The brain at rest

Spontaneous rhythms in a dish Connected neural populations tend to synchronize and oscillate together.

EEG Alpha (10 Hz) Over occipital electrodes. Different time scales of synchronization Close eyes

Slow changes Ultra slow changes in neural firing rates and LFP in auditory cortex of a resting and sleeping human. Nir Y., Nat. Neurosci. (2010)

Slow changes Similar fluctuations in fMRI signal during rest Nir Y., Neuroimage (2006)

Energy costs Brain takes up 20% of the metabolites in the body during rest. Nir Y., Neuroimage (2006)

Energy costs Energy cost breakdown for running the cortex. Most of the energy is spent on neural signaling.

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

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

Structure of rest activity Spontaneous neural activity during rest and sleep is not random “noise”. 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 Cortical areas with similar functionality (e.g. right and left auditory cortex) show strong and selective correlations. Very slow hemodynamic changes over time.

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 Is the brain separated into two general antagonistic networks? Measuring default mode system correlations during rest. “Intrinsic” ROI “Extrinsic” ROI

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 Fox, Nat. Neurosci. (2006) Right hand button press LH ROI Functionally correlated RH ROI

Motor response variability LH responsesRH responses Subtracting out RH spontaneous activity, allowed reduction of trial by trial evoked response variability.

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 Weaker resting state correlations between “default mode” network (precuneus area) and hippocampi. Fare comparison? ControlAlheimer’s 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 1-4 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.

Summary Spontaneous brain activity is the largest and least understood component of brain function. Different temporal and spatial scales of organization. Immense importance – development, maintenance, health.

To the lab!