Early neurodevelopmental disorders (N=You) Flashcards
What is wrong with how autism would be diagnosed with this test?
It is very general and biased → either you are autistic because you like pokemon (and are over 11 yrs old) or you are not autistic because you do not like pokemon. Autism is much more than only having autism or not, especially since autism is on a spectrum and can come in different ways.
What are two characteristics that are described in the DSM-V book for Autism Spectrum Disorder (ASD)?
- Poor social communication and interaction
- Limited repetitive behavior patterns, interests and activities.
What does this picture imply?
That Autism Spectrum Disorder (ASD) is not dichotomous (i.e. you have or don’t have ASD), but rather a random cut-off in a continuum (i.e. on a spectrum).
What does this picture imply?
That children with ASD are ‘made’ of the same building blocks, but the way these building blocks are organized and build up is different (i.e. ASD is on a spectrum).
The picture depicts different ‘symptoms’ that are associated with ASD.
Just remember that behind these labels and symptoms, there are also other mechanism that are associated with these labels and symptoms. For disorders such as ASD, it is never that one thing causes the other. Multiple different causes can be the basis of disorders.
What is the difference between:
- Traditional medicine
- Stratified medicine
- Precision medicine
- Traditional medicine → is diagnosis driven i.e. patients with the same disease are given the same drug.
- Stratified medicine → is subtype driven i.e. patients with certain shared disease characteristics are given the same drugs, while patients with different shared disease characteristics are given another drug.
- Precision medicine → is patient driven i.e. every individual patient is given a drug that fits with the patient’s individual needs and characteristics.
What is specific for precision medicine (N=you)?
That after a patient is characterized (e.g. for their disease) and a drug or certain treatment is given, the outcome of this treatment is evaluated. Based on this evaluation, the initial patient characterisation and drug/treatment administration are optimalized (prediction optimalization).
In regard to a personalized treatment, what things need to be considered?
- Context → what influences or blocks the mechanism?
- Mechanism → what drives the mechanism and what causes the outcome?
- Outcomes → what changes with whom or what?
What is the excitation inhibition balance (E/I balance)?
The relative contributions of excitatory and inhibitory synaptic inputs corresponding to some neuronal event, such as a response evoked by sensory stimulation. The balance controls excitability, dynamic range, and input gating in many brain circuits.
What are neural oscillations?
Rhythmic and/or repetitive eletrical acitivity generated spontaneously and in response to stimuli by neural tissue in the central nervous system.
Note: oscillations are dependent on the E/I balance (among others).
What is epileptiform activity and how does it relate to E/I balance?
Epileptiform activity are spike waves, sharp wavses, spake and wave activity, or other rhythmic waveforms that imply epilepsy or may be associated with epilepsy. Epileptiform activity is a result of an imbalanced E/I ratio, where the amount of inhibitory activity is reduced.
What are EEG biomarkers for measuring brain activity and E/I balance?
Brain waves (i.e. oscillations) are a result of E/I balance. Thus, the biomarkers that can be used to identify oscillations can also be used to identify the E/I balance. Parameters/biomarkers of oscillations are:
- amplitude
- phase
- frequency
- structure
- etc.
Just study and see if you can understand the picture.
There are many treatments available that influence the E/I balance. Amongst others, bumetanide is an example of an E/I treatment. What is the function of bumetanide?
Bumetanide is a chloride importer blocker.
To understand the function of bumetanide, it is important to know that when chloride enters the cell (upon binding of GABA to its postsynaptic receptor) it hyperpolarizes the cell, thus inhibiting the generation of an action potential (i.e. excitation). With the use of bumetanide, chloride is no longer able to enter the cell. With this, less/no hyperpolarization occurs and the cell is able to generate (more) action potentials, which cause excitation of the cell.
Just study the picture.
Most importantly, you can see that with the use of bumetanide, the fE/I ratio increases.
Ok
Explain the procedure of an N=1 trial desgin.
Here, the effect of e.g. bumetanide can be tested. For this, a small number of patients are used, where these patients can have multiple measurements/interventions.
So e.g. in an N=1 trial, the effects of bumetanide are researched. The individual patient will start with the administration of bumetanide for an x amount of time. After this, a placebo will be adminstered for an x amount of time. The administration of bumetanide and a placebo will be repeated throughout a certain period at varying lenghts of time. The experiment can be repeated with other individual patients.
