fMRI Methods
Lecture 9 – The brain at rest
The brain never rests!
Brain takes up 20% of
the metabolites in the
body during rest.
Energy costs
Energy consumption measured
with PET (radioactive glucose
consumption) during 4 conditions.
Which is rest and which is task?
Energy costs
Brain is always at max power: similar costs in all conditions
Energy costs
Energy cost breakdown
for running the cortex.
Most of the energy is
spent on neural
signaling.
Information encoding
Given that energy consumption is almost constant:
Only relatively small
populations of neurons
respond strongly at any
given time.
Relatively local, transient
changes in neural
activity represent stimuli
evoked responses.
Hence the importance of:
Attention and neurovascular coupling
Brain is never static!
Connected neural populations tend to synchronize
and oscillate together.
EEG Alpha (10 Hz)
Close eyes
Over occipital electrodes.
Different time scales of synchronization
Slow changes
Similar fluctuations in
fMRI signal during rest
Nir Y., Neuroimage (2006)
Structure of rest activity
Spontaneous neural activity during rest and sleep may
be random over time, but it’s not random over space.
Large neural populations are synchronized.
What are the characteristics of this activity?
How can we study them? No experimental structure?
Are there differences between rest, sleep, anesthesia?
Local spatial structure
Anesthetized cat primary visual cortex
Orientation columnar map – voltage sensitive dye imaging
Kenet, Nature (2003)
Local spatial structure
Many occurrences of strong correlation between
spontaneous and evoked columnar maps.
Local spatial structure
Correlation between spontaneous “snapshots” and
particular orientation columnar maps.
Visual cortex randomly moves from one map to another in
the absence of stimulation (relatively quick transitions).
Large spatial structure
Very slow hemodynamic
changes over time.
Cortical areas with similar functionality (e.g. right and left
auditory cortex) show strong and selective correlations.
Functional connectivity
Areas that are connected anatomically because of shared
functionality will be active together.
In reality this is just correlation – problematic interpretation
Inter-hemispheric correlations
Strongest correlations are between corresponding locations
in the two hemispheres
Default mode system
Three areas that show reduced activity during “external”
tasks (e.g. visual, auditory, somatosensory stimulation)
Default mode system at rest
“Extrinsic”
ROI
“Intrinsic”
ROI
Is the brain separated into two general antagonistic networks?
Measuring default mode system correlations during rest.
Source of fMRI correlations
Several “less interesting “ sources contribute to an fMRI
signal. Are they driving correlations during rest?
Source of fMRI correlations
Simultaneous fMRI and electrophysiology:
Shmuel et. al. HBM 2008
Source of fMRI correlations
Significant correlations between
neural activity and BOLD during
rest…
Source of fMRI correlations
Similar inter-hemispheric
correlations in epilepsy
patients
Nir Y., Nat. Neurosci. (2010)
Source of fMRI correlations
Correlations during rest correspond to anatomically
connected areas that are commonly active during task.
Fox, Nat. Rev. Neurosci. (2007)
Patient lacking corpus callosum
Inter-hemispheric
correlations
disappear after
section of corpus
callosum.
Spontaneous and evoked activity
There’s a lot of variability in
the neural response to the
same repeating visual
stimulus.
Arieli, Science (1996)
Spontaneous and evoked activity
The spontaneous state right before stimulation predicted
the amplitude of the response 42 ms later.
Spontaneous and evoked activity
Changing the spatial response pattern in a predictable way.
Is the evoked
response to a
trial the sum of
spontaneous
and evoked
activity?
Motor response variability
Right hand
button press
LH ROI
Functionally
correlated RH
ROI
Fox, Nat. Neurosci. (2006)
Motor response variability
Subtracting out RH spontaneous activity, allowed
reduction of trial by trial evoked response variability.
LH responses
RH responses
Diagnosis by rest scans
If resting state correlations represent the functionality of
the brain, abnormal correlations may represent abnormal
functionality and enable an easy form of diagnosis.
Build a distribution of “normal” correlation values and test
whether these deviate in particular neurological or
psychiatric disorders.
Alzheimer’s disease
Alheimer’s
Control
Weaker resting state correlations between “default mode”
network (precuneus area) and hippocampi.
Fare comparison?
Greicius, PNAS (2004)
Alzheimer’s disease
Direct comparison:
Voxels that showed
stronger correlation
with PPC timecourse
in controls versus
Alzheimer’s patients.
Comma
Patients in reduced states of awareness show
decreased inter-hemispheric correlations.
Autism
1-3 year old children with
autism or language delay,
during natural sleep.
Strong inter-hemispheric
correlations are already
evident at extremely
young ages.
Autism
Decreased inter-hemispheric correlations in language areas
Autism
Inter-hemispheric
correlation strength
predicts language
ability and autism
symptom severity.
Rest activity and development
Visual system development (e.g. ocular dominance) before
birth (i.e. before visual experience)
Hebbian learning during rest?
In the absence of externally evoked responses?
Summary
Spontaneous brain activity is the largest and least
understood component of brain function.
Different temporal and spatial scales of organization.
To the lab!