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The Prefrontal Cortex: Brain Waves and Cognition Earl K. Miller The 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. - PowerPoint PPT Presentation
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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)
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.
Siegel, Warden, and Miller (2009) Proc. Nat. Acad. Sci.
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
Siegel, Warden, and Miller (2009) Proc. Nat. Acad. Sci.
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
Siegel, Warden, and Miller (2009) Proc. Nat. Acad. Sci.
P = 0.0007
Objects were balanced by order
Siegel, Warden, and Miller (2009) Proc. Nat. Acad. Sci.
Object Information in Activity of Individual Neurons by Brain Wave Phase
P = 0.0007
P < 0.0001
Objects were balanced by order
Difference = 62 degP = 0.0002
Siegel, Warden, and Miller (2009) Proc. Nat. Acad. Sci.
Object Information in Activity of Individual Neurons by Brain Wave Phase
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.
Siegel, Warden, and Miller (2009) Proc. Nat. Acad. Sci.
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 …
Baseline Drug Washout------------//-----------
1 2 3 4 5 6 7 8 9 …
Baseline Drug Washout------------//-----------
Session type #1
Session type #2
Session type #3
Recording with Multiple Electrodes while Injecting a D1R Blocker
Puig, M.V. and Miller, E.K. (in preparation)
-60 -40 -20 0 20 40 6040
60
80
100
Per
cent
Cor
rect
-60 -40 -20 0 20 40 6040
60
80
100
Trial From Block Switch-60 -40 -20 0 20 40 60
40
60
80
100
-60 -40 -20 0 20 40 6040
60
80
100
Per
cent
Cor
rect
-60 -40 -20 0 20 40 6040
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80
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-60 -40 -20 0 20 40 6040
60
80
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Blocking D1R Receptors Impairs New Learning But Not Long-Term Memory
Performance novel associations Performance familiar associations
170
75
80
85
90
95
100
Baseline Saline Washout
Perc
ent c
orre
ct
170
75
80
85
90
95
100
Baseline SCH Washout
Perc
ent c
orre
ct
ns
Saline
SCH23390
Baseline Washout
WashoutBaseline
Criterion
Chance
Blocking D1Rs Decreases Attention and Increases Impulsivity
1 2 30
20
40
60
80
1 2 30
50
100
150
200
250
300
Fixation breaks per block Early trials per block
Baseline Treatment Washout
Baseline Treatment Washout
SalineSCH
Effect on attention Effect on impulsivity
***
***
******
Puig, M.V. and Miller, E.K. (in preparation)
Blocking D1R Receptors Causes Neuronal Avalanches: Super-synchronous activity
0 4 8 12 16 20 24 28-0.5
-0.4
-0.3
-0.2
-0.1
0
0.1
0.2
0.3
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Am
plitu
de (m
V)
Time (min)0 2 4 6 8 10
-0.5
-0.4
-0.3
-0.2
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0
0.1
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Am
plitu
de (m
V)
Time (sec)
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)
Puig, M.V. and Miller, E.K. (in preparation)
Blocking D1R Receptors Causes a Broad-Band Increase in PFC Brain Waves
Cue
Delay
Response
Nor
mal
ized
spe
ctru
m d
B
BaselineSCH
Task Interval:
Brain wave frequency
Nor
mal
ized
spe
ctru
m d
BAbnormal brain waves are a bad thing
Puig, M.V. and Miller, E.K. (in preparation)
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