Shackman Psyc210 Module09 IntermediatePhenotypesImaging2

PowerPoint Presentation

Stable individual differencesin temperament and personality reflect variation inthe structure and function ofthe brain 1PSYC 612

Tools for measuring the brain:

What You Can and Cant Do WithEEG and MRIAJ Shackman13 October 2014Just As People Differ, Brains Differ3Individual 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 Differ4Neurons video (4 min)https://www.youtube.com/watch?v=GIGqp6_PG6kThere are many ways to measure the brainResolving Time & SpaceTemporal ResolutionSpatial ResolutionResolving Time & Space

Temporal ResolutionSpatial ResolutionResolving Time & Space

Temporal ResolutionSpatial ResolutionNote: Techniques also differ in the amount of the brain they can survey at one timeWhadya Mean by Spatial Resolution?

Temporal resolution is analogousEEG/ERP

Hans Berger 1924EEG (0:44 to 4:21)https://www.youtube.com/watch?v=YUAPUoV56gMSee also Jackson & Bolger Psychophysiol 2014

How do you compute ERPs?

You compute the average potential (voltage) evoked by a particular event

Strengths & Weaknesses of EEG/ERPStrengthsCheap

EEG can be used in more places than fMRI/PET, as these techniques require bulky and immobile equipment (fMRI requires the use of a multi-ton magnet in a shielded room)

Millisecond temporal resolution

Relatively tolerant of subject movement, unlike most other neuroimaging techniques (kids!)

Silent, which allows for better study of the responses to auditory stimuli.

Does not aggravate claustrophobia, unlike fMRI

Does not involve exposure to radioligands, unlike positron emission tomography

WeaknessesPoor spatial resolution, particularly for deep structures

Correlational (not mechanistic), like all brain imaging techniquesStrengths & Weaknesses of EEG/ERPStrengthsCheap

EEG can be used in more places than fMRI/PET, as these techniques require bulky and immobile equipment (fMRI requires the use of a multi-ton magnet in a shielded room)

Millisecond temporal resolution

Relatively tolerant of subject movement, unlike most other neuroimaging techniques (kids!)

Silent, which allows for better study of the responses to auditory stimuli.

Does not aggravate claustrophobia, unlike fMRI

Does not involve exposure to radioligands, unlike positron emission tomography

WeaknessesPoor spatial resolution, particularly for deep structures

Correlational (not mechanistic), like all brain imaging techniquesStrengths & Weaknesses of EEG/ERPStrengthsCheap

EEG can be used in more places than fMRI/PET, as these techniques require bulky and immobile equipment (fMRI requires the use of a multi-ton magnet in a shielded room)

Millisecond temporal resolution

Relatively tolerant of subject movement, unlike most other neuroimaging techniques (kids!)

Silent, which allows for better study of the responses to auditory stimuli.

Does not aggravate claustrophobia, unlike fMRI

Does not involve exposure to radioligands, unlike positron emission tomography

WeaknessesPoor spatial resolution, particularly for deep structures

Correlational (not mechanistic), like all brain imaging techniquesStrengths & Weaknesses of EEG/ERPStrengthsCheap

EEG can be used in more places than fMRI/PET, as these techniques require bulky and immobile equipment (fMRI requires the use of a multi-ton magnet in a shielded room)

Millisecond temporal resolution

Relatively tolerant of subject movement, unlike most other neuroimaging techniques (kids!)

Silent, which allows for better study of the responses to auditory stimuli.

Does not aggravate claustrophobia, unlike fMRI

Does not involve exposure to radioligands, unlike positron emission tomography

WeaknessesPoor spatial resolution, particularly for deep structures

Correlational (not mechanistic), like all brain imaging techniquesStrengths & Weaknesses of EEG/ERPStrengthsCheap

EEG can be used in more places than fMRI/PET, as these techniques require bulky and immobile equipment (fMRI requires the use of a multi-ton magnet in a shielded room)

Millisecond temporal resolution

Relatively tolerant of subject movement, unlike most other neuroimaging techniques (kids!)

Silent, which allows for better study of the responses to auditory stimuli.

Does not aggravate claustrophobia, unlike fMRI

Does not involve exposure to radioligands, unlike positron emission tomography

WeaknessesPoor spatial resolution, particularly for deep structures

Correlational (not mechanistic), like all brain imaging techniquesStrengths & Weaknesses of EEG/ERPStrengthsCheap

EEG can be used in more places than fMRI/PET, as these techniques require bulky and immobile equipment (fMRI requires the use of a multi-ton magnet in a shielded room)

Millisecond temporal resolution

Relatively tolerant of subject movement, unlike most other neuroimaging techniques (kids!)

Silent, which allows for better study of the responses to auditory stimuli.

Does not aggravate claustrophobia, unlike fMRI

Does not involve exposure to radioligands, unlike positron emission tomography

WeaknessesPoor spatial resolution, particularly for deep structures

Correlational (not mechanistic), like all brain imaging techniquesStrengths & Weaknesses of EEG/ERPStrengthsCheap

EEG can be used in more places than fMRI/PET, as these techniques require bulky and immobile equipment (fMRI requires the use of a multi-ton magnet in a shielded room)

Millisecond temporal resolution

Relatively tolerant of subject movement, unlike most other neuroimaging techniques (kids!)

Silent, which allows for better study of the responses to auditory stimuli.

Does not aggravate claustrophobia, unlike fMRI

Does not involve exposure to radioligands, unlike positron emission tomography

WeaknessesPoor spatial resolution, particularly for deep structures

Correlational (not mechanistic), like all brain imaging techniquesStrengths & Weaknesses of EEG/ERPStrengthsCheap

EEG can be used in more places than fMRI/PET, as these techniques require bulky and immobile equipment (fMRI requires the use of a multi-ton magnet in a shielded room)

Millisecond temporal resolution

Relatively tolerant of subject movement, unlike most other neuroimaging techniques (kids!)

Silent, which allows for better study of the responses to auditory stimuli.

Does not aggravate claustrophobia, unlike fMRI

Does not involve exposure to radioligands, unlike positron emission tomography

WeaknessesPoor spatial resolution, particularly for deep structures

Correlational (not mechanistic), like all brain imaging techniquesStrengths & Weaknesses of EEG/ERPStrengthsCheap

EEG can be used in more places than fMRI/PET, as these techniques require bulky and immobile equipment (fMRI requires the use of a multi-ton magnet in a shielded room)

Millisecond temporal resolution

Relatively tolerant of subject movement, unlike most other neuroimaging techniques (kids!)

Silent, which allows for better study of the responses to auditory stimuli.

Does not aggravate claustrophobia, unlike fMRI

Does not involve exposure to radioligands, unlike positron emission tomography

WeaknessesPoor spatial resolution, particularly for deep structures

Correlational (not mechanistic), like all brain imaging techniquesStrengths & Weaknesses of EEG/ERPStrengthsCheap

EEG can be used in more places than fMRI/PET, as these techniques require bulky and immobile equipment (fMRI requires the use of a multi-ton magnet in a shielded room)

Millisecond temporal resolution

Relatively tolerant of subject movement, unlike most other neuroimaging techniques (kids!)

Silent, which allows for better study of the responses to auditory stimuli.

Does not aggravate claustrophobia, unlike fMRI

Does not involve exposure to radioligands, unlike positron emission tomography

WeaknessesPoor spatial resolution, particularly for deep structures

Correlational (not mechanistic), like all brain imaging techniquesMagnetic Resonance Imaging (MRI)Scanner

Skip video clipMRI Intro Video (6 min; stop at 5:55)https://www.youtube.com/watch?v=BmQR57V5TVUHow Does MRI Work?

You will not be responsible for the detailsstructural MRI vs. functional MRI32I is for Imaging

Imaging parameters are different MRI Anatomicals aim to maximize tissue contrast

fMRI to maximize functional contrast.

MRIfMRIOne 3D volumeseries 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 MRI33I is for Imaging

Imaging parameters are different MRI Anatomicals aim to maximize tissue contrast

fMRI to maximize functional contrast.

fMRI Does NOT Measure Neuronal Activity

It Measures Blood Oxygenation

(Details Not Important)

How do we estimate fMRI activation?Conceptually Similar to ERPs

Events (Dog)

Events (Dog)fMRI Signal

Events (Dog)fMRI SignalAverage Response to Event (in arbitrary units!)But complex psychological phenomena (T&P) reflect the coordinated activity of distributed neural circuits

How do we assess the connectivity of functional circuits in the brain?Dummies Guide to Functional Connectivity

fMRI CaveatsfMRI CaveatsMeasuring blood oxygenation 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 entirely clear whether fMRI signal reflects neuronal activationWe also know, however, that the fMRI signal is often unable to differentiate between function-specific processing and neuromodulation, between bottom-up and top-down signals, and it may occasionally confuse excitation and inhibition (Logothetis, 2008). [Logothetis Neuroimage 2012]

Not clear whether functional connectivity (cross-correlation of time-series) reflects true coupling between regions (e.g., regulation or the transmission of information)fMRI CaveatsMeasuring blood oxygenation 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 entirely clear whether fMRI signal reflects neuronal activationWe also know, however, that the fMRI signal is often unable to differentiate between function-specific processing and neuromodulation, between bottom-up and top-down signals, and it may occasionally confuse excitation and inhibition (Logothetis, 2008). [Logothetis Neuroimage 2012]

Not clear whether functional connectivity (cross-correlation of time-series) reflects true coupling between regions (e.g., regulation or the transmission of information)fMRI CaveatsMeasuring blood oxygenation 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 entirely clear whether fMRI signal reflects neuronal activationWe also know, however, that the fMRI signal is often unable to differentiate between function-specific processing and neuromodulation, between bottom-up and top-down signals, and it may occasionally confuse excitation and inhibition (Logothetis, 2008). [Logothetis Neuroimage 2012]

Not clear whether functional connectivity (cross-correlation of time-series) reflects true coupling between regions (e.g., regulation or the transmission of information)Strengths & Weaknesses of fMRIStrengthsVery good spatial resolutionNon-invasive (no radiation)Common at most universities and larger hospitals

WeaknessesPoor temporal resolution (seconds)Noisy, unnaturalExpensive ($600/hour @ UMCP)Requires participants to remain completely still!Neuronal source of signal is not entirely clear (but correlated with spiking)Correlational, not causalStrengths & Weaknesses of fMRIStrengthsVery good spatial resolutionNon-invasive (no radiation)Common at most universities and larger hospitals

WeaknessesPoor temporal resolution (seconds)Noisy, unnaturalExpensive ($600/hour @ UMCP)Requires participants to remain completely still!Neuronal source of signal is not entirely clear (but correlated with spiking)Correlational, not causalStrengths & Weaknesses of fMRIStrengthsVery good spatial resolutionNon-invasive (no radiation)Common at most universities and larger hospitals

WeaknessesPoor temporal resolution (seconds)Noisy, unnaturalExpensive ($600/hour @ UMCP)Requires participants to remain completely still!Neuronal source of signal is not entirely clear (but correlated with spiking)Correlational, not causalSome Things Are Just Plain Hard to Do with fMRIAnything requiring subject to speak or moveOne word or sound can be OKRequires censoring out data during subject speech jaw motion is bad for images

Anything that uses subtle sounds (music, language)Scanner is very loudWorkaround: silent period between scans

Very long duration tasks (learning; drug infusion)Hard to tell long activation changes from MRI signal drifting up or down (e.g., head drift)Not impossible, but requires special analysis or pulse sequence (ASL)Some Things Are Just Plain Hard to Do with fMRIAnything requiring subject to speak or moveOne word or sound can be OKRequires censoring out data during subject speech jaw motion is bad for images

Anything that uses subtle sounds (music, language)Scanner is very loudWorkaround: silent period between scans

Very long duration tasks (learning; drug infusion)Hard to tell long activation changes from MRI signal drifting up or down (e.g., head drift)Not impossible, but requires special analysis or pulse sequence (ASL)Some Things Are Just Plain Hard to Do with fMRIAnything requiring subject to speak or moveOne word or sound can be OKRequires censoring out data during subject speech jaw motion is bad for images

Anything that uses subtle sounds (music, language)Scanner is very loudWorkaround: silent period between scans

Very long duration tasks (learning; drug infusion)Hard to tell long activation changes from MRI signal drifting up or down (e.g., head drift)Not impossible, but requires special analysis or pulse sequence (ASL)Some Things Are Just Plain Hard to Do with fMRIAnything requiring subject to speak or moveOne word or sound can be OKRequires censoring out data during subject speech jaw motion is bad for images

Anything that uses subtle sounds (music, language)Scanner is very loudWorkaround: silent period between scans

Very long duration tasks (learning; drug infusion)Hard to tell long activation changes from MRI signal drifting up or down (e.g., head drift)Not impossible, but requires special analysis or pulse sequence (ASL)Reality Check: Whats Lurking in a Voxel

Reality Check: Whats Lurking in a Voxel

A complex mesh of vessels, different kinds of neuronsand glia; all contributing 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

Reality Check: Whats Lurking in a Voxel

A complex mesh of vessels, different kinds of neuronsand glia; all contributing 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

40B synapses is a lotx 4This aint just theoretical

Pare & Duvarci Curr Opin Neurobiol 2012e.g., Amygdala contains complex microcircuits that gate and modulatethe expression of fear and anxietyDETAILS ARE NOT IMPORTANT!These microcircuits can not be resolved using fMRI60

Critical Thinking QuestionsPlease pick 2 of 3Critical Thinking Questions1. Watch Joe LeDouxs BigThink interviews:

https://www.youtube.com/watch?v=n8hpf4dC8H0https://www.youtube.com/watch?v=jZ3_-Z3Jycw

-OR-

2. Watch June Grubers interview of Tor Wager:

https://www.youtube.com/watch?v=z-8XCK9P430

Briefly describe the 2 most important or interesting things that you learned and 2 key challenges for future research.Critical Thinking Questions3. The brains structural connectome.

Briefly describe:

A) What is diffusion tensor imaging (DTI) and how can it be used to map the brains wiring?For some tips, see these handy references- Overview @ http://www.diffusion-imaging.com/2009/05/lectures-on-dti-basics-and-analysis.html

- Wiki @ https://en.wikipedia.org/wiki/Diffusion_MRI

- Film clip @ https://www.youtube.com/watch?v=i6ZqP04RhNI

- Film clip @ https://www.youtube.com/watch?v=TjbkepJRrZc

B) How can DTI be used to understand a facet of T&P?- For some tips, see - http://www.annualreviews.org/doi/full/10.1146/annurev-clinpsy-032210-104507

The End (No Review Questions)Material to ConsiderIncorporating as a Critical Thinking Q in the Future

Extra SlidesEEG Intro Video, Version #1 (1:12 to end)https://www.youtube.com/watch?v=kGuayTwqieM

SummaryEEGfMRIStrengthsexcellent temporalexcellent spatialWeaknessespoor spatialpoortemporalMeasuring?electrical currentsoxygen in blood

Upper wave in each pair = signal; lower = residual noise estDTI Video (60 sec)https://www.youtube.com/watch?v=i6ZqP04RhNI

And this one is 30 sec

https://www.youtube.com/watch?v=TjbkepJRrZc

fMRI Experiment Stages: Anatomicals4) 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

78-79-Some FMRI DataLeft = decent looking single subject activation mapFrom 300 s of data (150 time points)Right = data time series that gives activation mapThis is good data [strong activation, little head movement]

79Hemodynamic Response Function (HRF)Time course of fMRI is ~6 seconds (blood flow is slow!)

Dip because neurons begin to extract oxygen before oxyHb arrivesIncrease in oxyHb because new oxyHb has overcompensatedBack to baseline because neurons extract oxygen so oxyHb becomes deoxyHb10 seconds4-6 secondsCheesy class demonstration Im neuron, first have pass through in single file I pat each and hands go up for deoxyHB. Then when I fire come in mob, I pat some then check how many oxy. that is fmri signal.80FMRI ExperimentFSFFFSSSSFaces

Scrambled Faces

How do we use these signal properties to do an fmri experiment?81fMRI Analysis

Condition I Condition S (If significant)Voxel

I = Intact faceS = Scrambled facefMRI relies on subtraction method

fMRI Experiment Stages: Functionals5) 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

84Reverse Engineering Marion Barry

Confusions & DistinctionsBrain vs. MindNeuroscience vs. Cognitive scienceMass level vs. Micro-circuitryConnecting blobs to cell-level actions?Excitation & Inhibition both consume energyWhat does active mean?Active vs. Necessary (e.g., lesion studies)Modulated here? Or there?MVPA vs. SpecificityResting State: Function vs. Physiology-86-BART ProcedureComputer 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

Earnings ($)MIN MAXNot Just PsychiatryOther syndromes with complex etiology and overlapping symptoms

E.g., Diabetes, hypercholesterolemia, hypertension

Clinical presentation: Patient complains of fatigue; whats the Dx?

Differential Diagnosis: challenges (stress test) and assays to determine a primary etiology and Dx

E.g., glucose tolerance test, serum cholesterol, BP

Similar symptoms, different endophenotypes, different genetic underpinnings

Gottesman & Gould Amer J Psychiatry 2003

Promises to enhance:

Etiology (cause)What is the proximal biological cause(s) of the disorder/T&P?

Nosology (Dx)Unlike many physical diseases, psychiatric disorders/T&P are defined by symptoms not pathophysiology; understanding the etiology 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 reflect similar vs. different causes?E.g., growing biological evidence that SZ and BPD are related

PrognosisIf we understood the etiology, we could better predict the likely outcome (cf. Moffitt)

Treatment (Personalized or Precision Medicine)Most disorders resist treatment; extant treatments work for a subset of patientsIf we understood the etiology, we could target treatments, enhancing cost/benefit

Early intervention for high-risk populations (e.g., cholesterol test statins)Screen identify intervene before the deleterious secondary consequences emergeThe PromiseMRI vs. fMRI

fMRI Simplified

TimeCondition 1Condition 2~2s...~ 5 minTimefMRISignalIntensityROI Time CourseCondition

Simplified fMRI experiment, we take multiple volumes of BASELINE, and then turn on some visual stimulation for the next 3 volumes CONDITION 2. repeat.

All fMRI data is: an intensity value of every voxel every time point , plot Time Course

perform our analysis on., and colorful blobs are what end up in publications*When a brain region is working, it requires more oxygen, the signal in those tissues rises and falls in a way that is correlated to the testing paradigm.. As we can see in the time course

94fMRI Setup

95

96