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Amygdala and emotionality in Parkinson's
disease: An integrative review of the
neuropsychological evidence
Radek T
1,2, Jozef H
2,3,4, Inna Č
1,5, Martin K
1,2,
Peter T
2, Tomáš N
1,6
1 Prague College of Psychosocial Studies, Prague, Czech Republic
2 OUSHI, Palacky University, Olomouc, Czech Republic
3 Slovak Medical University, Bratislava, Slovak Republic
4 St. Elisabeth University of Health and Social Sciences, Bratislava, Slovak Republic
5 Faculty of Humanities, Charles University, Prague, Czech Republic
6 Department of Neurology and Centre of Clinical Neuroscience, 1st Faculty of Medicine, Charles
University, Prague, Czech Republic
Correspondence to: Jozef Hašto, Heydukova 27, 811 08 Bratislava, Slovak Republic
.: 00421 908 764 549; -: j.hasto.tn@gmail.com
Submitted: 2018-03-05 Accepted: 2018-04-05 Published online: 2018-07-12
Key words: Parkinson disease; amygdala; emotions; affect; neuropsychology
Neuroendocrinol Lett 2018; 39(2):105–110 PMID: 29919988 NEL390218A03 © 2018 Neuroendocrinology Letters • www.nel.edu
Abstract
Parkinson's disease (PD) is often accompanied by significant changes in emo-
tionality, such as apathy, anhedonia, anxiety and depression. The present review
summarizes the empirical evidence, including amygdala changes and psycho-
logical changes in emotionality in people suffering from PD. Seventeen empirical
full-text articles including research on both amygdala and emotionality in PD
were reviewed. The changes in amygdala volumes as well as changes in binding
potentials, functional connectivity, regional homogeneity and regional cerebral
blood flow were found to have various impacts on emotionality in people with
PD. The integration of the results showed that some effects of amygdala changes
on emotionality were lateralized. Some of the reviewed studies indicated that the
volume loss in the left amygdala was found to be related to increased anxiety,
whereas bilateral volume loss in amygdala was linked to increased depressivity.
The reviewed results also support a hypothesis of bradylimbic affective distur-
bance in patients with PD. The disturbed activation of amygdala accompanying
the evaluation of negative facial expressions implies that the evaluation of the
content of affective stimuli in terms of their affective meanings is disturbed in
PD patients. Impaired evaluation of affective attributes given by amygdala-based
translational deficits is likely to be related to problems in translating the results of
cognitive appraisal into somatomotor, arousal and other changes. This mechanism
is suggested to be responsible for apathy as well as for other changes in emotional-
ity accompanying PD.
106
Copyright © 2018 Neuroendocrinology Letters ISSN 0172–780X • www.nel.edu
Radek Trnka, Jozef Hašto, Inna Čábelková, Martin Kuška, Peter Tavel, Tomáš Nikolai
Abbreaviations:
PD - Parkinson's disease
INTRODUCTION
Parkinson's disease (PD) is suggested to be a very
suitable prolific model for studying the neurobiology
of normal human emotional behavior as well as psy-
chiatric disorders (Garlovsky et al. 2016). Therefore,
an in-depth understanding of the brain mechanism
underlying Parkinson's disease is a recent, very impor-
tant challenge for many fields of neurosciences and
neuropsychology. It is well-documented that the PD
is accompanied by significant changes in emotionality,
such as anhedonia, i.e. a lowered ability to experience
pleasure (Loas et al. 2012), apathy (Bogart 2011), anxi-
ety and depression (Garlovsky et al. 2016). Despite the
detrimental impact of these emotional changes on the
quality of emotional life of people suffering from PD,
there is a lack of reviews focusing on the role of amyg-
dala in relation to nonmotor symptoms. Therefore, the
present review aims to summarize the empirical evi-
dence, including amygdala changes and psychological
changes, in the emotionality of people with PD.
The amygdala is an almond-shaped structure on
the medial temporal lobe located adjacent and anterior
to the hippocampus (Phelps 2006). The amygdala is a
key neural structure responsible for human emotions
(LeDoux 2000) due to its role in the detection and
processing of emotional stimuli (Němcová et al. 2015;
Phelps 2006). This structure is part of the limbic-based
circuitry involved in the generation and modulation
of normal fear responses (Bowers et al. 2006; LeDoux
2000). This circuitry is responsible for initiating behav-
ioral, autonomic and neuroendocrine processes essen-
tial for appropriate reactions to threats and danger.
Furthermore, given the role of amygdala in the encod-
ing and storage of hippocampal-dependent emotional
memories (Phelps 2006), this structure also influences
the retrieval of emotional life events. The amygdala
can also modulate the recognition of facial expres-
sions because of its functional involvement in episodic
memory for emotional stimuli. Functional abnormali-
ties in the amygdala are related to depression, anxiety
and posttraumatic stress disorder (Grambal et al. 2015;
LeDoux, 2000; Zach et al. 2016).
Changes in the amygdala are well-documented
in PD patients. Volumetric changes, a reduction in
amygdala dopamine-agonist binding, an increased
occurrence of Lewy body pathology and increased pre-
synaptic axonal pathology all accompany PD (Bowers et
al. 2006). Bowers et al. (2006) proposed a bradylimbic
affective disturbance in patients with PD, hypothesizing
that evaluation of affective attributes, such as valence
or arousal, is disturbed in PD because of changes in the
amygdala and other parts of limbic-based circuitry. The
muted reactivity to aversive stimuli that is present in PD
patients is suggested to be related to a deficit in translat-
ing the results of cognitive appraisal into somatomotor
(Vastik et al. 2016), arousal and other changes associ-
ated with an aversive motivational state. In other words,
cognitive appraisal is not necessarily disturbed, but the
outputs of this appraisal are suggested to be insufficient
to induce a particular motivational state. The authors
proposed that this mechanism may be responsible for
the apathy frequently observed in PD patients (Bogart
2011). However, it is also possible that impaired evalua-
tion of affective attributes, resulting from an amygdala-
based translational defect, may play an important role
also in other changes in emotionality in PD.
There are many insistent questions relating to
changes in human amygdala in patients suffering from
PD. In the following text, we proceed through the cur-
rent findings concerning the amygdala in PD and show
what changes in the amygdala have been found to be
related to changes in emotionality in PD patients. The
aim of the present review is to expand our understand-
ing of the neurobiological basis of emotional processing
in PD.
METHODS
Search strategy
A systematic literature search was completed in Feb-
ruary 2018. Manuscripts published between 2000 and
2018 were accessed via the Web of Science and PubMed
electronic databases. Peer-reviewed literature provid-
ing empirical evidence was retrieved using a standard
search strategy based on the key words: Parkinson
AND amygdala. Meeting abstracts, reviews and edi-
torial materials were excluded in this phase. After the
exclusion, a total of 351 full-text articles were identified,
and the titles and abstracts were scanned for relevance.
Selection of the studies
Only patients diagnosed with idiopathic Parkinson's
disease were included. Articles that did not directly
report empirical research of amygdala in PD in relation
to emotionality, i.e. anhedonia, depression, anxiety or
emotional processing, were excluded. At the same time,
empirical research based on animal models, case-stud-
ies and post-mortem cases of PD were excluded. Only
articles written in English were included in the review.
Two authors (RT and MK) reviewed the methodological
quality of the included studies according to the selected
criteria. The results were re-reviewed by athird author
(TN), who made the final decision.
RESULTS
In total, 17 empirical full-text articles were selected
(Table 1). The outcomes were classified into 5 cat-
egories: depression, anxiety, apathy, disgust and fear,
and emotion recognition, according to the domain of
emotionality that the articles focused on. These catego-
ries were not created on a pre-determined conceptual
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Amygdala and emotionality in Parkinson
Tab. 1. Review of studies focusing on amygdala and emotionality in PD patients
Publication PD sample(s) Key findings
Tessitore et al. 2002 10 PD patients The imaging data revealed a robust bilateral amygdala response in healthy
controls that was absent in PD patients during the hypodopaminergic state.
Remy et al. 2005 20 PD patients Depression and anxiety in PD might be associated with a speci c loss of
dopamine and noradrenaline innervation in the limbic system.
Yoshimura et al. 2005 9 PD patients No neuronal activity was found in the amygdala when responding to fearful
expressions in PD patients in comparison with healthy subjects.
Delaveau et al. 2009 14 PD patients Similar right-amygdala activity was seen in both healthy subjects and PD
patients in the placebo session. After levodopa administration, this activity was
reduced in both groups.
Ibarretxe‐Bilbao et al.
2009
24 early PD patients Signi cant gray matter loss in the right amygdala and bilaterally in the
orbitofrontal cortex was found in PD patients.
Lawrence et al. 2011 20 PD patients Apathy was associated with a blunted response to money in the ventromedial
prefrontal cortex, amygdala, striatum and midbrain.
Baggio et al. 2012 39 PD patients Emotion recognition of sadness was positivelly correlated with gray matter
volume in the right orbitofrontal cortex, amygdala and postcentral gyrus in PD
patients.
Surdhar et al. 2012 33 non-demented
depressed PD patients
Depressed PD patients showed smaller amygdala volumes compared to
healthy controls. Amygdala atrophy was suggested to be present in PD with
depression.
Sheng et al. 2014 41 PD patients Compared with the non-depressed patients, those with depressive symptoms
exhibited signi cantly increased regional activity in the left middle frontal
gyrus and right inferior frontal gyrus, and decreased regional activity in the left
amygdala and bilateral lingual gyrus.
Hu et al. 2015 20 depressed PD patients,
40 non-depressed PD
patients
Compared to healthy controls, the depressed PD group showed increased left
amygdala functional connectivity with the bilateral mediodorsal thalamus,
but decreased left amygdala functional connectivity with the left putamen,
left inferior frontal gyrus and the right cerebellum, as well as decreased right
amygdala functional connectivity with the left inferior orbitofrontal gyrus, the
left gyrus rectus and the right putamen.
Huang et al. 2015 19 depressed PD patients,
19 non-depressed PD
patients
Left amygdala activity was increased in the PD group compared with
the healthy control group, and it correlated with depression. Functional
connectivity between the right amygdala and fronto-parietal areas was found
to be decreased in the depressed PD patients compared with non-depressed
PD patients.
Schienle et al. 2015 17 non-depressed and
non-demented PD
patients
Healthy control participants showed amygdala activation during experimental
fear induction, whereas no supra-threshold activation was detected in PD
patients. No di erences were found between PD patients and healthy controls
during disgust induction.
van Mierlo et al. 2015 67 PD patients Depression correlated negatively with bilateral hippocampus and right
amygdala volume and positively with the volume of the anterior cingulate
cortex.
Kim et al. 2016 35 depressed PD patients,
43 non-depressed PD
patients
Regional cerebral blood ow decreases in the amygdala, anterior cingulate
cortex, hippocampus and parahippocampal gyrus in depressed PD patients.
Vriend et al. 2016 110 early PD patients A reduction in left amygdala volume was associated with anxiety in PD
patients.
Chagas et al. 2017 15 PD patients with
current Major Depressive
Disorder, 10 PD patients
with previous MDD but
without current MDD,
18 PD patients with no
current or lifetime MDD
Current and lifetime Major Depressive Disorder (MDD) had a negative
impact on the neurodegenerative process of PD, with decreased volume and
reduction of cortical thickness in temporal and frontal areas, anterior cingulate
cortex, amygdala and cerebellar white matter.
Li et al. 2017 366 early PD patients Right amygdala grey matter density showed negative correlation with
autonomic dysfunction and positive correlation with cognitive performance in
PD patients. No signi cant interrelations were found with anxiety scores.
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Radek Trnka, Jozef Hašto, Inna Čábelková, Martin Kuška, Peter Tavel, Tomáš Nikolai
framework but were allowed to emerge from the data
in the course of the review procedure. Few studies
included results falling into more than one category.
The main results within each category are presented in
the following sections.
Depression
Gray matter volume loss within the limbic circuit has
been found to be related to the severity of depressive
symptoms in PD patients (van Mierlo et al. 2015). More
specifically, self-reported rating of depressive symptoms
correlated negatively with the volumes of bilateral hip-
pocampus and amygdala and positively with the volume
of the anterior cingulate cortex. Reduced amygdala vol-
umes relative to healthy controls were also found in PD
patients with depression in the study of Surdhar et al.
(2012). Interestingly, in the study of Huang et al. (2015)
volumetric changes were not significantly different in
the depressed PD patients compared to healthy control
and non-depressed PD patients.
When evaluating the role of a previous Major
Depressive Disorder, PD patients with a previous Major
Depressive Disorder had smaller bilateral amygdala
than PD patients without a previous or current Major
Depressive Disorder. The volumes of the right amyg-
dala were smaller in the group with current (and not
previous) Major Depressive Disorder compared to PD
patients without a previous or current Major Depres-
sive Disorder.
Regional cerebral blood flow was compared in
depressed and non-depressed PD patients (measured by
self-reported ratings) in the study of Kim et al. (2016).
Regional cerebral blood flow was found to be decreased
in the amygdala and other regions in depressed PD
patients compared to non-depressed PD patients.
Differences in amygdala functional connectivity
between PD patients and healthy subjects were found
in two reviewed studies (Huang et al. 2015; Hu et al.
2015). Furthermore, depressed PD patients showed
increased left amygdala functional connectivity with
the bilateral mediodorsal thalamus and increased right
amygdala functional connectivity with the left supe-
rior temporal gyrus and the calcarine gyrus in com-
parison to non-depressed PD patients (Hu et al. 2015).
In contrast, depressed PD patients showed decreased
connectivity between the right amygdala and the right
middle occipital gyrus, right middle frontal gyrus and
the left inferior parietal lobule when compared with
non-depressed PD patients in the study of Huang et al.
(2015).
Remy et al. (2005) examined the role of both dopa-
mine and noradrenaline transporter binding in depres-
sion. PD patients were divided into a depressed group,
i.e. with previous episodes of major depression based
on DSM-IV criteria, and a non-depressed group with-
out such episodes. Patients without previous episodes
of major depression showed significantly higher bind-
ing potential in the right amygdala than patients with
previous episodes of major depression.
Differences between depressed and non-depressed
PD patients were also found in the study of Sheng et
al. (2014), which focused on regional homogene-
ity during spontaneous neural activity. Depressed PD
patients showed decreased regional homogeneity in the
left amygdala and bilateral lingual gyrus and increased
regional homogeneity in the left middle frontal gyrus
and right inferior frontal gyrus. These results indicate
that decreased regional homogeneity in amygdala
reflects the local destruction of synchronization of
spontaneous low-frequency blood oxygen level-depen-
dent fluctuations in the region and consequently also
functional deficits of amygdala in PD patients.
Anxiety
The study of Vriend et al. (2016) showed that symptoms
of anxiety in PD patients had a negative correlation
with the volume of the left amygdala. The authors sug-
gested that PD pathology is responsible for the observed
volume loss of the left amygdala and the concomitant
development of anxiety symptoms.
Furthermore, Remy et al. (2005) measured anxiety by
standardized psychometric instrument in PD patients.
The anxiety score was negatively correlated with the
binding potential in the left ventral striatum, left cau-
date, left locus coeruleus, left inferior thalamic region
and bilaterally in the amygdala and medial thalamus.
The authors suggested that the loss of noradrenaline and
dopamine in the amygdala is likely to play a role in gen-
erating affective symptoms in PD. Interestingly, the study
of Li et al. (2017) found amygdala degeneration to be
related only to cognition and autonomous dysfunction,
but not to anxiety in patients in the early stages of PD.
Apathy
The role of apathy in alterations in the neural circuitry
underpinning the cognitive and emotional components
of goal-directed behavior was examined in the study
of Lawrence et al. (2011). PD patients participated in
an experimental task involving monetary reward cues.
Psychometrically measured apathy was associated
with adiminished response to money in several brain
regions: the left amygdala, ventromedial prefrontal
cortex, striatum and midbrain, all of which have been
previously shown to be integral to the representation
of reward value and goal-directed behavior. In other
words, higher apathy was related to decreased activity
in these brain regions during the reward-value experi-
mental task in PD patients.
Disgust and fear
In the fMRI study of Schienle et al. (2015), PD patients
were exposed to 10 disgust-eliciting (e.g. dirty toilets,
maggots), 10 fear-eliciting (attacks by humans and
animals) and 10 neutral pictures (e.g. nature scenes,
geometric figures) with the instruction to simply expe-
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Amygdala and emotionality in Parkinson
rience the elicited emotions. The group contrasting for
the disgust-inducing condition revealed no significant
differences in the activation of amygdala. In the fear-
inducing condition, the healthy control participants
showed the expected amygdala activation, whereas
no supra-threshold activation was detected in the PD
patients. In contrast, the PD patients showed activation
of the middle temporal gyrus during the fear-inducing
condition. The authors, however, concluded that this
fMRI investigation found no indication of diminished
disgust and fear experience in patients suffering from
moderate PD symptoms.
In the same study, proneness to dispositional dis-
gust was measured using a standardized psychometric
instrument, with no differences found between PD
patients and healthy controls.
Emotion recognition
Yoshimura et al. (2005) randomly presented PD patients
with fearful, surprised and neutral facial expressions in
their study. The visual event-related potentials elicited
in response to fearful facial expressions were gener-
ated within the amygdala and visual temporal cortex in
healthy controls, whereas the equivalent current dipoles
were located only in the parietal somatosensory cortex
in PD patients. These results indicate dysfunction of the
amygdala during emotion recognition in patients with
PD.
A reduced amygdala response during the perceptual
processing of angry and fearful faces was observed also
by Tessitore et al. (2002). Abnormal amygdala responses
in patients with PD were present both in drug-off
and drug-on conditions, i.e. 12 hours after their last
dopaminergic drug dose the night before as well as 1–2
hours after the first dose of the day.
In the study of Baggio et al. (2012) impaired recogni-
tion of sadness was associated with gray matter loss in
two areas of the right side in the amygdalae and orbito-
frontal cortex when examining amygdala atrophy. More
specifically, patients with decreased recognition of sad-
ness showed gray matter loss in the medial area and a
smaller, more lateral loss, in the dorsal part of the right
postcentral gyrus and in the medial right amygdala. In
contrast, amygdala gray matter volume did not corre-
late with the quality of emotion recognition in the study
of Ibarretxe-Bilbao et al. (2009).
The effect of dopaminergic medication on amygdala
activation during an emotional facial matching task was
evaluated in the study of Delaveau et al. (2009). Under
placebo conditions, amygdala was activated, whereas
this activation was disrupted after levodopa adminis-
tration both in PD patients and healthy subjects. This
study showed a detrimental levodopa overdose effect
for normal activation of the amygdala.
DISCUSSION
The present study integrates various bodies of research,
including changes in amygdala and emotionality in
patients with PD. Basically, two research streams may
be distinguished: research focusing on volumetric
changes relating to atrophy of brain structures in PD
and research focusing on differences in activation
of amygdala under various conditions. Aside from
observed changes in amygdala volumes, changes in
binding potentials, functional connectivity, regional
homogeneity and regional cerebral blood flow have
also been shown to have an impact on various realms of
emotionality in people with PD.
Interestingly, some effects of amygdala changes on
emotionality in PD were lateralized. When searching
for the lateralized functions of amygdala in healthy
subjects, the left amygdala is considered to be more
involved in detailed emotional information processing
and detecting stimulus arousal, while the right amyg-
dala is suggested to be more important for rapid and
automatic stimulus detection (Vriend et al. 2016). In PD
patients, bilateral volume loss was found to be related to
the increased depressivity (van Mierlo et al. 2015), but
in contrast, volume loss only in the left amygdala was
found to be related to the increased anxiety (Vriend et
al. 2016). We may speculate about a possible lateralized
effect of volume loss in amygdala in developing anxiety
and depressivity in PD patients. Future research should
explore how volume loss in the left and right amygdala
participates in the development of anxiety and depres-
sion in PD patients and whether atrophy in the left and
right amygdala may also be responsible for the dis-
turbed evaluation of subjective experience in terms of
valence or arousal.
Some reviewed results indicated that the activation
of amygdala is disturbed in PD patients when evaluat-
ing negative affective stimuli. The study of Yoshimura
et al. (2005) showed insufficient activation of the amyg-
dala during recognition of fearful facial expressions, but
not during evaluation of surprised and neutral facial
expressions in comparison to healthy subjects. These
results support the hypothesis of bradylimbic affective
disturbance in patients with PD (Bowers et al. 2006).
The evaluation of affective stimuli in terms of their
affective meaning may be disturbed in PD patients
because of insufficient activation of the amygdala
during emotion recognition. This deficit in activation
of amygdala was also found during recognition of fear,
i.e. during evaluation of negative affective stimuli. This
finding is in line with the hypothesis of Bowers et al.
(2006) suggesting muted reactivity of amygdala to aver-
sive stimuli. The reduced amygdala response during the
perceptual processing of negative affective stimuli, i.e.
angry and fearful faces, was also found in the study of
Tessitore et al. (2002).
In contrast, incongruent results were found in
research focusing on the role of amygdala volume loss
110
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Radek Trnka, Jozef Hašto, Inna Čábelková, Martin Kuška, Peter Tavel, Tomáš Nikolai
in emotion recognition in PD patients. Baggio et al.
(2012) reported the impaired recognition of sadness
in association with gray matter loss in the right amyg-
dala. However, amygdala gray matter volume did not
correlate with the quality of emotion recognition in the
study of Ibarretxe-Bilbao et al. (2009). Future research
is needed in this field.
The role of dopaminergic medication on amyg-
dala activation is a big question in research focusing
on changes in emotionality in PD. Some studies have
indicated that dopaminergic medication disrupted
the functions of amygdala both in PD patients and
healthy subjects (Delaveau et al. 2009). A detrimental
dopaminergic overdose effect for the normal activa-
tion of amygdala should be taken into account when
interpreting results, including the impact of amygdala
changes on emotionality in patients suffering from PD.
This review has some limitations to be addressed.
First, our search was limited to Web of Science and
PubMed databases and included only articles written in
English. Second, we only discussed the role of amygdala
on emotional processes, whereas other neuroanatomic
systems are likely to be involved as well. Another limi-
tation is that we did not take into account the genetic
phenotypes of PD and the possible differences between
the phenotypes of PD patients (see e.g. Fiala et al. 2010)
ACKNOWLEDGMENTS
This work was supported by the Czech Science Foun-
dation (GACR), project no. 18-26094S "Emotional cre-
ativity and cognitive decline in the elderly".
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