LECTURE 5 – NEURAL MECHANISMS OF AUTISM

There is controversy on whether to define autism spectrum a disorder or a

trait.

Instead of disorder, there is an idea of a neurodiverse population, and we

are all in the autism spectrum. Neurodiversity emphasizes the natural
diversity that exists in human neurodevelopment.

Neurotypical refers to a person with typical neurodevelopment and

neurodivergent when a person diverges from the range constituting the
typical.

There are no neuromechanisms clearly identified for autism spectrum

condition (ASC), but there are some consistencies in findings.

ASC has a prevalence of 1-2%, with symptoms manifesting starting in

early development, more prevalent in males (1 female per 3 or 4 males),
but females are underdiagnosed. In addition, there are several
comorbidities associated, including epilepsy and other
neurodevelopmental conditions.

The diagnostics is done with ICD-11, and the diagnostic requirements are:
Persistent deficits in:
 Initiating and sustaining social communication and reciprocal social
interactions that are
o Outside the expected range of typical functioning given the
individual´s age and level of intellectual development
o Specific manifestations of these deficits vary according to
chronological age, verbal and intellectual ability, and disorder
severity
 Restricted, repetitive, and inflexible patterns of behavior interests,
or activities that are clearly atypical or excessive for the individual´s
age and sociocultural context

Specifiers

Co-occurring disorder of intellectual development

 With or without
Degree of functional language impairment
 With mild or no impairment of functional language
 With impaired functional language (not able to use more than single
words or simple phrases)
 With complete, or almost complete, absence of functional language

Alterations in social cognition are accompanied with different

perceptual experience of the world
Involving all sense. With large individual variety, all the way to intact,
enhanced or impaired. Some research suggests that sensory sumptoms
may be predictive to impaitments in social communication, as they can be
seen early in development (<6 months).

This sensory processing can be low-level involving different modalities and

multimodal perception. Deficit in social-emotional information processing
in ASD comprises at least touch, sight and sound.

Some of the theories to explain this sensory issues are regarding:

 Temporal binding hypothesis
o Timing information is crucial to binding and integrating
associated stimuli
 Intense world theory
o Excessive functioning of neural circuits, hyperactive
 Atypical hierarchical information processing
o Over-functioning of bottom-up sensory processing coupled
with under-utilizing top-down perception

Another important feature is motion processing. Research has shown

disruption in attending to and in recognizing biological motion in
individuals with ASD.

There is also disruption in tactile perception. Social-emotional processing

network showed less activation in response to CT-targeted touch.

There is also regarding multisensory integration, suggesting ASD

individuals being less sensitive for asynchrony, less susceptible to
integration to audiovisual speech, McGurk effect.

Social motivation theory

Objects with social importance are prioritized by attention

Social interactions are rewarding
Interpersonal behaviors are influenced by the desire to maintain and
enhance relationships

Literature shows aberrant neural processing of social, nonsocial, and

potentially restricted interest rewards in individuals with ASD
Domain general reward processing deficits in ASD supporting a broader
interpretation of the social motivation hypothesis
Heterogeneity with effects of age, sex and IQ

Neural basis of social behavior

Impossible to bring the social world to the laboratory. Research has shown
certain brain areas responding more to social behavior.

Neural circuits of perception of others.

Developmental trajectory

There is a clear developmental trajectory for social behavior, and how this
relates to ASD.

Clinically one of the most significantly early signs of ASD is joint attention.
Joint attention is coordination of one´s own attention wit another person
attention to adopt a common point of reference and share information.
Goal-oriented attention. And it is distinguished from face processing and
imitation by the triadic nature of social-spatial-referential information
processing.

Most consistent findings

 Brain volume outgrowth in infancy and early childhood, as

documented through differences in brain volume
 Children with ASD have accelerated brain development in early life
 Altered connectivity
o Inter-connections as well
o Correlation or causal interactions in activity of different
regions
 Overall brain under-connectivity, coupled with local over-
connectivity within specific regions often the frontal and occipital
regions

Neuroanatomical findings

 Significant heterogeneity across different aetiologies, neurobiology

and clinical phenotypes of ASC is reflected in neuroimaging-based
neuroanatomical abnormalities
 The abnormalities show age, gender and IQ-related variation
 Many regions are affected; changes in the growth of corpus
callosum, amygdala, and cerebellum
 Greater cortical thickness in individuals with ASD relative to controls
in the superior temporal gyrus and inferior frontal sulcus

Therefore, there is a need for large datasets

One can find 3 structural subtypes based on all these data.

Female population is lower.

Autism spectrum disorder is a term used to describe a constellation of

early-appearing social communication deficits and repetitive sensory–
motor behaviours associated with a strong genetic component as well as
other causes. The outlook for many individuals with autism spectrum
disorder today is brighter than it was 50 years ago; more people with the
condition are able to speak, read, and live in the community rather than in
institutions, and some will be largely free from symptoms of the disorder
by adulthood. Nevertheless, most individuals will not work full-time or live
independently. Genetics and neuroscience have identified intriguing
patterns of risk, but without much practical benefit yet. Considerable work
is still needed to understand how and when behavioural and medical
treatments can be effective, and for which children, including those with
substantial comorbidities.

autism is now seen as a spectrum that can range from very mild to
severe. Nevertheless, many (but not all) individuals with ASD require
lifelong support of some kind.

Although individuals with ASD are very different from one another, the
disorder is characterised by core features in two areas—social
communication and restricted, repetitive sensory–motor behaviours—
irrespective of culture, race, ethnicity, or socioeconomic group. ASD
results from early altered brain development and neural reorganisation.
However, there are no reliable biomarkers.

Given existing health systems, there are clear, continuing needs for
coordination between health-care, education, and other services (such as
intense support for challenging behaviours and planning for adult
residential and employment programmes for individuals with ASD). Even
the immediate demand on physicians’ time for counselling and support of
families facing potential early diagnoses is a controversy in the USA
because these are generally not billable services for paediatricians. To
date, scientific focus has primarily been on the development of more
accurate tools for identification; however, using community resources to
develop and promote use of more readily available treatment programmes
in which young children and adults can participate might make more
sense, because physicians are more likely to screen and refer when they
perceive a benefit to the family from doing so. Economic data—such as a
2012 report that indicated that, in the USA, for every $1000 spent on
respite care, there was an 8% decrease in spending on inpatient
psychiatric services on Medicaid-enrolled children with ASD136—could be
helpful in justifying the cost of services such as respite care. In basic
science research, much has been learned; however, the clinical
implications remain few, partly because of findings from both genetics and
imaging studies that ASD is not typically caused by a specific gene or
highly localised lesion, but might result from combined or not-yet-
understood genetic risks and disruptions in very early developing neural
pathways. Although the idea of continuous traits underlying ASD is
appealing to many scientists, it should also be recognised that many of
these traits, such as intelligence, language level, activity level, anxiety,
motivation, and aggression, interact with each other in complex ways, and
thus simple models do not represent actual development. In terms of
global health, focusing on the goals of children and adults with ASD and
their families, rather than on how to plug gaps in existing systems, might
help to set appropriate priorities. Innovative solutions, such as adaptations
of evidence-based interventions for low-resource settings through
empowering front-line health-care workers, are underway.137,138
Conclusions Life for many children and adults with ASD is improved today
compared with 50 years ago. More adults with ASD can talk, read, drive,
graduate from school, and live in the community—even accounting for the
differences in which people would meet the diagnostic criteria now and in
the past, and their respective levels of intelligence. Caregivers can be
reassured that the situation has improved, and will continue to improve,
for most people with ASD. We hope that research directs attention to
individuals who still have substantial difficulties and provides pathways to
fuller inclusion and greater independence for more people. Science and
public policy both have the potential to contribute to such changes.
Working with families, schools, and community providers, clinicians can
make differences in the lives of individual children and adults by providing
accurate and realistic information, support, and hope.