Development and Psychopathology 17 ~2005!

, 1197–1206
Copyright © 2005 Cambridge University Press
Printed in the United States of America
DOI: 10.10170S095457940505056X

Defining the neurocircuitry of borderline

personality disorder: Functional
neuroimaging approaches

GARY R. BRENDEL, EMILY STERN, and DAVID A. SILBERSWEIG

Weill Medical College of Cornell University

Abstract
Functional neuroimaging recently has been used to localize brain dysfunction in borderline personality disorder
~BPD!. Initial studies have examined baseline activity or emotional reactivity, and our group has investigated what
we consider to be a crucial interaction between negative emotion and behavioral ~dys!control. This research is
beginning to identify abnormal frontolimbic circuitry likely underlying core clinical features of this condition. We
review the evidence for dysfunction in specific frontolimbic regions, leading to a mechanistic model of symptom
formation in BPD. In addition, we offer an integration of these neuroimaging findings with developmental
perspectives on the emergence of borderline psychopathology, focusing on the ways in which early psychosocial
experience may interact with developing brain systems. We also consider possible mechanisms of psychotherapeutic
change at the neural systems level in BPD. Finally, we propose that future neuroimaging studies of BPD should
integrate multiple levels of observation ~structural, functional, neurochemical, genetic, and clinical! in a
model-driven fashion to further understand the dynamic relationship between biological and psychological factors in
the development and treatment of this difficult condition.

Using a variety of imaging technologies and Initially focused on the investigation of

methodologies, neuroimaging investigations
are shedding light on brain structure and func-
tion in both normal and pathological states
including psychotic, mood, anxiety, and de-
velopmental disorders ~Dougherty & Rauch,
2001; Stern & Silbersweig, 2001!. These var-
ied approaches include using structural neuro-
imaging, positron emission tomography ~PET!,
and functional magnetic resonance imaging
~f MRI! in the setting of symptom provoca-
tion studies, cognitive activation paradigms,
and resting state studies. By defining the dys-
functional neural circuitry in individuals with
these conditions, neuroimaging studies pro-
vide the possibility of enhanced diagnostic
specificity, novel targets for therapeutic inter-
ventions, and more reliable predictors of treat-
ment response.
Address correspondence and reprint requests to: Gary R.
Brendel, 295 Central Park West, Suite 2, New York, NY
10024; E-mail: grbrendel@verizon.net.
Axis I disorders, psychiatric neuroimaging re-
searchers are beginning to study the functional
neuroanatomy of Axis II disorders, including
borderline personality disorder ~BPD!. BPD is
a complex psychiatric disorder characterized
by affect dysregulation and behavioral impul-
sivity. Individuals with this condition experi-
ence rapid alterations of mood and intense
emotional responses, as well as impulsive, po-
tentially self-destructive behaviors ~substance
abuse, self-mutilations, suicidal behaviors, binge
eating, sexual promiscuity!. Focusing on these
domains of emotion and behavior, neuroimag-
ing studies have begun to elucidate the neural
correlates of this disorder.
Functional neuroimaging studies using cog-
nitive activation paradigms in which subjects
are presented with emotional stimuli have be-
gun to examine neural dysfunctions associated
with emotional reactivity in individuals with
BPD.An fMRI study using negative versus neu-
tral valenced images showed activations in bi-
lateral amygdala, bilateral fusiform gyri, left

1197
1198
medial prefrontal ~Brodmann area @BA# 10!,
and right ventrolateral prefrontal ~BA 47! cor-
tices in BPD subjects compared with normal
controls ~Herpertz et al., 2001!. In another fMRI
study, investigators found greater activation in
the left amygdala in response to facial expres-
sions of emotion ~happy, sad, fearful! in BPD
patients versus normal control subjects ~Done-
gan et al., 2003!. A PET study by Schmahl, El-
zinga, et al. ~2003!, in which subjects listened
to personalized scripts of abandonment expe-
riences, found increased activity in bilateral dor-
solateral prefrontal cortex ~DLPFC; BAs 8, 9,
10! and decreased activity in right dorsal ante-
rior cingulate ~BAs 24, 32!, left superior0middle
temporal gyri, left fusiform gyrus ~BA 37!, left
visual association cortex ~BA 19!, and right
amygdala0hippocampus in BPD subjects com-
pared with non-BPD subjects who had compa-
rable sexual abuse histories. Although the
direction of change in neural activation be-
tween BPD subjects and controls varies in these
studies, probably related to the specific meth-
odologies used, these results nonetheless sup-
port the broad notion of dysfunction in limbic
and prefrontal regions in this disorder. In ad-
dition, frontolimbic ~amygdala0hippocampus,
orbitofrontal cortex @OFC#! volume loss ~Rusch
et al., 2003; Schmahl, Vermetten, Elzinga, &
Bremner, 2003; Tebartz van Elst et al., 2003!
provides further evidence of dysfunction in these
regions, and suggests an underlying neuropath-
ological correlate in BPD in regions that can be
associated with the symptomatology of this
disorder.
@ 18 F#Fluorodeoxyglucose PET ~FDG-PET!
imaging studies of BPD subjects consistently
have demonstrated evidence of frontal dys-
function, most prominent in the prefrontal cor-
tical areas ~De la Fuente et al., 1997; Juengling
et al., 2003; Soloff, Meltzer, Greer, Constan-
tine, & Kelly, 2000!. Metabolic challenge
FDG-PET neuroimaging studies using fenflur-
amine, a serotonergic agonist, have found
blunted neural responses in a variety of re-
gions including medial, orbital, dorsolateral,
and ventromedial prefrontal cortices, as well
as in anterior cingulate cortex in BPD sub-
jects ~Siever et al., 1999; Soloff et al., 2000!.
Overall, these studies support the hypothesis
that diminished serotonergic function in PFC,
G. R. Brendel, E. Stern, and D. A. Silbersweig
a region with neurotransmitter and neuroana-
tomical systems known to be involved in emo-
tional regulation and inhibitory behavioral
control, may constitute a biologic diathesis
for disinhibition, impulsivity, and affect dys-
regulation in individuals with BPD.
Using PET with a-@ 11 C#methyl-l-trypto-
phan ~a-MTrp, an l-tryptophan analog! to as-
sess brain serotonin ~5-HT! synthesis capacity,
Leyton et al. ~2001! found significantly lower
a-MTrp trapping in male BPD subjects com-
pared with healthy controls in bilateral medial
frontal cortices extending into the OFC, bilat-
eral anterior cingulate cortex, left superior tem-
poral gyrus ~BA 22!, bilateral fusiform gyri
~BAs 19, 37!, left globus pallidum, and the
right hippocampal formation ~BA 35!. Corre-
lational analysis between a-MTrp trapping and
commission error rates on a Go0No-Go Task
revealed significant negative correlations in
the medial frontal gyrus, anterior cingulate
cortex, and striatum in both male and female
BPD subjects. Because these areas are in-
volved in mediating the planning, initiation,
and inhibition of behavior, low 5-HT synthe-
sis capacity in these regions in individuals
with BPD may contribute to the behavioral
disinhibition characteristic of this patient pop-
ulation. Likewise, a preliminary f MRI study
of response inhibition in patients with BPD
and antisocial personality disorder has found
that such individuals activate different neural
networks than normal controls to inhibit pre-
potent responses ~Vollm et al., 2004!, perhaps
a compensatory system resulting from deficits
in the normal prefrontal inhibitory circuits.
FDG-PET resting state studies comparing
BPD subjects to normal controls have demon-
strated significantly reduced activity in a num-
ber of cortical and subcortical regions including
the bilateral medial OFC ~Soloff et al., 2003!,
temporoparietal cortices ~Lange, Kracht, Her-
holz, Sachsse, & Irle, 2005!, as well as the right
premotor ~BA 6!, bilateral PFC ~BA 9!, mesial
and anterior PFC ~BAs 10, 32, 46!, bilateral
anterior cingulate cortex ~BA 25!, right ventral
striatum, bilateral thalamus, and bilateral cau-
date ~De la Fuente et al., 1997!. These findings
suggest dysfunction in a cortical–striatal–
thalamic–frontal network that normally sub-
serves important behavioral control functions.
Neuroimaging of BPD
Frontolimbic Circuitry in BPD
Prefrontal and limbic neural systems mediate
both the processing of and responses to emo-
tional stimuli ~Phillips, Drevets, Rauch, &
Lane, 2003!, and therefore dysfunction in these
circuits could mediate a number of core symp-
toms of BPD ~Figure 1!. Orbitofrontal dysfunc-
tion may underlie the impulsivity, aggression,
and mood instability seen in BPD because le-
sions of this region have been linked with such
behaviors in both animals and humans ~Mega
& Cummings, 1994!. Neurobehavioral studies
in animals suggest that an interplay between
PFC, particularly the OFC, and the amygdala
is important for affective style in humans
~Davidson, 2002!. In fact, extensive reciprocal
connections between the OFC and the amyg-
dala are well known, and these regions func-
tion as part of an integrated neural system
guiding socioemotional decision making and
adaptive response selection ~Baxter, Parker,
Lindner, Izquierdo, & Murray, 2000!.
Amygdala dysfunction has been impli-
cated in playing an important role in the
development of BPD because this limbic
structure is known to be involved in the pro-
cessing of negative valence stimuli, the estab-
lishment of fear conditioning, the production
of strong negative emotional states, and vig-
ilance for environmental stimuli with im-
portant survival value ~Davis & Whalen,
2001; Isenberg et al., 1999; LeDoux, 1996!.
Findings of amygdala dysfunction in the
above-mentioned f MRI studies likely reflect
abnormal processing of aversive paradigm
stimuli and0or the activation of emotional
memories induced by such stimuli ~Breiter,
Rauch, et al., 1996!. Furthermore, increased
amygdala activation in BPD subjects may re-
flect an oversensitization to aversive emo-
tional stimuli or a relative failure of normal
habituation. A strong habituation of the BOLD
f MRI signal in response to emotional stimuli
has been observed in normal controls ~Breiter,
Etcoff, et al., 1996; LaBar, Gatenby, Gore,
LeDoux, & Phelps, 1998!, and may be dys-
functional in BPD individuals with long-
lasting, intense emotional reactions.
Hippocampal dysfunction is not surprising
as well, given the susceptibility of this neural
1199
structure to stress in the setting of increased
cortisol and excitatory amino acids ~McEwen
& Magariños, 2001! and the prevalence of
early traumatization experienced by those with
BPD ~Zanarini, 2000!. Hippocampal volumes
in individuals with BPD have been negatively
correlated with the extent and duration of
self-reported traumatic experiences, suggest-
ing the presence of stress-induced structural
changes in this disorder ~Driessen et al., 2000!.
Because the hippocampus mediates fear re-
sponses to contextual features of the environ-
ment ~Phillips & LeDoux, 1992!, dysfunction
of this structure may result in a maladaptive
overgeneralization of fear responses ~e.g., fear
of abandonment! to a broad range of interper-
sonal situations as observed in those with BPD.
Activation of fusiform gyrus ~BA 37!, a
region implicated in complex visual feature
detection and recognition of facial expression
~George et al., 1993!, could be due to back-
projections from the amygdala for the purpose
of strengthening visual attention to emotion-
ally relevant stimuli, a finding consistent with
the hypervigilance for emotional aspects of
the environment seen in individuals with BPD.
Additional evidence for an emotion-based at-
tentional bias in BPD is provided by Arntz,
Appels, and Sieswerda’s ~2000! emotional
Stroop study in which BPD subjects had lon-
ger response times than normal controls to
negative versus neutral valence words. Inter-
estingly, this finding was not specific to words
reflecting BPD themes, but rather seemed to
reflect a more general hypervigilance for all
negative valence stimuli.
Dysfunction in medial prefrontal areas, in
particular anterior cingulate cortex, a region in-
volved in emotional regulation and with im-
portant inhibitory connections to the amygdala
that mediate the extinction of fear responses
~Carmichael & Price, 1995; Devinsky, Mor-
rell, & Vogt, 1995!, might underlie the diffi-
culty modulating anxiety and other intense
affects seen in individuals with BPD. Medial
PFC lesions in humans result in emotional dys-
function and deficits in interpersonal function-
ing that requires the correct interpretation of
the emotional expressions of others ~Damasio,
Grabowski, Frank, Galaburda, & Damasio,
1994!.Although normal individuals tend to have
1200
increased activity in the anterior cingulate dur-
ing the induction of angry affect states ~Dough-
erty et al., 1999; Kimbrell et al., 1999!, perhaps
reflecting adaptive modulating functions, in-
dividuals with BPD have been shown to have
decreased function of ~De La Fuente et al., 1997;
Goyer et al., 1994! and reduced gray matter vol-
ume in ~Hazlett et al., in press! this area. In
addition, anterior cingulate cortex recently has
been implicated in the processing of the sen-
sory and affective dimensions of pain ~Hof-
bauer, Rainville, Duncan, & Bushnell, 2001;
Olausson et al., 2001!, and diminished activity
in this region may account for the significantly
attenuated pain perception among individuals
with BPD and self-injurious behaviors ~Bohus
et al., 2000!.
Abnormal activity of ventrolateral PFC
~Herpertz et al., 2001!, with its direct connec-
tions with the basal nucleus of the amygdala,
could result in compromised inhibition of
amygdala-driven emotional responses thereby
undermining top-down control of this limbic
region in BPD ~Drevets, 1999!. Activation of
DLPFC ~Schmahl, Elzinga, et al., 2003! has
been observed in prior imaging studies using
personalized scripts in women with abuse-
related posttraumatic stress disorder ~PTSD;
Bremner et al., 1999; Shin et al., 1999!, pos-
sibly reflecting the role of this prefrontal re-
gion in the encoding and retrieval of verbal
memories ~Tulving, Kapur, Craik, Mosco-
vitch, & Houle, 1994! and0or its emerging
role in aspects of emotional processing
~Davidson, Jackson, & Kalin, 2000! and
emotional–cognitive interactions ~Liotti &
Mayberg, 2001; Sergerie, Lepage, & Armony,
2005!. Additional evidence of DLPFC dys-
function comes from Tebartz van Elst et al.’s
~2001! proton magnetic resonance spectros-
copy study demonstrating subtle prefrontal
neuropathology as indicated by reduced
N-acetylaspartate concentrations in this pre-
frontal region in individuals with BPD.
Interaction of Emotion and Behavior
in BPD
As summarized above, functional neuroimag-
ing studies have investigated the neural sys-
tems underlying emotional dysregulation in
G. R. Brendel, E. Stern, and D. A. Silbersweig
BPD using a variety of neuropsychological
probes. Numerous other imaging studies with
normal subjects and various patient popula-
tions have examined the neural basis of emo-
tion and behavior, but rarely the interaction
between these two domains. Our lab has de-
veloped an emotional Go0No-Go f MRI para-
digm to specifically investigate the functional
neuroanatomy underlying the interaction of
emotion and inhibitory behavioral control in
both normals and individuals with BPD. We
believe that this important interaction has rel-
evance to a wide range of human experience
and behavior in health and disease. The BPD
work is being performed in collaboration with
Dr. Otto Kernberg’s research group at the Per-
sonality Disorders Institute of the Weill
Medical College of Cornell University. This
approach can shed light on the neural circuits
underlying the clinically observed phenom-
enon of behavioral impulsivity in the context
of intense negative affect states so commonly
seen in this patient population. The method-
ological approach of using neuropsychologi-
cal probes that conjoin emotional stimuli with
nonemotional behavioral task demands is an
emerging line of investigation within the
cognitive neurosciences to further investigate
important interactions between emotion, cog-
nition, and behavior ~Dolan, 2002; Elliott,
Rubinsztein, Sahakian, & Dolan, 2002!.
Our f MRI paradigm is a variation on the
classic Go0No-Go Task ~Drewe, 1975! used
extensively in investigational neuropsychol-
ogy to probe response inhibition, and involves
the execution or inhibition of a prepotent mo-
tor response triggered by a go or no-go stim-
ulus, respectively. Our subjects are instructed
to execute or inhibit a response to visually
presented emotional stimuli. By experimen-
tally manipulating the emotional valence of
these stimuli that reflect themes salient for
individuals with BPD, we are able to investi-
gate the modulation of behavioral task de-
mand ~go or no-go! by emotional valence,
thereby probing the neural systems subserv-
ing the interaction of emotion and behavioral
control in this population.
We have hypothesized and detected dys-
function in medial OFC in individuals with
BPD while performing this emotional Go0
1201

Figure 1. Frontotemporo–limbic and subcortical brain regions relevant to neural models of BPD. Selected functional affiliations of
these regions ~see text! are briefly noted.
1202
No-Go Task, a finding consistent with this
region’s presumed role in regulating behavior
under changing contingencies and its role in
guiding adaptive behavioral responses within
socioemotional contexts ~Damasio et al., 1994;
Elliott et al., 2002; Rolls, 2000!. Specifically,
we have hypothesized differential neural ac-
tivity in this region in BPD subjects compared
with normals, reflecting the former’s greater
difficulty modulating behavioral responses un-
der conditions of negative emotion.
Medial OFC is believed to process viscero-
somatic afferent information as cues reflecting
the personal relevance of environmental con-
texts, and to integrate such emotional informa-
tion into decision making and response selection
~Bechara, Damasio, & Damasio, 2000; Dolan,
1999!. According to Damasio’s somatic marker
hypothesis ~1994!, dysfunction of medial OFC
results in an impaired capacity to adaptively
integrate emotional information into behav-
ioral response selection. This may have partic-
ular relevance for individuals with BPD who,
while experiencing intense negative affect states,
have greater difficulty regulating behavioral re-
sponses. In addition, medial OFC appears to be
involved in the suppression of context-activated
emotional memories irrelevant to current
cognitive0behavioral demands ~Treyer, Buck,
& Schnider, 2003!, thereby allowing for more
adaptive responses to the immediate environ-
ment. Individuals with BPD, however, seem to
respond in characteristically inflexible and mal-
adaptive ways based not upon current social
contexts, but rather according to implicit emo-
tional memories of past interpersonal experi-
ences, possibly reflecting OFC dysfunction.
Integration With Developmental
Perspectives
Evidence of dysfunction in limbic and prefron-
tal neural systems subserving affect regula-
tion and behavioral control is consistent with
developmental theories of BPD. Clarkin, Yeo-
mans, and Kernberg’s ~1999! psychoanalytic
developmental theory of BPD posits both con-
stitutional ~i.e., neurobiologic! and early envi-
ronmental factors giving rise to a psychic
structure populated by distorted, unidimen-
sional mental representations of self and oth-
G. R. Brendel, E. Stern, and D. A. Silbersweig
ers, which leads to maladaptive perceptions of
and responses to current interpersonal reality.
According to this model, the normal infant’s
early experiences with caregivers lead to a
multitude of distinct and contradictory inter-
nalized relationship patterns; for example, the
satisfied, calm self linked with an affect of
love to the nurturing other, and the needy,
frustrated self linked with an affect of hate to
the depriving other. Ideally, over the course of
development these split-off mental represen-
tations are integrated, resulting in a more com-
plex and realistic image of the other who can
both satisfy and frustrate, allowing for more
adaptive interpersonal functioning. Adaptive
integration of these early, distorted represen-
tations of self and others, and the intense af-
fects associated with them, likely requires
sufficient affect regulation. Individuals who
develop BPD appear not to reach this devel-
opmental stage, perhaps due to a primary ~ge-
netic! neurobiological deficit in those neural
systems subserving affect regulation, effects
of early trauma on these developing systems,
and0or deficits in parental modulation of this
emerging self-regulating capacity.
Deficits in affect regulation and impulse
control during early development may lead to
particularly conflictual experiences with care-
givers, experiences that become internalized
as prototypes for future relationships, eventu-
ally reflected in adult psychopathology. In ad-
dition, it is possible that these conflict-ridden
interpersonal experiences and the resultant in-
ternalized mental representations act back upon
the neurobiological substrate to produce fur-
ther dysfunction in neural circuits required for
affect0behavioral regulation. In animal mod-
els, chronic psychosocial and behavioral stress
have been shown to produce neuronal reorga-
nization and atrophy in medial PFC and hip-
pocampus ~Magariños, McEwen, Flugge, &
Fuchs, 1996; Radley et al., 2004!, as well as
neuronal growth in the amygdala ~McEwen,
2004!, in part mediated via glucocorticoid ac-
tion on these brain regions. Findings of reduced
prefrontal and hippocampal volumes in indi-
viduals with BPD from human neuroimaging
studies ~Brambilla et al., 2004; Driessen et al.,
2000; Irle, Lange, & Sachsse, 2005; Tebartz van
Elst et al., 2003! are consistent with these ani-
Neuroimaging of BPD
mal findings, and may reflect early psycho-
social stress-induced changes in these areas. For
example, Posner et al. ~2003! have suggested
that the anterior cingulate and the self-regulating
functions it subserves may be susceptible to the
effects of trauma during early development, pos-
sibly accounting for the deficits in effortful con-
trol observed in adults with BPD.
Epidemiological data strongly suggest that
numerous types of early psychosocial stress
~sexual0physical abuse, neglect! are involved
in the development of BPD ~Zanarini, 2000!,
perhaps accounting for the high comorbidity
of PTSD ~50%! seen in BPD patients ~McGlas-
han et al., 2000!. The effects of psychosocial
stress on the developing brain may be medi-
ated in part by genetic factors. Just as a poly-
morphism of the serotonin transporter ~5-HTT !
gene has been shown to moderate the influence
of stressful life events on the emergence of de-
pression ~Caspi et al., 2003!, certain genes may
render some individuals more susceptible to de-
veloping BPD in response to environmental
stressors via functional and structural changes
in the relevant neural circuits discussed above.
Although the functional consequences of these
morphological changes in prefrontal and lim-
bic areas remain unclear, they could result in
ongoing difficulties in affect regulation and
behavioral control leading to continued psy-
chosocial stress, resulting in a pathological re-
ciprocal interaction between neurobiology and
the environment in those with BPD.
An alternative to this psychosocial stress-
induced model of BPD comes from Fonagy,
Gergely, Jurist, and Target ~2002!, who pro-
pose that the development of effective affect
regulation takes place within the context of
the moment to moment interactions between
infant and caregiver. They propose a social
biofeedback model of parental affect mirror-
ing according to which the parent’s attuned
mirroring of the infant’s emotional expres-
sions is vital for the child’s development of
higher order mental representations of his in-
ternal feeling states, eventually providing the
basis for the infant’s emerging capacity to rea-
son about and to regulate his own affects. Ac-
cording to this theory, insufficient affect
mirroring leads to a developmental deficit in
the ability to mentalize about emotional states
1203
and may result in the relative failure of effec-
tive cognitive control over one’s affect states
observed in individuals with BPD. The emerg-
ing neuroimaging evidence of prefrontal dys-
function in BPD, a region involved in the
top-down cognitive control of limbic areas,
may in some cases reflect this early failure of
affect mirroring and provides another devel-
opmental model for the effects of early social
experience on the development of neural sys-
tems required for adaptive affect regulation.
Potential Neural Mechanisms of
Psychotherapeutic Change in BPD
Based upon recent neuroscientific findings of
dysfunctional neurocircuitry in BPD and these
developmental theories of borderline psycho-
pathology, we can begin to conceptualize pu-
tative mechanisms of psychotherapeutic action
at the neural systems level in the treatment of
this disorder. The psychotherapeutic use of
language to describe and talk about emotional
experience provides and fosters a representa-
tional0symbolic means to become aware of,
to reason about, and ultimately to modulate
affect states. This may be similar to the devel-
opmental emergence of mentalization ~Fonagy
et al., 2002!, and may reflect the therapeutic
enhancement of dysfunctional prefrontal re-
gions underlying the capacity to mentalize. In
addition, the activation of unconscious emo-
tional memories of early interpersonal experi-
ences with significant others within the
therapeutic relationship may present the
opportunity for enhanced declarative remem-
bering of the past and more adaptive reconsol-
idation of such pathological memories ~Ross,
2003!. In fact, evidence from animal models
demonstrates the possibility of altering emo-
tional memories via disruption of reconsolida-
tion at the level of the amygdala ~Debiec &
LeDoux, 2004!. Finally, psychodynamically
oriented psychotherapies that focus on the
patient’s transference to the therapist ~the pat-
terned and inflexible repertoire of emotional0
behavioral responses based on internalized
representations of past relationships; Clarkin
et al., 1999! may lead to a greater flexibility
of responses via alterations of frontolimbic
circuitry. For example, changes in the OFC
1204
and hippocampus that mediate emotional0
behavioral responses to contextual features of
the social environment could allow for a greater
capacity to process and respond to current in-
terpersonal reality in novel, more adaptive
ways rather than in repetitive, inflexible ways
based upon past experience. In addition,
transference-focused psychotherapies might
promote higher order prefrontal processes that
mediate the capacity for more complex men-
tal representations of self and others, thereby
changing the very quality of the subjective
interpersonal world of those with BPD.
Conclusions and Future Directions
Neuroimaging studies of BPD using a variety
of methodological approaches have identified
structural and functional abnormalities in spe-
cific frontolimbic regions. Findings of dysfunc-
tion in these areas that normally subserve affect
regulating and behavioral control functions are
consistent with the phenomenology of this dis-
order and may provide a neuropathological
correlate, as well as a dynamic, mechanistic un-
derstanding, of BPD. However, numerous meth-
odological limitations must be considered when
interpreting the results of individual studies.
These may include small sample sizes, histo-
ries of comorbid Axis I and II disorders, and
gender differences between patients and con-
trols. Past histories of major depressive disor-
der and PTSD, highly prevalent comorbidities
in the BPD population, are important issues ~al-
though not necessarily confounds! because these
other disorders also appear to involve dysfunc-
tion in similar prefrontal and limbic regions
~Drevets, 2001; Elliott et al., 2002; Shin et al.,
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