What do LLM's know?

 Listened to a very interesting lecture today at SfN.  by LA Paul.

Got me thinking about belief systems. 

Belief Systems in Humans and LLMs.

While LLMs can produce outputs that seem aligned with certain perspectives or mimic human belief-based reasoning, they do not possess beliefs in the true sense. The distinction lies in the lack of consciousness, subjective experience, and intentional reflection. Instead, LLMs generate text based on patterns they have learned, without the internal state that would constitute holding beliefs. What may look like a belief system is merely a complex simulation, an echo of the data from which they were trained.

Do we need to update our belief systems to better understand LLM?

To better understand LLMs, humans may need to update their belief systems and frameworks, shifting away from traditional notions of intelligence, understanding, and knowledge. This means recognizing the statistical, context-based nature of LLM outputs, reframing how we think about AI capabilities, and addressing the ethical considerations that arise from their use. These changes can help foster a more accurate and nuanced understanding of what LLMs are, how they work, and what their role can be in our lives and society.

• Reframing Concepts of Intelligence: People often equate intelligence with understanding, leading to misconceptions about AI. LLMs simulate understanding based on learned patterns, not conscious thought, so recognizing this distinction helps prevent overestimating their abilities.
• Redefining Knowledge: Unlike human knowledge, LLMs work through statistical associations. Viewing them as tools for generating information rather than sources of human-like knowledge helps set realistic expectations.
• Context in Outputs: Humans tend to attribute intention to LLMs, but their outputs depend on context and training data. Focusing on this can clarify that their responses reflect patterns, not intentions.
• Recognizing LLM Limits: LLMs can mimic expertise but cannot verify facts or produce original thoughts. Differentiating fluency from factuality helps maintain a critical perspective on AI-generated content.
• Adopting Ethical Perspectives: As LLMs become more prevalent, it's important to address biases and responsibility for their outputs. Recognizing the societal impact of AI helps frame it beyond just a technical tool.
• Developing Communication Strategies: Effective use of LLMs requires skill in prompting and understanding their strengths. Clear communication about their capabilities helps prevent misunderstandings about AI’s nature.

Vanderbilt Brain Institute Retreat

 This will be my 3rd VBI retreat as a grad student. 

Stress and Anxiety in Autism: The Role of the HPA Axis

Understanding Stress and Anxiety in Autism: The Role of the HPA Axis

Stress and anxiety are common experiences for everyone, but for individuals with autism, these feelings can be particularly intense and challenging. Understanding why this happens involves delving into the body’s stress response system, known as the hypothalamic-pituitary-adrenal (HPA) axis.

What is the HPA Axis?

The HPA axis is a complex network of interactions among three glands: the hypothalamus, the pituitary gland, and the adrenal glands. When we encounter a stressful situation, the hypothalamus releases a hormone called CRH (corticotropin-releasing hormone). This hormone signals the pituitary gland to release another hormone, ACTH (adrenocorticotropic hormone), into the bloodstream. ACTH then prompts the adrenal glands to produce cortisol, often referred to as the "stress hormone."

Cortisol helps our body manage stress by increasing energy levels, suppressing non-essential functions (like digestion), and preparing the body for a "fight or flight" response. Once the stressful situation is resolved, cortisol levels drop, and the body returns to a state of balance.

Stress and Anxiety in Autism

In Autism, the HPA axis can often be more reactive, leading to heightened stress and anxiety. Several factors contribute to this increased reactivity:

1. Sensory Sensitivities: Many autistics have heightened sensory perceptions. Everyday noises, lights, or textures can be overwhelming, triggering a stress response more frequently.
2. Social Interactions: Social situations, which can be difficult to navigate, often cause significant stress and anxiety. The effort required to interpret social cues and respond appropriately can be exhausting.
3. Routine and Change: Many autistics thrive on routine and predictability. Unexpected changes or disruptions can cause considerable anxiety, activating the HPA axis.

The HPA Axis in Autism

Research suggests that the HPA axis in autistic individuals may function differently. Autistic people can have higher baseline levels of cortisol, indicating a chronic state of stress. Additionally, their cortisol levels might not return to normal as quickly after a stressful event, prolonging the period of anxiety and stress.

This heightened and prolonged stress response can have several implications:

• Mental Health: Chronic stress and anxiety can contribute to other mental health issues, such as depression.
• Physical Health: Elevated cortisol levels over long periods can affect physical health, leading to issues like weakened immune function and digestive problems.
• Daily Functioning: High stress levels can interfere with daily activities, making it harder to concentrate, learn, and interact with others.

Supporting Stress Management

Understanding the role of the HPA axis in autism can help in developing strategies to manage stress and anxiety. Here are a few approaches:

• Sensory Management: Creating environments that minimize sensory overload can help reduce stress.
• Routine and Predictability: Maintaining a predictable routine can provide a sense of security and reduce anxiety.
• Relaxation Techniques: Practices like deep breathing, mindfulness, and other relaxation techniques can help manage the body's stress response.
• Professional Support:  **** See Caveat 

By recognizing the unique ways the HPA axis operates in autism, we can better support autistics

[*** Caveat from my personal experience as autistic is that most of autism therapy is geared towards maximizing profits and fame, and less about the autistic progressing, because lack of progress can easily be attributed as fault of the autistic, it's never the therapy or therapist. So why spend more and more $$$$ on therapy].

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

The nuts and bolts of PD

The nuts and bolts of Parkinson's Disease.

Parkinson's disease (PD) typically manifests in individuals over the age of 50, with about 5% prevalence in those over 85 years old. Most cases are sporadic with rare inherited variants, suggesting that environmental or toxin-related triggers are likely contributors. PD is characterized by symptoms such as rhythmic tremors in the hands and feet, especially at rest, bradykinesia (slow movement), and akinesia (difficulty initiating movement). These symptoms result from damage and cell death in the brain regions such as the substantia nigra in the brain stem and the locus coeruleus, leading to decreased levels of norepinephrine and dopamine (DA). The substantia nigra projects to the striatum, where DA is the principal neurotransmitter involved in relaying movement messages to the cortex. Neuromelanin, a byproduct formed from the oxidation of DA to quinones and semiquinones and subsequent metal ion binding, is evident in PD due to its black pigmentation. The disease also features Lewy bodies in the substantia nigra and other brain areas, which are composed primarily of the protein alpha-synuclein, abundant in presynaptic neuron terminals. The major treatment for PD is L-DOPA, but excessive DA can lead to the formation of hydrogen peroxide and reactive oxygen species when released into the cytoplasm. This oxidative stress contributes significantly to the neurodegeneration observed in PD 

Dopamine

 Brain Humor 

Check out more humor in this blog and on YouTube

Stress and Neck Pain

Insights from Neuroanatomy class. 

The Accessory XI nerve, a cranial nerve, is vital for controlling the trapezius muscle, which facilitates various neck and shoulder movements. When stress occurs, this muscle can tense up, leading to neck discomfort. Interestingly, in quadrupeds like cats, the trapezius muscle is crucial for lifting the head; this adaptation aids grazing animals in responding to external stimuli. Additionally, the short-term memory (STM) muscles also contribute to raising the head, illustrating the complexity of our muscular system's evolution and functionality.

The Complex Terrain of Muscle Contraction - Insights from Disability

(Based on topic covered in Neuroanatomy Class along with some additional disability perspectives. )

In the world of biology, muscle contraction is a fundamental process, enabling us to move and function. The way our muscles contract, however, can lead to various consequences, especially when disrupted by factors like bacterial infections.

Muscle contractions are driven by motor units. Whether the contraction is strong or weak depends on how many of these units are activated. So a fine precise motor action requires small number of units activated and need little strength.

Tetanus, caused by bacteria, takes this natural muscle contraction process to an extreme, forcing every single motor fiber in a muscle to contract simultaneously, causing intense pain that is hard to put into words.

Understanding muscle pain takes us to the basics of cellular respiration. Muscles, like all cells, need oxygen, which is supplied through arteries. When a muscle contracts and restricts this oxygen supply, it creates a problem. The muscle cells continue to function, breaking down glucose in the absence of oxygen. However, this process produces lactate, leading to a burning sensation, indicating the body's distress.

This pain can have severe consequences. In intense muscle contractions, essential muscles like the diaphragm, responsible for breathing, can weaken. Chest muscles may become so tense that they hinder the natural process of inhaling and exhaling.

In the complexity of our body's workings, this delicate balance between muscle contraction and relaxation defines our abilities. Understanding these intricacies not only enhances our knowledge of our biological marvel but also emphasizes the need to appreciate and preserve the balance that allows us to move and function seamlessly.

There exists a parallel narrative, one that often goes unnoticed — the experience of autistics. Consider a autistic whose sensory perceptions are heightened and processed differently. The involuntary muscle contractions experienced by autistics might not only induce physical discomfort but also trigger heightened sensory responses, amplifying the distress. In such cases, the pain isn't merely a physiological phenomenon; it extends into the realms of sensory overload, creating an overwhelming and sometimes unbearable experience.

Understanding muscle contraction through the lens of disability offers profound insights into the human experience. It urges us to delve deeper, to acknowledge the diverse ways in which individuals perceive and process pain. In doing so, we foster empathy and compassion, paving the way for inclusive healthcare practices that cater to the unique needs of every individual, irrespective of their physical or neurological differences. 

Consciousness

The exploration of consciousness is a central theme in both  Buddhism and Sanathana Dharma (Hinduism) philosophies, and modern scientific inquiry has begun to intersect with some of these ancient concepts. While there are parallels, there are also significant differences in the methodologies, foundational assumptions, and goals of spiritual traditions and scientific inquiry. The intersections, however, provide fertile ground for scientific enrichment.

Nature of Consciousness and Quantum Physics. Both Sanathana Dharma and Buddhism assert that consciousness isn't a byproduct but a fundamental aspect of reality. This perspective aligns, to some extent, with certain interpretations of quantum mechanics, which propose that consciousness plays a role in the process of quantum measurement or wave function collapse.

Meditation, Mindfulness, and Neuroscience: Neuroscientific research into the effects of meditation—a practice central to both Sanathana Dharma and Buddhist traditions—has shown that it can induce significant changes in areas of the brain associated with attention, emotion regulation, and self-awareness.

Self and Non-self:  Sanathana Dharma philosophy's exploration of the self through concepts like "Atman" (individual soul) and its relationship with "Brahman" (universal consciousness) can be seen in parallel with the scientific exploration of individual consciousness and its relationship with the world. Buddhism's concept of "Anatta" (non-self) proposes that there's no continuous, unchanging self. This idea resonates with certain findings in neuroscience, suggesting that the perception of a continuous "self" is an emergent property of various neural processes and not localized in one part of the brain. 

Levels and States of Consciousness: The Mandukya Upanishad, outlines different states of consciousness, including waking, dreaming, deep sleep, and a transcendent state known as "Turiya." Modern neuroscience also explores various states of consciousness, such as REM sleep, deep sleep, and altered states induced by substances or meditation. Buddhist meditation practices often aim to transcend ordinary states of consciousness and attain enlightened states. Neuroscientific studies on accomplished meditators have reported unique brainwave patterns and states of consciousness.

Interconnectedness: Both Sanathana Dharma and Buddhist philosophies emphasize the interconnectedness of all things. This idea has resonances with holistic perspectives in science, especially in fields like ecology and certain interpretations of quantum physics which emphasize non-locality and entanglement.

Plasticity and Transformation: Both Sanathana Dharma and Buddhist traditions emphasize the possibility of transforming one's mind and consciousness. The idea of neuroplasticity in modern neuroscience—that the brain is malleable and can be changed through experiences, especially practices like meditation—aligns with this.

Phenomenal Experience: Buddhism, particularly in schools like Yogacara, delves deep into the nature of experience, cognition, and perception. These explorations find parallels in cognitive science and phenomenological approaches in modern philosophy of mind.

Phrenology according to Gall. A Historical Curiosity

 

The 18th century consensus on the brain was steeped in ancient beliefs that depicted it as an formless mass governing bodily functions. Franz Josef Gall, challenged this orthodoxy: the brain wasn't a mere lump of flesh but the very seat of our mental faculties, with distinct regions governing specific functions. This revolutionary idea laid the foundation for what we now recognize as "phrenology." While Gall's phrenological theories have been largely discredited in modern neuroscience, his work marked a significant shift in the study of the brain.  Gall's work also contributed to the development of techniques for brain mapping and the understanding of cognitive processes.

Landing himself in plenty of hot water. 
The prevailing view of the era was dominated by religious or philosophical beliefs rather than empirical research. Gall's ideas  challenged long-held beliefs about the nature of the mind and the brain and landed in a lot of hot water. 

His beliefs were seen as a direct challenge to established religious doctrines, suggesting that human behavior and personality were products of physical attributes, not divine intervention. This incurred the wrath of religious authorities who deemed phrenology heretical. In 1805, Gall was banned from practicing phrenology in Prussia by the Prussian government, which considered his ideas subversive and potentially dangerous. He was eventually expelled from Prussia but that did not deter him from promoting phrenology elsewhere. He continued to travel and lecture about his theories in other European countries, where phrenology gained a following and influence, particularly in France and the UK.

And the hot water was not just religions, but also social. Phrenology also had practical implications, as some individuals and organizations began using it for character assessment in various contexts, such as education and employment. This raised ethical and legal questions about the fairness and validity of making judgments about people based on phrenological assessments.

Gall's  garnered both acclaim and criticism from his contemporaries. One notable figure was Johann Spurzheim, Gall's collaborator and rival, who further popularized phrenology and took it to international audiences. Another contemporary of interest is Marie-Jean-Pierre Flourens, a French physiologist who advocated for a more holistic view of brain function, emphasizing the importance of the brain as a whole rather than isolated "organs." Other scientific peers cast doubts upon his theories, criticizing the lack of empirical evidence and the inherently subjective nature of his observations. Phrenology, in their eyes, was more pseudoscience than genuine scientific inquiry. 

Gall's Neuroanatomy Diagram: A Window into the Mind
Gall's most notable contribution was his intricate neuroanatomy diagram, which depicted the brain as a series of localized faculties or organs, each responsible for a particular aspect of personality or behavior. The size of these organs corresponded to a person's character traits and abilities. Obviously this is quite incredulous by today's standards - a historical curiousity. 

• Firmness (in frontal lobe) Development of this area in the frontal lobe was associated with determination, willpower, and the ability to persevere in the face of challenges.
• Immortality: linked to religious and moral tendencies, as well as a sense of spirituality.
• Veneration (Parietal Love): related to feelings of respect, admiration, and reverence for authority figures or ideals
• Destructiveness (in lower back of brain): aggressive and combative behaviors, as well as a propensity for violence.
• Benevolence (frontal love): linked to kindness, empathy, and a compassionate nature.
• Acquisitiveness (forehead): desire for material wealth and possessions.
• Wit (Frontal Lobe):  responsible for humor, quick thinking, and cleverness.
• Love of Offspring (back of brain):linked to parental instincts and the love and care of one's children.
• Secretiveness (Upper back of brain): associated with the tendency to keep secrets and be discreet.
• Self-Esteem (upper back of head): related to self-confidence, pride, and a sense of self-worth.

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The Brain is Never Zero

The Brain is Never Zero

In the realm of thoughts, wonders reside
Brain pulses ceaselessly, a relentless tide
Neurons fire, synapses alight
The brain is never zero, its brilliance ignites.

Review v Meta Analysis

I continue to learn....as I navigate grad school

Review vs Meta-Analysis

A review paper /literature review, provides a comprehensive overview and evaluation of existing research on a particular topic. It involves gathering information from multiple sources, such as research articles, books, and other relevant publications, and synthesizing the findings to summarize the current state of knowledge on the topic. Review papers typically do not involve statistical analysis or original data collection.

A meta-analysis is a specific type of research synthesis that involves combining and analyzing quantitative data from multiple studies to generate more robust conclusions. Researchers identify relevant studies, extract relevant data from each study, and statistically analyze the combined data to derive overall effect sizes or estimates of the relationship between variables. Meta-analyses often include a systematic review of the literature as a first step to identify relevant studies for inclusion.

Self Referencing and Self Projecting

[Concepts in Sensorimotor Research]

Within the context of multisensory integration, self-referencing and self-projecting skills play important roles in our perception of time. 

• Self-Referencing:  general capacity of using one's own position in time to estimate/situate events in time. This skill relies on internal cues such as memory and self-awareness to place events within a temporal framework. By referencing our own experiences and the temporal context in which they occurred, we can make sense of the timing and sequence of events in our environment.
• Self-Projecting: ability to mentally move back and forward in time, maintaining the competence of correctly situating events in time. This skill allows us to anticipate future events, plan our actions, and make decisions based on the temporal context. Self-projecting skill involves mental time travel, where we can mentally simulate and project ourselves into different points in time, drawing upon past experiences and knowledge to predict and shape future events.

Both self-referencing and self-projecting skills are closely intertwined with our sensory experiences. Our senses provide us with temporal information through various cues. For example, visual stimuli provide temporal cues through motion and changes in spatial patterns, while auditory stimuli provide temporal cues through changes in pitch, intensity, and rhythm. By integrating these sensory cues with our self-referencing and self-projecting abilities, we can accurately perceive and situate events in time.

Principle of inverse effectiveness

[Concepts in Sensorimotor Research]

The principle of inverse effectiveness is a phenomenon observed in multisensory integration, which refers to how our brain combines information from multiple sensory modalities, such as vision, hearing, and touch. According to this principle, the strength or effectiveness of multisensory integration is greatest when the individual unisensory cues are weak or ineffective on their own.

Ergo, when the individual sensory cues are relatively weak or have low impact, the brain tends to rely more on multisensory integration to enhance the perception and processing of the stimuli. eg: people with hearing loss exhibit increased visual abilities, and increased crossmodal activation within the auditory cortex. 

This principle suggests that the brain optimally integrates sensory information from multiple modalities to improve perception and increase sensitivity, particularly in situations where the sensory cues are less informative or ambiguous.

The principle of inverse effectiveness highlights the advantage of combining multiple sensory inputs in situations where the individual senses may provide limited or unreliable information. By integrating sensory cues from different modalities, the brain can enhance the overall perception and make more accurate judgments about the external environment. This principle has been observed across various species and sensory domains and is believed to reflect a fundamental property of multisensory processing.

MBNCA Connectome Dataset

 

Researchers at the University of Melbourne have created a dataset that maps connectivity in 40,000 brains. The dataset, called the Melbourne Brain Network Connectivity Atlas (MBNCA) includes data on the structure and function of the brain, as well as information on the participants' demographics and health. The data in the MBNCA dataset comes from a variety of sources, including brain scans, genetic data, and behavioral data.

The MBNCA includes data from over 1,000 autistic individuals; making it one of the largest datasets of its kind. The MBNCA is freely available to researchers and may be a good resource to to study autistic brains to identify potential biomarkers and gain other insights.

https://www.biorxiv.org/content/10.1101/2023.03.10.532036v1

CRH-PVN Neuron and Stress Controllability Presentation

I survived it. 

OMG. lot of work went into this intense presentation the last couple of weeks with my classmate James. 

And right after our 50 min presentation, we were given feedback from the 3 TAs (Patrick, Matt & Elena) and by the Prof Teru Nakagawa and Prof Christine Konradi. Other students are literally sent out of the room, so that we could be given individual feedback from the grading team. I got to go first then James. 

Presenting with passion, nerves not intact,
Paper on CRH-PVN neurons stacked.
The audience watched, with eyes on me,
My words and slides, a neuroscience spree

CRH who?

Neuroscience humor. Studying CRH-PVN neurons and stress this week. 

Knock knock.

Who's there? 

CRH. 

CRH who? 

CRH releasing PVN, causing stress to you!

The Three T's

My classmate James and I met with Prof Christine Konradi to discuss our presentation strategy for the paper on the CRH-PVN neuron for our neuroscience class next friday.

"You start out by you telling them what you're going to tell them, then tell them, and then you tell them what you told them," was her starting advice.

She was referring to the Three T's approach - Tell Them, Tell Them, Tell Them -  a strategy for organizing a speech or presentation into three parts:

• introduction where you preview what you will discuss
• the body of content /message
• Conclusion where you summarize what you covered.

The idea is to make your message clear and memorable by emphasizing the key points multiple times.

Next week we'll be learning about mood disorders, the HPA axis, which the CRH neurons are part of. 

Each week, we have a different professor teaching the class in an area that's their specialty. Next week its with Professor Konradi who also picks the paper that we present. 

 I asked what had motivated her to pick this paper. She said, we were learning about mood disorders this week and the HPA axis  which the CRH neurons were part of. So not only is this topic related to what we have been learning for the week but also it is relevant for us in neuroscience because the kind of tools and methods used are very state of the art.  

So fingers crossed we do a good job. It's a lot of work putting a presentation together. and i've noticed my other classmates looking absolutely worn out during their presentation week. 

Fruit Fly Connectome

Lay Summary: Scientists have now mapped all the neural connections/pathways of a fruit fly (connectome). Why is this important? Fruit fly model is used in autism research, so this advance potentially helps autism research. 

https://www.science.org/doi/10.1126/science.add9330

Bayes Squad

 The Bayes Squad

A Probability Party with Formula Fellows

Bayes Theorem BT: Alright folks, let's get this Bayesian statistics party started! I'm Bayes Theorem, and I'm the king of the castle around here.

Prior Probability PA(A): Whoa, whoa, whoa. Slow down there, Bayes. You may be the main formula, but I'm the one who sets the foundation. I'm Prior Probability, and I establish the probability of events before any data is collected.

Likelihood P(A): And I'm Likelihood, the star of the show. I calculate the probability of evidence given the hypothesis.