Shackman Psyc210 Module09 IntermediatePhenotypesImaging2 030515
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Stable individual differences in temperament and personality reflect variation in the structure and function of the brain
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PSYC 612
Tools for measuring the brain:
What You Can and Cant Do With
EEG and MRI
AJ Shackman 13 October 2014
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Just As People Differ, Brains Differ
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Individual maps from 17 subjects These subjects are all supposed to be "the same Activation blobs are common, but strength (relative to noise) varies a lot
Just As People Differ, Brains Differ
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Neurons video (4 min) https://www.youtube.com/watch?v=GIGqp6_PG6k
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There are many ways to measure the brain
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Resolving Time & Space
Temporal ResoluBon
SpaB
al ResoluB
on
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Resolving Time & Space
Temporal ResoluBon
SpaB
al ResoluB
on
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Resolving Time & Space
Temporal ResoluBon
SpaB
al ResoluB
on
Note: Techniques also dier in the amount of the brain they can survey at one Bme
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Whadya Mean by Spatial Resolution?
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Temporal resoluBon is analogous
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EEG/ERP
Hans Berger 1924
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EEG (0:44 to 4:21) https://www.youtube.com/watch?v=YUAPUoV56gM
See also Jackson & Bolger Psychophysiol 2014
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How do you compute ERPs?
You compute the average potenAal (voltage) evoked by a parAcular event
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Strengths & Weaknesses of EEG/ERP Strengths Cheap
EEG can be used in more places than fMRI/PET, as these techniques require bulky and immobile equipment (fMRI requires the use of a mulN-ton magnet in a shielded room) Millisecond temporal resoluNon RelaNvely tolerant of subject movement, unlike most other neuroimaging techniques (kids!)
Silent, which allows for beUer study of the responses to auditory sNmuli. Does not aggravate claustrophobia, unlike fMRI
Does not involve exposure to radioligands, unlike positron emission tomography Weaknesses Poor spaNal resoluNon, parNcularly for deep structures CorrelaNonal (not mechanisNc), like all brain imaging techniques
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Strengths & Weaknesses of EEG/ERP Strengths Cheap
EEG can be used in more places than fMRI/PET, as these techniques require bulky and immobile equipment (fMRI requires the use of a mulN-ton magnet in a shielded room) Millisecond temporal resoluNon RelaNvely tolerant of subject movement, unlike most other neuroimaging techniques (kids!)
Silent, which allows for beUer study of the responses to auditory sNmuli. Does not aggravate claustrophobia, unlike fMRI
Does not involve exposure to radioligands, unlike positron emission tomography Weaknesses Poor spaNal resoluNon, parNcularly for deep structures CorrelaNonal (not mechanisNc), like all brain imaging techniques
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Strengths & Weaknesses of EEG/ERP Strengths Cheap
EEG can be used in more places than fMRI/PET, as these techniques require bulky and immobile equipment (fMRI requires the use of a mulN-ton magnet in a shielded room) Millisecond temporal resoluNon RelaNvely tolerant of subject movement, unlike most other neuroimaging techniques (kids!)
Silent, which allows for beUer study of the responses to auditory sNmuli. Does not aggravate claustrophobia, unlike fMRI
Does not involve exposure to radioligands, unlike positron emission tomography Weaknesses Poor spaNal resoluNon, parNcularly for deep structures CorrelaNonal (not mechanisNc), like all brain imaging techniques
-
Strengths & Weaknesses of EEG/ERP Strengths Cheap
EEG can be used in more places than fMRI/PET, as these techniques require bulky and immobile equipment (fMRI requires the use of a mulN-ton magnet in a shielded room) Millisecond temporal resoluNon RelaNvely tolerant of subject movement, unlike most other neuroimaging techniques (kids!)
Silent, which allows for beUer study of the responses to auditory sNmuli. Does not aggravate claustrophobia, unlike fMRI
Does not involve exposure to radioligands, unlike positron emission tomography Weaknesses Poor spaNal resoluNon, parNcularly for deep structures CorrelaNonal (not mechanisNc), like all brain imaging techniques
-
Strengths & Weaknesses of EEG/ERP Strengths Cheap
EEG can be used in more places than fMRI/PET, as these techniques require bulky and immobile equipment (fMRI requires the use of a mulN-ton magnet in a shielded room) Millisecond temporal resoluNon RelaNvely tolerant of subject movement, unlike most other neuroimaging techniques (kids!)
Silent, which allows for beUer study of the responses to auditory sNmuli. Does not aggravate claustrophobia, unlike fMRI
Does not involve exposure to radioligands, unlike positron emission tomography Weaknesses Poor spaNal resoluNon, parNcularly for deep structures CorrelaNonal (not mechanisNc), like all brain imaging techniques
-
Strengths & Weaknesses of EEG/ERP Strengths Cheap
EEG can be used in more places than fMRI/PET, as these techniques require bulky and immobile equipment (fMRI requires the use of a mulN-ton magnet in a shielded room) Millisecond temporal resoluNon RelaNvely tolerant of subject movement, unlike most other neuroimaging techniques (kids!)
Silent, which allows for beUer study of the responses to auditory sNmuli. Does not aggravate claustrophobia, unlike fMRI
Does not involve exposure to radioligands, unlike positron emission tomography Weaknesses Poor spaNal resoluNon, parNcularly for deep structures CorrelaNonal (not mechanisNc), like all brain imaging techniques
-
Strengths & Weaknesses of EEG/ERP Strengths Cheap
EEG can be used in more places than fMRI/PET, as these techniques require bulky and immobile equipment (fMRI requires the use of a mulN-ton magnet in a shielded room) Millisecond temporal resoluNon RelaNvely tolerant of subject movement, unlike most other neuroimaging techniques (kids!)
Silent, which allows for beUer study of the responses to auditory sNmuli. Does not aggravate claustrophobia, unlike fMRI
Does not involve exposure to radioligands, unlike positron emission tomography Weaknesses Poor spaNal resoluNon, parNcularly for deep structures CorrelaNonal (not mechanisNc), like all brain imaging techniques
-
Strengths & Weaknesses of EEG/ERP Strengths Cheap
EEG can be used in more places than fMRI/PET, as these techniques require bulky and immobile equipment (fMRI requires the use of a mulN-ton magnet in a shielded room) Millisecond temporal resoluNon RelaNvely tolerant of subject movement, unlike most other neuroimaging techniques (kids!)
Silent, which allows for beUer study of the responses to auditory sNmuli. Does not aggravate claustrophobia, unlike fMRI
Does not involve exposure to radioligands, unlike positron emission tomography Weaknesses Poor spaNal resoluNon, parNcularly for deep structures CorrelaNonal (not mechanisNc), like all brain imaging techniques
-
Strengths & Weaknesses of EEG/ERP Strengths Cheap
EEG can be used in more places than fMRI/PET, as these techniques require bulky and immobile equipment (fMRI requires the use of a mulN-ton magnet in a shielded room) Millisecond temporal resoluNon RelaNvely tolerant of subject movement, unlike most other neuroimaging techniques (kids!)
Silent, which allows for beUer study of the responses to auditory sNmuli. Does not aggravate claustrophobia, unlike fMRI
Does not involve exposure to radioligands, unlike positron emission tomography Weaknesses Poor spaNal resoluNon, parNcularly for deep structures CorrelaNonal (not mechanisNc), like all brain imaging techniques
-
Strengths & Weaknesses of EEG/ERP Strengths Cheap
EEG can be used in more places than fMRI/PET, as these techniques require bulky and immobile equipment (fMRI requires the use of a mulN-ton magnet in a shielded room) Millisecond temporal resoluNon RelaNvely tolerant of subject movement, unlike most other neuroimaging techniques (kids!)
Silent, which allows for beUer study of the responses to auditory sNmuli. Does not aggravate claustrophobia, unlike fMRI
Does not involve exposure to radioligands, unlike positron emission tomography Weaknesses Poor spaNal resoluNon, parNcularly for deep structures CorrelaNonal (not mechanisNc), like all brain imaging techniques
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Magnetic Resonance Imaging (MRI) Scanner
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Skip video clip
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MRI Intro Video (6 min; stop at 5:55) https://www.youtube.com/watch?v=BmQR57V5TVU
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How Does MRI Work?
You will not be responsible for the details
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structural MRI vs. functional MRI
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MRI fMRI
One 3D volume
series of 3D volumes (i.e., 4D data) (e.g., every 2 sec for 5 mins)
high spatial resolution
(1 mm)
lower spatial resolution (~3 mm)
structural MRI vs. functional MRI
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fMRI Does NOT Measure Neuronal Activity
It Measures Blood Oxygenation
(Details Not Important)
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How do we estimate fMRI activation?
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Conceptually Similar to ERPs
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Events (Dog)
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Events (Dog)
fMRI Signal
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Events (Dog)
fMRI Signal
Average Response to Event (in arbitrary units!)
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But complex psychological phenomena (T&P) reect the
coordinated acAvity of distributed neural circuits
How do we assess the connecAvity of
funcAonal circuits in the brain?
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Dummies Guide to Functional Connectivity
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fMRI Caveats
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fMRI Caveats Measuring blood oxygenaNon not neurons!
Although recent work suggests that, unlike EEG, the BOLD signal is strongly correlated with neuronal spiking (Lima et al J Neuro 2014)
Not enNrely clear whether fMRI signal reects neuronal acNvaNon
We also know, however, that the fMRI signal is o6en unable to dieren;ate between func;on-specic processing and neuromodula;on, between boAom-up and top-down signals, and it may occasionally confuse excita;on and inhibi;on (Logothe;s, 2008). [LogotheNs Neuroimage 2012]
Not clear whether funcNonal connecNvity (cross-correlaNon of Nme-series) reects true coupling between regions (e.g., regulaNon or the transmission of informaNon)
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fMRI Caveats Measuring blood oxygenaNon not neurons!
Although recent work suggests that, unlike EEG, the BOLD signal is strongly correlated with neuronal spiking (Lima et al J Neuro 2014)
Not enNrely clear whether fMRI signal reects neuronal acNvaNon
We also know, however, that the fMRI signal is o6en unable to dieren;ate between func;on-specic processing and neuromodula;on, between boAom-up and top-down signals, and it may occasionally confuse excita;on and inhibi;on (Logothe;s, 2008). [LogotheNs Neuroimage 2012]
Not clear whether funcNonal connecNvity (cross-correlaNon of Nme-series) reects true coupling between regions (e.g., regulaNon or the transmission of informaNon)
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fMRI Caveats Measuring blood oxygenaNon not neurons!
Although recent work suggests that, unlike EEG, the BOLD signal is strongly correlated with neuronal spiking (Lima et al J Neuro 2014)
Not enNrely clear whether fMRI signal reects neuronal acNvaNon
We also know, however, that the fMRI signal is o6en unable to dieren;ate between func;on-specic processing and neuromodula;on, between boAom-up and top-down signals, and it may occasionally confuse excita;on and inhibi;on (Logothe;s, 2008). [LogotheNs Neuroimage 2012]
Not clear whether funcNonal connecNvity (cross-correlaNon of Nme-series) reects true coupling between regions (e.g., regulaNon or the transmission of informaNon)
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Strengths & Weaknesses of fMRI Strengths
Very good spaNal resoluNon Non-invasive (no radiaNon) Common at most universiNes and larger hospitals
Weaknesses
Poor temporal resoluNon (seconds) Noisy, unnatural Expensive ($600/hour @ UMCP) Requires parNcipants to remain completely sNll! Neuronal source of signal is not enNrely clear (but correlated with spiking)
CorrelaNonal, not causal
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Strengths & Weaknesses of fMRI Strengths
Very good spaNal resoluNon Non-invasive (no radiaNon) Common at most universiNes and larger hospitals
Weaknesses
Poor temporal resoluNon (seconds) Noisy, unnatural Expensive ($600/hour @ UMCP) Requires parNcipants to remain completely sNll! Neuronal source of signal is not enNrely clear (but correlated with spiking)
CorrelaNonal, not causal
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Strengths & Weaknesses of fMRI Strengths
Very good spaNal resoluNon Non-invasive (no radiaNon) Common at most universiNes and larger hospitals
Weaknesses
Poor temporal resoluNon (seconds) Noisy, unnatural Expensive ($600/hour @ UMCP) Requires parNcipants to remain completely sNll! Neuronal source of signal is not enNrely clear (but correlated with spiking)
CorrelaNonal, not causal
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Some Things Are Just Plain Hard to Do with fMRI
Anything requiring subject to speak or move One word or sound can be OK Requires censoring out data during subject speech jaw moNon is bad for images
Anything that uses subtle sounds (music, language)
Scanner is very loud Workaround: silent period between scans
Very long duraBon tasks (learning; drug infusion)
Hard to tell long acNvaNon changes from MRI signal drijing up or down (e.g., head drij)
Not impossible, but requires special analysis or pulse sequence (ASL)
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Some Things Are Just Plain Hard to Do with fMRI
Anything requiring subject to speak or move One word or sound can be OK Requires censoring out data during subject speech jaw moNon is bad for images
Anything that uses subtle sounds (music, language)
Scanner is very loud Workaround: silent period between scans
Very long duraBon tasks (learning; drug infusion)
Hard to tell long acNvaNon changes from MRI signal drijing up or down (e.g., head drij)
Not impossible, but requires special analysis or pulse sequence (ASL)
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Some Things Are Just Plain Hard to Do with fMRI
Anything requiring subject to speak or move One word or sound can be OK Requires censoring out data during subject speech jaw moNon is bad for images
Anything that uses subtle sounds (music, language)
Scanner is very loud Workaround: silent period between scans
Very long duraBon tasks (learning; drug infusion)
Hard to tell long acNvaNon changes from MRI signal drijing up or down (e.g., head drij)
Not impossible, but requires special analysis or pulse sequence (ASL)
-
Some Things Are Just Plain Hard to Do with fMRI
Anything requiring subject to speak or move One word or sound can be OK Requires censoring out data during subject speech jaw moNon is bad for images
Anything that uses subtle sounds (music, language)
Scanner is very loud Workaround: silent period between scans
Very long duraBon tasks (learning; drug infusion)
Hard to tell long acNvaNon changes from MRI signal drijing up or down (e.g., head drij)
Not impossible, but requires special analysis or pulse sequence (ASL)
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Reality Check: Whats Lurking in a Voxel
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Reality Check: Whats Lurking in a Voxel A complex mesh of vessels, dierent kinds of neurons
and glia; all contribuAng to the fMRI signal
A single voxel contains
* 5.5 million neurons * 22 km of dendrites * 220 km of axons * 4 x 1010 (40B) synapses
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Reality Check: Whats Lurking in a Voxel A complex mesh of vessels, dierent kinds of neurons
and glia; all contribuAng to the fMRI signal
A single voxel contains
* 5.5 million neurons * 22 km of dendrites * 220 km of axons * 4 x 1010 (40B) synapses
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40B synapses is a lot
x 4
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This aint just theoreAcal
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Pare & Duvarci Curr Opin Neurobiol 2012
e.g., Amygdala contains complex microcircuits that gate and modulate
the expression of fear and anxiety
DETAILS ARE NOT IMPORTANT!
These microcircuits can not be resolved using fMRI
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CriBcal Thinking QuesBons
Please pick 2 of 3
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CriBcal Thinking QuesBons 1. Watch Joe LeDouxs BigThink interviews: hUps://www.youtube.com/watch?v=n8hpf4dC8H0 hUps://www.youtube.com/watch?v=jZ3_-Z3Jycw
-OR- 2. Watch June Grubers interview of Tor Wager: hUps://www.youtube.com/watch?v=z-8XCK9P430 Briey describe the 2 most important or interes;ng things that you learned and 2 key challenges for future research.
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CriBcal Thinking QuesBons 3. The brains structural connectome. Briey describe: A) What is diusion tensor imaging (DTI) and how can it be used to map the brains wiring?
For some Nps, see these handy references - Overview @ hUp://www.diusion-imaging.com/2009/05/lectures-on-dN-basics-and-analysis.html
- Wiki @ hUps://en.wikipedia.org/wiki/Diusion_MRI
- Film clip @ hUps://www.youtube.com/watch?v=i6ZqP04RhNI
- Film clip @ hUps://www.youtube.com/watch?v=TjbkepJRrZc
B) How can DTI be used to understand a facet of T&P?
- For some Nps, see - hUp://www.annualreviews.org/doi/full/10.1146/annurev-clinpsy-032210-104507
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The End (No Review QuesBons)
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Material to Consider IncorporaBng as a CriBcal Thinking Q
in the Future
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Extra Slides
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EEG Intro Video, Version #1 (1:12 to end)
https://www.youtube.com/watch?v=kGuayTwqieM
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Summary EEG fMRI
Strengths excellent temporal excellent spatial
Weaknesses poor spatial poor
temporal
Measuring? electrical currents oxygen in
blood
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Upper wave in each pair = signal; lower = residual noise est
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DTI Video (60 sec)
https://www.youtube.com/watch?v=i6ZqP04RhNI And this one is 30 sec https://www.youtube.com/watch?v=TjbkepJRrZc
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fMRI Experiment Stages: Anatomicals 4) Take anatomical (T1) images
high-resolution images (e.g., 0.75 x 0.75 x 3.0 mm) 3D data: 3 spatial dimensions, sampled at one point in time 64 anatomical slices takes ~4 minutes
64 slices x 3 mm
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-79-
Some FMRI Data
Left = decent looking single subject activation map From 300 s of data (150 time points)
Right = data time series that gives activation map This is good data [strong activation, little head movement]
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Hemodynamic Response FuncNon (HRF)
Time course of fMRI is ~6 seconds (blood ow is slow!)
Dip because neurons begin to extract oxygen before oxyHb arrives
Increase in oxyHb because new oxyHb has overcompensated
Back to baseline because neurons extract oxygen so oxyHb becomes deoxyHb
10 seconds
4-6 seconds
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FMRI Experiment
F
S
F
F
F
S
S
S
S
Faces
Scrambled
Faces
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fMRI Analysis
Condition I Condition S (If significant)
Voxel
I = Intact face
S = Scrambled face
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fMRI relies on subtracNon method
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fMRI Experiment Stages: Functionals 5) Take functional (T2*) images
images are indirectly related to neural activity usually low resolution images (3 x 3 x 6 mm) all slices at one time = a volume (sometimes also called an image) sample many volumes (time points) (e.g., 1 volume every 2 seconds for 136
volumes = 272 sec = 4:32) 4D data: 3 spatial, 1 temporal
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Reverse Engineering Marion Barry
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Confusions & Distinctions Brain vs. Mind
Neuroscience vs. Cognitive science Mass level vs. Micro-circuitry
Connecting blobs to cell-level actions? Excitation & Inhibition both consume energy
What does active mean? Active vs. Necessary (e.g., lesion studies) Modulated here? Or there? MVPA vs. Specificity Resting State: Function vs. Physiology
-86-
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BART Procedure
Computer simulated sequence of balloons $0.05 per balloon pump (in temporary bank) Must hit collect $$$ button to earn money Balloon explosion = temporary money lost Explosion point for balloons (1 128) Earnings after session in gift certificates
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Earn
ings
($)
MIN MAX
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Not Just Psychiatry Other syndromes with complex eBology and overlapping symptoms E.g., Diabetes, hypercholesterolemia, hypertension
Clinical presentaNon: PaNent complains of faNgue; whats the Dx?
DierenNal Diagnosis: challenges (stress test) and assays to determine a primary eNology and Dx
E.g., glucose tolerance test, serum cholesterol, BP
Similar symptoms, dierent endophenotypes, dierent geneNc underpinnings
GoUesman & Gould Amer J Psychiatry 2003
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Promises to enhance: EAology (cause)
What is the proximal biological cause(s) of the disorder/T&P?
Nosology (Dx) Unlike many physical diseases, psychiatric disorders/T&P are dened by symptoms not
pathophysiology; understanding the eNology would lead to a restructuring of nosology (or the Big 3 or 5 Factors)
Challenging to know how disorders/factors should be clumped together what if symptoms reect similar vs. dierent causes?
E.g., growing biological evidence that SZ and BPD are related Prognosis
If we understood the eNology, we could beUer predict the likely outcome (cf. MoU) Treatment (Personalized or Precision Medicine)
Most disorders resist treatment; extant treatments work for a subset of paNents If we understood the eNology, we could target treatments, enhancing cost/benet
Early intervenAon for high-risk populaAons (e.g., cholesterol test staAns) Screen idenNfy intervene before the deleterious secondary consequences emerge
The Promise
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MRI vs. fMRI
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fMRI Simplified
Time
~2s
~ 5 min
Time
fMRI Signal
Intensity
ROI Time Course
Condition
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fMRI Setup