Psychology and Aging

2009, Vol. 24, No. 4, 792 808

2009 American Psychological Association

0882-7974/09/$12.00 DOI: 10.1037/a0017798

Neural Underpinnings of Within-Person Variability in Cognitive

Functioning
Stuart W. S. MacDonald

Shu-Chen Li

University of Victoria and Karolinska Institutet

Max Planck Institute for Human Development

Lars Backman
Karolinska Institutet
Increased intraindividual variability (IIV), reflecting within-person fluctuations in behavioral performance, is commonly observed in aging as well as in select disorders including traumatic brain injury,
schizophrenia, attention-deficit hyperactivity disorder (ADHD), and dementia. Much recent progress has
been made toward understanding the functional significance of IIV in cognitive performance (MacDonald,
Nyberg, & Backman, 2006) and biological information processing (Stein, Gossen, & Jones 2005), with
parallel efforts devoted to investigating the links between older adults deficient neuromodulation and
their more variable neuronal and cognitive functions (Backman, Nyberg, Lindenberger, Li, & Farde,
2006). Despite these advances in the study of IIV, there has been little empirical examination of
underlying neural correlates and virtually no synthesis of extant findings. The present review summarizes
the accumulating empirical evidence linking age-related increases in IIV in cognitive performance to
neural correlates at anatomical, functional, neuromodulatory, and genetic levels. Computational theories
of neural dynamics (e.g., Li, Lindenberger, & Sikstrom, 2001) are also introduced to illustrate how
age-related neuromodulatory deficiencies may contribute to increased neuronal noise and render information processing in aging neurocognitive systems to be less robust. The potential benefits of stochastic
resonance and external noise are also discussed with respect to processing subthreshold stimuli (e.g., Li,
von Oertzen, & Lindenberger, 2006). We conclude by highlighting important challenges and outstanding
research issues that remain to be answered in the study of IIV.
Keywords: cognition, aging, within-person variability, brain, neuromodulation

indexed from a single measurement occasion can result in

flawed estimates of mean-group differences with implications
for both theory and practice (Hultsch & MacDonald, 2004;
Hultsch, Strauss, Hunter, & MacDonald, 2008; Stuss & Binns,
2008). On a related note, when within-person variability is
large, it poses considerable challenges for the estimation of
long-term cognitive change (e.g., Salthouse, 2007). Further,
systematic and sizeable variability across measurements raises
questions about the foundations of classical test theory and the
utility of true score values (Lindenberger & von Oertzen, 2006).
Thus, an exclusive emphasis on mean levels in the absence of
considering variability represents a critical oversimplification
of patterns of behavior that may lead to erroneous inference
(Nesselroade, 2002). Recognition of these shortcomings has
given rise to models (e.g., diffusion models) that explain performance based on multiple distribution parameters, not just
central tendency (e.g., Ratcliff, Van Zandt, & McKoon, 1999).
Inclusion of variance parameters confers unique predictive information about cognitive functioning independent of mean performance (e.g., West, Murphy, Armilio, Craik, & Stuss, 2002), with
specific analyses of variability facilitating discrimination among
groups along multiple dimensions, such as patients with dementia
versus healthy controls or patients with dementia subtypes (Hultsch,
MacDonald, Hunter, Levy-Bencheton, & Strauss, 2000;
Murtha, Cismaru, Waechter, & Chertkow, 2002).

Most cognitive and neuropsychological research has focused on

mean differences in performance across persons. This orientation
has largely overshadowed research on performance variability
within persons. This is a serious theoretical and practical oversight
because, given large processing fluctuations, behavioral performance assessed from a single occasion is less accurate and representative. To the extent that variability in performance is small,
mean-level differences provide useful predictive information.
However, as within-person variability increases and represents
systematic as opposed to random sources of error, performance

Stuart W. S. MacDonald, Department of Psychology, University of

Victoria, Victoria, British Columbia, Canada, and Aging Research Center,
Karolinska Institutet, Stockholm, Sweden; Shu-Chen Li, Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin,
Germany; Lars Backman, Aging Research Center, Karolinska Institutet.
This research was supported by grants from the Swedish Research Council
and Swedish Brain Power to Lars Backman, who was also supported by an
Alexander von Humboldt Research Award. Shu-Chen Li was supported by
grants from the German Ministry of Education and Research and the Max
Planck Society, and Stuart MacDonald was supported by a Scholar Career
Investigator Award from the Michael Smith Foundation for Health Research.
Correspondence concerning this article should be addressed to Stuart
W. S. MacDonald, Department of Psychology, University of Victoria,
P.O. Box 3050 STN CSC, Victoria BC V8W 3P5, Canada. E-mail:
smacd@uvic.ca
792

SPECIAL SECTION: NEURAL UNDERPINNINGS OF IIV

The recent impetus toward examining variability in cognitive

functioning, as both outcome and predictor, derives from a growing literature showing performance fluctuations that (a) are neither
due to random error nor measurement unreliability, (b) often share
a negative association with mean cognitive performance (e.g.,
Hultsch & MacDonald, 2004; Hultsch et al., 2008), and (c) are
linked to theories explicating processing dynamics (e.g., Ratcliff
et al., 1999) or the roles and potential neuronal sources of noise in
affecting information processing (e.g., Li, Lindenberger, & Sikstrom, 2001). Although the stability perspective has dominated
developmental research for years (Nesselroade, 2002), the current
focus on variability is not new (see Cattell, 1957; Fisk & Rice,
1955; Head, 1926; Wohlwill, 1973). For example, intraindividual
variability was a primary influence in formulating the statetrait
anxiety distinction (Cattell & Scheier, 1961). The renewed vigor
for the study of variability likely reflects improved means and
methods for exploring performance fluctuations (Nesselroade &
Salthouse, 2004). Within this literature, three primary indices of
variability have been operationalized vis-a`-vis the minimum conditions necessary to observe it with reference to a threedimensional data box defined by persons, measures, and occasions
(Cattell, 1966; Hultsch, MacDonald, & Dixon, 2002). Between
persons, variability has been operationalized as differences in
performance measured on a single task on a single occasion
(referred to as individual differences).
Within persons, variability has been operationalized in two
ways. The first concerns variability associated with measuring
a single person on a single occasion across multiple tasks
(referred to as intraindividual differences). For example,
Holtzer, Verghese, Wang, Hall, and Lipton (2008) indexed this
form of within-person variability across a battery of neuropsychological tests to predict risk of incident dementia. The second
form of within-person variability is defined by the minimum
condition of measuring a single person on a single task across
multiple occasions (referred to as intraindividual variability or
IIV). Such intraindividual fluctuations in performance have
been indexed across multiple trials within a session or across
multiple sessions spanning longer intervals (e.g., hours, days,
weeks) for a single measure (Li, Huxhold, & Schmiedek, 2004).

Analytical Perspectives in the Study of Variability

Developmentalists and aging theorists alike are inherently interested in change over time, and thus variability within persons
and across occasions (i.e., IIV) has garnered particular attention for
researchers in these fields. To be sure, a thorough understanding of
the wider field of variability research requires an appreciation of
the distinctions between several analytical perspectives. To help
orient the reader, we briefly will introduce how time scales, task
characteristics, and intraindividual dynamics are key factors to
consider in any operationalization of within-person variability.

Time Scales
One dichotomy that is fundamental to the study of variability
concerns differentiating ontogenetic versus microgenetic forms of
within-person change according to two criteria: permanence of
change and time scale (Nesselroade, 1991). Intraindividual change
represents a relatively slow and enduring process that unfolds

793

across months, years, or decades (e.g., progressive changes associated with development and aging, long-term learning, and skill
acquisition) and has been referred to as becoming (Ford, 1987) or
developing (Li, Huxhold, & Schmiedek, 2004). In contrast, IIV
represents relatively rapid and transient short-term change indexed
across minutes, days, or weeks for various types of behavior (e.g.,
shifts in emotional state, variability in cognitive accuracy or processing speed, fluctuations in physical performance). The shorter
time frame is said to reflect being (Ford, 1987) or functioning (Li,
Huxhold, & Schmiedek, 2004), with indices of IIV variously
referred to as inconsistency, lack of processing robustness, wobble,
and lability (for a review, see Hultsch et al., 2008). IIV can be
distinguished from more enduring intraindividual change. Although both variants of within-person change represent important
developmental phenomena, recent research has been focused on
IIV as a common component of aging-related cognitive decline, as
well as in relation to behavioral changes associated with neurodegenerative diseases (e.g., Alzheimers disease) and other brainrelated disorders (e.g., traumatic brain injury, schizophrenia). Considering the diverse populations that exhibit increasing IIV and
concomitant cognitive deficits, more variable cognitive functioning likely reflects a behavioral proxy for endogenous neural
changes underlying impairment.
The time scale for measuring IIV itself is also important. For
example, IIV indexed from moment to moment (e.g., fluctuations
in reaction time [RT] trials) versus day to day or week to week
(e.g., fluctuations in mood) likely reflects different underlying
sources (e.g., Martin & Hofer, 2004; Rabbitt, Osman, Moore, &
Stollery, 2001; Ram, Rabbitt, Stollery, & Nesselroade, 2005;
Rocke, Li, & Smith, in press). In several studies, IIV has even been
examined across different retest intervals for the same task in the
same sample. Rabbitt and colleagues (2001) found that RT variability from trial to trial versus week to week was related, although
individual differences in within-session variability did not account
for all the variance in between-session variability. Similarly,
Hultsch and colleagues (Fuentes, Hunter, Strauss, & Hultsch,
2001; Hultsch et al., 2000) reported that the magnitude of IIV
across trials is approximately twice as large as IIV across weeks.
If a theoretical model assumes that endogenous sources underlie
cognitive variability (e.g., neural correlates such as changes in the
efficiency of neurotransmitters), then IIV may be better captured
over short intervals (e.g., trial-to-trial fluctuations in RT tasks). In
contrast, exogenous modulators of variability (e.g., fatigue, perceived stress) may be better indexed over days or weeks.

Task Characteristics
Recent reviews have chiefly focused on the negative association
between IIV and cognitive performance (e.g., Hultsch et al., 2008;
Luszcz, 2004; MacDonald, Nyberg, & Backman, 2006). However,
variability is not always a harbinger of maladaptive functioning;
rather, variability can be adaptive depending on specific task
characteristics. For example, performance variability in the child
development literature is related to cognitive development (not
impairment), with such variability reflecting diverse strategy exploration for complex tasks. Children who try a variety of strategies for complex tasks exhibit greater success. In contrast, more
constrained tasks (including many of the response latency measures examined in the cognitive aging literature on variability) are

MACDONALD, LI, AND BCKMAN

794

less amenable to multiple response strategies, and varying strategies to such tasks could be maladaptive. Siegler (1994) has referred to such fluctuations in performance as the ebbing and
flowing of new and old ways of thinking. Similar positive associations between increased IIV and cognitive functioning have been
reported for older adults. Allaire and Marsiske (2005), for example, computed IIV across performance accuracy trials for three
cognitive tasks that permitted implementation of new performance
strategies with practice. Results indicated that increased IIV was
positively correlated with level of task performance and the magnitude of practice-related gains. In contrast, IIV estimates derived
from cognitive tasks that provide little opportunity for strategic
processing or practice-related gains (e.g., sensorimotor or perceptual processing speed) are typically associated with maladaptive
outcomes (e.g., Hultsch & MacDonald, 2004, Hultsch et al., 2008).
Furthermore, depending on the domains of functioning (e.g., cognitive vis a vis affective), aging is not always associated with
increasing within-person variability. For instance, recently Rocke
et al. (in press) reported that older adults exhibited less daily
fluctuations in positive and negative affect than young adults.

Subtypes of Variability
It is important to emphasize that variation could be operationalized in numerous forms, even for the most basic cognitive
information processing tasks. Indices of variability can be indexed
across trials versus sessions or across all response latency trials
versus only correct responses and could even be examined in the

drift rate or diffusion coefficient across or within trials (cf. Ratcliff

et al., 1999).
To better understand the characteristic nature of variability (e.g.,
adaptive vs. maladaptive), Li, Huxhold, and Schmiedek (2004)
proposed a taxonomy of intraindividual dynamics, reflecting variations in an individuals processes or performance over time that
are due to both endogenous and exogenous influences. For example, the classification of intraindividual dynamics allows for distinctions to be drawn between adaptive versus maladaptive types
of variability (see Figure 1). Adaptive forms of variability are
typically observed to the extent that a task is amenable to strategy
use. These adaptive subtypes include plasticity (the functional
malleability to obtain large learning gains following task exposure), diversity (exploratory behaviors and various strategies used
for performing a complex task), and adaptability (ability to quickly
recover peak functioning in the face of challenging task conditions). In contrast, continued fluctuation in performance subsequent to mastering a given level of functioning indicates a lack of
processing robustness, defined by an increased ebb and flow in
processing, and diminished stability in performance over brief
intervals (Li, Huxhold, & Schmiedek, 2004, Li, Lindenberger, et
al., 2004). It is this form of maladaptive IIV that characterizes
virtually all findings reported in the present review.

The Present Review

For the purposes of the present review, we focus on within-task
IIV reflecting intraindividual change in behavior that is relatively

Figure 1. Varieties of intraindividual dynamics. Adaptive forms of variability are typically observed for tasks
amenable to strategy use. Adaptive subtypes include plasticity (the ability to exhibit learning gains following task
exposure), diversity (exploratory strategy use when performing a complex task), and adaptability (capacity to
quickly recover peak functioning despite challenging task conditions). As a maladaptive form of variability, lack
of processing robustness reflects continued performance fluctuations and diminished stability subsequent to
mastering a given level of functioning. This form of maladaptive variability characterizes most findings reported
in the present review. From Aging and Processing Robustness: Evidence From Cognitive and Sensorimotor
Functioning, by S.-C. Li, O. Huxhold, and F. Schmiedek, 2004, Gerontology, 50, p. 30. Copyright 2004 by
Karger. Adapted with permission.

SPECIAL SECTION: NEURAL UNDERPINNINGS OF IIV

rapid and transient (e.g., trial-to-trial fluctuations on RT tasks).

Irrespective of analytical perspective (e.g., task type, time scale,
behavior vs. brain), most of the empirical studies reviewed indexed
a maladaptive form of IIV, largely derived from within-person
standard deviations (or related measures) computed across correct
(i.e., accurate) trials of response latency tasks for various cognitive
outcomesa form of compromised processing robustness according to the Li, Huxhold, and Schmiedek (2004) taxonomy. Such IIV
increases characterize performance of older adults as well as
populations with various conditions including dementia, head injury, schizophrenia, and attention-deficit hyperactivity disorder
(ADHD). Although select evidence substantiates the hypothesized
neural underpinnings of increased IIV from both behavioral
(Hultsch et al., 2008) and neuroimaging (Hedden & Gabrieli,
2004; MacDonald, Nyberg, & Backman, 2006; Winterer et al.,
2004) perspectives, there has been little examination of underlying
neural correlates and virtually no synthesis of extant findings. We
begin by reviewing variability findings from the life span literature, as well as discussing potential origins of IIV. Next, we
summarize evidence linking age-related increases in IIV for cognitive functioning to neural correlates at anatomical, functional,
neuromodulatory, and genetic levels. Although these distinct neural correlates imply that increased IIV is multidetermined (for a
review, see MacDonald et al., 2006), they may also reflect different levels of related phenomena. For example, fluctuations at the
functional level (e.g., in blood oxygenlevel dependent [BOLD]
signal) may be directly linked to neuromodulation (e.g., dopamine
biomarkers). Finally, we conclude by emphasizing important challenges and identifying key questions that remain to be answered in
the study of IIV.

IIV: A Life Span Perspective

IIV in cognitive performance across the life span is characterized by a U-shaped function. Whereas IIV in cognitive functioning
is initially high in childhood, it decreases through adolescence,
only to reverse course with advancing age, where clear links
between increasing IIV and concomitant cognitive impairments
are observed (e.g., Hultsch et al., 2002; Li, Lindenberger, et al.,
2004; Rabbitt et al., 2001; Williams, Hultsch, Strauss, Hunter, &
Tannock, 2005; Williams, Strauss, Hultsch, & Hunter, 2007). This
developmental pattern parallels the inverted U-shaped function
observed for age-related changes in intellectual functioning (Li,
Lindenberger, et al., 2004), with maturation and senescence
imposing age-specific constraints, particularly under executively demanding conditions (Kray, Eber, & Lindenberger,
2004; Li, Hammerer, Muller, Hommel, & Lindenberger, 2009).
The preponderance of data on IIV concerns older adults, with
most studies revealing clear age-related increases in IIV and concomitant impairments in memory, attention, and language (e.g.,
Anstey, 1999; Hultsch et al., 2000; Nesselroade & Salthouse,
2004; Rabbitt et al., 2001). Such within-person fluctuations in
cognitive performance could correspond to as much as several
decades of between-person age differences (Nesselroade & Salthouse, 2004). At cross section, IIV correlates negatively with level
of performance for diverse measures representing both fluid (e.g.,
perceptual speed, working memory) and crystallized (e.g., vocabulary) abilities. The magnitude of IIV cognition correlations is
age- and task-dependent, with older adults exhibiting larger cor-

795

relations between IIV and cognitive performance regardless of task

complexity. In contrast, associations for young adults are attenuated (albeit still negative) and are typically only observed for select
measures characterized by higher cognitive demands (e.g., frontally based executive processes; Hultsch et al., 2002).
Several more stringent longitudinal assessments of the IIV
cognition association are available. For example, MacDonald,
Hultsch, and Dixon (2003) examined longitudinal changes in IIV
on four RT tasks administered over a 6-year period (three occasions) to 446 older adults from the Victoria Longitudinal Study
(VLS). Findings showed that 6-year increases in IIV were associated with 6-year cognitive decline for various cognitive outcomes
(e.g., episodic memory, working memory), supporting claims that
behavioral IIV is a predictor of cognitive aging. A key feature of
this study was the proven link between change in IIV and cognition at the within-person level. In an intriguing study, Lovden, Li,
Shing, and Lindenberger (2007) examined the supposition that
variability may represent both a precursor, signaling impending
decline in cognitive performance (see Figure 2a), and outcome of
change. Bivariate dual change score models were used to test the
dynamic coupling between trial-to-trial RT variability for a measure of perceptual speed (identical pictures) and change in mean
levels of performance for both perceptual speed and category
fluency. Of particular interest was whether individual differences
in IIV at baseline preceded subsequent change in cognitive functioning. These models were applied to five-occasion 13-year longitudinal data from the Berlin Aging Study (N 447; 70 102
years old at baseline). At baseline, individual differences in IIV
across RT trials for the perceptual speed task were coded into three
groups: individuals with scores greater than 0.5 standard deviations (SDs) above the mean (high-variability group), those with
scores 0.5 SDs of the mean (median-variability group), and those
with scores more than 0.5 SDs below the mean (low-variability
group). Notably, individuals in the high-variability group showed
accelerated decline in category fluency relative to those in the
low-variability group (see Figure 2b). In contrast, individual differences in mean levels of category fluency at baseline did not
reliably influence subsequent change in IIV. These findings suggest that shifts in variability precede changes in mean performance, provide arguably the most convincing developmental test
of the variability hypothesis to date, and imply that theories of
cognitive aging should recognize and account for the developmental cascade between senescent changes in variability and central
tendency.
Increased IIV in cognitive functioning has also been linked to
impairments and fluctuations in biomarkers of aging, including
sensory acuity and physiological functioning (Li, Aggen, Nesselroade, & Baltes, 2001; MacDonald, Hultsch, & Bunce, 2006;
Strauss, MacDonald, Hunter, Moll, & Hultsch, 2002), in accord
with interpretations of IIV as a behavioral indicator of central
nervous system (CNS) integrity. Other biomarkers such as forced
expiratory volume and grip strength also account for considerable
variance in IIV and RT latency (Anstey, Dear, Christensen, &
Jorm, 2005).
Additional behavioral findings linking variability to cognitive
performance in the latter part of the life span indicate that IIV is
systematically related to death (e.g., Shipley, Der, Taylor, &
Deary, 2006). In one study, IIV uniquely predicted terminal cog-

MACDONALD, LI, AND BCKMAN

796

b
70
60
50
40
30

Initial level of variability +0.5 SD

Initial level of variability

20

Initial level of variability -0.5 SD

10
1

Assessment Occasion

Figure 2. (a) Hypothetical depiction of level of intraindividual variability (IIV) as a precursor of cognitive
change for several individuals. (b) Longitudinal change in category fluency plotted as a function of performance
variability. At baseline, three variability groups (high, median, and low) were formed on the basis of individual
differences in IIV across reaction time trials of a perceptual speed task. Individuals with IIV scores greater than
0.5 standard deviations (SDs) above the mean were coded in the high-variability group, those with IIV scores
0.5 SDs of the mean were coded in the median-variability group, and those with IIV scores more than 0.5 SDs
below the mean were coded in the low-variability group. Individuals who exhibited the most variability in
perceptual speed at baseline also showed steeper longitudinal decline in category fluency, relative to individuals
in the low- or median-IIV groups. From Within-Person Trial-by-Trial Variability Precedes and Predicts
Cognitive Decline in Old and Very Old Age: Longitudinal Data from the Berlin Aging Study, by M. Lovden,
S.-C. Li, Y. L. Shing, and U. Lindenberger, 2007, Neuropsychologia, 45, p. 12. Copyright 2007 by Elsevier.
Adapted with permission.

nitive decline as many as 15 years prior to the death, with IIV

increasing every year closer to death (MacDonald, Hultsch, &
Dixon, 2008). In this study, lower IIV scores also predicted the
probability of survival independent of age, cardiovascular health,
and cognitive performance level, supporting the view that IIV is an
early behavioral marker of neurological dysfunction associated
with impending death.

Origins of Increased IIV

Research on the origins of IIV remains sparse. At the cognitive
level, postulated mechanisms include momentary lapses of atten-

tion (e.g., Bunce, Warr, & Cochrane, 1993) and failure to maintain
executive control (e.g., West et al., 2002). Such accounts imply a
disproportionately high number of very slow responses in the RT
distribution, a proposition supported by recent findings (e.g., Williams et al., 2005). Although most extant research on IIV has relied
on such behavioral data, brain correlates have begun to be delineated in recent neuroscientific investigations. Closer inspection of
related literatures (life span developmental psychology, neuropsychology, neuroscience) reveals that increased IIV shares definitive
links to numerous age- and non-age-related conditions, including
increasing adult age, cognitive decline, impending death, ADHD,

SPECIAL SECTION: NEURAL UNDERPINNINGS OF IIV

Parkinsons disease, frontotemporal dementia, traumatic brain injury, and a specific allele (Val) of the catechol-O-methyl transferase (COMT) gene (for reviews, see Hultsch et al., 2008;
MacDonald, Nyberg, & Backman, 2006). Converging evidence
indicates that IIV in cognitive functioning is linked to these aforementioned outcomes independent of mean-level performance, underscoring the unique importance of variability (e.g., for promoting early detection of impending disease and improving
differential diagnosis). Thus, IIV is not solely the province of
aging at the behavioral level but rather reflects multiple endogenous brain correlates. For example, rapid changes in IIV from one
moment to the next in a cognitive task may reflect brain mechanisms, such as fluctuations in the connectivity of neuronal pathways (e.g., Kelly, Uddin, Biswal, Castellanos, & Milham, 2008),
and the efficacy of neurotransmitter systems (e.g., Backman et al.,
2006). In the remaining sections of this review, we focus on links
between increased IIV in cognitive performance and key brain
correlates and speculate as to mechanisms underlying increased
variability in behavior and brain alike.

Neural Correlates of IIV

Structural Brain Correlates
A growing body of evidence links structural brain correlates to
IIV. Structural alterations associated with increased performance
variability include lesions to frontal gray matter (e.g., Sowell et al.,
2003; Stuss, Murphy, Binns, & Alexander, 2003) as well as
changes to white matter, including volumetric decline, demyelination, and hyperintensities that reflect abnormalities on magnetic
resonance imaging (MRI) scans due to age-related changes in
cerebral blood flow, vascular injury, or neurological conditions
(e.g., Anstey et al., 2007; Britton, Meyer, & Benecke, 1991; Bunce
et al., 2007; Walhovd & Fjell, 2007).
Lesions to frontal gray matter and associated increases in performance variability have a rich history in neuropsychology (e.g.,
Goldstein, 1939; Head, 1926). With regard to structural correlates,
an immediate question concerns whether elevated IIV exhibits
regional specificity. Neuropsychological evidence suggests that
the frontal lobes (particularly the prefrontal cortex [PFC]) share a
strong association with IIV. For example, Murtha and colleagues
(2002) reported that persons with frontotemporal dementia were
more variable than those with Alzheimers disease for a similar
level of disease severity, implying differential relevance of frontal
versus medial temporal regions to elevated IIV. Stuss et al. (2003)
examined whether frontal regions shared a stronger association
with IIV and, if so, whether there were regional frontal variations.
They examined 48 patients between 43 and 67 years old who had
brain lesions due to various acute conditions including infarction,
hemorrhage, and trauma (25 patients with frontal lesions, 11
patients with nonfrontal lesions, and 12 control participants). Four
different RT tasks were employed that required distinct levels of
feature discrimination and identification: simple (respond to a
single shape); easy (four different shapes with one designated as
the target on 25% of the trials); complex (discrimination based on
shape, color, and internal texture, with the target defined as a
combination of these features); and redundant (also containing
three features, but the nontarget trials did not contain any target
features). Consistent with expectations, those with circumscribed

797

frontal lesions were more variable than those with nonfrontal

lesions or controls. Moreover, for those with frontal lesions, a
different profile of variability was observed depending on location.
Individuals with lesions in right and left dorsolateral PFC, as well
as in the superior medial frontal cortex, exhibited the most pronounced variability, which increased with task difficulty. These
findings indicate that damage to the frontal lobes impairs stability
of cognitive performance.
Given the well-documented associations between white matter
integrity and select cognitive deficits (e.g., processing speed, attention), potential links between white matter status and IIV have
been examined in several recent studies. With increasing age, the
corpus callosum (CC) is known to atrophy, with the area of the CC
potentially reflecting an important indicator of white matter disease related to demyelination or vascular insult (Pfefferbaum,
Rosenbloom, Serventi, & Sullivan, 2002). In light of these associations, Anstey and colleagues (2007) investigated links among
the CC area (traced on the mid-sagittal slice), IIV, and cognitive
status. They examined differences in IIV across RT trials for both
simple and choice RT tasks for two groups of adults who were
60 64 years old: a healthy adult group (n 432) and a group
characterized as having mild cognitive disorders (n 57). For the
normative sample, no reliable association was observed between
the CC area and IIV; IIV accounted for less than 1% of the
between-person variance in the CC area. However, individuals in
the mild cognitive disorders group who were more variable also
had a smaller CC area, with IIV explaining as much as 12.7% of
the variance. The fact that a stronger association between the CC
area and IIV was observed for the at-risk group suggests a role of
white matter alterations in both cognitive impairment and increased performance variability. Moreover, dividing the CC into
three distinct regions (anterior, intermediate, and posterior) yielded
the largest associations between the anterior CC and IIV, consistent
with previously reported links among frontal structures, attention, and
IIV (e.g., West et al., 2002).
Among potential explanations for the increased CC areaIIV
link in the mild cognitive disorders group, Anstey and colleagues
(2007) invoked a concept based on biological limits of cognitive
processing (e.g., Baltes, Staudinger, & Lindenberger, 1999). Such
limits may be defined in terms of brain reserve (i.e., the integrity
of brain structure and neural circuitry) or in terms of cognitive
reserve reflecting the ability to efficiently use existing brain structures or to recruit alternate ones if necessary (Stern, 2002). Constraints on brain or cognitive reserve may be due to numerous
factors including structural or functional changes. The reserve
premise is supported by functional imaging studies showing patterns of individual differences in neural activation. With increasing
task difficulty, pathology-free individuals typically exhibit increased activation for the same brain regions that were activated
for less demanding versions of the same task. However, there are
clear individual differences in terms of these activation patterns;
for a given level of task difficulty, individuals with greater reserve
capacity exhibit less (i.e., more efficient) neural activation to
achieve the same level of performance and could presumably
perform better than less skilled individuals at maximum exertion
(e.g., Grady et al., 1996; Nyberg et al., 2003; Stern, 2002; Stern
et al., 2003). Anstey and colleagues (2007) speculated that individual differences in the CC area in the mild cognitive disorders
group could share a stronger association with deterioration in the

798

MACDONALD, LI, AND BCKMAN

PFC that may, in turn, give rise to attentional deficits and increased
IIV (Andres, Parmentier, & Escera, 2006; Raz, Gunning-Dixon,
Head, Dupuis, & Acker, 1998). Such an interpretation is consistent
with previous research showing that increased executive demands
result in increased IIV in response latency (West et al., 2002).
Individuals in the mild cognitive disorders group who were the
most variable also had the most diminished brain reserve (in the
form of a smaller CC area, likely indicating pathological white
matter alterations). This groups increased IIV in response latency
for a simple RT task could reflect such constraints to brain reserve
but may also reflect lessened cognitive reserve (the greater burden
of structural brain changes may lead to failures of task-relevant
processing or to deficiencies in basic cognitive resources). Either
diminished brain or cognitive reserve could exacerbate IIV in
cognitive performance.
A related study by Bunce and colleagues (2007) examined the
association between white matter hyperintensities (WMHs) in various brain regions (e.g., frontal, temporal, parietal) and increased
IIV across RT trials for 469 healthy community-dwelling adults
(60 64 years old). Findings indicated that frontal WMHs were
linked to increased IIV but not to performance on other cognitive
measures including global cognition, perceptual speed, and episodic memory. In contrast, WMH in other brain regions did not
share a significant association with IIV. These patterns imply that
increased WMH and the associated deterioration of neural pathways in the frontal cortex play a key role in increased IIV observed
for older adults and those at risk of cognitive impairment.
In summary, lesions to frontal gray and white matter share a
robust association with increased IIV. The developmental evolution and involution of gray and white matter corresponds, at least
grossly, to increasing and then decreasing intellectual functioning
(Kray et al., 2004; Li, Lindenberger, et al., 2004) as well as to
decreasing and then increasing IIV (MacDonald et al., 2003;
Williams et al., 2005) across the life span. For example, the
reported decreases in IIV from early childhood through adolescence (cf. Williams et al., 2005) may reflect systematic changes in
brain morphology, particularly in the frontal cortex (Gogtay et al.,
2004). The reductions in gray matter density and synaptic pruning
that occur during adolescence and young adulthood (Sowell et al.,
2003) may promote increased neural efficiency and decreased
noise in cognitive functioning that underlie the concomitant decreases in IIV during development (Williams et al., 2005, 2007).
Similarly, gray matter atrophy and increased neural noise in older
adults may underlie increased IIV (Raz et al., 2004; Sowell et al.,
2003).
Life span changes in white matter volume, approximating an
inverted U-shaped function, mirror closely the U-shaped life span
changes observed for patterns of IIV (Gogtay et al., 2004; Sowell
et al., 2003). Disconnectivity in associative pathways, whether
caused by immature or degraded white matter tracts, can also
increase variability. Such structural changes in performance may
result in increased neural noise (e.g., due to white matter disconnectivity), leading to less distinct cortical representations, poorer
cognitive performance, and increased performance variability. Effectively, the neural system matures, levels off, and declines with
a direct correspondence between increasing and then decreasing
intellectual functioning to decreasing and then increasing IIV in
cognitive performance (MacDonald, Nyberg, & Backman, 2006).

Functional Brain Correlates

Functional MRI. As interest in performance variability as a
marker of CNS integrity has increased (Hultsch & MacDonald,
2004; Hultsch et al., 2008), functional brain imaging studies have
begun to emerge. Bellgrove, Hester, and Garavan (2004) conducted the first neuroscientific investigation of the functional
neuroanatomy of executive control in relation to IIV. A total of 42
healthy participants, 18 46 years old, completed a Go/No-Go
response inhibition task in an event-related functional magnetic
resonance imaging (fMRI) design. The Go/No-Go task presented
two letters, X and Y, in an alternating pattern (i.e., X Y X Y X . . .).
Participants were instructed to press the response button for all Go
trials but to withhold responses to No-Go stimuli that interrupted
the alternating pattern (e.g., X Y X X). Findings indicated that
increased IIV across Go trials of this response-inhibition task was
associated with lower inhibitory success, slower responding, and
increased brain activity in left and right middle frontal regions.
Individuals with increased IIV activated inhibitory regions to a
greater extent, likely reflecting greater demands for executive
control to maintain task performance. Consistent with research
underscoring important connections between the frontal lobes and
increased IIV (e.g., Stuss et al., 2003), these findings imply that IIV
may result from deficient attentional control (e.g., Bunce
et al.,1993; Bunce, MacDonald, & Hultsch, 2004) and could serve to
index the efficiency of executive control processes (Bellgrove
et al., 2004). Moreover, the findings are notable given that the
functional correlates of IIV were robust for even a healthy young
to middle-aged sample.
In a related fMRI investigation in older adults, the functional
correlates of IIV were examined in relation to episodic retrieval
success (MacDonald, Nyberg, Sandblom, Fischer, & Backman,
2008). IIV was computed across latency trials in a word recognition task and then examined in relation to the magnitude and
anatomical location of BOLD activations. The 19 older adults
(70 79 years old) were presented with 80 words during an initial
encoding session. During the subsequent retrieval session, both
brain scans and response latencies were recorded. Lower variability across successful word retrieval trials was linked to better word
recognition (r 0.37), faster RTs (r .66), and increased
BOLD activation (r 0.49) in the supramarginal gyrus in the
inferior parietal cortex, a structure implicated in sustained attention, deep semantic encoding, and retrieval success (e.g., Cabeza &
Nyberg, 2000; Shannon & Buckner, 2004; Wagner, Shannon,
Kahn, & Buckner, 2005). In contrast, more variable individuals did
not recruit this area of inferior parietal cortex to the same extent
and exhibited lower retrieval success. The observed links between
decreasing IIV and parietal activations associated with retrieval
success support the hypothesis that behavioral IIV represents a
proxy for neural integrity.
As a putative indicator of CNS efficiency, IIV may not only
share associations with activations in circumscribed brain regions
but also be linked to activity across functional networks. In a
recent investigation, Kelly et al. (2008) explored how IIV may be
modulated by competition between functional networks. One network of particular interest, the default-mode network, comprises
brain regions that show coherent activity at rest (e.g., stimulusindependent thought) and are routinely deactivated during
attention-demanding cognitive tasks (Buckner & Vincent, 2007;

SPECIAL SECTION: NEURAL UNDERPINNINGS OF IIV

Raichle et al., 2001). An inability to suppress such default-mode

activity has been linked to attentional lapses (e.g., Weissman,
Roberts, Visscher, & Woldorff, 2006), altered task-relevant activation in PFC and anterior cingulate cortex, and various conditions
including Alzheimers disease, ADHD, and schizophrenia (e.g.,
Buckner et al., 2005; Liang et al., 2006; Tian et al., 2006). As these
patterns and conditions are also well-known correlates of IIV,
Kelly and colleagues surmised that IIV and default mode activity
may be directly related. To pursue this idea, they used the Eriksen
flankers task to examine whether increased IIV and associated
attentional lapses could be explained by competition between the
default mode network (activations at rest) and regions of a taskrelevant dorsal attentional network (activations during the flankers
task). Recent studies have shown that this competitive association
is represented in the brain as an antiphase (i.e., negative) correlation between activation in these two networks. Larger negative
correlations are said to reflect better activity regulation between
the two networks, with the expectation that such larger antiphase
associations would be linked to less IIV in performance. Active
(flankers task) and resting state scans were obtained for 26 adults
(mean age 28.1 years). For each target network, the time series
of BOLD activations were extracted, and then the correlation between

799

activations in each network was computed (see Figure 3a). The

magnitude of the negative association between spontaneous activity in the default-mode network versus task-positive activity in the
attentional network was subsequently correlated with IIV (coefficient of variation) for congruent and incongruent RT trials in the
flankers task. The findings indicated that as IIV for incongruent
RT trials increased, the strong negative association between activations in the default mode versus those in the attentional networks
diminished (see Figure 3b). These results indicate that increasing
IIV is not only related to select anatomical regions of the brain but
is also associated with compromised regulation and coordination
of neural networks.
Electroencephalography (EEG)/event-related potentials (ERP).
Whole-brain functional activation techniques such as EEG have
also been used to link behavioral IIV in cognitive performance to
event-related oscillations in various EEG spectra. For example,
psychometric intelligence is inversely correlated with eventrelated potential variability (averaged evoked potentials) in the
parietal and temporal lobes (Barrett & Eysenck, 1994). Early
research in this area also linked increased variability in P300
latencies, an electrophysiological marker of various cognitive processes including attention and decision making (e.g., Sutton,

Figure 3. (a) Correlation between time series of blood oxygen level dependent (BOLD) activations for the
default mode network (activations at rest) and the dorsal attentional network (activations during the flankers
task). Competition between the default mode and dorsal attentional networks is represented in the brain as an
antiphase association, with larger negative correlations reflecting better activity regulation between the two
networks. TRs repetition times. (b) Correlation between antiphase time series (see Figure 3a) and intraindividual variability (IIV; coefficient of variation) for incongruent reaction time (RT) trials on the flankers task. As
IIV for incongruent RT trials increases, the strong negative association between activations in the default mode
versus attentional network is weakened. These results suggest that IIV is associated with compromised regulation
and coordination of neural networks. CV coefficient of variation. From Competition Between Functional
Brain Networks Mediates Behavioral Variability, by C. A. M. Kelly, L. Q. Uddin, B. B. Biswal, F. X.
Castellanos, and M. P. Milham, 2008, NeuroImage, 39, p. 11. Copyright 2008 by Elsevier. Adapted with
permission.

800

MACDONALD, LI, AND BCKMAN

1969), to old age and morbidity (Kugler, Taghavy, & Platt, 1993).
More recently, increased prefrontal broadband noise in the thetafrequency band (6.0 8.0 Hz) for patients with schizophrenia was
associated with increased BOLD signal in the dorsolateral PFC
during a working memory task, a pattern interpreted to reflect
inefficient neural processing (Winterer & Weinberger, 2004). The
link between increases in prefrontal EEG noise (i.e., activity not
time-locked to stimuli) during information processing and impaired working memory in those with schizophrenia may reflect
asynchronous field potential oscillations by cortical pyramidal
neurons (Callicott et al., 2000).
In a recent study, Fjell, Rosquist, and Walhovd (in press) examined instability at both the electrophysiological and behavioral
levels. Variability in P3a and P3b ERPs was indexed for a group
of 133 adults (20 88 years old) for a simple visual task measuring
response latency (a visual oddball task composed of 210 stimuli
with a 10% probability for both targets and distractors). The P3a
and P3b potentials are putative indicators of different attentional
processes; the former is related to attention switching and voluntary allocation of attention as elicited by distractor stimuli (but see
Sutton, 1969, who discussed numerous functional interpretations
of P3 potentials), with the latter thought to reflect stimulus evaluation and controlled attentional processes (elicited by target stimuli). IIV in response latencies for the simple visual task represents
a third distinct source of information characterizing response selection and execution. The focus of this investigation was to
identify the locus of age-related cognitive instability in the information processing stream (e.g., at the level of stimulus evaluation
vs. response execution). With increasing age of the participants,
significant increases in variability were observed across RT trials
but not in variability in P3a or P3b latency. In light of the patterns
observed, Fjell and colleagues (in press) concluded that age-related
increases in IIV seem to be localized to later stages of processing
(e.g., response decision or execution, as indicated by age-related
increases in IIV) as opposed to earlier stages in the response
decision stream (e.g., stimulus evaluation as indexed by P3b). This
interpretation is consistent with findings by West and colleagues
(2002); in that study, young and older adults showed the same
level of IIV for a low executive demand condition of the n-back
task, with the older group showing increased IIV as a function of
increased executive demands.

Neuromodulatory Correlates
In addition to structural and functional brain changes, alterations
in select neurotransmitters, including those in the catecholamine
and acetylcholine systems, may give rise to increased neural noise
(see Backman et al., 2006, for review) that undergirds increased
IIV in cognitive performance. In particular, alterations in dopamine (DA) neuromodulation have been documented for select
populations who also exhibit increased behavioral IIV; these populations include not only older adults (Hultsch et al., 2002; Rabbitt
et al., 2001) but also children with ADHD (Castellanos & Tannock, 2002; Bellgrove, Gill, Hawi, Kirley, & Robertson, 2005) and
patients with schizophrenia (Manoach, 2003) and Parkinsons disease (Burton, Strauss, Hultsch, Moll, & Hunter, 2006). One working hypothesis is that reduced DA activity increases neural noise,
resulting in less distinct cortical representations manifest as decreases in cognitive performance and increases in behavioral IIV

(Li, Lindenberger, & Sikstrom, 2001). In this section, we discuss

evidence from neurocomputational models, as well as recent empirical findings, that directly link DA dysregulation to increased
IIV.
Computational models. Various computational approaches
have been advanced to explain the mechanisms whereby dopaminergic modulation affects cognition (see Rolls, Loh, Deco, &
Winterer, 2008, for review). These attempts range from realistic
biophysical firing rate models of how D1 and D2 receptors affect
the stability of working memory representations (Durstewitz,
Seamans, & Sejnowksi, 2000; see also Seamans & Yang, 2004, for
a review) to more abstract models of dopaminergic effects on the
dynamic connectivity between prefrontal cortex and basal ganglia
(e.g., OReilly & Frank, 2006). Other models focus on the general
computational role of DA in affecting the signal-to-noise ratio of
neuronal signal transduction (e.g., Cohen & Servan-Schreiber,
1992; Li, Lindenberger, & Sikstrom, 2001) or outcome-based
evaluation in reinforcement learning (see Montague, Hyman, &
Cohen, 2004, for review).
Although the various computational approaches differ in level
of analysis and biophysical specificity, one basic assumption
shared by most theories is that dopaminergic modulation influences the properties of neuronal representations of cognitive and
perceptual events. For instance, a two-stage model of dopaminergic modulation of working memory aims at capturing the dynamic
interactions between DA and glutamate receptors in affecting the
neuronal representations of memory items in the prefrontal cortex
(Durstewitz et al., 2000). Specifically, when D2 receptor modulation predominates during the first stage, the PFC network is
supposed to be in an exploratory state with multiple weak representations. However, in the second stage when D1 receptor modulation predominates, heightened inhibitory mechanisms weed out
weaker representations and enhance the representation of the
stronger inputs (Seamans & Yang, 2004). This effect is nicely
paralleled by results from other models that aim at explicating the
computational effects of dopaminergic modulation on the signalto-noise ratio of information processing at a more molar level
(Cohen & Servan-Schreiber, 1992; Li, Lindenberger, & Sikstrom,
2001). In these models, DA is commonly assumed to facilitate the
responsivity in activity transmission both within and between
modules of a neural network. As the gain parameter of a neural
networks activation function is attenuated or increased to mimic
deficient or excessive dopaminergic modulation, respectively, the
distinctiveness of internal representations of stored perceptual or
memory items is reduced, resulting in impaired cognitive performance and increased behavioral IIV (e.g., Li, Lindenberger, &
Sikstrom, 2001; Li & Sikstrom, 2002).
In vivo positron emission tomography (PET) research. Building on these neurocomputational findings, investigators recently
attempted to directly link a PET-derived in vivo marker of dopaminergic neurotransmission (D2 binding potential) to IIV in cognitive performance (MacDonald, Cervenka, Farde, Nyberg, &
Backman, 2009) in a group of middle-aged adults (N 16; 41 65
years old). D2 binding potential was derived for striatum and three
extrastriatal brain regions (orbitofrontal cortex [OFC], anterior
cingulate cortex [ACC], and hippocampus [HC]); selection of the
region of interest was based on extant findings suggesting that
frontal and medialtemporal regions may differentially influence
IIV (Bellgrove et al., 2004; Murtha et al., 2002; Takahashi et al.,

SPECIAL SECTION: NEURAL UNDERPINNINGS OF IIV

2007). IIV in response latencies was indexed for measures of

episodic memory and executive functioning on the basis of the
established association these tasks share with IIV (see Hultsch et
al., 2008). Finally, relative to other DA receptors (e.g., D1), D2
binding may be especially relevant for the study of IIV. D2
receptors serve a critical role in facilitating rapid shifts between
different targets (cf. IIV), in contrast to D1 receptors, which have
greater relevance for tonic DA levels involved in maintaining a
specific cognitive set (e.g., Bilder, Volavka, Lachman, & Grace,
2004; Cohen, Braver, & Brown, 2002). Given the key role of DA
modulation for cognitive performance and IIV in the neurocomputational models, we hypothesized that decreased D2 binding
potential would be linked to increased IIV.
Consistent with expectations, lower D2 binding in the ACC,
HC, and OFC, but not in the striatum, was systematically linked to
increased IIV in both memory and executive functioning. This
study is the first in which a direct link was found between in vivo
measures of DA function and behavioral measures of IIV in
cognitive performance. The findings complement the neurocomputational work of Li and colleagues (Li, Lindenberger, &
Sikstrom, 2001; Li & Sikstrom, 2002), suggesting that DA dysregulation alters the signal-to-noise ratio of neural information
processing, impairing neurons sensitivity to afferent signals, leading to less distinct cortical representations, and ultimately resulting
in increasing IIV and impaired cognitive functioning.
The MacDonald et al. (2009) data are also consistent with
regional brain correlates identified in the neuropsychological and
neuroscience literatures, reinforcing the importance of frontal regions as structural correlates of IIV (e.g., Bellgrove et al, 2004;
Murtha et al., 2002; Stuss et al, 2003). The strongest association
was observed between D2 binding in the ACC and IIV for an
executive task that indexed set shifting. This implies that if the
ACC is not functioning optimally (e.g., due to reduced D2 binding), the resulting diminished executive control coupled with the
ACCs central processing role may lead to increased IIV in performance, particularly for executively demanding tasks (e.g., West
et al., 2002). These findings provide a nice extension of research
by Takahashi and colleagues (2007). Whereas they examined D2
binding potential in select extrastriatal regions and found that D2
binding in HC was associated with performance on episodic memory tasks as well as frontally mediated executive tasks, our findings clearly show the relation of D2 binding in ACC and HC to
measures of IIV in memory and executive tasks.

801

on cognitive tasks requiring cognitive stability and tonic levels of

DA activation but hamper performance on tasks that require cognitive flexibility and phasic activation. To examine this hypothesis,
Stefanis and colleagues administered the continuous performance
test (identical pairs version), which requires participants to respond
whenever two rapidly flashed identical stimuli (e.g., four-digit
numbers), among the 300 stimuli pairs, appear over the course of
a 5-min trial. Findings indicated that Val carriers exhibited greater
IIV than Met carriers across trials of the continuous performance
test, thereby linking the COMT polymorphism and frontal DA
activity to IIV. The authors concluded that the greater performance
stability for the Met genotype may be a consequence of increased
extracellular DA, serving to stabilize neural representations in the
prefrontal cortex.
The link between genetic and neuromodulatory influences underscores that, although multidetermined, the neural and genetic
correlates of IIV likely reflect different levels of related phenomena. Further emphasizing this point, percentage of change in the
BOLD signal in the left PFC is also known to vary as a function
of the COMT genotype. Mattay and colleagues (2003) found that
for a fixed level of n-back performance, participants who were
homozygous for the Val allele with less available DA in the
synaptic cleft exhibited increased BOLD activity in the PFC relative to homozygous Met carriers. Moreover, this difference was
exacerbated with increasing executive task load (i.e., 2-back vs.
1-back condition). The increased PFC activity in Val carriers was
interpreted as a less efficient physiological response, perhaps due
to diminished neuronal signaling in the PFC (Li & Sikstrom, 2002;
Stefanis et al., 2005). This interpretation is supported by other
neuroscientific findings showing that older adults nonselectively
recruit neural tissue in task-irrelevant brain regions during episodic
and working memory performance (e.g., Cabeza, 2001; Logan,
Sanders, Snyder, Morris, & Buckner, 2002). In synthesizing these
findings, we note that a less efficient frontal response during
cognitive processing characterizes patients with schizophrenia,
COMT Val carriers, and older adultsall groups displaying increased IIV in cognitive performance as well as alterations in the
DA system. Although the aforementioned findings reveal some
promising associations between COMT and IIV, there is a clear
need for future research on the links between IIV and other genes
that influence DA functions, as well as other systems (e.g., neurotransmitter, immune) altogether.

Key Issues and Future Research

Genetic Correlates
In addition to neuromodulators and other brain-based correlates,
emerging evidence indicates that IIV is under genetic influence as
well. The catechol-O-methyl transferase (COMT) enzyme degrades DA in the frontal cortex, with carriers of the Val allele of
the COMT gene having lower extracellular DA levels in prefrontal
cortex than Met carriers due to elevated enzymatic activity (Weinshilboum, Otterness, & Szumlanski, 1999). Stefanis and colleagues (2005) examined whether IIV in cognitive performance
varied as a function of COMT allele (Val vs. Met) in a sample of
521 men (mean age 21 years). The relation of DA signaling
(tonic vs. phasic) to performance on cognitive tasks is dependent
upon the characteristics of the task itself. The Met allele, with its
lower enzymatic activity, may differentially benefit performance

Despite explosive growth in variability research in the past

decade, a number of key challenges remain. In this final section,
we address several important themes including measurement issues related to IIV, the potential adaptivity of neural noise, and
several intriguing avenues for future research.

Measurement Issues and IIV

At the outset of this review, we introduced several analytical
perspectives (e.g., task characteristics, time scale) known to influence observed patterns of performance variability. Although often
an afterthought, the manner in which IIV is assessed may impact
both the magnitude and valence of associations between IIV and
select outcome measures. For example, there are several reasons

802

MACDONALD, LI, AND BCKMAN

that age differences are more likely to be found for measures of

IIV indexed by response speed versus those indexed by response
accuracy. Relative to accuracy-based measures, chronometric response latencies permit a more precise index of rapidly changing
internal processes (Gazzaniga, Ivry, & Mangun, 2002). If such
moment-to-moment fluctuations represent the best time frame to
assess efficacy of age-related cognitive functioning, then measures
of IIV over brief intervals likely confer the purest index. Moreover, accuracy measures are often derived from complex tasks,
which may be quite sensitive to strategy use (Hultsch et al., 2008);
as noted, IIV for tasks amenable to strategy use may be positively
related to other cognitive outcomes. Finally, latency measures
should provide a more sensitive scale compared with indicators of
accuracy due to measurement reliability. Accuracy-based cognitive measures often contain a limited number of items, potentially
leading to unreliable estimates of variability. Recent findings suggest that, regardless of metric, a sufficient number of trials (7)
are required to reliably index IIV (Schmiedek, 2006). It is also
important to keep in mind that relative to measures of IIV, the
arithmetic mean has a greater proportion of systematic variance
available for association with cognitive outcomes. Thus, observed
differences in the strength (but not valence) of association between
mean versus IIV may reflect differences in reliability. If the
reliability of IIV is lower than that of the mean, it is not surprising
that it would share a comparatively weaker association with the
same cognitive outcome. Such measurement properties of variability represent important considerations as numerous researchers
collectively attempt to understand patterns observed in the extant
literature.

The Adaptive Potential of Noise: Stochastic Resonance

Although our focus has rarely strayed from the negative aspects
of IIV, the point that variability or noise is not always suboptimal
is perhaps best illustrated in a phenomenon called stochastic resonance (SR). SR denotes the fact that optimal levels of input (i.e.,
externally introduced) noise are beneficial for detecting and transmitting weak signals in nonlinear physical and biological systems
(see Moss, Ward, & Sannita, 2004, for review). A basic aspect of
SR (threshold SR) results from the interaction between a response
(or activation) threshold, a subthreshold stimulus, and input noise.
Consider an example of a hardly recognizable image of Big Ben,
with most of its pixels degraded below a certain threshold of gray
scale. In this case, with an optimal amount of random noise added
to the gray scale, the subthreshold image gradually emerges above
the threshold and becomes visible. However, if more noise is
added, the image blurs again. Returning to the example of the brain
and models of spike-generating neurons, a subthreshold signal
cannot cross the threshold to produce action potentials, thus losing
the information content of the weak signal. However, the benefit of
adding noise in this case is to permit some spikes to cross the
threshold, thereby transmitting information about the signal.

Aging, Neuromodulation, and SR

At first glance, the notion of variability as a prime indicator or
cause of age-related cognitive deficits conflicts with ample empirical and theoretical evidence showing the functional relevance and
benefit of SR noise. This apparent paradox leads to a pivotal

question: To what extent are the functions of synaptic noise and

characteristics of SR altered in aging neurobiological systems as
well as in other conditions marked by suboptimal neuromodulation? Formal theories are helpful in guiding empirical research on
the interactive dynamics between synaptic noise as a regulatory
mechanism of cortical neurons response properties and other
mechanisms of neuronal gain control, such as neuromodulation
and neuronal synchronization (e.g., Diesmann, Gewaltig, & Aertsen, 1999). Models comparing systems with deficient neuromodulation (e.g., in the case of senescence or pathology) to intact
systems have generated insights about the interactions between
neuromodulatory and synaptic noise gain control.
Using the stochastic gain-tuning model of neuromodulatory
aging (Li, Lindenberger, & Sikstrom, 2001) to simulate experimental effects observed in paradigms of subthreshold perceptual
processing, we recently investigated how interactions between the
benefit of input noise and deficient neuromodulation jointly affect
SR in older neurobiological systems (Li et al., 2006). Less efficient
neuromodulation in old age was modeled by reducing the gain
parameter (G) from optimal to suboptimal levels to yield activation
functions with less steep slopes. Neural networks with attenuated
system gain modulation reacted to input noise less effectively,
resulting in SR functions with lower and right-shifted peaks (see
Figure 4). These findings suggest that noise added to weak signals
continues to yield beneficial effects in suboptimally modulated
systems. However, in aging, the benefits of SR are affected in three
major ways: (a) the absolute peak of SR is reduced, (b) the range
within which noise operates optimally is reduced, and (c) more
external noise is required to reach the peak of the SR function.
SR has recently attracted attention in research on aging because
of its promising utility in attenuating the functional consequences
of older adults deficits in sensory and sensorimotor functions. For

Figure 4. Different levels of stochastic gain modulation that simulate

age-related differences in neuromodulatory efficiency, result in stochastic
resonance (SR) functions that differ in peak magnitude and the extent of
right shift of the peak. The bell-shaped SR function depicts the rise and fall
of noise-enhanced benefits in signal processing. Neural networks with
attenuated system gain parameter (G) react to input noise less effectively,
yielding SR functions with lower and right-shifted peaks. Introducing noise
can be beneficial for subthreshold signals, but too much noise can obscure
the signal. E expected value or mean. From A Neurocomputational
Model of Stochastic Resonance and Aging, by S.-C. Li, T. von Oertzen,
and U. Lindenberger, 2006, Neurocomputing, 69, p. 1558. Copyright 2006
by Elsevier. Adapted with permission.

SPECIAL SECTION: NEURAL UNDERPINNINGS OF IIV

instance, keeping ones balance while standing is an important

basic sensorimotor function that declines substantially during aging (e.g., Huxhold, Li, Schmiedek, & Lindenberger, 2006) and is
often associated with serious negative consequences, such as falls.
It has recently been shown that subthreshold electromechanical
noise delivered through shoe insoles (Harry, Niemi, Priplata, &
Collins, 2005) reduces older adults body sway while standing.
Important challenges remain if researchers are to fully understand the positive versus negative characteristics of variability and
noise. Research on SR clearly indicates that providing external
noise into a system can improve signal processing (Li et al., 2006).
Even white noise can produce an action potential for an otherwise
weak signal. However, as shown in Figure 4, introducing too much
noise can also serve to obscure the signal. Additional research is
required into how age-related increases in neuronal noise due to
endogenous sources may be countered by the introduction of
external noise to augment signal processing. In contrast, many
examples of the negative repercussions of noise were reviewed,
showing clear links between increased variability and disadvantaged characteristics (e.g., impaired cognitive functioning, smaller
CC area). On the basis of the preponderance of data available, it
seems that the maladaptive forms of IIV reflect changes in endogenous brain mechanisms, such as white matter disconnectivity or
DA dysregulation with increasing age. Such changes in brain
structure, function, and neuromodulation likely influence cellular
processes that give rise to increased neural noise (i.e., reduced
signal to noise) and impaired cognitive representations, which is
subsequently manifest as increased performance variability and
impaired cognitive functioning. For example, endogenous forms of
neural noise underlying increased behavioral variability could
be due to a lack of coherence in neuronal firing patterns or to
uncoordinated firing within individual cells. Although some
data have linked the timing of neuronal firing to behavior (e.g.,
Johansson & Birznieks, 2004), it remains to be determined whether
cellular synchronization patterns map onto IIV in behavior. Also
required are single-cell studies in which across-trial variability in
firing rate for individual cells is measured directly (see MacDonald,
Nyberg, & Backman, 2006).

Future Research
With regard to IIV in behavior for select cognitive outcomes,
most of the extant research is based upon an evaluation of
between-person differences in within-person performance fluctuations. Future researchers clearly would benefit from additional
within-person analyses of the intraindividual covariation between
change in IIV for a given task and mean level change for other
cognitive outcomes (cf. Lovden et al., 2007). Such analyses will
provide a more stringent methodological assessment of whether
change in IIV is temporally linked to change in mean performance.
Future studies may explore within-person associations between
relevant features of a given task, such as the coupling between
response accuracy (correct vs. incorrect trials) and the vicissitudes
of response latency. As interest for this topic continues to grow, it
is imperative to move from univariate to multivariate conceptualizations of variability, which is akin to examining alterations in a
single local function versus alterations in the global organization
of numerous functions (e.g., how IIV across trials of a given RT
task is affected by, or may influence, shifts in cognitive resource

803

allocation or functional organization of the brain; Lindenberger &

von Oertzen, 2006).
More mechanistic evidence on the brainIIV relationship is
needed. Several important avenues of research could be pursued
that would provide better understanding of neural mechanisms
underlying IIV, including experimental manipulation of IIV, as
well as the examination of IIV in the brain itself. With regard to
experimental approaches, manipulating brain correlates hypothesized to influence performance variability represents one method
to directly link IIV to brain function. This could involve pharmacological manipulations of potential neural substrates of variability
such as DA. For example, dopaminergic agonists or antagonists
that respectively enhance or hamper neuromodulation could be
administered to examine the influence of DA signaling on IIV
in cognitive performance. A strong correlative triad is well
documented among DA, adult age, and cognitive performance
(Backman et al., 2006). Given the hypothesized importance of DA
to IIV, administering DA might decrease IIV in RT for older
adults, whereas an antagonist could increase IIV in the very same
measure of RT for young adults.
Although recent investigations linking behavioral IIV in cognitive functioning to neural indicators represent an important first
step, a perhaps even more intriguing avenue of future investigation
involves the direct examination of variability in the brain itself. In
light of the hypothesis that endogenous sources underlie IIV in
cognitive functioning, brain-imaging techniques with excellent
temporal resolution should be used to precisely index neural variability. One such direct approach would be to examine fluctuations
in the BOLD signal across individual trials. Technological advances in event-related fMRI (e.g. high-field 4-Tesla MRI) make
it possible to resolve rapid changes in the hemodynamic signal
(Yamaguchi, Hale, DEsposito, & Knight, 2004). As a consequence, it is possible to compute an IIV index for rapid changes
across BOLD activation trials within individuals. Note that doing
so can also lead to strong developmental tests regarding the nature
of variability. Specifically, if increased behavioral IIV is a proxy
for impaired neural processes, then it follows that indices of
increased brain IIV should be systematically associated with increased IIV in cognitive functioning. Following this logic, one
could conduct a stringent test of within-person coupling by examining the time-varying covariation between IIV in behavior (e.g.,
variability across discrete blocks of latency trials) and IIV in the
brain (e.g., variability in the BOLD signal for the corresponding
behavioral trials).
A similar logic applies to examining variability in electrical
brain activity as indexed with EEG, which provides even better
temporal resolution than fMRI for indexing IIV in the brain.
Recently, a novel demonstration of this approach was used to
examine the relation between variability of evoked electrical activity and performance on a cognitive task (face memory) for
children (8 15 years old) and young adults (20 33 years old;
McIntosh, Kovacevic, & Itier, 2008). Relative to the young adults,
children exhibited increased behavioral IIV in response latencies
as well as poorer face memory. Notably, however, variability in
the brain signal itself increased with age, sharing a negative
association with both behavioral IIV and accuracy, consistent with
previous patterns observed for behavioral data in younger samples
(cf. Siegler, 1994). McIntosh and colleagues (2008) argued that as
the brain continues to mature, such increased moment-to-moment

804

MACDONALD, LI, AND BCKMAN

variability in EEG signals may reflect enhanced neural complexity

and greater functional adaptivity (Gogtay et al., 2004). On the
surface, the findings by McIntosh and colleagues (2008) run
counter to the expectation that increased variability in the brain
and behavior go hand in hand. However, upon closer scrutiny,
these results are expected from the perspective of nervous system
nonlinear dynamics. Specifically, increased brain variability is
adaptive to the extent that it facilitates the parsing of weak incoming signals (e.g., Destexhe & Contreras, 2006) or assists in the
formation of functional networks (e.g., Fuchs, Ayali, Robinson,
Hulata, & Ben-Jacob, 2007). At least from childhood through early
adulthood, increased brain variability is indicative of enhanced
neural complexity (e.g., increased integration of neuronal circuits,
formation of new network connections), with corresponding benefits for cognitive adaptability. Clearly, it is of paramount interest
to examine patterns of variability in older age groups and to
determine in particular whether brain variability for these individuals is positively or negatively correlated with cognitive functioning (including behavioral IIV). As summarized earlier, variability
can confer both positive and negative benefits. In future research,
investigators should not neglect the potential benefits of variability
and the ways in which age-related differences in neuronal noise
may interact with processes by which external noise aids or hampers signal processing (e.g., SR and how the addition of noise to
systems can improve signal processing; Li et al., 2006).
In addition, it may be beneficial to include other neuroimaging
techniques such as event-related optical signal (EROS) as well as
transcranial magnetic stimulation (TMS; see Gazzaniga et al.,
2002). In EROS, optical fibers and infrared light are used to index
cerebral activity through measurement of the scattering properties
of neurons. EROS has good spatial (millimeters) and temporal
(milliseconds) measurement properties but cannot be used to index
subcortical structures. In TMS, weak electric currents excite neurons and facilitate the study of brain connectivity, and thus it is a
potentially interesting tool in light of findings linking IIV to
network competition (Kelly et al., 2008). Finally, multimodal
assessments (e.g., combining fMRI and near-infrared specstroscopy) could help maximize temporal and spatial precision in the
study of brain variability.

IIV likely reflect different levels of related phenomena, with some

levels exhibiting empirical links (e.g., DA, COMT genotype, and
fMRI). Examining potential associations among these different
sources requires a novel fusion of existing methodologies (e.g., Li,
Lindenberger, Nyberg, Heekeren, & Backman, in press). Whereas
molecular imaging techniques (e.g., PET) are well suited for
investigating neuromodulatory correlates of IIV, fMRI techniques
are better suited for examining select brain regions and neural
circuits linked to IIV. Pursuing multimodal imaging studies combining PET-derived DA markers and functional imaging data
during cognitive activity for the same individuals will address the
question of whether these neurobiological underpinnings jointly
influence IIV. An emerging literature suggests a link between DA
activity and the magnitude of the BOLD signal during cognitive
performance (Landau, Lal, ONeill, Baker, & Jagust, 2009;
Nyberg et al., 2009; Schott et al., 2008). Of particular import in the
present context, Landau et al. observed a link between a measure
of striatal DA synthesis capacity and the load-dependent BOLD
response during working memory in the left PFC, as well as to
activations in the supramarginal gyrus (a region frequently coactivated with PFC during working memory performance). MacDonald et al. (2008) reported that highly variable persons showed
underrecruitment of the supramarginal gyrus during episodic recognition. These patterns suggest a linkage between dopaminergic
neurotransmission, functional brain activation, and IIV that should
be further scrutinized in future research. Moreover, increased IIV
in cognitive performance could have a bottom-up origin (e.g.,
dysregulated DA neurotransmission in old age or in Parkinsons
disease) or may be due to deficient top-down regulation by prefrontal regions (e.g., following traumatic brain injury). Finally, it is
important to emphasize that the concepts of noise and variability
are not exclusively negative. Research on SR indicates that white
noise added to a system can positively influence performance
(Harry et al., 2005; Priplata et al., 2002), and brain variability in
early adulthood and behavioral variability for older adults may
reflect greater functional variability and neural complexity (McIntosh et al., 2008), as well as adaptability (Allaire & Marsiske,
2005).

References
Summary
Extant evidence suggests that there are numerous neural underpinnings of increased IIV in cognitive performance. Increased IIV
may be modulated by changes in gray matter density (e.g., due to
development, lesions, or neurodegeneration), changes in the integrity of white matter (e.g., disconnectivity in associative pathways,
immature or degraded white matter tracts), and neuromodulatory
changes (e.g., age-related dysregulation of dopaminergic neuromodulation). In addition, an emerging literature links IIV to genetic factors. Findings from neuropsychology and neuroscience
alike underscore that increased IIV shares a robust association with
the frontal cortex (e.g., IIV is exacerbated for frontal vs. nonfrontal
lesions, and less efficient patterns of BOLD activation in frontal
regions are linked to increased IIV). In fMRI research, inefficiency
is said to denote excessive activity for a given level of performance, presumably reflecting unfocused or unstable response circuits (MacDonald, Nyberg, & Backman, 2006; Winterer & Weinberger, 2004). These neurobiological underpinnings of increased

Allaire, J. C., & Marsiske, M. (2005). Intraindividual variability may not

always indicate vulnerability in elders cognitive performance. Psychology and Aging, 20, 390 401.
Andres, P., Parmentier, F. B., & Escera, C. (2006). The effect of age on
involuntary capture of attention by irrelevant sounds: A test of the
frontal hypothesis of aging. Neuropsychologia, 44, 2564 2568.
Anstey, K. J. (1999). Sensorimotor and forced expiratory volume as
correlates of speed, accuracy, and variability in reaction time performance in late adulthood. Aging, Neuropsychology, and Cognition, 6,
84 95.
Anstey, K. J., Dear, K., Christensen, H., & Jorm, A. F. (2005). Biomarkers,
health, lifestyle, and demographic variables as correlates of reaction time
performance in early, middle, and late adulthood. Quarterly Journal of
Experimental Psychology Section A, 58, 521.
Anstey, K. J., Mack, H. A., Christensen, H., Li, S.-C., Reglade-Meslin, C.,
Maller, J., . . . Sachdev, P. (2007). Corpus callosum size, reaction time
speed and variability in mild cognitive disorders and in a normative
sample. Neuropsychologia, 45, 19111920.
Backman, L., Nyberg, L., Lindenberger, U., Li, S.-C., & Farde, L. (2006).
The correlative triad among aging, dopamine, and cognition: Current

SPECIAL SECTION: NEURAL UNDERPINNINGS OF IIV

status and future prospects. Neuroscience and Biobehavioral Reviews,
39, 791 897.
Baltes, P. B., Staudinger, U. M., & Lindenberger, U. (1999). Lifespan
psychology: Theory and application to intellectual functioning. Annual
Review of Psychology, 50, 471507.
Barrett, P. T., & Eysenck, H. J. (1994). The relationship between evoked
potential component amplitude, latency, contour length, variability,
zero-crossings, and psychometric intelligence. Personality and Individual Differences, 16, 332.
Bellgrove, M. A., Gill, M., Hawi, Z., Kirley, A., & Robertson, I. H. (2005).
Dissecting the attention deficit hyperactivity disorder (ADHD) phenotype: Sustained attention, response variability and spatial attentional
asymmetries in relation to dopamine transporter (DAT1) genotype.
Neuropsychologia, 43, 18471857.
Bellgrove, M. A., Hester, R., & Garavan, H. (2004). The functional
neuroanatomical correlates of response variability: Evidence from a
response inhibition task. Neuropsychologia, 42, 1910 1916.
Bilder, R. M., Volavka, J., Lachman, H. M., & Grace, A. A. (2004). The
catechol-O- methyltransferase polymorphism: Relations to the tonicphasic dopamine hypothesis and neuropsychiatric phenotypes. Neuropsychopharmacology, 29, 19431961.
Britton, T. C., Meyer, B. U., & Benecke, R. (1991). Variability of cortically
evoked motor responses in multiple sclerosis. Electroencephalography
and Clinical Neurophysiology, 81, 186 194.
Buckner, R. L., Snyder, A. Z., Shannon, B. J., LaRossa, G., Sachs, R.,
Fotenos, A. F., . . . Mintun, M. A. (2005). Molecular, structural, and
functional characterization of Alzheimers disease: Evidence for a relationship between default activity, amyloid, and memory. Journal of
Neuroscience, 25, 7709 7717.
Buckner, R. L., & Vincent, J. L. (2007). Unrest at rest: The importance of
default activity and spontaneous network correlations. NeuroImage, 37,
10911096.
Bunce, D. J., Anstey, K. J., Christensen, H., Dear, K., Wen, W., &
Sachdev, P. (2007). White matter hyper intensities and within-person
variability in community-dwelling adults aged 60 to 64 years. Neuropsychologia, 45, 2009 2015.
Bunce, D. J., MacDonald, S. W. S., & Hultsch, D. F. (2004). Inconsistency
in serial choice responding decision and motor reaction times dissociate
in younger and older adults. Brain and Cognition, 56, 320 327.
Bunce, D. J., Warr, P. B., & Cochrane, T. (1993). Blocks in choice
responding as a function of age and physical fitness. Psychology and
Aging, 8, 26 33.
Burton, C. L., Strauss, E., Hultsch, D. F., Moll, A., & Hunter, M. A.
(2006). Intraindividual variability as a marker of neurological dysfunction: A comparison of Alzheimers disease and Parkinsons disease.
Journal of Clinical and Experimental Neuropsychology, 28, 67 83.
Cabeza, R. (2001). Cognitive neuroscience of aging: Contributions of
functional neuroimaging. Scandinavian Journal of Psychology, 42, 277
286.
Cabeza, R., & Nyberg, L. (2000). Imaging cognition II: An empirical
review of 275 PET and fMRI studies. Journal of Cognitive Neuroscience, 12, 1 47.
Callicott, J. H., Bertolino, A., Mattay, V. S., Langheim, F. J. P., Duyn, J.,
Coppola, R., . . . Weinberger, D. R. (2000). Physiological dysfunction of
the dorsolateral prefrontal cortex in schizophrenia revisited. Cerebral
Cortex, 10, 1078 1092.
Castellanos, F. X., & Tannock, R. (2002). Neuroscience of attention deficit
hyperactivity disorder: The search for endophenotypes. Nature Reviews
Neuroscience, 3, 617 628.
Cattell, R. B. (1957). Personality and motivation: Structure and measurement. New York, NY: World Books.
Cattell, R. B. (1966). The data box: Its ordering of total resources in terms
of possible relational systems. In R. B. Cattell (Ed.), Handbook of

805

multivariate experimental psychology (pp. 67128). Chicago, IL: Rand

McNally.
Cattell, R. B., & Scheier, I. H. (1961). The meaning and measurement of
neuroticism and anxiety. New York, NY: Ronald Press.
Cohen, J. D., Braver, T. S., & Brown, J. W. (2002). Computational
perspectives in dopamine function in prefrontal cortex. Current Opinion
in Neurobiology, 12, 223229.
Cohen, J. D., & Servan-Schreiber, D. (1992). Context, cortex, and dopamine: A connectionist approach to behavior and biology in schizophrenia. Psychological Review, 99, 4577.
Destexhe, A., & Contreras, D. (2006). Neuronal computations with stochastic network states. Science, 314, 8590.
Diesmann, M., Gewaltig, M.-O., & Aertsen, A. (1999, December 2). Stable
propagation of synchronous spiking in cortical neural networks. Nature,
402, 529 533.
Durstewitz, D., Seamans, J. K., & Sejnowski, T. J. (2000). Neurocomputational models of working memory. Nature Neuroscience, 3, 1184
1191.
Fisk, D. W., & Rice, L. (1955). Intra-individual response variability.
Psychological Bulletin, 52, 217250.
Fjell, A. M., Rosquist, H., & Walhovd, K. B. (in press). Instability in the
latency of P3a/P3b brain potentials and cognitive function in aging.
Neurobiology of Aging.
Ford, D. H. (1987). Humans as self-constructing living systems: A
developmental perspective on behavior and personality. Hillsdale,
NJ: Erlbaum.
Fuchs, E., Ayali, A., Robinson, A., Hulata, E., & Ben-Jacob, E. (2007).
Coemergence of regularity and complexity during neural network development. Developmental Neurobiology, 67, 18021814.
Fuentes, K., Hunter, M. A., Strauss, E., & Hultsch, D. F. (2001). Intraindividual variability in cognitive performance in persons with chronic
fatigue syndrome. The Clinical Neuropsychologist, 15, 210 227.
Gazzaniga, M. S., Ivry, R. B., & Mangun, G. R. (2002). Cognitive neuroscience: The biology of the mind (2nd ed.). New York, NY: Norton.
Gogtay, N., Giedd, J. N., Lusk, L., Hayashi, K. M., Greenstein, D.,
Vaituzis, A. C., . . . Thompson, P. M. (2004, May 25). Dynamic mapping of human cortical development during childhood through early
adulthood. Proceedings of the National Academy of Sciences of the
United States of America, 101, 8174 8179.
Goldstein, K. (1939). The organism. New York, NY: American Book.
Grady, C. L., Horwitz, B., Pietrini, P., Mentis, M. J., Ungerleiter, L.,
Rapoport, S. I., & Haxby, J. (1996). The effect of task difficulty on
cerebral blood flow during perceptual matching of faces. Human Brain
Mapping, 4, 227239.
Harry, J. D., Niemi, J. B., Priplata, A. A., & Collins, J. J. (2005, April).
Balancing act: Noise is the key to restoring the bodys sense of equilibrium. IEEE Spectrum, 36 41.
Head, H. (1926). Aphasia and kindred disorders of speech. Cambridge,
England: Cambridge University Press.
Hedden, T., & Gabrieli, J. D. E. (2004). Insights into the ageing mind: A
view from cognitive neuroscience. Nature Reviews Neuroscience, 5,
8797.
Holtzer, R., Verghese, J., Wang, C., Hall, C. B., & Lipton, R. B. (2008).
Within-person acrossneuropsychological test variability and incident
dementia. Journal of the American Medical Association, 300, 823 830.
Hultsch, D. F., & MacDonald, S. W. S. (2004). Intraindividual variability
in performance as a theoretical window onto cognitive aging. In R. A.
Dixon, L. Backman, and L.-G. Nilsson (Eds.), New frontiers in cognitive
aging (pp. 65 88). New York, NY: Oxford University Press.
Hultsch, D. F., MacDonald, S. W. S., & Dixon, R. A. (2002). Variability
in reaction time performance of younger and older adults. Journal of
Gerontology, Series B: Psychological Sciences and social Sciences, 57,
P101P115.
Hultsch, D. F., MacDonald, S. W. S., Hunter, M. A., Levy-Bencheton, J.,

806

MACDONALD, LI, AND BCKMAN

& Strauss, E. (2000). Intraindividual variability in cognitive performance in older adults: Comparison of adults with mild dementia, adults
with arthritis, and healthy adults. Neuropsychology, 14, 588 598.
Hultsch, D. F., Strauss, E., Hunter, M. A., & MacDonald, S. W. S. (2008).
Intraindividual variability, cognition, and aging. In F. I. M. Craik &
T. A. Salthouse (Eds.), The handbook of aging and cognition (3rd ed.,
pp. 491556). New York, NY: Psychology Press.
Huxhold, O., Li, S.-C., Schmiedek, F., & Lindenberger, U. (2006). Dualtasking postural control: Aging and the effect of cognitive demand in
conjunction with focus of attention. Brain Research Bulletin, 69, 294
305.
Johansson, R. S., & Birznieks, I. (2004). First spikes in ensembles of
human tactile afferents code complex spatial fingertip events. Nature
Neuroscience, 7, 170 177.
Kelly, C. A. M., Uddin, L. Q., Biswal, B. B., Castellanos, F. X., & Milham,
M. P. (2008). Competition between functional brain networks mediates
behavioral variability. NeuroImage, 39, 527537.
Kray, J., Eber, J., & Lindenberger, U. (2004). Age differences in executive
functioning across the lifespan: The role of verbalization in task preparation. Acta Psychologica, 115, 143165.
Kugler, C. F. A., Taghavy, A., & Platt, D. (1993). The event-related P300
potential analysis of cognitive human brain aging: A review. Gerontology, 39, 280 303.
Landau, S. M., Lal, R., ONeill, J. P., Baker, S., & Jagust, W. J. (2009).
Striatal dopamine and working memory. Cerebral Cortex, 19, 445 454.
Li, S.-C., Aggen, S. H., Nesselroade, J. R., & Baltes, P. B. (2001).
Short-term fluctuations in elderly peoples sensorimotor functioning
predict text and spatial memory performance: The MacArthur successful
aging studies. Gerontology, 47, 100 116.
Li, S.-C., Hammerer, D., Muller, V., Hommel, B., & Lindenberger, U.
(2009). Lifespan development of stimulus-response conflict cost: Similarities and differences between maturation and senescence. Psychological Research, 73, 777785.
Li, S.-C., Huxhold, O., & Schmiedek, F. (2004). Aging and processing
robustness: Evidence from cognitive and sensorimotor functioning. Gerontology, 50, 28 34.
Li, S.-C., Lindenberger, U., Hommel, B., Aschersleben, G., Prinz, W., &
Baltes, P. B. (2004). Lifespan transformations in the couplings of mental
abilities and underlying cognitive processes. Psychological Science, 15,
155163.
Li, S.-C., Lindenberger, U., Nyberg, L., Heekeren, H. R., & Backman, L.
(in press). Dopaminergic modulation of cognition in human aging. In W.
Jagust & M. DEsposito (Eds.), Imaging the aging brain. New York,
NY: Oxford University Press.
Li, S.-C., Lindenberger, U., & Sikstrom, S. (2001). Aging cognition: From
neuromodulation to representation. Trends in Cognitive Sciences, 5,
479 486.
Li, S.-C., & Sikstrom, S. (2002). Integrative neurocomputational perspectives on cognitive aging, neuromodulation, and representation. Neuroscience and Biobehavioral Reviews, 26, 795 808.
Li, S.-C., von Oertzen, T., & Lindenberger, U. (2006). A neurocomputational model of stochastic resonance and aging. Neurocomputing, 69,
15531560.
Liang, M., Zhou, Y., Jiang, T., Liu, Z., Tian, L., Liu, H., & Hao, Y. (2006).
Widespread functional disconnectivity in schizophrenia with resting
state functional magnetic resonance imaging. NeuroReport, 17, 209
213.
Lindenberger, U., & von Oertzen, T. (2006). Variability in cognitive aging:
From taxonomy to theory. In F. I. M. Craik & E. Bialystok (Eds.),
Lifespan cognition: Mechanisms of change (pp. 297314) Oxford: Oxford University Press.
Logan, J. M., Sanders, A. L., Snyder, A. Z., Morris, J. C., & Buckner, R. L.
(2002). Under-recruitment and non-selective recruitment: Dissociable
neural mechanisms associated with aging. Neuron, 33, 827 840.

Lovden, M., Li, S.-C., Shing, Y. L., & Lindenberger, U. (2007). Withinperson trial-by-trial variability precedes and predicts cognitive decline in
old and very old age: Longitudinal data from the Berlin Aging Study.
Neuropsychologia, 45, 28272838.
Luszcz, M. A. (2004). Whats it all about: Variation and aging. Gerontology, 50, 5 6.
MacDonald, S. W. S., Cervenka, S., Farde, L., Nyberg, L., & Backman, L.
(2009). Extrastriatal dopamine D2 receptor binding modulates intraindividual variability in episodic memory and executive functioning. Neuropsychologia, 47, 2299 2304.
MacDonald, S. W. S., Hultsch, D. F., & Bunce, D. (2006). Intraindividual
variability in vigilance performance: Does degrading visual stimuli
mimic age-related neural noise? Journal of Clinical and Experimental
Neuropsychology, 28, 655 675.
MacDonald, S. W. S., Hultsch, D. F., & Dixon, R. A. (2003). Performance
variability is related to change in cognition: Evidence from the Victoria
Longitudinal Study. Psychology and Aging, 18, 510 523.
MacDonald, S. W. S., Hultsch, D. F., & Dixon, R. A. (2008). Predicting
impending death: Inconsistency in speed is a selective and early marker.
Psychology and Aging, 23, 595 607.
MacDonald, S. W. S., Nyberg, L., & Backman, L. (2006). Intra-individual
variability in behavior: Links to brain structure, neurotransmission and
neuronal activity. Trends in Neurosciences, 29, 475 480.
MacDonald, S. W. S., Nyberg, L., Sandblom, J., Fischer, H., & Backman,
L. (2008). Increased response-time variability is associated with reduced
inferior parietal activation in recognition memory in aging. Journal of
Cognitive Neuroscience, 20, 779 786.
Manoach, D. S. (2003). Prefrontal cortex dysfunction during working
memory performance in schizophrenia: Reconciling discrepant findings.
Schizophrenia Research, 60, 285298.
Martin, M., & Hofer, S. M. (2004). Intraindividual variability, change, and
aging: Conceptual and analytical issues. Gerontology, 50, 711.
Mattay, V. S., Goldberg, T. E., Fera, F., Hariri, A. R., Tessitore, A.,
Egan, M. F., . . . Weinberger, D. (2003, May 13). Catechol
O-methyltransferase val158 met genotype and individual variation in
the brain response to amphetamine. Proceedings of the National Academy of Sciences of the United States of America, 100, 6186 6191.
McIntosh, A. R., Kovacevic, N., & Itier, R. J. (2008). Increased brain
signal variability accompanies lower behavioral variability in development. PLoS Computational Biology, 4, 19.
Montague, P. R., Hyman, S. E., & Cohen, J. D. (2004, October 14).
Computational roles for dopamine in behavioural control. Nature, 431,
760 767.
Moss, F., Ward, L. M., & Sannita, W. G. (2004). Stochastic resonance and
sensory information processing: A tutorial and review of application.
Clinical Neurophysiology, 115, 267281.
Murtha, S., Cismaru, R., Waechter, R., & Chertkow, H. (2002). Increased
variability accompanies frontal lobe damage in dementia. Journal of the
International Neuropsychological Society, 8, 360 372.
Nesselroade, J. R. (1991). The warp and woof of the developmental fabric.
In R. Downs, L. Liben, & D. S. Palermo (Eds.), Visions of aesthetics, the
environment, and development: The legacy of Joachim F. Wohlwill (pp.
213240). Hillsdale, NJ: Erlbaum.
Nesselroade, J. R. (2002). Elaborating the different in differential psychology. Multivariate Behavioral Research, 37, 543561.
Nesselroade, J. R., & Salthouse, T. A. (2004). Methodological and theoretical implications of intraindividual variability in perceptual-motor
performance. Journal of Gerontology, Series B: Psychological Sciences
and Social Sciences, 59, P49 P55.
Nyberg, L., Andersson, M., Forsgren, L., Jakobsson-Mo, S., Larsson, A.,
Marklund, P., . . . Backman, L. (2009). Striatal dopamine D2 binding is
related to frontal BOLD response during updating of long-term memory
representations. NeuroImage, 46, 1194 1199.
Nyberg, L., Sandblom, J., Jones, S., Neely, A. S., Petersson, K. M., Ingvar,

SPECIAL SECTION: NEURAL UNDERPINNINGS OF IIV

M., & Backman, L. (2003, November 11). Neural correlates of trainingrelated memory improvement in adulthood and aging. Proceedings of
the National Academy of Sciences of the United States of America, 100,
13728 13733.
OReilly, R. C., & Frank, M. J. (2006). Making working memory work: A
computational model of learning in the prefrontal cortex and basal
ganglia. Neural Computation, 18, 283328.
Pfefferbaum, A., Rosenbloom, M., Serventi, K. L., & Sullivan, E. V.
(2002). Corpus callosum, pons, and cortical white matter in alcoholic
women. Alcoholism: Clinical & Experimental Research, 26, 400 406.
Priplata, A., Niemi, J., Salen, M., Harry, J., Lipsitz, L. A., & Collins, J. J.
(2002). Noise-enhanced human balance control. Physical Review Letters, 89, 238101.
Rabbitt, P., Osman, P., Moore, B., & Stollery, B. (2001). There are stable
individual differences in performance variability, both from moment to
moment and from day to day. Quarterly Journal of Experimental Psychology Section A, 54, 9811003.
Raichle, M. E., MacLeod, A. M., Snyder, A. Z., Powers, W. J., Gusnard,
D. A., & Shulman, G. L. (2001, January 16). A default mode of brain
function. Proceedings of the National Academy of Sciences of the United
States of America, 98, 676 682.
Ram, N., Rabbitt, P., Stollery, B., & Nesselroade, J. R. (2005). Cognitive
performance inconsistency: Intraindividual change and variability. Psychology and Aging, 20, 623 633.
Ratcliff, R., Van Zandt, T., & McKoon, G. (1999). Connectionist and
diffusion models of reaction time. Psychological Review, 106, 261300.
Raz, N., Gunning-Dixon, F. M., Head, D., Dupuis, J. H., & Acker, J. D.
(1998). Neuroanatomical correlates of cognitive aging: Evidence from
structural magnetic resonance imaging. Neuropsychology, 12, 95114.
Raz, N., Gunning-Dixon, F. M, Head, D., Rodrigue, K. M., Williamson,
A., & Acker, J. D. (2004). Aging, sexual dimorphism, and hemispheric
asymmetry of the cerebral cortex: Replicability of regional differences in
volume. Neurobiology of Aging, 25, 377396.
Rocke, C., Li, S.-C., & Smith, J. (in press). Intraindividual variability in
positive and negative affect over 45 days: Do older adults fluctuate less
than young adults? Psychology and Aging.
Rolls, E. T., Loh, M., Deco, G., & Winterer, G. (2008). Computational
models of schizophrenia and dopamine modulation in the prefrontal
cortex. Nature Reviews Neuroscience, 9, 696 709.
Salthouse, T. A. (2007). Implications of within-person variability in cognitive and neuropsychological functioning on the interpretation of
change. Neuropsychology, 21, 401 411.
Schmiedek, F. (2006, April). The dark side of the mean: Plenary on
intraindividual variability. Paper presented at the 11th biennial Cognitive Aging Conference, Atlanta, GA.
Schott, B. H., Minuzzi, L., Krebs, R. M., Elmenhorst, D., Lang, M., Winz,
O. H., . . . Bauer, A. (2008). Mesolimbic functional magnetic resonance
imaging activations during reward anticipation correlate with rewardrelated ventral striatal dopamine release. Journal of Neuroscience, 28,
1431114319.
Seamans, J. K., & Yang, C. R. (2004). The principal features and mechanisms of dopamine modulation in the prefrontal cortex. Progress in
Neurobiology, 74, 158.
Shannon, B. J., & Buckner, R. L. (2004). Functionalanatomic correlates
of memory retrieval that suggest nontraditional processing roles for
multiple distinct regions within posterior parietal cortex. Journal of
Neuroscience, 24, 10084 10092.
Shipley, B. A., Der, G., Taylor, M. D., & Deary, I. J. (2006). Cognition and
all-cause mortality across the entire adult age range: Health and lifestyle
survey. Psychosomatic Medicine, 68, 1724.
Siegler, R. S. (1994). Cognitive variability: A key to understanding cognitive development. Current Directions in Psychological Science,
3, 15.
Sowell, E. R., Peterson, B. S., Thompson, P. M., Welcome, S. E., Henkenius,

807

A. L., & Toga, A. W. (2003). Mapping cortical change across the human life
span. Nature Neuroscience, 6, 309 315.
Stefanis, N. C., van Os, J., Avramopoulos, D., Smyrnis, N., Evdokimidis,
I., & Stefanis, C. N. (2005). Effect of COMT Val158Met polymorphism
on the continuous performance test, identical pairs version: Tuning
rather than improving performance. American Journal of Psychiatry,
162, 17521754.
Stein, R. B., Gossen, E. R., & Jones, K. E. (2005). Neuronal variability:
Noise or part of the signal? Nature Reviews Neuroscience, 6, 389 397.
Stern, Y. (2002). What is cognitive reserve? Theory and research application of the reserve concept. Journal of the International Neuropsychological Society, 8, 448 460.
Stern, Y., Zarahn, E., Hilton, H. J., Flynn, J., DeLaPaz, R., & Rakitin, B.
(2003). Exploring the neural basis of cognitive reserve. Journal of
Clinical and Experimental Neuropsychology, 25, 691701.
Strauss, E., MacDonald, S. W. S., Hunter, M. A., Moll, A., & Hultsch,
D. F. (2002). Intraindividual variability in cognitive performance in
three groups of adults: Cross-domain links to physical status and selfperceived affect and beliefs. Journal of the International Neuropsychology Society, 8, 893906.
Stuss, D. T., & Binns, M. A. (2008). The patient as a moving target: The
importance to rehabilitation of understanding variability. In D. T. Stuss,
G. Winocur, & I. H. Robertson (Eds.), Cognitive neurorehabilitation:
Evidence and application (2nd ed., pp. 36 61). Cambridge, England:
Cambridge University Press.
Stuss, D. T., Murphy, K. J., Binns, M. A., & Alexander, M. P. (2003).
Staying on the job: The frontal lobes control individual performance
variability. Brain, 126, 23632380.
Sutton, S. (1969). The specification of psychological variables in an
average evoked potential experiment. In E. Donchin and D. B. Lindsley
(Eds.), Average evoked potentials: Methods, results and evaluations
(NASA SP-191, pp. 237262). Washington, DC: U.S. Government
Printing Office.
Takahashi, H., Kato, M., Hayashi, M., Okubo, Y., Takano, A., Ito, H., &
Suhara, T. (2007). Memory and frontal lobe functions; possible relations
with dopamine D2 receptors in the hippocampus. NeuroImage, 34,
16431649.
Tian, L., Jiang, T., Wang, Y., Zang, Y., He, Y., Liang, M., . . . Zhuo, Y.
(2006). Altered resting-state functional connectivity patterns of anterior
cingulate cortex in adolescents with attention deficit hyperactivity disorder. Neuroscience Letters, 400, 39 43.
Wagner, A. D., Shannon, B. J., Kahn, I., & Buckner, R. L. (2005). Parietal
lobe contributions to episodic memory retrieval. Trends in Cognitive
Sciences, 9, 445 453.
Walhovd, K. B., & Fjell, A. M. (2007). White matter volume predicts
reaction time instability. Neuropsychologia, 45, 22772284.
Weinshilboum, R. M., Otterness, D. M., & Szumlanski, C. L. (1999).
Methylation pharmacogenetics: Catechol O-methyltransferase, thiopurine methyltransferase, and histamine N-methyltranferase. Annual
Review of Pharmacology and Toxicology, 39, 19 52.
Weissman, D. H., Roberts, K. C., Visscher, K. M., & Woldorff, M. G.
(2006). The neural bases of momentary lapses in attention. Nature
Neuroscience, 9, 971978.
West, R., Murphy, K. J., Armilio, M. L., Craik, F. I. M., & Stuss, D. T.
(2002). Lapses of intention and performance variability reveal agerelated increases in fluctuations of executive control. Brain and Cognition, 49, 402 419.
Williams, B. R., Hultsch, D. F., Strauss, E., Hunter, M. A., & Tannock, R.
(2005). Inconsistency in reaction time across the lifespan. Neuropsychology, 19, 88 96.
Williams, B. R., Strauss, E., Hultsch, D. F., & Hunter, M. A. (2007).
Reaction time inconsistency in a spatial Stroop task: Age-related differences through childhood and adulthood. Aging, Neuropsychology, and
Cognition, 14, 417 439.

MACDONALD, LI, AND BCKMAN

808

Winterer, G., Coppola, R., Goldberg, T. E., Egan, M. F., Jones, D. W.,
Sanchez, C. E., & Weinberger, D. R. (2004). Prefrontal broadband noise,
working memory, and genetic risk for schizophrenia. American Journal
of Psychiatry, 161, 490 500.
Winterer, G., & Weinberger, D. R. (2004). Genes, dopamine, and cortical signalto-noise ratio in schizophrenia. Trends in Neurosciences, 27, 683690.
Wohlwill, J. F. (1973). The study of behavioral development. New York,
NY: Academic Press.

Yamaguchi, S., Hale, L. A., DEsposito, M., & Knight, R. T. (2004). Rapid
prefrontal hippocampal habituation to novel events. Journal of Neuroscience, 24, 5356 5363.

Received November 7, 2008

Revision received August 24, 2009
Accepted September 25, 2009

Call for Nominations

The Publications and Communications (P&C) Board of the American Psychological Association
has opened nominations for the editorships of Experimental and Clinical Psychopharmacology,
Journal of Abnormal Psychology, Journal of Comparative Psychology, Journal of Counseling
Psychology, Journal of Experimental Psychology: General, Journal of Experimental Psychology: Human Perception and Performance, Journal of Personality and Social Psychology:
Attitudes and Social Cognition, PsycCRITIQUES, and Rehabilitation Psychology for the years
20122017. Nancy K. Mello, PhD, David Watson, PhD, Gordon M. Burghardt, PhD, Brent S.
Mallinckrodt, PhD, Fernanda Ferreira, PhD, Glyn W. Humphreys, PhD, Charles M. Judd, PhD,
Danny Wedding, PhD, and Timothy R. Elliott, PhD, respectively, are the incumbent editors.
Candidates should be members of APA and should be available to start receiving manuscripts in
early 2011 to prepare for issues published in 2012. Please note that the P&C Board encourages
participation by members of underrepresented groups in the publication process and would particularly welcome such nominees. Self-nominations are also encouraged.
Search chairs have been appointed as follows:

Experimental and Clinical Psychopharmacology, William Howell, PhD

Journal of Abnormal Psychology, Norman Abeles, PhD
Journal of Comparative Psychology, John Disterhoft, PhD
Journal of Counseling Psychology, Neil Schmitt, PhD
Journal of Experimental Psychology: General, Peter Ornstein, PhD
Journal of Experimental Psychology: Human Perception and Performance,
Leah Light, PhD
Journal of Personality and Social Psychology: Attitudes and Social Cognition,
Jennifer Crocker, PhD
PsycCRITIQUES, Valerie Reyna, PhD
Rehabilitation Psychology, Bob Frank, PhD

Candidates should be nominated by accessing APAs EditorQuest site on the Web. Using your
Web browser, go to http://editorquest.apa.org. On the Home menu on the left, find Guests. Next,
click on the link Submit a Nomination, enter your nominees information, and click Submit.
Prepared statements of one page or less in support of a nominee can also be submitted by e-mail
to Emnet Tesfaye, P&C Board Search Liaison, at emnet@apa.org.
Deadline for accepting nominations is January 10, 2010, when reviews will begin.