Brain Rhythms and Short-Term Memory

Earl K. MillerThe Picower Institute for Learning and Memory and

Department of Brain and Cognitive Sciences,Massachusetts Institute of Technology

www.ekmiller.org

Adler Foundation SymposiumFebruary 2010

Monkey

Human

The prefrontal cortex

Our Goal:To understand the neural basis of high-level cognition.

Our Approach:

Multiple-electrode recording in trained monkeys.

Allows detailed comparisons of the timing of activity between neurons.

The ability to hold multiple items in short-term memory is critical for planning and executing goal-directed behavior.

Increasing evidence for a role of oscillatory activity in short-term memory.

One model suggests phase-dependent coding of memory items (e.g., Lisman and Idiart, Science, 1995).

How Do We Hold Multiple Thoughts in Mind?

This model attempted to explain why short-term memory has a severe limitation in capacity.

Cognitive capacity: How many things can you hold in mind simultaneously?

Individual differences in capacity limits can explain about 25-50% of the individual

differences in tests of intelligence

It is linked to normal cognition and intelligence:

Capacity is highest in younger adults and reduced in many neuropsychiatric disorders

Schizophrenia

Parkinson’s Disease

Vogel et al (2001); Gold et al (2003); Cowan et al (2006); Hackley et al (2009)www.ekmiller.org

Q1: Is there oscillatory synchronization during short-term memory?

Q2: Do spikes at particular phases of LFP oscillations carry more information about items in memory?

Q3: Is there more information about different memory items in different LFP phases?

How Does the Brain Hold Multiple Items in Memory?

Behavioral Task and Neurophysiological Recording

Siegel, Warden, and Miller (2009) Proc. Nat. Acad. Sci.

• Two monkeys

• New stimulus set (4 objects) each day. Object identity fully balanced with order.

• Eight electrodes simultaneously implanted in the DL prefrontal cortex

• Local field potentials and multi-unit spikes from 140 recording sites

Sustained LFP Gamma Oscillations During Memory Delays

LFP power at differentfrequencies

Siegel, Warden, and Miller (2009) Proc. Nat. Acad. Sci.

1st delay(one

stimulus)

2nd delay(two stimuli sequence)

Average of all randomly selected spikes

LFP power at differentfrequencies

Siegel, Warden, and Miller (2009) Proc. Nat. Acad. Sci.

1st delay(one

stimulus)

2nd delay(two stimuli sequence)

Average of all randomly selected spikes

Q1: Is there oscillatory synchronization during short-term memory?Yes

Do Spikes Synchronize to LFP Oscillations?

32 Hz

3 Hz

Siegel, Warden, and Miller (2009) Proc. Nat. Acad. Sci.

Preferred spiking phase across recording sites

Proportion of recording sites with significant spike-LFP phase-locking

32 Hz

3 Hz

Siegel, Warden, and Miller (2009) Proc. Nat. Acad. Sci.

Preferred spiking phase across recording sites

Proportion of recording sites with significant spike-LFP phase-locking

Q2: Do spikes at particular phases of LFP oscillations carry more information about items in memory? Yes

Stimulus Information in Average Spiking Activity

Information about stimulus identity (Neural variance

explained by stimulus factor)

Siegel, Warden, and Miller (2009) Proc. Nat. Acad. Sci.

Average firing rate does not clearly distinguish object order

Information about stimulus identity from spiking activity in

each LFP phase bin.

Stimulus Information in Average Spiking ActivityBy LFP Phase

Siegel, Warden, and Miller (2009) Proc. Nat. Acad. Sci.

Stimuli were balanced by order

Stimulus Information By Stimulus Order in Different LFP Phases

32 Hz

Objects were balanced by order

LFP Power

Siegel, Warden, and Miller (2009) Proc. Nat. Acad. Sci.

Object Information By Object Order in Different LFP Phases

Siegel, Warden, and Miller (2009) Proc. Nat. Acad. Sci.

32 Hz

3 HzCoding of objects in different

phases was observed at 32 Hz, not 3 Hz

Siegel, Warden, and Miller (2009) Proc. Nat. Acad. Sci.

32 Hz

Object phases overlap

Error trials (32 Hz)(corrects + errors)

Even though overall spike-phase synchrony is unchanged

Object Information By Object Order in Different LFP Phases

Siegel, Warden, and Miller (2009) Proc. Nat. Acad. Sci.

32 Hz

Object phases overlap

Error trials (32 Hz)(corrects + errors)

Even though overall spike-phase synchrony is unchanged

Q3: Is there more information about different memory items in different LFP phases?Yes

Conclusions

During short-term memory, prefrontal activity shows oscillatory synchronization in gamma and theta bands.

Spikes carry more information about stimuli held in memory at particular LFP phases.

The first stimulus of the memorized sequence is encoded earlier in the LFP cycle than the second stimulus for the gamma band but not the theta band.

Phase-dependent coding may serve to flexibly represent sequences in memory on a generic neuronal time-scale.

This may also explain why short-term memory has a capacity limitation.

Siegel, Warden, and Miller (2009) Proc. Nat. Acad. Sci.

Gamma band = spike-timing dependent plasticity?

Miller Lab

Oct 2009www.ekmiller.org