yana-notes

Autism

5-13-2021 links: reference:

Autism #

Pruning/Neurogenesis #

  • Local hyperconnectivity and long-range hypoconnectivity and disconnection between neural circuits in ASD:
    • Why the frontal cortex in autism might be talking only to itself: local over-connectivity but long-distance disconnection (Courchesne 2005)
      • Neuroinflammatory reactions involving glial activation, migration defects and excess cerebral neurogenesis and/or defective apoptosis might generate frontal neural pathology early in development. It is hypothesized that these abnormal processes cause malformation and thus malfunction of frontal minicolumn microcircuitry.
      • Disorganized and inadequately selective. Toddlers have enlarged brain volumes [R](Early brain overgrowth in autism associated with an increase in cortical surface area before age 2 years), but this is not maintained; followed by slow/arrested growth: R
      • Frontal and temporal sulci are abnormally shifted superiorly and posteriorly in autistic children: Cortical sulcal maps in autism
      • Increased frontal cortical folding in autism: a preliminary MRI study frontal cortex gyrification.
      • Identified the presence of activated glia and neuroinflammatory response in frontal and cerebellar cortices
      • Reduced correlation of frontal cortex and parietal cortex activity, indicating impaired connection: R
      • Functional connectivity in an fMRI working memory task in high-functioning autism (Koshino 2004) n=28 (14 control)
        • Reduced activation of right DLPFC. Increased/decreased activation of the right/left inferior parietal lobe respectively. Greater temporal lobe activation.
        • Since verbal and nonverbal working memory is associated with left and right PFC, it’s possible they processed the task using visual codes instead of verbal.
    • Brain functional networks in syndromic and non-syndromic autism: a graph theoretical study of EEG connectivity (Peters 2013) pretty good; just corroborating the idea above.
    • Autism as a disorder of neural information processing: directions for research and targets for therapy (Belmonte et al. 2004)
      • Low signal-to-noise in developing neural assemblies?
      • The numbers of Purkinje cells, and to a lesser extent granule cells, in cerebellar cortex are abnormally low [16] —presum- ably leading to disinhibition of the cerebellar deep nuclei and consequent overexcitation of thalamus and cerebral cortex.
      • Neurons in hippocampus, amygdala, and other limbic regions are abnormally densely packed [16], [17] (unlike the Golgi analysis below)
      • Minicolumnar pathology in autism (Casanova 2003) smaller cortical minicolumns, and an increase in cell dispersion within minicolumns—characteristics that could increase the total number of them and thus the degree of connectivity between them. This could contribute to decreased signal-noise ratio.
      • An Artificial Neural Network Analogue of Learning in Autism (Cohen 1994) pretty good basic computational !Neuroscience.
        • Weights are modified in many systems according to a gradient descent rule which forces the network to find a configuration of weights in which the objective is to lead to a global minimum error solution in what is known as “weight space - this is the optimal state of a network. But local minima are undesirable, but thus noise facilitates pushing the network over such energy barriers. This is fascinating and surely is key for the Free Energy Principle:
        • 290 300
        • Children with autism are superior to controls in recognizing upside-down faces.
        • Savantism seen in people with e.g. eidetic memory could be excessive neurons in areas associated with learning, acquiring numerous unique details which end up interfering with discrimination->generalization.
        • However, some ASD children may lack neurons/connections in associative areas such as the amygdala and hippocampus, impairing discrimination->generalization (Raymond et al 1989)
          • Hippocampus in autism: a Golgi analysis (Raymond 1995) showed smaller and fewer dendritic branching of CA4 and CA1 neurons.
          • Yet, in the case of excessive hippocampal interconnectivity, you would see the spatial overfitting (like a room being completely different when one thing changes) another example of impaired ‘generalization’.
      • Abnormally high activity in stimulus-driven areas () and decreased activity in areas associated with higher-order processing ().
        • In the absence of a normally functional mechanism to bias sensory processing towards attended stimuli, all stimuli receive much the same degree of sensory evaluation, and the irrelevant stimuli must then be actively discarded in a manner that creates a processing bottleneck
FMRP #

Prenatal #

  • Things in the environment, or substances produced in reactions to environmental stress, that might cause autism, include prenatal and neonatal exposure to: Radiation, including isotopes from the power industry, bomb testing, Chernobyl, and Fukushima; Exposure to air pollution, including nitrogen oxides, ozone, carbon monoxide, sulfur dioxide, and particles (Jung, et al., 2013) Aluminum (Mold, et al., 2018), lead, mercury, manganese, arsenic, cadmium, chromium, nickel (Windham, et al., 2006) Acetaminophen, infections, endotoxin, endogenous and exogenous estrogens, hypothyroidism, Progesterone deficiency, Agmatine deficiency, serotonin excess, endogenous Nitric Oxide (Sweeten, et al., 2004) And Vitamin D deficiency. All of these have established associations with risk of autism. - Ray Peat - Autism and Causality (May 2018)
    • In contrast: Autism correlated with high prenatal Progestin exposure. R
  • Serotonin, pregnancy and increased autism prevalence: is there a link?
    • This study makes the case that prenatal hyperserotonemia actually leads to downregulation of 5HT terminal production, which leads to specific neuroanatomical defects. Not the impression I got reading the body of the study.

Neuroanatomy #

Neurotransmitters #

Serotonin #
Dopamine #

  • Elevated Homovanillic Acid (in the cerebrospinal fluid) R

    • Considering HVA is a Dopamine metabolite, degraded by COMT, it seems it’s likely due to a dysfunction of the dopaminergic system.

  • LGD targets in affected females significantly overlap the targets in males of lower intelligence quotient (IQ), but neither overlaps significantly with targets in males of higher IQ. R

  • The prevalence of the A1 allele of the D2 receptor is significantly increased in autism, whereas the D1 receptor gene may be a risk gene… R

Glutamate/GABA #

Genetics/Synapse #

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