Autism Flashcards
True or false? Explain your answer if necessary. (1)
Epidemiological studies suggest that ASD aetiology is entirely environmental, and does not have a genetic component.
False - Epidemiological studies suggest that ASD aetiology has a strong genetic component
What is the concordance rate for autism amongst monozygotic twins? (1)
60-70%
What is the concordance rate for autism amongst siblings? (1)
18-33%
Give the two core diagnostic criteria for ASD. (2)
- Persistent deficits in social communication and interactions
- Perseverative behaviours and interests
Fill the gaps relating to ASD. (4)
In addition to the core diagnostic criteria, most affected individuals also show aberrant reactivity to …………………… or ‘unusual interest’ in …………………… aspects of the environment.
They may also display deficits in ………………….., or general clumsiness, which may exacerbate ……………………….
sensory input
sensory
motor skills
social exclusion
Give three examples of specific sensory behaviours which may be seen in ASD. (3)
- Adverse responses to sounds or textures
- Excessive smelling or touching of objects
- Visual fascination with lights or movement
True or false? Explain your answer if necessary. (1)
25% of people on the autistic spectrum cannot drive due to difficulties interacting with dynamic objects.
False - it is actually more than 75%
Describe how difficulties interacting with dynamic objects in autistic people may manifest in childhood. (1)
Individuals with autism often describe the difficulties they had as children engaging in athletic games or team sports on the playground.
Fill the gaps relating to ASD. (6)
People with ASD often have difficulties interacting with ………………….. objects.
Several studies have shown that basic ……………………. and …………………… thresholds are largely unimpaired in autism.
However, to interact with a dynamic object, there is a crucial step beyond simple detection - ………………….. of where the moving object is likely to be at a given moment in the future.
Accurate anticipation skills help us to plan our ………………………… appropriately to intercept or avoid objects.
Even the seemingly simple task of keeping track of a moving object requires such ……………………
dynamic
object motion detection
direction perception
anticipation
motor movements
anticipation
Briefly describe the rubber hand illusion. (4)
- Patient has their hand in a box but cannot see it
- They can see a rubber hand placed near their own hand
- Give tactile stimuli to rubber hand and/or own hand and see reaction (i.e. does person retract hand)
- Then give a subsequent task involving reaching and grasping movements
How do people with ASD react to the perceptual effects of the rubber hand illusion? (1)
They react typically - no difference between ASD and non-ASD individuals
How do people with ASD react to the subsequent motor task following the rubber hand illusion? (2)
The influence of the illusion was reduced compared to controls
People with ASD perform better on the reaching and grasping movements
Give a possible explanation as to why individuals with ASD perform better on a motor task after the rubber hand illusion (the influence of the illusion is reduced in ASD). (1)
They may assign stronger weighting (precision) to proprioceptive sensory input relative to prior contextual information.
Fill the gaps relating to ASD. (9)
The Rubber Hand illusion study highlights the relatively lower weighting assigned by people with ASD to …………………………… versus ………………………….
Sensory information can be noisy and ambiguous, and so integrating ……………………… and ……………………………. into motor movements is necessary to optimally ………………………….. and predict the …………………….. of objects in the external world.
Motor incoordination in ASD can be explained by the increased weighting of ………………………. in perceptual inference.
Relying too heavily on incoming sensory information at the expense of prior information usually leads to a less accurate sense of ……………………….., which may contribute to clinical symptoms of ……………………… (and the reduced smoothness of movement observed for the clinical group in this study).
prior or contextual information
sensory feedback
prior beliefs
contextual information
interact with
motion
sensory information
body position
motor incoordination
The rubber hand illusion can mislead performance in neurotypical subjects.
Suggest why this might be. (1)
What is the advantage of this? (1)
They have an increased weighting of higher-order contextual information versus sensory input.
This increased weighting of higher-order contextual information to guide movement will usually be of benefit when engaged in skilled motor performance tasks (e.g., when performing movement without visual feedback).
True or false? Explain your answer if necessary. (1)
Sensory hypersensitivities in ASD can be explained by abnormal enhancements in sensory organs and in the lower-level processing of sensory information.
False - sensory hypersensitivities CANNOT necessarily be explained by these concepts
Complete the sentence. (1)
Sensory hypersensitivities in ASD may arise due to a reduced ability to ……………………………..
*Hint: it is a phrase
habituate to novel environmental stimuli.
Fill the gaps relating to sensory hypersensitivities in ASD. (4)
Sensory hypersensitivities may arise due to a reduced ability to ……………………… to novel environmental stimuli.
A key determinant of our ability to do this is ………………………….
The lack of predictability of our surroundings would compromise ………………………. and lead to ………………………….
habituate
stimulus predictability
habituation
hypersensitivity
Describe what is meant by ‘habituation’, and give an example. (4)
A type of learning that involves a decrease in behavioural response
to a repeated stimulus over time.
It’s a conscious or active shift in attention that can occur without much thought.
For example, if you hear a loud, sudden sound like a siren or thunderclap, you might jump or stop what you’re doing.Once you confirm that you’re not in danger, you’ll calm down and resume your activities.
Describe how loudness adaptation is affected in adults with ASD. (1)
Adults with ASD tend to display decreased loudness adaptation.
Describe why adults with ASD tend to show decreased loudness adaptation. (2)
Could be caused by a failure to update prior beliefs (predictions)
and a dampening of the ability to reduce surprise during a series of predictable stimuli.
What is ‘loudness adaptation’? (1)
A decrease in how loud a constant sound is perceived as over time.
Finish the sentence. (1)
Being immersed in a novel ambiguous (noisy) environment can feel like we are being unrelentingly bombarded by salient sensory stimuli.
Our capacity to habituate is dependent on …
**Hint: it is a phrase
our ability to suppress this sustained stimulation and prevent sensory overload.
Finish the sentence. (1)
Sensory bombardment is a known stressor and a cause of anxiety even in non-ASD subjects.
Thus, the aversion to environmental sounds that individuals with autism exhibit could arise from …
**Hint: it is a phrase
a reduced capacity to habituate.
True or false? Explain your answer if necessary. (1)
Environmental unpredictability is strongly correlated with anxiety.
True
Fill the gaps relating to ASD. (5)
Environmental unpredictability is strongly correlated with …………………..
A reduction in the ability to predict events, even non-threatening social situations, enhances ……………………..
Anxiety, especially when it is elevated chronically, is known to give rise to ………………………..
The behaviours that emerge under conditions of unpredictability serve as a …………………… response to an …………………….. These behaviours may be as benign as leg-swinging in school children who are working on a stressful math examination or more alarming stereotypies that inflict self-injury.
anxiety
anxious responses
ritualistic behaviour
calming
external stressor
How does the incidence rate of ASD change in rural settings vs cities? (1)
Higher rates in children living in cities (is this because there is more unpredictable stimuli?)
Fill the gaps relating to ASD. (6)
Sometimes referred to as ……………………, compulsive ritualistic behaviours in ASD can often be regarded as …………………………. and resemble ………………………….
They can manifest as an …………………….. response to a chaotic world and function to drown out the influx of ……………………………. through an increase in self-generated periodic and, hence, ……………………. stimuli.
self-stimulating behaviours (stimming)
socially inappropriate
involuntary motor ticks
anxiolytic-type
unpredictable environmental information
more predictable
A key feature of ASD is the ‘insistence on sameness’. Give five examples of how this trait may manifest. (5)
- Repetitive thoughts and actions
- Behavioural rigidity
- Reliance on routines
- Resistance to change
- Obsessive adherence to rituals
Fill the gaps relating to ASD. (10)
Highly functioning individuals on the autism spectrum used to be referred to as having …………………………….. These individuals usually lacked a general retardation in …………………… and did not display ……………………….
This term has been retired as a diagnostic classification and the autism spectrum has been widened to now include individuals who display …………………………………… at first sight.
However, their ability to cope with the demands of daily social situations and changing complex environmental settings can be ………………
This chronic stress can cause significant ……………………. and …………………….., and can predispose people with ASD to comorbidities, e.g., ………………….., ………………., or …………………
Asperger syndrome
language
intellectual disability
only a few classical symptoms of ASD
frail
mental exhaustion
internal suffering
depression
anxiety
substance misuse
Describe how ASD features may change over the lifespan. (2)
May remain hidden until they are unmasked by increasing social interactions and demands during childhood.
May also become less noticeable in adulthood due to the development of situational coping strategies.
Give four examples of situational coping strategies that may be used in ASD. (4)
- Repeating phrases exactly as others have said them
- Creating scripts to use in social situations
- Using behaviours learned from watching other interactions
- Practicing facial expressions and body language
Fill the gaps relating to ASD and Bayesian information processing. (6)
Autism spectrum disorder is clinically characterized by prominent disruptions to one’s ……………………., which may be explained by an impairment of …………………………
Individuals with ASD have striking difficulties in distinguishing between ……………………. details and ……………………. changes in their environment.
Apparent subtle changes in environment (e.g., variations in location or timing) can be sufficient to induce feelings of ………………….. and a …………………..
perception
hierarchical Bayesian inference
relevant/informative
irrelevant/random
uncertainty
lack of control
Give 2 examples of a person with ASD being unable to distinguish between relevant and irrelevant changes in their environment or situation. (2)
During social interactions, a person with ASD may direct more attention to a bright colourful pullover rather then to the emotional expression on a friend’s face.
Meeting a friend in a pub in the evening may feel like a very alien situation compared to their usual afternoon meet-up in the university cafe.
Describe how generative/internal models of the outside world are affected in people with ASD. (2)
People with ASD struggle to establish abstract and generalisable representations that can be applied to a broad range of environmental situations.
Instead, they tend to generate overly precise models (priors) of single observations and sensory stimuli.
True or false? Explain your answer if necessary. (1)
People with ASD tend to establish overly-generalisable internal models that can be applied to many different situations.
False - people with ASD struggle to establish abstract and generalisable representations
Fill the gaps relating to ASD and Bayesian information processing. (4)
In people with ASD, the fact that they struggle to establish generalisable internal models can induce a chronic sensation of being …………………. for whatever may happen, unless they can exert …………………. (and thus avoid …………………) in a stable, well-known environment.
This feeling may underlie their desire for …………………., such as never changing the exact order of a sequence of actions in everyday life.
unprepared
control
surprise
fixed rituals
True or false? Explain your answer if necessary. (1)
Several recent articles have suggested that aberrant Bayesian inference underlies perceptual abnormalities in ASD.
True
Describe two theories regarding aberrant Bayesian inference underlying ASD (specifically relating to prior beliefs). (2)
ASD is characterized by overly flat (imprecise) priors, which lead to percepts dominated by the sensory input.
In ASD, an overly high weighting is assigned to sensory stimuli which may increase prediction errors and lead to overly precise (non-generalizable) priors.
Fill the gaps relating to ASD and Bayesian information processing. (6)
Lawson et al. suggest that the ………………… of top-down predictions need to be weighted against the ………………….. of bottom-up sensory input. They highlighted the importance of ………………………. as a potential neurobiological mechanism for precision weighting and hypothesized that neuromodulators such as ………………, ……………., or …………….. could play a central role in fine tuning prediction errors at each hierarchical level of sensory neural pathways.
precision
expected precision
postsynaptic gain control
GABA
acetylcholine
oxytocin
What is meant by ‘postsynaptic gain control’? (6)
Brain and spinal cord have many neural ensembles, which are modulated by interneurons
Higher cognitive centres send predictions down the hierarchical sensory processing pathway
Predictions regulate the postsynaptic gain (level of signals which get through each gate in the hierarchy)
Imprecise prior models = imprecise predictions = lots of prediction errors getting to brain
So higher postsynaptic gain and more precision weighting applied to sensory input
Therefore, internal models are constantly being updated using new information (prediction errors) which gets to brain
Describe the pathway that predictions (priors) take when they are generated and sent down the hierarchical information processing nodes. (4)
cortex
thalamus
midbrain
spinal cord
Fill the gaps relating to postsynaptic gain control. (5)
In terms of neuronal signals, predictions may take the form of ……………………. that function to modulate ……………………… activity in key neural ensembles of the …………………….. pathways.
Thus, any deviations between sensory inputs and prior beliefs ascend up the hierarchy and are integrated as …………………….. that serve to …………………………….
trains of action potentials
inhibitory interneurone
afferent sensory
prediction errors
update our model of the external world
Give four different ‘types’ of inhibition by interneurones, in terms of how interneurones are connected with projection neurones. (4)
Feedforward inhibition
Recurrent feedback inhibition
Lateral feedback inhibition
Disinhibition
Give four ways to classify interneurones. (4)
Why are these important when looking at postsynaptic gain control? (1)
- Morphology
- Connectivity
- Markers
- Intrinsic properties
A combination of these properties will determine how the interneurone acts to modify postsynaptic gain control.
Describe feedforward inhibition. (2)
Principle (projection) cell and interneurone both activated by same input neurone
Interneurone then inhibits principle cell.
Describe recurrent feedback inhibition. (2)
Principle cell activates interneurone
which acts to inhibit principle cell.
Describe lateral feedback inhibition. (2)
Principle cell activates interneurone
which then inhibits another local principle cell.
Describe disinhibition in terms of interneurones. (2)
One interneurone inhibits a second interneurone
which results in more activation of the principle cell.
True or false? Explain your answer if necessary. (1)
In ASD, there is aberrant updating and overfitting of the internal model.
True
Explain the potential cause behind the aberrant updating and overfitting of the internal model in ASD. (1)
Over-estimation of the precision of bottom-up sensory input when compared to the precision of top-down predictions.
Describe how the aberrant updating and overfitting of the internal model in ASD may alter perception. (1)
May lead to an altered style of perception dominated by detailed but irrelevant aspects of the environment.
Fill the gaps relating to ASD. (4)
People with ASD may have difficulties in establishing …………….. and ………………. representations (models) of the world at the highest cognitive levels which neurotypical individuals use to ………………….. novel environmental situations.
Therefore, ASD may be thought of as an impairment of ……………………………………
stable
precise
generalise
hierarchical Bayesian inference
Fill the gaps relating to perception in ASD. (9)
The overweighting of ……………………………… leads to constant fluctuations and large uncertainty at higher levels in the generative model, which should represent ………………………. that can be used to predict a wide range of ……………………….
Aberrant …………………………… or the continuous …………………………. of high-level generative models may mean that relatively predictable stimuli are continuously perceived as ……………………….
The result is an ………………….. generative model that is dominated by ………………………. and has limited ……………………..
uninformative sensory prediction errors
abstract concepts
situations
predictive coding
updating
surprising
over-fitted
sensory details
generalisability
Describe how people with ASD typically use generative models and sensory inputs to perceive novel environments or unpredictable dynamic social situations. (2)
Difficulty in establishing abstract generative models to represent novel or unpredictable situations
so instead rely heavily on sensory inputs to guide their actions.
True or false? Explain your answer if necessary. (1)
ASD can be seen as a general disorder of hierarchical inference that manifests most prominently in the social domain without being limited to it.
True
Describe how generative models that concentrate on detailed aspects of the sensory world in ASD affect the prediction errors reaching the brain, and may result in perseverative autistic rituals. (2)
Result in an overly high precision of sensory prediction errors
and elicit actions that try to ‘explain away’ prediction errors (which could be observed and described as perseverative autistic rituals).
Fill the gaps relating to ASD. (1)
An internal model lacking higher levels of abstraction is able to represent ……………………… very precisely, which may be why people with ASD seek out known environments and repetitive actions.
stable environments
Give four ways in which ASD may be proposed to affect Bayesian information processing in terms of likelihood and priors. (4)
- Overprecise sensory input (likelihood)
- Imprecise priors
- Inflexible priors (struggle to update model)
- Altered hierarchical priors
Give an equation that describes how a change in belief (posterior) is ‘calculated’ in Bayesian information processing. (4)
Change in belief is proportional to:
- Pi sensory input
- Divided by pi prior belief
- All multiplied by the prediction error
Fill the gaps relating to ASD. (3)
With compromised ……………………. skills, an individual with autism inhabits a seemingly ………………………… and stressful world where events can occur unexpectedly and without a ………………………………
Such an environment can prove to be overwhelming, and it can be quite challenging to effectively interact with it.
prediction
unpredictable
recognisable cause
Fill the gaps relating to ASD. (3)
At the molecular level, autism is a disorder of ……………………….., and at the behavioural levels, autism is a disorder of ……………………………
However, Bayesian information processing is dependent on synaptic plasticity and …………………………………….. – it is therefore important to understand the molecular mechanisms at play.
synaptic plasticity
Bayesian information processing
connections between neuronal ensembles
Fill the gaps relating to ASD. (6)
Many of the genetic risk factors for the development of ASD, identified so far, appear to primarily impact molecular mechanisms of ………………………, thus altering the …………………… and ……………………. of neural circuits.
Disruptions to synaptic plasticity are also present in ………………………, …………………….. and ………………………… and this common mechanism means that chronic stress can predispose individuals with ASD to these comorbidities.
synaptic plasticity
connectivity
malleability
depression
anxiety
substance misuse
Give five specific examples of cellular mechanisms/processes that may be disrupted due to genetics in ASD. (5)
- Synaptogenesis and synaptic plasticity
- Protein synthesis
- Chromatin remodelling and transcription
- Protein degradation
- Cytoskeleton dynamics
Fill the gaps relating to ASD. (2)
ASD risk genes are often involved in the ……………………….. and ……………………… of the synapse.
structural organisation
functional activity
Fill the gaps relating to ASD. (6)
One of the most studied pathways associated with ASD is the interaction between ………………………. and …………………….., which is found at the ……………………… This pathway also includes more than 20 genes that encode for cell adhesion molecules, scaffolding proteins at glutamatergic synapse (eg. the …………………. protein), cytoskeletal organization molecules, & neurotransmitter receptors that are found both at ……………………….. and ………………………. synapses.
neurexin
neuroligin
postsynaptic density (PSD)
SHANK
glutamatergic
GABAergic
Describe how proteins encoded by ASD risk genes are connected to each other at the molecular level. (1)
Via protein-protein interaction (PPI) networks
Complete the sentence regarding ASD. (1)
ASD risk genes impact neurotransmission and result in dysregulations of ……………………………..
**Hint: it is a phrase
the excitatory-inhibitory balance.
Briefly describe what the SHANK protein is. (1)
Long scaffolding protein that organises glutamatergic receptors on the postsynaptic membrane.
Give three other proteins that the SHANK protein is connected to in the PSD. (3)
Actin cytoskeleton
PSD-95
SynGAP
The SHANK protein helps to organise which receptors at the postsynaptic density? (3)
AMPA
NMDA
mGluR
Fill the gaps relating to ASD. (2)
Dysregulations in ……………………… and …………………………. may cause maladaptive plasticity in neural networks, leading to ASD symptoms.
protein-protein interactions
molecular pathways
What are neurexins and neuroligins? (1)
What are their roles? (2)
- Synaptic cell adhesion molecules
Maintain synapse maturation
and modulate excitatory and inhibitory synaptic transmission.
Which chromosome are the genes NLGN3 and NLGN4 found on? (1)
X chromosome
Several single amino-acid substitutions in which 2 X-linked genes have been identified in patients with ASD? (2)
Give an example of one of these substitutions. (1)
What would be the result of these substitutions? (1)
NLGN3 and NLGN4
NLGN3 Arg451Cys
Enhanced inhibitory neurotransmission
The Arg451Cys mutation in the NLGN3 gene has been identified in patients with ASD.
Give two electrophysiological consequences of this mutation. (2)
Increased frequency of spontaneous mIPSCs
Increased amplitude of evoked IPSCs
Describe how the NLGN3 mutation Arg451Cys in ASD may affect levels of neuroligin3 mRNA, ER export, and protein levels. (3)
mRNA levels normal
ER export reduced
protein levels reduced
True or false? Explain your answer if necessary. (1)
Abnormal levels of synaptic proteins may contribute to ASD symptoms.
True
Fill the gaps relating to ASD. (4)
Dysregulations in local ……………………… may disrupt rapid synthesis of synaptic proteins which play critical roles in higher cognitive brain functions through the regulation of ………………………….., ………………………., and ……………………………
mRNA translation
signal transduction pathways
network connectivity
axonal and synaptic morphology
Briefly describe the function of fragile X mental retardation protein (FMRP). (1)
Regulates synaptic plasticity processes
Give two ways in which the fragile X mental retardation protein (FMRP) regulates synaptic plasticity processes. (2)
Interacting with the mRNA of synaptic and chromatin regulatory proteins (inhibitor of translation)
controlling the mTOR signalling pathway in embryonic and postnatal brains.
How does the fragile X mental retardation protein (FMRP) affect NLGN mRNA translation? (2)
Acts as an inhibitor of translation
so negatively regulates NLGN mRNA translation.
Give an example of how the fragile X mental retardation protein (FMRP) is involved in activity-dependent synaptic remodelling during critical periods. Specifically, hippocampal CA1 neurones in ASD. (2)
FMRP binds ASD-related transcripts encoding postsynaptic proteins
such as SHANK1, SHANK3, SYNGAP1, and PSD-95.
Briefly describe the role of mTOR. (2)
Important roles in mRNA translation and synaptic plasticity.
Acts as an mRNA translation activator.
Describe changes that occur in rodent brains in shankopathies. (8)
- Decreased mIPSC frequency
- Disrupted excitation/inhibition balance
- Decreased spine density and length
- Decreased PSD thickness and proteins
- Decreased glutamatergic receptors and their activity
- Decreased LTD
- Altered/decreased synaptic plasticity
- Defective synapse maturation
Give four overall molecular/cellular changes that occur in ASD due to genetic risk factors. (4)
Changes in expression, localisation, and/or trafficking of synaptic proteins
Ion channel function or expression
Excitatory/inhibitory balance
Dendritic morphology
True or false? Explain your answer if necessary. (1)
Cellular/molecular changes in ASD due to risk genes may affect dendritic excitability and integrative functions of neurons, therefore, interfering with neuronal transmission, neuronal excitability, and synaptic plasticity.
True
True or false? Explain your answer if necessary. (1)
The effects of altered synaptic plasticity in ASD in a certain brain area is restricted to that brain area.
False - Changes in specific brain areas will have knock-on effects on other neural pathways. E.g. changes in PFC activity may affect reward pathways as this brain region is highly connected to the nucleus accumbens and ventral tegmental area. Hippocampus also connected to the PFC. This shows that altered synaptic plasticity ‘restricted to a certain brain area’ will actually have huge effects on many different neuronal circuits, meaning that resultant behaviour is very complex.
Fill the gaps relating to ASD. (8)
An animal model for autism involves stimulating …………………………. to cause neuroinflammation in the developing brain. This would be done in …………………, and they tend to show altered …………………… in adulthood.
The inflammatory cytokines that the developing brain is exposed to may interact with ……………………….. to produce the ASD phenotype. They may prime …………………… to become hyperresponsive, which causes a hyperinflammatory response, and may result in excessive ……………………., altered ……………………, or altered ………………….. development.
maternal immune activation
rodents
sociability
risk genes
microglia
synaptic pruning
myelination
interneurone
Maternal immune activation is used in animal models to induce ASD.
Name three pro-inflammatory cytokines which may be produced due to maternal immune activation. (3)
Give two effects of these cytokines in the placenta. (2)
TNFa
IL-6
IL-1b
- Increased pro-inflammatory cytokines in placenta
- Activation of resident immune cells in placenta
Give three specific cellular/molecular effects of maternal immune activation on the developing foetal brain. (3)
- Microglial activation
- Oxidative stress
- Mitochondrial dysfunction
Give five specific cellular/network level CNS effects of maternal immune activation on the developing brain. (5)
- Cortical disorganisation
- Immature GABAergic neurones
- Altered astrocyte and microglial phenotype
- Cytokine-mediated alterations in development
- Altered myelination
Give three effects of maternal immune activation on the bloodstream. (3)
Peripheral alterations in cytokines
Increased number of neutrophils and eosinophils
Changes in macrophage profile
Fill the gaps relating to brain development. (13)
Different aspects of ………………….. develop at different stages of life.
Examples of the specific events that occur at different times include… (10 examples)
Any disruption to this intricate pattern of events may induce changes which result in ………………. or …………………. symptoms.
neuronal networks
- proliferation
- migration
- molecular specification
- neuronal aggregation and cytoarchitecture
- neuronal dendritic differentiation
- axonal outgrowth and ingrowth
- synaptogenesis and spinogenesis
- pruning and cell death
- neurochemical maturation
- myelination
autism
schizophrenia
Fill the gaps relating to ASD. (6)
A number of different changes occur in the brains of people with ASD.
These changes can interact with ………………. and can occur at different stages of ……………………..
Most importantly, these changes may cause disruptions within ………………….. and ……………………., which can alter the neural code and ……………………..
This means that there might be issues with sensory coding and adaptation, and also altered ……………………… between different brain regions, which can cause the symptoms of ASD.
each other
brain development
neural networks
neural ensembles
sensory perception
synchrony
Give 8 brain changes which can be present in the brains of people with ASD. (8)
- Excitation/inhibition ratio changes and hyperexcitability
- Parvalbumin interneurone hypofunction
- Impaired, abnormal, or maladaptive homeostatic plasticity
- Abnormal synaptic plasticity
- Impaired critical period plasticity and synapse maturation
- Degraded sensory coding
- Failure of sensory adaptation
- Oscillations and altered synchrony
True or false? Explain your answer if necessary. (1)
ASD risk genes involved in synapse formation and function (eg. CNTNAP2, FMR1, MECP2, NLGN, NRXN, SHANK) are only expressed, and therefore only affect the CNS.
False - ASD risk genes are also expressed by primary sensory neurones
Mutations in which 3 genes in mice impair touch discrimination and cause hypersensitivity to tactile stimuli? (3)
*This is related to autism
Fmr1
Mecp2
Shank3
Fill the gaps relating to ASD. (4)
Mutations in some ASD risk genes can impair ……………. discrimination and cause ……………………… to tactile stimuli.
As such, aberrant sensory input may cause altered …………………… in patients with ASD.
Abnormal sensory experience during ………………………… may represent a pathophysiological mechanism in ASD.
touch
hypersensitivity
synaptic development
critical developmental periods
ASD gene disruption in primary sensory neurones during development or in adulthood causes similar alterations of sensory behaviour.
What additional effects are seen if these genes are removed during development? (3)
- Anxiety
- Reduced social behaviour
- Brain circuitry changes
Describe the molecular effects of loss of Mecp2 in primary sensory neurones in ASD. (3)
Reduced Mecp2 leads to reduced GABAa receptor B3 subunit
This reduces the amount of presynaptic inhibition which can be carried out by descending tracts or interneurones
Therefore there is increased tactile sensitivity and anxiety
Fill the gaps relating to peripheral synaptic dysfunction in ASD. (4)
Loss of Cntnap2 leads to ……………………… in d-hairs, which are a type of …………………….. This is due to loss of …………………….. channel function.
Soma loss of Cntnap2 also impacts nociceptor function, resulting in ………………………… of Aδ and C fibers.
hyperexcitability
low threshold mechanoreceptor (LTM)
Kv1 (voltage gated K channel)
hyperexcitability
Describe how loss of Shank3 affects nociceptors. (2)
Reduces the functional expression of TRPV1
which is a transduction channel important in heat hyperalgesia.
Fill the gaps relating to peripheral (or spinal cord) synaptic dysfunction in ASD. (3)
At the level of the dorsal horn synapse, loss of MECP2 results in the down regulation of ……………………….. and loss of ………………………. on LTMRs leading to increased sensitivity to ………………………..
GABA receptors
presynaptic inhibition
tactile stimuli
True or false? Explain your answer if necessary. (1)
ASD displays a pronounced heterogeneity, both with respect to the behavioural phenotype and the severity of impairments.
True
The hypothesised fundamental mechanism affected in ASD, hierarchical Bayesian learning, is based on which 3 main pillars? (3)
- Predictions
- Prediction errors
- Their respective precisions
True or false? Explain your answer if necessary. (1)
Impairments in hierarchical Bayesian learning in ASD may be caused by dysfunctions in neural coding.
True
Fill the gaps relating to the dysfunctional Bayesian brain in ASD. (3)
Predictions and/or prediction errors could be incorrectly calculated at the level of ……………………… (e.g., abnormal integration of ……………………… inputs to supragranular pyramidal cells), or they could be conveyed incorrectly to …………………………….. (e.g., presynaptic or postsynaptic deficiencies of long-range connections).
specific neurones
dendritic
target neurones
Fill the gaps relating to dysfunction of the Bayesian brain in ASD. (6)
Genetic alterations in ASD may result in altered ………………………………, which may affect how descending predictions interact with ………………………………
For example, the activities or connections of ………………………….. which are usually activated by predictions may be altered.
This may result in ……………………….. of prior beliefs and prediction errors being misinterpreted, which affects the …………………………. reaching the brain, and the updating of the …………………………….
neuronal connectivity
ascending prediction errors
interneurones
precisions
prediction errors
generative model
Fill the gaps relating to the dysfunctional Bayesian brain in ASD. (4)
People with ASD don’t have very accurate …………………………. (they are overfitted). Therefore the ………………………………. are inaccurate and cannot cancel out the prediction errors. This means that they are constantly updating their ………………………… and these become more overfitted and not ………………………………
prior beliefs
descending predictions
generative models
generalisable
True or false? Explain your answer if necessary. (1)
Due to stochasticity (randomness) in the environment and noise inherent to all sensory organs, not all prediction errors signal true changes in learnable regularities.
True
Describe why it might not be beneficial to update the generative model in response to each and every input. (4)
There is randomness and irrelevant noise in the environment
so not all prediction errors signal true changes in learnable regularities
and constantly updating the generative model in response to all prediction errors could result in overfitting
which makes an overly precise and brittle model with limited generalisability over time.
Instead of updating the generative model in response to each and every input, it is proposed that belief updates should be governed by the balance between which two factors? (2)
What is the name of the equation which describes this? (1)
- Uncertainty about the sensory input (i.e. expected signal to noise ratio)
- Uncertainty of the prior belief
The precision ratio
Describe the precision ratio, when referring to Bayesian information processing, in words. (4)
Any change in belief
is proportional to the prediction error
but weighted by the ratio of the precision of the sensory input
and the precision of the prior belief.
Fill the gaps relating to ASD treatment and the Bayesian brain hypothesis. (11)
The hypothesis that ASD is characterized by …………………….. bottom-up sensory input compared to the precision of ……………………… allows clinicians to test and refine the most optimal learning conditions under which ASD patients can benefit.
Behavioural therapy for children with ASD has converged over the years to include optimal conditions in a ………………………… environment that causes little ……………………… and offers new inputs with little ………………….. (unexplainable variability) across many repetitions.
New actions may be best learned by …………………………. (as opposed to mere observation), and abstract concepts are learned through ………………………… (rather than by intuition).
If such conditions are present and an affected individual is exposed to enough inputs over ………………………, a sufficiently rich representation of the world and successful ……………………………. can be learned.
Variations in these controlled conditions at different stages in life could reduce ……………………… over time or strengthen ……………………………. and aid functional adjustments through repeated training.
overprecise
top-down predictions
well-known
surprise
noise
step-by-step instruction
explicit definition
repeated sessions
behavioural strategies
symptoms
coping strategies
