Visual

and

musculoskeletal

underpinnings

of

anchoring

in

rhythmic

visuo-motor

tracking

Anchoring

that

is

a

local

reduction

in

kinematic

-LRB-

i.e.

spatio-temporal

-RRB-

variability

is

commonly

observed

in

cyclical

movements

often

at

or

around

reversal

points

Two

kinds

of

underpinnings

of

anchoring

have

been

identified

visual

and

musculoskeletal

yet

their

relative

contributions

and

interrelations

are

largely

unknown

We

conducted

an

experiment

to

delineate

the

effects

of

visual

and

musculoskeletal

factors

on

anchoring

behavior

in

visuo-motor

tracking

Thirteen

participants

-LRB-

reduced

to

in

the

analyses

-RRB-

tracked

a

sinusoidally

moving

visual

target

signal

by

making

flexion

extension

movements

about

the

wrist

while

both

visual

-LRB-

i.e.

gaze

direction

-RRB-

and

musculoskeletal

-LRB-

i.e.

wrist

posture

-RRB-

factors

were

manipulated

in

a

fully

crossed

-LRB-

-RRB-

design

Anchoring

was

affected

by

both

factors

in

the

absence

of

any

significant

interactions

implying

that

their

contributions

were

independent

When

gaze

was

directed

to

one

of

the

target

turning

points

spatial

endpoint

variability

at

this

point

was

reduced

but

not

temporal

endpoint

variability

With

the

wrist

in

a

flexed

posture

spatial

and

temporal

endpoint

variability

were

both

smaller

for

the

flexion

endpoint

than

for

the

extension

endpoint

while

the

converse

was

true

for

tracking

with

the

wrist

extended

Differential

anchoring

effects

were

absent

for

a

neutral

wrist

posture

and

when

gaze

was

fixated

in

between

the

two

target

turning

points

Detailed

analyses

of

the

tracking

trajectories

in

terms

of

velocity

profiles

and

Hooke

's

portraits

showed

that

the

tracking

dynamics

were

affected

more

by

wrist

posture

than

by

gaze

direction

The

discussion

focuses

on

the

processes

underlying

the

observed

independent

effects

of

gaze

direction

and

wrist

posture

on

anchoring

as

well

as

their

implications

for

the

notion

of

anchoring

as

a

generic

feature

of

sensorimotor

coordination

Introduction

Although

cyclical

movements

have

often

been

understood

and

modeled

as

self-sustained

oscillators

or

limit

cycles

-LRB-

Beek

et

al.

Haken

et

al.

Kay

et

al.

-RRB-

their

trajectories

in

phase

space

-LRB-

velocity

against

position

-RRB-

are

typically

wrinkled

and

asymmetric

rather

than

perfectly

harmonic

and

symmetric

A

better

approximation

can

be

achieved

by

adding

Gaussian

white

noise

to

the

limit

cycle

description

-LRB-

Kay

-RRB-

but

this

is

insufficient

to

account

for

the

observation

that

cyclical

movements

are

characterized

by

specific

regions

of

reduced

kinematic

-LRB-

i.e.

spatio-temporal

-RRB-

variability

which

are

often

but

not

solely

located

at

or

around

the

maximal

angular

excursions

or

movement

endpoints

Such

regions

have

been

dubbed

anchor

points

implying

that

they

serve

as

intentional

attractors

or

organizing

centers

within

and

for

the

entire

cycle

production

-LRB-

Beek

pp

cf.

Beek

et

al.

-RRB-

Beek

-LRB-

-RRB-

conjectured

that

at

or

around

anchor

points

critical

task-specific

information

is

available

for

organizing

a

cyclical

act

-LRB-

in

his

case

ball

juggling

-RRB-

In

line

with

this

conjecture

Kelso

and

Jeka

-LRB-

-RRB-

concluded

from

the

representation

of

patterns

as

a

single

trajectory

on

a

torus

that

the

essential

information

for

coordination

is

confined

or

localized

to

discrete

regions

in

phase

space

In

several

subsequent

studies

on

rhythmic

movement

conducted

from

a

dynamical

systems

perspective

anchor

points

or

anchoring

phenomena

have

been

observed

discussed

and

even

modeled

In

order

to

motivate

the

purpose

and

design

of

the

present

study

it

is

necessary

to

highlight

the

various

aspects

of

anchoring

that

have

been

identified

so

far

in

the

literature

Further

evidence

for

anchoring

was

obtained

in

a

study

by

Byblow

et

al.

-LRB-

-RRB-

in

which

participants

performed

bimanual

cyclical

wrist

movements

in

both

in-phase

and

antiphase

coordination

either

at

a

self-paced

tempo

or

to

the

beat

of

a

metronome

that

increased

in

frequency

In

both

cases

a

local

reduction

of

spatial

variability

was

found

at

maximal

angular

excursions

which

was

more

pronounced

for

the

dominant

than

for

the

non-dominant

hand

and

more

so

for

pronation

than

for

supination

-LRB-

see

also

Carson

et

al.

-RRB-

In

a

subsequent

study

Byblow

et

al.

-LRB-

-RRB-

reported

the

same

spatial

anchoring

phenomenon

for

unimanual

rhythmic

movements

that

were

synchronized

to

either

a

discrete

or

a

continuous

visual

pacing

signal

which

led

the

authors

to

conclude

that

anchoring

is

not

dependent

on

discrete

information

pulses

but

may

also

occur

if

the

external

pacing

signal

is

continuous

Importantly

in

this

series

of

studies

anchoring

was

defined

in

terms

of

reduced

endpoint

variability

The

authors

assumed

that

the

movement

reversal

points

were

also

the

regions

of

the

kinematics

where

information

is

specified

-LRB-

p.

-RRB-

However

for

paced

movements

this

need

not

be

the

case

because

reduced

endpoint

variability

does

not

necessarily

imply

that

participants

also

timed

their

maximal

excursions

to

the

-LRB-

discrete

or

continuous

-RRB-

external

signal

For

this

reason

it

is

important

to

distinguish

between

anchoring

as

reduced

spatial

variability

and

as

reduced

variability

in

the

timing

of

the

movement

excursions

relative

to

the

beats

or

the

reversal

points

of

the

metronome

This

difference

is

illustrated

in

Fig.

which

shows

the

phase

plane

of

a

unimanual

rhythmic

wrist

movement

that

is

synchronized

to

a

continuous

visual

signal

with

a

stationary

frequency

As

can

be

readily

appreciated

from

the

figure

the

reduced

variability

at

one

of

the

endpoints

-LRB-

as

indicated

by

the

arrows

-RRB-

does

not

imply

that

the

temporal

locations

of

the

visual

signal

-LRB-

as

indicated

by

the

circles

-RRB-

coincided

with

the

movement

reversal

points

Therefore

both

aspects

should

be

addressed

in

a

complete

analysis

of

anchoring

behavior

Fig.

phase

portrait

of

rhythmic

isofrequency

wrist

oscillations

during

an

in-phase

visuo-motor

tracking

task

Spatial

anchoring

that

is

points

or

regions

of

reduced

movement

variability

are

typically

observed

at

or

around

movement

reversal

points

-LRB-

viz.

at

peak

wrist

flexion

-LRB-

left

-RRB-

in

this

example

-RRB-

White

and

gray

circles

represent

the

time

indices

of

left

and

right

target

turning

points

-LRB-

i.e.

the

movement

reversals

of

the

visual

metronome

-RRB-

which

were

used

to

determine

temporal

anchoring

The

finding

of

Byblow

et

al.

-LRB-

-RRB-

that

anchoring

depended

on

whether

a

pronation

or

a

supination

movement

was

performed

was

replicated

by

Byblow

et

al.

-LRB-

-RRB-

and

led

to

the

notion

that

anchor

points

are

differentiated

in

terms

of

their

stability

due

to

differences

in

musculoskeletal

properties

Further

support

for

this

notion

was

found

by

Carson

-LRB-

-RRB-

and

Carson

and

Riek

-LRB-

-RRB-

in

an

experimental

set-up

in

which

participants

were

instructed

to

either

flex

or

extend

their

index

finger

to

an

auditory

metronome

Performance

was

found

to

be

more

stable

in

the

flex-on-the-beat

pattern

than

in

the

extend-on-the-beat

pattern

especially

when

the

forearm

was

in

a

supine

position

as

opposed

to

a

prone

or

neutral

position

With

this

series

of

studies

the

notion

of

anchoring

became

confined

to

the

situation

in

which

a

particular

point

in

the

movement

cycle

is

synchronized

with

an

auditory

metronome

in

spite

of

its

more

generic

original

definition

As

a

result

of

this

narrowing

anchoring

was

reduced

to

a

purely

local

effect

which

gave

Fink

et

al.

-LRB-

-RRB-

the

opportunity

to

emphasize

that

anchoring

so

defined

also

carries

global

consequences

for

the

overall

coordinative

pattern

even

though

this

aspect

was

already

inherent

to

the

original

formulation

of

anchoring

by

Beek

-LRB-

-RRB-

The

point

was

driven

home

by

showing

that

the

bimanual

coordination

was

more

stable

when

both

movement

reversal

points

of

each

finger

movement

-LRB-

i.e.

peak

flexion

and

peak

extension

-RRB-

were

paced

or

anchored

-LRB-

so-called

double-metronome

condition

-RRB-

as

opposed

to

when

only

one

reversal

point

was

anchored

-LRB-

single-metronome

condition

-RRB-

These

effects

were

explicitly

modeled

by

Jirsa

et

al.

-LRB-

-RRB-

using

a

parametric

stabilization

term

which

preserves

the

stability

properties

of

bimanual

coordination

as

captured

by

the

well-known

model

of

Haken

et

al.

-LRB-

-RRB-

for

phase

transitions

in

rhythmic

arm

and

hand

movements

while

also

explaining

the

varying

stability

of

movement

under

the

two

metronome

conditions

Another

form

of

anchoring

in

the

literature

on

eye

hand

coordination

is

known

as

gaze

anchoring

which

refers

to

the

phenomenon

of

an

enforced

ocular

target

fixation

for

the

duration

of

the

entire

pointing

movement

-LRB-

Neggers

and

Bekkering

-RRB-

When

pointing

to

a

target

the

pointing

movement

is

preceded

by

a

saccadic

eye

movement

to

the

target

-LRB-

Prablanc

et

al.

-RRB-

This

saccadic

eye

movement

is

not

only

correlated

to

the

start

of

the

arm

movement

but

the

coupling

between

gaze

and

aiming

movements

is

also

observable

after

pointing

initiation

and

it

appears

that

the

central

nervous

system

demands

ocular

fixation

of

the

pointing

target

until

pointing

is

completed

-LRB-

Neggers

and

Bekkering

-RRB-

When

participants

do

not

foveate

on

the

homing-in

phase

of

movements

pointing

accuracy

deteriorates

-LRB-

Neggers

and

Bekkering

Prablanc

et

al.

Vercher

et

al.

-RRB-

which

suggests

that

gaze

anchoring

serves

to

facilitate

the

planning

and

execution

of

pointing

movements

The

significance

of

gaze

fixations

for

the

dynamical

characteristics

of

cyclical

movements

became

apparent

in

a

recent

study

on

the

-LRB-

de

-RRB-

stabilizing

effects

of

transformed

feedback

on

visuo-motor

tracking

by

Roerdink

et

al.

-LRB-

-RRB-

When

feedback

was

absent

-LRB-

i.e.

during

normal

tracking

-RRB-

right

endpoint

variability

was

smaller

than

left

endpoint

variability

when

participants

fixated

at

the

right

whereas

the

converse

was

true

when

participants

fixated

at

the

left

Left

and

right

endpoint

variability

was

similar

during

gaze

fixations

at

the

center

and

when

smoothly

pursuing

the

target

signal

Those

findings

may

be

interpreted

to

imply

that

participants

actively

created

visuo-motor

anchors

by

fixating

their

gaze

at

one

of

both

endpoints

without

being

instructed

to

do

so

-LRB-

i.e.

gaze

direction

was

not

manipulated

in

the

experiment

-RRB-

However

the

observation

that

gaze

fixations

may

promote

motor

anchoring

does

not

exclude

the

possibility

that

musculoskeletal

properties

played

into

the

observed

anchoring

phenomena

as

well

Indeed

Roerdink

et

al.

-LRB-

-RRB-

also

found

clear

indications

that

anchoring

was

affected

by

musculoskeletal

properties

In

the

conditions

with

visual

feedback

gaze

fixation

at

the

right

resulted

in

reduced

right

endpoint

variability

as

was

the

case

without

feedback

but

now

gaze

fixation

at

the

center

also

resulted

in

reduced

endpoint

variability

at

the

right

while

no

anchoring

was

observed

for

gaze

fixation

at

the

left

Detailed

analyses

of

the

data

revealed

that

compared

to

the

condition

without

visual

feedback

participants

had

shifted

the

center

of

their

hand

excursions

to

the

right

in

the

conditions

with

visual

feedback

in

an

apparent

effort

to

align

the

feedback

signal

with

the

target

signal

This

rightward

shift

could

well

have

affected

the

relative

contributions

of

antagonistic

muscle

groups

-LRB-

i.e.

by

increasing

the

active

contribution

of

the

wrist

extensors

and

decreasing

that

of

the

wrist

flexors

to

the

hand

excursions

that

were

performed

with

the

right

hand

-RRB-

as

well

as

the

possibilities

for

storage

and

recovery

of

elastic

strain

energy

in

muscles

and

tendons

Although

the

viscosity

of

the

wrist

joint

is

negligible

and

passive

elastic

torques

are

generally

small

the

latter

become

sizeable

at

larger

wrist

excursions

-LRB-

Lehman

and

Calhoun

-RRB-

and

are

known

to

affect

the

muscular

production

of

wrist

movement

-LRB-

Schieber

and

Thach

-RRB-

In

sum

Roerdink

et

al.

-LRB-

-RRB-

found

firm

support

for

visual

underpinnings

of

anchoring

in

the

form

of

anchoring

promoting

effects

of

gaze

fixations

as

well

as

clear

indications

of

musculoskeletal

contributions

in

line

with

the

existing

evidence

in

the

literature

that

anchoring

phenomena

are

governed

by

both

visual

and

musculoskeletal

factors

However

as

the

preceding

summary

of

the

pertinent

literature

illustrates

the

effects

of

visual

and

musculoskeletal

factors

of

anchoring

have

not

yet

been

investigated

in

any

systematic

fashion

and

several

theoretically

important

issues

still

need

to

be

addressed

For

one

the

relative

contributions

of

visual

and

musculoskeletal

factors

to

anchoring

are

unknown

with

researchers

placing

theoretical

emphasis

on

either

type

of

factor

Furthermore

it

is

unknown

whether

the

effects

of

visual

and

musculoskeletal

factors

on

anchoring

are

independent

-LRB-

i.e.

additive

-RRB-

or

dependent

-LRB-

i.e.

interactive

-RRB-

To

resolve

those

issues

we

conducted

an

experiment

that

was

specifically

designed

to

systematically

delineate

the

effects

of

visual

and

musculoskeletal

factors

on

anchoring

behavior

in

visuo-motor

tracking

Our

choice

for

this

particular

experimental

task

and

set-up

was

motivated

from

our

previous

study

on

the

effects

of

visual

feedback

on

visuo-motor

tracking

which

revealed

clear

instances

of

visuo-motor

anchoring

with

marked

effects

of

gaze

direction

and

strong

hints

of

wrist

posture

effects

even

though

neither

of

these

factors

was

varied

explicitly

-LRB-

Roerdink

et

al.

-RRB-

Based

on

those

previous

results

we

expected

that

systematic

manipulations

of

both

factors

with

other

variables

such

as

tracking

frequency

and

tracking

mode

being

kept

constant

would

have

clearly

discernible

effects

on

anchoring

both

in

terms

of

its

spatial

and

temporal

characteristics

Due

to

the

absence

of

relevant

data

however

we

had

no

specific

expectations

with

respect

to

their

relative

contributions

to

anchoring

or

the

possibility

of

interaction

effects

in

that

regard

In

line

with

the

original

definition

of

anchoring

as

well

as

the

insights

of

Fink

et

al.

-LRB-

-RRB-

we

expected

both

gaze

direction

and

wrist

posture

to

not

only

influence

local

features

of

the

dynamics

of

visuo-motor

tracking

but

also

its

global

organization

Methods

Participants

Thirteen

persons

-LRB-

men

and

women

aged

years

-RRB-

volunteered

to

participate

in

the

study

All

participants

were

right-handed

according

to

their

scores

on

a

shortened

version

of

the

Edinburgh

handedness

inventory

-LRB-

Oldfield

-RRB-

and

had

normal

or

corrected

to

normal

vision

Participants

gave

their

written

informed

consent

prior

to

the

experiment

which

was

approved

by

the

ethics

committee

of

the

Faculty

of

Human

Movement

Sciences

at

VU

University

Amsterdam

Apparatus

Participants

were

seated

on

a

height-adjustable

chair

behind

a

rack

on

which

a

vertically

oriented

manipulandum

was

mounted

-LRB-

Fig.

upper

panel

-RRB-

The

manipulandum

was

attached

to

a

rotatable

horizontal

lever

whose

axis

was

aligned

with

the

wrist

's

flexion

extension

axis

The

right

hand

was

strapped

to

the

flat

manipulandum

-LRB-

fingers

extended

and

thumbs

up

-RRB-

allowing

flexion

and

extension

movements

about

the

wrist

Angular

position

of

the

wrist

was

registered

by

means

of

a

potentiometer

-LRB-

Labmaster

sampling

frequency

Hz

-RRB-

which

was

positioned

underneath

the

manipulandum

An

armrest

with

two

adjustable

supports

located

on

both

sides

of

the

forearm

just

proximal

of

the

wrist

joint

was

used

to

prevent

forearm

movement

Fig.

representation

of

the

experimental

set-up

Upper

panel

Schematic

side

view

of

the

experimental

set-up

Lower

panel

LED

bow

from

participant

's

perspective

with

the

calibration

field

superimposed

by

means

of

the

nine

white

circles

A

semicircular

projection

bow

was

positioned

in

front

of

the

participant

at

a

distance

of

cm

from

the

rotation

axis

of

the

potentiometer

matching

the

radius

of

the

bow

-LRB-

see

Fig.

lower

panel

-RRB-

The

projection

bow

consisted

of

a

continuous

array

of

light-emitting

diodes

-LRB-

LEDs

-RRB-

A

harmonically

oscillating

target

signal

was

projected

on

the

LED

bow

Concurrent

visual

feedback

of

the

angular

position

of

the

wrist

was

provided

by

means

of

a

laser

pointer

attached

to

the

manipulandum

pointing

mm

below

the

trace

of

the

target

signal

The

participant

's

chin

was

placed

on

a

height-adjustable

chinrest

and

the

head

was

secured

with

straps

between

two

vertical

supports

to

prevent

head

movements

A

horizontal

cover

was

attached

to

the

chinrest

which

prevented

vision

of

the

moving

hand

-LRB-

Fig.

-RRB-

Left

eye

orientation

was

monitored

via

reflection

of

pupil

cornea

boundaries

in

near-infrared

light

-LRB-

Applied

Systems

Laboratories

series

Eye

Tracker

sampling

frequency

Hz

spatial

error

-RRB-

To

determine

the

participant

's

point-of-gaze

eye

orientation

was

calibrated

using

a

nine-point

calibration

field

attached

to

the

LED

bow

-LRB-

Fig.

lower

panel

-RRB-

The

experimenter

received

online

feedback

of

the

point-of-gaze

on

a

video

screen

Eye

orientation

was

recalibrated

when

necessary

-LRB-

i.e.

in

case

of

an

apparent

mismatch

between

the

actual

point-of-gaze

and

its

appearance

on

the

video

screen

-RRB-

The

rack

with

armrest

and

manipulandum

could

be

positioned

in

different

orientations

with

respect

to

the

LED

bow

allowing

manipulation

of

wrist

posture

-LRB-

see

below

-RRB-

Each

rack

orientation

was

calibrated

to

the

LED

bow

to

facilitate

direct

comparison

of

target

and

feedback

signals

as

well

as

for

offline

comparison

of

target

signal

and

potentiometer

data

-LRB-

both

expressed

in

-RRB-

Point-of-gaze

was

expressed

in

allowing

for

a

comparison

of

point-of-gaze

and

the

target

signal

Eye-tracker

data

were

synchronized

with

potentiometer

and

LED

bow

data

Procedure

In

the

experimental

trials

participants

were

instructed

to

follow

the

oscillating

target

signal

The

amplitude

of

the

target

signal

was

selected

to

correspond

to

of

hand

motion

because

Peper

and

Beek

-LRB-

-RRB-

had

established

that

this

was

on

average

the

preferred

amplitude

for

this

kind

of

experimental

task

and

set-up

The

target

signal

oscillated

at

Hz

that

is

with

a

frequency

at

which

frequency-locked

point-of-gaze

oscillations

were

found

to

be

absent

for

this

experimental

task

and

set-up

-LRB-

cf.

Roerdink

et

al.

-RRB-

Participants

tracked

the

target

signal

under

experimental

manipulation

of

gaze

direction

and

wrist

posture

Participants

were

instructed

to

direct

their

gaze

to

one

of

three

fixation

points

defined

in

relation

to

the

oscillating

target

signal

that

is

the

left

target

turning

point

the

right

target

turning

point

or

the

center

in

between

the

two

target

turning

points

-LRB-

Fig.

-RRB-

Wrist

posture

was

manipulated

by

bringing

the

wrist

in

a

flexed

neutral

or

extended

posture

-LRB-

Fig.

-RRB-

In

the

flexed

posture

the

rack

with

armrest

and

manipulandum

was

positioned

such

that

the

participant

's

forearm

was

rotated

clockwise

with

respect

to

the

neutral

position

whereas

in

the

extended

posture

the

forearm

was

rotated

counterclockwise

with

respect

to

the

neutral

posture

Prior

to

the

experiment

the

participant

's

range

of

motion

was

determined

the

hand

was

secured

to

the

manipulandum

and

the

voluntarily

achieved

maximal

wrist

flexion

and

extension

positions

were

measured

The

center

of

this

range

was

considered

the

neutral

wrist

posture

for

the

participant

in

question

In

the

neutral

posture

the

wrist

was

on

average

flexed

-LRB-

-RRB-

relative

to

the

position

in

which

the

forearm

was

aligned

with

the

palm

of

the

hand

For

all

participants

the

range

of

experimental

wrist

postures

fell

well

within

the

individually

determined

maximal

range

of

motion

-LRB-

-RRB-

covering

on

average

when

the

additional

excursions

corresponding

to

the

amplitude

of

the

target

signal

were

taken

into

account

Fig.

representation

of

the

experimental

design

consisting

of

all

nine

combinations

of

wrist

posture

-LRB-

flexed

neutral

extended

-RRB-

induced

by

altering

the

orientation

of

the

forearm

with

respect

to

the

oscillating

hand

and

gaze

direction

-LRB-

left

center

right

-RRB-

schematically

represented

by

transparent

rectangles

The

three

wrist

postures

-LRB-

i.e.

flexed

neutral

and

extended

-RRB-

were

crossed

with

the

three

gaze

directions

-LRB-

i.e.

left

center

and

right

region

of

the

target

signal

-RRB-

resulting

in

nine

experimental

conditions

-LRB-

see

Fig.

for

a

schematic

representation

-RRB-

Participants

performed

all

conditions

five

times

amounting

to

a

total

of

trials

per

participant

Trials

were

presented

in

blocks

with

the

three

wrist

postures

providing

the

first

level

of

blocking

-LRB-

trials

-RRB-

and

gaze

direction

-LRB-

trials

-RRB-

the

next

The

order

of

the

wrist

posture

blocks

was

counterbalanced

over

participants

-LRB-

with

each

order

being

performed

by

two

participants

full

counterbalancing

was

possible

because

the

data

of

one

participant

were

discarded

see

below

-RRB-

The

gaze

direction

blocks

within

the

wrist

posture

blocks

were

presented

in

random

order

Prior

to

each

wrist

posture

block

participants

were

invited

to

familiarize

themselves

with

each

new

wrist

posture

through

making

self-paced

wrist

movements

The

laser

pointer

provided

direct

feedback

of

the

hand

movement

during

both

familiarization

and

experimental

trials

Participants

were

instructed

to

move

their

hand

in

phase

with

the

oscillating

target

signal

as

accurately

as

possible

while

directing

their

gaze

to

the

instructed

fixation

point

-LRB-

left

center

or

right

-RRB-

To

facilitate

trial

initiation

the

target

signal

always

started

at

the

attended

area

All

trials

lasted

s

-LRB-

i.e.

cycles

-RRB-

Data

analysis

The

data

of

one

participant

were

excluded

from

the

analysis

because

the

point-of-gaze

data

were

disturbed

-LRB-

i.e.

pupil

cornea

boundaries

were

often

undetectable

due

to

squeezing

of

the

eyes

i.e.

partial

eye

closures

-RRB-

For

the

remaining

participants

point-of-gaze

was

assessed

-LRB-

in

-RRB-

for

each

trial

to

ensure

that

they

had

adhered

to

the

task

instructions

regarding

gaze

direction

Specifically

the

horizontal

point-of-gaze

data

were

classified

according

to

three

groups

viz.

left

center

and

right

defined

by

regions

of

centered

around

-LRB-

left

target

turning

point

-RRB-

around

-LRB-

center

in

between

the

two

target

turning

points

-RRB-

and

around

-LRB-

right

target

turning

point

-RRB-

respectively

As

is

common

in

eye-tracking

missing

or

disturbed

values

occasionally

occurred

due

to

blinking

or

brief

eye

closures

For

a

trial

to

be

included

in

the

analyses

at

least

of

the

horizontal

point-of-gaze

samples

had

to

fall

within

the

range

from

to

while

in

turn

at

least

of

those

samples

had

to

fall

within

the

instructed

region

Based

on

this

nested

criterion

out

of

the

total

of

trials

were

discarded

For

the

included

trials

gaze

was

directed

to

the

instructed

region

-LRB-

i.e.

left

center

or

right

-RRB-

on

average

of

the

time

All

participants

successfully

performed

the

tracking

task

in

that

the

mean

tracking

frequency

defined

as

the

inverse

of

the

period

between

maximal

extensions

of

the

wrist

of

the

included

trials

was

Hz

with

a

very

small

overall

standard

deviation

-LRB-

Hz

-RRB-

One

trial

was

removed

because

of

phase

wrapping

which

occurred

to

catch

up

after

a

late

start

Pre-processing

Potentiometer

data

-LRB-

hand

movement

-RRB-

and

LED

coordinates

-LRB-

target

-RRB-

of

the

included

trials

were

transformed

into

and

low-pass

filtered

using

a

bi-directional

second-order

Butterworth

filter

-LRB-

cut-off

frequency

Hz

-RRB-

The

first

five

cycles

of

each

trial

were

excluded

from

analysis

to

eliminate

possible

transient

effects

From

the

remaining

cycles

several

dependent

variables

were

calculated

Those

variables

related

to

tracking

performance

anchoring

and

global

kinematics

respectively

Tracking

performance

Tracking

accuracy

was

determined

by

calculating

the

root

mean

square

-LRB-

RMS

-RRB-

of

the

continuous

error

between

target

and

hand

movement

which

was

obtained

by

subtracting

the

actual

position

from

the

required

position

In

addition

the

continuous

relative

phase

-LRB-

in

-RRB-

between

the

target

signal

and

the

hand

movement

was

calculated

by

subtracting

the

phase

of

the

hand

oscillations

from

that

of

the

target

oscillations

Mean

relative

phase

-LRB-

ϕ

-RRB-

and

its

transformed

circular

variance

-LRB-

TCV

-RRB-

were

quantified

using

circular

statistics

-LRB-

cf.

Burgess-Limerick

et

al.

Mardia

-RRB-

Anchoring

In

both

discretely

and

continuously

paced

cyclical

movements

as

well

as

in

self-paced

rhythmic

movements

anchoring

typically

occurs

at

or

around

the

movement

reversal

points

-LRB-

see

also

Fig.

-RRB-

where

it

may

become

manifest

as

a

reduction

of

spatial

-LRB-

e.g.

Byblow

et

al.

Fink

et

al.

Roerdink

et

al.

-RRB-

or

temporal

-LRB-

e.g.

Roerdink

et

al.

-RRB-

variability

or

both

We

therefore

determined

-LRB-

a

-RRB-

the

spatial

variability

of

maximal

wrist

flexion

and

extension

excursions

by

calculating

the

respective

standard

deviations

-LRB-

SD

in

-RRB-

and

-LRB-

b

-RRB-

the

temporal

variability

between

the

time

instances

of

the

left

and

right

target

turning

points

and

the

corresponding

time

instances

of

maximal

wrist

flexion

and

extension

excursions

-LRB-

SD

in

ms

-RRB-

To

quantify

the

presence

or

absence

of

anchor

points

in

the

tracking

trajectories

variants

of

the

following

general

anchoring

index

-LRB-

AI

dimensionless

-RRB-

were

calculated

in

which

SDl

and

SDr

represent

the

spatial

or

temporal

variability

corresponding

to

the

left

and

right

target

turning

point

respectively

If

SDl

and

SDr

are

equal

AI

AI

corresponds

to

smaller

spatial

or

temporal

variability

at

the

left

than

at

the

right

target

turning

point

-LRB-

i.e.

anchoring

at

peak

flexion

-RRB-

whereas

the

opposite

is

true

for

AI

-LRB-

i.e.

anchoring

at

peak

extension

-RRB-

AIspatial

and

AItemporal

denote

the

anchoring

index

for

spatial

and

temporal

variability

respectively

The

anchoring

index

captures

local

effects

of

wrist

posture

and

gaze

direction

in

predefined

regions

of

the

tracking

trajectories

In

theory

anchor

points

or

regions

may

be

found

elsewhere

in

the

movement

cycle

but

a

first

inspection

of

the

data

indicated

that

anchoring

occurred

at

or

near

the

endpoints

-LRB-

see

also

Fig.

-RRB-

as

indeed

was

found

in

the

previous

studies

on

anchoring

cited

in

the

Introduction

However

to

avoid

that

we

would

miss

important

kinematic

aspects

of

the

tracking

trajectories

we

not

only

focused

on

the

effects

of

wrist

posture

and

gaze

direction

around

movement

reversal

points

but

also

on

more

global

properties

of

the

tracking

trajectories

Global

kinematics

The

global

properties

of

the

tracking

trajectories

were

assessed

by

means

of

the

velocity

profiles

-LRB-

i.e.

wrist

angular

velocity

as

a

function

of

cycle

time

-RRB-

and

Hooke

's

portraits

-LRB-

i.e.

wrist

angular

acceleration

as

a

function

of

wrist

angular

position

-RRB-

To

assess

those

properties

wrist

angular

position

time

series

were

normalized

to

the

amplitude

of

the

target

signal

-LRB-

i.e.

implies

target

turning

point

on

the

flexion

side

implies

target

turning

point

on

the

extension

side

-RRB-

after

which

the

normalized

position

time

series

were

mean

centered

Next

velocity

and

acceleration

time

series

were

computed

from

the

position

time

series

by

means

of

a

conventional

difference

algorithm

and

normalized

to

the

angular

velocity

of

the

target

signal

-LRB-

i.e.

divided

by

π

-RRB-

Based

on

the

minima

of

the

position

time

series

corresponding

to

maximal

wrist

flexion

each

cycle

was

cut

from

the

velocity

time

series

-LRB-

i.e.

from

maximal

flexion

via

maximal

extension

to

maximal

flexion

-RRB-

The

individual

velocity

profiles

were

time-normalized

to

points

using

a

spline

interpolation

procedure

i.e.

a

normalization

to

percentage

cycle

time

and

the

average

velocity

profile

was

calculated

for

each

participant

for

each

included

trial

From

this

average

velocity

profile

the

duration

of

flexion

and

extension

movements

were

taken

and

summarized

in

the

movement

duration

index

-LRB-

MDI

dimensionless

-RRB-

expressed

as

in

which

MDflexion

-LRB-

MDextension

-RRB-

is

the

duration

from

maximal

wrist

extension

-LRB-

flexion

-RRB-

to

maximal

wrist

flexion

-LRB-

extension

-RRB-

If

MDflexion

and

MDextension

are

equal

MDI

MDI

corresponds

to

shorter

duration

of

the

flexion

than

the

extension

half

cycle

whereas

the

opposite

is

true

for

MDI

Furthermore

peak

velocities

for

the

flexion

and

extension

movements

were

taken

-LRB-

i.e.

PVflexion

and

PVextension

respectively

-RRB-

and

represented

in

the

peak

velocity

index

-LRB-

PVI

dimensionless

-RRB-

expressed

as

If

PVflexion

and

PVextension

are

equal

PVI

PVI

indicates

that

flexion

peak

velocity

is

smaller

than

extension

peak

velocity

whereas

the

opposite

is

true

for

PVI

Note

that

for

harmonic

wrist

oscillations

PVI

and

MDI

both

approach

The

Hooke

's

portraits

were

constructed

as

follows

Based

on

the

extrema

in

the

normalized

wrist

angular

position

time

series

corresponding

to

peak

flexion

and

extension

each

half

cycle

was

cut

from

the

position

and

acceleration

time

series

-LRB-

i.e.

from

peak

flexion

to

peak

extension

and

from

peak

extension

to

peak

flexion

-RRB-

The

position

and

acceleration

half

cycles

were

time-normalized

to

points

using

a

spline

interpolation

procedure

Next

the

average

position

and

acceleration

time

series

were

computed

for

every

half

cycle

for

each

trial

of

each

participant

A

linear

-LRB-

harmonic

-RRB-

oscillator

implies

a

straight

line

in

the

Hooke

's

portrait

whereas

a

deviation

from

a

straight

line

represents

the

contribution

of

nonlinear

components

The

amount

of

variance

that

can

be

attributed

to

a

harmonic

oscillation

can

be

readily

quantified

by

the

of

the

linear

regression

of

position

onto

acceleration

-LRB-

i.e.

for

a

purely

harmonic

oscillation

such

as

the

target

signal

-RRB-

The

explained

variance

of

the

summed

contribution

of

nonlinear

terms

was

expressed

as

NL

-LRB-

Mottet

and

Bootsma

for

a

similar

approach

see

Beek

and

Beek

-RRB-

Statistical

analysis

To

determine

the

effects

of

wrist

posture

and

gaze

direction

on

tracking

behavior

each

dependent

variable

was

submitted

to

a

repeated

measures

analysis

of

variance

-LRB-

ANOVA

-RRB-

with

within-subject

factors

wrist

posture

-LRB-

levels

flexed

neutral

extended

-RRB-

and

gaze

direction

-LRB-

levels

left

center

right

-RRB-

Individual

scores

per

condition

were

obtained

by

averaging

the

values

of

the

included

trials

for

the

condition

in

question

Significant

effects

-LRB-

P

-RRB-

are

reported

and

effect

sizes

are

represented

as

partial

eta

squared

values

Post-hoc

analysis

was

performed

using

two-tailed

paired-samples

t

tests

-LRB-

with

Bonferroni

correction

-RRB-

One-sample

t

tests

were

conducted

to

see

whether

AIspatial

and

AItemporal

differed

significantly

from

-LRB-

the

value

indicating

that

spatial

or

temporal

variability

corresponding

to

the

left

and

right

target

turning

point

are

similar

-RRB-

Results

Effects

of

wrist

posture

Wrist

posture

had

significant

effects

on

the

variability

of

the

relative

phase

between

tracking

and

the

target

signal

-LRB-

TCV

-RRB-

the

spatial

and

temporal

anchoring

indices

-LRB-

AIspatial

AItemporal

-RRB-

the

velocity

profile

characteristics

-LRB-

MDI

PVI

-RRB-

and

the

harmonicity

-LRB-

NL

-RRB-

of

tracking

trajectories

-LRB-

see

Table

-RRB-

Tracking

accuracy

-LRB-

RMS

mean

standard

error

-RRB-

and

mean

relative

phase

-LRB-

ϕ

indicating

that

wrist

oscillations

were

slightly

leading

the

target

signal

-RRB-

did

not

differ

significantly

over

wrist

postures

Post-hoc

analysis

indicated

that

TCV

was

significantly

larger

for

the

extended

wrist

posture

-LRB-

-RRB-

than

for

the

flexed

posture

-LRB-

-RRB-

while

TCV

for

the

neutral

posture

-LRB-

-RRB-

was

not

significantly

different

from

the

flexed

and

extended

posture.Table

of

the

repeated

measures

ANOVA

on

dependent

variablesDependent

variableWrist

postureGaze

directionPosture

gazeF

-LRB-

-RRB-

PF

-LRB-

-RRB-

PF

-LRB-

-RRB-

ϕ0

NS

NS

NS

NS

Main

effects

of

wrist

posture

and

gaze

direction

and

wrist

posture

gaze

direction

interaction

effects

are

presentedRMS

root

mean

square

of

the

continuous

error

between

target

and

hand

movement

ϕ

mean

relative

phase

between

target

and

hand

movement

TCV

transformed

circular

variance

of

ϕ

AIspatial

spatial

anchoring

index

AItemporal

temporal

anchoring

index

PVI

peak

velocity

index

MDI

movement

duration

index

NL

contribution

of

nonlinear

terms

to

tracking

trajectories

AIspatial

for

the

extended

wrist

posture

differed

significantly

from

that

for

the

neutral

and

flexed

posture

while

AItemporal

differed

significantly

between

all

wrist

postures

Importantly

both

anchoring

indices

differed

from

for

the

flexed

and

extended

postures

but

not

for

the

neutral

posture

-LRB-

see

Fig.

left

panels

-RRB-

One-sample

t

tests

revealed

that

AIspatial

and

AItemporal

were

significantly

smaller

-LRB-

and

respectively

-RRB-

than

in

the

flexed

posture

-LRB-

t

-LRB-

-RRB-

P

and

t

-LRB-

-RRB-

P

respectively

-RRB-

and

significantly

greater

-LRB-

and

respectively

-RRB-

than

in

the

extended

posture

-LRB-

t

-LRB-

-RRB-

P

and

t

-LRB-

-RRB-

P

respectively

-RRB-

indicating

that

anchoring

occurred

at

maximal

flexion

and

extension

respectively.Fig

and

temporal

anchoring

indices

as

a

function

of

wrist

posture

-LRB-

left

panels

-RRB-

and

gaze

direction

-LRB-

right

panels

-RRB-

Asterisks

indicate

significant

differences

with

AI

Error

bars

represent

standard

error

These

indications

of

anchoring

were

accompanied

by

significant

changes

in

the

tracking

trajectories

as

can

be

appreciated

from

the

averaged

velocity

profiles

depicted

for

each

wrist

posture

in

Fig.

-LRB-

left

column

-RRB-

The

cycle

duration

of

the

flexion

-LRB-

extension

-RRB-

phase

was

shorter

than

for

tracking

with

the

wrist

in

a

flexed

-LRB-

extended

-RRB-

posture

Furthermore

flexion

peak

velocity

was

higher

than

extension

peak

velocity

for

tracking

with

a

flexed

wrist

posture

while

the

opposite

was

the

case

for

tracking

with

an

extended

wrist

posture

In

a

neutral

wrist

posture

the

velocity

profile

was

nearly

harmonic

with

similar

flexion

and

extension

half

cycle

durations

and

peak

velocities

These

observations

were

all

confirmed

statistically

Specifically

a

significant

main

effect

of

wrist

posture

was

observed

for

PVI

and

MDI

-LRB-

see

Table

-RRB-

post-hoc

analysis

indicated

that

PVI

and

MDI

differed

significantly

for

all

three

wrist

postures

One-sample

t

tests

revealed

that

in

the

flexed

wrist

posture

the

duration

of

the

flexion

phase

was

significantly

shorter

than

that

of

the

extension

phase

-LRB-

i.e.

MDI

t

-LRB-

-RRB-

P

-RRB-

while

flexion

peak

velocity

was

significantly

higher

than

extension

peak

velocity

-LRB-

i.e.

PVI

t

-LRB-

-RRB-

P

-RRB-

In

the

extended

wrist

posture

the

converse

was

true

-LRB-

MDI

t

-LRB-

-RRB-

P

PVI

t

-LRB-

-RRB-

P

-RRB-

indicating

shorter

extension

phase

duration

and

higher

extension

peak

velocity

In

the

neutral

wrist

posture

condition

both

PVI

-LRB-

-RRB-

and

MDI

-LRB-

-RRB-

did

not

differ

significantly

from

Fig.

normalized

velocity

profiles

as

a

function

of

wrist

posture

-LRB-

left

panel

-RRB-

and

gaze

direction

-LRB-

right

panel

-RRB-

For

a

harmonic

oscillator

extension

and

flexion

peak

velocities

equal

and

respectively

while

the

zero

crossing

of

the

velocity

profile

occurs

at

the

vertical

dashed

line

indicating

that

the

extension

and

flexion

phase

have

the

same

duration

The

most

striking

aspect

of

the

Hooke

's

portraits

was

the

general

tendency

to

deviate

from

a

straight

line

-LRB-

representing

harmonic

oscillation

-RRB-

with

the

wrist

flexed

or

extended

Fig.

shows

averaged

Hooke

's

portraits

of

the

flexion

and

extension

half

cycles

for

each

combination

of

wrist

posture

and

gaze

direction

The

panels

in

the

rows

show

the

Hooke

's

portraits

for

each

wrist

posture

As

is

evident

from

the

figure

the

harmonicity

was

reduced

in

the

flexed

and

extended

wrist

posture

compared

to

the

neutral

wrist

posture

-LRB-

larger

deviations

from

the

line

acceleration

position

-RRB-

especially

for

tracking

with

the

wrist

extended

This

was

also

reflected

in

the

variance

that

was

attributed

to

nonlinear

components

as

quantified

by

NL

-LRB-

reflecting

the

residual

of

the

linear

regression

of

position

onto

acceleration

-RRB-

In

particular

a

significant

main

effect

of

wrist

posture

was

observed

for

NL

-LRB-

see

Table

-RRB-

Post-hoc

analysis

revealed

that

the

contribution

of

nonlinear

terms

was

significantly

greater

in

the

extended

wrist

posture

compared

to

the

neutral

wrist

posture

-LRB-

NL

and

respectively

-RRB-

NL

for

tracking

with

the

wrist

in

a

flexed

posture

-LRB-

NL

-RRB-

did

not

differ

significantly

from

the

other

two

wrist

postures

Note

that

the

reduced

harmonicity

of

tracking

in

the

extended

wrist

posture

may

well

have

caused

the

significant

increase

in

TCV

in

the

extended

wrist

posture

relative

to

that

of

the

flexed

posture.Fig

's

portraits

as

a

function

of

gaze

direction

-LRB-

columns

left

center

right

-RRB-

and

wrist

posture

-LRB-

rows

flexed

neutral

extended

-RRB-

with

flexion

and

extension

half

cycles

indicated

in

gray

and

black

respectively

The

dotted

black

line

represents

the

Hooke

's

portrait

for

the

harmonically

moving

target

signal

Effects

of

gaze

direction

Gaze

direction

had

significant

effects

on

mean

continuous

tracking

relative

phase

-LRB-

ϕ

-RRB-

the

spatial

anchoring

index

-LRB-

AIspatial

-RRB-

and

velocity

profile

properties

-LRB-

MDI

PVI

-RRB-

but

not

on

tracking

accuracy

-LRB-

RMS

-RRB-

relative

phase

variability

-LRB-

TCV

-RRB-

the

temporal

anchoring

index

-LRB-

AItemporal

-RRB-

and

the

harmonicity

-LRB-

NL

-RRB-

of

tracking

trajectories

-LRB-

see

Table

-RRB-

Post-hoc

analysis

revealed

that

ϕ

was

significantly

less

negative

when

gaze

was

directed

to

the

right

-LRB-

-RRB-

than

when

gaze

was

directed

to

the

left

-LRB-

-RRB-

or

the

center

-LRB-

-RRB-

region

Post-hoc

analysis

further

revealed

that

AIspatial

differed

significantly

between

all

three

gaze

directions

Moreover

one-sample

t

tests

revealed

that

AIspatial

was

significantly

smaller

than

when

gaze

was

directed

to

the

left

target

turning

point

-LRB-

t

-LRB-

-RRB-

P

-RRB-

indicating

smaller

left

-LRB-

corresponding

to

maximal

flexion

excursions

-RRB-

than

right

-LRB-

corresponding

to

maximal

extension

excursions

-RRB-

endpoint

variability

-LRB-

see

Fig.

upper

right

panel

-RRB-

Similarly

AIspatial

was

significantly

larger

than

when

gaze

was

directed

to

the

right

target

turning

point

-LRB-

t

-LRB-

-RRB-

P

-RRB-

indicating

anchoring

at

the

right

-LRB-

extension

-RRB-

endpoint

AIspatial

was

not

significantly

different

from

when

gaze

was

directed

at

the

center

region

between

the

two

target

turning

points

-LRB-

AIspatial

-RRB-

Whereas

gaze

direction

had

a

strong

effect

on

the

spatial

anchoring

index

the

effect

of

gaze

direction

on

AItemporal

was

not

significant

as

can

be

appreciated

from

Fig.

-LRB-

lower

right

panel

see

also

Table

-RRB-

The

right

panel

in

Fig.

depicts

the

averaged

velocity

profiles

as

a

function

of

gaze

direction

The

effect

of

gaze

direction

on

the

velocity

profile

characteristics

PVI

and

MDI

was

much

smaller

than

that

of

wrist

posture

-LRB-

i.e.

smaller

deviations

from

compare

also

the

corresponding

effect

sizes

in

Table

-RRB-

Nevertheless

the

significant

main

effect

of

gaze

direction

entailed

that

when

gaze

was

directed

to

the

right

target

turning

point

PVI

and

MDI

were

significantly

different

from

the

other

two

gaze

directions

-LRB-

for

left

center

and

right

respectively

PVI

and

MDI

and

-RRB-

One-sample

t

tests

indicated

that

when

gaze

was

directed

to

the

target

turning

points

-LRB-

left

or

right

-RRB-

the

hand

movements

in

that

direction

were

shorter

in

duration

with

a

larger

peak

velocity

As

is

apparent

from

a

comparison

of

the

Hooke

's

portraits

depicted

in

the

columns

of

Fig.

gaze

direction

only

had

a

limited

influence

on

the

nonlinear

terms

in

the

hand

oscillations

-LRB-

particularly

if

compared

to

the

effect

of

wrist

posture

as

presented

in

the

three

rows

of

Fig.

-RRB-

The

effect

of

gaze

direction

on

NL

was

not

significant

-LRB-

left

center

right

-RRB-

Wrist

posture

gaze

direction

interaction

effects

of

the

dependent

variables

showed

a

significant

wrist

posture

gaze

direction

interaction

effect

-LRB-

see

Table

-RRB-

implying

that

the

respective

effects

of

the

two

factors

were

independent

and

additive

in

case

both

yielded

significant

main

effects

A

case

in

point

is

the

spatial

anchoring

index

AIspatial

-LRB-

see

Table

-RRB-

Both

wrist

posture

and

gaze

direction

had

a

significant

effect

on

AIspatial

in

the

absence

of

a

significant

wrist

posture

gaze

direction

interaction

effect

Fig.

presenting

AIspatial

for

all

combinations

of

wrist

posture

and

gaze

direction

illustrates

the

additive

manner

in

which

the

two

factors

affected

spatial

anchoring

-LRB-

cf.

the

staircase

pattern

in

each

wrist

posture

condition

-RRB-

Fig.

anchoring

index

for

all

combinations

of

wrist

posture

-LRB-

flexed

neutral

extended

-RRB-

and

gaze

direction

-LRB-

left

-LSB-

L

-RSB-

center

-LSB-

C

-RSB-

right

-LSB-

R

-RSB-

-RRB-

Asterisks

indicate

significant

differences

with

AIspatial

Error

bars

represent

the

standard

error

Discussion

In

the

present

experiment

we

sought

to

systematically

delineate

the

effects

of

visual

and

musculoskeletal

factors

on

anchoring

phenomena

that

is

local

reductions

in

kinematic

variability

which

may

reflect

organizing

centers

for

perceptual-motor

control

In

particular

we

investigated

the

relative

contributions

of

gaze

direction

and

wrist

posture

on

both

spatial

and

temporal

anchoring

in

the

performance

of

a

rhythmic

unimanual

visuo-motor

tracking

task

In

addition

we

examined

the

velocity

profiles

and

Hooke

's

portraits

of

the

full

tracking

trajectories

to

gain

insight

into

the

relationship

between

the

local

anchoring

phenomena

and

the

global

organization

of

the

tracking

movements

In

the

following

we

first

outline

the

main

findings

of

both

types

of

analysis

before

discussing

their

broader

implications

for

the

theoretical

understanding

of

anchoring

Effects

on

spatial

and

temporal

anchoring

As

stated

in

the

introduction

previous

research

revealed

that

the

degree

of

anchoring

is

a

function

of

musculoskeletal

properties

such

as

the

type

of

movement

performed

-LRB-

i.e.

flexion

versus

extension

pronation

vs.

supination

-RRB-

and

the

relative

length

of

flexor

and

extensor

muscles

Besides

musculoskeletal

influences

Roerdink

et

al.

-LRB-

-RRB-

also

reported

evidence

for

visual

underpinnings

in

that

anchoring

was

found

to

depend

on

gaze

direction

Based

on

those

findings

we

expected

that

systematic

manipulations

of

gaze

direction

and

wrist

posture

would

have

clearly

discernable

effects

on

anchoring

which

was

indeed

the

case

Both

gaze

direction

and

wrist

posture

significantly

affected

endpoint

variability

in

the

expected

direction

-LRB-

see

Fig.

upper

panels

-RRB-

Specifically

when

gaze

was

directed

to

the

left

target

turning

point

left

-LRB-

i.e.

flexion

-RRB-

spatial

endpoint

variability

was

reduced

while

the

converse

was

true

when

gaze

was

directed

to

the

right

target

turning

point

In

contrast

differential

anchoring

effects

were

absent

when

gaze

was

fixated

in

between

the

two

target

turning

points

Furthermore

endpoint

variability

was

smaller

for

the

extension

endpoint

than

for

the

flexion

endpoint

when

the

wrist

was

in

an

extended

posture

whereas

differential

anchoring

effects

were

absent

when

tracking

was

performed

with

the

wrist

in

a

neutral

posture

All

of

these

findings

are

fully

in

line

with

those

of

Roerdink

et

al.

-LRB-

-RRB-

even

though

gaze

direction

and

wrist

posture

were

systematically

manipulated

only

in

the

present

study

Moreover

the

current

systematic

variations

of

wrist

posture

also

revealed

that

for

the

flexed

wrist

posture

flexion

endpoint

variability

was

lower

than

extension

endpoint

variability

In

addition

to

spatial

anchoring

we

examined

temporal

anchoring

that

is

local

reductions

in

the

variability

of

the

timing

of

the

maximal

movement

excursions

relative

to

the

reversal

points

of

the

visual

metronome

an

aspect

that

was

not

addressed

in

previous

studies

This

complementary

analysis

revealed

that

temporal

anchoring

was

affected

by

wrist

posture

but

not

by

gaze

direction

suggesting

that

wrist

posture

had

a

different

more

pronounced

effect

on

anchoring

than

gaze

direction

-LRB-

see

Fig.

lower

panels

-RRB-

Specifically

with

the

wrist

in

a

flexed

posture

the

variability

in

the

timing

of

flexion

excursions

relative

to

the

target

was

lower

than

that

of

extension

excursions

while

the

converse

was

true

with

the

wrist

extended

No

differential

effect

in

timing

variability

was

observed

for

tracking

with

the

wrist

in

a

neutral

posture

nor

for

the

three

different

gaze

directions

These

findings

suggest

that

movements

were

actively

timed

or

anchored

on

maximal

flexion

with

the

wrist

in

a

flexed

posture

and

on

maximal

extension

with

the

wrist

in

an

extended

posture

In

contrast

the

absence

of

an

effect

of

gaze

direction

on

temporal

anchoring

may

imply

that

gaze

direction

only

affected

the

spatial

accuracy

of

the

tracking

movements

but

not

their

timing

For

reasons

explained

in

the

introduction

we

had

no

specific

expectations

with

respect

to

the

issue

whether

the

effects

of

visual

and

musculoskeletal

factors

on

anchoring

were

independent

-LRB-

i.e.

additive

-RRB-

or

dependent

-LRB-

i.e.

interactive

-RRB-

in

nature

The

results

indicated

that

gaze

direction

and

wrist

posture

affected

anchoring

in

an

additive

rather

than

interactive

fashion

-LRB-

see

Fig.

-RRB-

because

no

significant

interactions

between

gaze

direction

and

wrist

posture

were

found

for

any

of

the

dependent

variables

-LRB-

see

Table

-RRB-

The

fact

that

gaze

direction

affected

only

spatial

anchoring

and

not

temporal

anchoring

provided

further

support

for

the

conclusion

that

the

contributions

of

gaze

direction

and

wrist

posture

to

anchoring

were

independent

Effects

on

global

tracking

behavior

The

analyses

of

the

velocity

profiles

and

Hooke

's

portraits

of

the

full

tracking

trajectories

revealed

that

wrist

posture

had

a

much

larger

effect

than

gaze

direction

on

the

global

tracking

behavior

As

can

be

observed

in

Fig.

velocity

profiles

were

asymmetric

when

tracking

was

performed

with

the

wrist

flexed

or

extended

as

opposed

to

a

neutral

wrist

configuration

which

resulted

in

symmetric

bell-shaped

velocity

profiles

The

three

different

gaze

directions

only

affected

the

velocity

profiles

to

a

limited

yet

significant

degree

Congruently

wrist

posture

affected

the

harmonicity

of

the

wrist

movements

much

more

than

gaze

direction

as

can

be

appreciated

from

Fig.

-LRB-

viz.

greater

deviation

from

the

straight

line

representing

harmonic

oscillation

-RRB-

Those

qualitative

observations

were

reflected

in

significant

differences

in

the

duration

peak

velocity

and

harmonicity

of

the

flexion

and

extension

phases

of

the

movement

as

determined

from

the

velocity

profiles

and

Hooke

's

portraits

Wrist

posture

strongly

affected

the

global

tracking

behavior

and

led

to

marked

differences

between

flexion

and

extension

for

wrist

postures

other

than

neutral

For

the

flexed

-LRB-

extended

-RRB-

wrist

posture

the

flexion

-LRB-

extension

-RRB-

phase

lasted

shorter

had

higher

peak

velocity

and

was

less

harmonic

than

the

extension

-LRB-

flexion

-RRB-

phase

Gaze

direction

also

significantly

affected

movement

duration

and

peak

velocity

of

the

flexion

and

extension

half

cycles

albeit

to

a

much

smaller

degree

If

gaze

was

directed

to

the

left

-LRB-

right

-RRB-

target

turning

point

the

duration

of

the

flexion

-LRB-

extension

-RRB-

phase

was

shorter

than

that

of

the

extension

-LRB-

flexion

-RRB-

phase

accompanied

by

higher

flexion

-LRB-

extension

-RRB-

peak

velocity

When

gaze

was

fixated

in

between

the

two

target

turning

points

velocity

profiles

were

symmetric

Tracking

harmonicity

was

not

significantly

affected

by

gaze

direction

Furthermore

Hooke

's

portraits

for

tracking

with

the

wrist

flexed

and

extended

should

be

rich

in

information

about

specific

conservative

and

dissipative

nonlinear

components

giving

rise

to

the

observed

anharmonicity

-LRB-

Beek

and

Beek

see

also

Beek

et

al.

Buchanan

et

al.

Mottet

and

Bootsma

-RRB-

As

can

be

appreciated

from

Fig.

local

stiffness

tended

to

increase

towards

the

anchored

endpoint

indicating

a

so-called

hardening

spring

corresponding

to

an

additional

Duffing

term

in

the

equation

of

motion

-LRB-

Beek

and

Beek

Mottet

and

Bootsma

-RRB-

Besides

this

nonlinear

conservative

term

also

nonlinear

dissipative

terms

appeared

to

be

operative

towards

the

anchored

endpoint

given

the

asymmetry

in

the

acceleration

and

deceleration

parts

of

the

half

cycle

in

question

Considering

that

zero

acceleration

-LRB-

i.e.

peak

velocity

-RRB-

occurred

in

the

first

part

of

the

flexion

-LRB-

extension

-RRB-

phase

for

a

flexed

-LRB-

extended

-RRB-

posture

a

self-sustaining

Rayleigh

oscillator

is

a

likely

candidate

for

the

dissipative

terms

contributing

to

the

anharmonic

tracking

behavior

-LRB-

Beek

and

Beek

Mottet

and

Bootsma

-RRB-

Finally

visual

inspection

of

the

nine

panels

of

Fig.

suggests

a

graded

modulation

of

those

nonlinear

conservative

and

dissipative

components

as

a

function

of

wrist

posture

and

gaze

direction

underscoring

again

that

both

factors

had

an

additive

rather

than

an

interactive

effect

on

the

organization

of

tracking

Musculoskeletal

underpinnings

of

anchoring

The

marked

effects

of

wrist

posture

on

anchoring

and

the

global

organization

of

tracking

may

be

related

to

a

variety

of

musculoskeletal

factors

including

the

possibility

of

saving

mechanical

energy

from

half

cycle

to

half

cycle

owing

to

the

ability

of

muscles

to

store

mechanical

energy

in

a

potential

elastic

form

towards

the

end

of

each

half

cycle

to

facilitate

the

production

of

the

next

half

cycle

-LRB-

Guiard

-RRB-

Although

this

storage

and

release

of

elastic

strain

energy

in

muscles

and

tendons

is

considered

to

play

a

limited

role

in

rhythmic

wrist

movements

passive

elastic

torques

become

sizeable

at

larger

wrist

excursions

-LRB-

Lehman

and

Calhoun

Schieber

and

Thach

-RRB-

Hence

this

energy-saving

mechanism

may

well

be

relevant

for

tracking

with

the

wrist

flexed

or

extended

and

underlie

the

conservative

and

dissipative

terms

identified

in

the

Hooke

's

portraits

as

will

be

discussed

further

below

The

temporal

anchoring

analysis

revealed

that

movements

were

actively

timed

or

anchored

on

maximal

flexion

with

the

wrist

in

a

flexed

posture

and

on

maximal

extension

with

the

wrist

in

an

extended

posture

In

either

case

movement

durations

were

shorter

-LRB-

and

peak

velocities

larger

-RRB-

towards

the

anchored

endpoint

Following

a

similar

line

of

reasoning

the

observed

deviation

from

harmonicity

in

the

Hooke

's

portraits

for

a

flexed

-LRB-

extended

-RRB-

wrist

posture

suggests

that

flexion

-LRB-

extension

-RRB-

movements

are

actively

steered

to

a

specific

point

in

the

perceptual-motor

workspace

-LRB-

i.e.

the

movement

cycle

is

anchored

on

maximal

flexion

-LRB-

extension

-RRB-

-RRB-

while

the

extension

-LRB-

flexion

-RRB-

half

cycle

simply

serves

to

bring

the

hand

out

again

for

the

next

flexion

-LRB-

extension

-RRB-

perhaps

in

part

passively

through

the

release

of

potential

energy

stored

in

the

elastic

tissues

around

the

wrist

The

observed

local

and

global

features

of

tracking

are

surely

consistent

with

such

an

interpretation

In

any

case

in

a

flexed

-LRB-

extended

-RRB-

wrist

posture

the

flexion

-LRB-

extension

-RRB-

reversal

point

or

phase

indeed

appears

to

act

as

an

organizing

center

within

and

for

the

entire

cycle

production

-LRB-

Beek

Beek

et

al.

-RRB-

Thus

by

actively

timing

or

controlling

the

flexion

-LRB-

extension

-RRB-

phase

the

movement

cycle

as

a

whole

is

produced

to

satisfy

the

imposed

synchronization

demand

of

the

tracking

task

Beek

-LRB-

-RRB-

submitted

that

anchor

points

contain

critical

task-specific

information

for

organizing

a

cyclical

act

The

results

of

the

present

study

suggested

that

the

anchor

points

may

also

possess

functional

task-specific

mechanical

properties

that

can

be

utilized

in

the

organization

of

the

cyclical

act

-LRB-

in

our

case

the

possibility

to

store

and

release

energy

-RRB-

Tracking

was

controlled

in

a

-LRB-

partly

-RRB-

discrete

manner

with

the

actively

controlled

flexion

-LRB-

extension

-RRB-

phase

apparently

acting

as

a

kind

of

biological

escapement

for

fueling

the

potential

energy

capacity

of

the

extensors

-LRB-

flexors

-RRB-

Visual

underpinnings

of

anchoring

The

absence

of

interaction

effects

between

gaze

direction

and

wrist

posture

in

combination

with

the

observations

that

gaze

direction

did

not

affect

temporal

anchoring

and

that

the

global

tracking

dynamics

was

more

strongly

influenced

by

wrist

posture

than

by

gaze

direction

implied

that

both

factors

had

different

and

independent

effects

on

the

tracking

dynamics

The

results

strongly

suggested

that

gaze

direction

predominantly

affected

the

spatial

accuracy

of

the

tracking

movements

and

-LRB-

by

and

large

-RRB-

not

its

temporal

organization

and

is

thus

associated

only

with

spatial

control

Surely

this

conclusion

is

consistent

with

the

results

of

ample

pointing

aiming

and

reaching

studies

For

example

pointing

accuracy

suffers

when

participants

do

not

foveate

at

a

target

during

the

homing-in

phase

of

aiming

movements

-LRB-

e.g.

Bekkering

et

al.

Neggers

and

Bekkering

Prablanc

et

al.

Vercher

et

al.

-RRB-

The

tight

coupling

between

gaze

and

aiming

movements

is

underscored

further

by

the

finding

that

the

eyes

can

not

saccade

away

from

the

target

until

the

aiming

movement

is

completed

which

has

led

to

the

insight

that

this

so-called

gaze

anchoring

serves

the

planning

and

execution

of

pointing

movements

-LRB-

Neggers

and

Bekkering

-RRB-

Although

online

concurrent

visual

feedback

of

the

tracking

movements

was

provided

in

the

present

study

the

positive

effect

of

gaze

direction

-LRB-

or

gaze

anchoring

in

general

-RRB-

on

spatial

endpoint

accuracy

appears

independent

of

the

availability

of

visual

information

from

the

pointing

or

tracking

movement

itself

-LRB-

either

directly

or

indirectly

through

extrinsic

visual

feedback

-RRB-

For

example

Neggers

and

Bekkering

-LRB-

-RRB-

also

observed

gaze

anchoring

phenomena

without

vision

of

the

moving

arm

while

Roerdink

et

al.

-LRB-

-RRB-

observed

reduced

endpoint

variability

in

the

direction

of

gaze

during

tracking

in

the

absence

of

visual

tracking

feedback

and

vision

of

the

moving

hand

These

findings

indicate

that

the

spatial

anchoring

results

mediated

by

gaze

direction

observed

in

the

present

experiment

do

not

necessarily

imply

increased

accuracy

in

the

foveated

direction

due

to

an

alignment

of

visual

target

and

feedback

signals

but

that

also

more

generic

gaze

anchoring

mechanisms

-LRB-

see

Neggers

and

Bekkering

-RRB-

are

implicated

in

the

observed

anchoring

phenomena

Future

studies

should

be

conducted

to

reveal

the

precise

contribution

of

gaze

anchoring

on

endpoint

variability

during

rhythmic

tracking

for

instance

by

comparing

unimanual

in-phase

and

antiphase

tracking

-LRB-

without

direct

or

extrinsic

visual

feedback

of

the

moving

hand

-RRB-

under

fixed

left

center

and

right

gaze

directions

Theoretical

implications

with

regard

to

anchoring

Over

the

years

the

study

and

with

it

the

notion

of

anchoring

has

become

confined

to

synchronization

of

a

particular

point

in

the

movement

cycle

with

a

discrete

or

continuous

metronome

Against

this

development

we

would

like

to

revive

the

more

generic

definition

of

anchoring

as

originally

given

by

Beek

-LRB-

-RRB-

who

described

anchor

points

as

organizing

centers

within

and

for

cyclical

movements

Inherent

to

this

description

are

at

least

four

theoretically

and

methodologically

relevant

features

First

anchoring

can

also

occur

without

an

external

pacer

as

has

been

reported

for

juggling

-LRB-

Beek

see

also

Beek

et

al.

-RRB-

and

self-paced

wrist

cycling

-LRB-

Byblow

et

al.

-RRB-

In

a

similar

vein

we

expect

that

the

present

results

regarding

wrist

posture

will

be

preserved

with

self-paced

rhythmic

wrist

movements

Second

in

the

case

of

paced

movements

performing

a

task

at

the

prescribed

frequency

does

not

necessarily

imply

anchoring

-LRB-

e.g.

as

a

case

in

point

in

the

present

study

AI

's

did

not

differ

from

for

a

neutral

wrist

posture

when

gaze

was

fixated

in

between

the

two

target

turning

points

see

Fig.

-RRB-

Conversely

it

is

only

useful

and

possible

to

examine

anchoring

to

a

pacing

signal

if

the

task

is

performed

at

or

at

least

very

close

to

the

prescribed

frequency

Third

anchoring

is

not

a

purely

local

effect

but

has

implications

for

the

overall

coordination

-LRB-

Beek

Fink

et

al.

Jirsa

et

al.

Maslovat

et

al.

-RRB-

as

is

captured

in

the

statement

that

anchor

points

serve

as

organizing

centers

within

and

for

the

entire

cycle

production

-LRB-

Beek

-RRB-

By

timing

the

movement

to

a

particular

point

in

the

cycle

the

movement

cycle

as

a

whole

is

timed

and

stabilized

Pattern

stability

may

be

improved

however

by

employing

more

than

one

anchor

point

-LRB-

Fink

et

al.

Jirsa

et

al.

Maslovat

et

al.

-RRB-

Finally

although

in

cyclical

tasks

anchoring

is

typically

observed

in

the

form

of

a

local

reduction

of

kinematic

variability

at

or

near

the

movement

endpoints

anchor

points

may

in

principle

be

observed

anywhere

throughout

the

cycle

-LRB-

e.g.

the

point

of

ball

release

in

juggling

Beek

-RRB-

Moreover

anchor

points

are

not

fixed

in

the

perceptual-motor

workspace

but

can

be

actively

created

or

assembled

for

example

by

fixating

gaze

at

one

of

both

target

turning

points

-LRB-

Roerdink

et

al.

-RRB-

Coda

In

the

present

study

we

delineated

the

effects

of

gaze

direction

and

wrist

posture

on

anchoring

phenomena

A

novel

methodological

feature

of

the

study

was

that

the

analysis

of

spatial

endpoint

variability

was

complemented

with

a

temporal

counterpart

by

quantifying

the

timing

variability

between

movement

reversals

and

target

turning

points

in

an

analogous

manner

We

found

that

both

visual

and

musculoskeletal

factors

affected

spatial

and

temporal

anchoring

phenomena

in

different

ways

the

former

by

making

use

of

task-specific

visual

information

available

at

the

gaze

anchored

point

the

latter

by

exploiting

task-specific

mechanical

properties

The

results

are

in

line

with

the

original

definition

of

anchoring

-LRB-

Beek

see

above

-RRB-

which

was

broadened

by

suggesting

that

besides

perceptual

information

task-specific

mechanical

properties

may

also

be

available

and

actively

utilized

at

the

anchor

point

in

favor

of

task

performance

or

task

economy

Finally

we

would

like

to

emphasize

that

anchoring

is

a

generic

aspect

of

coordination

dynamics

that

may

have

considerable

potential

for

practical

applications

such

as

in

learning

complex

coordination

patterns

-LRB-

e.g.

Maslovat

et

al.

-RRB-

or

in

restoration

of

pathological

gait

-LRB-

e.g.

Roerdink

et

al.

-RRB-

For

example

the

latter

study

on

the

effect

of

acoustically

paced

treadmill

walking

on

gait

coordination

in

stroke

patients

found

that

the

footfalls

of

the

nonparetic

limb

were

anchored

to

the

tones

of

the

metronome

-LRB-

Roerdink

et

al.

-RRB-

The

analysis

of

temporal

anchoring

provided

insight

into

the

manner

in

which

asymmetric

gait

patterns

are

coordinated

to

symmetric

acoustic

pacing

rhythms

More

importantly

the

notion

of

anchoring

may

also

provide

an

entry

point

for

improving

the

organization

of

paced

walking

in

stroke

patients

in

physical

therapy

-LRB-

Roerdink

et

al.

-RRB-

for

example

by

instructing

stroke

patients

to

coordinate

or

anchor

footfalls

of

the

paretic

limb

to

the

beat

of

the

metronome

anchoring
coordination dynamics
visual information

eye–hand coordination
manual tracking
wrist position
visuo-motor control
movement trajectories


Cardiovascular molecular MR imaging Introduction Cardiovascular molecular imaging is a rapidly evolving field of research , aiming to image and quantify molecular and cellular targets in vivo . MR imaging has some inherent properties that make it very suitable for cardiovascular molecular imaging . Until now , only a limited number of studies have been published on cardiovascular molecular imaging using MR imaging . Introduction Conventional imaging modalities , including magnetic resonance -LRB- MR -RRB- , are primarily based on anatomical , functional or metabolic properties to study -LRB- patho -RRB- physiology . Molecular imaging is a rapidly evolving field of research , aiming to image and quantify molecular and cellular targets in vivo . Molecular imaging can be applied to a wide range of scientific and clinical fields of interest . One of the most promising applications of molecular imaging is in the field of cardiovascular imaging . Imaging of cardiac anatomy , dimensions and function has some limitations concerning , for example , prediction of therapy outcome . Addition of specific information on , for instance , plaque composition and total plaque burden can be very helpful in guiding therapy . Imaging of molecular processes is desirable because cardiovascular disease may be detected earlier , risk stratification may be more accurate , monitoring of innovative therapies may be improved , or a more accurate prognosis may be provided -LSB- 1 -RSB- . MR imaging has some inherent properties that make it very suitable for cardiovascular molecular imaging . The interaction between inherent tissue properties and specific contrast agents may lead to more specific clinical conclusions and prediction of therapy outcome . Thereby , cardiovascular molecular MR imaging may help in diagnosing cardiovascular disease , and in deciding whether expected beneficial effects of -LRB- invasive -RRB- therapy counterbalance the risk of complications of therapy . A conventional approach to molecular MR imaging concerns MR spectroscopy . Furthermore , there are two main innovative contrast agents that may be used clinically soon : -LRB- 1 -RRB- iron oxide MR contrast agents and -LRB- 2 -RRB- fibrin-targeted MR contrast agents . MR spectroscopy MR spectroscopy -LRB- MRS -RRB- allows non-invasive characterisation of myocardial metabolism . In principle , MRS is a pure form of molecular ` imaging ' technique . Clinically , several nuclei allow noninvasive MRS of the heart . Initially , human MRS research was focussed on the 31P nucleus to study high-energy phosphate metabolism . An example concerning the effects of diabetes type 2 on myocardial high-energy phosphate metabolism is shown in Fig. 1 -LSB- 2 -RSB- . Another interesting new application of 31P-MRS was published by Smith et al. -LSB- 3 -RSB- , who measured myocardial creatine kinase -LRB- CK -RRB- metabolite concentrations and adenosine triphosphate synthesis through CK , the primary energy reserve of the heart , to test the hypothesis that ATP flux through CK is impaired in patients with left ventricular hypertrophy -LRB- LVH -RRB- and chronic heart failure . It turned out that myocardial ATP levels were normal , but creatine phosphate levels were 35 % lower in LVH patients than in normal subjects . Furthermore , the myocardial CK rate constant was normal in LVH , but halved in patients with LVH combined with chronic heart failure . Thereby , they could show that it is not the relative or absolute CK metabolite pool size but rather the kinetics of ATP turnover through CK that distinguishes failing from non-failing hypertrophic hearts . These observations support the hypothesis that a deficit in myofibrillar energy delivery contributes to chronic heart failure pathophysiology in human LVH . The same technique was applied by Weiss et al. to study ATP flux through CK in the normal , stressed and failing human heart -LSB- 4 -RSB- . The latter studies are elegant examples of the capability of MR to measure non-invasively the concentration of metabolites and even the rate constant of enzyme turnover . Fig. 1Left panel : planscan of the volume of interest on transverse and sagittal spin-echo MR images . Right panel : phosphorus-31 magnetic resonance spectroscopy -LRB- 31P-MRS -RRB- obtained at rest from the anterior left ventricular wall in a patient with diabetes type 2 -LRB- left -RRB- and a healthy subject -LRB- right -RRB- . Note the decreased signal amplitude of phosphocreatine in the type 2 diabetes patient . Courtesy of Diamant et al. -LSB- 2 -RSB- Another interesting application of metabolic imaging is 23Na MR imaging , as show by Jansen et al. . They applied this innovative spectroscopic imaging technique as a diagnostic modality for early detection of myocardial ischaemia and viability in a rat model -LSB- 5 -RSB- . They tested whether 23Na MR imaging can be used to assess viability after low-flow ischaemia . 23Na MR chemical shift imaging was alternated with 23Na MR spectroscopy . Na image intensity increased with increasing severity of ischaemia . 23Na image intensity at end low-flow ischaemia was well correlated with CK release during reperfusion , as well as with infarct size . Therefore , their study indicates that 23Na MR imaging is a promising tool for the assessment of myocardial viability . Ouwerkerk et al. applied 23Na MR imaging to measure cardiac tissue sodium concentrations in the human myocardium -LSB- 6 -RSB- . They used a surface coil at 1.5 T MR to non-invasively quantify regional myocardial sodium concentrations in the left ventricular free wall , septum and adipose tissue . Their 23Na MR imaging results were consistent with prior invasive measurements on biopsy and autopsy specimens . In the past , 1H-MRS of the myocardium was first applied to non-invasively study creatine depletion in non-viable infarcted myocardium -LSB- 7 -RSB- . Total creatine was measured in the posterior and anterior left ventricle and septum , and was significantly lower in regions of infarction than in non-infarcted regions of myocardium in patients or in the myocardium of healthy controls . Therefore , they showed for the first time that spatially localised 1H-MRS can be used to measure total creatine non-invasively throughout the human heart . The detection of regional creatine depletion may provide a metabolic means to distinguish healthy from infarcted non-viable myocardium . Szczepaniak et al. used 1H-MRS to measure myocardial lipid content -LSB- 8 -RSB- . Studies in rat tissue ex vivo and in healthy humans in vivo provided evidence that 1H-MRS constitutes a reproducible technique for the measurement of myocardial triglyceride . Increased myocardial triglyceride content was accompanied by elevated LV mass and suppressed septal wall thickening as measured by cardiac imaging . More recently , 1H-MRS of the human myocardium was improved by implementing the respiratory navigator technique to monitor diaphragmatic motion , and thereby correct data acquisition prospectively for breathing motion . First -LRB- unpublished -RRB- results from our institution show improved reproducibility of human cardiac 1H-MRS measurements when using the respiratory navigator technique , as compared with conventional continuous breathing . Respiratory navigator gated 1H-MRS was recently applied in an experimental setting in our institution to evaluate the effects of a very low calorie diet on myocardial triglyceride content . First -LRB- unpublished -RRB- results show that after a short very low calorie diet , there is an increase in intramyocardial triglyceride content -LRB- Fig. 2 -RRB- . Fig. 2The surface coil was positioned just below the mitral valve level of the heart -LRB- a , b -RRB- . Spectroscopic volume localisation in the interventricular septum on four-chamber -LRB- c -RRB- and short axis -LRB- d -RRB- views . Special care was taken to avoid contamination from epicardial fat . -LRB- e -RRB- Typical water-suppressed 1H-MR spectrum of myocardial tissue located in the interventricular septum . Peak heights are in arbitrary units Gadolinium-based contrast agents Gadolinium-based contrast agents can be applied to study regional myocardial perfusion . After a rapid intravenous contrast injection , there is marked signal enhancement first in the RV cavity , then in the LV cavity , and subsequently in the LV myocardium -LSB- 9 -RSB- . The peak signal intensity is related to the concentration of the contrast agent in the local tissue and is directly proportional to the coronary blood flow . Perfusion MR at rest and after infusion of pharmacological agents -LRB- adenosine and persantine -RRB- have been compared with standard methods -LRB- angiography or radionuclide scintigraphy -RRB- and demonstrated reasonable sensitivity -LRB- 67 -- 83 % -RRB- and specificity -LRB- 75 -- 100 % -RRB- -LSB- 9 -RSB- . Currently , multiple MR imaging techniques are available to assess myocardial viability . Cardiovascular MR imaging can be used to assess end-diastolic wall thickness and contractile function at rest -LSB- 10 -RSB- . Segments with an end-diastolic wall thickness < 6 mm most likely represent transmural scar formation , and contractile function will not improve after myocardial revascularisation . Dobutamine MR imaging can be used to evaluate contractile reserve , in a similar manner to dobutamine echocardiography . Gadolinium contrast-enhanced MR imaging -LSB- 11 -RSB- allows for detection of the extent and transmurality of scar tissue -LRB- Fig. 3 -RRB- . Recently reported sensitivity and specificity are in the range of 74 % and 82 % respectively . Fig. 3Left panel : short-axis MR images at rest and during dobutamine stress . Note the lack of improvement in myocardial wall motion in the anteroseptal region when dobutamine stress is applied . Right panel : delayed gadolinium contrast-enhanced MR images in two-chamber , four-chamber and short-axis views . Note the almost transmural delayed enhancement of the anteroseptal/apical region , corresponding to the region without contractile response due to dobutamine stress in the left panel . The anteroseptal region is considered as ` non-viable ' myocardial tissue Based on as yet unpublished scientific developments , it is expected that gadolinium-based delayed enhancement of the vessel wall may become reality . This MR imaging technique may allow fast total body screening for total plaque burden , an important predictor for morbidity and mortality . In general , gadolinium-based contrast agents are not perfectly suited for molecular imaging because of the inherent high threshold of detectability . Therefore , new contrast agents are under development to potentiate the effect of distortion of the magnetic field . Iron oxide MR contrast agents Superparamagnetic iron oxide -LRB- SPIO -RRB- particles can be detected at micromolar concentrations of iron , and offer sufficient sensitivity for MR imaging -LSB- 12 -RSB- . SPIO-based cellular imaging has become an established technique to label and detect cells of interest . Imaging of macrophage activity was the initial and is still the most significant application , with several products either approved for or in clinical trials -LSB- 12 -RSB- . Another exciting application of SPIOs is labelling of myocardial stem cells . In a swine model for myocardial infarction , magnetically labelled stem cells were injected in the infarcted myocardial region -LRB- Fig. 4 -RRB- . Using delayed contrast-enhanced MR imaging , the infarcted area can be identified with high accuracy . New technical developments may even allow specific delivery of magnetically labelled therapeutics to the infarcted myocardial region -LSB- 12 -RSB- . Combined with measurements of myocardial function , MR imaging seems an excellent modality for planning , delivery and follow-up of myocardial stem cells as therapy for ischaemic heart disease . Fig. 4Detection of delivery and migration of Feridex-labelled myocardial stem cells in a swine model . Hypointense lesions in spin-echo -LRB- SE -RRB- , gradient-echo -LRB- GRE -RRB- and delayed-enhanced -LRB- Delayed -RRB- MR imaging -LRB- upper panel -RRB- of injection sites -LRB- arrows -RRB- within 24 h of intramyocardial injection . Cells were injected in the myocardial infarct -LRB- MI -RRB- . Long-axis MR images -LRB- lower panel -RRB- show hypointense lesions -LRB- arrows -RRB- caused by labelled myocardial stem cells acquired within 24 h and 1 week . LV left ventricle , RV right ventricle . Courtesy of Bulte andKraitchman -LSB- 12 -RSB- Another promising application of SPIO MR imaging is visualisation of vessel wall inflammation . SPIOs are ` digested ' by macrophages , involved in inflammatory processes . Imaging of the SPIO-induced magnetic inhomogeneities allows for imaging of inflammation . Such an approach is currently only available in a research setting ; it is , however , expected that these contrast agents will become available for clinical application soon . Fibrin-targeted MR contrast agents Exciting recent developments allow selective and non-invasive molecular MR imaging of thrombus -LSB- 13 -RSB- . The principle of the contrast agent is that it is targeted to fibrin . In an elegant study by Spuentrup et al. , a swine model was used to test the innovative fibrin-targeted MR imaging contrast agent , which can be administered intravenously -LSB- 14 -RSB- . The imaging protocol consisted of coronary MR angiography to demonstrate the lumen of a coronary artery , combined with molecular thrombus MR imaging . Thereby , anatomical information could be linked to specific information of vessel wall components . In an area of focal coronary artery stenosis , intraluminal thrombus could be detected -LRB- Fig. 5 -RRB- . Fig. 5Coronary thrombus visualisation with a fibrin-targeted molecular MR imaging contrast agent . Left panel : double-oblique white blood coronary MR angiography -LRB- multiplanar reconstruction -RRB- demonstrating the lumen of the left anterior descending artery with bright signal -LRB- arrowheads -RRB- . Right panel : double-oblique MR images after administration of the fibrin-targeted contrast agent -LRB- multiplanar reconstruction , same orientation -RRB- . Note the increased signal -LRB- arrow -RRB- in the left anterior descending coronary artery , corresponding to thrombus . Courtesy of Spuentrup et al. -LSB- 14 -RSB- The same contrast agent can be applied to detect , for example , right atrial thrombus , a potential source of more distal emboli -LRB- Fig. 6 -RRB- . An atrial clot could be visualised easily with this molecular MR imaging technique , by intravenous administration of the fibrin-targeted contrast agent . Furthermore , MR clot imaging can be combined with functional imaging of the heart in the same imaging session . An even more exciting application of this fibrin-targeted contrast agent is detection of pulmonary emboli -LRB- Fig. 7 -RRB- . Fig. 6Molecular MR imaging of atrial clot in a swine model . The left panel shows pre-contrast -LRB- upper -RRB- and post-contrast -LRB- lower -RRB- coronal images . Note the presence of high MR signal in the area of the right atrium , indicating an atrial clot . The right panel shows increased MR signal in the left atrium -LRB- LA -RRB- , corresponding to a left atrial clot -LRB- arrow -RRB- . These clots are potential sources for more distal emboli . LV left ventricle . Courtesy of Spuentrup et al. -LSB- 14 -RSB- Fig. 7Examples of molecular MR imaging of pulmonary embolus . Two examples are shown , each consisting of three adjacent coronal slices -LRB- horizontal -RRB- . The MR imaging technique is such that signal from surrounding blood pool and lung parenchyma is suppressed . The upper row shows pulmonary embolus -LRB- arrow -RRB- in the right lower lobe . The lower panel shows bilateral pulmonary emboli -LRB- arrows -RRB- after intravenous administration of fibrin-targeted MR imaging contrast agent . Courtesy of Spuentrup et al. -LSB- 14 -RSB- The above-described applications of molecular MR imaging may be especially suitable for fast screening for cardiovascular disease in an emergency setting . Patients presenting with chest pain in the emergency room can be studied by MR imaging to confirm or rule out ischaemic heart disease or pulmonary embolus . Molecular MR imaging using fibrin-targeted contrast agents allows selective visualisation of acute coronary , cardiac and pulmonary thrombi . Additional functional cardiac imaging can help determine the functional effects of detected thrombi . Conclusion Molecular MR imaging is an exciting and rapidly evolving new area of cardiovascular imaging . MR imaging seems very suitable for molecular imaging , although many technical difficulties have to be overcome . The main current limitation is the low sensitivity of MR imaging to detect small changes in magnet homogeneity . We expect that in the next decade , currently promising MR molecular imaging agents will be introduced into the clinical arena to guide diagnosis and therapy of cardiovascular disease .

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

mr spectroscopy
contrast agents
cardiovascular molecular imaging
cardiovascular disease