by Robert DePaolo
Abstract
This article is written in a Piagetian mold. It revolves around of the case of an autistic man whose development in described in a way similar to Piaget’s observations of his nephew, Laurent. However unlike Piaget’s detailed studies, this discussion does not employ a single subject, empirical approach. “Alexander” is actually a composite of numerous autistic clients with whom this writer has worked and conducted evaluations. In one sense that makes it less precise. In another sense, the description of trends in behavior, speech and cognitive development might be perhaps more broadly applicable. In that context, there is discussion of recent research on autism with implications for establishing causation and future treatment options.
PROLOGUE
Alexander is a young man of twenty-five who was diagnosed with autism at around the age of two. He is in some ways an ideal subject, because he is neither in the high functioning nor low functioning range. From an observational standpoint that is important. So-called high functioning autistics are often so normal in terms of language skills and life style (eg. Temple Grandin) that it is hard to describe their limitations in stark neuropsychological terms. Moreover, in some instances high functioning autistics are misdiagnosed. For example the symptoms of childhood schizophrenia, organic brain disorders and even severe attention deficit disorders can overlap with autism. By the same token individuals with severe autism, with no language and profound deficits in the areas of cognition, motor skills etc. might not be able to provide clear indicators of what they can and cannot do. That makes their development difficult to describe in specific terms, making it hard to conceptualize with respect to causation and treatment possibilities.
Alexander is somewhere in the middle. He is quite capable on some ways. He is tuned in to his environment - rigidly, but tuned in nonetheless. He anticipates when others need help and often jumps in to assist. The problem is, he does not understand social mores or the need for ice-breaking skills. Family, friends, strangers – he knows the difference, but when it comes to acting in the moment, it doesn’t matter to him. Life is a series of dos and don’ts – mostly do’s. His outlook is to the point: see the circumstances, respond to the circumstances. Thus his abilities and social outlook tend to be literal and fragmented. The word “context” is as foreign to him as the Swahili word for pomegranate might be to us.
He uses speech, though unlike so-called high functioning autistic persons he won’t write books about his life experience or make presentations to groups. When he talks it is in a muffled tone and often askew of the interaction. He cannot look another person in the eye and converse. Maybe one or the other but not both, at least not in the usual rhythmic sequence familiar to the rest of us. Instead he might, after hearing a question, wander a bit, then in either sing-song or muffled tone provide a phrase that constitutes a delayed reply. The reply will be rough around the grammatical edges but usually apropos the interaction. Unfortunately this often goes unnoticed. The delay and intervening behaviors occurring between the first speaker’s comment and his response is often so long such that a less than perceptive person might not think he can speak at all. Over time much of his language will be so often ignored or unnoticed that he will lose his enthusiasm for communicating vocally.
In the clinical and social domains world Alexander is seen as having a severe neuro-behavioral disorder. To Alexander the disorder is not solely his. Rather it is one of proportion; in part, his deficiency in not being able to orchestrate the energy required to adhere to the language, social and behavioral rhythm codes of the outside world, in part our deficiency in not being able to comprehend, perceive and operate in his choppy, dysrhythmic world.
Alexander is misunderstood by many who are not familiar with his habits and the primary point of contention between he and the outside world boils down to two components. One is speed. While he reacts with great alacrity in many instances and requires much proactive cueing to abstain from impulsive behaviors he is also very delayed in his comprehension and expression. Thus Alexander is at once too fast and too slow in his pace.
The other component is energy. Alexander is a tall, robust man and when aroused his hand grip can be unfathomably strong. Under such conditions he can lift heavy objects – when for example helping (sans introductions) unsuspecting strangers. Consequently many assume he also has stamina, particularly his day program staff who might expect him to engage in activities for several hours on a daily basis. He typically resists doing so and when he is able to endure the demands of a daily program he ends up extremely tired and even more reluctant to engage the next day. A cloud - an inexplicable paradox - hovers over his handsome head. How can so strong a man be so lacking in task durability? What indiscernible weakness lies behind this man’s global reluctance to participate, his occasional behavior issues and his overall development?
Alexander’s behavior includes other confusing elements. For example his expressive capacities present a conundrum. He never “took off” in his early language development, in fact did not speak at all until he was around ten years old. Nor did he respond very well to directives, that is, unless he could put them into some visual or experiential context. Yet every once in a while he would utter a phrase he did not apparently learn and/ or never used before. Sometimes it can be profane: for example an f bomb occasionally emerges when he is frustrated. At other times it is more profound than profane – for example, a barely audible… “I am very intelligent.”
Alexander’s mode of acquisition (aka learning style) can be quite mysterious. To someone working with or living with Alexander it would appear he is somehow able to learn in latent manner; that is, without being taught, without giving any inclination that he is absorbing stimuli around him. Questions arise: does he actually absorb inputs? If so, is it done in the same way we do, whereby short term memory converts to long term memory, leading to subsequent retrieval? Or is it something else; some compensatory or adaptive memory process we don’t understand? And even though he seems not to absorb readily, information presented to him he is able to retrieve it later – perhaps hours later, sometimes days later.
Alexander’s language is almost never its own entity. Instead it seems to require extra “push” from other response systems. For example he moves a lot when he speaks, occasionally provides his own musical vocal accompaniment, and he will often cock his head as if using some sort of body English. Only with that added somatic thrust can he speak – or so it seems.
Still another feature of Alexander’s behavior is a spillover effect. Once aroused, he tends to remain aroused. Input has a pervasive impact and is so singularly influential in prompting his behavior that he is often unable to divert his focus from the first stimulus. As a result he tends to miss the experiential forest for the trees. Because of the singular, fervent impact of stimuli on his brain he soon learns to avoid stimuli that are too blatant or complex. The former overloads him, the latter is too hard to process sequentially with any real efficiency; due, once again to the spillover effect.
In observing Alexander it becomes clear that one crucial aspect of his developmental disability involves a kind of “neuro-burial” process. Whatever he takes in is buried, whatever he wants to say is buried, whatever social nuances he can comprehend are extant on some level yet buried within the confines of his central nervous system. Behaviors and memories are trapped in an endless neurobiological maze –or perhaps just weighted down like the gravitational pull of a black hole. While he has changed and improved considerably since childhood the burial factor seems to persist. Stuff comes out on occasion; words, behaviors suggesting a surprising insight, anticipatory reactions that seem almost clairvoyant, but not consistently. He clearly has but cannot summon this knowledge at will.
Alexander cannot simply described as being autistic. As a biological organism he must also be defined in terms of the laws of physics. Those laws mandate that in order for any type of work to transpire - be it lifting, speaking, thinking or playing a piano requires a series of energy bursts. Yet Alexander is faced with a problem. He appears to lack the capacity to produce those energy bursts.
That was ost evident in his early development. As a child Alexander could be swayed by the wind, with head movements unavoidably drifting in its direction. Speaking to him would be pointless, since he could not power his way past that wind’s distraction toward other matters.
Over time Alexander has learned, matured and improved, but he is still plagued by the lack of energy needed to focus past singular distractions, to search for and bring out responses, take on energy-demanding integrative tasks or push words out beyond low-key whisper talk. At times he can speak above the din but only with a boost from the somatic orchestra – as he sings and rocks his way past an ergonomic deficiency.
His emotions and behavior make sense in that context. His avoidance of eye contact, loud noises and crowds serves to ameliorate the impact of inputs. It is as though stimulus traces do not disperse democratically around his brain. If they did it might lead to the integrative access and perceptual input cushion enjoyed by the rest of us. Instead inputs run roughshod along narrow circuits so that perception poses a constant threat.
Alexander sees these tendencies in himself and does what all of us do when faced with an aversion. He tries to avoid stimuli that entail discomfort. He knows this has something to do with an energy-effort deficiency and most of his behavior outbursts result from his frustration at being asked to expend energy he does not have. Thus he is well-versed in the feeling and threat of fatigue. He recognizes that. He tries constantly to tell us, in effect…I lack the energy needed to live the way you want me to live. Yet many of us, intent on helping Alexander improve and enhance his skills through elaborate IEPs, behavior plans and service plans, insist that he engage, behave, expend energy - practice, because in our world practice leads to improvement. Alexander on the other hand fears that too much practice will lead to regression.
Alexander knows more than we think he knows and he’s probably aware of that fact. One can determine this from the logic of his behavior. For example Alexander has a penchant for worrying and his behavior clearly indicates a capacity for anticipatory thinking. That would not be the case if he were oblivious to outside circumstances, unable to comprehend, predict and memorize. Thus on some level Alexander’s anxiety, worries, fears, anticipatory emotional reactions signify the presence of knowledge that he cannot readily express.
Perhaps this line of reasoning can also be applied to his odd motor behavior (i.e. self stimulation). Assuming optimistically that Alexander is knowledgeable in a latent or “buried” sort of way, he must also have some sense of what is normal. If so, why behave in such odd ways? Is it because he doesn’t know any better – or something else?
If he could fluidly retrieve words Alexander’s answer might be that his odd behavior is employed (ironically) in order to conform to social standards. In other words, he might say that he acts this way primarily because of us. More specifically, in combining his knowledge and anticipatory capacities with his self knowledge, including an understanding of his own energy limitations, he self-stimulates to please those of us who make demands on him that exceed his energy resources. By hand flapping, noise making, rocking etc. he is not exhibiting signs of a pathology. Rather he is making a concession to (and a statement about) our own ignorance of his condition. The motor behaviors are an attempt to provide extra gross-bodily energy to meet our demands. He is “motor-psyching” himself up for the task, summoning extra power. (Imagine his dismay when instructors insist that he both engage in task and refrain from the energy-inducing actions needed to complete them). As a corollary: one cannot help but wonder if severe autism has a psychiatric component, reflecting a psychological breakdown resulting from a profound helplessness-inducing, irresolvable conflict inherent in some instructional programs that prompt task behavior yet discourage the self stimulatory (energy-inducing) behaviors needed to complete the task.
Alexander knows there is more to him than meets the eye. If appraised, he might not challenge research findings refuting the efficacy of Facilitative Communication because he is not familiar with Shakespearean phrases and does not ponder philosophical truths. Yet he undoubtedly would insist that while much of his knowledge is buried, it is extant nonetheless. If by some method his ideas and language could be “unearthed” and he were asked to explain the nature of his problem he might simply say…my motor is not as powerful as yours. In order to think, speak and do many of the things you take for granted I must borrow energy from other places in my brain and body. I operate with a power deficiency and the only way I can navigate through my world (or more precisely, yours) is to mobilize my entire mind, senses and body. That’s why I do weird things. As you can imagine, it entails a lot of work and frankly I’m exhausted most of the time.
CONFIRMATION/RECONCILIATION
Since Alexander has hypothetically identified for us the nature of his problem, we might as well pivot off that in discussing whether his “theory” of causation coincides with research findings. First, recall that Alexander conceives of his problem as being a grounded in an energy-summoning deficiency that interferes with cognitive, perceptual, language and motor stamina. His odd neuro-muscular priming activities are not the sine qua non of autism or even diagnostically meaningful. In his view, many autistic behaviors represent attempts to build a bridge between his low energy world and the high energy world of the normal person. Are his assumptions correct?
ENERGY AND THE BRAIN
A recent study discussed by in Science Daily (2011) describes a process by which the brain creates and transports what might be called “the power that fuels cognition.” When it comes to brain and energy a paradox is involved. To begin with, all the cells in the body contain energy packets called mitochondria. These are organelles that produce the primary fuel enabling us to act, think, speak and remember. The fuel produced by the mitochondria is a sugar called ATP - or adenosine triphosphate. Since all cells contain mitochondria and produce ATP it stands to reason that brain cells (neurons) would do the same and that a normal adequate brain would be consistently able to summon the energy needed to perform various human functions.
It turns out the process is a bit more complicated than that. Brain cells are more elongated and include branches called axons (leading away from the neuron) and dendrites (leading to the neuron). For the brain to function requires that energy be provided not just within a given cell but transported along these branches because ATP is needed to fuel each action and connection along the way. With a depletion of ATP at any point, transmission would be faulty and faculties would be adversely affected. Beyond that, some of the ATP must return to the source neuron because it too must continue its work and cannot be left devoid of fuel. That means that the energy transmission process in the brain involves a higher degree of complexity and uncertainty, as well as a greater error factor.
As if that weren’t enough, it seems the brain operates via an inherent energy depletion state. While our breathing takes in oxygen at a 20% rate our brains only consume oxygen at a rate of 2.5 percent. That would seem to imply that all human brains are prone to rapid fatigue and are inherently, naturally ergonomically deficient – except for one thing. Certain proteins in the brain provide compensation. One is called HUMMR (hypoxia-unregulated-mitochondria movement response). It is called into action during low oxygen states. Another is HIF-1 (hypoxic inducible factor-1) which operates in similar fashion. These proteins facilitate the energy-compensating process so that low oxygen levels can be replenished. A malfunction in mitochondria, ATP production among nerve branches or a protein deficiency in synthesizing ATP could create a low energy state that could slow down and make considerably more difficult the functions of learning, retrieving, speaking and integrating experience.
The thrust of these findings seems to indicate that the brain tends toward a quasi-normal state of low oxygen (hypoxia). It is as though autism is a primal, normal state within the brain that is corrected for by mitochondrial functions. The brain seems to require a low oxygen state to call it to action so that the compensatory protein-generated energy replenishment that produces behavior can occur. Thus, despite their experiential connotations, cognition, behavior, emotions and other phenomena are ultimately the result of renewed states of energy via a negative feedback mechanism. Our faculties consist most essentially of a conversion from an abnormal state to a normal one, which raises the question of what would happen if that conversion process somehow went awry.
Another aspect of the mitochondria-ATP-protein sequence is that when functioning properly it also serves immune functions. Consequently, a depletion or malfunction of this process would tend to create a susceptibility within the immune system. That might involve a hypersensitivity to allergens, vaccines, or conceivably any substance that is harmless to most infants but not those with this deficiency.
In reviewing the research it appears Alexander’s theory has some support. For example, Atwell & Loughlin (2001) have shown that the brain budgets energy and that spiking activity, which is typical in autism (Hashimoto, et al 2001 ) creates more energy depletion than well distributed, integrative activity (which is not typical in autism). From this one can derive that the autistic brain has to work harder and expends more energy in executing even simple tasks. Just why that occurs was an issue not addressed in the Atwell study.
It was addressed to an extent by Belmonte et al (2004) who found that the autistic brain’s architecture tends to be more fragmented than the normal brain, particularly in the energizing, initiative-producing,-cognitive-enhancing circuit known as the cerebellum. The separation of neural columns in this site foments to some extent the kind of spiking activity and high regulatory demands that lead to more rapid energy depletion. The question in that regard is whether autism is related somehow to increased energy demands in light of columnar fragmentation, or whether the energy is required to integrate the columns is lacking. In the case of the former the autistic symptoms would result from ongoing fatigue. With the latter, low energy resources would prevent the autistic person from being able to do the work of integrating experience – other than with the added thrust of self stimulation.
With respect to the immunological issue, studies by Krause et al (2002), Warren et al (1996), and van Gent et al (1997) have shown a greater susceptibility to allergies and immunity problems in autistic subjects. With regard to the question of whether this has to do with mitochondrial function, the research of Tsao & Mendell (2007), Pons, et al (2004), Poling et al (2006), Oliviera et al (1998) and Vicente (2005) offers support. The Oliviera study found that the ratio of normals with mitochondrial malfunction at birth is 1 in 4,000 (.025 percent) whereas that of autistic children is 5 % - a rate twenty times that of normals.
THE METABOLISM OF MEMORY RETRIEVAL
If Alexander’s theory is correct, there should be some sort of extraordinary metabolic effort required to retrieve memories, because that could be at the core of his problem. This would not necessarily involve learning words, grammatical sequences, faces, names etc. Rather it would entail sifting (powering) through brain circuits to find and express them. With regard to the question of whether it involves fragmented columnar wiring, of a lack of energy to conduct the search and create the extra columnar interactions in the brain, a studies by Hoyer (2003) is indicative. He was able to show that memory retrieval involves a complex catabolic process anchored by ATP that involves a break down of glucose via a regulatory assist from insulin in the brain. Depletion of any of those neuro-chemicals will lead to memory loss.
The term “memory loss” is more often associated with Korsakoff’s, Alzheimer’s and other organic disorders than with autism. Therefore it might seem trite to say that autism entails memory loss, that is, unless one substitutes memory retrieval for memory. The latter suggests an ingrained mental state – a passive storage process. In fact what we typically refer to as memory is an active process and invariably involves search functions within the brain. To carry out that search activity requires a sound metabolic capacity whereby which mitochondria, ATP and various neurochemical transmissions interact fluidly.
Alexander’s theory of extreme fatigue and a related search-deficiency makes sense on that context. In fact it might be reasonable to give his syndrome a new name, first by tossing out the awkward word “autism” - which sounds more like a state of social isolation than a neurological or developmental disorder, and replacing it with the complex but perhaps more descriptive word neuropsychasthenia, which connotes a profound state of CNS fatigue, whereby the energy supply ordinarily needed to facilitate integration and retrieval, preclude the need for neuromuscular priming to meet task demands, help modulate inputs and produce enough energy/excitatory mobilization for language expression is depleted. Autism…or “NPA” would then be considered at least partially akin to a chronic state of lethargy, and highly reminiscent of Rudy’s description of autism as being tantamount to a chronic state of sleep (2010).
OXYGEN-SEQUENCING AND LANGUAGE ACQUISITION
In the prior discussion of energy dynamics in the brain, the functions of mitochondria and ATP were discussed. While both are crucial aspects of energy provision and maintenance, there is a third factor involved. It is the last step in the energy consumption cycle – the burning of oxygen to foment activity. If mitochondria is the engine of behavior, ATP the fuel, then oxygen is the byproduct of this cycle. For that reason recent research has focused on the dispersion and consumption of oxygen in various sites in the brain.
One of the more recent and interesting projects was conducted by Ecker et al (2010). Using PET scans, the team discovered what appears to be a reliable tool for diagnosing autism. They found that oxygen levels in the left cortical hemisphere (involved in language and sequential reasoning) had a low oxygen dispersion. In effect the flow of oxygen was fragmented, not fluid and conceivably unable to provide mental continuity for exertion in cognitive and linguistic functions. Interestingly, it was also discovered that the pattern of blood flow to the right hemisphere of autistic subjects was virtually the same as occurred in the left hemisphere of normal subjects – making it appear that autism might involve some sort of “wiring reversal.” The Ecker study was conducted with high functioning autistic subjects, thus some have questioned its applicability to the syndrome as a whole. Yet the correlations between poor oxygen dispersion and a diagnosis of autism was extremely high – with virtually no false positives occurring among normal subjects in the study. Thus it clearly has significance as a diagnostic tool. It also has parallels to research on oxygen depletion in the brain of autistic individuals. For example a study by Rossignol et al (2010) indicated that hyperbaric oxygen treatments led to amelioration of autistic symptoms.
The results of the Ecker study raises the question of why one side of the brain would receive more oxygen than another. One possibility is that sequential faculties require more energy than those providing spontaneous and holistic processing – as seen in the right hemisphere. This assumption is based on the idea that sequential, organized thinking, which is required in the use of grammar, logic and step by step analysis demands more inhibitory restraint. in order to speak it is necessary to excite circuits devoted to word memory. However a sentence has to be understood, which means it also requires a particular cadence, ie. a breakdown of parts of speech and various other parsing skills and deliberation. That entails complex interactions and apportioning among excitatory and inhibitory neurons on the brain. Presumably the orchestration of stop and go neural substrates of sequential behaviors would be a high-energy endeavor and thus require more oxygen.
In that context one way to look at the Ecker study on autism is to assume that normal blood flow in the right hemisphere is not indigenous to the syndrome but rather the end product of an adaptation/energy redistribution learning process occuring in the brain of the autistic subjects. This implies that insufficient oxygen and energy resources in the left hemisphere lead to a compensatory shift in thought and action to the right hemispheric so that the autistic subjects can negotiate through their world in a global manner. In other words, oxygen distribution in the brain of autistics might be less of a pure diagnostic tool than a statement about a post-morbid adaptation. Whether or not this has validity, it is consistent with the tendency among autistic individuals to problem solve through gross motor rather than language faculties, and to globalize their feelings, thoughts and behavior into “lump sums” of experience.
In either case much of the research thus far discussed would tend to support Alexander’s theory that at least one of central feature of autism is neuropsychasthenia.
HYPOPLASIA IN THE CEREBELLUM
Another study on autistic subjects have shown a lack of maturation of cells in a part of the brain known as the cerebellum – a condition referred to as hypoplasia. (Belmonte 1998) Not all subjects exhibited this characteristic, in fact some showed an opposite tendency. However one of the benefits of the research on cerebellar functioning in autistic subjects is that this massive circuit has been discovered to have many more functions than previously thought.
The classical description of the cerebellum was as a motor circuit providing a movement backdrop against finer movements that emanate from the cerebral cortex. In the past it was viewed as a computer-like circuit providing organisms with a motor anchor point so that certain movement prerequisites could be taken for granted in conducting activity. It now appears the cerebellum provides more than a motor stabilizing function, and that it also provides an anchor point (and sense of automaticity) for language and cognition.
The ostensible relationship between energy and cerebellar functions is interesting. One could assume, as did Belmonte that impairment or lack of maturation (hypoplasia) in this lobe would remove the stabilizing, “automatic” aspect of behavior, which would make each experience seem new and potentially threatening. That would certainly account for the memory deficiencies in autism as well as the repetitive behavior, need for structure and rituals.
More recent research on the cerebellum seems to indicate that it plays not only a more extensive role in cognitive, language and memory functions. It also appears to provide intent, which means it creates an apriori template for expectations that drive behavior. It is a highly redundant circuit, not in itself complex enough to produce myriad functions but nonetheless richly connected to other brain sites. That means it provides impetus and stability, intent and confirmation. Also since it is comprised mostly of Purkinje cells, which produce a pleasure chemical called serotonin it has a role in generating emotion as well. Could this have something to do with the flat affect typically seen in autistic individuals?
If one attributes a drive-sustaining function to the cerebellum then it too ultimately could be viewed in ergonomic terms and it would have to depend on adequately distributed, intact mitochondrial systems, ATP production and fluid patterns of and oxygen consumption.
NEW HORIZONS
In not being able to specify as to the causes or core bio-genetic aspects of autism it is difficult to speculate on possible future treatments. If mitochondria deficiencies are involved, then as of the moment there are no reversible treatments. Some research is being conducted by Dr. Christoph Westphal on development of enzyme catalysts that will enhance mitochondrial function. He elaborated on this topic in an interview in Mitoaction. Also, there are traditional ways of improving mitochondrial function. Weight loss is one way. The body automatically compensates for this by mobilizing energy-enhancing enzymes for survival purposes. Vitamin substances and exercise are other mitochondria enhancers. Hyperbaric chambers – where an intense flow of oxygen is fed to the brain, might offer some hope, though this method has its doubters. Finally there is the hope embodied in stem cell treatment which is the ultimate method for ‘starting over’ and rectifying ontogenic errors via implants and chemical infusion.
Clearly much remains to be discovered about this syndrome. Yet autism is one of those rare phenomena. In a sense everyone knows that it is – the behaviors, developmental tendencies all point to integration deficits, high arousal patterns, cognitive fragmentation etc. We just don’t know. Because the neuropsychological data have not kept pace with colloquial understanding of the cause (mostly because it requires a more stringent standard of proof) the goal of matching what we observe with what the brain of an autistic person does is not easily attained. Yet it does seem that at some point the studies of the energy producing apparatus in the brain and body that under normal conditions propels speech, cognition, social interest, attachment through pleasure-perceiving capacities will yield valuable information on how to energize the surprisingly knowledgeable, but under-expressive people we refer to as being autistic.
REFERENCES
Atwell, D & Laughlin, SB (2001) An Energy Budget for Signalling in the Grey Matter of the Brain. Journal of Cerebral Blood Flow & Metabolism. 21 1133-1145.
Belmonte. M. Allen, G. Becktel-Mitchener, A. Boulanger, L. Carper, R & Webb, S. (2004) Autism and Abnormal Development of Brain Connectivity. Journal of Neuroscience 24 (42) 9228- 9231.
Belmonte, M & Carper,R (1998) Neuroanatomical and Neurophysiological Clues to the Nature of Autism; In Garreau, B (Ed) Neuro-imaging in Child Neuropsychiatric Disorders. Springer-Verlag pp. 157-171
Ecker, C. Marquand, A. Mourau-Miranda, J. Johnston, P. Daly, E. Brammer, Murphy, C. Robertson, D. Williams, S & Murphy, D. (2010) Describing the Brain in Autism in Five Dimensions; Magnetic Resonance Imaging-Assisted Diagnosis of Autistic Spectrum Disorder Using a Multi-parameter Classification Approach, Journal of Neuroscience 30 (32) 10612-10623
Hashimoto, T. Sasaki, M. Sugai, K. Hanaoka, S. Fukumizu, M. Kato, T (2001) Paroxysmal Discharges on EEG in young Autistic Patients are Frequent in Frontal Regions. Journal of Medical Investigation 48 (34)
Hoyer, S (2003) Memory Function and Brain Glucose Metabolism. Pharmacological Psychiatry. 36 (1) 62-67.
Interview with Dr. Christoph Westphal in Mitoaction, Online Magazine discussed new drugs being researched to treat mitochondrial disease. In this interview he stated that many less severe diseases will soon be found to have mitochondrial causation, including neurobiological dysfunctions and type II diabetes.
Krause, I, He, X-S, Gershwin. ME Shoenfield, Y (2002) Brief Report: Immune Functions in Autism: A Critical Review. Journal of Autism and Developmental Disorders. 32: 337-345
Mitochondria in Brain Cells; Article Journal of Cell Biology July 6, 2009. Retrieved for Science Daily Jan. 25, 2011.
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Abstract
This article is written in a Piagetian mold. It revolves around of the case of an autistic man whose development in described in a way similar to Piaget’s observations of his nephew, Laurent. However unlike Piaget’s detailed studies, this discussion does not employ a single subject, empirical approach. “Alexander” is actually a composite of numerous autistic clients with whom this writer has worked and conducted evaluations. In one sense that makes it less precise. In another sense, the description of trends in behavior, speech and cognitive development might be perhaps more broadly applicable. In that context, there is discussion of recent research on autism with implications for establishing causation and future treatment options.
PROLOGUE
Alexander is a young man of twenty-five who was diagnosed with autism at around the age of two. He is in some ways an ideal subject, because he is neither in the high functioning nor low functioning range. From an observational standpoint that is important. So-called high functioning autistics are often so normal in terms of language skills and life style (eg. Temple Grandin) that it is hard to describe their limitations in stark neuropsychological terms. Moreover, in some instances high functioning autistics are misdiagnosed. For example the symptoms of childhood schizophrenia, organic brain disorders and even severe attention deficit disorders can overlap with autism. By the same token individuals with severe autism, with no language and profound deficits in the areas of cognition, motor skills etc. might not be able to provide clear indicators of what they can and cannot do. That makes their development difficult to describe in specific terms, making it hard to conceptualize with respect to causation and treatment possibilities.
Alexander is somewhere in the middle. He is quite capable on some ways. He is tuned in to his environment - rigidly, but tuned in nonetheless. He anticipates when others need help and often jumps in to assist. The problem is, he does not understand social mores or the need for ice-breaking skills. Family, friends, strangers – he knows the difference, but when it comes to acting in the moment, it doesn’t matter to him. Life is a series of dos and don’ts – mostly do’s. His outlook is to the point: see the circumstances, respond to the circumstances. Thus his abilities and social outlook tend to be literal and fragmented. The word “context” is as foreign to him as the Swahili word for pomegranate might be to us.
He uses speech, though unlike so-called high functioning autistic persons he won’t write books about his life experience or make presentations to groups. When he talks it is in a muffled tone and often askew of the interaction. He cannot look another person in the eye and converse. Maybe one or the other but not both, at least not in the usual rhythmic sequence familiar to the rest of us. Instead he might, after hearing a question, wander a bit, then in either sing-song or muffled tone provide a phrase that constitutes a delayed reply. The reply will be rough around the grammatical edges but usually apropos the interaction. Unfortunately this often goes unnoticed. The delay and intervening behaviors occurring between the first speaker’s comment and his response is often so long such that a less than perceptive person might not think he can speak at all. Over time much of his language will be so often ignored or unnoticed that he will lose his enthusiasm for communicating vocally.
In the clinical and social domains world Alexander is seen as having a severe neuro-behavioral disorder. To Alexander the disorder is not solely his. Rather it is one of proportion; in part, his deficiency in not being able to orchestrate the energy required to adhere to the language, social and behavioral rhythm codes of the outside world, in part our deficiency in not being able to comprehend, perceive and operate in his choppy, dysrhythmic world.
Alexander is misunderstood by many who are not familiar with his habits and the primary point of contention between he and the outside world boils down to two components. One is speed. While he reacts with great alacrity in many instances and requires much proactive cueing to abstain from impulsive behaviors he is also very delayed in his comprehension and expression. Thus Alexander is at once too fast and too slow in his pace.
The other component is energy. Alexander is a tall, robust man and when aroused his hand grip can be unfathomably strong. Under such conditions he can lift heavy objects – when for example helping (sans introductions) unsuspecting strangers. Consequently many assume he also has stamina, particularly his day program staff who might expect him to engage in activities for several hours on a daily basis. He typically resists doing so and when he is able to endure the demands of a daily program he ends up extremely tired and even more reluctant to engage the next day. A cloud - an inexplicable paradox - hovers over his handsome head. How can so strong a man be so lacking in task durability? What indiscernible weakness lies behind this man’s global reluctance to participate, his occasional behavior issues and his overall development?
Alexander’s behavior includes other confusing elements. For example his expressive capacities present a conundrum. He never “took off” in his early language development, in fact did not speak at all until he was around ten years old. Nor did he respond very well to directives, that is, unless he could put them into some visual or experiential context. Yet every once in a while he would utter a phrase he did not apparently learn and/ or never used before. Sometimes it can be profane: for example an f bomb occasionally emerges when he is frustrated. At other times it is more profound than profane – for example, a barely audible… “I am very intelligent.”
Alexander’s mode of acquisition (aka learning style) can be quite mysterious. To someone working with or living with Alexander it would appear he is somehow able to learn in latent manner; that is, without being taught, without giving any inclination that he is absorbing stimuli around him. Questions arise: does he actually absorb inputs? If so, is it done in the same way we do, whereby short term memory converts to long term memory, leading to subsequent retrieval? Or is it something else; some compensatory or adaptive memory process we don’t understand? And even though he seems not to absorb readily, information presented to him he is able to retrieve it later – perhaps hours later, sometimes days later.
Alexander’s language is almost never its own entity. Instead it seems to require extra “push” from other response systems. For example he moves a lot when he speaks, occasionally provides his own musical vocal accompaniment, and he will often cock his head as if using some sort of body English. Only with that added somatic thrust can he speak – or so it seems.
Still another feature of Alexander’s behavior is a spillover effect. Once aroused, he tends to remain aroused. Input has a pervasive impact and is so singularly influential in prompting his behavior that he is often unable to divert his focus from the first stimulus. As a result he tends to miss the experiential forest for the trees. Because of the singular, fervent impact of stimuli on his brain he soon learns to avoid stimuli that are too blatant or complex. The former overloads him, the latter is too hard to process sequentially with any real efficiency; due, once again to the spillover effect.
In observing Alexander it becomes clear that one crucial aspect of his developmental disability involves a kind of “neuro-burial” process. Whatever he takes in is buried, whatever he wants to say is buried, whatever social nuances he can comprehend are extant on some level yet buried within the confines of his central nervous system. Behaviors and memories are trapped in an endless neurobiological maze –or perhaps just weighted down like the gravitational pull of a black hole. While he has changed and improved considerably since childhood the burial factor seems to persist. Stuff comes out on occasion; words, behaviors suggesting a surprising insight, anticipatory reactions that seem almost clairvoyant, but not consistently. He clearly has but cannot summon this knowledge at will.
Alexander cannot simply described as being autistic. As a biological organism he must also be defined in terms of the laws of physics. Those laws mandate that in order for any type of work to transpire - be it lifting, speaking, thinking or playing a piano requires a series of energy bursts. Yet Alexander is faced with a problem. He appears to lack the capacity to produce those energy bursts.
That was ost evident in his early development. As a child Alexander could be swayed by the wind, with head movements unavoidably drifting in its direction. Speaking to him would be pointless, since he could not power his way past that wind’s distraction toward other matters.
Over time Alexander has learned, matured and improved, but he is still plagued by the lack of energy needed to focus past singular distractions, to search for and bring out responses, take on energy-demanding integrative tasks or push words out beyond low-key whisper talk. At times he can speak above the din but only with a boost from the somatic orchestra – as he sings and rocks his way past an ergonomic deficiency.
His emotions and behavior make sense in that context. His avoidance of eye contact, loud noises and crowds serves to ameliorate the impact of inputs. It is as though stimulus traces do not disperse democratically around his brain. If they did it might lead to the integrative access and perceptual input cushion enjoyed by the rest of us. Instead inputs run roughshod along narrow circuits so that perception poses a constant threat.
Alexander sees these tendencies in himself and does what all of us do when faced with an aversion. He tries to avoid stimuli that entail discomfort. He knows this has something to do with an energy-effort deficiency and most of his behavior outbursts result from his frustration at being asked to expend energy he does not have. Thus he is well-versed in the feeling and threat of fatigue. He recognizes that. He tries constantly to tell us, in effect…I lack the energy needed to live the way you want me to live. Yet many of us, intent on helping Alexander improve and enhance his skills through elaborate IEPs, behavior plans and service plans, insist that he engage, behave, expend energy - practice, because in our world practice leads to improvement. Alexander on the other hand fears that too much practice will lead to regression.
Alexander knows more than we think he knows and he’s probably aware of that fact. One can determine this from the logic of his behavior. For example Alexander has a penchant for worrying and his behavior clearly indicates a capacity for anticipatory thinking. That would not be the case if he were oblivious to outside circumstances, unable to comprehend, predict and memorize. Thus on some level Alexander’s anxiety, worries, fears, anticipatory emotional reactions signify the presence of knowledge that he cannot readily express.
Perhaps this line of reasoning can also be applied to his odd motor behavior (i.e. self stimulation). Assuming optimistically that Alexander is knowledgeable in a latent or “buried” sort of way, he must also have some sense of what is normal. If so, why behave in such odd ways? Is it because he doesn’t know any better – or something else?
If he could fluidly retrieve words Alexander’s answer might be that his odd behavior is employed (ironically) in order to conform to social standards. In other words, he might say that he acts this way primarily because of us. More specifically, in combining his knowledge and anticipatory capacities with his self knowledge, including an understanding of his own energy limitations, he self-stimulates to please those of us who make demands on him that exceed his energy resources. By hand flapping, noise making, rocking etc. he is not exhibiting signs of a pathology. Rather he is making a concession to (and a statement about) our own ignorance of his condition. The motor behaviors are an attempt to provide extra gross-bodily energy to meet our demands. He is “motor-psyching” himself up for the task, summoning extra power. (Imagine his dismay when instructors insist that he both engage in task and refrain from the energy-inducing actions needed to complete them). As a corollary: one cannot help but wonder if severe autism has a psychiatric component, reflecting a psychological breakdown resulting from a profound helplessness-inducing, irresolvable conflict inherent in some instructional programs that prompt task behavior yet discourage the self stimulatory (energy-inducing) behaviors needed to complete the task.
Alexander knows there is more to him than meets the eye. If appraised, he might not challenge research findings refuting the efficacy of Facilitative Communication because he is not familiar with Shakespearean phrases and does not ponder philosophical truths. Yet he undoubtedly would insist that while much of his knowledge is buried, it is extant nonetheless. If by some method his ideas and language could be “unearthed” and he were asked to explain the nature of his problem he might simply say…my motor is not as powerful as yours. In order to think, speak and do many of the things you take for granted I must borrow energy from other places in my brain and body. I operate with a power deficiency and the only way I can navigate through my world (or more precisely, yours) is to mobilize my entire mind, senses and body. That’s why I do weird things. As you can imagine, it entails a lot of work and frankly I’m exhausted most of the time.
CONFIRMATION/RECONCILIATION
Since Alexander has hypothetically identified for us the nature of his problem, we might as well pivot off that in discussing whether his “theory” of causation coincides with research findings. First, recall that Alexander conceives of his problem as being a grounded in an energy-summoning deficiency that interferes with cognitive, perceptual, language and motor stamina. His odd neuro-muscular priming activities are not the sine qua non of autism or even diagnostically meaningful. In his view, many autistic behaviors represent attempts to build a bridge between his low energy world and the high energy world of the normal person. Are his assumptions correct?
ENERGY AND THE BRAIN
A recent study discussed by in Science Daily (2011) describes a process by which the brain creates and transports what might be called “the power that fuels cognition.” When it comes to brain and energy a paradox is involved. To begin with, all the cells in the body contain energy packets called mitochondria. These are organelles that produce the primary fuel enabling us to act, think, speak and remember. The fuel produced by the mitochondria is a sugar called ATP - or adenosine triphosphate. Since all cells contain mitochondria and produce ATP it stands to reason that brain cells (neurons) would do the same and that a normal adequate brain would be consistently able to summon the energy needed to perform various human functions.
It turns out the process is a bit more complicated than that. Brain cells are more elongated and include branches called axons (leading away from the neuron) and dendrites (leading to the neuron). For the brain to function requires that energy be provided not just within a given cell but transported along these branches because ATP is needed to fuel each action and connection along the way. With a depletion of ATP at any point, transmission would be faulty and faculties would be adversely affected. Beyond that, some of the ATP must return to the source neuron because it too must continue its work and cannot be left devoid of fuel. That means that the energy transmission process in the brain involves a higher degree of complexity and uncertainty, as well as a greater error factor.
As if that weren’t enough, it seems the brain operates via an inherent energy depletion state. While our breathing takes in oxygen at a 20% rate our brains only consume oxygen at a rate of 2.5 percent. That would seem to imply that all human brains are prone to rapid fatigue and are inherently, naturally ergonomically deficient – except for one thing. Certain proteins in the brain provide compensation. One is called HUMMR (hypoxia-unregulated-mitochondria movement response). It is called into action during low oxygen states. Another is HIF-1 (hypoxic inducible factor-1) which operates in similar fashion. These proteins facilitate the energy-compensating process so that low oxygen levels can be replenished. A malfunction in mitochondria, ATP production among nerve branches or a protein deficiency in synthesizing ATP could create a low energy state that could slow down and make considerably more difficult the functions of learning, retrieving, speaking and integrating experience.
The thrust of these findings seems to indicate that the brain tends toward a quasi-normal state of low oxygen (hypoxia). It is as though autism is a primal, normal state within the brain that is corrected for by mitochondrial functions. The brain seems to require a low oxygen state to call it to action so that the compensatory protein-generated energy replenishment that produces behavior can occur. Thus, despite their experiential connotations, cognition, behavior, emotions and other phenomena are ultimately the result of renewed states of energy via a negative feedback mechanism. Our faculties consist most essentially of a conversion from an abnormal state to a normal one, which raises the question of what would happen if that conversion process somehow went awry.
Another aspect of the mitochondria-ATP-protein sequence is that when functioning properly it also serves immune functions. Consequently, a depletion or malfunction of this process would tend to create a susceptibility within the immune system. That might involve a hypersensitivity to allergens, vaccines, or conceivably any substance that is harmless to most infants but not those with this deficiency.
In reviewing the research it appears Alexander’s theory has some support. For example, Atwell & Loughlin (2001) have shown that the brain budgets energy and that spiking activity, which is typical in autism (Hashimoto, et al 2001 ) creates more energy depletion than well distributed, integrative activity (which is not typical in autism). From this one can derive that the autistic brain has to work harder and expends more energy in executing even simple tasks. Just why that occurs was an issue not addressed in the Atwell study.
It was addressed to an extent by Belmonte et al (2004) who found that the autistic brain’s architecture tends to be more fragmented than the normal brain, particularly in the energizing, initiative-producing,-cognitive-enhancing circuit known as the cerebellum. The separation of neural columns in this site foments to some extent the kind of spiking activity and high regulatory demands that lead to more rapid energy depletion. The question in that regard is whether autism is related somehow to increased energy demands in light of columnar fragmentation, or whether the energy is required to integrate the columns is lacking. In the case of the former the autistic symptoms would result from ongoing fatigue. With the latter, low energy resources would prevent the autistic person from being able to do the work of integrating experience – other than with the added thrust of self stimulation.
With respect to the immunological issue, studies by Krause et al (2002), Warren et al (1996), and van Gent et al (1997) have shown a greater susceptibility to allergies and immunity problems in autistic subjects. With regard to the question of whether this has to do with mitochondrial function, the research of Tsao & Mendell (2007), Pons, et al (2004), Poling et al (2006), Oliviera et al (1998) and Vicente (2005) offers support. The Oliviera study found that the ratio of normals with mitochondrial malfunction at birth is 1 in 4,000 (.025 percent) whereas that of autistic children is 5 % - a rate twenty times that of normals.
THE METABOLISM OF MEMORY RETRIEVAL
If Alexander’s theory is correct, there should be some sort of extraordinary metabolic effort required to retrieve memories, because that could be at the core of his problem. This would not necessarily involve learning words, grammatical sequences, faces, names etc. Rather it would entail sifting (powering) through brain circuits to find and express them. With regard to the question of whether it involves fragmented columnar wiring, of a lack of energy to conduct the search and create the extra columnar interactions in the brain, a studies by Hoyer (2003) is indicative. He was able to show that memory retrieval involves a complex catabolic process anchored by ATP that involves a break down of glucose via a regulatory assist from insulin in the brain. Depletion of any of those neuro-chemicals will lead to memory loss.
The term “memory loss” is more often associated with Korsakoff’s, Alzheimer’s and other organic disorders than with autism. Therefore it might seem trite to say that autism entails memory loss, that is, unless one substitutes memory retrieval for memory. The latter suggests an ingrained mental state – a passive storage process. In fact what we typically refer to as memory is an active process and invariably involves search functions within the brain. To carry out that search activity requires a sound metabolic capacity whereby which mitochondria, ATP and various neurochemical transmissions interact fluidly.
Alexander’s theory of extreme fatigue and a related search-deficiency makes sense on that context. In fact it might be reasonable to give his syndrome a new name, first by tossing out the awkward word “autism” - which sounds more like a state of social isolation than a neurological or developmental disorder, and replacing it with the complex but perhaps more descriptive word neuropsychasthenia, which connotes a profound state of CNS fatigue, whereby the energy supply ordinarily needed to facilitate integration and retrieval, preclude the need for neuromuscular priming to meet task demands, help modulate inputs and produce enough energy/excitatory mobilization for language expression is depleted. Autism…or “NPA” would then be considered at least partially akin to a chronic state of lethargy, and highly reminiscent of Rudy’s description of autism as being tantamount to a chronic state of sleep (2010).
OXYGEN-SEQUENCING AND LANGUAGE ACQUISITION
In the prior discussion of energy dynamics in the brain, the functions of mitochondria and ATP were discussed. While both are crucial aspects of energy provision and maintenance, there is a third factor involved. It is the last step in the energy consumption cycle – the burning of oxygen to foment activity. If mitochondria is the engine of behavior, ATP the fuel, then oxygen is the byproduct of this cycle. For that reason recent research has focused on the dispersion and consumption of oxygen in various sites in the brain.
One of the more recent and interesting projects was conducted by Ecker et al (2010). Using PET scans, the team discovered what appears to be a reliable tool for diagnosing autism. They found that oxygen levels in the left cortical hemisphere (involved in language and sequential reasoning) had a low oxygen dispersion. In effect the flow of oxygen was fragmented, not fluid and conceivably unable to provide mental continuity for exertion in cognitive and linguistic functions. Interestingly, it was also discovered that the pattern of blood flow to the right hemisphere of autistic subjects was virtually the same as occurred in the left hemisphere of normal subjects – making it appear that autism might involve some sort of “wiring reversal.” The Ecker study was conducted with high functioning autistic subjects, thus some have questioned its applicability to the syndrome as a whole. Yet the correlations between poor oxygen dispersion and a diagnosis of autism was extremely high – with virtually no false positives occurring among normal subjects in the study. Thus it clearly has significance as a diagnostic tool. It also has parallels to research on oxygen depletion in the brain of autistic individuals. For example a study by Rossignol et al (2010) indicated that hyperbaric oxygen treatments led to amelioration of autistic symptoms.
The results of the Ecker study raises the question of why one side of the brain would receive more oxygen than another. One possibility is that sequential faculties require more energy than those providing spontaneous and holistic processing – as seen in the right hemisphere. This assumption is based on the idea that sequential, organized thinking, which is required in the use of grammar, logic and step by step analysis demands more inhibitory restraint. in order to speak it is necessary to excite circuits devoted to word memory. However a sentence has to be understood, which means it also requires a particular cadence, ie. a breakdown of parts of speech and various other parsing skills and deliberation. That entails complex interactions and apportioning among excitatory and inhibitory neurons on the brain. Presumably the orchestration of stop and go neural substrates of sequential behaviors would be a high-energy endeavor and thus require more oxygen.
In that context one way to look at the Ecker study on autism is to assume that normal blood flow in the right hemisphere is not indigenous to the syndrome but rather the end product of an adaptation/energy redistribution learning process occuring in the brain of the autistic subjects. This implies that insufficient oxygen and energy resources in the left hemisphere lead to a compensatory shift in thought and action to the right hemispheric so that the autistic subjects can negotiate through their world in a global manner. In other words, oxygen distribution in the brain of autistics might be less of a pure diagnostic tool than a statement about a post-morbid adaptation. Whether or not this has validity, it is consistent with the tendency among autistic individuals to problem solve through gross motor rather than language faculties, and to globalize their feelings, thoughts and behavior into “lump sums” of experience.
In either case much of the research thus far discussed would tend to support Alexander’s theory that at least one of central feature of autism is neuropsychasthenia.
HYPOPLASIA IN THE CEREBELLUM
Another study on autistic subjects have shown a lack of maturation of cells in a part of the brain known as the cerebellum – a condition referred to as hypoplasia. (Belmonte 1998) Not all subjects exhibited this characteristic, in fact some showed an opposite tendency. However one of the benefits of the research on cerebellar functioning in autistic subjects is that this massive circuit has been discovered to have many more functions than previously thought.
The classical description of the cerebellum was as a motor circuit providing a movement backdrop against finer movements that emanate from the cerebral cortex. In the past it was viewed as a computer-like circuit providing organisms with a motor anchor point so that certain movement prerequisites could be taken for granted in conducting activity. It now appears the cerebellum provides more than a motor stabilizing function, and that it also provides an anchor point (and sense of automaticity) for language and cognition.
The ostensible relationship between energy and cerebellar functions is interesting. One could assume, as did Belmonte that impairment or lack of maturation (hypoplasia) in this lobe would remove the stabilizing, “automatic” aspect of behavior, which would make each experience seem new and potentially threatening. That would certainly account for the memory deficiencies in autism as well as the repetitive behavior, need for structure and rituals.
More recent research on the cerebellum seems to indicate that it plays not only a more extensive role in cognitive, language and memory functions. It also appears to provide intent, which means it creates an apriori template for expectations that drive behavior. It is a highly redundant circuit, not in itself complex enough to produce myriad functions but nonetheless richly connected to other brain sites. That means it provides impetus and stability, intent and confirmation. Also since it is comprised mostly of Purkinje cells, which produce a pleasure chemical called serotonin it has a role in generating emotion as well. Could this have something to do with the flat affect typically seen in autistic individuals?
If one attributes a drive-sustaining function to the cerebellum then it too ultimately could be viewed in ergonomic terms and it would have to depend on adequately distributed, intact mitochondrial systems, ATP production and fluid patterns of and oxygen consumption.
NEW HORIZONS
In not being able to specify as to the causes or core bio-genetic aspects of autism it is difficult to speculate on possible future treatments. If mitochondria deficiencies are involved, then as of the moment there are no reversible treatments. Some research is being conducted by Dr. Christoph Westphal on development of enzyme catalysts that will enhance mitochondrial function. He elaborated on this topic in an interview in Mitoaction. Also, there are traditional ways of improving mitochondrial function. Weight loss is one way. The body automatically compensates for this by mobilizing energy-enhancing enzymes for survival purposes. Vitamin substances and exercise are other mitochondria enhancers. Hyperbaric chambers – where an intense flow of oxygen is fed to the brain, might offer some hope, though this method has its doubters. Finally there is the hope embodied in stem cell treatment which is the ultimate method for ‘starting over’ and rectifying ontogenic errors via implants and chemical infusion.
Clearly much remains to be discovered about this syndrome. Yet autism is one of those rare phenomena. In a sense everyone knows that it is – the behaviors, developmental tendencies all point to integration deficits, high arousal patterns, cognitive fragmentation etc. We just don’t know. Because the neuropsychological data have not kept pace with colloquial understanding of the cause (mostly because it requires a more stringent standard of proof) the goal of matching what we observe with what the brain of an autistic person does is not easily attained. Yet it does seem that at some point the studies of the energy producing apparatus in the brain and body that under normal conditions propels speech, cognition, social interest, attachment through pleasure-perceiving capacities will yield valuable information on how to energize the surprisingly knowledgeable, but under-expressive people we refer to as being autistic.
REFERENCES
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Belmonte, M & Carper,R (1998) Neuroanatomical and Neurophysiological Clues to the Nature of Autism; In Garreau, B (Ed) Neuro-imaging in Child Neuropsychiatric Disorders. Springer-Verlag pp. 157-171
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Interview with Dr. Christoph Westphal in Mitoaction, Online Magazine discussed new drugs being researched to treat mitochondrial disease. In this interview he stated that many less severe diseases will soon be found to have mitochondrial causation, including neurobiological dysfunctions and type II diabetes.
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