lecture 4 - BOLD signal physiology Flashcards
neurovascular coupling
The process by which neural activity leads to changes in cerebral blood flow
–> This ensures rapid delivery of oxygen (etc) to active neural tissue
- Active neurons, when firing, trigger a cascade of events that lead to vasodilation (widening of blood vessels).
- This vasodilation increases blood flow locally, delivering more oxygen and potentially other nutrients to the area where the neurons are active.
- The increased blood flow and the resulting change in the balance of oxygenated and deoxygenated blood is what’s measured by certain brain imaging techniques.
discovery of neurovascular coupling (roy & sherrington)
- initial observations of changes in blood flow response to increased brain activity in animals
- experiment: measuring cranial pressure changes following peripheral nerve stimulation
- key observation: the pressure in the head changes when peripheral nerves are stimulated, linking neural activity to cerebral blood flow
Kety-Schmidt technique
- Measuring cerebral blood flow (invasively) in humans
- experiment: participant inhales N₂O while blood is repeatedly taken from arteries and veins to measure the concentration of N₂O over time.
- results: N₂O rich blood takes time to reach the veins, and N₂O diffuses while in the brain, which allows estimating cerebral blood flow
- key observation: by measuring differences in N₂O concentration in arterial blood (going to the brain) and venous blood (coming from the brain), cerebral blood flow can be estimated and compared across tasks
tracers
- substance introduced into the blood stream that either emits a signal or changes another
example 1: PET
example 2: Gadolinium-enhanced MRI
tracers potential problems
health risks due to
- allergic reactions
- radiation damage
- tracer accumulation in tissues
- ethical problems with informed consent
PET imaging
imaging emissions of radioactive material for quantitative assessment of metabolism and detection of pathologies with high sensitivity (e.g., cancer)
Gadolinium-enhanced MRI
gadolinium is the most paramagnetic element at body temperature (i.e., it affects the magnetic field).
once injected, it allows imaging the cerebral blood volume (CBV) for individual parts of the brain.
BOLD signal definition
the signal detected by fMRI scanners that is used to infer neural activity in the brain.
An endogenous contrast agent for non-invasive imaging of human brain activity
-> new research field
-> indirect measure of neural activity
-> pattern can be compared to those obtained with other techniques
BOLD signal mechanism
- erythrocytes contain hemoglobin
- hemoglobin contains iron
- iron is oxygenated or deoxygenated
blood oxygenation interacts with the magnetic field of the scanner, which can be measured – combined with neurovascular coupling
oxyhemoglobin and deoxyhemoglobin
- oxygenated: diamagnetic (repelled by magnetic field)
- deoxygenated: paramagnetic (attracted to magnetic field)
- BOLD fMRI takes advantage of the difference in T2* between oxygenated and deoxygenated hemoglobin
- as the concentration of deoxyhemoglobin decreases, the fMRI signal increases
Linking the BOLD to simultaneously recorded local field potentials (LFP)
key observation: the BOLD response can be predicted based on the LFP
-> implies a direct correlation between neural electrical activity and the BOLD signal measured in fMRI
-> BOLD = indirect, LFP = direct
Hemodynamic response function (HRF)
= the brain’s blood flow response to neural activity
- neural event: increased neural activity
- initial dip (not always shown): rapid signal decrease, likely reflecting oxygen consumption
-
peak of response: regional blood flow increases disproportionally to the neural event
-> watering the garden for a flower in need - undershoot: many theories, likely delayed vascular recovery & continued metabolic demand
- signal goes back to baseline
why the BOLD signals can be difficult to interpret
- correlations: different LFP frequency bands/components (Delta, Theta, Alpha, Beta, Gamma, and Multi-Unit Activity - MUA) all show distinct correlations with BOLD. Also, which component correlates with the BOLD response differs based on where in the brain it is measured.
- input/output: LFP is thought to reflect the input to a brain circuit, not (only) its output
-
varying response shape: the HRF is a compound response of multiple interacting factors (oxygen, metabolism, blood flow, blood volume) with varying shape across cortex
–> the HRF is not a simple, uniform response but varies across different regions of the brain -
neurotransmitters: effects of different neurons & transmitters is poorly understood
–> the relationship between these neurotransmitters and the BOLD signal is not fully understood - non-neural processes: neural activity correlates with non-neural processes (e.g., in glia cells, transmitter re-uptake)
- dissociation: BOLD responses can occur without neural firing – dissociation between neural acitivity and BOLD response
advances in neuroimaging: How do we currently study the physiological underpinnings of the BOLD signal?
-
high-resolution fMRI
EX1: differentiate activity in different layers of the cortex
EX2: test predictions about neural mechanisms, such as distinguishing between feed-forward and feedback processes in the brain. -
combining BOLD & other recording or simulation techniques
EX3: BOLD + calcium imaging
EX:4 awake opto-fMRI in rodents (Optogenetic stimulation of specific cell types while measuring the effect on brain-wide BOLD signals)
HRF properties
- magnitude of signal changes is quite small
- response is delayed and quite slow
- exact shape of the response varies across subjects and regions
