W1: Introduction to neuroimaging

What do neuroimaging techniques produce?

Bio-markers.

Which two medical imaging modalities were sparked by basic physics ideas?

MRI and PET.

Who is considered the father of modern physics?

Albert Einstein.

What does special relativity describe?

The relationship between space and time, and how they are affected by the motion of objects.

What is one implication of special relativity?

Nothing can move faster than the speed of light; all is relative, including time.

What was Bohr's hydrogen model based on?

Standing wave orbits of electrons.

Who postulated that electrons could stay in orbit around a nucleus due to standing wave orbits?

De Broglie.

What is a standing wave orbit?

Three-dimensional wave-like patterns that electrons form around the nucleus of an atom.

What did Dirac's equation add to De Broglie's model?

Relativistic effects.

What is the basic principle behind MRI?

The magnetic moment of water protons

How do protons respond in a magnetic field during an MRI?

They align in the direction of the magnetic field at a rotating speed depending on the field's intensity.

What are the main components of an MRI machine?

Strong magnetic field, gradient coils, radio frequency coil, and radio frequency detector.

What occurs when the pulse is switched off in MRI?

Water protons return to their initial state, creating a magnetic decay.

What does the BOLD effect depend on?

The paramagnetic properties of hemoglobin.

What is a positron?

An element of antimatter with the same mass as an electron but opposite charge.

Who visualized a positron using cosmic radiation?

Carl Anderson.

What type of radiation do positron-electron annihilations emit?

Gamma photons.

What is the only known reaction by which mass is completely converted into energy?

Electron-positron annihilation.

What information can PET scans provide?

Visualize biodistribution of substances and measure their kinetics across tissues.

What is the definition of a biomarker?

Any biological characteristic that can be objectively measured.

What are the two important elements in defining a biomarker?

Biological target and quantitative measurement.

What does an imaging biomarker allow for in biological research?

Non-invasive access to in vivo functional and structural biological characteristics.

What disease is identified as the most common form of cognitive decline in the Western world?

Alzheimer's Disease (AD).

What type of imaging is used to detect brain atrophy in Alzheimer's Disease?

Structural MRI.

What is a limitation of using multiple biomarkers together?

Different biomarkers inform about different aspects of a disease and may not occur simultaneously.

What is sensitivity in relation to biomarker performance?

The ratio of truly diseased population identified as diseased by the test.

What is specificity in relation to biomarker performance?

The fraction of non-diseased people correctly identified by the test.

What is the ROC curve?

A summary of the capacity of a test to separate two groups as its discrimination threshold is varied.

What is the main goal of drug discovery in the context of CNS diseases?

To find novel drugs to treat symptoms of nervous system dysfunction.

What approach did early psychotropic drug discoveries rely on?

Serendipity (chance).

What is the main challenge in modern drug discovery?

Finding new drugs for CNS diseases.

What advancement greatly increased the number of assays performed in drug discovery?

High throughput screening using mechanization and robotics.

What does pharmacokinetics focus on in drug development?

Ensuring the drug reaches the target (i.e., brain) in sufficient concentrations.

What is reverse pharmacology?

Identifying a drug's mechanism after it has been found to work.

What is needed for improved preclinical success in drug discovery?

More focus on target identification and ensuring assays measure the same psychological constructs in humans and animals.

What can oxygen amperometry be used for in rat studies?

As a surrogate for functional imaging.

What effect can AMPA potentiators have in animals?

They can reverse the effects of alcohol and morphine.

What psychiatric approach has shown potential in drug discovery?

Close alignment of techniques used in animals with human studies.

How can the same methodology strengthen drug discovery validation?

By invoking consistent methods in both animal models and patients.

What should be the focus when translating cognitive tasks for animal versions?

Assess cognitive inflexibility and relevant brain circuits.

What classification is used to evaluate biomarker performance?

Sensitivity, specificity, true positives, true negatives, false positives, and false negatives.

What can impact the positive and negative predicted values of a biomarker?

Prevalence of the disease in the population.

How does variability manifest in biomarker performance measures?

Groups tend to overlap and distribution of measures can vary from case to case.

What is pharmacokinetics?

Pillar of drug development; branch of pharmacology focused on ensuring that the drug reaches the target in sufficient concentrations to exert desired effect, factoring in how long the drug remains effective in the system.

How is oxygen amperometry in rats similar to human MRI?

It detect slow oscillations and regional connectivity in the rat brain, similar to the default mode network observed in human MRI studies