Substance Use & Misuse, 46:669–677, 2011

Copyright

C 2011 Informa Healthcare USA, Inc.
ISSN: 1082-6084 print / 1532-2491 online
DOI: 10.3109/10826084.2010.528123

ORIGINAL ARTICLE

P3a Amplitude Predicts Successful Treatment Program Completion in

Substance-Dependent Individuals

Nathaniel E. Anderson, Robyn M. Baldridge and Matthew S. Stanford

Department of Psychology & Neuroscience, Baylor University, Waco, Texas, USA

of program failure. While certain demographic, behav-

This study examined P3a amplitude as a direct predic-
tor of treatment success for substance dependence. Par-
ticipants were 35 adults (27 men, 8 women) undergoing
treatment for substance dependence at an urban res-
idential treatment facility between October 2005 and
July 2007. Diagnostic and Statistical Manual of Mental
Disorders, Fourth Edition, Text Revision (DSM-IV-TR)
criteria were used to confirm substance dependence.
P3a amplitude was significantly smaller for those who
dropped out of treatment. Discriminant function anal-
ysis confirmed that P3a amplitude was a robust predic-
tor of treatment completion, more sensitive than other
measures including substance abuse severity. Implica-
tions for the interpretation of P3a amplitude as an in-
dex of executive function are discussed.
Keywords event-related potentials, substance abuse, P300, P3a,
treatment success
INTRODUCTION
Treatment facilities focused on the rehabilitation and
continued abstinence of substance abusers1 have been
among the most successful options for drug and alcohol
use interventions among the heterogeneous range of
users who complete them. Not surprisingly, however, a
primary factor affecting the success of these programs is
a high rate of attrition (e.g., Crits-Christoph & Sigueland,
1996; Kelly & Moos, 2003). Consequently, a great deal
of effort has been focused toward identifying factors that
contribute to successful retention and reliable predictors
ioral, and personality correlates have been associated
with patterns of substance use and treatment outcomes
(Kelly & Moos, 2003; McKellar, Kelly, Harris, & Moos,
2006), psychophysiological and neurocognitive traits
are receiving increasing attention and may prove to be
more objective markers directly related to the genes that
influence the complex behavioral outcomes relevant to
substance users and their treatment2 (Singh & Basu,
2009).
One physiological marker that has proven particularly
useful in the evaluation of substance abuse populations is
the P300 (P3; Singh & Basu, 2009). The P3 is an event-
related potential (ERP), recognized as a positive deflec-
tion in the electroencephalogram (EEG) approximately
300 ms after the onset of an attended stimulus that has
task-relevant properties or must be categorized in some
way. It is generally considered an index of information
processing related to the use of incoming information for
updating or modifying the mental representation of the
stimulus environment (Donchin & Coles, 1988). P3 am-
plitudes are reliably modified by a variety of task con-
ditions, such as stimulus rarity and task difficulty, which
have led to the increasing use of P3 amplitude as a measure
of processing capacity or a relative index of the allocation
of attentional resources to a task (Kok, 2001). Addition-
ally, P3 amplitude has been shown to be a genetically her-
itable trait (Katsanis, Iacono, McGue, & Carlson, 1997;
Smit, Posthuma, Boomsma, & de Geus, 2007), making it
an attractive candidate as an endophenotype for geneti-
cally influenced psychopathology.

1
The journal’s style utilizes the category substance abuse as a diagnostic category. Substances are used or misused; living organisms are and can be
abused. Editor’s note.
2
Treatment can be briefly and usefully defined as a planned, goal-directed, temporally structured change process of necessary quality,
appropriateness, and conditions (endogenous and exogenous), which is bounded (culture, place, time, etc.) and can be categorized into
professional-based, tradition-based, mutual-help-based (AANA, etc.), and self-help (“natural recovery”) models. There are no unique models or
techniques used with substance users—of whatever types and heterogeneities—which are not also used with nonsubstance users. In the West, with
the relatively new ideology of “harm reduction” and the even newer Quality of Life (QOL) treatment-driven model, there is now a new set of goals
in addition to those derived from/associated with the older tradition of abstinence-driven models. Treatment is implemented in a range of
environments; ambulatory, within institutions that can include controlled environments. Editor’s note.
Address correspondence to Mr. Nathaniel E. Anderson, M.A., Department of Psychology & Neuroscience, Baylor University, One Bear Place
97334, Waco, TX 76798-7334; E-mail: nathaniel anderson@baylor.edu
669
670 N. E. ANDERSON ET AL.
While some have argued that reduced P3 amplitude
may be attributed to the deleterious effects of substance
use (e.g., Porjesz & Begleiter, 1993; Porjesz, Begleiter, &
Samuelly, 1980), smaller P3s have also been associated
with familial risk for alcohol misuse (Cohen, Wang, Por-
jesz, & Begleiter, 1995; Polich, Pollock, & Bloom, 1994)
and is a reliable predictor of future alcohol misuse among
adolescents (Hill, Steinhauer, Lowers, & Locke, 1995).
Apart from substance misuse, it has been demonstrated
that P3 amplitude is reliably smaller in those manifest-
ing antisocial personality disorder (ASPD; Bauer, 1997;
Bauer, O’Connor, & Hesselbrock, 1994; Costa et al.,
2000), violent offenders (Bernat, Hall, Steffen, &
Patrick, 2007), impulsive aggressive individuals (Barratt,
Stanford, Kent, & Felthouse, 1997; Houston, Stanford,
Villemarette-Pittman, Conklin, & Helfritz, 2003), and
adolescents with conduct disorder (Bauer & Hesselbrock,
2003).
Given that smaller P3s have been associated with
such a wide variety of related behavioral outcomes, it
has been suggested that this reduction in amplitude is an
endophenotype indicative of a more general disinhibitory
psychopathology or externalizing vulnerability (Iacono,
Malone, & McGue, 2003; Patrick et al., 2006) rather than
a symptom of substance abuse, per se. Furthermore, this
relationship appears to depend on the heritable expression
of a set of genes common to both externalizing and P3
amplitude (Hicks et al., 2007; Hicks, Krueger, Iacono,
McGue, & Patrick, 2004). The outcomes of several other
studies have supported the notion of a causal genetic link
between disinhibited personality traits and externalizing
disorders (e.g., Carlson & Iacono, 2008; Krueger et al.,
2002). If behavioral outcomes such as substance abuse,
conduct disorder, and adult criminal behavior can indeed
be traced back to a common disinhibited personality
style, influenced by genes that also encode differences
in P3 amplitude, then this physiological marker may be
an ideal index predictive of treatment outcome for those
manifesting substance abuse disorders.3 Indeed, many of
the personality factors such as impulsivity, aggression,
and sensation seeking that have been associated with
externalizing behavior have turned out to be reliable
predictors of treatment outcome in their own right (Patkar
et al., 2004). Furthermore, several investigations have
determined P3 amplitude to be a reliable predictor of
relapse into drug use versus sustained abstinence in
specific substance-dependent populations (Bauer, 1997;
Glenn, Sinha, & Parsons, 1993; Parsons, 1994), although
none of these studies have directly examined treatment
compliance, which comprises a wider set of behavioral
outcomes than abstinence versus relapse.
3
The reader is reminded that substance use disorder is a relatively new
(American Psychiatric Association. Diagnostic and Statistical Manual
of Mental Disorders (DSM-IV), 4th ed.; American Psychiatric Associ-
ation: Washington, DC, 1994), consenualized, medicalizing diagnosis,
which is not based upon empirical evidence and which does not supply
three basic functions of any effective and utilizable diagnosis: etiology,
process, and prognosis. Editor’s note.
Much of the existing literature relating P3 character-
istics to substance use and externalizing disorders has
also failed to differentiate between two relevant forms
of this ERP component. Attempts to localize the origin
of P3 ERPs have determined that there are multiple
neuroanatomical generators responsible for differences
in its size and latency (e.g., Halgren, Marinkovic, &
Chauvel, 1998). This information has contributed to the
topographical and functional distinction between P3a and
P3b. The more posterior potential, occurring later (usually
300–600 ms) that is associated with attended target cat-
egorization is referred to as P3b. The more anterior
potential, occurring earlier (often before or very near
300 ms) that is associated with orienting to a novel,
nontarget stimuli is referred to as P3a or novelty P3 (see
Friedman, Cycowicz, & Gaeta, 2001; Polich, 2007 for
reviews). Since P3a and P3b are sensitive to different sets
of stimulus characteristics and potentially have separate
sets of neural generators, it is possible that individual
differences in the amplitudes of these components could
reflect distinct deficits or vulnerabilities, which should be
taken into account in ongoing research.
While the relationship between P3 amplitude, sub-
stance use, and externalizing vulnerability has become
increasingly clear, only a few studies that have supported
this relationship have specifically measured the more
anterior P3a. Among these, Bauer (1997) has associated
reduced P3a amplitudes with eventual relapse, and
Biggins, MacKay, Clark, and Fein (1997) reported
reduced P3a amplitudes in dependent subjects; however,
both of these reports are specific to cocaine addicts. The
current study examined P3a amplitude as a potential
predictor of treatment compliance at two local residential
treatment facilities, housing individuals with nonspecific
substance dependence problems, described in detail
below. It was hypothesized that participants who failed
to complete the program, designed to last at least 90
days, would exhibit reduced P3a amplitudes and that
this physiological marker would therefore prove to be a
reliable predictor of treatment completion.
METHOD
Participant Recruitment and Treatment Program
Thirty-five individuals (27 men and 8 women) being
treated for drug and alcohol dependence at two local resi-
dential treatment centers (one for men and one for women)
were recruited for the study. The participants referred
themselves for treatment at the centers, where they lived
full time at no cost. No participants were court ordered
to complete treatment. These programs required that in-
dividuals first be screened for Axis I thought disorders
and mental retardation by a trained counselor at a social
services center run by the same organization. Any person
classified in one of these categories was referred to more
appropriate treatment centers (i.e., Veterans Affairs hos-
pitals or Mental Health and Mental Retardation). Prior to
admission into the treatment facility, individuals also had
to provide a negative urine drug test (for alcohol, cocaine,
 P3a AMPLITUDE
marijuana, opiates, benzodiazepines, amphetamines, and
barbiturates). Once admitted into the program, individuals
were subject to weekly drug testing, and a positive urinal-
ysis at any time during their treatment resulted in imme-
diate dismissal from the program.
Successful completion of the program entailed ful-
fillment of three consecutive phases, each lasting a
minimum of 30 days. These phases progressed from
mandatory group meeting attendance, working with a
sponsor/mentor, and life-summary writing in Phases
I and II to relapse prevention and life skills training
in Phase III (similar to standard 12-step programs).
Additionally, residents were required to do daily chores at
their respective treatment facilities and were encouraged
to do volunteer work in the community, as long as these
activities did not interfere with group meeting attendance.
Residents in good standing at the treatment facilities
were made aware of the opportunity to participate in the
current study. Volunteers were required to be at least
21 days sober at the time of testing. Participants were
compensated with a $25 gift card and provided with a
“brown bag” lunch by the researchers on site at no cost.
All testing took place in a laboratory setting at the uni-
versity. All recruitment and experimental procedures were
reviewed and approved by the university’s institutional re-
view board. After providing informed consent, all partici-
pants completed a battery of self-report measures prior to
ERP recordings.
Materials
Drug Abuse Screening Test (DAST; Skinner, 1982). This
20-item self-report test is designed to measure self-
reported problematic substance use in the previous year. A
higher DAST total score indicates more problematic drug-
related behavior. This measure was used to assess severity
of drug use.
Alcohol Use Disorders Identification Test (AUDIT;
Saunders, Aasland, Babor, De La Fuente, & Grant,
1993). The AUDIT is a self-report 10-item questionnaire
designed to identify individuals whose alcoholism has
become detrimental to their physical health. A higher
AUDIT total score indicates more severe alcohol usage.
This measure was used to assess severity of alcohol use.
SCID-I Screen Patient Questionnaire-Extended
(SSPQ-X; First, Gibbon, Spitzer, Williams, & Benjamin,
1991). The SSPQ-X is a computer-administered, 589
question diagnostic tool that covers the major areas of
Diagnostic and Statistical Manual of Mental Disorders,
Fourth Edition (DSM-IV) Axis I including mood disor-
ders, psychotic symptoms, anxiety disorders, substance
use disorders, eating disorders, and somatoform disorders.
This measure was used to confirm substance use disorders
in participants and to assess major comorbidities per
individual.
Wechsler Abbreviated Scale of Intelligence (WASI;
Wechsler, 1999). The WASI is a relatively brief scale of
intelligence useful in adults and children. Two of the four
subtests (vocabulary as a measure of Verbal Scale IQ and
matrix reasoning as a measure of Performance Scale IQ)
671
were administered in an interview style in order to gen-
erate a Full-2 IQ (FSIQ) score. This scale was used for
comparisons of intelligence among participants.
Psychophysiological Procedures
Participants were seated in a comfortable chair in a sound
and light attenuated radio-frequency anechoic chamber,
designed to reduce electrical noise. The scalp and mas-
toid areas were prepared with isopropyl alcohol solu-
tion and a mildly abrasive gel (NuPrep) to help reduce
impedances. The participant’s head was fitted with an
elastic cap (Electro-Cap, Inc.) with 64 tin electrodes,
arranged according to the International 10–20 system
with standard and intermediate positions, referenced to
the mastoids during recording. Four additional electrodes
were affixed around the eyes to record horizontal and ver-
tical eye movements (electrooculography) for recognition
and removal of artifacts in postprocessing. Conductive gel
was used as a conducting medium at each electrode site,
and all impedances were kept below 5 k
. EEG data were
recorded continuously at a sampling rate of 1000 Hz and
amplified by SynAmps2 amplifiers (Compumedics Neu-
roscan) with a gain of 1000. Off-line analysis consisted
of a digital band-pass filter (0.1–35 Hz, 12 dB/oct slope),
isolating epochs from −100 ms to 900 ms poststimulus,
removal of artifacts, rereferencing to the mastoids, imple-
menting a correction to the baseline, and averaging trials
within subjects, all using Scan 4.3 software by Neuroscan.
The removal of artifacts consisted of an off-line spatial
filter created for each subject using the electrooculogra-
phy and was applied to reduce contamination of the EEG
by eye movements. This process was followed by man-
ual deletion of contaminated epochs. Groups were nearly
equal in the number of retained epochs per subject.
P3s were defined as the most positive voltage between
200 ms and 600 ms following stimulus onset and were
averaged at nine electrodes (F3, Fz, F4, C3, Cz, C4, P3,
Pz, P4) as a representation of the electrode array to ac-
count for potential regional differences in distribution of
the ERP between groups. ERPs were generated using an
auditory perseveration task similar to the one described
by Bauer and Hesselbrock (2003). The task requires dis-
crimination between two stimuli—a low-pitch (500 Hz)
tone and a high-pitch (1000 Hz) tone, each requiring a cor-
responding button response from the participant. A third
stimulus, a white-noise burst, indicates that the participant
must reverse their corresponding button selections for the
two tones. The low- and high-pitch tones were both targets
of equal probability. Behavioral data indicate the number
of hits (correct responses), omissions (failure to respond),
and perseverative errors (failure to switch responses). The
(nontarget) white-noise burst was the stimulus for which
P3 data were analyzed. This event produced an early, an-
terior positive potential, characteristic of a P3a.
Statistical Analysis
Two groups were defined by participants who success-
fully completed the treatment program and those who
dropped out of treatment. Univariate analysis of variances
672 N. E. ANDERSON ET AL.

TABLE 1. Demographics and sample characteristics

Variable Completers (n = 22) Mean (SD) Noncompleters (n = 13) Test statistics

Age 36.4(11.0) 38.1(11.6) F (1, 33) = 0.19

Gender (% male) 77.3 76.9 χ 2 (l) = 0.01
Years of education 12.0(2.87) 15.0(2.2) F (1, 33) = 0.43
Ethnicity (% White) 59.1 69.2 χ 2 (3) = 0.98
FSIQ 100.3(127) 99.9(14.5) F (1, 33) = 0.01
DAST total 13.0(4.6) 12.0(5.7) F (1, 33) = 0.32
AUDIT total 17.1(10.5) 16.3(11.4) F (1, 33) = 0.04
Number of days sober 66.4(40.5) 48.4(27.3) F (1, 33) = 2.02
Auditory perseveration task
Perseverative errors 7.5(5.9) 7.9(5.3) F (1, 33) = 0.03
Omissions 10.3(10.5) 11.5(10.2) F (1, 33) = 0.10
Hits 21.2(118) 19.7(11.1) F (1, 33) = 0.14

Note: No significant differences between groups for these data. FSIQ, Full Scale Intelligence Quotient; DAST, Drug Abuse Screening Test;
AUDIT, Alcohol Use Disorders Identification Test.

(ANOVAs) and Pearson’s chi-square analyses were used other Axis I psychopathology, including posttraumatic
to evaluate group differences on assessment scores and stress disorder, obsessive–compulsive disorder, and panic
demographic information. Group differences in P3 ampli- disorder. The distribution of Axis I psychopathology was
tudes were first assessed using a 2 × 3 × 3 mixed-model similar for both groups; Table 2 summarizes these sample
ANOVA with completion group as a between-subjects characteristics.
variable (completers and noncompleters) and regional
scalp differences accounted for by two within-subjects
ERP AND DISCRIMINANT ANALYSIS
variables, each with three levels (left, midline, and
right electrodes in frontal, central, and parietal regions). The omnibus ANOVA of P3a amplitude revealed two sig-
One-way ANOVAs were then used to determine regional nificant main effects for lateral differences [left, midline,
specificity of ERP effects and to identify the best site right; F(2,32) = 13.28, p < .01] and anteroposterior differ-
for prediction. Finally, a stepwise discriminant function ences [frontal, central, parietal; F(2,32) = 21.56, p < .01].
analysis was used to assess the predictive power of These main effects revealed a tendency for amplitudes to
selected variables on treatment outcome. be greater at the midline and anterior regions, a typical
topographical effect for the P3a. There was a significant
difference between groups interaction with laterality
RESULTS [F(2,32) = 3.384, p < .05], which suggested a difference
Treatment Outcome, Demographics, and SCID in P3a amplitude between program completers and
Diagnostics. noncompleters for at least one lateral region. A follow-up
Of the participants who did not successfully complete the ANOVA confirmed that those who failed to complete
program (n = 13), nine were discharged for noncompli- treatment had significantly smaller P3a amplitudes at
ance with the stated rules—other than a positive urine test midline electrodes (Fz, Cz, Pz) than those who completed
for drugs, two chose to leave the program with no reason [F(1,33) = 5.55, p < .03; see Figure 1]. While there was
given, one was dismissed for treatment of an eating disor- a consistent trend for larger amplitudes among program
der, and one participant was released after testing positive completers across all electrode sites, these differences
for drugs. Groups defined as program completers and non-
completers did not differ significantly in age, years of ed- TABLE 2. DSM-IV-TR-lV SCID Diagnoses
ucation, days sober at time of testing, FSIQ, or substance
use severity, nor did they differ in their performance ac- Completers Noncompleters
curacy on the auditory perseveration task (see results in (n = 22) (n = 13)
Table 1). Axis I diagnosis/diagnoses n % n %
According to SCID diagnostics, all 35 participants
met DSM-IV-TR diagnostic criteria for dependence of at Single substance dependence
least one substance, and 14 met criteria for dependence Alcohol 3 13.6 2 15.4
on two or more substances. In total, 18 met criteria for Cocaine 1 4.5 3 23.1
alcohol dependence, 18 met criteria for cocaine depen- Opioid 1 4.5 0 0.0
dence, 5 met criteria for stimulant dependence, 1 met Polysubstance dependence 17 77.3 8 61.5
Comorbid Axis I diagnoses
criteria for sedative–hypnotic–anxiolytic dependence,
Posttraumatic stress disorder 6 27.0 2 15.0
and 5 met criteria for opioid dependence. In addition to Obsessive–compulsive disorder 3 14.0 0 0.0
dependence, 10 participants met criteria for substance Panic disorder 0 0.0 1 8.0
abuse, and several participants also met criteria for
 P3a AMPLITUDE 673

FIGURE 1. A comparison of group-averaged ERPs at midline electrode sites illustrates differences in P3a amplitude between those who
completed treatment and those who did not.

were greatest at the midline with no indication of other
regional differences between groups (see Figure 2). La-
tency differences for P3a were not expected, but were also
analyzed, and revealed no differences between groups.
P3a amplitudes at electrode Cz were entered as a
predictor of treatment completion in a discriminant
analysis, and while an ANOVA revealed no differences
between groups on measures of age, education, FSIQ, or
severity of substance use, these variables were included
as additional predictors, in a stepwise fashion. P3a ampli-
tude remained the only significant predictor of treatment
TABLE 3. Summary of discriminant function analysis
completion [F(1,33) = 6.20, p < .02], with no other
variables reaching criterion in step zero or one (results
summarized in Table 3). The resulting equation [Y =
(0.148 × P3a amplitude) – 2.039] successfully identified
72.7% of those who completed treatment and 76.9%
of those who did not complete treatment. The overall
treatment completion data from this program estimate a
success rate near 50%. Since 2001, the overall success
rate has been 46.6%, and the overall success rate during
data collection was 44.1%. Comparing the accuracy rates
for group prediction by P3a amplitude with these values
supports the value of this psychophysiological feature as
a predictor with a reasonably large effect size.

Wilks’ DISCUSSION
Step Independent variable Tolerance F to enter lambda
The outcome of the current study supported the hypoth-
Step 0 P3a amplitude (at Cz) 1.00 6.20 0.842∗ esis that P3a amplitude would reliably predict treatment
Days sober 1.00 2.02 0.942
completion in a substance-dependent population. Similar
Years of education 1.00 0.43 0.987
DAST total 1.00 0.32 0.990
results have been reported for the more posterior P3b ERP
Age 1.00 0.19 0.994 evoked by rare target stimuli in various tasks (Glenn et al.,
AUDIT total 1.00 0.04 0.999 1993; Parsons, 1994; Wan, Baldridge, Colby, & Stanford,
FSIQ 1.00 0.01 1.000 2010). Also, Bauer (1997) reported that anterior P3a
Step 1 amplitude was a reliable predictor of relapse in cocaine-
Days sober 0.999 1.79 0.797 dependent individuals, but the current study is the first to
Years of education 0.999 0.42 0.831 report P3a amplitude as a significant predictor of treat-
DAST total 0.997 0.15 0.838 ment compliance. It should not be assumed that failure
Age 0.774 0.60 0.827 to complete treatment is synonymous with relapse. For
AUDIT total 0.922 0.72 0.823 example, in the current study, only one of the individuals
FSIQ 0.987 0.03 0.841
was dismissed for failing a drug screen. The majority of
Note: DAST, Drug Abuse Screening Test; FSIQ, Full Scale In- those who failed to complete the program were dismissed
telligence Quotient; AUDIT, Alcohol Use Disorders Identification for violation of behavioral expectations, which may have
Test. included failure to submit to drug screens but which also
∗
p < .05. categorically included behaviors such as lying to program
674 N. E. ANDERSON ET AL.
FIGURE 2. P3a amplitude differences between groups were con-
sistent across the electrode array and largest at the midline.
facilitators, hostility, theft, and other forms of miscon-
duct. Therefore, when considering predictors of treatment
success, it is important to remember the wide variety of
factors involved. Individuals who failed to complete treat-
ment did not show significant differences in severity of ad-
diction, age, FSIQ, or comorbid psychopathology, which
may suggest that P3a amplitude is a more sensitive pre-
dictor of treatment outcome than any of these variables.
While P3a amplitude is confirmed as a sensitive pre-
dictor of individual treatment outcome, it remains to be
decided what kind of vulnerability reduced P3a amplitude
represents; and what, if any, differences exist between
the interpretation of the early, anterior P3a and the later,
posterior P3b amplitudes. On the basis of existing reports,
a strong case can be made for interpreting P3a ampli-
tudes as an index of executive function. Furthermore,
the relationships between P3a, executive function, and
treatment compliance build a convincing framework for
understanding more general externalizing vulnerability.
For instance, Fjell, Walhovd, Fischl, & Reinvang (2007)
reported a relationship between P3a amplitude and cor-
tical thickness that, in turn, predicted executive function.
Reductions in gray matter in the prefrontal cortex often
accompany disorders characterized by executive dysfunc-
tion. This reduction in gray matter has been reported for
substance abuse disorders (De Bellis et al., 2005), antiso-
cial behavior (Raine, Lencz, Bihrle, LaCasse, & Colletti,
2000), impulsivity (Boes et al., 2009), major depression
(Vasic, Walter, Höse, & Wolf, 2008), and schizophrenia
(Kawada et al., 2009), to name only a few. Furthermore,
there are clearly strong relationships between executive
dysfunction per se and substance misuse (Dolan, Bechara,
& Nathan, 2008), and it may be among the leading factors
influencing patient dropout from substance use treatment
programs (e.g., McKellar et al., 2006).
Interestingly, this connection between gray matter vol-
ume, executive function, and P3 amplitude carries over
into the literature on aging, where decline in cognitive
function is a serious concern. Fjell et al. (2007) demon-
strated that age and cognitive function share a large por-
tion of variance in explaining P3a amplitudes; but while
controlling for age, cortical thickness still accounted for
significant variation in P3a amplitudes. Early theories had
suggested that substance use caused premature aging in
the brain, leading to common findings of reduced ERP
amplitude and reduced cognitive functioning (Porjesz
et al., 1980); however, more recent data suggest that these
differences are present prior to the damaging effects of
substance use, supporting the theory of a genetically in-
herited vulnerability. Bauer and Hesselbrock (2003) have
suggested that those at risk for substance dependence and
ASPD have impaired development of frontal brain areas
demonstrated by the absence of the normal maturational
increases usually seen in P3a amplitude through adoles-
cence. Furthermore, it appears that age-related changes in
frontal P3a characteristics seen later in life are accompa-
nied by decrements in executive function in older adults
(Friedman, Nessler, Johnson, Ritter, & Bersick, 2008;
West, Schwarb, & Johnson, 2010).
 P3a AMPLITUDE
While both P3a and P3b amplitudes are related to sub-
stance abuse disorders, there are important differences be-
tween the characteristics of these ERPs, which should be
considered when applying them as indexes of pathology
or vulnerability. At a discriminatory level, stimulus nov-
elty is an important factor in generating P3a potentials,
while P3b seems to reflect the involvement of memory
systems in stimulus categorization (Polich, 2007). Fjell
et al. (2007) constructed path models describing relation-
ships between cognitive ability and these ERPs and con-
cluded that P3a is a better index of executive function,
whereas P3b has a closer relationship with fluid func-
tion. Bauer (1997, 2001) noted that amplitude differences
and source analyses of P3a suggest a deficit in prefrontal
processes serving behavioral inhibition in those who are
vulnerable to relapse. Furthermore, among adolescents at
high risk for future substance dependence and ASPD, mat-
urational deficits appear to be limited to the frontal brain,
whereas parietal generators of P3b appear to mature nor-
mally in these individuals (Bauer & Hesselbrock, 2003).
It is reasonable to suspect that the relationship between
P3a amplitude and treatment success depends on the value
of P3a amplitude as a marker for deficits in frontal lobe
executive processes, which result from inherited matura-
tional deficits that may also impact overall gray matter
volume in this brain region important for behavioral con-
trol and planning.
STUDY’S LIMITATIONS
The present study is limited in its scope, presenting data
from a convenience sample at two local drug treatment
facilities; therefore we were unable to gather additional
data related to cortical anatomy or long-term changes in
the P3a waveform. Given the available context of many
existing reports, the data here emphasize the value of P3a
as a predictor of treatment success while drawing further
attention to some necessary components of future similar
research. It will be valuable for future research to con-
tinue distinguishing between P3a and P3b in determining
their relative values, not only as predictors of treatment
outcome but also as indexes of more specific cognitive-
processing characteristics. This will require more mul-
timodal studies, incorporating ERPs, neuropsychiatric
tests, structural and possibly functional imaging to fully
elucidate the nature of this deficit and what possible in-
terventions may be most helpful in combating substance
dependence.
Declaration of Interest
The authors report no conflicts of interest. The authors
alone are responsible for the content and writing of this
article.
RÉSUMÉ
Cette étude a examiné P3a amplitude comme un lien di-
rect harmoniques de succès de traitement pour toxico-
675
manie. Les participants ont été 35 adultes (27 hommes,
8 femmes) en traitement pour toxicomanie à un mi-
lieu urbain résidentiel installation de traitement entre
Octobre, 2005 et Juillet, 2007. DSM-IV-TR critères ont
été utilisées pour confirmer la pharmacodépendance. P3a
amplitude était considérablement plus petit pour ceux qui
ont abandonné de traitement. Analyse discriminante fonc-
tion a confirmé que P3a amplitude était un robuste har-
moniques de traitement achèvement, plus sensibles que
d’autres mesures, y compris la toxicomanie gravité. Im-
plications pour l’interprétation de P3a amplitude comme
un indice de fonction exécutive sont discutées.
RESUMEN
Este estudio examinó P3a amplitud como consecuencia
directa predictor de éxito del tratamiento de la depen-
dencia de sustancias. Los participantes fueron 35 adultos
(27 hombres, 8 mujeres) sometidos a tratamiento para la
dependencia de sustancias en un medio urbano residen-
cial instalación de tratamiento entre Octubre de 2005 y
Julio, 2007. DSM-IV-TR criterios fueron utilizados para
confirmar la dependencia de sustancias. P3a amplitud fue
significativamente menor para quienes abandonaron de
tratamiento. Análisis de funciones Discriminantes con-
firmó que P3a amplitud fue un sólido predictor de final-
ización del tratamiento, más sensibles que otras medi-
das, como abuso de sustancias severidad. Consecuencias
para la interpretación de P3a amplitud como un ı́ndice de
función ejecutiva.
THE AUTHORS
Nathaniel E. Anderson,
M.A., is a doctoral candidate
in behavioral neuroscience at
Baylor University in Waco, TX,
were he has conducted research
on the psychophysiological
correlates of substance use,
impulsivity, psychopathic
traits, and posttraumatic stress
disorder. Further research
interests include the biological
basis of personality and
individual differences, especially
as these relate to affect and behavioral inhibition.
Robyn Baldridge, M.A., is a
doctoral candidate in
Psychology at Baylor University
(Waco, TX). Her research
interests include substance abuse
populations, electroencephalo-
graphic correlates of executive
cognitive dysfunction, the
P300 event-related potential,
impulsivity, aggression, and
addictive behaviors.
676 N. E. ANDERSON ET AL.
Matthew S. Stanford, Ph.D.,
is Professor of Psychology,
Neuroscience, and Biomedical
Studies at Baylor University
where he directs the doctoral
program in psychology. His
research focuses primarily on
the biological basis of impulsive
and aggressive behavior. He has
conducted psychophysiological
research in a variety of clinical
populations including those
with aggression, schizophrenia,
personality disorders, posttraumatic stress disorder, stroke,
substance dependence, and traumatic brain injury. He is a fellow
of the Association for Psychological Science.
GLOSSARY
Antisocial Personality Disorder (ASPD): An Axis II per-
sonality disorder in the American Psychiatric Associa-
tion’s diagnostic manual, characterized by a pervasive
pattern of disregard for and violation of the rights of
others.
DSM-IV-TR: The current version of the American Psychi-
atric Association’s diagnostic and statistical manual of
mental disorders.
Endophenotype: A stable set of physical and/or behavioral
characteristics with a common genetic basis.
Electroencephalograph (EEG): Brain wave fluctuations
recorded at the scalp surface.
Event-Related Potential (ERP): A time-locked average
fluctuation in brain wave activity occurring predictably
in a given time range after the delivery of an evoking
stimulus.
Full Scale IQ (FSIQ): A scaled IQ measure from the
Wechsler Abbreviated Scale of Intelligence.
P300 (P3): An event-related potential occurring as a pos-
itive fluctuation in the electroencephalogram approx-
imately 300 milliseconds after the delivery of a task-
relevant stimulus which must be categorized by the ob-
server.
P3a: A subtype of the P300 ERP, which is more pro-
nounced at frontal electrodes and occurs when a rare,
novel stimulus must be determined to be either task rel-
evant or not.
P3b: A subtype of the P300 ERP, which is more pro-
nounced at parietal electrodes and occurs in response
to the detection of a target stimulus.
SCID-I: A computer-administered assessment tool used
for indicating the possible presence of various forms
of psychopathology.
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