by Robert DePaolo
This article presents a diagnostic model to encompass not only differing functional levels of autism but also extreme introversion and psychopathology rooted in social aversion and anxiety. The model is based on the idea that specific structural, genetic and functional (i,e, neurological and neuro-chemical) research results and theories of these disorders leave certain questions of causation and remediation unanswered and that a factor underlying all of these processes – energy production orchestrated by mitochondrial functions – could be considered a root causative element. The fact that mitochondrial influence is broad and influential, affecting genetic assembly, protein synthesis and brain development gives it the advantage of being “graded”, thus capable affecting various functions differentially.
The Vagaries of Pathology…
One problem in diagnosing autism, particularly those said to be on the “spectrum” is that the variations in cognition, intelligence, language and perceptual ability can be so wide as to render the diagnosis uninformative. For example some autistic individuals lack language capacity while others travel around the world giving public speeches and writing lengthy books. Some are unable to tolerate or understand social relationships for lack of what Adolphus et al have called a “theory of mind” ( 2018 ) while others resort to introspection in describing their idiosyncratic behaviors. Some autistic persons join aerobics classes, run marathons while others lack the energy to engage in even normal daily activities (conceivably out of fear that the unmanageable arousal levels resulting from stimulus inputs will lead to catastrophic hyper-arousal).
At face value such functional discrepancies would seem to contradict the notion that all these individuals and skill levels could possibly reflect a single diagnosis.
There are similarities within this general population, however, which makes the picture rather confusing. Aversion to eye contact, tactile hyper-sensitivity, perceptual intolerance, fragmented social perception, repetitive behavior patterns and other traits seem common to those on the spectrum and also among schizophrenics, persons with social anxiety disorder, social phobias, extreme introverts (the so-called “tender-minded” groups) and even some with attention deficit disorder.
That raises obvious questions. For example, it seems apparent that a language deficit would lead to a lack of control over one’s environment. Still, if language is an experiential buffer, enabling us to categorize, marginalize and dampen the influence of input sensations and emotions, why can’t anxiety prone individuals with normal language capacities self regulate more effectively?
With respect to language/self regulation, it is often assumed that non linguistic autistic persons experience chronic anxiety and social confusion because they cannot interpret experiences or communicate with others to make their needs met and feelings acknowledged. As to why some have no language, the reason has yet to be determined. Autistic individuals have a hyoid bone (necessary for tonal and oral fine motor expression) and they do not lack the FOX 2 gene that is a factor in language acquisition. Nor do they typically have hearing impairments. That raises the question of why they can’t put all the functional packages together to enact a skill so quintessentially characteristic of the human species. We all talk, regardless of intellect, emotional disposition, in many instances irrespective of neurological impairment.
There are various explanations as to why they cannot speak. As research by Gow (2012) has shown language is not a specific function but a broad encoding system that spreads among virtually all brain areas – particularly the cerebral cortex. As such, language expression would seem to require a broadly integrative capacity, in other words a search and retrieve capability dependent on network interactions and neural cooperation. To search around a voluminous human brain requires effective coordination between inhibitory and excitatory neural circuits to avoid severe noise. To resolve that noise requires neurological work – which requires adequate energy. The fact that chronic spiking, often referred to as “kindling” occurs in the autistic brain (Gilby & O’Brien, 2012) suggests an uneven distribution of neural activity whereby: for example, when circuit A does not provide a fluid neuro-experiential check on circuit B. Lacking such neural fluidity would interfere with pan-cerebral access needed for normal language expression. If so, that would mean the autistic individual experiences pervasive noise in the CNS. Being unable to override that cacophony, while enduring an inevitable increase in brain arousal as per the word finding search would comprise an aversive experience for the autistic person – making he or she not just unable to speak but fearful of the effort as well.
With regard to the CNS noise factor, some research has shown that whereas normal brains stop expanding at some point in development, and actually shed tissue (Courchesne 2012), a process referred to as “pruning” (presumably enabling thought and cognition to be more conceptual and streamlined) the brains of many autistic individuals continue to expand beyond the pruning process. That means there are more neural circuits, thus more potential for noise within the CNS. Also, in typical brain development two systems become aligned sequentially. Vertically arranged neurons come first, possibly to allow for simple stimulus associations to ensue. This is followed by cross sectional, horizontally aligned circuits which interconnect (merge with vertical circuits and allow them to talk to each other across the brain). In a perhaps overly simplistic analogy, it seems the ability to interact with others depends on the ability for neurons to first interact with one another in a fluid, (low noise) manner. In other words, social interaction depends on rhythmically efficient inter-neuronal communication. That corresponds to what Pavlov, (Dance 2006), Alexander Luria (Kostyanaya, 2013) and Richard Lazarus (1984) described as an internal speech capability, i.e. a dual language skill that is both external/communicative and internal/self regulatory.
Some have surmised that this cross sectional connectivity is problematic in the brain development of autistic children. (Tye & Bolton 2013). That night explain why, in early development, some autistic children seem initially to have language of an associative nature only to lose it as the brain veers off course and integrative cognition is compromised.
While interesting and logical as per typical autistic features, this still leaves some questions unanswered; most notably why high functioning autistic persons are able to communicate. Is it a question of inter-connective proportion rather than an all or none process, whereby a higher percentage of fluid inter-connectivity allows the higher functioning individual to speak while the lower functioning autistic individual, with more involved cross cortical diffusion, cannot.
One way to broach this question is to ask, what are the first signs of abnormality in the autistic child? Rather than referring to research and clinical findings, this writer will resort to something more basic – parental anecdotes.
While developing an autistic program with the Easter Seals foundation decades ago,this writer and the head teacher brought parents in to discuss their observations of their autistic children. When asked: “when did you first notice something was wrong,” some of the answers were fairly typical, referring to lack of language or motor skills at between 9 months and 2 years. Others noted what is called “W sitting” a sign of immature motor development along with a centralized gait – for example difficulty climbing stairs using a left-right rhythmic leg alternation. Still others referred to lack of eye contact and social interest – especially in comparison with normal siblings. Since many of these signs came well after birth, when child to child comparisons could be made, we probed deeper, by asking about the very first, subtle signs of oddness. Parents thought a bit and many came up with interesting observations. It seems all of the children appeared swept up by outside stimuli; for example their heads being swayed by the direction of the wind without an apparent muscular anchor point, or being unable to orient to stimuli for even a few seconds. They also noted that the child did not have enough strength or resilience in his or her ocular/head/neck musculature to maintain a focus on other people. While their normal infants would stare endlessly at people a department store line the autistic child did not have enough “oomph” – in the words of one parent – to maintain such a focus. It was as if the social aspect of an autistic brain (presumed to be compromised) was really peripheral to, a strength deficiency in the head, neck and eyes, that would otherwise enable the child to attend to social stimuli. The idea that what we typically refer to as social interest is to some degree a function of neuro-muscular and perceptual “strength” – or stamina provided an interesting twist on what Piaget referred to as perceptual constancy.
Each of the parents asked why their son or daughter could not resist the influence of external stimuli. One parent believed his son simply wasn’t strong enough to do so – a suspicion supported by the child’s physical therapy evaluation. Based on this discussion we surmised there might be some correlation between a problem with stimulus orientation and strength in the perceptual-motor system and, more broadly, the central nervous system
While some of the children seemed less affected than others the strength factor became a seedbed for subsequent discussion, as well as a focal point in therapy – the point being that if one could strengthen the child in various sensory, motor and auditory areas a generative effect might occur.
Some of the children made significant gains, others did not. The factor we all overlooked was encompassed in the definition of “strength”- which is ultimately a function of energy production. Energy (in all bio-functional systems) comes from one prime source – cellular mitochondria. Mitochondria are energy packets fueled by adenosine tri-phosphates situated in each cell and in the nucleus of each cell. A deficiency in mitochondrial structure or function could affect various systems and lead to the general deficiencies in language, cognition and sustaining a social focus, as seen in autism.
Some research provided a degree of verification for these assumptions. For example Tang (2014) found a correlation between autism and mitochondrial dysfunction. Many clinical studies point a strength deficits in small and gross motor skills. If a fundamental diagnostic variable is an energy deficiency that could have significance not only for autism but for related psychological disorders that, while not including all the symptoms of autism exhibit more than a few.
For that argument to make sense one has to assume the presence of a “fragility factor” in those afflicted, analogous to Eysenck’s notion of tender mindedness” (1975) that prevents the CNS from controlling noise, irrespective of any given point on the fragility continuum. It is perhaps not an outrageous assumption, particularly because it encompasses children with varying abilities and lends itself to other diagnostic categories. In that context, anxiety disorders often feature obsessiveness, self stimulation behaviors, social avoidance, withdrawal, and even mood swings ranging from extreme sadness and isolation to outbursts of rage.
While extending the energy depletion-causation/noise interference model to include not just autism but other diagnostic categories might seem overly broad there is research lending a modicum of support. For example in studies on autism Packer (2012) found that the main activation center in the brain (the reticular activating system) sends signals to the cerebral cortex and other brain sites, helping those functional centers process the relevance of inputs so as to select efficient responses to those inputs. However that study showed that the pathways are rather noisy. Many do not send direct and clear signals. Some R.A.S pathways drift off into branches with no information content comprising what one might call “junk arousal.”
It is almost as if in designing the human brain, nature selected a brain founded on mandatory neural confusion. That creates noise and the way in which the noise is reduced is by an influx of nor-epinephrine, (which through neuro-chemical “oomph” can override the noise and establish signal clarity.
This is an example of strength overcoming uncertainty, acting as a shield against input diffusion. More specifically; neuro-chemical strength as a noise buster. A deficiency in that mechanism could lead to mood instability, depression, anxiety and social phobia: all positions on a continuum of neuro-functional fragility as well as autism, depending on the level of involvement.
A look at introversive (fragility-based) pathologies points to some interesting parallels with autism. For example neuroticism- with apologies for using a very old term – has been equated with an extreme state of (high noise) uncertainty (Mineka & Kohlstrom 1998). A state of prolonged confusion, precluding closure or efficient response selection will tend to result in repetitious, vicious cycle behaviors similar to those seen in autism
Another comparison can be drawn to depression, which is viewed as a state of learned helplessness (Seligman 1975 ). In this model the client lacks a capacity or access to behavioral resolution to an impending problem or state of mind. Once again this is reflective of uncertainty, possibly an endpoint whereby psychic defenses are finally depleted and anxiety (which can be more a adaptive emotional state because it at least fosters a state of readiness and vigilance) is no longer operative.
A depressive state of mind is reflected in the inter-neuronal connectivity within the brain. That has a cognitive correlate. Continuity in neural interactions keeps the thought and emotional sequence running. which sustains hope, futuristic concerns, planning and adaptation to current stressors. When, through energy depletion that neural extension fizzles out, so too does hope and resilience-sustaining cognition. Here too the energy depletion factor could be involved.
The root of these various fragility-based pathologies can be presumed to lie in mitochondrial dysfunction, because it is the latter that fuels neural transmission, allows for the neuron-to neuron connectivity in the brain needed to sustain experience and thereby establish hope, build language concepts, sustain the attention span, facilitate mood readiness, create resistance to noise, build task-learning tolerance and in general override the uncertainty of various perceptions and experiences.
Correlations Across the Board…
Although there is some evidence of a correlation between mitochondrial dysfunction and anxiety (Filiou & Sandi 2019) this idea is speculative. Establishing a link between autism and less involved disorders in terms of a mitochondrial-based fragility would require an analysis of several correlated factors. One would be family histories. There is some evidence that depression runs in the families of autistic individuals, as do Attention deficit disorder, anxiety disorders obsessive-compulsive disorder and extreme introversion. (Akdag 2003) Could it be that these are all incremental variations of an energy-based pathology rooted in mitochondrial dysfunction? Much work would have to be done to make that determination, including genetic assessments, learning history reviews, sibling comparisons, twin studies and more. Yet since energy seems to be the ultimate source of all actions (and actually, everything in the universe) results of such inquiries might prove useful.
To embark on such a quest would require a new deterministic framework, with neuro-psychology borrowing from the field of physics, by seeking a central (graded) etiology of a wide range of high fragility (extreme introversive) disorders based on an apparent energy summoning deficiency which prevents the afflicted from handling social demands and set backs, attending to tasks, developing coherence between thoughts and emotions, acquiring language concepts, shielding against dissonant or intense inputs, providing motor strength and resilience and adapting to changing stimulus conditions.
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