Sensory

and

cognitive

mechanisms

of

change

detection

in

the

context

of

speech

The

aim

of

this

study

was

to

dissociate

the

contributions

of

memory-based

-LRB-

cognitive

-RRB-

and

adaptation-based

-LRB-

sensory

-RRB-

mechanisms

underlying

deviance

detection

in

the

context

of

natural

speech

Twenty

healthy

right-handed

native

speakers

of

English

participated

in

an

event-related

design

scan

in

which

natural

speech

stimuli

de

-LRB-

deh

-RRB-

and

deI

-LRB-

day

-RRB-

-LRB-

te

-LRB-

teh

-RRB-

and

teI

-LRB-

tay

-RRB-

served

as

standards

and

deviants

within

functional

magnetic

resonance

imaging

event-related

oddball

paradigm

designed

to

elicit

the

mismatch

negativity

component

Thus

oddball

blocks

could

involve

either

a

word

deviant

-LRB-

day

-RRB-

resulting

in

a

word

advantage

effect

or

a

non-word

deviant

-LRB-

deh

or

tay

-RRB-

We

utilized

an

experimental

protocol

controlling

for

refractoriness

similar

to

that

used

previously

when

deviance

detection

was

studied

in

the

context

of

tones

Results

showed

that

the

cognitive

and

sensory

mechanisms

of

deviance

detection

were

located

in

the

anterior

and

posterior

auditory

cortices

respectively

as

was

previously

found

in

the

context

of

tones

The

cognitive

effect

that

was

most

robust

for

the

word

deviant

diminished

in

the

oddball

condition

In

addition

the

results

indicated

that

the

lexical

status

of

the

speech

stimulus

interacts

with

acoustic

factors

exerting

a

top-down

modulation

of

the

extent

to

which

novel

sounds

gain

access

to

the

subject

's

awareness

through

memory-based

processes

Thus

the

more

salient

the

deviant

stimulus

is

the

more

likely

it

is

to

be

released

from

the

effects

of

adaptation

exerted

by

the

posterior

auditory

cortex

Introduction

The

mismatch

negativity

-LRB-

MMN

-RRB-

component

of

the

event-related-potentials

-LRB-

ERPs

-RRB-

is

assumed

to

reflect

the

operation

of

a

pre-attentive

memory-based

comparison

mechanism

-LRB-

e.g.

Näätänen

et

al.

-RRB-

For

a

wide

range

of

stimuli

there

is

evidence

that

the

MMN

is

elicited

by

a

cognitive

mechanism

based

on

auditory

sensory

memory

that

compares

between

the

incoming

deviant

stimulus

and

the

standard

template

-LRB-

Näätänen

and

Alho

Näätänen

et

al.

-RRB-

The

contrasting

view

is

that

attention

switch

to

novel

sounds

is

based

on

the

transient

frequency-specific

adaptation

of

posterior

auditory-cortex

feature-detector

neurons

-LRB-

Desimone

Näätänen

Ulanovsky

et

al.

Jääskeläinen

et

al.

-RRB-

Specifically

it

has

been

suggested

that

MMN

arises

because

of

selective

adaptation

of

the

response

by

preceding

standard

stimuli

-LRB-

sensory

component

-RRB-

leading

to

its

attenuation

This

attenuation

is

interpreted

in

terms

of

neural

refractoriness

-LRB-

Näätänen

-RRB-

Thus

this

account

of

MMN

elicitation

does

not

rely

on

memory

representations

and

is

sensorial

in

nature

Previous

research

has

shown

that

the

MMN

is

sensitive

to

acoustic

as

well

as

to

phonetic

attributes

of

phonemes

-LRB-

e.g.

Tampas

et

al.

-RRB-

Furthermore

it

was

demonstrated

that

the

MMN

reflects

the

activation

of

memory

networks

for

language

sounds

and

spoken

words

-LRB-

e.g.

Pulvermüller

et

al.

Shtyrov

et

al.

Pulvermüller

and

Shtyrov

-RRB-

the

latter

referred

to

as

the

word

advantage

effect

-LRB-

Pettigrew

et

al.

-RRB-

The

design

of

the

current

functional

magnetic

resonance

imaging

-LRB-

fMRI

-RRB-

study

was

a

combination

of

modified

protocols

utilized

in

previous

studies

-LRB-

i.e.

Pettigrew

et

al.

Opitz

et

al.

-RRB-

that

enabled

to

disentangle

cognitive

and

sensory

contributions

to

change

detection

-LRB-

Opitz

et

al.

Maess

et

al.

-RRB-

when

the

deviant

stimulus

could

be

either

a

word

-LRB-

day

-RRB-

resulting

in

the

word

advantage

effect

or

a

non-word

deviant

-LRB-

deh

or

tay

-RRB-

We

hypothesized

that

the

sensory

component

will

be

located

bilaterally

in

regions

posterior

to

Heschl

's

gyrus

-LRB-

HG

-RRB-

including

the

posterior

superior

temporal

gyrus

-LRB-

STG

-RRB-

regardless

of

the

identity

of

the

deviant

stimulus

-LRB-

deh

day

or

tay

-RRB-

This

component

relies

on

frequency-specific

neurons

in

the

auditory

cortex

responsible

for

the

repetition-related

decrement

of

and

its

counterpart

the

-LRB-

Romani

et

al.

Jääskelainen

et

al.

Opitz

et

al.

-RRB-

Moreover

it

was

shown

that

the

region

posterior

to

HG

is

broadly

tuned

with

respect

to

phonetic

features

-LRB-

Ahveninen

et

al.

-RRB-

In

contrast

it

was

shown

that

areas

anterior

to

HG

process

sound-identity

cues

such

as

speech

-LRB-

Binder

et

al.

Obleser

et

al.

Ahveninen

et

al.

-RRB-

and

pitch

-LRB-

Warren

and

Griffiths

-RRB-

Therefore

we

assumed

that

the

cognitive

component

which

involves

the

representation

of

the

current

auditory

event

-LRB-

Schröger

-RRB-

will

differentiate

between

the

deviant

word

-LRB-

day

-RRB-

and

the

non-words

-LRB-

teh

and

tay

i.e.

the

word

advantage

effect

-RRB-

and

will

be

located

anterior

to

HG

Methods

Subjects

Twenty

right-handed

adult

healthy

subjects

native

speakers

of

English

women

and

men

participated

in

the

study

Subjects

ranged

in

age

from

to

All

subjects

gave

informed

consent

to

participate

in

the

study

Experimental

protocol

The

procedure

is

a

modification

of

the

one

used

by

Opitz

et

al.

-LRB-

-RRB-

Each

subject

participated

in

functional

imaging

runs

The

speech

stimuli

were

grouped

into

two

types

of

blocks

oddball

and

control

In

the

first

type

of

block

the

oddball

block

deviant

exemplars

occurred

quasi-randomly

embedded

within

standard

stimuli

so

that

the

frequency

of

occurrence

throughout

the

block

was

balanced

among

exemplars

The

interval

between

two

successive

deviants

varied

quasi-randomly

with

gaps

of

or

standards

with

the

constraint

that

gap

size

was

balanced

throughout

the

block

In

the

Oddball

blocks

deviants

appeared

times

out

of

a

total

of

stimuli

-LRB-

probability

of

occurrence

-RRB-

In

the

control

blocks

the

same

physical

deviants

and

standards

as

in

the

oddball

blocks

-LRB-

deviant-counterparts

and

standard-counterparts

respectively

-RRB-

occurred

quasi-randomly

while

deviants

were

constrained

by

the

same

spacing

rule

mentioned

above

However

each

of

the

control

blocks

contained

eight

different

equiprobable

stimuli

including

the

deviant

and

standard

counterparts

Thus

in

the

control

runs

the

seven

stimuli

beside

the

deviant-counterpart

served

as

filler

or

contextual

stimuli

which

were

added

to

the

sequence

so

that

the

deviant-counterpart

will

appear

at

the

same

probability

as

any

other

stimulus

in

the

sequence

Each

of

the

stimuli

in

the

control

block

-LRB-

a

total

of

eight

different

stimuli

-RRB-

repeated

times

and

appeared

with

equal

probability

which

was

identical

to

that

of

the

deviants

in

the

oddball

block

-LRB-

-RRB-

There

were

three

blocks

of

each

type

-LRB-

oddball

control

-RRB-

Each

block

was

repeated

twice

In

total

blocks

of

approximately

min

each

were

randomly

presented

for

each

subject

within

a

session

Three

non-words

de

deh

te

teh

and

teI

tay

and

one

word

deI

day

were

recorded

from

a

male

native

English

speaker

in

a

sound-proof

chamber

These

stimuli

comprised

the

following

standard-deviant

pairs

that

resulted

in

the

three

oddball

runs

-LRB-

-RRB-

deh

-LRB-

standard

-RRB-

day

-LRB-

deviant

-RRB-

-LRB-

-RRB-

day

deh

and

-LRB-

-RRB-

teh

tay

Thus

deh

and

day

swapped

their

roles

as

standard

and

deviant

in

the

second

oddball

block

whereas

the

third

block

controlled

for

the

acoustic

change

associated

with

the

transition

from

a

monophthong

-LRB-

e

-RRB-

to

a

diphthong

-LRB-

eI

-RRB-

occurring

in

the

first

standard-deviant

pair

Additional

four

stimuli

pe

peh

peI

pay

be

beh

and

beI

bay

together

with

the

previous

four

mentioned

above

were

embedded

within

three

control

runs

each

containing

a

deviant-counterpart

either

day

deh

or

tay

appearing

with

the

same

probability

and

obeying

the

same

spacing

rule

as

in

the

oddball

blocks

Three

exemplars

for

each

stimulus

-LRB-

e.g.

-RRB-

were

selected

-LRB-

out

of

a

pool

of

recordings

per

stimulus

-RRB-

on

the

basis

of

acoustic

similarity

-LRB-

see

Table

for

the

values

of

the

lowest

three

formants

-RRB-

The

parameters

that

were

used

to

choose

similar

exemplars

for

each

stimulus

included

the

shape

of

the

spectrogram

at

the

voice

onset

vowel

durations

pitch

and

formant

values

-LRB-

Hz

-RRB-

of

the

first

three

formants

at

the

beginning

-LRB-

ca.

ms

-RRB-

and

end

-LRB-

ca.

ms

-RRB-

of

the

e

segment

-LRB-

ca.

ms

duration

-RRB-

of

each

stimulus

The

stimuli

were

truncated

to

ms

and

normalized

to

the

same

loudness

level

by

using

Adobe

Audition

trial

version

software

package

Spectral

analysis

of

the

stimuli

was

conducted

by

PRAAT

software

version

-LRB-

-RRB-

Table

and

frequencies

of

the

main

speech

stimuli

-LRB-

in

Hz

-RRB-

onset

of

end

of

onset

of

end

of

onset

of

end

of

pitch

and

indicate

the

frequencies

-LRB-

Hz

-RRB-

of

the

first

second

and

third

formants

respectively

and

frequencies

are

given

for

the

beginning

and

end

of

the

e

segment

common

to

the

four

main

stimuli

of

the

study

The

mean

frequency

across

the

length

of

the

common

e

section

is

also

indicated

The

reason

for

using

three

tokens

for

each

consonant-vowel

stimulus

was

to

control

as

much

as

possible

for

acoustic

factors

other

than

those

inherent

in

the

structure

of

the

stimulus

which

could

confound

the

elicitation

of

a

deviant

response

Using

three

different

exemplars

for

each

consonant-vowel

-LRB-

CV

-RRB-

stimulus

diminished

the

likelihood

of

a

contingency

developing

between

a

specific

deviant-standard

pair

because

of

an

uncontrolled

acoustic

facet

associated

with

either

the

deviant

or

the

standard

As

could

be

seen

in

Table

the

frequency

parameters

across

homogeneous

exemplars

-LRB-

i.e.

the

three

representatives

of

the

same

CV

-RRB-

were

very

similar

to

each

other

In

addition

the

ratio

in

teh

and

tay

is

similar

to

the

ratio

in

deh

and

day

respectively

Thus

the

comparison

between

the

responses

to

teh

and

tay

could

serve

as

a

suitable

control

for

the

latter

pair

-LRB-

Jacobsen

et

al.

-RRB-

The

speech

stimuli

appeared

randomly

within

each

block

and

their

occurrence

was

balanced

throughout

the

block

for

standards

as

well

as

deviants

Stimuli

were

presented

with

an

SOA

-LRB-

stimulus

onset

asynchrony

-RRB-

of

s

at

dB

SPL

via

headphones

to

subjects

with

ear-plugs

-LRB-

see

Table

for

an

example

of

a

control

and

oddball

blocks

in

case

of

the

deh

day

contrast

-RRB-

Stimulus

presentation

was

carried

out

by

E-Prime

-LRB-

-RRB-

-LRB-

Psychology

Software

Tools

-RRB-

Table

Oddball

and

control

sequences

for

the

deh

-LRB-

standard

-RRB-

day

-LRB-

deviant

-RRB-

-LRB-

A

-RRB-

-LRB-

B

-RRB-

-LRB-

C

-RRB-

-LRB-

D

-RRB-

A

D

indicate

the

stimuli

contrasted

to

evaluate

the

deviance

effect

-LRB-

B

vs.

A

-RRB-

the

cognitive

effect

-LRB-

B

vs.

D

-RRB-

and

the

sensory

effect

-LRB-

A

vs.

C

-RRB-

The

numbers

attached

to

the

stimuli

indicate

different

exemplars

of

the

same

CV

stimulus

Each

contrast

was

computed

across

all

exemplars

of

a

specific

CV

In

the

oddball

sequence

serves

as

a

deviant

and

functions

as

a

standard

In

the

control

condition

is

a

standard

control

counterpart

and

serves

as

a

deviant

control

counterpart

Contrasting

oddball

deviants

and

standards

with

the

corresponding

stimuli

in

control

runs

-LRB-

deviant

and

standard

counterparts

-RRB-

allowed

disentangling

the

two

mechanisms

of

deviance

detection

namely

the

sensory

one

based

on

refractoriness

-LRB-

Näätänen

and

Picton

-RRB-

from

the

cognitive

one

based

on

memory-based

processes

-LRB-

Näätänen

Näätänen

and

Winkler

-RRB-

The

subjects

were

instructed

to

count

every

stimulus

press

a

button

when

they

reached

and

then

reset

their

count

and

restart

counting

from

zero

again

This

task

was

chosen

to

control

for

a

possible

contamination

by

and

ERP-components

which

are

elicited

when

deviants

are

being

discriminated

from

standards

-LRB-

Donchin

et

al.

Opitz

et

al.

-RRB-

Behavioral

assessment

of

discrimination

between

stimuli

Thirteen

subjects

-LRB-

out

of

the

participating

in

the

study

-RRB-

rated

the

stimuli

in

a

behavioral

session

performed

outside

of

the

magnet

The

behavioral

assessment

was

carried

out

in

a

different

session

Stimuli

were

presented

simultaneously

with

recorded

MR

scanner

noise

The

stimuli

and

the

scanner

noise

were

both

presented

in

dB

SPL

which

was

a

convenient

hearing

level

for

both

the

stimuli

and

the

noise

presented

together

Subjects

were

presented

with

triplets

comprised

of

stimuli

containing

e

and

eI

In

each

block

triplets

were

presented

separated

by

a

s

interval

of

silence

allowing

the

subject

to

respond

The

stimuli

were

the

same

as

those

presented

in

the

fMRI

experiment

There

were

several

patterns

of

triplet

presentation

in

each

block

as

follows

There

were

three

triplets

in

which

day

was

presented

first

followed

by

two

deh

s

three

triplets

in

which

day

was

presented

last

and

preceded

by

two

deh

s

three

triplets

where

deh

was

presented

first

followed

by

two

day

s

and

three

triplets

were

deh

was

last

and

preceded

by

two

day

s

In

addition

there

were

three

triplets

in

which

day

deh

and

tay

each

appeared

in

the

middle

position

respectively

while

the

neighboring

stimuli

-LRB-

in

the

first

and

third

positions

-RRB-

where

either

the

eI

or

e

counterparts

-LRB-

i.e.

deh

day

deh

day

deh

day

and

teh

tay

teh

-RRB-

Overall

four

blocks

of

triplets

each

were

presented

to

the

subjects

The

order

of

triplets

was

randomized

within

each

block

The

three

different

exemplars

representing

each

CV

stimulus

were

balanced

across

the

four

blocks

The

subjects

were

required

to

indicate

the

outlier

in

each

triplet

by

pressing

the

key

-LRB-

either

or

on

the

keyboard

-RRB-

that

corresponded

to

the

position

of

the

outlier

in

the

triplet

The

outliers

were

assigned

mainly

to

the

extreme

positions

-LRB-

or

-RRB-

in

the

triplet

to

simulate

more

closely

the

oddball

design

in

which

the

deviant

is

surrounded

by

repetitive

standards

The

trials

with

the

outlier

appearing

in

the

middle

position

were

introduced

to

minimize

the

probability

of

guessing

the

identity

of

the

third

stimulus

in

the

triplet

after

hearing

the

first

two

which

were

non-identical

Thus

subjects

could

guess

the

identity

of

the

outlier

with

more

confidence

only

after

hearing

two

identical

stimuli

in

a

row

Data

acquisition

parameters

Data

was

collected

on

a

Siemens

Trio

scanner

Each

study

began

with

two

localizers

a

three-plane

localizer

and

a

multiple-slice

sagittal

localizer

These

were

followed

by

the

acquisition

of

twenty-five

mm

axial

slices

-LRB-

TR

ms

TE

ms

flip

angle

FOV

mm

acquisition

matrix

-RRB-

For

each

subject

functional

imaging

scans

were

collected

with

slices

in

the

same

locations

as

the

anatomical

data

Functional

images

were

recorded

using

a

gradient-echo

EPI

sequence

-LRB-

TR

ms

TE

ms

flip

angle

FOV

mm

acquisition

matrix

-RRB-

Each

functional

run

involved

the

acquisition

of

volumes

with

twenty-five

axial

slices

Images

were

converted

to

analyze

format

and

the

first

ten

volumes

of

each

functional

series

were

removed

to

account

for

the

approach

to

steady-state

magnetization

leaving

volumes

for

analysis

Image

analysis

Preprocessing

First

using

sinc

interpolation

the

data

from

each

slice

were

adjusted

for

slice

acquisition

time

and

then

all

data

were

motion

corrected

using

for

six

rigid

body

motions

-LRB-

displacement

in

the

x

y

z

direction

and

rotation

for

pitch

roll

yaw

-RRB-

Flags

were

set

for

de-correlation

and

masking

so

a

pixel

was

set

to

zero

for

every

time

point

if

it

moved

outside

the

volume

Functional

image

data

were

motion

corrected

by

realigning

the

time

sequence

imaging

to

the

first

image

in

the

middle

run

of

the

sequence

using

Individual

subject

data

-LRB-

responses

to

the

deviants

standards

and

control

stimuli

-RRB-

were

analyzed

using

a

General

Linear

Model

on

each

voxel

in

the

entire

brain

volume

-LRB-

Rajeevan

et

al.

-RRB-

The

data

were

normalized

to

a

signal

measure

of

and

were

spatially

smoothed

with

a

mm

Gaussian

kernel

to

account

for

variations

in

the

location

of

activation

across

participants

The

output

maps

are

normalized

beta-maps

which

are

in

the

acquired

space

-LRB-

mm

mm

mm

-RRB-

To

take

these

data

into

a

common

reference

space

three

registrations

were

calculated

within

the

Yale

BioImage

Suite

software

package

-LRB-

Papademetris

et

al.

-RRB-

using

the

intensity-only

component

of

the

method

reported

in

Papademetris

et

al.

-LRB-

-RRB-

The

first

registration

performs

a

linear

registration

between

the

individual

subject

raw

functional

image

and

that

subject

's

anatomical

image

The

anatomical

image

was

then

linearally

registered

to

the

individual

's

anatomical

image

The

differs

from

the

in

that

it

has

a

mm

resolution

whereas

the

z-dimension

is

set

by

slice-thickness

and

its

x

y

dimensions

are

set

by

voxel

size

Finally

a

non-linear

registration

is

computed

between

the

individual

anatomical

image

and

a

reference

image

The

reference

brain

used

was

the

Brain

-LRB-

Holmes

et

al.

-RRB-

commonly

applied

in

SPM

and

other

software

packages

All

three

registrations

were

applied

sequentially

to

the

individual

normalized

beta-maps

to

bring

all

data

into

the

common

reference

space

Statistical

analyses

We

used

a

two-stage

random-effects

model

to

analyze

the

data

In

the

first

stage

statistical

maps

were

calculated

in

the

comparison

of

interest

for

each

subject

as

described

above

In

the

second

stage

across

subject

analyses

were

conducted

and

the

distribution

of

the

individual

subjects

statistics

were

tested

for

significance

Within

subject

analyses

For

each

of

the

three

deviants

-LRB-

deh

day

and

tay

-RRB-

the

following

six

types

of

maps

were

calculated

-LRB-

-RRB-

Deviant

maps

computed

from

oddball

runs

extracting

the

response

to

low

frequency

stimuli

-LRB-

-RRB-

Standard

maps

computed

from

oddball

runs

extracting

the

response

to

high

frequency

stimuli

-LRB-

-RRB-

Deviant

control

maps

computed

from

control

runs

extracting

the

response

to

the

same

physical

stimuli

that

served

as

deviants

in

the

oddball

runs

-LRB-

deviant-counterparts

-RRB-

-LRB-

-RRB-

Standard

control

maps

computed

from

control

runs

extracting

the

response

to

the

same

physical

stimuli

that

served

as

standards

in

the

oddball

runs

-LRB-

standard-counterparts

-RRB-

The

contrasts

extracting

each

deviant-counterpart

and

standard-counterpart

stimuli

were

carried

out

against

the

same

baseline

that

formed

part

of

the

filler

stimuli

i.e.

beh

peh

bay

and

pay

The

stimuli

that

served

as

deviants

and

standards

-LRB-

i.e.

deh

day

teh

tay

-RRB-

were

taken

out

of

the

baseline

so

that

their

extraction

could

be

conducted

against

a

common

baseline

-LRB-

-RRB-

A

Word

map

computed

from

control

runs

contrasting

the

response

to

the

meaningful

word

-LRB-

day

-RRB-

with

the

non-words

that

formed

part

of

the

filler

stimuli

i.e.

deh

beh

peh

-LRB-

-RRB-

A

Non-word

map

computed

from

control

runs

contrasting

the

response

to

the

non-word

-LRB-

tay

-RRB-

with

the

non-words

that

formed

part

of

the

filler

stimuli

-LRB-

i.e.

deh

beh

peh

-RRB-

The

non-word

tay

was

excluded

from

the

baseline

since

it

was

the

only

non-word

with

a

diphthong

-LRB-

eI

-RRB-

and

to

avoid

contrasting

it

with

itself

Across

subject

analyses

Composite

maps

Two

types

of

composites

were

created

three

composites

of

deviant

maps

one

for

each

deviant

-LRB-

deh

day

tay

-RRB-

and

three

composites

of

the

deviant-control

maps

one

composite

for

each

control

run

that

included

either

deh

day

or

tay

as

a

deviant-counterpart

respectively

Paired

t

tests

The

contrast

between

deviants

and

their

respective

counterparts

isolates

the

cognitive

component

of

deviance

detection

For

this

contrast

a

paired

t

test

was

calculated

between

the

Deviant

map

and

the

Deviant

control

map

The

contrast

between

standards

and

their

respective

counterparts

accounts

for

the

sensory

component

based

on

refractoriness

For

this

contrast

a

paired

t

test

was

calculated

between

the

Standard

map

and

the

Standard

control

map

Statistical

images

were

corrected

for

multiple

comparisons

over

the

whole

brain

using

a

magnitude

threshold

derived

from

Monte

Carlo

simulation

that

takes

into

account

the

number

of

contiguous

activated

voxels

-LRB-

Forman

et

al.

-RRB-

Individual

voxel

thresholds

were

set

at

P

for

both

the

composites

and

paired

t

test

maps

Data

were

corrected

for

multiple

comparisons

by

spatial

extent

of

contiguous

supra-threshold

individual

voxels

-LRB-

experiment-wise

P

for

a

cluster

-RRB-

In

a

Monte

Carlo

simulation

within

the

AFNI

software

package

using

a

smoothing

kernel

of

mm

a

connection

radius

of

mm

on

mm

mm

mm

voxels

it

was

determined

that

an

activation

volume

of

μl

satisfied

the

P

threshold

Regions

of

interest

analyses

The

different

regions

of

interest

-LRB-

ROIs

-RRB-

were

identified

on

the

basis

of

the

results

obtained

by

the

paired

t

test

maps

prior

to

cluster-size

correction

-LRB-

P

-RRB-

reflecting

the

cognitive

and

sensory

mechanisms

of

change-detection

Then

each

participant

's

model

estimate

of

the

percent

signal

change

for

each

region

of

activation

averaged

across

voxels

within

the

region

was

calculated

for

each

of

the

six

composite

maps

-LRB-

three

deviant

maps

and

three

deviant-control

maps

-RRB-

The

ROIs

identified

were

analyzed

in

a

-LRB-

ROI

anterior

auditory

cortex

posterior

auditory

cortex

superior/middle

frontal

gyrus

-RRB-

-LRB-

task-type

oddball

control

-RRB-

-LRB-

deviant

deh

day

tay

-RRB-

-LRB-

laterality

left/right

-RRB-

repeated

measures

ANOVA

with

subjects

-LRB-

n

-RRB-

as

a

random

factor

ROI

analysis

for

the

Word/Non-word

maps

To

further

investigate

the

word

effect

each

participant

's

model

estimate

of

the

percent

signal

change

for

each

region

of

activation

averaged

across

voxels

within

the

region

was

calculated

for

the

Word

map

and

Non-word

map

Both

types

of

maps

were

calculated

from

control

blocks

Specifically

to

create

the

Word

map

day

was

contrasted

with

a

baseline

comprised

of

filler

or

contextual

stimuli

that

were

non-words

-LRB-

i.e.

beh

peh

deh

the

-RRB-

To

create

the

Non-Word

map

tay

was

contrasted

with

the

same

baseline

The

delta

blood-oxygen-level-dependent

-LRB-

BOLD

-RRB-

measures

were

subjected

to

a

-LRB-

Laterality

left/right

-RRB-

-LRB-

ROI

anterior

auditory

cortex

posterior

auditory

cortex

superior/middle

frontal

gyrus

-RRB-

-LSB-

Lexical

Status

word

-LRB-

day

-RRB-

vs.

non-word

-LRB-

tay

-RRB-

-RSB-

repeated

measures

ANOVA

with

subjects

-LRB-

n

-RRB-

as

a

random

factor

Results

Behavioral

results

There

were

no

differences

in

response

accuracy

scores

computed

across

the

three

possible

positions

of

the

outlier

among

the

three

CVs

The

response

accuracy

for

day

was

-LRB-

-RRB-

for

tay

-LRB-

-RRB-

and

for

deh

-LRB-

-RRB-

-LRB-

the

number

in

brackets

denotes

the

standard

deviation

-RRB-

A

paired

t

test

that

was

run

on

the

individual

response

accuracy

data

for

each

CV

confirmed

that

there

was

no

difference

in

accuracy

levels

between

CVs

-LRB-

in

all

three

possible

comparisons

P

-RRB-

We

have

also

examined

the

response

accuracy

scores

for

the

first

and

third

positions

in

the

triplet

for

each

of

the

CVs

The

response

accuracy

scores

ranged

between

and

among

the

three

different

CV

stimuli

as

well

as

between

the

first

and

third

positions

-LRB-

since

there

were

only

four

triplets

per

block

in

which

the

outlier

appeared

in

the

middle

the

middle

position

was

excluded

from

the

latter

calculation

-RRB-

Table

displays

the

reaction

time

data

for

each

deviant

and

for

each

of

the

three

possible

positions

of

the

outlier

within

a

triplet

As

expected

it

could

be

seen

that

the

reaction

time

for

the

third

position

in

the

triplet

was

the

shortest

To

evaluate

this

trend

statistically

a

two-way

ANOVA

was

run

with

Stimulus

-LRB-

day

tay

deh

-RRB-

and

Position

-LRB-

first

second

third

-RRB-

as

factors

and

with

Greenhouse

Geisser

adjustment

to

account

for

sphericity

Only

the

Position

factor

was

significant

-LSB-

F

-LRB-

-RRB-

P

-RSB-

Paired

comparisons

-LRB-

Bonferroni

corrected

P

-RRB-

confirmed

that

reaction

time

associated

with

stimuli

in

the

first

and

second

position

in

the

triplet

was

prolonged

relative

to

that

associated

with

the

third

stimulus

in

the

triplet

Taken

together

there

is

dissociation

between

response

accuracy

and

reaction

time

data

While

no

differences

in

response

accuracy

were

found

reaction

time

was

shorter

when

the

outlier

CV

stimulus

was

in

the

third

position

in

the

triplet

Table

time

-LRB-

ms

-RRB-

in

the

behavioral

triplet

Reaction

time

is

given

for

each

of

the

three

positions

in

the

triplet

and

for

each

stimulus

that

served

as

a

deviant

in

the

oddball

blocks

Standard

deviation

This

confirms

our

prediction

that

reaction

time

will

be

shorter

in

case

of

an

outlier

presented

in

the

third

position

following

two

identical

stimuli

However

the

fact

that

the

main

effect

of

Stimulus

as

well

as

the

interaction

between

Stimulus

and

Position

did

not

reach

significance

confirms

that

the

stimuli

were

equally

discriminable

in

the

context

of

the

oddball

paradigms

used

in

this

experiment

Composite

maps

Deviance

effect

The

spread

of

activation

associated

with

tay

deviant

was

very

similar

to

that

in

response

to

day

-LRB-

Fig.

-RRB-

To

elucidate

the

positions

and

extents

of

the

activated

brain

regions

associated

with

the

similar

responses

to

the

deviants

day

and

tay

images

in

the

coronal

and

sagittal

planes

were

included

-LRB-

Fig.

bottom

panels

-RRB-

Fig.

maps

brain

regions

in

response

to

deviant

stimuli

embedded

within

the

oddball

paradigms

BOLD

contrasts

were

superimposed

on

a

reference

anatomical

image

-LRB-

Holmes

et

al.

-RRB-

Upper

panels

axial

sections

displaying

responses

to

the

deviants

deh

-LRB-

left

-RRB-

day

-LRB-

middle

-RRB-

and

tay

-LRB-

right

-RRB-

Bottom

panels

coronal

-LRB-

two

left

panels

-RRB-

and

sagittal

-LRB-

two

right

panels

-RRB-

sections

of

the

responses

to

the

deviants

day

and

tay

Axial

sections

range

from

z

to

-LRB-

by

increments

of

mm

-RRB-

Coronal

sections

range

from

y

to

-LRB-

by

increments

of

mm

-RRB-

Sagittal

sections

range

from

x

to

-LRB-

by

increments

of

mm

-RRB-

Display

follows

radiological

convention

-LRB-

left

side

of

the

brain

is

displayed

on

the

right

side

of

the

screen

-RRB-

The

size

of

the

right

STG

region

activated

in

the

word

condition

-LRB-

i.e.

day

-RRB-

was

similar

to

that

activated

in

the

non-word

condition

-LRB-

i.e.

tay

-RRB-

-LRB-

Table

-RRB-

In

contrast

the

size

of

the

left

STG

region

activated

in

the

word

condition

was

almost

twofold

larger

than

that

activated

by

the

tay

condition

In

both

hemispheres

the

brain

regions

activated

in

the

day

and

the

tay

conditions

were

larger

than

those

observed

for

the

deh

condition

Furthermore

the

day

tay

and

deh

stimuli

appear

to

activate

different

regions

of

the

STG

The

day

stimulus

activated

parts

of

the

posterior

STG

-LRB-

i.e.

BA

-RRB-

whereas

the

tay

and

deh

stimuli

activated

large

parts

of

the

superior

and

middle

temporal

cortices

-LRB-

i.e.

BA

-RRB-

-LRB-

Table

-RRB-

Table

regions

activated

in

Deviant

maps

-LRB-

Fig.

-RRB-

StimulusVolume

size

-LRB-

-RRB-

Mean

t

valueTalairach

coordinates

-LRB-

mm

-RRB-

SideIdentified

coordinates

-LRB-

Talairach

and

Tournoux

-RRB-

are

given

for

the

center

of

mass

The

mean

t

value

was

computed

across

the

voxels

within

an

anatomical

region

Maps

were

thresholded

at

P

corrected

for

multiple

comparisonsSTG

superior

temporal

gyrus

RT

right

LT

left

BA

Brodmann

area

-LRB-

s

-RRB-

Similar

brain

regions

to

those

implicated

in

the

deviance

response

were

also

found

in

the

study

of

Opitz

et

al.

-LRB-

-RRB-

in

the

context

of

tones

Specifically

in

that

study

the

deviance

effect

also

implicated

HG

-LRB-

primary

auditory

cortex

-RRB-

and

the

superior

temporal

plane

-LRB-

Talairach

coordinates

of

peak

location

respectively

-RRB-

Deviant

control

maps

While

activity

extended

from

the

STG

across

the

lateral

sulcus

to

the

central

sulcus

in

response

to

day

deh

had

a

similar

but

more

focal

response

in

the

vicinity

of

the

primary

auditory

cortex

To

elucidate

the

positions

and

extents

of

the

activated

brain

regions

associated

with

the

more

similar

responses

to

the

deviants

day

and

deh

images

in

the

coronal

and

sagittal

planes

were

included

-LRB-

Fig.

bottom

panels

-RRB-

In

response

to

tay

activity

in

the

STG

did

not

reach

significance

and

activation

was

only

observed

in

the

left

precentral

gyrus

-LRB-

Fig.

Table

-RRB-

Fig.

control

maps

brain

regions

in

response

to

deviant-counterparts

stimuli

embedded

within

the

control

paradigms

Upper

panels

axial

sections

displaying

responses

to

the

deviant

controls

deh

-LRB-

left

-RRB-

day

-LRB-

middle

-RRB-

and

tay

-LRB-

right

-RRB-

Bottom

panels

coronal

-LRB-

two

left

panels

-RRB-

and

sagittal

-LRB-

two

right

panels

-RRB-

sections

of

the

responses

to

the

deviant

controls

day

and

deh

Additional

display

details

as

in

Fig.

regions

activated

in

Deviant

control

maps

-LRB-

Fig.

-RRB-

StimulusVolume

size

-LRB-

-RRB-

Mean

t

valueTalairach

coordinates

-LRB-

mm

-RRB-

SideIdentified

postcentral

gyrus

PrCG

precentral

gyrus

SFrG

superior

frontal

gyrus

STG

superior

temporal

gyrus

RT

right

LT

left

OCCP

occipital

pole

BA

Brodmann

area

-LRB-

s

-RRB-

Other

details

as

in

Table

The

size

of

STG

activation

was

the

most

extensive

over

the

left

STG

for

deviant

day

in

comparison

to

tay

where

it

did

not

reach

statistical

significance

and

deh

where

it

was

more

than

five

times

smaller

-LRB-

Fig.

Table

-RRB-

In

addition

in

response

to

day

a

negative

differential

BOLD

was

evident

in

the

left

superior

frontal

gyrus

and

left

occipital

pole

-LRB-

Fig.

Table

-RRB-

Paired

t

test

maps

Cognitive

effect

The

cognitive

effect

was

derived

by

contrasting

the

Deviant

maps

with

the

corresponding

Deviant

control

maps

Only

the

contrast

map

for

day

showed

activations

at

the

significance

level

used

throughout

this

study

-LRB-

P

corrected

for

multiple

comparisons

-RRB-

reflecting

the

word-advantage

effect

The

negative

differential

BOLD

associated

with

the

cognitive

effect

implicated

bilaterally

the

region

extending

from

the

postcentral

gyrus

to

HG

including

parts

of

the

Sylvian

fissure

lateral

sulcus

and

insula

-LRB-

Table

Fig.

-RRB-

The

location

of

this

region

is

proximal

to

the

one

obtained

by

Opitz

et

al.

-LRB-

-RRB-

that

was

associated

with

the

cognitive

mechanism

and

located

bilaterally

in

a

non-primary

auditory

area

within

the

lateral

temporal

lobe

in

the

anterior

rim

of

HG

-LRB-

Talairach

coordinates

of

peak

location

and

-RRB-

Table

regions

implicated

in

the

cognitive

effect

-LRB-

Fig.

-RRB-

StimulusVolume

size

-LRB-

-RRB-

Mean

t

valueTalairach

coordinates

-LRB-

mm

-RRB-

SideIdentified

lateral

sulcus

INS

insulaaRegion

chosen

for

ROI

analysis

Other

details

as

in

Table

regions

implicated

in

the

cognitive

effect

showing

less

activation

in

the

Deviant

map

than

in

the

Deviant

control

map

for

day

BOLD

contrasts

were

superimposed

on

a

reference

anatomical

image

-LRB-

Holmes

et

al.

-RRB-

Axial

sections

range

from

z

to

-LRB-

by

increments

of

mm

-RRB-

Refractoriness

effect

By

looking

at

the

t

test

images

associated

with

refractoriness

-LRB-

Fig.

-RRB-

a

negative

differential

BOLD

could

be

observed

posterior

to

HG

in

response

to

each

of

the

standard-deviant

pairs

-LRB-

Table

-RRB-

In

case

of

the

refractoriness

effect

when

deh

served

as

the

standard

activity

also

extended

to

the

superior

temporal

sulcus

-LRB-

Fig.

left

panel

-RRB-

Opitz

et

al.

-LRB-

-RRB-

have

also

found

activations

in

a

proximal

brain

region

in

the

lateral

aspect

of

the

posterior

rim

of

HG

bilaterally

that

was

associated

with

the

sensory

mechanism

of

change

detection

-LRB-

Talairach

coordinates

of

peak

location

and

-RRB-

Fig.

regions

implicated

in

the

sensory

-LRB-

refractoriness

-RRB-

effect

showing

less

activation

in

Standard

maps

than

in

Standard

control

maps

Responses

for

the

contrasts

with

deh

-LRB-

left

-RRB-

day

-LRB-

middle

-RRB-

and

teh

are

shown

BOLD

contrasts

were

superimposed

on

a

reference

anatomical

image

-LRB-

Holmes

et

al.

-RRB-

Axial

sections

range

from

z

to

-LRB-

by

increments

of

mm

-RRB-

Table

regions

implicated

in

the

sensory

-LRB-

refractoriness

-RRB-

effect

-LRB-

Fig.

-RRB-

StimulusVolume

size

-LRB-

-RRB-

Mean

t

valueTalairach

coordinates

-LRB-

mm

-RRB-

SideIdentified

superior

temporal

gyrus

S/MFrG

superior/middle

frontal

gyrus

ACC

anterior

cingulate

cortexaRegion

chosen

for

ROI

analysis

other

details

as

in

Table

From

here

on

we

will

refer

to

the

region

posterior

to

HG

-LRB-

Fig.

Table

-RRB-

as

posterior

auditory

cortex

This

region

was

defined

functionally

as

showing

a

refractoriness

effect

in

the

current

study

The

region

anterior

to

HG

extending

from

the

postcentral

gyrus

to

HG

-LRB-

Fig.

Table

-RRB-

will

be

referred

to

as

anterior

auditory

cortex

This

region

was

defined

functionally

as

showing

a

cognitive

effect

in

the

current

study

This

terminology

is

based

on

the

one

used

by

Opitz

et

al.

-LRB-

-RRB-

that

described

the

regions

implicated

in

the

sensory

and

cognitive

effects

as

residing

in

the

vicinity

of

the

posterior

and

anterior

rim

of

HG

respectively

In

addition

when

the

sensory

component

was

extracted

for

deh

standard

-LRB-

Fig.

left

panel

and

Table

-RRB-

positive

differential

BOLD

was

observed

in

the

superior/middle

frontal

gyrus

as

well

as

in

the

anterior

cingulate

cortex

-LRB-

ACC

-RRB-

Thus

the

positive

differential

BOLD

observed

in

the

ACC

and

in

the

frontal

gyrus

is

a

direct

result

of

contrasting

deh

with

a

baseline

of

day

deviants

to

create

the

map

reflecting

the

sensory

component

for

deh

standard

ROI

analysis

Six

ROIs

were

chosen

to

be

included

in

the

ROI

analysis

These

ROIs

were

defined

on

the

basis

of

previous

findings

and

the

data

obtained

in

the

current

study

We

have

chosen

the

ROIs

which

were

directly

linked

to

the

mechanisms

associated

with

change

detection

namely

the

cognitive

and

sensory

effects

or

those

that

might

be

related

to

both

change-detection

and

to

the

processing

of

linguistic

stimuli

This

is

described

in

more

detail

in

the

section

Discussion

The

following

ROIs

were

identified

on

the

basis

of

the

paired

t

test

maps

From

the

paired

t

test

map

reflecting

the

cognitive

effect

-LRB-

Fig.

-RRB-

the

anterior

auditory

cortex

was

chosen

bilaterally

From

the

paired

t

test

map

reflecting

the

refractoriness

effect

when

day

served

as

a

standard

the

posterior

auditory

cortex

was

chosen

bilaterally

-LRB-

Fig.

middle

panel

-RRB-

From

the

paired

t

test

map

reflecting

the

sensory

component

when

deh

served

as

the

standard

the

superior/middle

frontal

gyrus

was

chosen

bilaterally

-LRB-

Fig.

left

panel

Table

-RRB-

Note

that

all

the

ROIs

were

defined

based

on

the

t-maps

prior

to

cluster-size

correction

-LRB-

P

-RRB-

All

except

the

right

superior/middle

frontal

gyrus

were

apparent

in

the

t

test

maps

after

cluster-size

correction

Figure

displays

the

average

delta

BOLD

for

each

condition

-LRB-

oddball

control

-RRB-

and

hemisphere

-LRB-

left/right

-RRB-

as

a

function

of

deviant

stimulus

and

ROI

From

Fig.

it

can

be

seen

that

the

largest

differences

in

delta

BOLD

between

conditions

-LRB-

oddball

control

-RRB-

are

evident

over

the

left

hemisphere

mainly

the

anterior

auditory

cortex

and

superior

frontal

gyrus

These

were

larger

for

day

than

deh

and

smallest

for

tay

The

latter

was

associated

with

diminished

levels

of

delta

BOLD

within

the

posterior

auditory

cortex

in

the

control

condition

Fig.

delta

BOLD

for

each

condition

-LRB-

oddball

control

-RRB-

and

hemisphere

-LRB-

left/right

-RRB-

as

a

function

of

ROI

and

deviant

stimulus

-LRB-

deh

day

or

tay

-RRB-

anterior

auditory

cortex

posterior

auditory

cortex

Sup/Mid

Frontal

superior/middle

frontal

gyrus

The

ROI

data

was

subjected

to

a

four-way

ANOVA

with

Laterality

-LRB-

Left

Right

-RRB-

ROI

-LRB-

anterior

auditory

cortex

posterior

auditory

cortex

superior/middle

frontal

gyrus

-RRB-

Deviant

-LRB-

deh

day

tay

-RRB-

and

Task

type

-LRB-

Control

Oddball

-RRB-

as

independent

factors

with

an

appropriate

adjustment

for

sphericity

-LRB-

Greenhouse

Geisser

correction

-RRB-

A

main

effect

of

ROI

was

found

-LSB-

F

-LRB-

-RRB-

P

-RSB-

as

well

as

a

Laterality

ROI

-LSB-

F

-LRB-

-RRB-

P

-RSB-

Deviant

ROI

-LSB-

F

-LRB-

-RRB-

P

-RSB-

Task

Type

ROI

-LSB-

F

-LRB-

-RRB-

P

-RSB-

and

Deviant

Task

Type

ROI

-LSB-

F

-LRB-

-RRB-

P

-RSB-

interactions

The

Laterality

ROI

interaction

was

due

to

enhanced

delta

BOLD

over

the

left

hemisphere

associated

with

the

anterior

auditory

cortex

-LRB-

P

Bonferroni

corrected

-RRB-

The

Deviant

Task

Type

ROI

interaction

is

depicted

in

Fig.

A

set

of

paired

comparisons

-LRB-

Bonferroni

corrected

P

-RRB-

were

conducted

separately

within

each

task-type

-LRB-

oddball

control

-RRB-

In

the

oddball

condition

the

comparisons

were

conducted

among

the

three

deviants

for

the

posterior

auditory

cortex

only

where

a

gradient

of

delta

BOLD

could

be

observed

as

a

function

of

deviant

type

In

the

control

condition

comparisons

were

performed

among

the

three

deviants

for

each

of

the

ROIs

In

the

oddball

condition

a

significantly

larger

delta

BOLD

was

found

in

response

to

tay

than

to

deh

in

the

posterior

auditory

cortex

In

the

control

condition

delta

BOLD

to

the

word

day

in

the

anterior

and

posterior

auditory

cortices

was

significantly

larger

than

that

associated

with

the

non-word

tay

Fig.

stimulus

-LRB-

deh

day

tay

-RRB-

condition

-LRB-

oddball

control

-RRB-

interaction

The

interaction

was

obtained

by

calculating

the

individual

percent

signal

change

in

each

ROI

-LRB-

across

hemispheres

-RRB-

for

each

of

the

six

composite

maps

-LRB-

three

Deviant

maps

and

three

Deviant-control

maps

-RRB-

See

text

for

the

results

of

the

a

priori

tests

Abbreviations

as

in

Fig.

In

a

separate

set

of

paired

comparisons

-LRB-

Bonferroni

corrected

P

-RRB-

the

averages

of

delta

BOLD

between

conditions

-LRB-

oddball

control

-RRB-

were

compared

for

each

of

the

three

deviant

stimuli

and

each

of

the

ROIs

-LRB-

across

hemispheres

-RRB-

A

larger

delta

BOLD

was

found

for

the

response

to

day

in

the

control

condition

relative

to

the

oddball

condition

implicating

the

anterior

auditory

cortex

ROI

analysis

for

the

Word

and

Non-word

maps

To

further

investigate

the

word

effect

each

participant

's

model

estimate

of

the

percent

signal

change

for

each

region

of

activation

was

calculated

separately

for

the

Word

map

and

Non-word

map

-LRB-

Fig.

Table

-RRB-

The

ROI

data

was

subjected

to

a

three-way

ANOVA

with

Laterality

-LRB-

left

right

-RRB-

ROI

-LRB-

anterior

auditory

cortex

posterior

auditory

cortex

superior/middle

frontal

gyrus

-RRB-

and

Lexical

Status

-LSB-

word

-LRB-

day

-RRB-

non-word

-LRB-

tay

-RRB-

-RSB-

as

independent

factors

with

an

appropriate

adjustment

for

sphericity

-LRB-

Greenhouse

Geisser

correction

-RRB-

A

main

effect

of

ROI

was

found

-LSB-

F

-LRB-

-RRB-

P

-RSB-

as

well

as

a

Lexical

Status

ROI

interaction

-LSB-

F

-LRB-

-RRB-

P

-RSB-

-LRB-

Fig.

-RRB-

Paired

comparisons

-LRB-

Bonferroni

corrected

P

-RRB-

found

a

significant

difference

between

day

and

tay

only

within

the

anterior

auditory

cortex

Fig.

Word

and

Non-Word

maps

Brain

regions

in

response

to

day

deviant-counterpart

-LRB-

Word

map

-RRB-

and

tay

deviant-counterpart

-LRB-

Non-word

map

-RRB-

Stimuli

were

contrasted

against

a

baseline

comprised

of

the

non-word

fillers

-LRB-

i.e.

peh

beh

deh

teh

-RRB-

Left

panel

response

to

the

Word-map

Right

panel

response

to

the

Non-word

map

BOLD

contrasts

were

superimposed

on

a

reference

anatomical

image

-LRB-

Holmes

et

al.

-RRB-

Axial

sections

range

from

z

to

-LRB-

by

increments

of

mm

-RRB-

Table

regions

activated

in

Word

and

Non-word

maps

in

response

to

day

and

tay

respectively

-LRB-

Figs.

-RRB-

StimulusVolume

size

-LRB-

-RRB-

Mean

t

valueTalairach

coordinates

-LRB-

mm

-RRB-

SideIdentified

regionBAxyzday

-LRB-

Word-map

-RRB-

-LRB-

Word-map

-RRB-

-LRB-

Non-Word-map

-RRB-

postcentral

gyrus

PrCG

precentral

gyrus

STG

superior

temporal

gyrus

other

details

as

in

Table

Lexical

Status

interaction

The

interaction

was

obtained

by

calculating

the

individual

percent

signal

change

in

each

ROI

for

the

Word

and

Non-word

maps

Abbreviations

as

in

Fig.

The

distribution

of

percent

signal

change

across

subjects

To

learn

more

about

the

consistency

and

extent

of

activation

of

specific

brain

regions

data

were

analyzed

for

individual

subjects

Specifically

the

percent

signal

change

of

individual

subjects

was

computed

for

each

of

the

six

ROIs

chosen

for

the

group

level

analysis

as

well

as

for

additional

two

brain

regions

that

might

be

implicated

in

speech

perception

that

is

the

left

occipital

pole

and

the

left

precentral

gyrus

The

results

showed

that

the

majority

of

subjects

within

each

statistical

test

showed

the

same

pattern

of

activity

-LRB-

see

Table

-RRB-

Table

distribution

of

percent

signal

change

across

subjectsBrain

regionSideMap

typeNo

of

subj

displaying

increases

-LRB-

-RRB-

decreases

-LRB-

-RRB-

-LRB-

n

-RRB-

Mean

SD

signal

changeLS/INSRTCognitive

-LRB-

day

-RRB-

Fig.

-LRB-

-RRB-

LS/INSLTCognitive

-LRB-

day

-RRB-

Fig.

-LRB-

-RRB-

STGRTRefractoriness

-LRB-

day

-RRB-

Fig.

-LRB-

-RRB-

STGLTRefractoriness

-LRB-

day

-RRB-

Fig.

-LRB-

-RRB-

S/MFrGRTRefractoriness

-LRB-

deh

-RRB-

Fig.

-LRB-

-RRB-

S/MFrGLTRefractoriness

-LRB-

deh

-RRB-

Fig.

-LRB-

-RRB-

PrCGLTDeviant

control

-LRB-

tay

-RRB-

Fig.

-LRB-

-RRB-

OCCPLTDeviant

control

-LRB-

day

-RRB-

Fig.

-LRB-

-RRB-

SD

standard

deviation

For

each

region

and

hemisphere

the

number

of

subjects

presenting

increases

or

decreases

in

percent

signal

change

is

indicated

as

well

as

the

mean

and

SD

across

subjects

The

stimulus

in

brackets

denotes

the

specific

map

from

which

the

brain

region

was

selected

For

the

regions

associated

with

the

t

test

maps

of

the

cognitive

and

refractoriness

effects

data

are

reported

for

the

difference

percent

signal

change

between

the

contrasted

conditions

in

the

t

testLS

lateral

sulcus

INS

insula

STG

superior

temporal

gyrus

S/MFrG

superior/middle

frontal

gyrus

PrCG

precentral

gyrus

OCCP

occipital

pole

RT

right

LT

left

No

of

subj

number

of

subjects

n

total

number

of

subjects

that

participated

in

the

study

Discussion

Main

findings

Overall

the

results

of

the

current

study

confirmed

our

hypotheses

Specifically

the

sensory

mechanism

was

located

in

the

posterior

auditory

cortex

-LRB-

Fig.

Table

-RRB-

and

the

cognitive

mechanism

in

the

anterior

auditory

cortex

-LRB-

Fig.

Table

-RRB-

These

locations

match

respectively

those

found

in

the

context

of

tones

-LRB-

Opitz

et

al.

-RRB-

Moreover

as

expected

the

cognitive

effect

was

statistically

significant

only

when

the

deviant

was

a

word

-LRB-

i.e.

day

-RRB-

The

similarity

between

the

brain

regions

activated

by

speech

in

this

study

and

the

regions

activated

by

tones

-LRB-

Opitz

et

al.

-RRB-

could

not

be

explained

by

the

analysis

of

the

physical

sound

features

First

the

contribution

of

the

acoustic

component

to

the

cognitive

mechanism

in

this

study

was

removed

by

contrasting

deviants

with

their

physical

identical

control

counterparts

Second

our

data

suggest

that

the

salience

of

the

sounds

either

tones

or

speech

stimuli

accounts

for

the

activation

of

the

anterior

auditory

cortex

-LRB-

Jääskeläinen

et

al.

Ahveninen

et

al.

-RRB-

-LRB-

see

also

Support

for

the

existence

of

what

and

where

auditory

streams

-RRB-

Thus

the

acoustic

component

could

only

account

for

the

similar

activation

observed

in

the

posterior

HG

This

is

also

in

line

with

previous

findings

that

link

dorsal

temporal

brain

areas

including

HG

and

planum

temporale

with

the

analysis

of

auditory

features

of

complex

sounds

-LRB-

Binder

et

al.

Wessinger

et

al.

Hall

et

al.

Seifritz

et

al.

-RRB-

Activation

loci

in

superior

and

middle

temporal

areas

that

were

found

to

be

activated

in

the

Deviant

-LRB-

Fig.

-RRB-

and

Deviant

control

maps

-LRB-

Fig.

-RRB-

had

also

been

earlier

reported

to

contribute

to

lexical

and

semantic

processing

-LRB-

Price

Salmelin

et

al.

Scott

and

Johnsrude

Hickok

and

Poeppel

-RRB-

Similarly

the

left

dominance

for

processing

intelligible

speech

that

was

found

in

our

study

in

the

oddball

condition

match

previous

results

that

link

the

left

posterior

STG

to

higher

level

linguistic

processes

-LRB-

Narain

et

al.

-RRB-

Support

for

the

existence

of

what

and

where

auditory

streams

The

results

of

this

study

are

in

agreement

with

the

segregation

of

the

auditory

system

into

what

and

where

processing

streams

-LRB-

Jääskeläinen

et

al.

Ahveninen

et

al.

-RRB-

associated

with

the

analysis

of

auditory

object

content

and

location

features

that

reside

in

areas

anterior

and

posterior

to

primary

auditory

cortex

respectively

-LRB-

Rauschecker

and

Tian

-RRB-

It

was

suggested

-LRB-

Jääskeläinen

et

al.

-RRB-

that

the

where

system

is

responsible

both

for

fast

analysis

of

sound

location

which

is

important

for

attentional

orienting

and

for

detecting

the

degree

of

sound

novelty

which

affects

its

degree

of

distractibility

Specifically

the

degree

to

which

unattended

novel

sounds

distracted

visual

forced-choice

task

performance

coincided

with

the

extent

that

the

posterior

response

was

released

from

inhibition

On

the

other

hand

the

anterior

response

was

associated

with

the

processing

of

fine

object

features

-LRB-

Jääskeläinen

et

al.

-RRB-

Similarly

the

results

in

our

study

indicate

that

the

deviant

word

was

released

from

inhibition

in

the

control

condition

because

of

its

lexical

status

and

that

this

word

advantage

effect

was

located

anterior

to

HG

This

is

in

agreement

with

the

finding

that

neurons

in

the

anterior

auditory

cortex

are

more

sharply

tuned

to

phonetic

features

of

sounds

-LRB-

Ahveninen

et

al.

-RRB-

The

effect

of

speech

perception

Despite

the

general

similarity

to

the

results

obtained

in

the

context

of

tones

some

of

the

results

are

specific

to

speech

perception

as

follows

In

the

oddball

condition

the

brain

regions

activated

in

response

to

the

deviants

day

and

tay

were

larger

than

those

observed

for

the

deh

deviant

-LRB-

Deviant

maps

Fig.

-RRB-

In

addition

in

the

control

condition

the

precentral

gyrus

was

activated

in

response

to

both

day

and

tay

-LRB-

Fig.

-RRB-

These

similarities

between

day

and

tay

may

reflect

an

extra

processing

effort

associated

with

the

diphthong

vowel

eI

shared

by

day

and

tay

-LRB-

Sonty

et

al.

Bohland

and

Guenther

-RRB-

However

the

fact

that

the

similarity

between

the

responses

to

day

and

tay

diminished

in

the

control

condition

-LRB-

Fig.

-RRB-

may

indicate

that

the

eI

diphthong

associated

with

deviant

day

was

more

salient

among

repetitive

deh

standards

-LRB-

oddball

condition

-RRB-

than

among

the

variable

filler

stimuli

-LRB-

control

condition

-RRB-

-LRB-

Nordby

et

al.

Sabri

and

Campbell

-RRB-

The

more

similar

responses

between

day

and

deh

in

the

control

condition

-LRB-

Fig.

-RRB-

may

be

explained

by

the

shared

e

monophthong

that

might

have

elicited

an

expectation

to

hear

a

meaningful

word

-LRB-

day

-RRB-

while

presented

with

deh

This

expectation

could

account

for

the

more

extensive

response

in

the

STG

relative

to

tay

-LRB-

Fig.

-RRB-

The

finding

that

activation

in

the

left

anterior

auditory

cortex

dissociates

the

oddball

and

control

conditions

strengthens

this

interpretation

-LRB-

Scott

et

al.

-RRB-

as

well

as

the

observed

increase

in

the

percent

signal

change

in

that

region

associated

with

both

deh

and

day

-LRB-

Fig.

Left

panels

-RRB-

Thus

in

the

control

condition

-LRB-

Fig.

-RRB-

an

interaction

between

lexical

and

acoustic

features

affected

the

results

There

were

additional

findings

indicating

left

hemisphere

dominance

as

follows

The

size

of

STG

activation

was

the

most

extensive

over

the

left

STG

for

day

in

comparison

to

tay

where

it

did

not

reach

statistical

significance

and

deh

where

it

was

more

than

five

times

smaller

-LRB-

Deviant

control

maps

Fig.

Table

-RRB-

Furthermore

the

day

control

map

revealed

negative

differential

BOLD

in

the

left

superior

frontal

gyrus

as

well

as

in

the

left

occipital

pole

-LRB-

Fig.

Table

-RRB-

Left

hemisphere

dominance

was

also

evident

in

the

middle/superior

frontal

gyrus

in

the

sensory

mechanism

map

for

deh

-LRB-

Fig.

Table

-RRB-

In

addition

the

four-way

ANOVA

-LRB-

Fig.

-RRB-

has

shown

This

pattern

of

left

hemisphere

dominance

is

in

agreement

with

a

number

of

imaging

and

clinical

studies

-LRB-

for

a

review

see

Tervaniemi

and

Hugdahl

-RRB-

The

left

middle/superior

frontal

gyrus

activations

are

in

line

with

previous

findings

implicating

these

brain

regions

with

tasks

engaging

phonological

working

memory

-LRB-

Paulesu

et

al.

Burton

et

al.

Siok

et

al.

LoCasto

et

al.

-RRB-

and

with

the

suggestion

that

a

significant

portion

of

active

frontal

areas

is

recruited

for

extracting

acoustic

information

and

maintaining

it

in

memory

-LRB-

LoCasto

et

al.

-RRB-

The

negative

differential

activation

evident

in

the

left

occipital

pole

associated

with

the

day

control

map

-LRB-

Fig.

-RRB-

may

indicate

that

meaningful

words

are

more

likely

to

elicit

activity

in

visual

processing

regions

-LRB-

Billingsley-Marshall

et

al.

-RRB-

It

is

noteworthy

that

the

sensory

mechanism

map

for

deh

revealed

a

positive

differential

BOLD

in

the

ACC

-LRB-

Fig.

Table

-RRB-

The

ACC

is

implicated

in

initiating

or

inhibiting

action

and

is

considered

to

be

part

of

a

larger

network

that

includes

medial/lateral

frontal

prefrontal

and

temporal

regions

-LRB-

Wang

et

al.

Dias

et

al.

Gold

et

al.

-RRB-

Hence

it

is

possible

that

in

our

study

inhibitory

activations

occurred

in

the

ACC

-LRB-

as

well

as

in

the

superior

frontal

gyrus

-RRB-

in

response

to

day

since

it

was

a

meaningful

stimulus

that

interfered

with

the

main

counting

task

-LRB-

see

also

Rinne

et

al.

-RRB-

Since

standard

deh

was

contrasted

with

deviant

day

to

create

the

deh

standard

map

the

positive

differential

BOLD

located

at

the

ACC

and

middle/superior

frontal

gyrus

-LRB-

Fig.

deh

-RRB-

might

have

been

caused

by

a

reduced

activation

associated

with

the

response

to

deviant

day

A

possible

effect

of

the

lexical

status

in

the

oddball

condition

It

appears

that

the

lexical

status

of

the

deviant

stimulus

affected

its

processing

not

only

in

the

control

condition

but

also

in

the

oddball

condition

in

which

the

effects

of

adaptation

caused

by

the

repeating

standards

were

more

pronounced

Specifically

the

day

stimulus

activated

parts

of

the

posterior

STG

-LRB-

i.e.

BA

-RRB-

whereas

the

tay

and

deh

stimuli

activated

large

parts

of

the

superior

and

middle

temporal

cortices

-LRB-

i.e.

BA

-RRB-

-LRB-

Table

-RRB-

However

the

size

of

the

left

STG

region

activated

by

day

deviant

was

almost

twofold

larger

than

that

activated

by

tay

deviant

-LRB-

Deviant

maps

Fig.

Table

-RRB-

This

is

in

agreement

with

the

assumption

that

the

left

posterior

STG

is

the

focus

of

a

multi-modal

network

associated

with

language

comprehension

-LRB-

Aboitiz

and

Garcia

Narain

et

al.

-RRB-

More

strongly

left-lateralized

posterior

superior-temporal

activation

is

associated

with

analysis

of

speech

sounds

for

mapping

onto

higher

levels

of

language

processing

-LRB-

e.g.

syllable

word

-RRB-

-LRB-

Price

et

al.

Zatorre

et

al.

-RRB-

Thus

although

the

word

advantage

effect

was

not

salient

in

the

oddball

condition

the

different

spread

of

activation

between

day

and

the

other

non-words

may

indicate

differential

processing

based

on

the

lexical

status

of

the

deviant

stimulus

Summary

Taken

together

the

results

of

the

current

study

corroborate

the

existence

of

two

independent

mechanisms

contributing

to

the

change-detection

response

-LRB-

Opitz

et

al.

Hoshiyama

et

al.

Maess

et

al.

-RRB-

a

sensory

mechanism

reflected

by

different

refractory

states

of

those

subpopulations

activated

by

the

standard

and

the

deviant

and

a

cognitive

mechanism

which

relies

on

auditory

sensory

memory

representations

which

gives

rise

to

the

word

advantage

effect

Thus

on

the

one

hand

our

results

support

the

view

that

the

MMN

represents

a

change-detection

mechanism

functionally

and

spatially

distinct

from

an

afferent

input

population

-LRB-

generators

-RRB-

-LRB-

Näätänen

et

al.

-RRB-

On

the

other

hand

our

results

indicate

that

a

release

from

the

inhibitory

effects

of

adaptation

is

a

prerequisite

for

the

full

realization

of

the

significance

of

the

deviant

stimulus

This

is

in

line

with

the

adaptation

hypothesis

that

assumes

that

the

posterior

auditory

cortex

gates

novel

sounds

to

awareness

-LRB-

Jääskeläinen

et

al.

-RRB-

Conclusion

Our

findings

serve

to

unify

the

two

opposing

views

suggested

by

Jääskeläinen

et

al.

-LRB-

-RRB-

and

Näätänen

et

al.

-LRB-

-RRB-

Specifically

the

gate

to

awareness

for

auditory

deviation

-LRB-

Jääskeläinen

et

al.

Näätänen

et

al.

-RRB-

relies

on

adaptation

that

modulates

the

extent

to

which

novel

sounds

will

be

accessible

to

memory-based

processes

In

case

of

the

present

study

the

sensory

component

serves

to

modulate

the

salience

of

the

speech

stimulus

by

the

degree

to

which

it

will

be

accessible

to

cortical

memory

traces

for

speech

sounds

-LRB-

Pulvermüller

and

Shtyrov

-RRB-

Furthermore

the

lexical

status

of

the

speech

stimulus

interacts

with

acoustic

factors

exerting

a

top-down

effect

on

the

novelty

value

of

the

auditory

object

that

affects

in

turn

its

degree

of

accessibility

to

the

cognitive

component

functional magnetic resonance imaging (fmri)


Three-year survival of single - and two-surface ART restorations in a high-caries child population The aim of this study was to evaluate the survival of single - and two-surface atraumatic restorative treatment -LRB- ART -RRB- restorations in the primary and permanent dentitions of children from a high-caries population , in a field setting . The study was conducted in the rainforest of Suriname , South America . ART restorations , made by four Dutch dentists , were evaluated after 6 months , 1 , 2 , and 3 years . Four hundred seventy-five ART restorations were placed in the primary dentition and 54 in first permanent molars of 194 children -LRB- mean age 6.09 ± 0.48 years -RRB- . Three-year cumulative survivals of single - and two-surface ART restorations in the primary dentition were 43.4 and 12.2 % , respectively . Main failure characteristics were gross marginal defects and total or partial losses . Three-year cumulative survival for single-surface ART restorations in the permanent dentition was 29.6 % . Main failure characteristics were secondary caries and gross marginal defects . An operator effect was found only for two-surface restorations . The results show extremely low survival rates for single - and two-surface ART restorations in the primary and permanent dentitions . The variable success for ART may initiate further discussion about alternative treatment strategies , especially in those situations where choices have to be made with respect to a well-balanced , cost-effective package of basic oral health care . Introduction The concept of minimal invasive dentistry has evolved as a consequence of an increased understanding of caries and the development of adhesive restorative materials -LSB- 27 -RSB- . Within this concept , prevention and hard tissue preservation are the primary goals , and dentists are encouraged to prefer a more conservative and biological approach rather than a surgical approach , although the latter is sometimes unavoidable . The atraumatic restorative treatment -LRB- ART -RRB- technique is part of a minimal invasive approach and , as such , a technique that meets the specific goals mentioned above . In brief , with ART , soft demineralized carious tooth tissue is removed using hand instruments only , followed by restoration of the tooth with an adhesive restorative material , often glass ionomer cement -LSB- 4 , 7 -RSB- . Because neither electricity nor running water is required for this treatment approach , ART can be applied in almost any setting . Although initially developed to provide restorative dental treatment in outreach or rural areas , ART or modified ART techniques are increasingly introduced into dental clinics in industrialized countries -LSB- 1 , 11 , 14 -RSB- . Since its introduction in the mid-1980s , ART has been evaluated in several community field trials . These studies served mainly to obtain information on technical aspects of the process , handling characteristics of the restorative material , and on the survival of the restorations . They led to improvement of the technique -LSB- 20 -RSB- and to the development of new , more appropriate glass ionomer restoration materials , especially for ART purposes . Studies focussing on the survival of ART restorations have shown that the ART approach is very successful in restoring single-surface dentine lesions in the permanent dentition : 3-year survival rates of 71 -- 92 % have been reported -LSB- 5 , 6 , 9 , 10 , 12 , 20 -RSB- . Regarding the survival rates of ART restorations in the primary dentition , only a few field studies were performed . They showed acceptable survival rates -LRB- 65 -- 96.7 % -RRB- for single-surface ART restorations , but generally low success rates -LRB- 31 -- 76.1 % -RRB- for multi-surface ART restorations , even with the newer glass ionomer materials -LSB- 2 , 3 , 11 -- 13 , 19 , 23 , 24 , 28 -RSB- . Although its performance under multisurface conditions is disappointing , ART is considered a valuable approach towards the treatment of dental caries . The use of ART has resulted in the retention of many teeth that would otherwise have been extracted in a later stage . Nevertheless , there still remain some controversies towards the technique , presumably based on the inconsistency in survival results . Moreover , a recent study , investigating the influence of dental treatment on the oral health of a Surinamese child population , concluded that performing ART restorations only , did not contribute significantly to an improvement of the oral health , suggesting that ART alone is not a sufficient solution in the battle against dental decay -LRB- van Gemert-Schriks et al. , submitted , 2007 -RRB- . Frencken et al. -LSB- 8 -RSB- described comprehensively that ART should be part of a basic package of oral care in which prevention and urgent care are also represented . However , within this package , these three components should be geared to one another as much as possible and the individual effects of all three components must be sufficient and beneficial under different circumstances . When the success of either component , particularly ART , can not be guaranteed , its contribution in the package should be reduced . Thus , the evaluation of ART in different countries or communities , among different kinds of caries-risk populations and under diverging conditions remains useful . Therefore , the aim of this study is to evaluate the survival of both single - and two-surface ART restorations in the primary and permanent dentitions of children from a high-caries population in a field setting on a longitudinal base . Materials and methods This cohort study was conducted in the rainforest of Suriname , South America . It was part of a large-scale project investigating the influence of dental treatment on the oral health of children -LRB- van Gemert-Schriks et al. , submitted , 2007 -RRB- . Within the scope of that particular project , 380 6-year-old children were divided randomly among four different treatment groups . Material presented in the current article concerns only those children who received restorative treatment , according to the ART method , either in their primary or permanent dentitions . The restorative treatments were performed in accordance with the ART guidelines -LSB- 4 , 7 -RSB- and took place in empty classrooms where four children were treated at the same time . Ketac-Molar -LRB- 3M-ESPE ® -RRB- was used as the restorative material of choice . The treatments were carried out by four Dutch dentists who were trained in ART during a 1-week ART course and by using ART in children from their own practices , for a period of 3 months , before the start of the treatment phase of the study . They were assisted by six Surinamese health care assistants from the Medical Mission who completed an ART course supplemented with some basic dental knowledge . The dentists were asked to note any contamination with blood and/or saliva during the restoration of the cavity . Furthermore , the presence or absence of adjacent teeth was noted . During the treatment , one of the authors -LRB- MGS -RRB- , who was not involved in the treatment phase , observed and classified the overall behavior of the child , based on a modified Venham scale -LSB- 23 , 29 -RSB- . Before the study , this observer was trained in using the Venham behavior scale by scoring 42 videotapes of children in a dental situation . These observations were compared to the consensus score of two calibrated observers . This comparison resulted in a Cohen 's Kappa of 0.87 , implying an excellent agreement . Restorations were not assessed at the time of placement -LRB- T0 -RRB- . The children were revisited for evaluation of the ART restorations 6 months -LRB- T1 -RRB- , 1 year -LRB- T2 -RRB- , 2 years -LRB- T3 -RRB- , and 3 years -LRB- T4 -RRB- after the initial treatment . The same author and dentist mentioned above -LRB- MGS -RRB- , evaluated the restorations according to the ART criteria -LRB- Table 1 -RRB- using a CPITN probe , a mouth mirror and a headlamp . Before the study , this person was calibrated against a `` gold standard '' -LRB- Kappa 0.94 -RRB- . This gold standard was achieved by the consensus of two experienced dentists during the assessment of 24 extracted molars with ART restorations . Restorations scored code 00 or 10 were considered successful , codes 11 -- 40 were classified as failures , and codes 50 -- 90 were assigned in case the tooth was unavailable for evaluation . If a tooth or restoration showed multiple defects , a marginal defect dominated an over - or underfilled restoration -LRB- 10 , 11 > 12 , 13 -RRB- , secondary caries dominated a marginal defect -LRB- 20 , 21 > 10 , 11 -RRB- , absence of a restoration dominated secondary caries -LRB- 30 > 20 , 21 -RRB- , and an overfilled cavity dominated an underfilled cavity -LRB- 13 > 12 -RRB- . Table 1Evaluation criteria for the ART restorationsCodeEvaluation characteristics00Restoration present , correct10Restoration present , slight marginal defect/wear of surface -LRB- < 0.5 mm -RRB- . No repair needed .11 Restoration present , gross marginal defect/wear of surface -LRB- > 0.5 mm -RRB- . Repair needed .12 Restoration present , underfilled -LRB- > 0.5 mm -RRB- . Repair needed .13 Restoration present , overfilled -LRB- > 0.5 mm -RRB- . Repair needed .20 Secondary caries , discoloration in depth , surface hard and intact , caries within dentin . Repair needed .21 Secondary caries , surface defect , caries within dentin . Repair needed .30 Restoration not present , bulk fracture , moving or partial lost . Repair needed .40 Inflammation of the pulp ; signs of dentogenic infection -LRB- abscesses , fistulae , pain complaints -RRB- . Restoration might still be in situ . Extraction needed .50 Tooth not present because of extraction60Tooth not present because of shedding70Tooth not present because of extraction or shedding90Patient not present Statistical analysis Statistical analyses were performed using SPSS for Windows , version 12.0.1 -LRB- SPSS , Chicago , USA -RRB- . All significant differences were detected at a 95 % confidence level . Kaplan -- Meier survival analyses were performed on the censored data of both single - and two-surface restorations . The significance of differences between survival curves was determined with log-rank tests . Possible confounding variables were taken into account using a Cox regression analysis . Results As stated in the `` Materials and methods '' section , the children in this study were derived from a larger study population of children participating in another project . The overall caries prevalence , expressed in terms of decayed , missing and filled surfaces -LRB- dmfs -RRB- among that group of children , was 11.51 -LRB- SD 10.5 ; range 0 -- 53 -RRB- in the primary dentition and 0.20 -LRB- SD 0.62 ; range 0 -- 5 -RRB- in the permanent dentition . According to the standards of the World Health Organisation -LSB- 17 -RSB- , this denotes a high-caries child population based on the caries prevalence in the primary dentition . Within the larger group , 194 children -LRB- mean age 6.09 ± 0.48 years -RRB- received ART restorations in either their primary or permanent teeth , or both . Only these children were included in the current study . Their baseline caries prevalence was 12.75 -LRB- SD 9.88 ; range 0 -- 53 -RRB- in the primary dentition and 0.23 -LRB- SD 0.67 ; range 0 -- 5 -RRB- in the permanent dentition . At baseline -LRB- T0 -RRB- , 475 ART restorations were placed in the primary dentition -LRB- mainly first and second molars -RRB- and 54 in the first permanent molars -LRB- predominantly mandibular -RRB- . Table 2 presents data for the ART restorations , performed at baseline . A Mann -- Whitney U test showed that children who received two-surface restorations scored higher on the Venham behavior scale -LRB- p = 0.005 -RRB- than children that received single-surface restorations , in the primary dentition . Furthermore , dentists reported more contamination -LRB- chi-square = 25.02 , df = 1 , p < 0.001 -RRB- when placing two-surface restorations than single-surface restorations . Table 2Baseline data for the ART restorations Primary dentitionPermanent dentitionNumber of filled surfaces121Number of restorations13334254Number of children -LRB- N -RRB- 6114734Mean number of restorations per child -LRB- SD ; range -RRB- 3.50 -LRB- 1.61 ; 1 -- 7 -RRB- 3.64 -LRB- 1.73 ; 1 -- 8 -RRB- 2.07 -LRB- 0.97 ; 1 -- 4 -RRB- Dentist143 -LRB- 32.3 % -RRB- 74 -LRB- 21.6 % -RRB- 12 -LRB- 22.2 % -RRB- 241 -LRB- 30.8 % -RRB- 84 -LRB- 24.6 % -RRB- 16 -LRB- 29.6 % -RRB- 334 -LRB- 25.6 % -RRB- 89 -LRB- 26.0 % -RRB- 7 -LRB- 13.0 % -RRB- 415 -LRB- 11.3 % -RRB- a95 -LRB- 27.8 % -RRB- 19 -LRB- 35.2 % -RRB- Adjacent tooth presentYes117 -LRB- 88.0 % -RRB- 303 -LRB- 88.6 % -RRB- 45 -LRB- 83.3 % -RRB- No16 -LRB- 12.0 % -RRB- 39 -LRB- 11.4 % -RRB- 9 -LRB- 16.7 % -RRB- Contamination blood/salivaYes13 -LRB- 9.8 % -RRB- 110 -LRB- 32.2 % -RRB- a5 -LRB- 9.3 % -RRB- No120 -LRB- 90.2 % -RRB- 232 -LRB- 67.8 % -RRB- 49 -LRB- 90.7 % -RRB- Venham behavior score050 -LRB- 37.6 % -RRB- 78 -LRB- 22.8 % -RRB- 8 -LRB- 14.8 % -RRB- 144 -LRB- 33.1 % -RRB- 137 -LRB- 40.1 % -RRB- 27 -LRB- 50.0 % -RRB- 226 -LRB- 19.5 % -RRB- 82 -LRB- 24.0 % -RRB- 13 -LRB- 24.1 % -RRB- 313 -LRB- 9.8 % -RRB- 33 -LRB- 9.6 % -RRB- 6 -LRB- 11.1 % -RRB- 4 -- 12 -LRB- 3.5 % -RRB- a -- 5 -- -- -- SD Standard deviationaStatistical significant difference at p = 0.005 . The lost-to-follow-up percentage of the restorations originally placed was 4.63 % . After 3 years , the cumulative survival of the single-surface ART restorations in the primary dentition was 43.4 % -LRB- standard error -LRB- SE -RRB- 10.9 % -RRB- . For the two-surface restorations , a cumulative survival of 12.2 % -LRB- SE 2.99 % -RRB- was observed . The survival curves , with censored data , are presented in Fig. 1a and b . The cumulative survival of the single-surface ART restorations in the permanent dentition was 29.6 % -LRB- SE 8.2 % -RRB- after 3 years -LRB- Fig. 2 -RRB- . Fig. 1a Survival curve single surface ART restorations , primary dentition . b Survival curve multisurface ART restorations , primary dentitionFig . 2Survival curve single-surface ART restorations , permanent dentition Table 3 represents the failure characteristics for the restorations in both primary and permanent dentitions at 3 years . The main failure characteristics of both single - and two-surface ART restorations in the primary dentition were gross marginal defects -LRB- score 11 -RRB- and total or partial losses -LRB- score 30 -RRB- . For restorations in the permanent dentition , the main failure characteristics were secondary caries -LRB- score 21 -RRB- and gross marginal defects -LRB- score 11 -RRB- . Table 3Failure characteristics for the ART restorations at 3 years Primary dentitionPermanent dentition1 surface2 surface1 surfaceRestorations baseline -LRB- N -RRB- 13334254Failures -LRB- N -RRB- 4225132Failure scoreGross marginal defect -LRB- 11 -RRB- 21 -LRB- 15.8 % -RRB- 86 -LRB- 25.1 % -RRB- 13 -LRB- 24.1 % -RRB- Restoration present , underfilled -LRB- 12 -RRB- 1 -LRB- 0.8 % -RRB- 9 -LRB- 2.6 % -RRB- -- Restoration present , overfilled -LRB- 13 -RRB- 2 -LRB- 1.5 % -RRB- 11 -LRB- 3.2 % -RRB- 2 -LRB- 3.7 % -RRB- Sec . caries , discoloration -LRB- 20 -RRB- -- -- -- Sec . caries , surface defect -LRB- 21 -RRB- 5 -LRB- 3.8 % -RRB- 1 -LRB- 0.3 % -RRB- 14 -LRB- 25.9 % -RRB- Total or partial loss -LRB- 30 -RRB- 13 -LRB- 9.8 % -RRB- 120 -LRB- 35.1 % -RRB- 3 -LRB- 5.6 % -RRB- Pulpal inflammation -LRB- 40 -RRB- -- 24 -LRB- 7.0 % -RRB- -- Restoration missing , extracted -LRB- 50 -RRB- -- -- -- Scores 60 -- 90 were not included -LRB- censored data -RRB- A log-rank test indicated that there were no statistically significant differences in survival times between the four dentists regarding single-surface restorations in both primary and permanent teeth . However , regarding the two-surface restorations in the primary dentition , statistically significant differences between the four dentists appeared -LRB- log-rank statistic 11.7 , df = 3 , p = 0.009 -RRB- . The separate survival curves are presented in Fig. 3 . Fig. 3Survival curves per dentist , multi-surface ART restorations primary dentition To detect any confounding variables on the survival of the ART restorations , a Cox regression analysis was performed . No significant relation could be found , indicating that neither the presence or absence of an adjacent tooth , nor contamination with blood and/or saliva , nor the behavior of the child during the restorative phase of the treatment had an influence on the 3-year survival of the restorations in the primary dentition . No effect also could be found regarding the number of restorations per child . Neither of these variables had an effect on the survival rates in the permanent dentition , except for the presence of adjacent teeth . Restorations in teeth where no adjacent tooth was present were found to be more likely to fail -LRB- hazard ratio = 6.53 , 95 % CI 2.66 -- 16.02 , p < 0.001 -RRB- . Discussion In contrast with other studies , the results of this study show extremely low survival rates for both single - and two-surface ART restorations in the primary and permanent dentitions . An operator effect was observed for two-surface restorations only . Neither the behavior of the child during restoration , and the number of restorations per child , nor the contamination of preparations with blood or saliva had a significant influence on the survival of the restorations in this study . This field study was performed correctly and the statistical power was sufficiently high to detect at least medium effects . However , because it was part of a large-scale randomized controlled clinical trial , no comprehensive criteria were formulated beforehand regarding , for example , the number of restorations per patient , and the location and the size of the cavities . This aspect is inherent to many cohort studies and it does not imply an inferior study quality , but it limits a meaningful comparison with other survival studies . Although all possible efforts were exercised to trace the participating children over the evaluation period , 22 restorations -LRB- 4.63 % , eight children -RRB- , all in primary molars , could not be evaluated at any of the recall visits . Either the children did not show up , or the teeth concerned had exfoliated before the first evaluation . These restorations were regarded as missing data and , therefore , excluded from further analysis . Twenty-six restorations -LRB- 5.47 % , 21 children -RRB- were `` lost '' for evaluation because the teeth either exfoliated or the child moved to another district during the course of the study , but after the first evaluation . These restorations -LRB- scores 60 -- 90 -RRB- were treated as censored data and not as true failures because they survived up to a certain moment . Many causative factors could be suggested that might explain the failure of the ART restorations , such as secondary caries , cervical margin gaps , material properties , and field conditions -LRB- outside temperature , atmospheric humidity -RRB- . However , many other ART studies face these or comparable problems and , therefore , these factors can not sufficiently explain the extremely low survival rates found in this particular study . The operator difference for the survival rates of the two-surface restorations was not unique , and not a sufficient explanation for the disappointing survival results . Operator effects are often found in ART studies -LSB- 4 , 9 , 15 , 21 , 26 -RSB- and , as in every profession , there will always be individual differences in technical skills . The finding that the absence of an adjacent tooth was related to a lower 3-year survival of single-surface ART restorations in permanent molars could not be explained . One can only speculate about possible reasons for this relationship , such as that these freestanding molars experience larger occlusal forces . A possible influence of the relatively high caries prevalence on the survival of the restorations could be hypothesized , but is very doubtful . A study in Indonesia , where the child population exhibited a much higher caries prevalence , also found disappointing survival rates for two-surface ART restorations -LSB- 28 -RSB- , but these rates were not as extreme as those found in the current study . The survival rates for single-surface ART restorations , derived from other earlier cited studies , were all very promising regardless of the caries profile of the study populations . Furthermore , no effect on the survival rates of the restorations was found when the number of restorations per child was included in the analysis . The ART protocol prescribes not to eat or drink within at least 1 h after the completion of the restorative treatment -LSB- 7 -RSB- . The children in the current study were not supervised after they received restorative treatment and consequently , their food intake could not be controlled . Future studies should take this aspect into account . Other patient-related factors that may influence the survival of the restorations are the behavior and saliva flow of the child . The survival of the ART restorations in this study was analyzed at the restoration level . This method requires independency of the restoration data and , with respect to the mentioned patient-related possible bias , this assumption could not be guaranteed . To control for this lack of independency , the survival analyses also were performed at the patient level , including only one randomly selected restoration per child . These analyses did not render higher survival rates . The predominant failure characteristics for both single - and two-surface ART restorations in the primary dentition were gross marginal defects and total or partial losses . This agrees with previous studies concerning the survival of ART restorations in the primary dentition -LSB- 6 , 13 , 25 , 26 -RSB- . Gross marginal defects could be induced by occlusal forces or insufficient wear resistance of the restorative material . Ketac-Molar was specifically developed for ART purposes -LSB- 13 -RSB- , and it has shown excellent results for posterior restorations in the primary dentition -LSB- 16 , 22 -RSB- . Glass ionomer restorations can be dislodged for a number of reasons , such as insufficient cleaning and conditioning of the cavity , and improper mixing of the material . None of these conditions was recorded at the time the tooth was restored . However , all dentists and chair-side assistants followed the ART guidelines and the manufacturer 's instructions as much as possible under the given circumstances . The main reasons for failure of the single-surface restorations in the permanent dentition were gross marginal defects and secondary caries . This latter finding is somewhat surprising and contrasts with earlier ART studies -LSB- 5 , 6 , 10 , 26 -RSB- . Glass ionomer cement has been the restorative material of choice for the ART technique , based mainly on its fluoride releasing and , thus , caries-preventive properties -LSB- 7 -RSB- . Many studies underline these characteristics of glass ionomer -LSB- 18 , 26 , 30 , 31 -RSB- . The extremely low survival of the ART restorations observed in this study remains unexplained . Circumstances that were not recognized as possible interfering factors at the start of the study might have played an important role , including cultural and seasonal dietary influences . People living in the rainforest of Suriname eat seasonal fruits such as mangos and fruits of the fiber palm -LRB- Awarra -RRB- . In particular , the latter may influence the survival of the restorations , given the frequency and method in which they are consumed . The authors have seen unusual wear patterns , also in adult dentitions , which might have been caused by excessive consumption of Awarras . A possible causality between these dietary habits and the survival of the ART restorations can only be disclosed by future controlled studies . Although previous studies have suggested that ART should not be considered as a routine procedure to restore multisurface cavities -LSB- 13 , 24 -RSB- , based on the results of this study , even the ART restoration of single-surface cavities might be reconsidered . This study underlines the inconsistency and variation in the success of the treatment . Apparently , certain conditions must be fulfilled to make ART successful . These conditions can be approached , but not always achieved , under all circumstances . Conclusion The uncertain predictability for the success of ART may introduce further discussion about alternative treatment strategies , especially in those situations where choices have to be made with respect to a well-balanced , cost-effective package of basic oral health care . To gain insight into factors determining the cumulative success rate of ART restorations , future studies should focus in more detail on variables that could possibly contribute to the failure of restorations .

O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O B I O O O O O O O O O O O O O O O O O O O O O O B I O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O B O O B O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O B O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O B I O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O B O O O O O O O O O O O O B I O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O B O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O B O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O 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O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O B I O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O B I O O O O O O O O O O O O O O O O O O O B O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O

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