2 The brain never rests!Brain takes up 20% of the metabolites in the body during rest.
3 Energy costsEnergy consumption measured with PET (radioactive glucose consumption) during 4 conditions.Which is rest and which is task?
4 Brain is always at max power: similar costs in all conditions Energy costsBrain is always at max power: similar costs in all conditions
5 Energy costs Energy cost breakdown for running the cortex. Most of the energy is spent on neural signaling.
6 Information encoding Given that energy consumption is almost constant: Only relatively smallpopulations of neuronsrespond strongly at anygiven time.Relatively local, transientchanges in neuralactivity represent stimulievoked responses.Hence the importance of:Attention and neurovascular coupling
7 Brain is never static!Connected neural populations tend to synchronize and oscillate together.
8 EEG Alpha (10 Hz) Close eyes Over occipital electrodes. Different time scales of synchronization
9 Slow changes Similar fluctuations in fMRI signal during rest Nir Y., Neuroimage (2006)
10 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?
11 Local spatial structure Anesthetized cat primary visual cortexOrientation columnar map – voltage sensitive dye imagingKenet, Nature (2003)
12 Local spatial structure Many occurrences of strong correlation between spontaneous and evoked columnar maps.
13 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).
14 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.
15 Functional connectivity Areas that are connected anatomically because of shared functionality will be active together.In reality this is just correlation – problematic interpretation
16 Inter-hemispheric correlations Strongest correlations are between corresponding locations in the two hemispheres
17 Default mode systemThree areas that show reduced activity during “external” tasks (e.g. visual, auditory, somatosensory stimulation)
18 Default mode system at rest “Intrinsic” ROI“Extrinsic” ROIIs the brain separated into two general antagonistic networks?Measuring default mode system correlations during rest.
19 Source of fMRI correlations Several “less interesting “ sources contribute to an fMRI signal. Are they driving correlations during rest?
20 Source of fMRI correlations Simultaneous fMRI and electrophysiology:Shmuel et. al. HBM 2008
21 Source of fMRI correlations Significant correlations between neural activity and BOLD during rest…
22 Source of fMRI correlations Similar inter-hemispheric correlations in epilepsy patientsNir Y., Nat. Neurosci. (2010)
23 Source of fMRI correlations Correlations during rest correspond to anatomically connected areas that are commonly active during task.Fox, Nat. Rev. Neurosci. (2007)
24 Patient lacking corpus callosum Inter-hemisphericcorrelations disappear after section of corpus callosum.
25 Spontaneous and evoked activity There’s a lot of variability in the neural response to the same repeating visual stimulus.Arieli, Science (1996)
26 Spontaneous and evoked activity The spontaneous state right before stimulation predicted the amplitude of the response 42 ms later.
27 Spontaneous and evoked activity Changing the spatial response pattern in a predictable way.Is the evokedresponse to atrial the sum ofspontaneousand evokedactivity?
28 Motor response variability Right hand button press LH ROIFunctionally correlated RH ROIFox, Nat. Neurosci. (2006)
29 Motor response variability Subtracting out RH spontaneous activity, allowed reduction of trial by trial evoked response variability.LH responsesRH responses
30 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.
31 Alzheimer’s diseaseControlAlheimer’sWeaker resting state correlations between “default mode” network (precuneus area) and hippocampi.Fare comparison?Greicius, PNAS (2004)
32 Alzheimer’s disease Direct comparison: Voxels that showed stronger correlation with PPC timecourse in controls versus Alzheimer’s patients.
33 CommaPatients in reduced states of awareness show decreased inter-hemispheric correlations.
34 Autism1-3 year old children with autism or language delay, during natural sleep.Strong inter-hemispheric correlations are already evident at extremely young ages.
35 AutismDecreased inter-hemispheric correlations in language areas
36 AutismInter-hemispheric correlation strength predicts language ability and autism symptom severity.
37 Rest activity and development Visual system development (e.g. ocular dominance) before birth (i.e. before visual experience)
38 Hebbian learning during rest? In the absence of externally evoked responses?
39 Different temporal and spatial scales of organization. SummarySpontaneous brain activity is the largest and least understood component of brain function.Different temporal and spatial scales of organization.