Showing posts with label Neuroscience of Autism. Show all posts
Showing posts with label Neuroscience of Autism. Show all posts

Temporal ventriloquism

Temporal ventriloquism is a phenomenon where the timing of one sensory modality, such as vision, influences the perception of timing in another modality, like sound. In multisensory integration research, temporal ventriloquism is explored through tasks where auditory and visual stimuli are presented slightly out of sync, but the brain often perceives them as occurring simultaneously or closer together in time. Researchers aim to understand how the brain resolves conflicting sensory information and determines which sensory input to prioritize in order to create a coherent perception of the environment.

In temporal ventriloquism tasks, participants might be asked to judge whether a sound and a visual flash are occurring at the same time, even when their timing is slightly offset. The extent to which vision can alter auditory perception—or vice versa—is key to understanding how the brain integrates sensory inputs. This task is particularly valuable in studying sensory processing in autism, where atypical multisensory integration is often reported.

In autism research, there is growing interest in how temporal ventriloquism might differ from typical sensory integration patterns. Autistic individuals may exhibit less flexibility in how sensory inputs are combined, potentially leading to difficulties in processing complex environments where timing discrepancies between senses occur. Studies have shown that autistics often rely more heavily on one sense over others, which might contribute to challenges in tasks like temporal ventriloquism (Noel et al., 2018). Understanding these differences in temporal processing can offer insights into sensory sensitivities and the broader challenges related to perception in autism.

PlainSpeak. In Plain Language for the Lay Audience

Temporal ventriloquism is when the brain tricks us into thinking that sounds and visuals are happening at the same time, even if they’re slightly out of sync. Imagine you see a light flash and hear a beep that’s just a little delayed, but your brain adjusts and makes you think they’re perfectly in sync. This is how the brain works to keep everything feeling smooth and connected across different senses.

In experiments, researchers test this by showing people lights and playing sounds that are a bit off in timing. They ask participants to judge if they think the sounds and visuals happened together. What’s interesting is that the brain can often ignore these small timing differences and make everything seem like it’s happening at once.

For autistic people, the way the brain handles sensory inputs like this might work a little differently. Some studies suggest that autistic individuals may have a harder time combining sounds and visuals when they’re slightly out of sync, which could be related to sensory sensitivities or challenges in processing multiple types of information at once. Understanding these differences could help explain why certain environments feel overwhelming for autistic individuals.

Weak Central Coherence Theory


 The Weak Central Coherence Theory (WCC) of autism, proposed by Uta Frith in the late 1980s and further developed by others, is a cognitive theory that attempts to explain some of the characteristic features of autism. The theory posits that autistics tend to process information in a detail-focused manner, often at the expense of global or contextual processing. 

Key Components of WCC Theory:

  1. Detail-Focused Processing:
    • Autistics are more likely to focus on the individual components of a stimulus rather than integrating these components into a coherent whole. This is sometimes referred to as "local processing" or "piecemeal processing.” Eg:  notice the specific features of a face, like the shape of the nose or the color of the eyes, rather than perceiving the face as a unified whole.
  2. Reduced Global Processing:
    • The theory suggests that there is a relative weakness in processing global or contextual information. This means that autistics might have challenges in seeing the "big picture" or understand the context in which details fit.
    • For example, they might have difficulty understanding the main idea of a story or the overall mood of a social situation because they are focused on specific details.

Implications of Weak Central Coherence:

  1. Cognitive Strengths:
    • The detailed-oriented processing style can lead to strengths in tasks that require attention to detail, such as certain types of puzzles, mathematical problems, or tasks involving pattern recognition.
    • Autistics may excel in fields that value precision and attention to minute details.
  2. Social and Communication Challenges:
    • Difficulty in integrating social cues and contextual information can contribute to challenges in social communication and understanding. For instance, recognizing social subtleties or understanding non-literal language (such as idioms or sarcasm) can be difficult.
    • Problems with central coherence might also affect understanding narratives, jokes, and metaphors that rely on context.
  3. Perceptual and Sensory Processing:
    • Some research suggests that weak central coherence is related to atypical sensory processing seen in autism, where individuals might have heightened or diminished sensitivity to sensory input.
    • This can manifest as either an intense focus on specific sensory details or difficulty in filtering out irrelevant sensory information.

Feelings and Body Signals in Autism

 [Plain Language for Lay Audience]

Alexithymia means having trouble recognizing and describing your own emotions. People with alexithymia often can't tell what they are feeling and find it hard to explain their emotions to others. This can make it difficult to connect with others and share feelings.

Interoception is the ability to sense and understand signals from inside your body. These signals include things like hunger, thirst, heartbeat, temperature, breathing, and the need to go to the bathroom. Interoception helps keep our bodies balanced and healthy by letting us know what we need and how we feel inside. It also plays a big role in how we experience and control our emotions by linking our body sensations to our feelings.

Both alexithymia and interoception issues can happen together in autism. 

Autistics might have unusual interoceptive awareness, meaning they can be more or less aware of their body signals than other people. This can cause problems like not noticing when they are uncomfortable or sick, or misunderstanding changes in their emotions, which are important for social interactions and taking care of their health.

Here are some examples of how this can affect autistics:

  • Eating: Not knowing when they feel full, which can lead to overeating.
  • Anxiety: Not feeling their heart race when they are anxious, making it harder to know they are stressed.
  • Pain: Feeling an injection as more painful than usual, or not showing pain, which can confuse doctors.
  • Exercise vs. Anxiety: Mixing up a racing heart from exercise (good) with a racing heart from fear (not good).
  • Toilet Training: Taking longer to learn to use the toilet or having random accidents even into adulthood  because their body can't recognize when they need to go.

From a brain science perspective, the insular cortex and the anterior cingulate cortex (ACC) are important for interoception. The insula helps combine body signals with thoughts and emotions, while the ACC is involved in feeling pain. In autism, these brain areas might work differently, affecting how body signals and emotions are processed. Studies using brain scans have shown that the insula reacts differently during body signal tasks in autism, which might explain their unique interoceptive experiences.

Addressing both alexithymia and interoception is important for improving emotional understanding and overall well-being. Helping autistics improve their interoceptive skills can lead to better emotional control and awareness, making it easier for them to connect with others and take care of their health.


2 Versions of this article: 

Academic/Scientific Audience

Plain Language for Lay Audience

Other Articles in Plain Language #PlainSpeak

Blindsight and its relevance to Autism

Autism Lexicon: Blindsight

Blindsight refers to the residual visual capabilities in individuals with damage to the primary visual cortex, allowing them to respond to visual stimuli without conscious perception. Its relevance to autism lies in investigating the potential for similar dissociations between conscious and subconscious sensory processing in autistic individuals.[Read More: Academic/Scientific Audience ]

PlainSpeak: Blindsight is a phenomenon where people with certain types of brain damage can respond to visual stimuli without consciously seeing them. Its connection to autism involves exploring how sensory information might be processed differently in both conditions, sometimes without conscious awareness. [Read more: PlainSpeak Plain Language for Lay Audience]



Understanding Neurophysiological and Neurobiological Perspectives in Autism

When discussing autism, we often focus on behaviors—how someone communicates or interacts with others. However, to truly understand autism, it’s important to look deeper into the brain's functioning. Neurophysiological and neurobiological perspectives offer insights into the brain's activity and structure in autism.

Neurophysiology: The Brain in Action

Neurophysiology refers to the study of the brain's electrical and chemical processes. In simpler terms, it looks at how the brain functions in real time. For autistics, neurophysiology can explain why sensory experiences might feel more intense or overwhelming. Research using EEG has shown that autistic brains often respond differently to sensory stimuli, with variations in brain wave patterns that suggest heightened sensitivity or delayed processing . This difference in neural activity can contribute to sensory overload and the need for certain sensory accommodations.

Neurobiology: The Brain's Structure and Development

Neurobiology, on the other hand, examines the brain's physical structure, development, and genetics. It looks at the brain's "hardware"—its neurons, synapses, and the genes that influence its development. In autism, neurobiological studies have found variations in brain regions involved in social behavior and emotion processing, such as the amygdala and prefrontal cortex . These differences can affect how autistic individuals perceive and respond to social stimuli, contributing to the diverse range of social behaviors seen in autism.

Genetic research also plays a significant role in neurobiology. Many studies have identified genes associated with autism, highlighting the genetic underpinnings that contribute to brain development and function . These insights are crucial for understanding the diverse expressions of autism and for developing personalized approaches to support autistic individuals.

Bridging Neurophysiology and Neurobiology

Combining neurophysiological and neurobiological perspectives provides a more comprehensive understanding of autism. For example, if an autistic person has a neurobiological difference in the connectivity between brain regions involved in emotion processing, this might lead to a neurophysiological response that is heightened or atypical when encountering emotional or social cues.

References

  1. Orekhova, E. V., Stroganova, T. A., Nyström, P., & Gillberg, C. (2006). Excess of high frequency electroencephalogram oscillations in boys with autism. Biological Psychiatry, 62(9), 1022-1029.
  2. Schumann, C. M., & Amaral, D. G. (2006). Stereological analysis of amygdala neuron number in autism. Journal of Neuroscience, 26(29), 7674-7679.
  3. Geschwind, D. H. (2011). Genetics of autism spectrum disorders. Trends in Cognitive Sciences, 15(9), 409-416.


Alexithymia and Interoception in Autism

Alexithymia is a term used to describe individuals who have difficulty recognizing and articulating their emotions. This condition can lead to significant challenges in emotional expression and interpersonal relationships. Those with alexithymia often struggle to identify their own emotions and may have trouble describing them to others, which can hinder effective communication and emotional connection.

Interoception refers to the perception and awareness of internal bodily states. It involves the ability to sense and interpret physiological signals originating from within the body, such as hunger, thirst, heartbeat, temperature, respiration, and the need for bodily functions. Interoception is crucial for maintaining homeostasis and overall well-being as it allows an individual to respond appropriately to bodily needs and emotional states. This internal sensory system plays a significant role in emotional experiences and self-regulation by linking physical sensations with emotional responses.

And yes, both can co-exist in autism.  

Autistics often exhibit atypical interoceptive awareness, which can be either heightened or diminished. This variance can lead to unique challenges, such as difficulty identifying states of discomfort or illness, or misinterpreting signals of emotional changes, which are critical for social interactions and personal health management.

For example, autistics might find it difficult to recognize a sensation of fullness to prevent overeating or to feel a racing heartbeat when anxious. Moreover, atypical interoceptive awareness can affect pain perception, complicating healthcare experiences. An injection might feel more painful than usual, or a lack of reaction to pain might make it appear to healthcare providers that there is no injury or less pain. Additionally, autistics might confuse a racing heartbeat resulting from exercise (a positive physical activity) with a racing heartbeat due to fear or anxiety, leading to difficulties in emotional and physical self-regulation.

Furthermore, atypical interoceptive awareness can result in challenges such as delayed toilet training. Recognizing the need for bodily functions like urination may be delayed, inconsistent or unclear, leading to practical and social difficulties like random incontinence even in adulthood. 

From a neuroscience perspective, the insular cortex and anterior cingulate cortex (ACC) are critical regions involved in interoception. The insula integrates interoceptive signals with emotinal and cognitive processes, while the ACC is associated with the emotional experience of pain. In individuals with autism, atypical functioning in these brain areas can contribute to altered interoceptive processing and emotional awareness. For example, fMRI studies have shown differences in insula activation in response to interoceptive tasks in autism, which may underpin the atypical interoceptive awareness observed clinically.

Impaired interoceptive awareness can exacerbate the challenges faced by individuals with alexithymia, making it harder to connect emotional experiences with physiological responses. Consequently, addressing both alexithymia and interoception is crucial for enhancing emotional intelligence and overall well-being. Research indicates that improving interoceptive skills may offer a pathway to better emotional regulation and awareness, fostering improved interpersonal connections and emotional health.

2 Versions of this article: 

Related Posts on #Interoception, #Alexithymia


Understanding Autistic Inertia

PlainSpeak. In Plain Language for the Lay Audience

Newton's Law of Inertia

Newton's Law of Inertia says that an object will stay still if it's already still, and if it's moving, it will keep moving in the same direction and speed unless something makes it change.

Autistic Inertia

We use this idea to describe how some autistic people have trouble starting or stopping tasks.

  • Starting Tasks: Just like an object at rest, some autistic people find it hard to begin tasks. They might feel stuck and need something to help them get going.

  • Stopping Tasks: Once they start a task, it can be hard to stop. They might keep doing the same thing over and over, like being stuck in a loop.

This difficulty also affects:

  • Switching Between Tasks: Changing from one activity to another can be tough.
  • Adjusting to Changes: Adapting to new environments or situations can be challenging.
  • Maintaining Focus: Staying focused on a task can be hard, but so can switching off that focus when needed.
  • Decision Making and Planning: Making decisions, planning, and following through with plans can be difficult.
  • Mental Health: Anxiety and depression can make these challenges worse.

Even if someone knows they need to start or stop a task, they might feel stuck and unable to do so, which can be exhausting. This can lead to burnout, where they feel completely worn out.

Causes

Autistic inertia can be caused by:

  • Sensory Overload: Too much sensory input can make it hard to start or stop tasks.
  • Motor Issues: Problems with movement and coordination.
  • Executive Dysfunction: Difficulty with planning and organizing.
  • Anxiety: High levels of anxiety can make these challenges worse.

This can make it hard to finish tasks, meet deadlines, and stick to a schedule for work or school, often leading to burnout.

Advantages

Sometimes, autistic inertia can help with hyper-focus, allowing someone to deeply concentrate on learning a specific topic.

Misconceptions

Autistic inertia is often misunderstood as laziness or lack of motivation. It can affect anyone, regardless of their support needs or ability to speak. It can be even more complex for those with movement issues, sensory challenges, and coordination problems.

What Can Help

To help manage autistic inertia:

  • Use Reminders: Set reminders on your watch or calendar.
  • Get Support: Ask others for help when needed.

Everyone’s needs are different, so the type and amount of help will vary from person to person.

Who Autism Research Leaves Out

I find that despite all the careers, promotions, and profits being made by thousands of autism-experts, the state of autism interventions right now is one hot mess. In reality, there still are no real “experts” in autism because there is no one-size fits all model.
-Hari Srinivasan, Time

 

Weak Central Coherence Theory of Autism

Caveat: There is no single theory that can fully explain autism. 

The Weak Central Coherence Theory posits that autistics exhibit a cognitive processing style characterized by a propensity for local over global information processing. This theory suggests that autistics have a heightened focus on fine details at the expense of integrating these details into a coherent whole. 

The Weak Central Coherence Theory provides a framework for understanding the distinct cognitive processing style in autism, characterized by a bias toward local over global processing. Neurobiological evidence supports this theory, showing enhanced local processing capabilities and impaired global integration due to altered neural connectivity. This theory helps explain the strengths and challenges faced by individuals with autism in various cognitive and social domains.

Key Concepts

  1. Detail-Focused Processing:

    • Cognitive Tendency: Autistics demonstrate superior performance on tasks requiring attention to fine details, suggesting an enhanced local processing bias.
    • Neurobiological Basis: Neuroimaging studies indicate increased activation in primary and secondary sensory cortices, particularly the visual cortex, which may underlie this enhanced local processing.
  2. Reduced Global Integration:

    • Cognitive Deficit: There is a relative impairment in synthesizing details into a unified, overarching context, which affects higher-order cognitive tasks.
    • Neurobiological Basis: This deficit is associated with reduced long-range connectivity and synchronization between frontal and posterior brain regions, impairing the integration of information across neural networks.
  3. Neuroanatomical Correlates:

    • Prefrontal Cortex: Involvement in executive functions and global processing is diminished, contributing to difficulties in integrating complex information.
    • Posterior Regions: Including the occipital and parietal lobes, these regions exhibit enhanced local processing but reduced integration with other cortical areas.

Examples and Implications

  1. Perceptual Tasks:

    • Enhanced Performance: Autistic individuals often excel at visual search tasks, identifying small differences in stimuli more quickly and accurately than neurotypical individuals.
    • Impaired Performance: They may struggle with tasks that require understanding the overall context, such as interpreting ambiguous figures or scenes.
  2. Cognitive Tasks:

    • Strengths: Detail-oriented tasks like pattern recognition or mechanical assembly are areas of strength.
    • Weaknesses: Tasks requiring abstract thinking, such as comprehending proverbs or making inferences, present challenges due to impaired global processing.
  3. Social Interaction:

    • Implications: Social difficulties can arise from an inability to integrate social cues into a cohesive understanding of social interactions. This can lead to literal interpretations of language and difficulties with nonverbal communication.

Neuroimaging Evidence

  1. Functional MRI (fMRI):
    • Findings: fMRI studies show atypical activation patterns in the frontal and parietal regions during tasks requiring global processing.
  2. Diffusion Tensor Imaging (DTI):
    • Findings: DTI studies indicate atypical white matter integrity, suggesting disrupted long-range connectivity essential for global information integration.
  3. EEG/MEG:
    • Findings: EEG and MEG studies reveal reduced coherence and synchronization across distant brain regions, supporting the notion of impaired global processing.
Two Versions of this post


Who Autism Research Leaves Out

"It’s time for researchers and technologists to rethink their methodologies and technologies, and explore other innovative approaches to give all members of the autistic community the care we need."
-Hari Srinivasan, Time

 

Exploring Short-Term Synaptic Plasticity and Its Implications in Autism

Short-term synaptic plasticity, a temporary change in synaptic strength lasting from seconds to minutes, is a crucial mechanism for neural communication and information processing. Two key types of short-term plasticity are paired pulse facilitation (PPF) and paired pulse depression (PPD). Understanding these mechanisms can provide insight into the molecular & genetic underpinnings of autism.

Paired Pulse Facilitation (PPF) occurs when two signals (pulses) arrive in quick succession at a synapse, with the second pulse producing a stronger response than the first. This is due to residual calcium (Ca2+) remaining in the presynaptic terminal after the first pulse, which enhances neurotransmitter release upon the arrival of the second pulse. This phenomenon is particularly significant at synapses with low initial release probability, ensuring that enough neurotransmitters are available for subsequent release.

Paired Pulse Depression (PPD), on the other hand, is characterized by a diminished response to the second pulse. This occurs at synapses with high initial release probability, where the first pulse depletes the readily releasable pool of neurotransmitters, leaving insufficient resources for the second pulse. The timing between the pulses is critical; if the interval is too long, Ca2+ dissipates, and vesicles are replenished, mitigating these effects.

In the context of autism, alterations in short-term plasticity have been linked to the disorder's characteristic neural and behavioral features. Research has shown that mutations in synaptic genes such as SYN1 and SYN2, which regulate synaptic vesicle dynamics, can disrupt short-term plasticity. These mutations result in increased PPF at excitatory synapses and enhanced synaptic depression at inhibitory synapses, leading to an excitatory/inhibitory (E/I) imbalance that contributes to network hyperexcitability and altered neuronal communication (Frontiers, 2015)​ (Frontiers)​.

Furthermore, neuroligin-3 mutations, associated with autism, have been found to differentially alter synaptic function in the hippocampus and cortex. These mutations can increase inhibitory synaptic transmission and disrupt endocannabinoid signaling, further impacting short-term plasticity and neural circuitry (Molecular Psychiatry, 2015)​ (Nature)​. These findings underscore the significant role of short-term plasticity in maintaining neural circuit function and how its disruption can contribute to pathogenesis.

2 versions of this post

For the Academic/Scientific Audience

PlainSpeak in plain language for the lay reader



The Role of Parvalbumin Neurons in Autism

A PlainSpeak version for the Lay Reader

The Role of Parvalbumin Neurons in Autism

Background

Scientists believe that a special type of brain cell called Parvalbumin (PV) interneurons (INs) may play a key role in autism. Even though autism can be caused by many different genetic and environmental factors, people with autism often show similar behaviors. This suggests that there might be a common issue in the brain across different individuals with autism (1).

Understanding the role of PV+ interneurons in autism helps us see why many symptoms of autism occur, like sensory sensitivity and seizures. 

The Balance of Brain Signals

Our brains need a balance between "go" signals (excitation) and "stop" signals (inhibition) to work properly. In autism, it was first thought that there is too much excitation and not enough inhibition, leading to an imbalance. This imbalance could explain why some people with autism have seizures (4,5). However, this idea is too simple because many types of brain cells are involved in maintaining this balance.

What We Know About PV+ Cells in Autism

Researchers have found that PV+ cells in the brains of autistics are often not working as they should:

  • Fewer PV+ cells: There are fewer of these cells in the brain, and they produce less of a protein called parvalbumin.
  • Changes in brain waves: These cells help control brain waves called gamma oscillations. In autism, the power of these gamma waves is higher than normal.
  • Reduced activity: PV+ cells show less activity in response to visual signals.

PV+ cells are the most common type of inhibitory ("stop/slow down") neuron in the brain, but other types of neurons may also be involved in autism.

Brain Excitability and Sensory Sensitivity

When PV+ cells don't function properly, the brain becomes overly excitable and synchronized, making seizures more likely. This can also cause exaggerated responses to sensory inputs, like touch or sound. For example, in a mouse model of autism, the response to whisker movement is weaker in certain brain cells.

Sensory Overload

Autistics often experience sensory overload because their brains can't tune out irrelevant information. This may be due to a failure of brain cells to adapt to continuous stimulation (2).

Visual Processing

PV+ neurons are important for fine-tuning the way we see things, helping us to distinguish between different visual inputs.

Brain Waves and Communication

Increased gamma wave activity, which is linked to sensory and communication issues, is common in autism. PV+ cells help generate these waves, and their dysfunction leads to irregular brain activity patterns (3).


2 Versions of this Post

For the Science/Academic Reader

PlainSpeak for the Lay Reader

A short definition




References

  • 1.Contractor, A., Klyachko, V. A., & Portera-Cailliau, C. (2021). Reduced density and activity of parvalbumin interneurons in autism. Journal of Neurodevelopmental Disorders, 13(1), 1-15.
  • 2.Green, S. A., & Gu, Y. (2015). Sensory hypersensitivity in autism spectrum disorders. Current Biology, 25(18), R876-R879.
  • 3.Guyon, N., & Nahmani, M. (2021). Role of parvalbumin interneurons in gamma oscillations and sensory processing in autism. Frontiers in Neuroscience, 15, 692872.
  • 4. Hussman, J. P. (2001). Suppressed GABAergic inhibition as a common factor in suspected etiologies of autism. Journal of Autism and Developmental Disorders, 31(2), 247-248.
  • 5. Rubenstein, J. L., & Merzenich, M. M. (2003). Model of autism: Increased ratio of excitation/inhibition in key neural systems. Genes, Brain and Behavior, 2(5), 255-267.

E-I Imbalance Theory of Autism

The E-I Imbalance hypothesis posits that an imbalance between excitatory and inhibitory signaling in the brain contributes to the sensory, cognitive, and behavioral features of autism.

PlainSpeak: This idea says that a mix-up between signals that excite and calm the brain can cause the sensory, thinking, and behavior issues in autism.


Read in more detail about E-I Imbalance


Understanding the E - I Imbalance Theory of Autism

In PlainSpeak for the Lay Reader
Caveat: Always keep in mind there is no single theory that perfectly explains autism.

The Excitatory-Inhibition (E-I) Imbalance idea says that a mix-up between signals that excite and calm the brain can cause the sensory, thinking, and behavior issues in autism.

What Can Cause the E-I Imbalance?

Too Much Glutamate and Overactive Exciting Neurons
Glutamate is the main chemical that makes brain cells more active. If there is too much glutamate or the exciting neurons are too active, it can make the brain overly excitable. This can cause people with autism to be very sensitive to sounds, lights, and other sensory inputs and make thinking and processing information harder.

Not Enough GABA to Calm the Brain
GABA is the main chemical that calms brain cells. In autism, there can be less GABA, problems with GABA receptors, or less active calming neurons. This means the brain doesn’t have enough calming signals to balance the exciting ones, making the E-I imbalance worse.

Problems with Exciting and Calming Neurons
Neurons are the cells in the brain that send and receive signals. Exciting neurons make other neurons more active, while calming neurons reduce activity. In autism, there might be differences in the number, function, or connections of these neurons. For example, changes in certain calming neurons can disrupt the brain’s local circuits, leading to more excitement and less calming.

Important Development Periods
The E-I balance is especially important during key development times when the brain is growing and changing rapidly. If the balance is off during these times, it can affect brain development and function in the long term. This can impact learning, memory, and the formation of proper brain connections.

Changes in Synaptic Proteins

Proteins like neuroligins and neurexins help brain cells stick together and send signals. In autism, changes or problems with these proteins can lead to abnormal connections between brain cells, affecting the E-I balance.

Ion Channel Problems
Ion channels help neurons send signals by letting ions in and out. Ions are tiny charged particles, like sodium, potassium, or calcium, that neurons need to function properly. In autism, problems with these ion channels can change how neurons send signals, affecting the E-I balance.

Problems with Synaptic Plasticity
Synaptic plasticity is the ability of connections between brain cells to get stronger or weaker over time. This is important for learning and memory. Long-term potentiation (LTP) is when these connections get stronger with activity, helping with learning new things. Long-term depression (LTD) is when these connections get weaker, which helps remove unnecessary information. In autism, problems with LTP and LTD can make it harder to learn and remember things.

Role of Supporting Brain Cells (Astrocytes and Microglia)
Astrocytes and microglia are supporting cells in the brain that help maintain E-I balance. Astrocytes manage levels of glutamate and GABA, while microglia help prune synapses during development. Pruning is like trimming a tree; it removes extra connections between brain cells to make the network more efficient. Problems with these cells can lead to too much excitation or not enough inhibition.

Genetic and Epigenetic Factors
Our genes, which are like instructions for how our body works, can influence the E-I balance. Changes in how these genes are turned on or off can also affect the brain. Many genes linked to autism affect how brain cells connect and communicate, leading to differences seen in autism.

Environmental Influences
Things in the environment, like exposure to toxins, infections, and stress during pregnancy, can impact the E-I balance. These factors can change how the brain develops and works, leading to long-term effects on brain signals.

Excitation/Inhibition Imbalance in Autism Rodent Models

E/I IMBALANCE AND AUTISTIC-LIKE BEHAVIORS:
  • Optogenetic stimulation of pyramidal neurons in the medial prefrontal cortex in mice induces social deficits associated with enhanced gamma oscillations.
  • Increased neocortical E/I ratio caused by malfunctions of PV-expressing interneurons induces excessive gamma oscillations and autistic-like behaviors.

Factors Contributing to E/I Imbalance
  • E/I balance at the circuit level involves the interplay between GABAergic interneurons and target pyramidal neurons, modulating long-range connections.
Excitatory Synapse Development
  • Neuroligin and neurexin genes play critical roles in synapse and circuit development.
  • Knockout of 4E-BP2 in mice upregulates neuroligins, increases hippocampal synaptic E/I ratio, and induces autistic-like behaviors.
  • Pharmacologic inhibition of eIF4E or knockdown of neuroligin-1 normalizes the E/I ratio and rescues autistic-like behaviors.
AMPAR 
  • Ampakine rescues impaired long-term potentiation and long-term memory in Ube3a-deficient mice, a model of Angelman syndrome.
  • Various gene mutations affect AMPAR transmission and synaptic functions in different mouse models.
  • IGF-1 treatment rescues reduced excitatory transmission in Shank3 and Mecp2 mice.
NMDAR
  • Mutations in genes like Nlgn1, Shank2, and Tbr1 lead to NMDAR hypofunction and social deficits in mice.
  • Both hypo- and hyperfunction of NMDARs can cause autistic-like behaviors in animal models.
  • mGluR5 hyperfunction in Fmr1 and BTBR mice is implicated in ASDs.
Signaling Pathways
  • The mTOR pathway and actin-modulatory pathways play crucial roles in rescuing autistic-like phenotypes in animal models.
  • Dopamine receptor agonists/antagonists and 5-hydroxytryptamine rescue behaviors in various mouse models.
Inhibitory Synapse Development and Function
  • Deletion of inhibitory synapse-specific Nlgn2 leads to decreased inhibitory synapse density and cognitive deficits.
  • Mutations in genes like Nlgn3 and Cntnap2 affect GABAergic transmission in different brain regions.
  • Deficiencies in GABA A receptor subunits and altered tonic GABAergic transmission are observed in ASD model animals.
Interneurons
  • PV interneurons are crucial for regulating gamma oscillations and are associated with psychiatric disorders.
  • Defects in PV, SST, and NPY interneurons lead to various phenotypes in mouse models.
  • Reduced interneuronal firing and GABAergic output contribute to social and cognitive deficits in ASD models.
Glial Cells
  • Astrocytes and nonastrocytic glial cells like microglia and oligodendrocytes play roles in regulating excitatory synapse structure and function.
  • Re-expression of MeCP2 in glial cells can restore disease-related phenotypes in ASD models.
Intrinsic Neuronal Excitability
  • Deficits in dendritic ion channels and intrinsic excitability are observed in various mouse models.
  • Neuregulin-ErbB4 signaling modulates the intrinsic excitability of PV interneurons.Homeostatic 
Synaptic Plasticity
  • Fmr1 mice show altered synaptic scaling in different brain regions.
  • GKAP/DLGAP1/SAPAP1 scaffold regulates bidirectional synaptic scaling in the hippocampus.

Temporal E/I Regulation
  • Temporal changes in E/I balance are crucial for normal brain development.
  • Early interventions with specific inhibitors can normalize E/I balance and rescue abnormal phenotypes in animal models.
  • Delayed restoration of certain genes can also rescue abnormal phenotypes in ASD models.

Perspectives
  • Careful interpretation of rescue results is necessary to understand the fundamental correction of pathogenic mechanisms.

Lee, E., Lee, J., & Kim, E. (2017). Excitation/inhibition imbalance in animal models of autism spectrum disorders. Biological psychiatry81(10), 838-847.

      MTT Mental Time Travel

      Mental Time Travel (MTT) refers to the cognitive ability to mentally project oneself backward in time to recall past events or forward in time to anticipate future scenarios. In relation to autism, MTT research explores how individuals with autism may experience differences in episodic memory and future-oriented thinking, potentially leading to challenges in recalling specific personal events or imagining detailed future scenarios. [ Read in more detail on MTT]

      PlainSpeak: Mental Time Travel (MTT) is our brain’s way of thinking back to past memories or imagining what might happen in the future. For people with autism, MTT might work differently, sometimes making it harder to remember personal events or imagine future plans. [Read in more detail, a PlainSpeak Version]

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      Related Posts: [Autism Theories], [Sensorimotor], [Neuroscience of Autism]

      Monotropism and Special Interests in Autism - a Neurocognitive Perspective

      Monotropism and special interests are closely related yet distinct constructs within the context of autism. Both concepts elucidate how autistic individuals exhibit profound engagement with specific domains, yet they underscore different facets of this phenomenon.

      Monotropism is a cognitive model positing that autistic individuals exhibit a narrowed attentional focus on a limited set of interests, in contrast to the broader attentional distribution observed in neurotypical individuals. This heightened attentional focus facilitates deep expertise and significant enjoyment in specialized areas. However, it also results in attentional inflexibility, making it challenging for individuals to shift focus to other tasks or interests that do not align with their core interests. Monotropism provides a framework for understanding why autistic individuals often demonstrate exceptional proficiency in their areas of passion but may face difficulties with tasks that are outside these focal points.

      Special Interests refer to the specific topics or activities that elicit intense focus and enthusiasm in autistic individuals. These interests often manifest as lifelong passions and serve as sources of comfort, identity, and competence. While special interests contribute positively to an autistic individual's life, they may be misunderstood or undervalued by others who fail to recognize their significance.

      Neurocognitive explanations for both monotropism and special interests suggest that these behaviors are underpinned by fundamental differences in brain function and information processing in autistic individuals. Monotropism is thought to involve an atypical allocation of cognitive resources, where autistic individuals preferentially allocate their cognitive bandwidth to areas of high personal significance. This preferential allocation can be understood through the lens of predictive coding theories, particularly those emphasizing 'slow-updating' and 'high-precision' or 'hypoprior' mechanisms. These theories propose that autistic individuals maintain highly precise and stable internal models for their areas of interest, leading to profound engagement and expertise in these domains but also to challenges in adapting to new or less predictable tasks.

      Special interests, on the other hand, may be conceptualized as emergent properties of these underlying neurocognitive mechanisms. The intense focus and enthusiasm associated with special interests reflect the heightened precision and stability of the predictive models governing these interests. The sustained engagement with special interests can be further understood through the framework of neural reward pathways, where dopaminergic activity reinforces behaviors that align with these precise internal models, thereby enhancing the salience and reward value of special interests.

      Understanding both monotropism and special interests from a neurocognitive perspective can inform the development of supportive environments that leverage the strengths of autistic individuals. By recognizing and building upon their focused cognitive styles, educators, clinicians, and caregivers can implement strategies that accommodate attentional inflexibility while fostering opportunities for growth and adaptation. This approach not only acknowledges the unique cognitive profiles of autistic individuals but also promotes their overall well-being and societal inclusion.

      Here are the different versions to help understand Monotropism and Special Interests 

      Neuroception - Safety Perception

      Autism Lexicon - Neuroception

      Neuroception is the brain's automatic process of evaluating environmental safety and threat levels, often dysregulated in autism, leading to heightened sensitivity to sensory input and potentially contributing to negative attribution bias and hostile attribution bias. [ Read in more detail on Neuroception here].

      PlainSpeak: Neuroception is how our brain unconsciously decides if we're safe or in danger. In autism, this process can be heightened, causing some people to see everyday situations as more threatening, which can affect how they respond to others. [ Read in more detail on Neurocepton here]. 


      Understanding Short-Term Brain Changes and Autism

      PlainSpeak Plain Language Version for the Lay Reader

      Our brains constantly change how neurons (nerve cells) communicate to help us learn and remember things. Some of these changes happen very quickly and are known as short-term synaptic plasticity. This is when the connection strength between two neurons changes for a few seconds to a few minutes. Two important types of these changes are paired pulse facilitation (PPF) and paired pulse depression (PPD).

      Paired Pulse Facilitation (PPF) happens when two signals arrive close together at a neuron connection, and the second signal is stronger than the first. This is because the first signal leaves behind some calcium, which helps release more chemical messengers for the second signal, making it stronger.

      Paired Pulse Depression (PPD) is the opposite. When two signals come close together, the second signal is weaker. This happens because the first signal uses up most of the available chemical messengers, leaving fewer for the second signal.

      These short-term changes are important for how our brains process information. In autism, scientists have found that these changes can be different. For example, certain gene mutations linked to autism can affect how well these short-term changes work. Some of these genes, like SYN1 and SYN2, help control the availability of chemical messengers at neuron connections. Mutations in these genes can lead to an imbalance in brain activity, making some signals too strong and others too weak (Frontiers, 2015)​ (Frontiers)​.

      Other studies have shown that mutations in another gene, neuroligin-3, which is also linked to autism, can change how neurons communicate in different parts of the brain. These mutations can increase the strength of certain signals and disrupt the balance of brain activity (Molecular Psychiatry, 2015)​ (Nature)​. This imbalance can contribute to some of the behaviors seen in autism.

      Understanding these short-term brain changes helps scientists learn more about how autism affects the brain and can lead to new ways to help people with autism.

      2 versions of this post

      For the Academic/Scientific Audience

      PlainSpeak in plain language for the lay reader



      LTP and LTD and their Role in Autism

      The Neuroscience of Autism 
      Long Term Potentiation (LTP),  Long Term Depression (LTD) and their role in Autism.

      LTP and LTD are critical forms of long term synaptic plasticity that underlie learning and memory. These processes are governed by Hebbian plasticity, a principle summarized as "cells that fire together, wire together." This means that the synaptic strength between two neurons increases when they are frequently active together (LTP), and decreases when they are less synchronized (LTD).

      Spike-Timing Dependent Plasticity (STDP), a form of Hebbian plasticity, emphasizes the precise timing of neuronal spikes:

      • LTP: Induced when a presynaptic neuron fires just before a postsynaptic neuron, typically within 20 milliseconds. This leads to a significant influx of calcium (Ca2+) through NMDA receptors and voltage-gated calcium channels (VGCCs), strengthening the synapse.
      • LTD: Occurs when the postsynaptic neuron fires before the presynaptic neuron, usually within 20-100 milliseconds. This results in a weaker Ca2+ signal, leading to synaptic weakening.

      Research has revealed substantial alterations in LTP, LTD, and Hebbian plasticity in autism, providing insights into the neural mechanisms that contribute to autism’s cognitive and behavioral characteristics

      1. Hippocampal Dysfunction:

        • Studies on animal models, such as the BTBR mouse model of autism, show impaired hippocampal LTP. This impairment correlates with the learning and memory deficits commonly observed in autism (Rubenstein & Merzenich, 2003; Bourgeron, 2015)​ (Frontiers)​​ (Nature)​.
      2. Cerebellar Abnormalities:

        • Atypical LTD has been noted in the cerebellum, a region critical for motor control and coordination. This could underlie the motor deficits observed in autism (Fatemi et al., 2012)​ (Nature)​.
      3. Genetic Factors:

        • Mutations in synaptic genes such as SHANK3, NRXN1, and NLGN3, which are vital for maintaining synaptic plasticity, have been linked to autism. These mutations can disrupt the balance of LTP and LTD, leading to synaptic dysfunctions associated with autism (Durand et al., 2007; Südhof, 2008)​ (Frontiers)​​ (Nature)​.
      4. Neuromodulators:

        • Dopamine (DA) is a key neuromodulator that can modulate the direction and extent of synaptic changes. It acts through D1/D5 receptors to enhance LTP or through D2 receptors to promote LTD. This modulation is essential for adaptive learning and behavior in autism (Yagishita et al., 2014)​ (Frontiers)​.


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      PlainSpeak. Plain Language for the Lay Reader

      For the Academic/Scientific Audience



      References:

      • Rubenstein, J. L., & Merzenich, M. M. (2003). Model of autism: increased ratio of excitation/inhibition in key neural systems. Genes, Brain and Behavior, 2(5), 255-267.
      • Bourgeron, T. (2015). From the genetic architecture to synaptic plasticity in autism spectrum disorder. Nature Reviews Neuroscience, 16(9), 551-563.
      • Fatemi, S. H., Aldinger, K. A., Ashwood, P., Bauman, M. L., Blaha, C. D., Blatt, G. J., ... & Welsh, J. P. (2012). Consensus paper: Pathological role of the cerebellum in autism. The Cerebellum, 11(3), 777-807.
      • Durand, C. M., Betancur, C., Boeckers, T. M., Bockmann, J., Chaste, P., Fauchereau, F., ... & Bourgeron, T. (2007). Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nature Genetics, 39(1), 25-27.
      • Südhof, T. C. (2008). Neuroligins and neurexins link synaptic function to cognitive disease. Nature, 455(7215), 903-911.
      • Yagishita, S., Hayashi-Takagi, A., Ellis-Davies, G. C., Urakubo, H., Ishii, S., & Kasai, H. (2014). A critical time window for dopamine actions on the structural plasticity of dendritic spines. Science, 345(6204), 1616-1620.