1229.58823
LeBlanc JJ, Fagiolini M. Autism: a "critical period" disorder? Neural Plast. 2011;2011:921680. doi: 10.1155/2011/921680. Epub 2011 Aug 3. PMID: 21826280; PMCID: PMC3150222.
Margari, L., De Giacomo, A., Craig, F., Palumbi, R., Peschechera, A., Margari, M., Picardi, F., Caldarola, M., Maghenzani, M. A., & Dicuonzo, F. (2018). Frontal lobe metabolic alterations in autism spectrum disorder: a 1H-magnetic resonance spectroscopy study. Neuropsychiatric disease and treatment, 14, 1871–1876.https://doi.org/10.2147/NDT.S165375
Mazarati, A.M., Lewis, M.L. and Pittman, Q.J. (2017), Neurobehavioral comorbidities of epilepsy: Role of inflammation. Epilepsia, 58: 48-56.
https://doi.org/10.1111/epi.13786
Minshew, N. J., & Williams, D. L. (2007). The new neurobiology of autism: cortex, connectivity, and neuronal organization. Archives of neurology, 64(7), 945–950. https://doi.org/10.1001/archneur.64.7.945
Rosenberg, A., Patterson, J., & Angelaki, D. (2015). A computational perspective on autism.
Proceedings of the National Academy of Sciences of the United States of America, 112(30), 9158-9165. Retrieved February 9, 2021, from https://www.jstor.org/stable/26464161
Subramanian K, Brandenburg C, Orsati F, Soghomonian JJ, Hussman JP, Blatt GJ. Basal ganglia and autism - a translational perspective. Autism Res. 2017
Nov;10(11):1751-1775. doi: 10.1002/aur.1837. Epub 2017 Jul 21. PMID:
28730641
Varcin, K. J., & Nelson, C. A., 3rd (2016). A developmental neuroscience approach to the search for biomarkers in autism spectrum disorder. Current opinion in neurology, 29(2), 123–129. https://doi.org/10.1097/WCO.0000000000000298
Wakefield, J. (2002). New Centers to Focus on Autism and Other Developmental Disorders. Environmental Health Perspectives, 110(1), A20-A21. Retrieved February 9, 2021, from http://www.jstor.org/stable/3455285
Zhou, Y., Shi, L., Cui, X., Wang, S., & Luo, X. (2016). Functional Connectivity of the Caudal Anterior Cingulate Cortex Is Decreased in Autism. PloS one, 11(3), e0151879. https://doi.org/10.1371/journal.pone.0151879