cognitive challenge summary analysis of phase ii data –240 sessions analyzed using bputil...

Cognitive Challenge Summary

• Analysis of Phase II data– 240 sessions analyzed using BPutil pipeline,

BIRN QA and Eventstats– ROI analysis of MFG, IPL, and STG– Comparison of FIPS and BPutil for Iowa data

• New task development– Emotional oddball (event-related)– Emotional executive (blocked)– Movie clips

Constant Fixation

15s

………

.5s 6-15 s 6-15 s

1000Hz 1200Hz

Slice Depth: Z=-11ControlsPatients

Controls:N=41, p<1x10-10

Patients:N=44, p<1x10-5

Vis

it 1

Vis

it 2

MFG, Right Hemisphere, Visit 1

MFG, Right Hemisphere, Visit 2

Voxel Counts by Visit and ROI

Time-Course by Visit and Diagnosis in MFG

Auditory Oddball

Auditory Oddball Summary

• Robust activations of dlPFC, IPL, STG, insula, cingulate, thalamus, and motor cortex– In all locations, controls > patients

• Strong visual cortex activation suggests that infrequent tones evoke an orienting response– Brainstem activation is also suggestive, but

less visible in count conditions

Learn

Probes (14 Total)

0 2 1 3 8 9 7 2 4 . . .7 * 5 * 4 4 6 5 1 . . .* * 9 * * 3 9 2 8 . . .

Prompt

Learn

Learn

…

Encoding

…

4s-20sFixation

0s 8s6s4s2s 10s … … 46s

4s-20sFixation

5 items

3 items

1 item

IPS SIRP

MFG SIRP

Preliminary SIRP Summary

• Strong co-activation of regions also activated by Auditory Oddball (except STG)

• At low and medium load, patients > controls during probe intervals

• At high load, patients ~= controls

MFG

IFG

STG

IPS Encode

IPS Probe

MFG Encode

MFG Probe

Cognitive Challenge Summary

New task development– Emotional oddball (event-related)– Emotional executive (blocked)– Movie clips

Dorsal executive control system

LC Amyg

Th BGVTA

Raphe vmPFC

dlPFC

Amyg

IPS

vlPFC

OFC

Ventral affective processing system

TargetsStandard NovelsNeutral Emotional

84% 8% 4% 4%

Emotional Distracter Task

Yamasaki, LaBar, McCarthy, PNAS, 2002

...

......

......

Emotional Distracter Task

Sad Stimulus Distracter Task

Wang, LaBar, McCarthy, Biol Psychiat, in press

Emotional Distracter

Emotional Distractor TaskMiddle Frontal Gyrus (anterior)

-0.10%

-0.05%

0.00%

0.05%

0.10%

0.15%

-3 0 3 6 9 12 15

Emotional novel

Neutral novel

Target

-0.10%

-0.05%

0.00%

0.05%

0.10%

0.15%

0.20%

0.25%

0.30%

-3 0 3 6 9 12 15

Emotional novel

Neutral novel

Target

Emotional Distractor TaskAmygdala

Emotional Distracter

Anterior MFG

Posterior IFG

-0.10%

-0.05%

0.00%

0.05%

0.10%

0.15%

-3 0 3 6 9 12 15

Emotional novel

Neutral novel

Target

-0.10%

-0.05%

0.00%

0.05%

0.10%

0.15%

0.20%

-3 0 3 6 9 12 15

Emotional novel

Neutral novel

Target

Emotional Distracter Task

Phase I (15s) Phase II (14s)

Memoranda Probe

3.5s 1.5s

Novel stimuli (6s)

+ ++

Emotional Distracters and Working Memory

Dolcos and McCarthy, J Neurosci, 2006

Increased distractibility to emotional distracters linked to differential patterns of activity in the dorsal executive vs. ventral affective neural systems.

MR

sig

nal c

hang

e (

%)

-0.2

-0.1

0.1

0.3 dlPFC

MR

sig

nal c

hang

e (

%)

-0.2

-0.1

0.1

0.3

0.4

AMY

0.5

0.6

0.7

0.8

Cor

rect

ed R

ecog

nitio

n S

core

s

Scrambled Scene DistractersNeutral Scene DistractersEmotional Scene Distracters

Amygdala activity to emotional distracters

5.5 6.75 8-0.1

0.05

0.2

0.35

-2 2 6 10 14 18 22 26

time (sec)

Scrambled Neutral Emotional

MR

sig

na

l ch

an

ge

(%

)

-0.2

-0.1

0.1

0.3

0.4

0.6

-2 2 6 10 14 18 22 26

-0.2

-0.1

0.1

0.3

0.4

0.6

-2 2 6 10 14 18 22 26

-0.2

-0.1

0.1

0.3

0.4

0.6

-2 2 6 10 14 18 22 26

-0.2

-0.1

0.1

0.3

0.4

0.6

-2 2 6 10 14 18 22 26

-0.1

0.1

0.3

0.5

0.7

-2 2 6 10 14 18 22 26

-0.1

0.1

0.3

0.5

0.7

-2 2 6 10 14 18 22 26

-0.1

0.1

0.3

0.5

0.7

-2 2 6 10 14 18 22 26

-0.1

0.1

0.3

0.5

0.7

-2 2 6 10 14 18 22 26

-0.6

-0.4

-0.2

0.1

0.3

-2 2 6 10 14 18 22 26

-0.6

-0.4

-0.2

0.1

0.3

-2 2 6 10 14 18 22 26

-0.6

-0.4

-0.2

0.1

0.3

-2 2 6 10 14 18 22 26

-0.6

-0.4

-0.2

0.1

0.3

-2 2 6 10 14 18 22 26

-0.2

0.2

0.6

0.9

1.3

-2 2 6 10 14 18 22 26

-0.2

0.2

0.6

0.9

1.3

-2 2 6 10 14 18 22 26

-0.2

0.2

0.6

0.9

1.3

-2 2 6 10 14 18 22 26

-0.2

0.2

0.6

0.9

1.3

-2 2 6 10 14 18 22 26

Negative DistracterMeaningless Distracter Neutral Distracter

Emotional Oddball

• Ayse Belger’s group collected data

• 10 CONTROLS, 11 SCZ PATIENTS

MFGCONTROLS SCZ PATIENTS

CONTROLS SCZ PATIENTSIfg/BA 47

CONTROLS SCZ PATIENTSOF

CONTROLS SCZ PATIENTSFFG

CONTROLS SCZ PATIENTSPosterior Parietal

CONTROLS SCZ PATIENTSAMYGDALA

0s 10s 30s20s 40s 60s50s 80s70s

Neutral BlockExecutive Block

Fixation

Emotional Block

…

Emotional Executive Task, Block-Design

……

……

Scrambled Images

…… ……

MFG

IFG

vmPFC

Blocked Emotional Executive

Left MFG

-0.15

-0.10

-0.05

0.00

0.05

0.10

0.15

0.20

0.25

-4 -2 0 2 4 6 8 10 12 14 16 18 20 22 24

Emotional

Neutral

Target

left MFG

Left IFG

-0.10

-0.05

0.00

0.05

0.10

0.15

0.20

0.25

0.30

0.35

-4 -2 0 2 4 6 8 10 12 14 16 18 20 22 24

Emotional

Neutral

Target

right IFG

Inferior Frontal Gyri

vmPFC

vmPFC

-0.20

-0.15

-0.10

-0.05

0.00

0.05

0.10

0.15

0.20

0.25

-4 -2 0 2 4 6 8 10 12 14 16 18 20 22 24

Emotional

Neutral

Target

vmPFC

Inferior Parietal Lobule and VOTC

Left Parietal

-0.10

-0.05

0.00

0.05

0.10

0.15

0.20

-4 -2 0 2 4 6 8 10 12 14 16 18 20 22 24

Emotional

Neutral

Target

left Parietal

Left VOTC

-0.20

-0.10

0.00

0.10

0.20

0.30

0.40

0.50

-4 -2 0 2 4 6 8 10 12 14 16 18 20 22 24

Emotional

Neutral

Target

left VOTC

CONTROLS SCZ PATIENTSINSULA

CONTROLS SCZ PATIENTSACG

CONTROLS SCZ PATIENTSThalamus

CONTROLS SCZ PATIENTSCaudate