In the last blog post, I discussed the Cognitive Action Pathways model, a schematic conceptual representation of the hierarchy of key components that underpin human thought and behaviour.

Small changes in the early processes within the Cognitive-Action Pathway model can snowball to effect every other part of the process. A real life example of this is ASD, or Autism Spectrum Disorder.

ASD has been present since time immemorial. Numerous bloggers speculate that Moses may have had ASD, while a couple of researchers proposed that Samson was on the spectrum (although their evidence was tenuous [1]). Thankfully, autism is no longer considered a form of demon possession or madness, or schizophrenia, or caused by emotionally distant “refrigerator mothers”, nor treated with inhumane experimental chemical and physical “treatments” [2, 3].

The autism spectrum is defined by two main characteristics: deficits in social communication and interaction, and restricted repetitive patterns of behaviour. People on the autism spectrum also tend to have abnormal sensitivity to stimuli, and other co-existing conditions like ADHD. The full diagnostic criteria can be found in DSM5. The new criteria are not without their critics [4-6], but overall, reflect the progress made in understanding the biological basis of autism.

ASD is recognized as a pervasive developmental disorder secondary to structural and functional changes in the brain that occur in the womb, and can be detected as early as a month after birth [7]. In the brain of a foetus that will be born with ASD, excess numbers of dysfunctional nerve cells are unable to form the correct synaptic scaffolding, leaving a brain that is large [8, 9], but out-of-sync. The reduced scaffolding leads to local over-connectivity within regions of the brain, and under-connectivity between the regions of the brain [10]. The majority of the abnormal cells and connections are within the frontal lobe, especially the dorsolateral prefrontal cortex and the medial prefrontal cortex [11], as well as the temporal lobes [12]. The cerebellum is also significantly linked to the autism spectrum [13]. There is also evidence that the amygdala and hippocampus, involved in emotional regulation and memory formation, are significantly effected in ASD [10].

There is also strong evidence for an over-active immune system in an autistic person compared to a neurotypical person, with changes demonstrated in all parts of the immune system, and the immune system in the brain as well as the rest of the body [14]. These immune changes contribute to the reduced ability of the brain to form new branches as well as develop new nerve cells or remove unnecessary cells.

There are a number of environmental and epigenetic associations linked to autism. These include disorders of folate metabolism [15, 16], pollutants [17], fever during pregnancy [18] and medications such as valproate and certain anti-depressants [19, 20] which are linked with an increase in autism[1]. Supplements such as folate [15, 21], omega-6 polyunsaturated fatty acids [22] and the use of paracetamol for fevers in pregnancy [18] have protective effects.

Although these factors are important, genes outweigh their influence by about 4:1. Twin studies suggest that between 70-90% of the risk of autism is genetic [23, 24]. Individual gene studies have only shown that each of the many single genes carry about a one percent chance each for the risk of autism [10]. It’s been proposed that the hundreds of genes linked with autism [10, 25] are not properly expressed (some are expressed too much, some not enough). The resulting proteins from the abnormal gene expression contribute to a different function of the cell’s machinery, altering the ability of a nerve cell to fully develop, and the ability of nerve cells to form connections with other nerve cells [26]. The effects are individually small, but collectively influential [24]. Autism is considered a complex genetic disorder involving rare mutations, complex gene × gene interactions, and copy number variants (CNVs) including deletions and duplications [27].

According to the Cognitive-Action Pathways model, the triad of the environment, epigenetics, and genes influence a number of processes that feed into our actions, thoughts, perceptions, personality and physiology. In ASD, the starting place is language processing.

New born babies from as young as two days old prefer listening to their own native language [28], which suggests that we are born already pre-wired for language. Auditory stimuli (sounds) are processed in the temporal lobes, including language processing. In neurotypical people, language processing is done predominantly on the left side, with some effect from the right side. But in people with autism, because of the abnormal wiring, there is only significant activity of the right temporal lobe [12]. Even more, from data so recent that it’s pending publication, loss of the processing of information of the left temporal lobe reversed the brains orientation to social and non-social sounds, like the sound of the babies name [7].

The change in the wiring of the left and right temporal lobes then alters the processing of language, specifically the social significance of language and other sounds. So already from a young age, people with autism will respond differently to environmental stimuli compared to a neurotypical person.

In the same way, the fusiform gyrus is part of the brain that processes faces. It’s quite specific to this task in a neurotypical person. However, the altered wiring of the brain in someone with autism causes a change, with different parts of the brain having to take up the load of facial processing [29].

Each time that one part of the brain can’t perform it’s normal function, the other parts take up the load. However that reduces the capacity for those parts of the brain to perform their own normal functions. In the case of the temporal lobes and the fusiform areas, this results in a reduced ability to discern subtleties especially those related to recognizing social cues. A neurotypical person and an autistic person could be standing in front of the same person, listening to the same words, and seeing the same facial expressions, but because of the way each persons brain processes the information, the perception of those words and cues can be completely different. This demonstrates how genetic changes can lead to changes in the perception of normal sensory input, resulting in differences in the physiological response, emotions, feelings, thoughts and actions, despite identical sensory input.

Physiology

The same changes that effect the cerebral cortex of the brain also have an influence on the deeper structures such as the hippocampus and the amygdala. The hippocampus is largely responsible for transforming working memory into longer term declarative memory. Studies comparing the size of the hippocampus in ASD children have shown an increase in size compared with typical developing children [30]. Combined with the deficits in the nerve cell structure of the cerebellum [13], autistic children and adults have a poor procedural memory (action learning, regulated by the cerebellum) and an overdeveloped declarative memory (for facts, regulated by the hippocampus). This has been termed the “Mnesic Imbalance Theory” [31].

The amygdala is also functionally and anatomically altered because of the changes to the nerve cells and their connections. The amygdala is larger in young children with ASD compared to typically developing children. As a result, young ASD children have higher levels of background anxiety than do neurotypical children [32]. It’s proposed that not only do ASD children have higher levels of background anxiety, they also have more difficulty in regulating their stress system, resulting in higher levels of stress compared to a neurotypical child exposed to the same stimulus [33].

Personality

On a chemical level, autism involves genes that encode for proteins involved in the transport of key neurotransmitters, serotonin and dopamine. Early evidence confirms the deficits of the serotonin and dopamine transporter systems in autism [34]. These neurotransmitters are integral to processing the signals of mood, stress and rewards within the brain, and as discussed in the last chapter, are significantly involved in the genesis of personality.

The abnormal neurotransmitter systems and the resulting deficiencies in processing stress and rewards signals contribute to a higher correlation of neuroticism and introverted personality styles in children with autism symptoms [35, 36].

So people with autism genes are going to process stress and rewards in a different way to the neurotypical population. As a result, their feelings, their thoughts and their resulting actions are tinged by the differences in personality through which all of the incoming signals are processed.

Actions

The underlying genes and neurobiology involved in autism also effect the final behavioural step, not only because genes and sensory input influence the personality and physiology undergirding our feelings and thoughts, but also because they cause physical changes to the cerebellum, the part of the brain involved in fine motor control and the integration of a number of higher level brain functions including working memory, behaviour and motivation [13, 37].

When Hans Asperger first described his cohort of ASD children, he noted that they all had a tendency to be clumsy and have poor handwriting [38]. This is a good example of how the underlying biology of ASD can effect the action stage independently of personality and physiology. The cerebellum in a person with ASD has reduced numbers of a particular cell called the Purkinje cells, effecting the output of the cerebellum and the refined co-ordination of the small muscles of the hands (amongst other things). Reduced co-ordination of the fine motor movements of the hands means that handwriting is less precise and therefore less neat.

A running joke when I talk to people is the notoriously illegible doctors handwriting. One of the doctors I used to work with had handwriting that seriously looked like someone had dipped a chicken’s toes in ink and let it scratch around for a while. My handwriting is messy – a crazy cursive-print hybrid – but at least it’s legible. I tell people that our handwriting is terrible because we spent six years at medical school having to take notes at 200 words a minute. But it might also be that the qualities that make for a good doctor tend to be found in Asperger’s Syndrome, so the medical school selection process is going to bias the sample towards ASD and the associated poor handwriting (Thankfully, those that go on to neurosurgery tend to have good hand-eye coordination).

But if your educational experience was anything like mine, handwriting was seen as one of the key performance indicators of school life. If your handwriting was poor, you were considered lazy or stupid. Even excluding the halo effect from the equation, poor handwriting means a student has to slow down to write neater but takes longer to complete the same task, or writes faster to complete the task in the allotted time but sacrificing legibility in doing so.

Either way, the neurobiology of ASD results in reduced ability to effectively communicate, leading to judgement from others and internal personal frustration, both of which feedback to the level of personality, molding future feelings, thoughts and actions.

Thought in ASD

By the time all the signals have gone through the various layers of perception, personality and physiology, they reach the conscious awareness level of our stream of thought. I hope by now that you will agree with me that thought is irrevocably dependent on all of the various levels below it in the Cognitive-Action Pathways Model. While thoughts are as unique as the individual that thinks them, the common genetic expression of ASD and the resulting patterns in personality, physiology and perception lead to some predictable patterns of thought in those sharing the same genes.

As a consequence of the differences in the signal processing, the memories that make their way to long-term storage are also going to be different. Memories and memory function are also different in ASD for other neurobiological reasons, as described earlier in the blog with the Mnesic Imbalance Theory.

Summary

The Cognitive-Action Pathways model is a way of describing the context of thoughts to other neurological processes, and how they all interact. It shows that conscious thoughts are one link of a longer chain of neurological functions between stimulus and action – simply one cog in the machine. The autistic spectrum provides a good example of how changes in genes and their expression can dramatically influence every aspect of a person’s life – how they experience the world, how they feel about those experiences, and how they think about them.

I used autism as an example because autism is a condition that’s pervasive, touching every aspect of a person’s life, and provides a good example of the extensive consequences from small genetic changes. But the same principles of the Cognitive-Action Pathways Model apply to all aspects of life, including conditions that are considered pathological, but also to our normal variations and idiosyncrasies. Small variations in the genes that code for our smell sensors or the processing of smells can change our preferences for certain foods just as much as cultural exposure. Our appreciation for music is often changed subtly between individuals because of changes in the structure of our ears or the nerves that we use to process the sounds. The genetic structure of the melanin pigment in our skin changes our interaction with our environment because of the amount of exposure to the sun we can handle.

So in summary, this blog was to set out the place that our thoughts have in the grand scheme of life. Thought is not the guiding or controlling force, it is simply a product of a number of underlying functions and variables.

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[1] A word of caution: While there’s good evidence that valproate increases the risk of autism, and a possible link between some anti-depressants and autism, that risk has to be balanced with the risk to the baby of having a mother with uncontrolled epilepsy or depression, which may very well be higher. If you’re taking these medications and you are pregnant, or want to become pregnant, consult your doctor BEFORE you stop or change your medications. Work out what’s right for you (and your baby) in your unique situation.