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Review
Emotion dysregulation in borderline personality
disorder: A fronto–limbic imbalance?
Maurizio Sicorello and Christian Schmahl
Abstract
Borderline personality disorder is most consistently charac-
terized as a disorder of the experience and regulation of
emotions. Neuropathological models have predominantly
explained these clinical traits with an imbalance between
prefrontal regulatory and limbic emotion generating structures.
Here, we review the current evidential state of the
fronto–limbic imbalance hypothesis of borderline personality
disorder, based on task-related functional magnetic resonance
imaging research. In turn, we discuss challenges to the notion
that (1) amygdala hyperreactivity underlies emotional hyper-
reactivity and deficits in (2) prefrontal activity or (3)
fronto–limbic connectivity underly emotion regulation deficits.
We offer several suggestions to improve consolidation and
interpretation of research in this area.
Addresses
Department of Psychosomatic Medicine and Psychotherapy, Central
Institute of Mental Health, Medical Faculty Mannheim, Heidelberg
University, C4, 11, 68159, Mannheim, Germany
Corresponding author: Sicorello, Maurizio (maurizio.sicorello@zi-
mannheim.de)
Current Opinion in Psychology 2021, 37:114–120
This review comes from a themed issue on Personality Pathology:
Developmental Aspects
Edited by Carla Sharp, Andrew Chanen and Marialuisa Cavelti
For a complete overview see the Issue and the Editorial
Available online 14 December 2020
https://doi.org/10.1016/j.copsyc.2020.12.002
2352-250X/© 2020 Elsevier Ltd. All rights reserved.
Keywords
Borderline personality disorder, Amygdala, Affective instability, Emotion
regulation, Magnet resonance imaging.
Borderline personality disorder (BPD) is characterized
by a broad set of emotional disturbances, often sum-
marized under the term emotion dysregulation. These
disturbances include a higher emotional sensitivity (i.e.
a lower threshold for emotions to occur), higher in-
tensities of experienced emotions, a slower return to a
person’s emotional baseline, and deficits in emotion
regulation [1]. Emotion dysregulation can already be
traced back to early childhood [2] and plays a central
role in developmental etiological models of the disorder
Current Opinion in Psychology 2021, 37:114–120
[3]. Investigating the neurobiological underpinnings of
these developmental findings has the potential to
improve our understanding of disorder processes, (ge-
netic) risk, and plasticity. Such neurodevelopmental
research programs are extremely challenging and require
neuropathological models which must first pass the test
of adequately explaining the emotional phenomenology
of BPD on a cross-sectional level.
About twenty years of neurobiological research on BPD
has been predominantly guided by the idea that
emotion dysregulation can be mapped onto an imbal-
ance between limbic structures, representing an
emotional response component, and prefrontal struc-
tures, representing a regulatory component [4]. This
idea is pervasive not only in the field of BPD, but also
depression, post-traumatic stress disorder (PTSD), and
maltreatment in general, fitting the notion of emotion
dysregulation as a transdiagnostic construct. Still, while
the frontoelimbic imbalance hypothesis has high face
validity and can be easily utilized in psychoeducation, it
faces several theoretical and methodological challenges.
Here, we review the current state of the frontoelimbic
hypothesis of emotion dysregulation in BPD, contextu-
alized with recent insights from affective neuroscience,
focusing on task-based functional magnet resonance
imaging (fMRI) research.
The amygdala in emotional reactivity
The amygdala is the central limbic target for
emotional reactivity. A recent meta-analysis of 24
studies confirmed that individuals with BPD exhibit
larger amygdala activity in response to threat-related
imagery than both healthy and depressed samples
(but not in the anterior insula or anterior cingulate
cortex [ACC], two other primary regions of interest)
[5]. Amygdala activity has also repeatedly been found
to be increased in BPD while viewing neutral stimuli
[6]. Moreover, amygdala habituation to repeatedly
presented negative stimuli is decreased in a larger
sample of patients with acute and remitted BPD [7].
Hence, the amygdala appears to be implicated in both
emotional sensitivity and intensity as well as lowered
habituation. These effects were reduced by dialectical
behavior therapy [8,9] and intranasal oxytocin treat-
ment [6]. Building on these findings, a recent one-
armed preepost intervention study reported an
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improvement of BPD symptoms after amygdala
neurofeedback training [10].
Although further replications of the intervention
studies above are necessary, the confirmation of
amygdala aberrations in BPD during emotion-related
tasks by meta-analyses [5] and by a study with larger
sample size [7] is an important achievement for the
field. Still, although amygdala aberrations are
commonly thought to indicate emotion dysregulation,
this interpretation needs to be put into context. To
infer psychological functions, a biomarker must be both
sensitive and specific to the function of interest
(reverse inference problem, Box 1). While the amyg-
dala does respond sensitively to emotional stimuli, its
involvement is not specific to negative affect (i.e.
similarly involved in positive affect [11]) or any
Box 1. The reverse inference problem in neuroimaging
research
Most neuroimaging studies measure brain activity (A) within
experimental tasks designed to involve a certain mental
process of interest (M). Here, in essence, studies start from
the psychological end to learn something about the brain.
This forward inference is formalized as the probability of
observing brain activity A given mental process M [p(A|M)]
[47]. Usually, however, clinical researchers are interested in
using the brain to learn something about a psychological
construct. For example, observing a heightened amygdala
response becomes practically relevant if it indicates a clinical
abnormality (e.g. emotional hyperreactivity), which can be
targeted with psychotropic medication, neurofeedback, or
brain stimulation. This reverse inference corresponds to the
probability of p(M|A), which can be derived using Bayes rule:
pðAjMÞ pðM Þ
pðM jAÞ ¼
pðAÞ
For this probability to be high, ensuring correct inference, the
targeted neural activity must be both sensitive and specific to
the construct of interest. This can be seen in the formula
above: The unconditional probability to observe activity
pattern A is in the denominator of the right-hand side of the
equation. Hence, a larger general probability to observe
activity in the region of interest p(A) is associated with less
certainty to infer a specific mental state p(M|A). To give a
practical example, while the dorsal anterior cingulate cortex
(dACC) is involved in cognitive control, it is also involved in
pain and affect. In fact, the dACC is among the regions with
the most significant results across research topics [48].
Therefore, activity in the dACC cannot clearly indicate the
occurrence of a specific affective mental event.
In contrast, machine learning can be used to discover brain
patterns which predict concepts such as negative affect with
high accuracy, even differentiating it from similar but distinct
concepts such as the subjective response to physical pain
[16]. These patterns can be reused and shared across labs,
facilitating the translation from basic to clinical neuroscience.
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Fronto–limbic imbalance in BPD Sicorello and Schmahl 115
discrete emotion and extents to nonemotional but
relevant experimental events [12]. Furthermore, deep
brain stimulation of the human amygdala does not
systematically lead to negatively toned emotional ex-
periences [13]. Rather, affect and emotions are
empirically best represented by complex activation
patterns which span multiple distributed subsystems
across the brain [12]. These findings support the long-
standing argument that the amygdala’s main role is a
functionally related combination of relevance detec-
tion, associative learning, and response facilitation.
The view of the amygdala as part of a defensive survival
circuit ignores its involvement in positive and nonaf-
fective states, which is more easily accommodated by
viewing the amygdala as a co-regulator of allostatic
physiological responses more generally [14,15].
Notably, one well-powered study suggests that amyg-
dala activity does not increase monotonically with
higher negative affective responses, plateauing after
small increases in negative affect and not distinguish-
ing between very high and very low negative affect
above chance. In contrast, a multivariate pattern
reached over 90% accuracy [16].
Even if the amygdala does not allow strong reverse
inference to negative emotional states in the labo-
ratory due to nonspecificity and non-monotonicity, it
might still contribute to psychopathological models
by capturing general differential relevance of affec-
tive stimuli such as faces or scenes, the most
common stimuli in fMRI research. Nevertheless, it is
unclear whether this is informative about the core
concept of emotion dysregulation. Group comparisons
between BPD patients and healthy controls are
severely limited, as these groups might differ on
many dimensions. From a trait perspective, there
appears to be no association between amygdala
reactivity and neuroticism [17], which maps on the
negative affectivity trait characteristic for BPD [18].
Similarly, there was no relationship between amyg-
dala reactivity to negative stimuli and affective
reactivity in daily life [19].
Another possible explanation for amygdala hyperreac-
tivity in BPD might be a higher relevance of experi-
mental stimuli due to past negative experiences. The
previously mentioned meta-analysis found that amyg-
dala hyperreactivity is present in both BPD and
PTSD [5], which overlap not only in their phenom-
enology, but also the presence of such experiences.
Amygdala hyperreactivity is also present in adults with
adverse childhood experiences [20,21], even in the
absence of psychopathology [22]. In further support,
amygdala habituation to negative stimuli was related
to adverse childhood experiences, but not to BPD
symptom severity or clinical state in a well-powered
study [7].
Current Opinion in Psychology 2021, 37:114–120
116 Personality Pathology: Developmental Aspects
The prefrontal cortex in emotion regulation
deficits
While the BPD meta-analysis described earlier revealed
both hyperactive and hypoactive clusters in the pre-
frontal cortex (PFC) during emotion processing in BPD
[5], only few fMRI studies have probed neural deficits
during explicit emotion regulation. Most studies
employed cognitive reappraisal strategies such as hy-
pothetical distancing, where participants imagine
negative scenes as not being real [23]. The dorsal ACC
(dACC) is the prefrontal brain region most consistently
associated with emotion regulation deficits in BPD and
has been argued to underlie cognitive control abilities.
Three studies found that the dACC was deactivated,
instead of activated, during reappraisal in individuals
with BPD [24e27]. As for the amygdala, these findings
were also apparent in healthy but trauma-exposed con-
trols [25]. Lower ACC recruitment during distancing
was also associated with a continuous measure of
emotion regulation difficulties in BPD [28]. In addition,
recruitment of the dACC during distancing was
increased after dialectical behavior therapy in a clinical
trial [29].
Although these results might seem consistent at the
first glance, they lack evidence of spatial overlap. The
inference from brain measures to psychological states
not only requires psychological but also a degree of
spatial specificity. In neuroimaging, replication success
is predominantly attested when studies find significant
Figure 1
Prefrontal regions with lower activity during emotion regulation in BPD. BPD, borderline personality disorder.
Current Opinion in Psychology 2021, 37:114–120
effects in the same gross anatomical brain region, even if
the significant voxels are separated by considerable
margins [30]. The dACC peak voxel for emotion regu-
lation deficits in BPD are roughly between 2 and 4 cm
apart, which is above the median of most replication
studies and especially problematic for this particular
brain region: The dACC is unspecifically involved in a
broad set of processes, including pain, affect, and
cognitive control. These different processes are likely
enacted by different adjacent neuron populations,
making spatial distinctions essential [31].
On an epistemological level, interpreting group dif-
ferences in any prefrontal area as aberrations in
emotion regulation is a very broad hypothesis with low
falsifiability, as the PFC makes up more than 20% of
the gray matter volume in humans. Meta-analyses on
the neural basis of emotion regulation are becoming
increasingly refined, offering a more constrained hy-
pothesis space. Powers and LaBar [23] published a
meta-analysis of 22 studies on brain regions involved
in distancing together with a neurocognitive model,
mapping psychological aspects on neural structures,
which can be used to more strongly constrain hy-
potheses and interpretations. Figure 1 displays the
regions they identified, together with prefrontal re-
gions which exhibited reduced activity during emotion
regulation in BPD. None of these single-study regions
overlapped with the meta-analytical network or each
other, granting no evidence for prefrontal emotion
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regulation deficits in BPD when employing constraints
based on prior neurobiological knowledge (but see the
figure caption for details and limitations). Importantly,
low statistical power likely plays a major role in these
inconsistent findings, increasing spatial uncertainty
and potentially obscuring smaller but relevant over-
lapping effects [32]. For between-person hypotheses,
low testeretest reliability of classic fMRI measures
further exacerbates this problem [33] (but refer
Kragel et al. [34]).
This figure depicts prefrontal regions involved in the
emotion regulation strategy distancing in a meta-
analysis [23] and prefrontal regions which exhibited
reduced recruitment in BPD during emotion regula-
tion in single studies. The meta-analytic map was
retrieved from neurovault (https://identifiers.org/
neurovault.collection:8386). Regions of interest from
single studies were created as spheres around reported
peak voxels while maintaining the same cluster
volume. Importantly, the original clusters might be
nonspherical, impeding the inference to overlap be-
tween regions. This is especially relevant for the
clusters from van Zutphen et al. [26] and the
distancing meta-analysis, which are relatively close but
nonoverlapping in the figure above. While the clusters
appear to be approximately spherical in van Zutphen
et al. [26], there is still a degree of uncertainty
concerning overlap. Note, the meta-analysis and single
studies reported further significant differences in non-
PFC regions, which are not shown here. Moreover,
Silvers et al. [28] investigated neural correlates of
Table 1
Avenues toward consolidation and interpretation.
Recommendation
1. Use maps from meta-analyses on basic
processes to spatially
constrain hypotheses
2. Publish (un-)thresholded group level maps
of single experiments
3. Use psychometric principles to develop paradigms which
capture individual differences
4. Use established (or develop novel) machine learning-
based brain activity/connectivity patterns which are sen-
sitive and specific to the construct of interest
5. Consider hyperalignment as an additional preprocessing
step
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Fronto–limbic imbalance in BPD Sicorello and Schmahl 117
trait emotion regulation in BPD instead of comparing
a BPD group to a clinical control group.
On a psychological level, hypothetical distancing rep-
resents one of the major emotion regulation strategies
used in fMRI research, but a recent review questions its
practical relevance [23]. While it might be effective in
the laboratory to imagine the content of aversive pic-
tures as not being real (which in fact is often staged), it
is therapeutically questionable whether this strategy
also makes sense outside the lab. As a further sign of
limited ecological validity, none of the BPD emotion
regulation studies found group differences in self-
reported emotion regulation success during the task
and most did not report group differences in amygdala
attenuation during regulation.
Brain connectivity and fronto–limbic
inhibition
The frontoelimbic imbalance hypothesis is guided by a
causal assumption. Especially the dorsolateral PFC
(dlPFC) is argued to (indirectly) exert inhibitory control
over presumably emotion generating regions like the
amygdala during emotion regulation [23,35]. Connec-
tivity analyses can provide information on the commu-
nication between regions beyond task-related activation
[36] and PFCeamygdala connectivity during emotion
regulation has been argued to underly emotion regula-
tion success and related traits [37]. Unfortunately, to
our knowledge, none of the around 30 published con-
nectivity studies on BPD-targeted individual differ-
ences in connectivity during an explicit cognitive
Advantage Paper
suggestions
(References)
A smaller search space can increase [19]
statistical power and facilitate interpretability.
Can be used as regions of interest to [30]
conduct spatially precise replications
and improve meta-analytic aggregation
Reduces error variance, which increases effect sizes and [49,50]
statistical power for
between-person effects
Facilitates reverse inference. Increases statistical power [51,52]
through a smaller number of tests and higher reliability
Reduces noise of intrinsic spatial between-person [53]
variability in brain function (potentially for
the price of lower between-study comparability
in some instances)
Current Opinion in Psychology 2021, 37:114–120
118 Personality Pathology: Developmental Aspects
emotion regulation paradigm to provide a strong test of
this hypothesis.
A considerable number of studies looked at connectivity
during rest, with some reporting decreased medial
PFCeamygdala connectivity [38e40], whereas others
did not find this effect [41,42]. Still, a basis to infer
deficits in specific clinical phenomena is needed, as the
role of the medial PFC in emotion regulation has been
argued to be less about regulation and more about the
representation and transmission of information on af-
fective states [35,43]. Especially, the relationship be-
tween resting state connectivity and trait emotion
regulation deficits is still unclear [44].
As for neural activity, these inconsistencies might be
explained by the very low reliability of resting state con-
nectivity [45], which can be substantially alleviated by
engaging participants in a task [46]. Nevertheless, even
when broad frontoelimbic connectivity aberrations are
identified during emotional tasks, interpretation has to be
guided by prior knowledge on neural correlates of emotion
regulation states and traits. Hence, as for prefrontal ac-
tivity, the hypotheses that frontoelimbic inhibition un-
derlies emotion regulation deficits has to be constrained
spatially (i.e. where in the PFC), directionally (i.e.
negative or positive, higher or lower), and psychologically
(i.e. which dimensional construct) to be informative.
Conclusions and future directions
Frontoelimbic imbalance is a central hypothesis to
explain emotion dysregulation, a core transdiagnostic
dimension of psychopathology. Here, we argue that
amygdala hyperactivity in BPD is a credible and rela-
tively consistent research finding, but currently lacks
the empirical basis to confidently infer emotional hy-
perreactivity on a psychological level. Rather, the hy-
perreactivity of this valence-unspecific brain region
might also be parsimoniously explained by a heightened
psychological relevance of the experimental stimuli,
which relate to past adverse experiences. This high-
lights the need for dimensional approaches, as BPD
patients can differ from healthy controls in many ways.
Establishing prefrontal deficits, in turn, is hindered by
the lack of spatial specificity concerning hypotheses and
findings. Taken together, there is currently only weak
evidence that a frontoelimbic imbalance underlies
emotion dysregulation in BPD.
Importantly, the issues we pointed out do not fully
disagree with the idea of a frontoelimbic imbalance.
They do, however, point toward crucial challenges for
the establishment and interpretation of neuropatho-
logical models. These include limited testeretest reli-
ability [33,45], spatial imprecision [30], and ambiguous
interpretations [47]. Such challenges are both inherent
Current Opinion in Psychology 2021, 37:114–120
and necessary for the scientific progress, especially
concerning the brain basis of complex traits. There is,
however, much than can be done. In Table 1, we high-
light several suggestions how research on emotion
dysregulation in BPD might be refined and consoli-
dated. Notably, most of these suggestions are applicable
even to existing data sets. Above all, building neuro-
pathological models from basic affective neuroscience
and emotion dysregulation as a dimensional trans-
diagnostic will be vital.
Credit author statement
Maurizio Sicorello: Conceptualization, Writing - Orig-
inal Draft, Visualization; Christian Schmahl: Writing -
Review & Editing, Supervision.
Conflict of interest statement
Nothing declared.
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