Secondary Schizophrenia (11 page)

through the visual system is disrupted.

VHs may also occur in healthy adults under periods of
Although lesion-based models afford some under-sensory deprivation
[42],
sleep deprivation
[43],
and
standing of the anatomy of normal and abnormal
starvation
[44].

visual processing, they do not shed light on functional or neurochemical changes that occur as a result,
and do not account for VHs that relate to substance
Neurobiology of visual hallucinations

intoxication or withdrawal, medication-related VHs,
The initial understanding of the pathophysiology
or VHs seen in global neurometabolic or neurode-of VHs postulated that VHs originated in irritative
generative disorders such as delirium and dementia.

foci, such as those causing epileptiform activity after
In particular, pharmacologically induced hallucina-infection or trauma in cortical regions involved in
tions suggest that medications with anticholiner-vision
[45].
These VHs are usually brief, intermittent,
gic (particularly antimuscarinic) properties are the
and stereotyped, meeting criteria for “simple” VHs
most visually hallucinogenic
[55],
particularly in the
[22],
and were informed by the cortical stimulation
elderly who generally have lower cholinergic tone than
studies by Penfield and Perot, whereby occipital stim-younger adults
[56].
VHs occur, although less com-ulation induced simple VHs, with temporo-occipital
monly, with perturbations to serotonergic transmis-and parieto-occipital stimulation resulting in more
sion with hallucinogen use, although visual distor-complex scenes
[46].
Simple VHs however are perhaps
tions and an exaggerated sense of reality are more
the least common form of VHs; this model does
frequent
[57, 58].
Additionally, altered dopaminergic
not account for more complex nonstereotyped and
transmission in stimulant misuse and dopaminergic
continuous (or more “complex”) VHs. These types of
treatment of Parkinson’s disease (PD) and other synu-hallucinations were most particularly seen in the blind,
cleinopathies suggest a role for dopamine transmis-leading to the theory, first postulated by West
[47],
that
sion in VHs
[59, 60]
. However, psychotogenic stim-loss of afferent input “releases” the visual and nearby
ulants tend to produce more auditory hallucinations
cortex. The theory of VHs as release phenomena,
and paranoia than VHs. When VHs occur in PD, they
elaborated by Cogan
[48],
provides a model for under-tend to occur in advanced disease when cholinergic
standing how VHs following lesions to more “proxi-deficit is more profound
[61].
The cortical serotonin
24

mal” structures occur, particularly in circumstances
to acetylcholine ratio is significantly increased
[62],

Chapter 3 – Secondary hallucinations

and respond to cholinergic medication
[63],
tending to
trigger, and are maintained by, a delusional system
suggest an interaction between the dopaminergic and
[69].
The higher rate of auditory hallucinations in
cholinergic (and possibly serotonergic) systems under-schizophrenia may reflect a greater pathoplastic effect
pinning VHs
[49].
This interaction between dopamin-on anterior rather than posterior corticocortical sys-ergic and cholinergic systems probably also results in
tems, and hence affect attribution of speech to a greater
the characteristic VHs of delirium, where metabolic
degree than visual phenomena.

stress results in dopamine release and subsequent
Whereas the neurocognitive origins of auditory
spreading neuronal depression
[64, 65].
Cholinergic
hallucinations in schizophrenia are slowly being elu-systems may be most vulnerable to these effects, result-cidated
[70]
, few models exist for the generation of
ing in attentional and memory deficits in addition to
VHs in schizophrenia; it is likely, however, that the
VHs. Finally, alterations in the GABAergic system that
core neurocognitive processes are similar. Patients
occur in benzodiazepine and alcohol withdrawal, often
with schizophrenia show deficits in shifting spatial
associated with CVHs, implicate a loss of GABAergic
attention
[71]
, which is strongly correlated with pos-cortical inhibition in withdrawal-associated VHs
[66],

itive symptoms including hallucinations
[72].
The
although this is likely to be mediated through other
perceptual-attentional model (discussed later) sug-monoaminergic systems
[49].

gests that hallucinations require attentional deficits
These otherwise disparate anatomical and neu-combined with visual processing deficits
[67];
the for-rochemical models of VHs have been united in the
mer is established as a core deficit of schizophrenia,
perception and attentional deficit (PAD) model of
and visual processing deficits are seen in schizophre-Collerton and colleagues, which focuses on deficits in
nia in “dorsal stream” functions such as motion detec-object-based attention due to dysfunction in lateral
tion, backward masking, and recognition of atypical
frontal cortical systems combined with object-based
objects
[73, 74, 75].
In schizophrenia, widespread cel-perceptual deficits due to dysfunction in the ventral
lular structural abnormalities that also affect the visual
(“what”) as opposed to dorsal (“where”) visual stream
cortex
[76],
combined with subtle impairments in dor-

[67].
Unlike other models, this can account for VHs
sal stream processes to degrade early visual processing
whose origin is either predominantly lesion-based or
and render it vulnerable to attentional deficits
[77].

neurochemically driven, in addition to VHs that occur
in states of sensory deprivation or in hypogogic or
hypnopompic states.

Delirium

One of the cardinal features of delirium, in addition
Visual hallucinations in psychiatric

to attentional dysfunction and impairments in con-

disorders

sciousness, is the presence of psychotic symptoms,
particularly VHs. The wide range of insults that can
result in delirium is illustrative that VHs in delirium
Schizophrenia

can result from perturbations in most of the neuro-Traditionally, VHs have been thought to be relatively
transmitter systems described above, including gluta-uncommon in schizophrenia in comparison to audi-matergic, GABAergic, cholinergic, dopaminergic and
tory hallucinations, due to work published by Gold-cholinergic function – as exemplified by alcohol with-berg in 1965 suggesting that only 18% of patients
drawal, anticholinergic delirium, and the serotonin
experience this phenomenon
[19],
and the belief that
syndrome
[78, 79]
. Other substances that stimulate
higher prevalence rates only occurred in specific cul-ventral tegmental area dopaminergic neurons, such
tures
[17,
68].
However Bracha and colleagues, exam-as opioids and corticosteroids, result in increasing
ined rates of VHs in patients enrolled for schizophre-nucleus accumbens dopamine release and consequent
nia studies at the National Institutes of Mental Health
reductions in thalamic and cortical acetylcholine
[80,

in the United States, and showed that VHs were present
81].
One integrative model of psychotic symptoms,
in approximately half of all patients but were often not
including VHs, in delirium proposes that the thalamus
inquired about by clinicians
[16].
When VHs occur,
is the final common pathway for most of these insults,
they tend to occur with auditory hallucinations and
impairing the thalamic filtering/modulation function
delusions, usually as part of a relatively systematized
on information flow to sensory cortex from thala-

25

psychotic experience where hallucinatory phenomena
mocortical afferents and thus producing attentional

Introduction – Section 1

Figure 3.1
Lesions giving rise to VHs, marked with white arrows. (A) An 85-year-old woman with bilateral pontine infarcts who saw
Lilliputian figures and the face of a famous actor superimposed on others’ heads. (B) A 68-year-old woman with a right thalamic infarct who
presented with VHs of small children wearing colorful uniforms. (C) A 33-year-old woman who had a previously embolized left
temporoparietal arteriovenous malformation – which recurred, and caused focal epileptiform activity – who described seeing the letters W, R,
and K on people’s faces, spikes coming from the floor, and disembodied heads and torsos floating 10 feet above the ground. (D) A 52-year-old
man with central pontine myelinolysis in the setting of chronic alcohol abuse, who presented with VHs of faces emerging from the walls with
grotesque, “alien-like” features and of multiple animals.

disturbance and psychotic symptoms such as VHs
VHs are usually clear, colorful and often Lilliputian
[82].

images of people, animals, and inanimate objects. They
tend to disappear on eye closure (unlike drug-induced
Visual hallucinations in neurological

states, which worsen with eye closure) and occur in
low light
[84].
In peduncular hallucinosis (PH)
[86],

disorders

vivid complex VHs occur in the presence of lesions
to the midbrain or thalamus, which alter the modula-Localized pathology
tion and flow of information through the visual system
As previously described, lesions that affect the visual
[29].
Jean Lhermitte first described PH in a 72-year-pathway from retina to occipital cortex, in addition to
old woman with hallucinations of strangely, colorfully
lesions affecting ascending brainstem/midbrain struc-attired people and groups of children which occurred
tures, can cause visual hallucinations
[27,
28,
29,
50].

at dusk
[87].
Common hallucinations include animals,
An analysis by Braun and colleagues demonstrated
people or children, grotesque and deforming faces or
that occipital and occipitoparietal regions were the
heads, landscapes and tessellated patterns, and groups
most commonly implicated cortical regions, and the
of people walking in file
[29].

midbrain, peduncles, pons, and thalamus were the
most affected subcortical structures
[83].
A wide range
of developmental, acquired and iatrogenic lesions have
Neurodegenerative disorders

been implicated, including vascular, neoplastic, trau-Alzheimer’s disease (AD), the most common form
matic, and infectious lesions, migraine, compression,
of dementia in the community, not uncommonly
demyelination, and surgical and angiographic inter-presents with VHs, with a prevalence higher than for
vention
[29].
Some examples of the lesion types that
auditory hallucinations (19% vs. 12%) and which tend
may give rise to visual hallucinations are described
to occur with more advanced disease
[88].
VHs in AD

in
Figure 3.1.
Two relatively well-described lesion-may be a result of pathology in the visual (association)
related syndromes are the Charles Bonnet Syndrome
cortex
[52]
, particularly periventricular white matter
and peduncular hallucinosis.

lesions
[89]
and occipital atrophy
[86].
This may relate
The Charles Bonnet Syndrome (CBS) has generally
to the predilection of neurofibrillary tangles for visual
been used to describe a syndrome of complex visual
association, rather than primary visual, cortex
[90];