Presentation on theme: "What are we measuring in fMRI? Ruth Stavy David Carmel"— Presentation transcript:
1What are we measuring in fMRI? Ruth Stavy David Carmel
2Outline Neuronal activity Physiology and Haemodynamics Physics of fMRI Use of physics to “see” neural activityWhat fMRI really tells us (?) about neural activity
3Physiology and haemodynamics functional Magnetic Resonance Imaging (fMRI) measures brain activity indirectly through changes in blood vasculature that accompany neural activity.
4Neuronal activity results in: An initial increase in oxygen consumption owing to increased metabolic demand.2. After a delay of ~2 secs, a large increase in local blood flow. which overcompensates for the amount of oxygen being extracted3. Local increase in cerebral blood volumeThe increase in blood oxyhaemoglobin is what we measure in fMRIThis is called the BOLD (Blood Oxygen Level Dependent) response
5MRI Images: What do we see? MRI images are usually based on the signal from protonsA Proton is the nucleus of the hydrogen atomHydrogen is the most common element in tissueThe signal from protons is due to their „spin“
6Atomic nuclei with an odd number of neutrons and/or protons have: - a small magnetic moment- an angular momentum called nuclear spinSpinning protons are little magnets which are frequently referred to as just spins.
7If an external magnetic field B0 is applied, they align with it. An MRI machine’s B0 is always kept on!MA slight excess number of protons align with B0 producing an additional magnetic field in the direction of B0 - we will refer to this field as M.
8In addition, when placed in the magnetic field B0 the hydrogen proton can absorb energy and turn (precess) around the applied magnetic field much like a spinning top when placed in the earth’s gravitational field:Each type of nucleus has a unique frequency of spin.This is also proportional to the strength of the magnetic field,and is known as its resonance.
9The resonance frequencies characteristic of today’s MRI machines are in the range of FM radio waves, which is why they are referred to as RF (Radio Frequency)Excitation: If a second magnetic field (another RF) is applied, orthogonal to the static field and at the precessing frequency of the atomic nuclei, the nuclei will all precess about the static field together, in-phase.A nearby coil can detect this precession: the precession causes a current through the coil, which has this characteristic frequency.
10Decay (relaxation): What Happens when the additional magnetic field is turned off? 1. Protons emit the energy they absorbed (they do so at their RF)- This is the "NMR“ (Nuclear Magnetic Resonance) signal detected by the nearby coil - At the radio frequency - Signal proportional to Proton Density2. M begins to return to its original orientation (B0)- At an Exponential rate defined by a certain formula- This formula contains a “Time constant” - T1- Signal intensity decreases with increasing T1- T1 is unique to every tissue. This is the basis of structural MRI.- T1 is quite long: tens of milisecs to secs.
123. Spins begin to dephase- At an Exponential rate- defined by a certain formula- This formula contains a different “Time constant” – T2- Signal intensity decreases with decreasing T2- The T2 rates are different for different tissues- The observed signaldecay T2 is fast: a fewmsec to tens of msec
14In the real world, the NMR signal decays faster than T2 would predict. To sum up, Relaxation:In the real world, the NMR signal decays faster than T2 would predict.There are many factors creating imperfections in the homogeneity of a magnetic field.Every tissue has a different magnetic susceptibility which distorts the field at tissue borders, particularly at air/tissue interfaces.The sum total of all of these random and fixed effects is called T2*
15BOLD (Blood Oxygen Level Dependent) contrast Takes advantage of the different magnetic properties of oxyhemoglobin (HbO) and deoxyhemoglobin (Hb)Hb is paramagnetic and introduces an inhomogeneity into the nearby magnetic field, whereas HbO is weakly diamagnetic and has little effect.Neuronal activity local blood flow increases overcompensating for oxygen consumption oxygen level in venous blood is elevated larger MR signal.
16How do we know where the signal comes from? The frequency f emitted by the protons is proportional to the magnetic field B0f = B0 is proportionality constant for specific atomic nucleiB0 is the strength of the static magnetic (e.g.,1.5T)
17If we modify the magnetic field B0 by applying a „gradient field“ (B rises from left to right):BDifferent B values Different f valuesB1B2B3B4…Values of frequencies indicate Position.This is done in all three axes to enable 3-dimensional localisation (blobs)
18What exactly does fMRI tell us? From sluggish Haemodynamic response to inferences on neural activityThe central assumption: the fMRI signal is approximately proportional to some measure of the local neural activity, averaged over several millimeters and several seconds. This is sometimes referred to as the linear transform model(Buckner, 2002)altered neuronal activitychanges in local haemodynamicsfMRI signalHow the three are related is unclear
19Altered neuronal activity Changes in local haemodynamics: We know that the fMRI signal is triggered by the metabolic demands of increased neuronal activity – but the details of this process are only partially understoodAltered neuronal activity Changes in local haemodynamics:- need for glucose?- For oxygen?- Some combination of both?Various conflicting bits of evidenceIn this talk: altered neuronal activity fMRI signal(the linear transform model)(Heeger & Ress, 2002)
20The success of fMRI as a research method depends on understanding the relationship between the fMRI signal and the underlying neuronal activityIf the linear transform model were satisfactory, this would be great (!):it would mean we could reliably estimate the underlying neural activity from the Haemodynamic Response Function (HRF)But can we? most studies simply assume we can; if the model weren’t a good approximation, this would make HRF measurements worthlessThis is important because some fMRI and neurophysiology experiments have yielded conflicting results
21For example, the role of V1 in spatial attention: Visual discrimination improves whencued to attend, without moving theeyes, to the stimulus locationDoes the attentional effect occur early in visual pathways (V1)?Single-cell recording in monkeys: NOfMRI in humans: YESattentional effects in further regions (e.g. V4) much larger in human fMRI than in monkey electrophysiologyIs this due to species difference, or a difference in what is being measured?X
22Things the fMRI signal MAY reflect (but we don’t know): Firing rates of the local neuronsbut also activity that doesn’t evoke spikes:Sub-threshold activitySimultaneous excitation and inhibitionModulatory inputs (e.g. top-down andfeedback from higher cortical areas)and other effects:Changes in neuronal synchrony without a concomitantchange in mean firing rateLarge changes in the firing rates of a few neuronsORsmall changes in the firing rate of many neurons
23To estimate the validity of the linear transform model, it is necessary to see how the fMRI signal correlates with measures of neural activity.But doing this is not so straightforwardThe relationship of fMRI data and neural activity depends on a few factors:
241. How ‘Neural activity’ is measured and quantified: fMRI: simultaneous activity of MANY neurons in a LARGE region of cortex (millimeters) over a LONG period (seconds). What component of the neural activity most predicts the fMRI signal?Average firing rate of all / a subpopulation of neurons?Degree of synchronous spiking?The Local Field Potential (LFP), believed to reflect dendritic currents?The Multi Unit Activity (MUA), believed to reflect spiking near the electrode tip?The current source density?Some measure of local average synaptic activity?Some measure of subthreshold electrical activity?All the above may correlate with each other under some circumstances, but can also vary independently of each other.Logothetis et.al. (Nature, 2001): simultaneous fMRI, LFPs and MUAs in rats. Concluded that BOLD fMRI signals “reflect the input and intracortical processing of a given area rather than its spiking output.”
252. fMRI acquisition technique BOLD (Blood Oxygen Level Dependent), the most common, provides a mixed signal dependant on:blood FLOWblood VOLUMEblood OXYGENATION.Variations on the technique can be used to emphasize or de-emphasize one or another of these components:Pefusion-based fMRI blood flowInjections of various compounds blood volumeDiffusion-based fMRI cell swelling (after excitation)So far, only little work has been done to quantify the relationship between different fMRI techniques.
263. Experimental protocol & data analysis Early days of fMRI:worry that the signalarises entirely/mostlyfrom large draining veins misleading on localizationFor example,visual stimuli at nearby locations activity in nearby (but distinct) loci in V1But if the fMRI signal were only evident in a large vessel draining blood from V1, The activity from both points would seem to occur in the location of that vessel
27The solution: appropriate experimental protocols For visual stimuli, retinotopic maps are produced by using stimuli that move through the visual field slowly, evoking a traveling wave of neural activity across the grey matterLarge veins draining a large portion of visual cortex are de-emphasized because the blood flow and oxygenation in these vessels are roughly constant throughout the experimentHence the experimental design can be crucial for precise localizationSo it is important to consider this each time a new protocol is developed
28Temporal summationAccording to the linear transform model, it should be possible to predict the response to a long stimulus presentation by summing the responses to shorter stimuliFor example, the response to a 12-second stimulus should be the same as summing the response to two identical consecutive 6-second stimuliThis temporal summation holds up well in some experiments, but fails in othersWhy?
29Two possibilities:Blood flow is proportional to neural activity, but BOLD fMRI signals have a non-linear dependence on flow:The BOLD signal might saturate at high levels of blood flow, as further increases in flow would cause negligible decreases in the concentration of deoxyhaemoglobin.So a moderately-strong stimulus could evoke a near-maximal fMRI response, leaving little room for further increase in response (even to a stronger stimulus).
30Two possibilities:2. Temporal summation works, but experiments may miss it:These experiments observed primary sensory and motorareas. In such areas, Short-duration stimuli are expected toevoke disproportionately large neural responses for ~3s.This is because such neurons:- Show large transient responses after stimulus onset- Adapt during prolonged stimulation- Their responses are boosted by attention, which islikely to be engaged automatically by stimulus onsetExperiments have not been carried out yet to measure thetemporal summation of fMRI responses while explicitlycontrolling for these factors
31Colocalization of fMRI and neural activity The linear transform model implies that the fMRI response should be at the same location as the underlying neural activityHowever, this may depend on the specific method of data analysis.For example:The specific HRF used may pinpoint the center of fMRI activity 2mm-1cm from the center of intrinsic optical-imaging activity (Cannestra et.al., 2001).Dibrow et.al. (2000) report a large discordance between fMRI and electrophysiological recordings in somatosensory cortex of anesthetized monkeys.On the other hand, Wandel et.al. (2000) report excellent agreement between fMRI and the electrophysiological literature for early visual areas.This difference between somatosensory and visual maps might reflect a fundamental difference in the basis of the Haemodynamic response in the two areas.
32ConclusionsIs the linear transform model a reasonable and useful approximation of the way fMRI data reflects neural activity?Heeger & Ress (2002):YES,for some recording sites / measures of neural activityin some brain areasusing certain experimental protocolsNO, under other circumstances.We need to know more about the relationship between various measures of neural activity, and determine whether they reflect different aspects of neural function.