the prefrontal cortex: brain waves and cognition earl k. miller

The Prefrontal Cortex: Brain Waves and Cognition

Earl K. MillerThe Picower Institute for Learning and Memory and

Department of Brain and Cognitive Sciences,Massachusetts Institute of Technology

www.ekmiller.org

Our Goal:To understand the neural basis of higher cognition.

Our Approach:Multiple-electrode recording in trained monkeys.

The prefrontal cortex (PFC)

Measures electrical activity of neurons near electrode tip

Single-electrodeRecording

The primary tool for investigation of brain-

behavior relationships for over 60 years

A useful tool for studying the details of properties of individual neurons. Ideal for an understanding at the level of individual neurons.

Less appropriate for studying networks and systems of neurons.

Does not allow measurements of the precise timing of activity between neurons that give insight into how they communicate and interact.

The classic single-electrode approach only allows indirect inferences about neural networks.

The result: a piecemeal understanding of brain function

A More Global View of Brain Function: FMRI. However….

FMRI measures patterns of blood flow to brain areas (the BOLD signal). Result of neurons needing energy (oxygen) when they fire electrical impulses (“action potentials”).

The Good:Provides a global view of which brain areas are engaged by a cognitive function.

The Bad:It takes five-six seconds for the BOLD signal to build. A lot can happen in the brain in 5-6 seconds.

Our approach: Multiple-electrode Recording in Monkeys Performing Cognitive-demanding Tasks

Electrode arrays with 500 um spacing to investigate

microcircuitry

Electrode arrays in different brain areas to investigate large-scale

networks.

Allows direct measurements of the networks that underlie cognition.

Working memory is the ability to hold and manipulate information in mind.

It is central to normal cognition and closely linked to a wide range of cognitive abilities such as attention, planning, reasoning, etc.

Working Memory – The “Sketchpad” of Conscious Thought

Fixate until fixation cross disappears. Then look at the cued position

A Classic Test of Working Memory: Oculomotor Spatial Delayed Response Task (Goldman-Rakic and colleagues)

The Classic Approach to Studying Neurons: Measure Average Level of Neural Activity of Individual Neurons

From Funahashi and Goldman-Rakic (1989)

This neuron “remembers” the upper left location. It is more active when the remembered cue was in the upper left.

Holding a single thought or memory in mind is a fundamental, but relatively simple, cognitive function.

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

How Do You Hold and Order Multiple Items in Working Memory?

Just examining the activity of individual neurons does not clearly distinguish object order

The classic approach:Information about each object from the average activity of individual PFC neurons

Task: Remember two objects and their order of appearance

Brain waves are rhythmic, coordinated oscillations between neurons (1 – 100 Hz). They reflect how and when networks of neurons communicate.

They allow local networks of neurons to synchronize with one another and with distant networks. This allows the brain to orchestrate billions of neurons to produce elaborate behaviors.

The idea is that when neurons fire in synchrony with one another, they are better able to communicate than when they fire out of sync.

Mounting evidence that brain waves play a critical role in attention, working memory, memory storage, recall, learning, sequencing, planning and more. Abnormal brain waves are associated with neuropsychiatric disorders.

So, How Do You Hold and Order Multiple Items in Working Memory?

A solution: Brain waves

• Parkinson’s patients show increased beta band brain waves (which can be decreased by DA therapy)

• Schizophrenia patients show decreased gamma band brain waves.• Guanfacine (ADHD treatment) increases brain wave (EEG) synchrony in rats.• Methylphenidate (ADHD) increases theta brain waves in the hippocampus.


How Do You Hold and Order Multiple Items in Working Memory?Task: Remember two objects and their order of appearance

Hypothesis: Brain waves act as a “carrier signal” that helps order multiple thoughts held in mind.

32 Hz Brain Waves During Memory Delays


Information about which object is held in memory from activity in

each brain wave phase bin.

Object Information in Activity of Individual Neurons by Brain Wave Phase


P = 0.0007

Objects were balanced by order



P = 0.0007

P < 0.0001

Objects were balanced by order

Difference = 62 degP = 0.0002



ConclusionsDuring working memory, prefrontal activity shows 32 Hz brain waves.

Information about the different objects line up on different parts (phases) of the brain waves according to their memorized order.

This may help order thought and keep multiple thoughts from interfering with one another. A reduction in gamma band brain waves was recently seen in schizophrenics.

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


32 Hz brain waves = spike-timing dependent plasticity?

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

Cognitive capacity is the bandwidth of cognition. It may be directly related to brain waves.

A Potential Application for Brain Waves: A Cognitive Enhancer?

www.ekmiller.org

If we could (slightly) slow down the frequency, or increase the amplitude, of the gamma band oscillations, we could, in theory, add an additional memory slot and increase cognitive capacity.

This could increase the bandwidth of cognition and effectively increase general intelligence.

Cognitive capacity(the width of one wave)

Bottom-up vs top-down attentionTop-down (search):

Goal-directed, knowledge-based, volitional

Bottom-up (pop-out):Stimuli-driven, reflexive

Other examples: fire alarms, looming objects

Bottom-up (Reflexive) vs Top-down (Volitional) Attention

Buschman and Miller (2007) ScienceBuschman and Miller (2009) Neuron

indicates monkeys’ eye position

Bottom-up (pop-out)

Top-down (search)

How Do We Search a Crowded Visual Scene?

Serial search:A moving “spotlight” of attention

It is well known that neurons in many brain areas reflect the ultimate focusing of attention on a target (e.g., Waldo).

However, neural correlates of shifting attention to search for the target have not been observed with the classic single-electrode approach.

Behavioral Reaction Times Suggest That Monkeys Use a Clockwise Covert Serial Search Strategy

Example of behavioral reaction time from one monkey during one testing session.

This monkey tended to start covert search at the lower right location (4 o’clock) and then searched clockwise.

Each monkey chose a different starting point; both showed evidence for clockwise covert search.

Buschman and Miller (2009) Neuron

Serial Shifts of Covert Attention Were Synchronized to 25 Hz Brain Waves in the Prefrontal Cortex

Neuron’s receptive field

location

Upperright

Lowerright

Lowerleft

Upperright

(target)

Shifts of attention every

40 ms

Target Attention Found target

Brain Wave Frequency Was Correlated with Search Time

Target

Slower oscillations = slower shifts of attention = more time required to search = longer reaction time

Buschman and Miller (2009) Neuron

Correlation between brain wave frequency and time to find the target

Top-down (volitional) attention:• Signals originate from prefrontal cortex• Serial shifts of attention (every ~40 ms)• 25 Hz brain waves may act as a ‘clock’ that

controls the shifts in attention.Top-down

Bottom-up

Buschman and Miller (2007) ScienceBuschman and Miller (2009) Neuron

Hypothesis: A reduction in beta-band oscillations might explain why some people have trouble shifting attention away from distracting things.

Novel images

Familiar images

Fixation

Cue Delay Target onset

800 ms

500 ms 1000 ms Response

40 %

40 %

10 %

10 %

The Role of Dopamine (D1R) Receptors in the Prefrontal Cortex During Learning

Monkeys learned by trial and error to associate two novel visual cues with either an eye movement to the right or left

Puig, M.V. and Miller, E.K. (in preparation)

1 2 3 4 5 6 7 8 9 …

Injection schedules

Block number

Location of the injections and grid configuration

Saline 3 µlSCH 23390 (D1 antagonist) 30 µg in 3 µl

Infusion rate: 0.3 µl/min (3 µl in 10 minutes)

Baseline Drug Washout------------//-----------

1 2 3 4 5 6 7 8 9 …


1 2 3 4 5 6 7 8 9 …


Session type #1

Session type #2

Session type #3

Recording with Multiple Electrodes while Injecting a D1R Blocker


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Blocking D1R Receptors Impairs New Learning But Not Long-Term Memory

Performance novel associations Performance familiar associations

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Baseline Saline Washout

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Saline

SCH23390

Baseline Washout

WashoutBaseline

Criterion

Chance

Blocking D1Rs Decreases Attention and Increases Impulsivity

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Fixation breaks per block Early trials per block

Baseline Treatment Washout

Baseline Treatment Washout

SalineSCH

Effect on attention Effect on impulsivity

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Blocking D1R Receptors Causes Neuronal Avalanches: Super-synchronous activity

0 4 8 12 16 20 24 28-0.5

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Avalanches appeared in 47 of 68 electrodes (~70% of 9 sessions)

Duration 18 ± 5min (~10-30 min)

Frequency of deflections0.44 ± 0.03 Hz (0.2-0.6 Hz)

Amplitude of deflections is huge: in most cases over 500 mV

Performance7 sessions with impairment: drops to 56 ± 15 %

Ampl

itude

(mV)


Blocking D1R Receptors Causes a Broad-Band Increase in PFC Brain Waves

Cue

Delay

Response

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BaselineSCH

Task Interval:

Brain wave frequency

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BAbnormal brain waves are a bad thing


Brain waves are central to brain function. They regulate communication between neurons and there is mounting evidence that they play specific and important roles in higher cognition. Abnormal brain waves are apparent in neuropsychiatric disorders.

Multiple-electrodes offer a new tool for directly measuring the effects of potential drug therapies on cognition. They allow direct examination of the functioning of microcircuits and large-scale networks of neurons. This gets directly at the network mechanisms underlying cognition.

The combination of cutting-edge multiple-electrode technology and sophisticated behavioral paradigms in monkeys can provide a powerful diagnostic of the cellular mechanisms that underlie cognitive enhancements by potential drug therapies.

CONCLUSIONS

Miller Lab

Oct 2009www.ekmiller.org

the prefrontal cortex: brain waves and cognition earl k. miller

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