Using Event-Related Potentials (ERPs) to Investigate the Neuropathophysiology of Pediatric Affective Disorders

Cecile D. Ladouceur, Ph.D. Assistant Professor of Psychiatry Western Psychiatric Institute & Clinic June 21, 2007

Basics of ERP Techniques

Brain generated electrical activity is measured by electrodes on the surface of the scalp. Scalp recorded electrical activity is thought to reflect the intermittent synchronization of small populations of predominantly cortical neurons. The signal measured at any one electrode is not an absolute voltage, but a relative one. An event-related potential (ERP) is the average response evoked by a particular type of stimulus or response.

DENSE ARRAY EEG

Geodesic Sensor Net (EGI Inc.)

(Reference: www. egi.com)

(Reference: http://hdeegerp.psych.sc.edu)

Deriving ERPs
Amplifier & Filters Analog to Digital Converter Data Acquisition & Processing

Subject Monitor

Experimental Computer (E-prime)

EEG

Averaging

(Reference: http://www.rotman-baycrest.on.ca/content/science/eeg.html)

Description of ERPs
4 3
amplitude (microvolts)

2 1 0 -20 -1 -2 -3 -4 Response Onset

Baseline Area 80 PeaktoPeak

180

BasetoPeak

280

Peak Latency
m sec

Pediatric Affective Disorders

Pediatric Affective Disorders

Anxiety disorders are among the most common child mental health problems (Roblek and Piacentini 2005) affecting between 10-20% of youth (Pine 1994; Shaffer et al 1996). As in adult anxiety disorders, pediatric anxiety disorders are characterized by hypervigilance, rapid automatic responses to threat and selective attention to threat (Vasey et al., 2001). Children diagnosed with an anxiety disorder are at greater risk of developing depression (Pine et al., 1998).

Pediatric Affective Disorders

There is evidence suggesting that anxiety and depression are associated with impairments in emotion regulation, namely difficulties regulating attention to emotional information and regulating emotion-related behavior. Focus: neural correlates of processes at the interface of cognitive control processes and emotion as a way to understand the neuropathophysiology of pediatric affective disorders.

Anterior Cingulate Cortex

Cognitive Neuroscience Model of Cognitive Control

Carter et al., 1998, Botvinick et al., 2001

Response Monitoring ERPs

Error-related negativity (ERN):
a sharp negative deflection in the EEG that occurs about 80 msec following errors localized to the dorsal region of the anterior cingulate cortex (ACC) in adults

Error-related positivity (Pe):

a positive deflection in the EEG that occurs about 200-400 msec following errors localized to the rostral region of the ACC in adults

ERIKSEN FLANKER TASK

+

Time

100 ms + +

Congruent
(Correct Response: Right)

Incongruent
(Correct Response: Left)

840 trials (7 blocks) + 1 practice block incentive: cash bonus at the end

Normal Development of the ERN and Pe

Participant Characteristics
Young Adolescents
(8-14 years old)

Older Adolescents
(15-18 years old)

Adults 16 6/10

n M/F

15 7/8

16 5/11

M Age (SD)

12.3 (1.6)

16.6 (1.7)

28.7 (10.3)

Behavioral Performance: Reaction Time

600 500

msec

400 300 200 100 0 Young Old Adult

Behavioral Performance: Percentage of Errors

20 15 10 5 0
Young Old Adult

% errors

Development of ERN and Pe

Young Adolescents
12 8

Old Adolescents
Pe
Pe
12 8 4 0

Adults
12 8 4 0

Pe

microvolts

4 0 -200 -4 0 200 400 600 800

-400 -200

-400

0 -4 -8

200

400

600

800

-400

-200

msec
-8

msec

-4 -8

200

400

600

800 msec

-12

-12

ERN

-12

ERN

Error

Correct

Ladouceur et al., 2007

Summary
Pe was present across groups. ERN was significantly greater in older adolescents & adults compared to young adolescents, which suggests that:
there are important maturational changes in the ACC that take place later in adolescence these changes may be associated with increased sensitivity or more efficient error-related response monitoring processes

These findings support recent developmental results regarding ERN and Pe (Davies et al., 2004) and set the foundation for work in clinical populations.

ERN and Pe in Pediatric Anxiety Disorders

ERN in Anxiety Disorder

Increased ERN in: Adults with OCD (Ghering et al., 2000) Adults high in trait anxiety (Hajcak et al., 2003) Adults high in negative affect (Hajcak et al., 2004)

Neuropathophysiology of Anxiety Disorders: over-

activity of the ACC?

Goal: examine whether children with an anxiety disorder showed increased ERN/Pe

ERN and Pe at Cz in Children with an Anxiety Disorder

Anxiety Disorder Group
12

Low-risk Control Group

12 8 4 0

Pe

Pe

microvolts

8 4 0 -4 -8 -12

msec

-4 -8

msec

ERN

-12

Note: No differences in behavioral performance

Ladouceur et al., 2006

Topographic Map and Source Localization of ERN in the Anxiety Disorder Group
i) ii)

Ladouceur et al., 2006

Topographic Map and Source Localization of Pe in the Anxiety Disorder and Low-risk Control Groups
i) ii)

Anxiety Disorder

Low-risk Control

Effects of Treatment on ERN/Pe in Anxious Children

12 8
microvolts

Pe

4 0
-400 -200 0 200 400 600
msec

800

-4 -8 -12

ERN

Baseline

Post-treatment

ERN and Pe in Pediatric Anxiety and Depression

ERN in Depression
Increased ERN in adult and pediatric anxiety disorders. Evidence of decreased ERN associated with adult depression along with oversensitivity to errors and perceived failure (Pizzagelli et al., 2006; Ruchsow et al., 2004, 2006). Little is known about changes in ERN in pediatric depression and comorbid anxiety-depression. Examining distinctions within these clinical groups may have important implications for understanding neuropathophysiology of pediatric anxiety and depression and the developmental course from pediatric anxiety to depression.

Participant Characteristics
Anxiety Disorder Major Depression Comorbid Anxietydepression Low-risk Controls Entire Sample (age 8-17)

n M/F M Age

12 8/4 11

9 4/5 14

10 4/6 14

15 7/8 13

46 23/23 13

Ladouceur et al., in prep

ERN in Pediatric Anxiety, Depression, and Comorbid Anxiety-Depression

Anxiety Disorder
6 2 -150 -2 -6 50 250
-150

Major Depression
6 2 -2 -6 50 250

Correct

Error

Comorbid Anxiety-Depression
6 2

Low-risk Control
6 2 -150 -2 -6 50 250

-150

-2 -6

50

250

Note: No significant differences in performance.

Ladouceur et al., in prep

Increased ERN Amplitude to Errors in Anxiety but not Depression

Correct
0 -1 -2 -3 -4 -5 -6 -7

Error

microvolts

ANX

MDD

COM

CONT
Ladouceur et al., in prep

Conclusion
ERPs are a useful tool to investigate the neural correlates of response monitoring processes in pediatric affective disorders. Source localization analyses provide information about the location of the neural generators of these ERPs, suggesting that differences in ERP amplitudes may be related to abnormalities in the development of the ACC. The goal of future studies is to:
include emotional stimuli or reward/punishment contingencies. cross-register ERP and fMRI data in order to obtain more a complete description of the neural correlates (temporal and spatial resolution) of response monitoring in pediatric affective disorders.