28Th International Colloquium on the Pupil

28TH INTERNATIONAL COLLOQUIUM ON THE PUPIL

August 17-21, 2009 Pittsburgh, Pennsylvania, USA

Program and Abstracts

Hosts: Stuart R. Steinhauer, Ph.D. VA Pittsburgh Healthcare System Department of Psychiatry, University of Pittsburgh School of Medicine

Greg J. Siegle, Ph.D., Program Chair Departments of Psychiatry and Psychology, University of Pittsburgh School of Medicine 2009 Pupil Colloquium

Welcome to the Allegheny mountains of western Pennsylvania and the 28th Colloquium on the Pupil

Since 1961, physiologists, ophthalmologists, neurologists, psychiatrists, psychologists, engineers, and other clinicians and scientists have participated in the Colloquia on the Pupil every two years. Meeting Overview The meeting will begin with a reception on the evening of Monday August 17, 2009, and end with breakfast Friday morning, August 21, 2009. Meeting presentations will take place on Tuesday, Wednesday, and Thursday. Registration will include a welcoming reception on Monday evening, coffee and refreshment breaks, lunches and dinners, including a traditional American outdoor barbecue. We are also planning to visit Fallingwater, the world-famous home designed by architect Frank Lloyd Wright. The Irene E. Loewenfeld lecture will be delivered by Paul D. Gamlin, Ph.D., Professor of Visual Science, School of Optometry, University of Alabama at Birmingham.

Meeting Location and Event Information

The location of the meeting is the Seven Springs Mountain Resort in Champion, Pennsylvania, located an hour from downtown Pittsburgh. Address: 777 Waterwheel Drive, Champion, PA 15622

A full buffet breakfast is provided each morning beginning at 7:00 AM in the Slopeside Dining Room for all registered guests; beverages will also be available in the meeting room at the start of the morning and at morning and afternoon breaks.

All lectures will be presented in the Seasons Room on the 2nd floor (one floor beneath the Convention center). Room locations for lunches and dinners are noted in the program.

Wednesday evening dinner will be an outdoor barbeque at the Ski Lodge

A box lunch will be provided on Thursday prior to the trip to Fallingwater (the bus will leave from the main entrance of the hotel at 12:30 PM). Support for this meeting was provided in part by:

Western Psychiatric Institute and Clinic, Department of Psychiatry, University of Pittsburgh School of Medicine

VA Pittsburgh Healthcare System (Department of Veterans Affairs)

VA Mental Illness Research, Education and Clinical Center (MIRECC)

Additional support provided by ISCAN, Inc., Woburn Massachusetts

1 2009 Pupil Colloquium Organizers of the Colloquia on the Pupil

1st Boston, 1961 15th Hamamatsu, 1986 Stark Ishikawa

2nd Boston, 1962 16th New York, 1987 Stark Behrens, Odel

3rd New York, 1963 17th Vancouver, 1988 Lowenstein, Loewenfeld Thompson, Cox

4th Washington, DC, 1965 18th Berkeley, 1989 Feinberg Stark, Myers

5th Philadelphia, 1967 19th Woods Hole, 1991 Laties Loewenfeld

6th Bethesda, 1969 20th Iowa City, 1993 Wagner Thompson, Kardon

7th Rochester, Minnesota, 1971 21st Tübingen, 1995 Martens Wilhelm, Wilhelm

8th Detroit, 1973 22nd Birmingham, 1997 Loewenfeld Gamlin

9th Iowa City, 1975 23rd Nottingham, 1999 Thompson Szabadi, Howarth

10th Flushing, NY, 1977 24th Asilomar, 2001 Hakerem Larson, Howarth

11th London, 1979 25th Crete, 2003 Smith, Turner Bitsios, Howarth

12th Winnipeg, 1981 26th New York, 2005 Janisse Wyatt, Rosenberg

13th Toronto, 1983 27th Hamamatsu, 2007 Czarnecki Ishikawa

14th Vancouver, 1985 28th Pittsburgh, 2009 Cox Steinhauer, Siegle

2 2009 Pupil Colloquium Meeting Schedule

Day Time Activity Host / Presenter Chair Monday Aug 17 Wintergreen Room 6:00 pm Reception Tuesday Aug 18 Slopeside Room 7:00-9:00 Breakfast Seasons Room 9:00-9:15 Welcome Steinhauer / Siegle 9:15-10:00 Presentation – Lesions Randy Kardon Barbara Wilhelm 10:00-10:45 Presentation – Lesions François-Xavier Borraut 10:45-11:00 Break 11:00-11:45 Presentation – Lesions Helmut Wilhelm 11:45-12:30 Presentation – Pain Neilly Buckalew Wintergreen Room 12:30-1:30 Lunch Seasons Room 1:30-2:15 Presentation – Emotion / Kids Greg Siegle Elke van der Meer 2:15-3:00 Presentation – Emotion / Kids Jennifer Silk 3:00-3:15 Break 3:15-3:30 Introduction: cognition and pupils Stuart Steinhauer Stuart Steinhauer 3:30-4:15 Presentation – Cognition Jan Ries 4:15-5:00 Presentation – Cognition Tsunhin Wong 5:00-5:45 Presentation – Cognition Naho Ichikawa Wintergreen Room 6:30-8:30 Dinner

Wednesday Aug 19 Slopeside Room 7:00-9:00 Breakfast Seasons Room 9:00-9:45 Presentation – Light Reflex Tobias Peters Sam Berman 9:45-10:30 Presentation – Light Reflex / Samay Jain Parkinson's Break 10:45-11:30 Presentation – Cognition/Psychiatry Amanda Collier Greg Siegle 11:30-12:15 Presentation – Cognition/Psychiatry Neil Jones Alpine Room 12:15-1:15 Lunch Seasons Room 1:15-2:00 Presentation – Cognition/Psychiatry Beatrice Chakraborty 2:00-2:45 Presentation – Cognition / Psychiatry Stuart Steinhauer 2:45-3:30 Presentation – Sleep Peter Franzen Helmut Wilhelm 3:30-3:45 Break 3:45-4:30 Presentation – Sleep / Kids Barbara Wilhelm 4:30-5:45 Loewenfeld Lecture - Biology Paul Gamlin Stan Thompson Ski Lodge 6:30-8:30 Dinner – Barbeque Thursday Aug 20 Slopeside Room 7:00-9:00 Breakfast Seasons Room 9:00-9:45 Presentation – Cognition Martina Zellin Randy Kardon 9:45-10:30 Presentation – Cognition Elke van der Meer 10:30-10:45 Break 10:45-11:30 Presentation – Light Sam Berman 11:30-12:00 Business meeting Seasons Room 4&5 12:00-12:30 Box Lunch; Prepare for trip Bus: Main Entrance 12:30-4:15 Fallingwater trip 4:15-6:30 Free time Seasons Room 2&3 6:30-9:00 Dinner – Banquet Friday Aug 21 Slopeside Room 7:00-10:00 Breakfast 10:00-11:00 Depart to University of Pittsburgh 11:00-1:00 University of Pittsburgh lab tours Greg Siegle, Peter Franzen, Jennifer Silk

3 2009 Pupil Colloquium Abstracts (alphabetical order)

At normal reading distance, workplace light spectra affect occupant pupil size and visual performance...... 6 Sam Berman, Brian Liebel, Robert Clear, Marc Fountain, Rita Lee

The orbital sympathetic pathways: A clinical correlation ...... 8 François-Xavier Borruat, Aki Kawasaki

Is Pupillary Response an Objective Bio-Marker for Disability and Brain Dysfunction in ...... 9 Older Adults with Chronic Low Back Pain? Neilly Buckalew, Greg J. Siegle, Marc W. Haut, Howard Aizenstein, Lisa Morrow, Subashan Perera, Debra Weiner

Pupillary Responses During Digit Span Under Light and Darkness in Psychiatric Patients...... 10 Beatrice H. Chakraborty, Greg J. Siegle, Ruth Condray, Adam L. Clarke, Stuart R. Steinhauer

Examining the effects of cognitive task training on dysphoria...... 11 Amanda L. Collier, Greg J. Siegle

Sleep deprivation increases pupillary reactivity to negative emotional information in healthy young adults .... 12 Peter L. Franzen, Denise N. Duryea,, Greg J. Siegle

Pupil dilation as an index of reactivity to errors in early adolescence...... 13 Naho Ichikawa, Jennifer S. Silk, Cecile Ladouceur, Ronald E. Dahl, Neil S Ryan, Greg J. Siegle

Sympathetic, parasympathetic and medication effects on pupil reactivity to light in Parkinson disease...... 14 Samay Jain, Greg J. Siegle, Stephanie Studenski, J. Timothy Greenamyre, Stuart R. Steinhauer

Features of Borderline Personality Disorder and Pupil Reactivity While Viewing Emotional Faces...... 15 Neil P. Jones, Stephanie D. Stepp, Greg J. Siegle, and Paul A. Pilkonis

Diagnosis of Horner Syndrome Using the Topical Effects of ...... 16 Apraclonidine on the Eyelids and Pupils Randy Kardon, Susan Anderson, and Andrew Lee

Sensitivity of test paradigms for assessing antimuscarinic effects of pupillary light reflex...... 17 A Randomised Double-Blind Double-Dummy Placebo Controlled Crossover Pilot Methodology Trial With Tolterodine and Oxybutynine in Healthy Volunteers Tobias Peters, Barbara Wilhelm and Helmut Wilhelm

Differential effects on learning in a highly complex geometrical task in highly vs. averagely gifted high-school students...... 18 Jan Ries, Martin Brucks, Manja Foth, Judith Horn, Boris Bornemann, Elke van der Meer

Seeing eye to eye: First examinations of concurrent pupillary reactivity during mother-child interactions...... 19 Greg J. Siegle, Jennifer Silk, Erika Joyce, Ronald Dahl

Pupil Dilation to Affective Words as a Marker of Risk for Early Onset Depression...... 20 Jennifer S. Silk, Ronald E. Dahl, Neal D. Ryan, & Greg J. Siegle

4 2009 Pupil Colloquium Working memory and pupillary dilation: ...... 21 Impairments in Schizophrenia, Depression, and Alcohol-related Disorders Stuart R. Steinhauer, Greg J. Siegle, Ruth Condray

Mathematical Cognition - Individual Differences in Resource Allocation ...... 22 Elke van der Meer, Boris Bornemann, Manja Foth, Judith Horn, Jan Ries, Elke Warmuth, Isabell Wartenburger

How do pupils of pupils oscillate? -...... 23 Feasibility and reference values for the pupillographic sleepiness test in children and adolescents Barbara Wilhelm, Katharina Weible, Jutta Diem, Katrin Heine, Pablo Brockmann, Tobias Peters, Wilhelm Durst, Michael S. Urschitz

Explaining unexplained visual loss by the pupil – possibilities and limitations...... 24 Helmut Wilhelm

Catching the 'Aha!' moments in puzzle problems using pupillometry and blinks analyses...... 25 Tsunhin John Wong, Christian Schunn, Greg J. Siegle

Passive and Active Discourse Processing - Effects of Task Instruction on the Pupillary Response...... 26 Martina Zellin, Ann Pannekamp, Elke van der Meer

5 2009 Pupil Colloquium At normal reading distance, workplace light spectra affect occupant pupil size and visual performance.*

Sam Berman**, Brian Liebel, Robert Clear, Marc Fountain, Rita Lee. After Image + Space, Oakland, CA.

Objectives: Past laboratory studies have shown that visual acuity and contrast sensitivity can be manipulated via light spectrum induced pupil size changes. This study examines to what extent those conclusions can be applied to the more realistic conditions where the spectrum variations are a consequence of commercially available lamps typically used in workplace environments and visual tasks that are not purely threshold. The question of the possible trade-off between spectrum and light level is also investigated. This evaluation is of particular important to the US Dept of Energy (research sponsors) as they are considering this approach for implementation as a national energy policy. Furthermore we examine whether the relatively small spectral differences associated with typical interior lamp choices induce consistent pupil size changes in a population of adults while the visual the task is viewed in near vision. We also examine whether spectrally induced pupil size changes can be explained from the spectral sensitivity of the photosensitive retinal ganglion cells (pRGC’s).

Methods: A simulated office is employed for testing where the ceiling has been outfitted with 2 different computer controlled but commonly used luminaires (indirect and parabolic) with each luminaire further outfitted with 2 spectrally different standard lamps namely with CCT of 3000K and 6500K and with nominal S/P (light level independent ratio of scotopic to photopic intensity) values of 1.30 and 2.0 respectively. (The S/P value directly measurable by a meter can be used as the proxy for estimating the spectral weighting of the pRGC’s). An ASL eye tracker/pupilometer with a 60 Hz data acquisition rate was employed to obtain pupil sizes and fixation frequency and duration. Forty-seven naïve subjects both male and female ranging in age from 20 to 50 years were selected through public advertising. Visual acuity was obtained onsite for all subjects by a licensed optometrist and measured acuities ranged from 20/12 to 20/25. A special visual task with a bare minimum of cognition and language proficiency was developed specifically for this study wherein subjects would read aloud at normal reading distance pairs of equal syllable numbers of varying and gradually decreasing contrast (7 levels). Recording performance with a video camera allowed both speed and accuracy to be obtained for all conditions. The eye/tracker/pupilometer measured pupil size, fixture duration and number of fixations while the subjects performed the reading task. Four different task pages each with the 7 levels of contrast were presented for reading along with the conditions of 2 fixture types, 3 light levels (65, 49.5 and 37.8 cd/m2 respectively) and 2 light spectra.

Results: The data was analyzed with an ANOVA procedure. All subjects showed highly significant pupil size differences for the 2 different lamp spectra at all light levels with the higher CCT or S/P lamp always producing relatively smaller pupils. The difference in mean pupil size could be explained by applying to the 2 lamp spectra, the recently published spectral sensitivity of the pRGC’s as modified by the spectral absorbtivity of the combined lens and cornea. Light level also produced significant but smaller pupil size differences. Surprisingly for the whole population there was also a small but significant luminaire effect on pupil size indicating the possibility of an interaction effect between light spacial distribution and spectrum on pupil size. Pupil size was also affected by task difficulty with pupils decreasing in size as the task became more visually difficult with a slight trend towards dilation for the last and most difficult number pair. Performance as determined by an approximately unbiased method of combining speed and accuracy also showed a significant spectral and light level effect as well as the unanticipated luminaire effect. The spectrally related performance effect was significant for the group as a whole with about 2/3 of the subject sample showing better performance with the higher S/P lamp. There was also significant correlation between pupil size and performance as well as a clear trade-off between light level and spectrum. (Detailed tables and graphs will be presented at the colloquium.)

6 2009 Pupil Colloquium

Conclusions: In conditions of near vision pupil size is affected by both spectrum and light level. The spectrum effect can be explained by the influence of the pRGC’s. Reading speed and accuracy are also affected by spectrum. There is a trade-off between light level and spectrum in that a lamp spectrum with more bluish content can provide the same visual performance at a lower light level than a lamp with less bluish spectral content.

*This work was supported by the US Dept of Energy, Assistant Secretary for Conservation and Renewable Energy, Office of Building Technology. ** Corresponding author email, [email protected] .

Parabolic Fixtures: ANOVA

4.4

4.2

HP830 3.8 HP865 MP830 MP865 3.6 LP830 LP865 Pupil diameter (mm)

3.4

3.2

3 1234567 Contrast Level

7 2009 Pupil Colloquium

The orbital sympathetic pathways: A clinical correlation

François-Xavier Borruat, Aki Kawasaki Hôpital Ophtalmique Jules Gonin University of Lausanne Eye Center Lausanne, Switzerland

Corresponding author : François-Xavier Borruat Avenue de France 15 Lausanne 1004 Switzerland 41-21-626-8660 [email protected]

Objectives. (1)To review recent studies using immunohistochemical (anti-tyrosine hydroxylase antibodies) markers which elucidate the pathways of the sympathetic nerves to and within the orbit. (2)To present 2 patients with an oculosympathetic defect (Horner syndrome) presumably due to an orbital mass and propose reasons for why this association is so rare.

Methods. Case report and literature review

Results. Sympathetic branches leave the internal carotid artery in the cavernous sinus and form a retro-orbital plexus near the annulus of Zinn. The majority of sympathetic fibers travel alongside sensory nerves. Our two patients with a discrete orbital mass had evidence of sympathetic deficit to the iris but not to the eyelid, suggesting sparing of the infratrochlear and lacrimal branches of the ophthalmic nerve.

Conclusions. Patients with an orbital mass typically present with proptosis, diplopia or visual loss. Our patients presented with only an oculosympathetic deficit, specifically the iris dilator muscle was affected. Anatomical segregation of sympathetic fibers within the orbit as based on their function might explain such a presentation.

8 2009 Pupil Colloquium Is Pupillary Response an Objective Bio-Marker for Disability and Brain Dysfunction in Older Adults with Chronic Low Back Pain?

Neilly Buckalew, MS-IV;1 Greg J. Siegle;2 Marc W. Haut, PhD;5 Howard Aizenstein, MD, PhD; 6,7 Lisa Morrow, PhD; 2 Subashan Perera, PhD;4 Debra Weiner, MD2-4,8

University of Pittsburgh School of Medicine (UPSOM) (1) Clinical Scientist Training Program and Departments of (2) Psychiatry, (3) Anesthesiology, and (4) Internal Medicine Geriatric Division; (5) Department of Behavioral Medicine and Psychiatry, Neurology, and Radiology at the WVU School of Medicine; Pittsburgh (6) John A. Hartford Center of Excellence in Geriatric Psychiatry and (7) Geriatric Research, Education, and Clinical Center; and (8) VA Pittsburgh Healthcare System.

Objectives: Chronic low back pain (CLBP) is the most common musculoskeletal disorder affecting older adults. Differences in brain structure and function have been proposed as key contributors to chronic pain and related disability (Buckalew 2008, Weiner 2006). In a recent pilot study we found significant differences in brain structure in older adults with CLBP self-reported as disabling compared to non-disabling, including poorer white matter integrity (P < 0.05) of the corpus callosum’s splenium and reduced (P < 0.02) left superior parietal lobe volumes. Given these findings, we hypothesized that the disabled CLBP participants would demonstrate differences in saccadic eye movements (higher response-suppression errors and increased error correction reaction time). We report preliminary findings from this ancillary study that investigated 1) group differences in saccadic eye movements and pupillary response as a measure of resource allocation and 2) relationships among eye measures with brain structure and function.

Methods: Sixteen cognitively intact community-dwelling older adults (> 65 years of age) with CLBP of at least moderate intensity experienced every day or almost every day for > 3 months were categorized into two groups: 1) Disabling CLBP - pain that necessitated cutting back on daily activities or resulted in being bed bound for > 6 weeks over the past 6 months; and 2) Non-disabling CLBP - pain that had not limited function for > 6 weeks over the past 6 months. All participants underwent an antisaccade task and concurrent measurement of pupillary response using an ISCAN table- mounted RK- 464 eye-tracker at 60 Hz. For the antisaccade task participants were instructed to fixate on a central stimulus when presented (3s) and to look to the mirror opposite of a peripheral stimulus when presented (1.5 s) at one of three locations (left or right of the center of fixation) for a total of 36 trials. The central stimulus would extinguish during the peripheral stimulus. Once the peripheral stimulus extinguished feedback appeared at the location where participants should have made the antisaccade. Percent response-suppression error and error-correction time were calculated. Participants in the main pilot study also underwent brain structural and resting state functional MRI, and neuropsychological testing. Important exclusions are psychiatric or neurological disorders, substance abuse, opioid use, or diabetes. Statistics include T-test for between group comparisons and Spearman’s correlation coefficients for association analysis combining groups.

Results: Though there is no difference between groups (disabled = 7, nondisabled = 8) in percent response-suppression errors in the antisaccade task, the mean pupillary response is statistically different (P < 0.02) during the antisaccade task period (defined as 1.6-2.25s) where the disabled group’s pupil diameter remained significantly smaller from 1.60-2.38s. In the principal pilot study we found differences in resting state fMRI where the subtraction contrast map for disabled- nondisabled demonstrated activation of the right medial prefrontal cortex (rMPFC) at rest and for nondisabled-disabled activation of the left lateral prefrontal cortex (lLPFC). Combined groups analysis reveals a strong positive correlation of pupillary response with the lLPFC resting state intensities (R = 0.6539, P < .006) and a strong negative correlation with rMPFC (R = - 0.4971, P < 0 .05).

Conclusions: This study is the first to demonstrate a fundamental difference in brain function by proxy of pupillary response in older adults with disabling CLBP. The reduced diameter during the antisaccade task suggests disabling chronic pain may be an objectively measurable state where allocation of neural resources contributes to disability. Though in contralateral regions, the finding of a strong positive correlation of pupillary response with lLPFC and negative correlation with the rMPFC may indicate a reciprocal relationship between these regions. A recent study of professional athletes demonstrated that autobiographical negative emotions activated the MPFC while concomitantly suppressing premotor and motor regions of the LPFC. Conversely, cognitive behavioral intervention resulted in decreased MPFC and restored premotor/motor region activation (Davis, 2008). Physical therapy and analgesics may be insufficient if brain structure and function are key contributors to chronic-pain-related disability. Therapies targeting brain function may be important in the standard of care; pupillary response may provide an objective measure for targeting treatment and measuring treatment effects. Whether the difference in brain function is the result of chronic pain or a predisposition to disabling chronic pain is unknown.

Support: NIH National Institute on Aging, UPSOM Claude D. Pepper Older Americans Independence Center.

9 2009 Pupil Colloquium Pupillary Responses During Digit Span Under Light and Darkness in Psychiatric Patients

Beatrice H. Chakraborty, PsyD.1, 2, Greg J. Siegle, Ph.D.2, Ruth Condray, Ph.D.2, Adam L. Clarke, B.A. 1,2 , Stuart R. Steinhauer, Ph.D.1,2 1VA Pittsburgh Healthcare System 2University of Pittsburgh School of Medicine.

Corresponding author: Beatrice H. Chakraborty; Biometrics Research, 151R, VA Pittsburgh Healthcare System, 7180 Highland Drive, Pittsburgh PA 15206 [email protected], 412-954-5362

Objectives: Missing from the pupil and digit span literature on healthy or patient subjects is any exploration of the differential autonomic contributions to the pupillary dilation which characterize encoding or overload due to digit string length. We conducted preliminary analyses of pupillary responses for healthy controls and psychiatric patients during performance of a digit span task in light and darkness to evaluate the extent to which the sympathetic and parasympathetic pathways are differentially associated with the pattern of pupillary motility.

Methods: Subjects included 8 controls, 7 schizophrenia patients, 12 subjects diagnosed with alcohol dependency, and 18 depressed persons. An auditory digit span recall task was employed in which 4, 7, or 10 digits were presented to elicit low to high levels of working memory load. Pupil diameter was digitized at 60 Hz during presentation of digits until subject’s verbal recall was completed.

Results: For normal subjects, the pattern of increasing dilation with increasing numbers of digits was greater in the light than in the dark and showed greater differences between conditions in the light. Only in the light, controls showed a decreased diameter following the presentation of the last digit and prior to the first digit of their verbal response. While dilation was greater overall for controls than all patient groups in the light, the differences were significant only for controls compared to schizophrenics and alcohol dependent patients, especially during the report period. The differences between patient groups which were most prominent in the light included greater dilation during the report period for schizophrenics compared to alcohol dependent and depressed patient groups. In the dark, all patient groups showed evidence of significantly increased dilation to the initial few digits in the presentation period compared to controls.

Conclusions: Decreased pupillary dilation was associated with processing difficulties at higher cognitive loads among all patient groups compared to healthy controls. Findings suggest that dilation during digit span in moderate illumination is related primarily to the inhibition of the parasympathetic pathway. Reduced central parasympathetic inhibition is evident immediately following stimulus reception. In addition, recordings in darkness suggest that patient groups exhibit a transient sympathetic activation at the start of encoding that is not seen among healthy individuals.

Supported by the Department of Veterans Affairs; NIMH Grants MH55762 and MH082998 ; Clinical and Translational Science Institute (CTSI), University of Pittsburgh

10 2009 Pupil Colloquium Examining the effects of cognitive task training on dysphoria

Amanda L. Collier1, Greg J. Siegle2,1 1Department of Psychology, University of Pittsburgh School of Arts and Sciences, 2Department of Psychiatry, University of Pittsburgh School of Medicine

Corresponding author: Amanda Collier [email protected] 412-901-2938 141 Loeffler Building, 121 Meyran Avenue, Pittsburgh, PA 15213

Objectives. Negative information processing biases have been proposed to maintain depressive mood state. This work will explore one type of bias in a non-clinical sample of dysphoric undergraduates, prediction bias, a tendency to predict negative outcomes more often than healthy controls. In addition to documenting the bias, this study examined whether changes in the prediction bias were associated with decreased symptoms and changes in other information processing biases.

Methods. Subjects included 43 undergraduates. The dysphoric group contained 25 students who scored above 8 on the Quick Inventory of Depressive Symptomatology (QIDS) administered as an online screening. All students participated in four lab visits which included pre and post-training assessments of symptoms and task performance. Training was guided by feedback and involved prediction of positive or negative outcomes in response to neutral cues. Two versions of this task were developed; one version contained equal numbers of positive and negative outcomes and another version exposed participants to positive outcomes on 70% of all trials. Pupil dilation was recorded during all tasks, as an index of cognitive and emotional reactivity.

Results. Dysphoric individuals assigned to the equal version of the task were less likely to predict positive outcomes than controls. Dysphoric subjects were more reactive to all types of feedback on day one. Measured bias decreased incrementally with each training session. After training, dysphoric students in both conditions consistently predicted more positive outcomes than negative outcomes, suggesting that a positive bias had been induced. Consistent with this idea, dysphoric students displayed heightened reactivity only on trials where they had predicted a negative outcome, regardless of the trial outcome. Symptoms decreased as did bias on other emotional information processing tasks.

Conclusions. Prediction biases exist in dysphoric undergraduates and can be modified with training. Also, reactivity to feedback may prove informative when examining possible mechanisms leading to the development and maintenance of negative cognitive biases in dysphoria and depression. These findings show promise for the use of cognitive training to modify the cognitions, physiology, and symptoms associated with dysphoria and mild depression.

Supported by: NIMH Undergraduate Fellowship 5R25MH054318-13 to ALC, NIMH K02 MH 082998 to GJS

11 2009 Pupil Colloquium

Sleep deprivation increases pupillary reactivity to negative emotional information in healthy young adults

Peter L. Franzen, Ph.D., Denise N. Duryea, B.A., Greg J. Siegle, Ph.D. University of Pittsburgh School of Medicine

Corresponding author (name, address, email, phone): Peter Franzen, WPIC, 3811 O’Hara St, Pittsburgh, PA 15213, [email protected], 412-586-9038

Objectives. Many studies have documented sleep deprivation-induced subjective mood impairments. Few studies have employed objective measures, and therefore little is known about the specific emotional processes that are affected by sleep deprivation. We used pupil dilation as an objective, physiological indicator to examine emotional reactivity while anticipating and in response to negative emotional information.

Methods. Using a within-subjects crossover design, 13 young adults 18–25 years old without psychiatric, medical, or sleep disorders were tested under two experimental conditions separated by one week: sleep deprivation (SD; following one night of total SD) and rested wakefulness (RW; following one night of normal sleep). Two tasks assessing responses to affective auditory and visual stimuli were presented. The auditory task involved identifying the valence of positive, neutral, and negative auditory sounds (14 each). The stimuli were 6-seconds in duration and were drawn from the International Affective Digitized Sounds. For the visual task, negative and neutral pictures (24 each) from the International Affective Picture System were presented in a random order. Trials consisted of a 6-second cue (half of the cues indicated the valence of the upcoming stimulus, while the other half did not indicate whether the upcoming picture was negative or neutral), a 2- second picture presentation, and an 8-second inter-stimulus interval. During both tasks, pupil diameter was continuously acquired at 60 Hz using an ISCAN pupilometer. Baseline-corrected waveform averages were then compared to detect differences between negative and non-negative stimuli in participants tested under SD versus RW conditions.

Results. In comparing negative minus neutral waveforms to the auditory stimuli, pupil dilation was significantly larger during SD compared to RW (F(1,12)=5.2, p=0.04). SD impacted the time course of responses to negative sounds; significant differences between the negative versus non-negative pupil dilation waveforms emerged 1 second earlier and persisted 1.8 seconds longer in SD compared to RW. Similarly, SD potentiated responses to negative visual stimuli. During SD, negative pictures resulted in a sustained and exaggerated pupil dilation response compared to neutral pictures (F(1,12)=9.7, p=0.009) and compared to responses to negative pictures during RW (F(1,12)=13.1, p=0.003), whereas pupillary responses did not differ between negative and neutral pictures during RW.

Conclusions. Sleep deprived individuals displayed significantly greater emotional reactivity as indexed by larger pupil dilation responses in response to negative auditory and visual stimuli. These findings suggest that acute sleep loss specifically impairs the central processing of negative emotion, and may have implications for the link between sleep disturbances and mood disorders.

Supported by: MH077106, RR024153, and the National Sleep Foundation

12 2009 Pupil Colloquium

Pupil dilation as an index of reactivity to errors in early adolescence

Naho Ichikawa, M.A.1, Jennifer S. Silk,, Ph.D., Cecile Ladouceur, Ph.D., Ronald E. Dahl, M.D., Neil S Ryan, M.D., Greg J. Siegle, Ph.D.1 1University of Pittsburgh, School of Medicine

Corresponding author: Naho Ichikawa, Loeffler, 121 Meyran Ave., Pittsburgh, PA 15213, [email protected], 412-383-8214

Objectives. Error-related processing in the brain has been successfully examined using the “error-related- negativity” (ERN) event-related brain potential. Pupil dilation has also been associated with errors, and has been found to reflect activitity in the rostral ACC activity which has also been implicated in the ERN. Although both the ERN and pupil reactivity to errors have been observed in adults (e.g. Critchley et al., 2005), the ERN hasn’t been as clearly observed in early adolescents (Ladouceur et al., 2007). This presentation shows initial results of pupil reactivity associated with error processing in early adolescents.

Methods. We collected pupilometric data during a Flanker task in which participants had to judge the orientation of a central stimulus surrounded by either similar or differently oriented stimuli (e.g. “>>>>>” or “>><>>” were presented as congruent and incongruent conditions respectively). Data was collected using an ISCAN pupilometer at 60 Hz digital sampling. Thirty five healthy children (age range: 9-13) completed five consecutive five minute blocks of the flanker task. Data from one subject was rejected because of technical problems in data collection. Data were preprocessed via interpolation through blinks and detrending across blocks, as in our previous studies (e.g., Siegle et al., 2008).

Results. As shown in Figure 1, increased pupillary responses to error were clearly observed in response-onset averaged data. To confirm this observation statistically, a one-way ANOVA was conducted on each time point. In order to control Type I error, the difference was considered significant only when there are at least 14 significant contiguous test in a row at p<.05 (233 ms), which exceeds the expected the threshold given the autocorrelation of component waveforms (r=.92) in the length of simulated time interval (2000 ms), as recommended by Guthrie and Buchwald (1991). As a Figure 1: Flanker Task: Response-onset Pupil Dilation(n=34) result, the difference between error and correct responses 0.1 was significant from 530 ms to 1450 ms after the Error response, F(1,33)=27.35, p<0.0005. Correct

Conclusions. Our data suggests that error-related changes 0.05 in pupil dilation were clearly and significantly observable

in healthy early adolescents. This index may be more Dilation Pupil robust than the ERN for this age group. 0

Supported by: MH082998, MH41712, MH080215

-0.05 0 0.5 1 1.5 Response-onset, time(sec)

13 2009 Pupil Colloquium Sympathetic, parasympathetic and medication effects on pupil reactivity to light in Parkinson disease

Samay Jain M.D. M.S.1, Greg J. Siegle Ph.D1, Stephanie Studenski M.D. M.P.H.1, J. Timothy Greenamyre M.D. Ph.D. 1, Stuart R. Steinhauer, Ph.D.1,2 1University of Pittsburgh School of Medicine, 2VA Pittsburgh Healthcare System

Corresponding author: Samay Jain, Department of Neurology, 3471 Fifth Ave., Suite 811 Kaufman Medical Building, Pittsburgh PA 15213-3232. [email protected], 412-692-2394.

Objectives: Recent clinicopathological evidence indicates that neurodegeneration in Parkinson disease (PD) is more widespread that previously thought, affecting autonomic function. Non-invasive measures of such changes may aid in earlier diagnosis or surveillance of PD. We sought to determine if pupil reactivity to light is affected in PD.

Methods: Participants included 8 controls and 8 PD patients (anti-parkinsonian medications were held in 4/8 PD participants). The light reflex was performed with eleven “flashes” (a white circle; 1 second duration, every 10 seconds). Horizontal pupil diameter measured in darkness from the right eye was digitized using an ISCAN pupillometer at 60 Hz at a resolution of .04mm. Measures derived from averaged waveforms across subject groups and across repeated trials include: initial diameter, latency to beginning of constriction, maximum constriction velocity, maximum constriction, maximum redilation velocity, 50% redilation and 75% redilation. At each point, response time, pupil diameter, speed and velocity were assessed. Group comparisons were made between controls and PD participants as well as between PD participants taking all medications and those in which anti-parkinsonian medications were withheld. Measures were evaluated at an alpha level < 0.1 for magnitude and variance with one-sided t-tests and F-tests of equal variance (test of equality for standard deviations), respectively and as appropriate.

Results: Compared to controls, PD participants had a higher maximum redilation velocity, a longer time to maximum redilation velocity and a higher velocity at 75% redilation. Compared to controls, PD participants had lower variance for latency to beginning of constriction and maximum constriction velocity. Higher variance was found in PD for time to 50% redilation, maximum redilation velocity and time to 75% redilation. When comparing participants with PD taking medication to those with PD in whom medication was withheld, PD participants taking medication had a shorter time to maximum constriction. These participants also had lower variance for latency to beginning of constriction and time to 75% redilation.

Conclusions: Our results suggest that compared to controls, in PD there is a relatively higher predominance of pupillary sympathetic activity given that velocity at 75% redilation was higher. This may be due to increased sympathetic or decreased parasympathetic activity, either or both of which can account for the higher maximum redilation velocity and the longer time to its onset. Variance - a measure of the range of autonomic activity - was lower in PD for latency to beginning of constriction and maximum constriction velocity. This suggests a restricted range of parasympathetic pupillary activity in PD. The higher variance seen in specific measures of redilation suggests an increase in the range of predominantly sympathetic pupillary activity. Also suggested are parasympathetic effects of anti-parkinsonian medications (shorter time to maximum constriction). These medications may also restrict the range of parasympathetic and sympathetic activity as suggested by lower variance for latency to beginning of contraction and time to 75% redilation, respectively. Further study is warranted to determine if pupillography may have clinical applications for PD.

Supported by: NIH grants KL2 RR024154, KMH082998, MH55762, Dept. of Veterans Affairs, and the American Parkinson Disease Association Center for Advanced Research

14 2009 Pupil Colloquium Features of Borderline Personality Disorder and Pupil Reactivity While Viewing Emotional Faces Neil P. Jones, Stephanie D. Stepp, Greg J. Siegle, and Paul A. Pilkonis

Objective: Borderline Personality Disorder (BPD) is multifaceted, characterized by four features that emerge from factor analytic studies and content evaluation of the DSM criteria: Affective Instability, Impulsivity, Negative Relationships, and Identity Disturbance (Morey, 1991; Linehan, 1993; APA, 2000; Sanislow et al, 2002; & Crick et al, 2005). BPD patients demonstrate greater activation in brain regions associated with processing negative emotional stimuli potentially due to poor regulation of the emotional response (Herpetz et al., 2001; New et al., 2007). Studies have yet to which specific BPD features are related to physiological processes. In this study, our aim is to investigate the relation between a physiological index of cognitive- emotional processing (i.e., pupil dilation) and specific features of BPD in order to elucidate which aspects of the BPD phenotype are associated with disruptions in social-cognitive processes.

Methods. The sample (N=40) comprised of both community (60%) and psychiatric (40%) participants. The mean age was 46 (SD=11.57). Participants completed the Personality Assessment Inventory-Borderline Features Scale (PAI-BOR; Morey, 1991), which contains 24 items rated on a four-point scale. We examined potential biases in social cognition using 24 faces (Negative Condition = 4 sad, 4 fearful, 4 angry; Positive Condition = 4 happy, and Neutral Condition= 8 neutral) from the Ekman stimulus materials (Matsumoto & Ekman, 1988). For purposes of this study, we are focusing on pupil dilation during the viewing of emotional faces period. We recorded pupil dilation continuously during the Faces Task. Pupil dilation reflects activity in a variety of brain regions involved in information processing (e.g., sensory, attention, or memory) including regions that subserve emotion (e.g., amygdala; Koikegami & Yoshida, 1953). Pupil size increases with processing demands and in response to emotional information (see Beatty, 1982b; Steinhauer & Hakerem, 1992 for reviews).

Results: PAI-BOR Total Score was negatively related to pupil dilation while viewing negative emotional faces (r=.35, p=.03). However, there was no significant relation between PAI-BOR Total Score and pupil dilation while viewing neither positive nor neutral faces. Disaggregating negative faces, yielded a negative association between PAI-BOR Total Score and pupil dilation while viewing angry (r=.38, p=.02) and fearful (r=.31, p=.05) faces but not while viewing sad faces. Next, we examined which specific features of BPD were related to pupil dilation while viewing angry and fearful faces. Interestingly, only the Negative Relationships feature was significantly negatively related to pupil dilation while viewing angry (r=.40, p=.01) and fearful (r=.32, p=.04) faces.

Conclusions: Individuals with high levels of the Negative Relationships BPD feature demonstrated decreased pupil dilation in response to viewing angry and fearful faces. This could potentially reflect that individuals who have stormy interpersonal relationships characteristic of the BPD phenotype experience a blunted emotional response or difficulties with emotion regulation when faced with negative social cues. We will further examine these potential explanatory factors for the relation between pupil dilation and Negative Relationships BPD feature. Specifically, it is of interest to determine whether physiological decreased cognitive and emotional processing while viewing angry faces reflects difficulties with emotion regulation.

15 2009 Pupil Colloquium Diagnosis of Horner Syndrome Using the Topical Effects of Apraclonidine on the Eyelids and Pupils

Randy Kardon M.D. Ph.D.1, Susan Anderson B.S.1, and Andrew Lee M.D

1Department of Ophthalmology and Visual Sciences, University of Iowa and Veterans Administration, Iowa City, IA USA., 2Department of Ophthalmology, Methodist Hospital and Weill Cornell Medical School, Houston, TX USA

Corresponding author (name, address, email, phone): Randy Kardon M.D. Ph.D, Department of Ophthalmology and Visual Sciences, PFP, UIHC, 200 Hawkins Drive, Iowa City, IA 52242, [email protected], 319- 356-2260

Purpose: Alternative methods for diagnosing oculosympathetic palsy are needed because of false positive and false negative results that can occur with cocaine testing and pupillography of pupil dilation. Apraclonidine has been reported to offer a new pharmacologic method based on its agonist effects on alpha-2 receptors and weak agonist effects on alpha-1 receptors on the smooth muscle of the iris dilator and Mueller’s eyelid muscle.

Methods: 18 consecutive patients with Horner’s syndrome diagnosed clinically were recorded by infrared videography and computerized pupillography to quantify the effects of 0.5% apraclonidine on the eyelids and pupils when given to both eyes. On separate days, the same patients were tested with cocaine, localized with hydroxyamphetamine, and underwent neuroimaging.

Results: One patient tested as early as 60 hours (2.5 days) after carotid dissection showed a differential apraclonidine effect on the pupils, indicating adrenergic supersensitivity. All 10 patients with compressive lesions had a positive apraclonidine test, indicating that supersensitivity can occur in this cause.2 patients initially were misdiagnosed with cocaine testing; a negative apraclonidine test confirmed pseudo-Horner’s syndrome. There was a highly significant negative correlation between percent pupil change after apraclonidine and percent pupil change after cocaine testing in the same eye. All cases of ptosis reversed after topical apraclonidine.

Conclusion: Apraclonidine appears to have specific advantages that may exceed those offered by cocaine for pharmacologic diagnosis of Horner’s syndrome. However, its use in infants may be limited by reports of CNS depression in a few cases reported in the literature.

Supported by: Department of Veterans Affairs Center of Excellence and Merit Review Grant, Unrestricted grant from Research to Prevent Blindness, and Pomerantz Family Chair in Ophthalmology.

16 2009 Pupil Colloquium

Sensitivity of test paradigms for assessing antimuscarinic effects of pupillary light reflex

A Randomised Double-Blind Double-Dummy Placebo Controlled Crossover Pilot Methodology Trial With Tolterodine and Oxybutynine in Healthy Volunteers

Tobias Peters, Barbara Wilhelm and Helmut Wilhelm Pupil Research Group at the Centre for Ophthalmology, University Hospital Tübingen

Objectives. To define appropriate and optimal test parameters of the pupillary light reflex (PLR) and glare for subsequent studies with the M3-inhibitors tolterodine and oxybutinine in patients.

Methods. Study Design: double-blind, double-dummy, 3-period, 3-treatment cross-over study, three 96-hour treatment periods spanning over 5 days, separated by washout periods (6d), 12 male and 12 female subjects were randomised to study both sexes adequately. Pupillography: The PLR was recorded by an automated infrared pupillograph (Compact Integrated Pupillograph, AMTech GmbH, Weinheim, Germany). PLR was elicited by light impulses of 200 msec and 4 seconds duration of 2.4 lx and 75 lx corneal illumination intensities at background light intensities 2 2 of 0.1 cd/m (mesopic) and 10 cd/m (photopic). Various parameters of the PLR were measured. In addition the Mesoptometer II (Oculus, Ger), Straylightmeter, PowerRefractor and Accomodometer (Oculus, Ger) were used for further measurements. The mean difference of the drug group compared to the placebo group was calculated along with 95% confidence intervals (CIs) for these differences in the ITT population.

Results. The PLR parameters had high p-values for the treatment/condition interaction and sequence for each of the 3 visits. In general the following test conditions proofed to be optimal in showing differences between the Tolterodine/Oxybutynin/Placebo: 2,4lx corneal illumination at 10cd/m2 background illumination. A stimulus duration of 200ms showed optimal differences in the parameters baseline pupil diameter (PD; mm), minimal PD (mm) and absolute amplitude (mm). A 4s stimulus duration showed strongest effects on relative amplitude, latency and maximal speed of constriction (mm/s).

Conclusions. Pupillary light reflex analysis provides parameters suitable for the assessment of drug effects by M3 inhibitors. Photopic conditions and longer stimulus durations of 4s (compared to common standards of 200ms) may be considered for such purposes.

Grant: Supported by Pfizer Germany. Trial A8121145

Corresponding author: Tobias Peters, MD Pupil Research Group Centre for Ophthalmology Schleichstr 12-16 D-72076 Tübingen phone ++49 7071 298 4894 [email protected]

17 2009 Pupil Colloquium Differential effects on learning in a highly complex geometrical task in highly vs. averagely gifted high-school students.

Jan Ries1, Martin Brucks1, Manja Foth1, Judith Horn1, Boris Bornemann1, Elke van der Meer1,2

1) Humboldt University at Berlin, Department of Psychology, Germany 2) Berlin School of Mind and Brain, Charité, Germany

cand.-psych. Jan Ries, Humboldt University at Berlin, Department of Psychology – Cognitive Psychology, Rudower Chaussee 18, 12489 Berlin, Germany, [email protected], +49 30 2093 9384

Objectives. In higher order cognition problems are most often comprised of a large amount of variables that are to be taken into account or are at least to be considered as necessary for reaching a decision. Efficient solving of such problems thus requires the ability to decide and to learn where valid cues are located. In this most recent study, we investigated the question how learning of a difficult and complex geometrical task modulates allocation of resources and use of strategies in highly vs. averagely gifted subjects. Performance increases in a novel task such as this one could be obtained by shifting from processing to fact retrieval (cf. Ischebeck et al., 2009), by acquiring procedural knowledge or by training metacognitive skills. To tackle this question we had particular interest in transfer effects onto novel stimuli. Methods. We tested a sample of 11th graders, for which psychometric data (IQ scores, working memory capacity, attention) were extensively at hand, with a learning experiment on the recognition of mirroring in abstract geometrical patterns. The experiment consisted of a learning phase, in which subjects learned the task on a limited set of items. A second transfer phase extended the amount of patterns with new but similarly constructed patterns as well as structurally new patterns, to investigate transfer effects on different levels. Beside behavioral parameters (reaction time, accuracy), we measured peak pupil dilation as an indicator of cognitive resource consumption in general (cf. Just et al., 2003) and attentional allocation in special (cf. Verney et al., 2004) as well as gaze tracking data to identify strategies (cf. Vigneau et al., 2006). Results. Data analysis shows that superiorly gifted subjects perform significantly better right from the beginning of the learning experiment and even for the easiest trials. They also generally invest more resources while solving the task, and most interestingly: while the plus in resource investment as compared to normal controls is constant, behavioral data (especially reaction times) show an overproportional advantage on most difficult trials (diagonal mirroring). Conclusions. These result give further support to the resource hypothesis, we identified in earlier experiments (cf. van der Meer et al., 2009). This hypothesis states that subjects of greater abilities outperform the averagely gifted by being able to invest more resources. This is especially evident in most difficult tasks, where gifted subjects were able to maintain performance to a certain degree, while the controls’ performance was significantly suffering beyond expectations. We interpret this last detail in such way, that these most difficult trials exceeded the available resources of averagely gifted subjects and forced a shift towards a more time consuming strategy, whereas subjects of superior intelligence could still successfully administer the same strategy used for easier trials.

Supported by: German Federal Ministry for Education and Research (NIL-I/II)

18 2009 Pupil Colloquium Seeing eye to eye: First examinations of concurrent pupillary reactivity during mother-child interactions

Greg J. Siegle, Ph.D.1, Jennifer Silk, Ph.D.1, Erika Joyce, B.A.1,Ronald Dahl, M.D.2 1University of Pittsburgh School of Medicine

Corresponding author (name, address, email, phone): Greg J. Siegle, WPIC, 3811 O’Hara St, Pittsburgh, PA 15213, [email protected], 412-383-5444

Objectives. Parent-child interactions are some of the most formative developmental experiences. Yet, little is known regarding the dynamics of brain mechanisms of cognitive and emotional information processing during these interactions on the time-scale of cognitive events, from milliseconds to seconds. Pupillary motility represents an important vehicle for this type of investigation as it 1) can be measured non-intrusively during naturalistic interactions and 2) reflects brain mechanisms of cognitive and emotional information processing on a millisecond timescale. This presentation represents the first such examination using data collected during concurrent acquisition of pupillary motility from mothers and children during naturalistic interactions.

Methods. We developed technology that allowed mothers and their children to interact dynamically while wearing head-mounted pupilometers (ISCAN model 746, 60 Hz, digital acquisition). 44 mother-child dyads completed three consecutive five minute discussions on themes of support, conflict, and planning a fun activity during pupilometric assessment. Data from representative participants with the cleanest data were subjected to smoothed lagged cross-correlation and vector-autoregressive (“Granger causal”) analyses, and evaluated on a case-by-case basis to understand dyad-wise differences in reactivity during mother-child interactions.

Results. Across participants, correlations between mother and Figure 1: Mother and child pupillary waveforms for two dyads. A) Child’s pupillary motility preceded the mother’s child pupillary motility were of moderate magnitude (~0.3) and by 20 seconds. B) Mother’s motility preceded the child’s higher than expected by chance, following smoothing with an by 14 seconds. A Smoothing = 0.01Hz, Relationship with lag 19.62 seconds: r=0.38 optimal low-pass filter of 0.01Hz, suggesting that dyadic- 0.6 Parent 0.4 Child reactivity was best measured on the time-scale of seconds to 0.2 minutes. Correlations were maximal with 13-20 second lags mm 0 -0.2 suggesting that pupillary motility was a useful measure of dyadic -0.4 0 500 1000 1500 seconds B reactivity. As shown in Figure 1, for some dyads strongest Smoothing = 0.01Hz, Relationship with lag -13.95 seconds: r=0.35 0.5 Parent relationships involved mothers’ pupils increasing up to 20 Child seconds following reactivity in the child. In others, the child’s mm 0

-0.5 pupil was positively or negatively related to the changes in the 0 200 400 600 800 1000 1200 1400 mother’s pupil up to 20 seconds later. seconds

Conclusions. Data suggest that that there are strongly observable dyad-wise differences in the nature of mother- child interactions. Children variously appear to react strongly to changes in a mother’s cognitive and emotional information processing with either increased or decreased indices of their own cognitive and emotional information processing up to 20 seconds later.

Supported by: DA024144, MH082998

19 2009 Pupil Colloquium Pupil Dilation to Affective Words as a Marker of Risk for Early Onset Depression

Jennifer S. Silk Ph.D., Ronald E. Dahl, M.D., Neal D. Ryan, M.D., & Greg J. Siegle, Ph.D.

Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA

Corresponding author: Jennifer S. Silk, Western Psychiatric Institute and Clinic, University of Pittsburgh, 3811 O’Hara Street, Pittsburgh, PA 15213. Phone: 412-383-8136. Fax: 412-383-5426. Email: [email protected].

Objectives: Previous studies have reported that depressed adults show sustained pupil dilation to emotional words (Siegle et al. 2001, 2003), but Silk et al. 2007 reported a reversal of this pattern in depressed youth in which youth with MDD showed diminished late pupil dilation relative to controls 9-12 seconds after a negative word was presented. This study sought to investigate sustained pupillary reactivity to negative words in healthy youth at high risk for MDD. Method: Participants were 21 children at high risk for Major Depressive Disorder based on familial psychiatric history and 22 controls ages 8-17. Both high-risk and low-risk youth had no history of psychiatric diagnoses. Pupil dilation was measured using an ISCAN head-mounted RK-726 or table-mounted RK- 464 eye-tracker at 60 Hz during a Valence Identification Task. Participants were instructed to identify the emotional valence of 22 positive, 22 negative, and 22 neutral words, chosen from a corpus of emotional words normed for use with children, by pressing a corresponding button for each valence. The average pupil diameter over the 167ms preceding the onset of the stimulus, was subtracted from pupil diameter after stimulus onset to produce stimulus-related pupil dilation waveforms. Results: Healthy children at high risk for depression showed a pattern of diminished late pupil dilation relative to controls 9-10 seconds after a negative word was presented (t=1.87, p=0.07, d=0.57). High-risk youth did not differ from controls in pupil dilation to neutral words. This pattern was similar to the pattern reported for youth in a current episode of depression reported in Silk et al. 2007. Conclusions: Findings suggest that late pupil dilation to negative emotional material could serve as a biomarker for depression risk. This finding suggests that high risk youth devote decreased cognitive/affective resources to processing negative emotional words after a word is initially processed compared to children at low risk for depression. Multiple alterations in emotional reactivity or regulation could be responsible for such decreased resource recruitment, such as affective blunting resulting in decreased amygdala reactivity, decreased engagement of regulatory structures such as the dosolateral prefrontal cortex (DLPFC) in response to negative stimuli, or increased early recruitment of regulatory resources resulting in decreased later engagement with the stimulus. We are currently collecting concurrent pupillary/fMRI data on this task in high risk youth to better understand the neural mechanisms underlying altered pupillary motility to emotional information in youth at risk for depression.

Supported by: National Institute of Mental Health (NIMH) Grants P01 MH41712 (Ryan), K01 MHO73077 (Silk), and a NARSAD Young Investigator Award (Silk).

20 2009 Pupil Colloquium Working memory and pupillary dilation: Impairments in Schizophrenia, Depression, and Alcohol-related Disorders

Stuart R. Steinhauer, Ph.D.1,2 , Greg J. Siegle, Ph.D.2, Ruth Condray, Ph.D.2 1VA Pittsburgh Healthcare System 2University of Pittsburgh School of Medicine.

Corresponding author: Stuart R. Steinhauer; Biometrics Research, 151R, VA Pittsburgh Healthcare System, 7180 Highland Drive, Pittsburgh PA 15206 [email protected], 412-954-5366

Objectives: Deficits in cognitive processing among schizophrenia patients are known to be reflected by reduction in the amplitude of the pupillary response during a variety of task demands. We sought to determine the extent to which this would be observed in a parametric manipulation of working memory in both schizophrenia patients and in comparison to other neuropsychiatric disorders.

Methods: Subjects included 9 controls, 11 schizophrenia patients (7 with comorbid alcohol abuse or dependence), 26 patients with a major depressive disorder, and 24 patients with a history of alcohol abuse or dependence (but no other Axis I disorder). A digit sorting task was employed in which 3-5 initial digits were presented visually, requiring a mental sorting so that a subsequent target could be compared to the middle of the array. Pupil diameter was recorded with an ISCAN RK-406 pupillometer (60 Hz digitization rate). Averaged waveforms were evaluated across subject groups and across the repeated levels of task demand. Regions of significant differences among waveforms were evaluated using the Guthrie & Buchwald technique.

Results: As in previous studies, following stimulus array presentation, increasing number of digits resulted in an initial increased pupillary dilation. This was followed by decreased diameter during the interval preceding the target stimulus, a separate dilation following the target and subject’s motor response, and a final period of decreasing diameter. Significantly smaller initial dilations were observed for schizophrenia, depressed, and alcohol abuse patients as compared to healthy controls. No differences were seen between the patient groups for the early dilation, though schizophrenia patients showed a significantly prolonged period of recovery after the target stimulus compared to other patient groups in the high demand (sort 5) condition. In addition, the schizophrenia patient group showed a slower time course to the initial peak dilation.

Conclusions: Impairments in pupillary dilation suggest deficient activation of central processing, likely related to reduced resource allocation, in all of the patient groups as compared to healthy controls. Concurrent pupillary and fMRI recording with this task has shown coactivation of the pupil with prefrontal and parietal regions (Siegle et al, 2003). Note that all patient groups showed responsiveness to the varying task demands. Schizophrenia patients were further characterized by dysfunction in the recruitment of resources for initial task processing, as well as impaired resolution of demand characteristics under high levels of task complexity.

Supported by the Department of Veterans Affairs and NIMH Grants MH55762 and MH082998

21 2009 Pupil Colloquium

Mathematical Cognition - Individual Differences in Resource Allocation

Elke van der Meer1,4,Boris Bornemann1, Manja Foth1, Judith Horn1, Jan Ries1, Elke Warmuth2, Isabell Wartenburger3,4,

1) Humboldt University at Berlin, Department of Psychology, Germany 2) Humboldt University at Berlin, Department of Mathematics, Germany 3) University of Potsdam, Department of Linguistics, Germany 4) Berlin School of Mind and Brain, Charité, Germany

Corresponding author: Elke van der Meer, Humboldt University at Berlin, Department of Psychology, Berlin School of Mind and Brain, Rudower Chaussee 18, 12489 Berlin, Germany, [email protected], +49- (0)30-20939390

Objectives. Mathematics comprises different domains such as arithmetic, algebra, geometry and many more. Resource allocation in such tasks depends on characteristics of the task as well as on cognitive abilities of the individual. In this study, we investigated whether the superior performance of individuals with high cognitiver abilities rather results from the allocation of more cognitive resources or from more efficient processes (allocation of fewer resources).

Methods. We examined 11th-graders differing in cognitive abilities (intelligence, working memory capacity, attention) on a simple choice reaction time task, a geometric analogy task, and a task involving the simplification of algebraic expressions. We measured behavioural parameters (speed, accuracy) as well as pupil diameter as an indicator of resource allocation (cf. Just et al., 2003).

Results. Behaviourally, individuals of high cognitive abilities outperformed individuals of average cognitive abilities in all tasks. While in the choice reaction time task, pupil diameters were not dependent on cognitive abilities, individuals with high cognitive abilities displayed higher pupil diameters in the analogy and algebra task. Thus, in elementary tasks individuals with higher cognitive abilities profit from a higher cognitive efficiency, while superior performance in the more demanding mathematical tasks results from greater resource allocation. Furthermore, individuals with high cognitive abilities displayed a greater pre-experimental pupil baseline. These findings indicate that individuals with high cognitive abilities tend to scan the environment for a task of interest when no demand is at hand and tune their cognitive system to the respective demand when given a sufficiently interesting task (cf. Aston-Jones & Cohen, 2005).

Conclusions. The study provides insights that may help neuroscientists, cognitive psychologists and educational practitioners to understand why some students perform better in mathematical tasks, such as geometry or algebra. The presented neurophysiologic evidence suggests that individuals with higher cognitive abilities achieve superior performance through stronger task-orientation and the allocation of more cognitive resources in processing the task. Learning induced changes in resource allocation during mathematics education will be discussed (cf. Neubauer et al., 2004).

Supported by: German Federal Ministry for Education and Research (NIL-I/II), Berlin Neuroimaging Center

22 2009 Pupil Colloquium How do pupils of pupils oscillate? - Feasibility and reference values for the pupillographic sleepiness test in children and adolescents

Barbara Wilhelm1, Katharina Weible1, Jutta Diem2, Katrin Heine2, Pablo Brockmann2, Tobias Peters1, Wilhelm Durst1, Michael S. Urschitz2 1 Pupil Research Group at the Centre for Ophthalmology, University Hospital Tuebingen, Germany 2 Working Group on Paediatric Sleep Medicine, Department of Neonatology, University Children's Hospital Tuebingen, Germany

Objectives A simple screening method for diseases with excessive daytime sleepiness in children has been missing hitherto. We investigated the feasibility of the Pupillographic Sleepiness Test (PST) in schools, the effects of age and gender on the Pupillographic Unrest Index (PUI), and compared paediatric with previously obtained normative adult values.

Methods Headmasters of one primary school and one college located within the city limits of Tuebingen, Germany, received information about the study. If written informed parental consent was given, parents received a bundle of sleep-related questionnaires and the PST measurements and self-administered questionnaires were scheduled. All PST measurements were performed during winter 2008/9 in prepared school rooms protected against ambient light and noise. PST was performed according to clinical standard conditions for adults.

Results Recordings were performed in 163 children (age range 6 – 17 years). Nine measurements were not evaluable (3 in primary school, 6 in college) leaving a final sample of 154 participants (78 girls, 76 boys). lnPUI: min 1.09, max 3.22, median 2.01. There was a negative correlation between lnPUI and age (Spearman's rho -0.203, p- value 0.012). Boys (mean lnPUI ± SD: 2.15 ± 0.45) showed significantly higher (=sleepier) lnPUI values than girls (mean lnPUI ± SD: 1.92 ± 0.41, p-value 0.001). The examined group of school pupils (mean lnPUI ± SD: 2.03 ± 0.45) had higher lnPUI than the normative sample of adults (mean lnPUI ± S D: 1.50 ± 0.39, p-value <0.001).

Discussion and Conclusions The method proofed its feasibility during school age and its suitability as a screening method for excessive daytime sleepiness. Due to the pronounced gender differences not found in adults and due to the difference to the adult normative values, further examinations of larger samples are needed to define percentiles applicable for screening purposes during school age.

Acknowledgements We thank all pupils, parents and teachers of the Grundschule Hechinger Eck and the Carlo-Schmid-Gymnasium, Tübingen, the directors and their secretaries for their motivating interest, support and participation. This project was partly supported by AKF 226-0-0.

Corresponding author: Barbara Wilhelm, MD, PhD Pupil Research Group Centre for Ophthalmology Schleichstr 12-16 D-72076 Tübingen phone ++49 7071 298 4898 [email protected] 23 2009 Pupil Colloquium

Explaining unexplained visual loss by the pupil – possibilities and limitations

Helmut Wilhelm

University of Tuebingen, Medical School Centre of Ophthalmology, University Eye Hospital; Schleichstr. 12-16; D 72076 Tübingen Tel. +497071 2984830; Fax +497071 295361; [email protected]

In neuro-ophthalmology non-organic visual loss is a common differential diagnosis. The patient may simulate, suffer from a so called Münchhausen syndrome or from a histrionic disorder. As an objective sign pupil examination plays a major role in diagnosing non-organic visual loss. This presentation is thought to demonstrate different approaches in different clinical settings.

Complete blindness. To prove complete blindness pupillary light reaction needs to be absent but the pupil must be able to react on other stimuli. Bell’s phenomenon can be tested in such cases. It has to be kept in mind that in retinal receptor degeneration some pupillary light response may be preserved due to melanopsin retinal ganglion cells despite of complete blindness. This may be addressed by special stimulus characteristics.

Unilateral blindness or visual loss. In this case the swinging flashlight test demonstrates reduced light sensitivity of the involved eye. The swinging flashlight test will remain normal in optic media opacities except vitreous hemorrhage and some cases of macular disorders.

Visual hemifield loss. Pupil campimetry is suited to demonstrate hemifield loss independently from the site of the lesion, i.e. also in retrogeniculate lesions. Straylight and large receptive field of the ganglion cells serving pupillary light response may be pitfalls to be overcome by methodical approaches. Astonishingly enough, in our experience pupil perimetry renders better results in retrogeniculate lesions than in chiasmal or optic nerve disorders.

Visual field constriction. In retinitis pigmentosa pupil campimetry is able to demonstrate visual field constriction convincingly because dim small perimetric stimuli obviously do not address the melanopsin retinal ganglion cells.

Only rarely the diagnosis of non-organic visual loss can be based on pupil examination alone. Additional subjective tests and electrophysiological procedures may be necessary. In several examples typical work-up will be demonstrated.

24 2009 Pupil Colloquium

Catching the 'Aha!' moments in puzzle problems using pupillometry and blinks analyses

Tsunhin John Wong (1), Christian Schunn (1), Greg J. Siegle (2) Department of Psychology (1), Department of Psychiatry (2) University of Pittsburgh

Corresponding author (John Wong, [email protected], 412-370-1539)

Metcalfe & Wiebe (1987) demonstrated that problem solvers do not make reliable predictions about their performance on insight problems. We are interested in detecting the temporal emergence of insight (aka ‘Aha!’) using methods other than self-report. This study monitored pupillary motility and eyeblinks to track cognitive function during noninsight and insight problem solving of Matchstick Arithmetic problems. As predicted, the data suggested that shortly before an ‘Aha!’ solution for an insight problem, patterns of pupil dilation and eyeblinks were different from those observed during a noninsight problem. An acute peak of pupillary dilation is observed at the time of ‘Aha!’ solution, and lower eyeblink frequency was observed before and after the insight moment. Results reflect physiological differences preceding solution of insight and non-insight problems.

Objectives Our study looked in greater temporal detail at the time immediately before and after a person has just reached the solution for a problem. Also we seek methodologies other than self-report as previous studies have shown that there are nonreportable aspects of insight problem solving (Metcalfe & Wiebe, 1987; Schooler, Ohlsson, & Brooks, 1993). We have selected eye-tracking to meet these requirements.

Methods Our participants solved “match sticks puzzle” problems adopted from previous studies of insight problem solving (Knoblich, Ohlsson, Haider, & Rhenius, 1999; Knoblich, Ohlsson, & Raney, 2001) with timed hints, and similar routine problems that require a fixed step-by-step approach of arithmetic and counting to reach solutions. Each participant was presented these 16 of these problems in randomized order over two days. Mood and impression ratings were given after each solving each problem during which they were monitored using a Tobii 1750 eye-tracker.

Results & Conclusions We found that puzzle problems and routine problems led to different pupillary dilations with our perception and mood about the tasks as possible mediators of the effect. Profiles of pupillary responses and blinks are found to be indicators that depict characteristics of the task nature when a person is unable to predict his/her own problem solving performance on an insight problem. Second, we found that two characteristics: discontinuity and restructuring are possibly more important in characterizing these insight problem solving events. Third, our data suggested that an insight is possibly an emerging moment of a sense of clarity about the solution which takes time before the time of an ‘Aha!’ solution declaration rather than a pure discontinuity.

Supported by: National Science Foundation, SBE-0738071

25 2009 Pupil Colloquium

Passive and Active Discourse Processing - Effects of Task Instruction on the Pupillary Response.

Martina Zellin1, Ann Pannekamp1, Elke van der Meer1 1Department of Psychology, Humboldt University, Berlin, Germany

Corresponding author: Martina Zellin, Humboldt University, Rudower Chaussee 18, 12489 Berlin Phone: +49-030-2093-9391 Fax: +49-030-2093-9361 E-Mail: [email protected]

Objectives. The current study introduced pupillometry to the investigation of processing spoken discourses. The integration of grammatical information in discourse processing is discussed according to the neurocognitive model of auditory sentence processing (Friederici, 2002). Furthermore, the study deals with the task- dependency of the pupillary response. It is known to require a specific task to show distinct responses (e.g., Aston-Jones & Cohen, 2005; Beatty and Lucero-Wagoner, 2000).

Methods. Spoken dialogs consisting of a short question and answer sentence served as stimulus material. The context question queried either information that was not mentioned in the question (new), or information that was corrected in the answer sentence (correction). The answer sentences provided the corresponding information. Half of the answer sentences bore distinct intonations on the information (adequate) and half did not (inadequate). The independent variables were type of information (new or correction) and type of intonation (adequate or inadequate). The pupillary response was measured as the dependent variable. Two experiments were conducted. In the first experiment participants passively listened to the stimulus material. In the second experiment an explicit task was introduced.

Results. In the first experiment, the pupillary response did not differ between experimental conditions. The second experiment led to distinct pupillary responses. Processing correction information with adequate intonation resulted in the smallest peak dilation. Peak dilation for processing inadequate correction information was significantly higher. This was not found for new information. Peak pupillary dilation was significantly higher for processing new information in comparison to correction information with adequate intonation.

Conclusions. The study showed that a task requirement was needed to make the pupil respond. However, the pupillary response delivered profound insights on the processing of spoken dialogs. Correction information with adequate intonation was processed with less cognitive effort than new information. Inadequate intonation on correction information led to an increase in cognitive resource consumption. Results are discussed in terms of expectancy-driven language processing and in relation to the neurocognitive model of auditory sentence processing.

Supported by: This research was supported by the Deutsche Forschungsgemeinschaft (German Research Foundation, DFG) (ME 1362/12-1).