Pupillary PhysiologyStuart R. Steinhauer, Ph.D.Biometrics Research Program

University of Pittsburgh School of Medicine & VA Pittsburgh Healthcare System

(http://www.wpic.pitt.edu/research/biometrics)

Society for Psychophysiological Research Workshop, Boston, September 14, 2011

little is achieved by one alone,

Thanks to all of the following:

Greg J. Siegle, Ph.D.Ruth Condray, Ph.D.

Samay Jain, M.D.Beatrice Chakraborty, Psy.D.

Adam L. Clarke, B.S.Erin E. Kelly, B.S.

J. Richard Jennings, Shirley Y. Hill, Lisa A. Morrow

Gad Hakerem, Joseph Zubin, Samuel Sutton

Work has been supported by the Department of Veterans Affairs and National Institute of Mental Health

Pupil of the Eye.net     

• Pupil of the Eye ... United in Spirit ... In Service to All

•  • “Bahá'u'lláh once compared the coloured people

to the black pupil of the eye surrounded by the white. In this black pupil you see the reflection of that which is before it, and through it the light of the Spirit shines forth. In the sight of God colour makes no difference at all, He looks at the hearts of men. That which God desires from men is the heart...” 

Gray’s Anatomy, 20th Ed., via Wikipedia

http://www.ndrs.scot.nhs.uk/Train/Handbook/drh-21.htm

http://www.army-technology.com/features/feature1644/feature1644-4.html

www.center4sight.com/anisocoria

Measuring sustained cognitive load via pupil dilation

Horizontal Diameter Measured to .025 mm, 60/sec

Average Pupillary Light Reaction

5.5

6

6.5

7-2

00

20

0

60

0

10

00

14

00

18

00

22

00

26

00

30

00

34

00

Time (ms)

Pu

pil

Dia

mte

r (m

m)

Start

End

Light

Amplitude of Light Reaction

Alexandritis, 1985

n.III Oculomotor Nucleus

Edinger Westphal Nucleus (4 on right figure)

Alexandritis, 1985

Hypothalamic Nuclei

Posterior Hypothalamic

Nuclei(sympathetic)

Lowenstein, 1955

Dilation

Constriction

12 Oculomotor nucleus

7 Hypothalamus

Inhibition of

White & Depue, J.Pers.Soc.Psychol., 1999, quoting Ranson & Clark, 1959

White & Depue, J.Pers.Soc.Psychol., 1999, quoting Ranson & Clark, 1959

Autonomic Contributions to Pupillary Dilation

Parasympathetic Sympathetic

Time Course of Immediate Processing:

Prestimulus; 300-500 msec (motor) 600-1000 msec

1100-1500 msec

Task sensitivity:

Increasing Ambient Light:

Sustained Processing (memory, effort) Motor Initiation Anticipatory Responses Increased response with smaller initial diameter

Immediate Processing of Stimulus Significance Orienting Responses No substantial differences (within limits)

Experimental Dissociation of Sympathetic and Parasympathetic Components

Parasympathetic Sympathetic

Recording in Dark:

Recording in Light:

Minimize Dilation Increase Dilation

Normal Dilation Normal Dilation

Block sphincter:

Block dilator:

No Dilation Normal Dilation

Normal Dilation No Dilation

Tasks: Digit Span Serial Subtraction Motor Responses (Voluntary, Cued)

“Oddball” Counting & Choice Reaction Guessing Missing Stimulus Paradigm

Begin Data Collection

Verbalize

End Data Collection

Instructions:

Subtract 7

or Add 1

Serial “Subtraction” Task

Reticular Activating System inhibits Edinger-Westphal center of Oculomotor Nucleus

Prefrontal Cortex (PFC) inhibits E-W &

Activates Posterior Hypothalamus

5 sec 60 sec

Pupil Diameter Increases With Task Demand

Steinhauer et al., Int. J. Psychophysiology, 2004

What can interfere with the light reflex? (other than brightness, visual field, hue)

• Fear (Szabadi, Bitsios, 1996)

• Apprehension (Loewenfeld, 1958; 1993)

• Motor response (Loewenfeld, 1993; Gavriysky, 1991)

• Cognition (Steinhauer, 2000)

Light Reaction Amplitude by Cue Delay

1.1

1.2

1.3

1.4

1.5

1.6

1.7

1.8

No Cue -1000 -750 -500 -250 0 250 500

Cue to Light onset (msec)

Lig

ht

Rea

ctio

n (

mm

)

Control =8

Motor Response cued by tone inhibits Light Reaction even after onset of light stimulus

Light Duration = 1000 msec, Tone Duration = 40 msec

Effect of Task Demand on Light Reaction

Light Reaction, Superimposed at Baseline

Placebo

-1

-0.8

-0.6

-0.4

-0.2

0

0.2

-200 200 600 1000 1400 1800 2200 2600 3000 3400

Time (msec)

Ch

ang

e in

D

iam

eter

(m

m)

Placebo, Subtract 7

Placebo, Add 1

Placebo, No Task

Light Stimulus

(n = 29 healthy subjects)

Prestimulus Pupil Diameter

Serial -7Serial +1Light Only

Pre

-stim

ulus

Dia

met

er (

mm

)7.0

6.5

6.0

5.5

5.0

4.5

GROUP

Control

Schizophrenic

Alcoholic

Group: F1,35 = 5.6, p=0.008

Condition: F 1.4,50.1 = 47.1 , p < 0.001

Constriction: Group by Condition

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

Control = 12 Alcohol = 15 Schizophrenic = 11

Ch

ang

e in

Dia

met

er (

mm

)

Light Only

Add 1

Subtract 7

Condition: F 1.6,56.6 = 5.99, p = 0.007

Loewenfeld, 1993

Loewenfeld, 1993

Dapiprazole

Blockade of Sphincter or Dilator on Diameter in relation to Task Demand

Steinhauer et al., Int. J. Psychophysiology, 2004

Average Pupillary Light Reaction

5.5

6

6.5

7-2

00

20

0

60

0

10

00

14

00

18

00

22

00

26

00

30

00

34

00

Time (ms)

Pu

pil

Dia

mte

r (m

m)

Start

End

Light

Amplitude of Light Reaction

Placebo Dapiprazole Tropicamide

4

4.5

5

5.5

6

6.5

7

7.5

8

-20020

060

010

0014

0018

0022

0026

0030

0034

00 -20020

060

010

0014

0018

0022

0026

0030

0034

00-2

00 20060

010

0014

0018

0022

0026

0030

0034

00

Time (msec)

Dia

met

er (

mm

) Subtract 7

Add 1

No Task

No Task and Add 1 superimposed

(Block Dilator) (Block Sphincter)

Steinhauer & Zubin, 1982

Steinhauer & Hakerem, 1992

Cued Response: Placebo

-0.02

0

0.02

0.04

0.06

0.08

0.1

-992 -592 -192 208 608 100814081808 22082608

Time (msec)

Ch

an

ge

in P

up

il D

iam

ete

r (m

m)

Cued-Dark

Cued-Light

Self Initiated Response: Placebo

-0.07

-0.05

-0.03

-0.01

0.01

0.03

0.05

-992 -592 -192 208 608 1008 1408 1808 2208 2608

Time (msec)

Ch

an

ge

in P

up

il D

iam

ete

r (m

m)

Placebo-Dark

Placebo-Light

(n = 11 healthy subjects)

(n = 11 healthy subjects)

Harrison et al., SCAN, 2006

Irene E. Loewenfeld, Ph.D.

Dept. of Neurology, Columbia University

Kresge Eye Institute, Wayne State University

Funded by the National Library of Medicine Grant #G08 LM07919-02 A collaboration of the Spencer S. Eccles Health Sciences Library, University of Utah, and the North American

Neuro-Ophthalmology Society (NANOS)

H. Stanley Thompson, M.D. Randy Kardon, M.D.

Neuro-opthalmology Service, University of Iowa

Gad Hakerem & Irene Loewenfeld, 2005 Pupil Colloquium, NY

Eckhard Hess

Daniel Kahneman, Ph.D. Jackson Beatty, Ph.D.

Iridology?