Case Report
‘‘The Mind Is Its Own Place’’: Amelioration of Claustrophobia
in Semantic Dementia
Camilla N. Clark,1 Laura E. Downey,1 Hannah L. Golden,1 Phillip D. Fletcher,1
Rajith de Silva,2 Alberto Cifelli,2 and Jason D. Wa
en1
1 Dementia Research Centre, UCL Institute of Neurology, University College London, 8-11 Queen Square, London WC1N 3BG, UK
2 Essex Neurosciences Centre, Queen’s Hospital, Rom Valley Way, Romford RM7 0AG, UK
Co
espondence should be addressed to Jason D. Wa
en; jason.wa
XXXXXXXXXX
Received 1 March 2013; Accepted 17 June 2013; Published 6 March 2014
Academic Editor: Argye E. Hillis
Copyright © 2014 Camilla N. Clark et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
Phobias are among the few intensely fearful experiences we regularly have in our everyday lives, yet the
ain basis of phobic
esponses remains incompletely understood. Here we describe the case of a 71-year-old patient with a typical clinicoanatomical
syndrome of semantic dementia led by selective (predominantly right-sided) temporal lobe atrophy, who showed striking
amelioration of previously disabling claustrophobia following onset of her cognitive syndrome.We interpret our patient’s newfound
fearlessness as an interaction of damaged limbic and autonomic responsivity with loss of the cognitive meaning of previously
threatening situations. This case has implications for our understanding of
ain network disintegration in semantic dementia
and the neurocognitive basis of phobias more generally.
1. Introduction
Specific phobia is defined in DSM-IVR as marked, persistent,
and excessive or unreasonable fear when in the presence of,
or when anticipating an encounter with, a specific object
or situation [1]. Examples of specific phobias include ani-
mals (commonly mice, snakes, and spiders), natural envi-
onments (including heights, storms, or water),
eaches
of one’s physical integrity (blood, injections and injury)
and situations (notably, closed spaces or claustrophobia).
Specific phobias are collectively common, with an estimated
lifetime prevalence of around 10% in Western populations
[1]. As rare instances of powerfully arousing, intensely fearful
stimuli that are regularly encountered in modern developed
societies, phobias hold potentially unique insights for ou
understanding of the cognitive and neural machinery of fear.
Functional imaging in human subjects suggests that
specific phobias are neuroanatomically mediated by limbic
and paralimbic circuitry including the amygdala, anterio
cingulate, insula and dorsolateral prefrontal cortex, and
subcortical connections to the ventral striatumand
ainstem
nuclei including locus coeruleus [2–6]. These
ain regions
are involved in the representation and interpretation of
the phobic object, in amplification of the phobic response,
and generation of the characteristic somatic co
elates of
extreme fear. Proximity of the phobic stimulus modulates
activation in stria terminalis and o
itofrontal cortex, while
mismatch between predicted and experienced fear engages
the amygdala [2]. Supraliminally presented stimuli activate
amygdala bilaterally whereas subliminally presented stim-
uli demonstrate lateralised activity in the right amygdala
suggesting a role of the latter in hypervigilance to phobic
stimuli before these attain conscious awareness [4]. The role
of the amygdala is further underlined by the unique U
ach-
Wiethe syndrome in which selective amygdalar proteinosis
is accompanied by loss of fear responses [7]. Particula
phobias vary in the extent to which they engage cognitive and
autonomic components of the fear response [8, 9].
The frontotemporal lobar degenerations (FTLD) are a
diverse group of proteinopathies that present clinically with
impairments of social conduct and understanding, aphasias
or deficits of conceptual knowledge about the world at large
[10]. These diseases share a propensity to produce selective
ain network disintegration maximally affecting the frontal
Hindawi Publishing Corporation
Behavioural Neurology
Volume 2014, Article ID 584893, 5 pages
http:
dx.doi.org/10.1155/2014/584893
2 Behavioural Neurology
and anterior temporal lobes [10]. Abnormal reactivity to
and comprehension of a range of emotional stimuli are a
hallmark of FTLD and in particular the canonical syndromic
subtypes of behavioural variant frontotemporal dementia
and semantic dementia (SemD). These deficits of emotion
processing have been linked to regional atrophy and altered
connectivity in frontolimbic circuitry, including o
itofrontal
cortex, ventral striatum, insula, and amygdala [10–12]. The
SemD syndrome is of particular interest because it is under-
pinned by selective erosion of semantic memory: the human
memory system that governs conceptual and encyclopaedic
knowledge about words and objects based on an individual’s
accumulated experience of the world. SemD is associated
with progressive degeneration of a specific
ain network
centred on the anterior temporal lobes and their connections
with inferior frontal, limbic, andmore posterior
ain regions
[13]. SemD is most often led by loss of understanding of word
meanings (progressive semantic aphasia) but less commonly
can be led by deficits of nonve
al semantic memory, such as
impaired face recognition (progressive associative prosopag-
nosia) [14]. Even in patients presenting with ve
al semantic
deficits, nonve
al semantic deficits are often detectable [15],
and both ve
al and nonve
al deficits progress as SemD
unfolds, underlining the status of this syndrome as the
paradigmatic disorder of the semantic memory system. It
is increasingly recognised that SemD is associated with a
ange of behavioural distu
ances that may be at least partly
underpinned by severe deficits in comprehending affect-
laden as well as affectively neutral objects and social concepts
[12, 16, 17].
Here we describe the case of a patient in whom develop-
ment of SemD was accompanied by striking attenuation of
previously disabling claustrophobia, with implications both
for our understanding of the pathophysiology of SemD and
the
ain basis of specific phobias.
2. General Clinical Details
This 71-year-old right-handed retired medical secretary, LC,
presented with a seven-year history of cognitive decline led
y progressive difficulty recognising familiar faces. More
ecently she had been unable to recognise even close friends
and relatives and increasingly relied on other cues to thei
personal identity (e.g., the type of car they drove). She
had also experienced difficulty recognising voices over the
telephone. Word finding difficulties were an early feature
and she struggled in particular to retrieve personal and
and names. Increasingly she seemed unable to understand
how to use everyday household items or to comprehend
environmental sounds. Her family had noted an insidious
change in her personality and social behaviour beginning
around three years after the onset of prosopagnosia and
characterised by development of a sweet tooth, reduced
empathy, loss of humour and social sensitivity, and increasing
self-centredness, with obsessionality around time-keeping,
picture puzzles, and music. There was no history of topo-
graphical disorientation. There was a past history of severe
Figure 1: Representative coronal slice through the anterior temporal
lobes from
ain MRI in LC, six years after onset of symptoms
(the right hemisphere is displayed on the left). There is selective
atrophy of the anteroinferior and mesial temporal lobes including
amygdalae and hippocampi (more marked on the right) and less
marked atrophy of perisylvian cortices bilaterally.
claustrophobia with previous psychiatric contact but no othe
significant past personal or family history.
Neuropsychological assessment (summarised in Table 1)
co
oborated the clinical impression: LC showed deficits
of famous face recognition and visual object identification,
anomia, and reduced single word comprehension, but he
speech was fluent and normally constructed and there was
elative preservation of her mnestic, perceptual and exec-
utive functions. The general neurological examination was
unremarkable. BrainMRI (Figure 1) showed selective atrophy
predominantly affecting the anteroinferior and mesial tem-
poral lobes, more marked in the right hemisphere, with less
marked atrophy of perisylvian cortices bilaterally. Based on
LC’s characteristic neuropsychological and neuroanatomical
phenotype, a clinical diagnosis of SemD presenting with
progressive prosopagnosia was made. This clinical diagnosis
was additionally in linewith cu
ent consensus criteria for the
semantic variant of progressive aphasia, acknowledging that a
minority of patients in this group do present with prominent
difficulties with person recognition [13].
3. Alterations in Claustrophobia and
Other Emotional Responses
A noteworthy feature of LC’s history was striking attenuation
of her previously disabling, longstanding claustrophobia fol-
lowing the onset of cognitive decline. She had been diagnosed
y a psychiatrist with claustrophobia in her mid-twenties,
and this had remained a significant issue throughout he
adult life. Even in childhood, she had disliked being in
crowded places such as the school chapel, and in her late
teens and early twenties she exhibited mounting anxiety
when in confined spaces including lifts, trains, aeroplanes,
and other situations with no obvious route of escape. She
would develop full-blown panic symptoms with sustained
exposure to such situations and avoided them whereve
possible, sometimes at the cost of considerable inconvenience
(e.g., driving many kilometres out of her way to avoid road
Behavioural Neurology 3
Table 1: Neuropsychological profile of LC 6 years after onset of
symptoms.
Cognitive domain Raw score Percentile
∗
normal range†
General intellect (WASI)
Ve
al IQ 84
Performance IQ 93
Executive function
Stroop test: colour-word inhibition 60 s 25–50th
WMS-R Digit Span:
Forwards 9/12Max: 7 50th–75th
Backwards 9/12Max: 6 90th–95th
Episodic memory
Visual recognition:
Faces 39/50 10th
Words 27/50 5th
Language
Graded Naming Test 0/30 <1st
Synonyms:
Concrete 18/25 <2nd
Abstract 16/25 <2nd
British Picture Vocabulary Scale
(BPVS) 136/150 >144/150
†
Pyramids and palm
trees—pictures 45/52 <5th
Reading (NART) 27/50 N/A
Semantic memory: faces
Famous faces: recognition 7/12 <10th‡
Famous faces: naming 2/12 <5th†
Visual perceptual
Object decision VOSP 16 5–25th
Incomplete letters 20/20 >99th
Position discrimination 20/20 >99th
∗As applicable using WASI: Wechsler A
eviated Scale of Intelligence
[18]; Stroop, Delis-Kaplan Executive Function System Stroop Test [19];
Recognition Memory Tests [20]; GNT: Graded Naming Test [21]; Concrete
and Abstract Word Synonym Test [22]; BPVS: British Picture Vocabulary
Scale [23]; Pyramids and Palm Trees Test [24]; NART: National Adult
Reading Test [25]; VOSP: Visual Object and Space Perception Battery [26].
†Based on normative data from an historical group of 100 healthy controls
aged 55–70 years [27].
‡Local unpublished normative data from 310 controls aged 55–70 years.
tunnels or planning vacations around her fear). There had
een no suggestion of a generalised anxiety disorder nor any
history of other phobic responses. Her family reported that
LC’s claustrophobia settled within several years of onset of
her cognitive symptoms: she would, for example, now travel
willingly on the London Underground and enter crowded
lifts when accessing the platforms. A compelling illustration
occu
ed some six years following symptom onset, when she
agreed to have a
ain MRI and underwent the procedure
with no evidence of distress. Indeed, her family remarked that
loss of her claustrophobia was the one positive outcome of
LC’s SemD diagnosis.
On specific enquiry, there was the suggestion of a more
general alteration in LC’s emotional responses. In earlie
life she had been prone to fairly regular vociferous, angry
outbursts; these had abated following the onset of cognitive
decline. In addition, she now failed to react to situations
likely to have provoked disgust premo
idly (e.g., leaving
her washing machine filled with stagnant water and accu-
mulating cartons of mouldy food in her house). In contrast
to this reduction in certain strong premo
id emotional
esponses, LC had developed a craving for music (musi-
cophilia), repeatedly requesting to hear the same repertoire
of songs derived from Hollywood musicals. She evidently
derived considerable pleasure from these songs and, before
her family