Hemodynamic neuroimaging Flashcards
What is the history behind hemodynamic neuroimaging?
• Temperature of brain goes up during mental exercise
• Case study: auditory noise made by blood flow in an arteriovenous malformation correlated with effortful visual processing
• Hemodynamic imaging: neuroscience hype since the 1990’s
• Hemodynamic imaging to assess neural activity still not without criticism
What are 3 criticisms of hemodynamic neuroimaging?
• Indirect measure of neural activity
• Complex relationship between neural activity & hemodynamics
• Complex = cannot be trusted?
• Deep understanding allows discriminating (in)valid ways of using it
• Complexity of methods and analysis
What are 3 criticisms of hemodynamic neuroimaging?
• Indirect measure of neural activity
• Complex relationship between neural activity & hemodynamics
• Complex = cannot be trusted?
• Deep understanding allows discriminating (in)valid ways of using it
• Complexity of methods and analysis
What is the relation between hemodynamics and neural activity?
• Neurons require continuous supply of glucose and oxygen to function –> blood circulation
• Blood comes in through arteries and arterioles
• Exchange of glucose and oxygen in capillaries
• Oxygen removed from hemoglobin = deoxyhemoglobin
• To venules and to larger veins to leave the brain
• Energy = adenosine triphosphate (ATP), from glucose
• Neural activity –> hemodynamic response function (HRF)
What happens when neural activity occurs?
• Slightly delayed local increase in oxygen and glucose consumption
• Ratio oxygenated and deoxygenated hemoglobin (blood oxygenation) decreases
• Signal through neurovascular coupling mechanism, triggering increase in supply of blood
• Accompanied by marked increase in blood oxygenation
• Peak increase in blood oxygenation several seconds after initial oxygen consumption
• Blood volume and oxygenation decay again (negative overshoot to below baseline levels)
• Expand across larger territory than region of neural activity
What are the 3 components of HRF?
• Initial dip: Decrease in blood oxygenation and measured signal
• Primary (strongest) response: Influx oxygenated blood –> strong increase in signal
• Negative overshoot: signal decreases
What are 3 factors that influence hemodynamic signal?
• Which process and parameter dominates the measurement
• E.g. Blood volume instead of oxygenation: no initial dip
• Whether measurement very near to site of neuronal activity or average across a larger area
• Across larger area:
• No initial dip
• Only positive peak and negative overshoot
• Additivity assumption: in case of multiple stimuli, total hemodynamic
response (HR) is sum of HRF’s to individual stimuli
What is the relation between HR and electrical potential changes?
• Measure action potentials = measure output of a neuron
• Measure HR of a region, not sure whether it represents overall action potential output of that region
• Situations possible where energy consumption increases, while output of neuron stays the same
• Inhibitory input, energy consumption increases but output decreases or stays the same
What does the HR represent?
• Relation HR and other electrophysiological measures
• Multi-Unit Activity (MUA): number of action potentials
• Local Field Potentials (LFP): synaptic input of neurons (slow changes in post-synaptic membrane potential)
• Typical situation = everything correlates: HR, MUA, LFP
• When partially dissociated, e.g. through long stimulation: HR (in fMRI) slightly more correlated with LFP than with MUA
What is fMRI?
• Blood-oxygenation-level dependent (BOLD) signal
• Deoxygenated hemoglobin: magnetic momentum (paramagnetic)
• Alters spin-spin interactions –> faster T2 decay
• Increase in oxygenation –> increased fMRI signal
• More macroscopic side effects of paramagnetic particles:
• Field inhomogeneity
• Tissue susceptibility
–> Total dephasing = T2* decay
What is the relevance of fMRI?
• Decade of the brain
• Has pinpointed the neural basis of a range of mental processes
• Beyond mere localization of function
• Effects sometimes overestimated
• Group differences often not consistent enough between subjects to allow prediction at individual subject level
What is PET?
• 1980’s: dominant hemodynamic imaging method
• Unique contribution relative to fMRI:
• Measuring metabolism
• Detection of biomarkers and neurotransmitter concentrations
• Positron emission: involves injection of radioactive tracers
• Injection not of isolated isotope, but attached to a molecule with specific biological action
• Molecule and site of injection determines spread of the tracer
• Radionuclides: short half-life = positron emission decay
How does PET work?
• Positron is positively charged –> interacts with negatively charged electron –> annihilation
• Pair of photons travelling in opposite directions
• Detected by photo-sensitive tubes or diodes
• Original position of annihilation localized along a straight line
• 2 such photons have to be detected at the same time (coincidence detection)
• Production of radionuclides near the PET requires a cyclotron
How can we use PET to measure neural activity?
• Oxygen-15
• Short half-life of 2 minutes
• Distribution: linear relationship to incoming blood volume
• Total amount of oxygen in a brain region: indication of local neural activity
• Because of over-supply of oxygenated blood following neural activity
• Typical PET experiment
• Low number of conditions (4-8)
• Conditions are typically tested in blocks of around 1 minute
• Often only 2 blocks per condition
• In between blocks: short waiting period with new injection
What are 2 advantages and 3 disadvantages of PET?
+ Ability to measure blood volume quantitatively
+ Confronted with less unknown parameters when we try to relate measured signal to neural activity
- Injecting radionuclides
• Need for cyclotron
• Health risks of radioactivity - Poorer spatial resolution, about 1 cm
• Combination with (simultaneous) MRI helps to some extent - Poorer temporal resolution: minutes
What are 4 unique contributions of PET?
• Metabolism: tracer fluorine-18 (half live 110 minutes) attached to glucose = fluorodeoxyglucose (FDG)
• Diagnose cancer
• Diagnose brain diseases
• Hypometabolism of temporoparietal region in Alzheimer’s disease
• 11C Pittsburgh B PET for beta-amyloid deposits
• Target specific neurotransmitter system
• Tracer attached to molecule with concentration related to activity of one specific neurotransmitter
• Dopamine: 6-(18F)-fluoro-L-DOPA
What should we do before we start an experiment?
Think before you start an experiment
• Hard work
• Is it worth the effort?
• Know the methods and the theories
• Formulate relevant hypotheses
• Design study to provide evidence for or against some hypothesis
• Expensive machines do not think for you
How do we determine which conditions to include in our experiment?
• Subtraction method: comparison of two conditions that only differ in one mental process of interest
• Related to behavioural method of Donders: mental chronometry
• fMRI: subtract brain activation
• Multiple extensions:
• Multiple conditions, compared pairwise
• Factorial design
• Parametric design
What is the assumption of additivity?
• Also known as pure insertion
• The addition of a new mental process does not affect other processes
• If not correct, then comparison between conditions is confounded
• Empirically, violations of this assumption can be visible through interaction effects in the case of a factorial design
What are 3 ways to present the conditions?
• HRF peak delayed with 6s, total duration more than 12s from onset before at baseline again –> overlapping HRFs
• Option A: ISI of 16s; –> Inefficient!
• Option B: ISI of 2s; signal reaches asymptotic level –> low sensitivity for differences between conditions
• Option C: Block design: trials are blocked per condition
What is the block design?
• Alternate blocks of different conditions
• Within blocks: strong HRF because of additivity signal
• After a block: signal goes down again (possibly to baseline) before next block
• Condition-associated ups and downs in BOLD signal are large
• Large power and sensitivity to detect changes in BOLD signal
• Very efficient
• Many trials can be presented per unit of time
• No long waiting time between trials
What are 3 drawbacks of the block design?
• Predictability of conditions (tendency to prepare)
• Unwanted cognitive processes could confound the one process assumed to differ between conditions
• Can be boring to participants in comparison to less predictable situation
• Impossible for some experimental questions
• Impossible to estimate single-trial response function
• Effect that was elicited by one trial
• Possible if one makes strong assumptions about shape of HRF and additivity
• These assumptions are often invalid, e.g. exact form of HRF differs between regions
How does the block design work in practice? (5)
• Block length
• Short: 6-12s
• Intermediate: 12-21s
• Long: up to 30s or more
• Can vary between blocks
• Period of rest between blocks = rest interval
• Allows signal to go back to baseline
• Increases onset time asynchrony of successive blocks –> increases signal changes
• Less presentations of conditions of interest
• Only if interested in estimating the response to a block of trials
• Counterbalancing condition order to avoid that signal of condition X is predominantly biased by the condition that always precedes it
• One-back counterbalancing
• Number of blocks: 16-20 intermediate-length blocks sufficient for large effects; more needed for smaller effects
• Period of continuous data acquisition = runs
• Typically duration of 4-10 minutes
• Each condition in each run, for at least 2 blocks if possible
What is the event related design?
• Slow event-related design: long ISI (with or without jitter)
• Ideal for estimating HRF function by the event-related response
• Inefficient use of time and boring