Circular analysis in systems neuroscience – with particular attention to cross-subject correlation mapping Nikolaus Kriegeskorte Laboratory of Brain and.

Circular analysis in systems neuroscience– with particular attention to cross-subject

correlation mappingNikolaus Kriegeskorte

Laboratory of Brain and Cognition, National Institute of Mental Health

• Chris I Baker

• W Kyle Simmons

• Patrick SF Bellgowan

• Peter Bandettini

Collaborators

Part 1General introduction to circular analysis in systems neuroscience(synopsis of Kriegeskorte et al. 2009)

Part 2Specific issue: selection bias incross-subject correlation mapping(following up on Vul et al. 2009)

Overview

data results

analysis

data results

data results

analysis

data results

analysis

assumptions

data results

analysis

assumptions

Circular inference

data results

analysis

assumptions

Circular inference

data results

analysis

assumptions

How do assumptions tinge results?

Elimination(binary selection)

Weighting(continuous selection)

Sorting(multiclass selection)

– Through variants of selection!

data results

analysis

assumptions:selection criteria

Elimination(binary selection)

Example 1Pattern-information analysis

Experimental design

“Animate?” “Pleasant?”

ST

IMU

LU

S(o

bje

ct c

ateg

ory

)TASK

(property judgment)Simmons et al. 2006

• define ROI by selecting ventral-temporal voxels for which any pairwise condition contrast is significant at p<.001 (uncorr.)

• perform nearest-neighbor classificationbased on activity-pattern correlation

• use odd runs for trainingand even runs for testing

Pattern-information analysis

0

0.5

1d

eco

din

g a

ccu

racy

task

(judged property

)

stimulus

(object

category)

Results

chance level

fMRI data

using all datato select ROI voxels

using onlytraining data

to select ROI voxels

data from Gaussianrandom generator

0

0.5

1

0

0.5

1

0

0.5

1

0

0.5

1

dec

od

ing

acc

ura

cy

chance level

taskstim

ulus

...but we used cleanly independenttraining and test data!

?!

Conclusion for pattern-information analysis

The test data must not be used in either...• training a classifier or• defining the ROI

continuous weighting

binary weighting

Data selection is key to many conventional analyses.

Can it entail similar biases in other contexts?

Example 2Regional activation analysis

ROI definition is affected by noise

true region

overfitted ROI

RO

I-av

erag

eac

tiva

tio

n

overestimated effect

independent ROI

Data sorting

data results

analysis

assumptions:sorting criteria

Set-average tuning curves

stimulus parameter (e.g. orientation)

res

po

ns

e

...for data sorted by tuning

noise data

RO

I-av

erag

efM

RI r

esp

on

se

A B C Dcondition

Set-average activation profiles...for data sorted by activation

noise data

To avoid selection bias, we can...

...perform a nonselective analysis

OR

...make sure that selection and results statistics are independent under the null hypothesis,

because they are either:• inherently independent• or computed on independent data

e.g. independent contrasts

e.g. whole-brain mapping(no ROI analysis)

Does selection by an orthogonal contrast vector ensure unbiased analysis?

ROI-definition contrast: A+B

ROI-average analysis contrast: A-B

cselection=[1 1]T

ctest=[1 -1]T

orthogonal contrast vectors

Does selection by an orthogonal contrast vector ensure unbiased analysis?

not sufficient

contrastvector

The design and noise dependencies matter.design noise dependencies

– No, there can still be bias.

still not sufficient

Circular analysis

Pros

• highly sensitive

• widely accepted (examples in all high-impact journals)

• doesn't require independent data sets

• grants scientists independencefrom the data

• allows smooth blending of blind faith and empiricism

Cons

Circular analysis

Pros

• highly sensitive

• widely accepted (examples in all high-impact journals)

• doesn't require independent data sets

• grants scientists independencefrom the data

• allows smooth blending of blind faith and empiricism

Cons

Circular analysis

Pros

• highly sensitive

• widely accepted (examples in all high-impact journals)

• doesn't require independent data sets

• grants scientists independencefrom the data

• allows smooth blending of blind faith and empiricism

Cons• [can’t think of any right now]

Pros• the error that beautifies results

• confirms even incorrect hypotheses

• improves chances ofhigh-impact publication

Part 2Specific issue: selection bias in

cross-subject correlation mapping(following up on Vul et al. 2009)

Motivation

Vul et al. (2009) posed a puzzle:

Why are the cross-subject correlations found in brain mapping so high?

Selection bias is one piece of the puzzle.

But there are more pieces and we have yet to put them all together.

Overview

• List and discuss six pieces of the puzzle.(They don't all point in the same direction!)

• Suggest some guidelines for good practice.

Six pieces synopsis1. Cross-subject correlation estimates are very noisy.

2. Bin or within-subject averaging legitimately increases correlations.

3. Selecting among noisy estimates yields large biases.

4. False-positive regions are highly likely for a whole-brain mapping thresholded at p<.001, uncorrected.

5. Reported correlations are high, but not highly significant.

6. Studies have low power for finding realistic correlations in the brain if multiple testing is appropriately accounted for.

Vul et al. 2009

,,,,

population

The geometric mean of the reliability is an upper boundon the population correlation.The reliabilities provide no bound

on the sample correlation.

noise-freecorrelation

Sample correlationsacross small numbers of subjects

are very noisy estimatesof population correlations.

Piece 1

0.65

co

rre

lati

on

10 subjects

95%-confidenceinterval

Cross-subject correlation estimatesare very noisy

Cross-subject correlation estimatesare very noisy

The more we average(reducing noise but not signal),the higher correlations become.

Piece 2

Bin-averaging inflates correlations

Bin-averaging inflates correlations

Subjects are like bins...

For each subject, all data is averaged to give one number.

Take-home message

Cross-subject correlation estimates are expected to be...• high (averaging all data for each subject)• noisy (low number of subjects)

So what's Ed fussing about?We don't need selection bias to explain the high correlations, right?

Selecting the maximumamong noisy estimates

yields large selection biases.

Piece 3

Expected maximum correlationselected among null regions

exp

ecte

d m

axim

um

co

rrel

atio

n

16 subjects

bias

False-positive regions are likely to be found in whole-brain mapping

using p<.001, uncorrected.

Piece 4

Mapping with p<.001, uncorrectedGlobal null hypothesis is true

(population correlation = 0 in all brain locations)

Reported correlations are high,but not highly significant.

Piece 5

Reported correlations are high,but not highly significant

p<0.00001p<0.001 p<0.01p<0.05one-sided

two-sided

correlation thresholds as a functionof the number of subjects

Reported correlations are high,but not highly significant

p<0.00001p<0.001 p<0.01p<0.05one-sided

two-sided

correlation thresholds as a functionof the number of subjects

Reported correlations are high,but not highly significant

p<0.00001p<0.001 p<0.01p<0.05one-sided

two-sided

correlation thresholds as a functionof the number of subjects

(assuming each study reportsthe maximum of 500

independent brain locations)

What correlations would we expectunder the global null hypothesis?

Reported correlations are high,but not highly significant

p<0.00001p<0.001 p<0.01p<0.05one-sided

two-sided

(assuming each study reports the max.of 500 independent brain locations)

What correlations would we expectunder the global null hypothesis?

Most of the studies have low powerfor finding realistic correlations

with whole-brain mappingif multiple testing is appropriately

accounted for.

Piece 6

see also: Yarkoni 2009

Numbers of subjectsin studies reviewed by Vul et al. (2009)

nu

mb

er o

f co

rrel

atio

ns

esti

mat

es

number of subjects4 8 16 36 60 100

po

wer

In order to find a single region with across-subject correlation of 0.7 in the brain...

...we would needabout 36 subjects

16 subjects

po

wer

In order to find a single region with across-subject correlation of 0.7 in the brain...

...we would needabout 36 subjects

16 subjects

Take-home message

Whole-brain cross-subject correlation mapping

with 16 subjects

does not work.

Need at least twice as many subjects.

ConclusionsUnless much larger numbers of subjects are used,

whole-brain cross-subject correlation mapping suffers from either:– very low power to detect true regions

(if we carefully to correct for multiple comparisons)– very high rates of false-positive regions

(otherwise)

If analysis is circular, selection bias is expected to be high here (because selection occurs among noisy estimates).

...in other words,it doesn't work.

Suggestions• Design study to have enough power to detect realistic

correlations. (Need either anatomical restrictions or large numbers of subjects.)

• Consider studying trial-to-trial rather than subject-to-subject effects.

• Correct for multiple testing to avoid false positives.

• Avoid circularity: Use leave-one-subject out procedure to estimate regional cross-subject correlations.

• Report correlation estimates with error bars.