Neurotransmitters Flow in this Autism Mind

Feb 17 is Random Act of Kindness Day

Saw this on Canva. Did not know that there was a day. But a good thought nonetheless.

Loneliness

The room is empty

Loneliness creeps in slowly
Empty walls surround

Silence echoes all around

Pollina et al. 2023
The paper describes a new method called sBLISS-seq for identifying DNA damage sites in cells. The authors used this method to study the role of a protein called Ep400 in repairing DNA damage.

The paper suggests that the link between neuronal activity and DNA repair mediated by NPAS4-NuA4 may be relevant to NDD like autism. This is because damage at activity-dependent regulatory elements may be a source of neuronal dysfunction in these disabilities.

Key Takeaways & Contributions.

- Discovery of a specialized chromatin regulatory mechanism in the brain that couples synaptic activity to genome preservation.

- Identification of a link between neuronal activity and DNA repair mediated by NPAS4-NuA4, which suggests that damage at activity-dependent regulatory elements may be a source of neuronal dysfunction in NDD and autism .

- Potential role of NPAS4-NuA4 in sustaining neuronal vitality over time and contributing to cellular and organismal longevity.

- Development of a new method called sBLISS-seq for identifying DNA damage sites in cells

Methods

The development of a new method called sBLISS-seq for identifying DNA damage sites in cells.
The use of

chromatin immunoprecipitation (ChIP) to study the binding of proteins to DNA.
CRISPR-Cas9 genome editing to create knockout cell lines.
RNA sequencing (RNA-seq) to study gene expression.
immunofluorescence to study protein localization in cells.
comet assays to measure DNA damage.

Questions raised

What is the full extent of the role of NPAS4-NuA4 in sustaining neuronal vitality over time and contributing to cellular and organismal longevity?
How does the link between neuronal activity and DNA repair mediated by NPAS4
NuA4 contribute to NDD & autism, and can this mechanism be targeted for therapeutic purposes?
What other proteins and pathways are involved in the regulation of DNA repair in response to neuronal activity, and how do they interact with NPAS4-NuA4?
How can the sBLISS-seq method be further optimized and applied to other cell types and experimental conditions?
Findings implications in understanding relationship between neuronal activity and genome preservation in the brain?

Haikus for the love of spring

Its feb 14 and spring is upon us. I see flowers bloom on my neighbor's tree.

In the midst of bloom,

Petals entwine, a sweet embrace,

Love's essence inhaled.

TBI Regressive Autism

Ameliorating Hemianopia with Multisensory Training (Rowland et al., 2023)

Quick Summary of paper . An visual-auditory stimulation therapy was used on two older males who has loss of vision in the left hemifield (hemianopia). The cause was brain trauma (TBI) rather than lesion. Prior to joining the study both had been referred to PT and OT as rehabilitation measures.

64 year old JM joined the study 14 months after stroke (2 infracts)
74 year old CW joined the study ~18 months after 1 infract (better sighted field compared to JM).
Therapy took place over 8 months /10 sessions

The results were dramatic. Both patients recovered the ability to detect and describe visual stimuli throughout their formerly blind field within a few weeks. They could also localize these stimuli, identify some features, and perceive multiple visuals simultaneously in both fields. (more detail on paper here link)

Relating all this back to Autism

So impressive about being able to restore sight in a matter of 8 months, given therapy was started 14-18 months after infract and not immediately and it was in older adults.

Why is regressive autism not thought to be TBI at 18 mo, where there is a sudden loss of learned skills.

If TBI --> can those lost skills not be regained through targeted therapy. If you can restore skills in 60-70 yr old, should be able to, in a younger more plastic brain.
If TBI --> is this related to CW & JM having practice with vision for 60-70+ years vs toddlers who only have practice with the skills for 18 mo.

Rethink Traditional Therapies

CW & JM had PT/OT for 14-18 mo before joining study; implication these therapies not that useful for regaining lost skills.
Autistics kids are in insane amounts of therapy (childhood stuffed with ABA/speech/OT every waking hr with little advances to show for it other than the $$$ spent and lots of career advancement for therapists).
Maybe we need rethink early childhood therapy to be more targeted to restore lost skills. Even regaining that level of lost skills improves quality of life, let alone moving beyond.

One big vagary

Vagaries ubiquitous in autism.
Nothing standard, fractured light in a prism.
Can we conclude then, so far…..
… no evidence in any evidence really
….no clues. What’s going on in this gallery.
inexplicable me. I continue to be one big vagary.

Cellular neuroscience is tough.

=====

I'm like a library book, overdue
My brain's so full, it's about to bust in two
I feel like I'm stuck in a never-ending test
Studying so much, I'm starting to feel depressed!
Will it bring success to my quest?

This was the response from my friend in my neuroscience cohort. Thank you for the encouragement and empathy.

Will it bring success to my quest?
Simply stated, my answer is yes

Battling through the constant stress, through days, months, years of duress
Though now life may seem like a mess, the quest is not to be the best,
Prioritize self-care, remember to rest

Is it worth it, when all I see, are cloudy skies up over me?
Yes I say, the world will see, what's possible with a degree,
The journey to a PhD is sprinkled serendipity,
But even more importantly, be free to show YOU empathy!

Hari,
Above all you are my friend, one that will be there 'til the end,
Remember I am here for you, day in, day out, through and through.

WAIS - Wechsler Adult Intelligence Scale

Lexicon [Measures] - WAIS

The Wechsler Adult Intelligence Scale (WAIS-IV) is an IQ test used in adults (ages 16-90) to assess cognitive abilities across different domains. It can take around 60-90 minutes to complete

Limitations in the context of autism:

Language and communication challenges can impact performance on subtests that heavily rely on language abilities.
Sensory sensitivities and attentional difficulties affect their performance on tasks requiring sustained attention or visual processing.
Social and contextual factors/aspects of intelligence relevant to autism not considered as the test focuses on cognitive abilities.
[Also see post on why IQ tests problematic in autistics]

WAIS-IV has 10 core subtests which are organized into four index scores.

Verbal Comprehension Index (VCI):

Similarities: verbal reasoning and concept formation.
Vocabulary: ability to define words and understand their meaning.

Perceptual Reasoning Index (PRI):

Block Design: visual-motor coordination and spatial perception.
Matrix Reasoning: non-verbal reasoning and problem-solving skills.
Visual Puzzles: ability to analyze and synthesize visual information.
Picture Completion: visual perception and attention to detail. Presented with incomplete pictures and are required to identify the missing part or detail.

Working Memory Index (WMI):

Digit Span: attention, concentration, and working memory by assessing the ability to repeat a series of digits forward and backward.
Arithmetic: mental arithmetic skills and working memory.

Processing Speed Index (PSI):

Symbol Search: visual scanning speed and processing speed.
Coding:motor speed, attention, and visual-motor coordination.

Scoring and interpretation

Index scores are derived from specific combinations of subtests and provide an overall assessment of an individual's cognitive strengths and weaknesses in those domains.

The Full-Scale IQ (FSIQ) is the combination of the index scores. It represents overall intellectual functioning and is calculated based on the combined performance across all subtests.

Interpretation involves comparing an individual's performance to normative data (percentile ranks, confidence intervals, and descriptive categories), considering the person's age and the index and subtest scores obtained.

History
WAIS was first developed by David Wechsler as an adaptation of his earlier intelligence tests, the Wechsler-Bellevue Intelligence Scale (1st Ed 1955, 4th Ed 2008).

Equanimity is the steady hand that guides us through life's ups and downs

Towards a more humane society. #MentalHealth. Contemplation, one line a day.

The Neurotransmitter Showdown: GABA v Glutamate in the Courtroom.

The Neurotransmitter Showdown: GABA v Glutamate in the Courtroom.

GABA: Good day, Glutamate. How do you plead today?

Glutamate: Not guilty Your Honor. My actions were justified.

GABA: Oh, please. You know that you always overexcite the receptors and cause chaos in the brain.

Glutamate: That's simply untrue. I only activate the NMDA, AMPA, and kainate receptors as needed.

GABA: Needed?

Your excessive activation of those receptors leads to seizures and neurotoxicity and not to mention hyperactivity, mood swings, social communication challenges, and sensory dysfunction in autistics.

You are totally implicated in the Excitatory-Inhibition Imbalance theory in autism.

Hari: You Said It, GABA!! Tell it like it is.

Judge (pounding table with mallet): Order in the court! The audience is not allowed to speak.

Hari: Your Honor, I was not speaking out loud. It was all in my mind.

Judge: But we are in your mind so everyone here can hear you.

Hari: Oh, Ok. Then I'll go off and take a nap.

Judge. Thank you Hari.

(Pounding with mallet) Order! Order!I call order in the courtroom!

While no single theory fully explains all aspects of autism, each attempts to provide insights into different cognitive and behavioral characteristics.

ECCT posits that individuals with autism have difficulties with contextual control, which is the ability to modulate behavior based on the context. This can be related to challenges in executive function and flexibility.
Implications: Difficulty in adjusting behavior to suit different social contexts, rigidity in thought processes, and a tendency toward repetitive behaviors.

27 Genetic Variants Linked to ADHD

https://neurosciencenews.com/genetics-adhd-22476/

"imbalance in dopamine in the brains of people with ADHD is partly attributable to genetic risk factors"

"7,300 common genetic variants that increase the risk of ADHD. It is particularly interesting that the vast majority of these variants—84-98 percent—also have an influence on other mental disorders, e.g. autism, depression and schizophrenia"