Thought this was kinda interesting after hammering at Claude. Might be beneficial to others as well.

Comprehensive Framework for Understanding Sudden Neurological Sensitivity Changes

1. Central Sensitization and Neuroplasticity

Plausibility: Very High

• Mechanism:

  1. Repeated exposure to triggering stimuli causes sustained activation of NMDA receptors in the central nervous system.
  2. This leads to increased intracellular calcium and activation of calcium-dependent kinases.
  3. These kinases phosphorylate various receptor and ion channel proteins, increasing their responsiveness.
  4. Simultaneously, there's an upregulation of pro-nociceptive pathways and downregulation of anti-nociceptive pathways.
  5. The result is a lowered threshold for activation and increased responsiveness to both noxious and non-noxious stimuli.

• Sudden Shift Explanation: The process occurs gradually at a cellular level, but the perceived effect can be sudden once a critical threshold is reached. Insights from epilepsy research suggest that central sensitization can occur more rapidly than previously thought, potentially explaining very sudden onset of sensitivities.

• Cross-Stimulus Sensitivity: Once central sensitization occurs, it affects the processing of a wide range of stimuli.

• Biochemical Basis: Involves changes in neurotransmitter release (e.g., increased glutamate, substance P) and receptor density.

2. Thalamocortical Dysrhythmia

Plausibility: High

• Mechanism:

  1. Abnormal thalamic rhythms disrupt the normal gating and processing of sensory information.
  2. This disruption can be triggered by changes in input patterns.
  3. Altered thalamocortical oscillations lead to abnormal cortical processing of sensory information.

• Sudden Shift Explanation: Changes in sensory input characteristics can abruptly alter the pattern of input to the thalamus. In epilepsy, thalamocortical circuits can rapidly shift into pathological oscillatory patterns. This might explain how sensory processing can change abruptly in non-epileptic hypersensitivity conditions.

• Cross-Stimulus Sensitivity: Once established, thalamocortical dysrhythmia can affect the processing of inputs from various sources.

• Neurochemical Basis: Involves alterations in the balance of excitatory (glutamatergic) and inhibitory (GABAergic) neurotransmission in thalamocortical circuits.

3. Neuroinflammatory Response and Glial Activation

Plausibility: Moderate to High

• Mechanism:

  1. Intense or prolonged sensory stimulation triggers activation of glial cells (microglia and astrocytes).
  2. Activated glia release pro-inflammatory cytokines (e.g., IL-1β, TNF-α) and chemokines.
  3. This localized neuroinflammation alters synaptic function and neural excitability.
  4. Chronic neuroinflammation can lead to structural changes in neural circuits.

• Sudden Shift Explanation: While the inflammatory process is gradual, the cumulative effects can reach a tipping point, leading to sudden symptom onset. Recent epilepsy research highlights the role of rapid glial signaling in seizure propagation. This fast glial response could contribute to sudden onset of sensitivities in non-epileptic conditions.

• Cross-Stimulus Sensitivity: Neuroinflammation can spread beyond the initially affected areas, influencing broader neural networks.

• Biochemical Basis: Involves complex interactions between neural and immune systems, including changes in levels of inflammatory mediators and neurotrophic factors.

4. Trigeminal Pathway Sensitization

Plausibility: Moderate to High

• Mechanism:

  1. Repeated stimulation leads to sensitization of trigeminal nociceptors.
  2. This results in lowered activation thresholds and increased responsiveness of trigeminal neurons.
  3. Central sensitization in the trigeminal nucleus caudalis can occur, amplifying incoming signals.

• Sudden Shift Explanation: Accumulating subthreshold stimulation can lead to a sudden crossing of the sensitivity threshold.

• Cross-Stimulus Sensitivity: Sensitized trigeminal pathways can respond excessively to various types of sensory input.

• Neurochemical Basis: Involves release of neuropeptides (e.g., CGRP, substance P) and changes in ion channel properties in trigeminal neurons.

5. Disruption of Inhibitory Control Mechanisms

Plausibility: Moderate

• Mechanism:

  1. Normal sensory processing relies on a balance of excitatory and inhibitory signals.
  2. Prolonged or intense stimulation can lead to dysfunction of inhibitory interneurons.
  3. This is often mediated by changes in GABAergic transmission or alterations in chloride homeostasis.
  4. The result is a failure to properly filter and modulate incoming sensory information.

• Sudden Shift Explanation: Inhibitory dysfunction can occur rapidly if the system is pushed beyond its compensatory capacity. Epilepsy research shows that inhibitory control can break down rapidly under certain conditions, potentially explaining sudden shifts in sensory processing.

• Cross-Stimulus Sensitivity: Impaired inhibitory control affects the processing of various sensory inputs.

• Neurochemical Basis: Primarily involves changes in GABA signaling and expression of GABA receptors.

6. Aberrant Cortical Map Reorganization

Plausibility: Moderate

• Mechanism:

  1. Sensory cortices maintain dynamic representations (maps) of sensory inputs.
  2. Intense or unusual stimulation patterns can trigger rapid reorganization of these cortical maps.
  3. This reorganization can lead to altered processing of sensory information.

• Sudden Shift Explanation: Cortical map changes can occur rapidly under certain conditions.

• Cross-Stimulus Sensitivity: Reorganization in one sensory area can influence processing in related areas due to cortical interconnectivity.

• Neurobiological Basis: Involves rapid changes in synaptic strengths and potentially the formation of new synaptic connections.

7. Autonomic Nervous System Dysregulation

Plausibility: Moderate

• Mechanism:

  1. Chronic stress or intense sensory experiences can disrupt normal autonomic nervous system functioning.
  2. This leads to an imbalance between sympathetic and parasympathetic activity.
  3. Autonomic dysregulation can affect various physiological processes, including sensory processing and pain modulation.

• Sudden Shift Explanation: Acute stressors or intense stimuli can trigger rapid shifts in autonomic balance.

• Cross-Stimulus Sensitivity: Autonomic dysregulation can have widespread effects on multiple organ systems and sensory modalities.

• Biochemical Basis: Involves changes in catecholamine levels and alterations in hypothalamic-pituitary-adrenal (HPA) axis function.

8. Ephaptic Coupling and Neural Cross-talk

Plausibility: Low to Moderate

• Mechanism:

  1. Neurons can influence nearby neurons without synaptic connections, through electric fields (ephaptic coupling).
  2. In sensitized states, this could lead to abnormal activation of adjacent neural pathways.
  3. This might result in cross-activation between different sensory modalities or processing streams.

• Sudden Shift Explanation: Changes in local neural activity could suddenly enable significant ephaptic effects.

• Cross-Stimulus Sensitivity: Abnormal cross-talk between neural pathways could explain generalization of sensitivity across different types of stimuli.

• Biophysical Basis: Involves changes in extracellular ion concentrations and alterations in the electrical properties of neural tissue.

9. Sensory Gating Dysfunction and Hypervigilance

Plausibility: Moderate to High

• Mechanism:

  1. Stress or heightened awareness about potential sensitivities can alter sensory gating mechanisms.
  2. This leads to increased attention to and processing of previously ignored stimuli.
  3. The prefrontal cortex and limbic system become hypervigilant to specific sensory inputs.
  4. Normal filtering mechanisms are overridden, allowing more sensory information to reach conscious awareness.

• Sudden Shift Explanation: Acute stress or a triggering event can rapidly alter attentional focus and sensory processing.

• Cross-Stimulus Sensitivity: Hypervigilance can generalize across similar stimuli, explaining why sensitivity to one type might suddenly extend to others.

• Neurochemical Basis: Involves changes in norepinephrine and cortisol levels, affecting arousal and attention systems.

10. Ocular Surface Disruption and Sensory Adaptation

Plausibility: Moderate

• Mechanism:

  1. Changes in the ocular environment can alter the ocular surface conditions.
  2. This may lead to changes in tear film composition or corneal nerve sensitivity.
  3. Altered sensory input from the ocular surface can affect visual processing and comfort.
  4. The visual system may undergo maladaptive changes in response to this altered input.

• Sudden Shift Explanation: Acute changes in ocular surface conditions can rapidly alter visual comfort and processing.

• Cross-Stimulus Sensitivity: Changes in ocular surface sensitivity can affect viewing comfort across various types of visual stimuli.

• Physiological Basis: Involves alterations in corneal nerve function, tear film dynamics, and ocular surface inflammation.

11. Rapid Kindling and Seizure-Like Spreading Depression

Plausibility: Moderate to High

• Mechanism:

  1. Repeated subthreshold stimuli can lead to a rapid lowering of seizure threshold (kindling).
  2. This can result in a seizure-like spreading depression wave across the cortex.
  3. The spreading depression can alter the excitability of large brain areas rapidly.

• Sudden Shift Explanation: Kindling effects can accumulate silently and then manifest suddenly when a threshold is crossed.

• Cross-Stimulus Sensitivity: The spreading depression can affect multiple sensory processing areas, leading to generalized hypersensitivity.

• Neurophysiological Basis: Involves changes in ion concentrations, particularly potassium and calcium, altering neural excitability across broad areas.

12. Network State Transitions and Bistability

Plausibility: Moderate

• Mechanism:

  1. Neural networks can exhibit bistable states - normal functioning and hypersensitive/hyperexcitable.
  2. Certain triggers can cause a rapid state transition from one stable state to another.
  3. This transition can occur across multiple interconnected neural networks simultaneously.

• Sudden Shift Explanation: State transitions in neural networks can occur rapidly, explaining sudden onset of sensitivities.

• Cross-Stimulus Sensitivity: The new network state affects processing of multiple types of sensory input.

• Computational Neuroscience Basis: Based on principles of dynamical systems theory applied to neural networks.

13. Altered Neurovascular Coupling

Plausibility: Moderate

• Mechanism:

  1. Changes in neurovascular coupling can alter the relationship between neural activity and blood flow.
  2. This can lead to localized areas of hypoxia or altered metabolism in the brain.
  3. Affected areas may become hyperexcitable or hypersensitive to stimuli.

• Sudden Shift Explanation: Vascular changes can occur rapidly, altering neural function in specific brain regions.

• Cross-Stimulus Sensitivity: Altered neurovascular coupling can affect multiple brain areas involved in sensory processing.

• Physiological Basis: Involves changes in cerebral blood flow, oxygen metabolism, and neurotransmitter clearance.

14. Channelopathy-Induced Hyperexcitability

Plausibility: Moderate

• Mechanism:

  1. Mutations or functional changes in ion channels can alter neuronal excitability.
  2. Environmental factors or stress can unmask or exacerbate underlying channelopathies.
  3. This can lead to sudden changes in how neurons respond to sensory inputs.

• Sudden Shift Explanation: Channelopathies can be latent and then manifest suddenly under certain conditions.

• Cross-Stimulus Sensitivity: Altered channel function can affect multiple sensory pathways.

• Genetic and Molecular Basis: Involves specific ion channel dysfunctions, often with genetic components.

Additional Considerations:

1. Cumulative Sensitization: Exposure to multiple challenging stimuli over time may lead to a cumulative sensitization effect, eventually manifesting as intolerance to previously tolerable inputs.

2. Histamine-Mediated Sensitivity: Histamine-mediated mechanisms may play a role in sensory sensitivities, potentially interacting with neuroinflammatory processes.

3. Psychological Factors: The power of expectation and hypervigilance in altering sensory processing should not be underestimated, even when physical symptoms are present.

4. Stimulus-Specific Characteristics: Specific characteristics of stimuli beyond their general category may play a role in triggering sensitivities.

5. Individual Health Factors: Pre-existing health conditions, particularly those affecting sensory organs or the nervous system, may contribute to increased susceptibility to sensory discomfort.

6. Priming and Threshold Effects: Like in epilepsy, there may be a 'priming' period where the brain becomes more susceptible to developing sensitivities, followed by a threshold event that triggers sudden onset.

7. Rapidness of Neural Network Reorganization: Epilepsy research suggests that neural networks can reorganize more quickly than previously thought, potentially explaining sudden shifts in sensory processing.

8. Role of Subcortical Structures: Recent epilepsy research emphasizes the importance of subcortical structures in seizure initiation and propagation. These structures may play a crucial role in sudden sensitivity changes.

9. Interaction Between Systems: The interaction between neuronal, glial, vascular, and immune systems, as seen in epilepsy, may contribute to the complex and sudden nature of sensitivity changes.

10. Individual Variability in Network Resilience: Like epilepsy thresholds, there may be significant individual variability in resilience to developing sudden sensitivities, based on genetic, environmental, and physiological factors.

This comprehensive framework integrates multiple perspectives from neuroscience, including insights from epilepsy research, to provide a thorough understanding of how and why sudden shifts in sensory sensitivities might occur. It emphasizes the potential for rapid changes in neural function and highlights the complex interplay of various physiological systems in these phenomena. This framework can serve as a foundation for further research, clinical investigations, and the development of targeted interventions for individuals experiencing sudden sensitivity changes.

async I don't like these questions because they are really just accusatory and dismissive
They must not start with "First time".

QuitePainful

For sure. But before all that, you need to evaluate if these things appear outside of displays - in real world / nature.
Then you need to evaluate if there are sensitivities in the individual.
Then, it needs to be evaluated what worked historically and what not.
Afterwards, the comparison between that data and the new state needs to be made.

Note that if you do not get any eye-strain if you avoid all displays, then displays may have something in it, that triggers issues.
You may switch to a different technology, but your own eye-sight in real-life will always be a more realistic experience than exposure to artificial light emissions.

And yep, To say … "First time …" just feels like an insult.

I gave Chat-GPT a try. Here is what it says:

The post might feel insulting because it appears to make broad assumptions about people’s experiences with screens without acknowledging individual differences. Here are a few reasons why it might come across that way:

1. Assumptions About Sensitivity: It suggests that the user’s discomfort or difficulty might be due to "maladaptive changes" or specific features like True Tone or PWM, which could imply that the person isn’t paying enough attention to these factors or isn’t adaptable.

2. Technical Jargon and Theories: The post dives into technical details and theories without a clear understanding of how they might apply to everyone’s individual experiences. This can make it feel dismissive of personal experiences if they don't align with the stated theories.

3. Focus on Specific Products: Mentioning specific products like the MacBook Pro M1 and iPhones might come off as overly critical or dismissive of those who are using these devices and experiencing discomfort, potentially suggesting that their issues are minor or self-inflicted.

4. Generalization of Experience: The post is framed in a way that could be interpreted as suggesting there’s a “right” or “wrong” way to experience screen discomfort, which may invalidate or overlook individual experiences.

It might help to frame your inquiry more neutrally, acknowledging that different people have unique experiences and emphasizing that you’re interested in a variety of perspectives rather than focusing on specific technical causes or solutions.

async I understand your stance.
However, also try to understand me. The data-points you try to gather are pretty late in the chain of information
If the previous data-points are not assessed, it becomes a pointless exercise, because it will be hugely biased.
We shall not end up in wrong conclusions.

Let me explain in this hypothetical situation:
1. I eat toast from the brand foo.
2. After 6 years, I notice that my throat itches when I eat that particular toast
3. <=== Now you start Interviewing ===>
4. You ask me if it was the first time I ate that particular toast
5. I say no, I ate it for 6 years
6. You ask me if I ever tried a whole grain toast

Do you see the issue?
- We need to make sure the ingredients stayed consistent
- We need to make sure the health stayed consistent
- We need to make sure the dining ware stayed consistent
- And so much more!

To have the audacity to ask for a full-grain toast, even if the user didn't choose to, for trying to fix the situation, is dismissive, misleading and not scientific at all.
We need to make sure that all details are assessed. Not just those few - late data-points.

QuitePainful I did not omit it.
Specifically, 2. After 6 years, I notice that my throat itches when I eat that particular toast

- It could have been that the user became allergic ( yep this can happen over time )
- It could have been that the ingredients changed.

bluetail I must have misunderstood.

Wouldn't 2. After 6 years, I tried a different kind of toast that made my throat itch and now my throat itches when I eat my usual toast as well exemplify the premise better, making it reasonable to ask questions about the different kind of toast that was tried and that seems to have caused the change?

If a change like this occurred spontaneously without any clear cause, you would have a point, but async is talking about a situation where a plausible external cause does exist, namely exposure to a different screen.

I feel like we're veering a bit off topic here.

QuitePainful Oh, thats helpful. And rest assured, we are on-topic.
The first difficulty in the questions asked was to understand the intent properly.

This would fulfill the criteria to develop an allergy or sensitivity.
It is well known that consuming some food can cause allergies and cross-allergies you didn't had before.

To name one example I have read online: Exposure to latex can lead to latex allergy, and make you allergic to bananas, kiwis […]