Understanding Hallucinations (part II) - fMRI & EEG

Many people experience an auditory or visual percept in the absence of adequate
environmental stimuli, i.e. hallucinations, although they suffer from quite
different diseases. In schizophrenia, the vast majority of patients experience
hallucinations and some 25% of them fail to respond to antipsychotic medication
(Sommer et al. 2012). Schizophrenia patients facing chronic hallucinations
experience severely impaired quality of life and increased risk for suicide and
violence (Hor and Taylor 2010). Hallucinations frequently remain undiagnosed
and untreated in these patients (Brewin and Patel, 2010). Between 12 and 35% of
patients with visual loss develop hallucinations; the Charles Bonnet syndrome
(CBS) (Teunisse et al. 1996), from whom 28% are severely distressed by their
hallucinations (Teunisse et al. 1996). In patients with hearing loss, auditory
hallucinations can occur; the auditory equivalent of CBS (Teunisse et al.
2012). Hallucinations occur in approximately one-third of Parkinson's disease
(PD) patients (Fénelon and Alves 2010).
Hallucinations are currently treated in accordance to guidelines for the
underlying diagnostic entity. However, one subtype of hallucinations may occur
in several different disorders, while patients with the same diagnosis may
experience different subtypes of hallucinations. These subtypes may result from
different neuropathology and may be responsive to different treatment
strategies. Identification of the neuropathological origin of these subtypes of
hallucinations may improve prediction of treatment response and stimulate the
development of new treatment strategies.
To summarize, hallucinations are common and often stressful in all of the above
disorders, while treatment for hallucinations is far from optimal (Sommer,
Koops, & Blom, 2012). It is currently not possible to predict treatment
response in individual patients and pharmacotherapy is therefore based on
trial-and-error. At this point, we do not understand the complete
pathophysiological mechanism of hallucinations, but some factors associated
with hallucinations in particular diagnoses have been well established
(Meppelink et al., 2009; Meppelink, de Jong, van der Hoeven, & van Laar, 2010;
Sommer et al., 2008; Sommer et al., 2012). To associate different
phenomenological subtypes of hallucinations with different pathophysiological
mechanisms can help to make rational treatment decisions on an individual basis
and enhance the development of innovative treatment paradigms.

The primary objectives of this proposal are:

- to reveal specific abnormalities on resting state fMRI activity of the DMN
and connectivity between DMN, medial temporal lobe structures and perceptual
cortices related to the pathophysiology of different subtypes of hallucinations
- to examine the frequency of spontaneous synchronized burst activations in
auditory and visual cortices using fMRI.
- Reveal resting state EEG correlates (spectral analysis, synchronization
likelihood) related to the pathophysiology of different subtypes of
hallucinations.
- Reveal correlating patterns of EEG and fMRI that underlie the experience of
hallucinations across different disorders.

In the proposed study, we intend to examine neural correlates of hallucinations
over different disorders using resting state EEG, and fMRi in an observational
study.
A total of 325 participants will be included: 25 hallucinating participants per
diagnostic group and a control group. The control group will consist of 175
non-hallucinating individuals who have the same disorder as the hallucinating
individuals and are matched group-wise for severity of the disease, medication,
age, sex, handedness and education to minimize differences between groups that
may confound study results. Extensive diagnostic screening of the
hallucinations will already have been completed for all participants in the
previous study Understanding Hallucinations * Part 1 (13-059).
For each subject, an MRI scan of 40 minutes duration and an EEG scan of 5
minutes duration will take place. Including preparation time for the scan and
EEG, this visit will have a duration of 2,5 hours. All measurements will be
conducted at the University Medical Center in Utrecht.

An important benefit is that understanding the underlying pathophysiology of
different subtypes of hallucinations may enable rational selection of the most
adequate type of treatment on basis of the phenomenology of the patient's
hallucinations. Moreover, the outcome measures of the current study may help to
predict treatment response so that the risk of severe side-effects need not be
taken in the predicted non-responders.
In schizophrenia patients, hallucinations fail to respond to any type of
medication in 25% (Shergill, Murray, & McGuire, 1998). As schizophrenia is a
common and life-long disorder, a high number of schizophrenia patients
currently face chronic hallucinations. Understanding the genesis of (subtypes
of) hallucinations will provide new leads for treatment in all these patient
groups who can currently not be helped. If this project indicates that
decreased attention is an important mechanism in all or in some subtypes of
hallucinations, treatment to increase attention can be effective. Furthermore,
uncovering the exact pathophysiology of (subtypes of) hallucinations will
provide important knowledge for patients, their family and society. A clear
explanation on the genesis of hallucinations helps the patient understand what
is going on. Understanding the neural substrate of hallucinations will help
family and society to understand these experiences and decrease stigmatisation
of people with hallucinations, which facilitates their social reintegration.
Another benefit is that research into subtypes of hallucinations is bound to
enrich our understanding of perception, similar to how research into subtypes
of aphasia has vastly increased our understanding of the language system.

The risk to participants is considered minimal, while the potential benefits
are considerable. Undergoing an fMRI scan and EEG recordings may lead to
additional anxiety and/or fatigue in some patients. These risks are considered
to be reasonable and minimal. As the potential benefits in terms of knowledge
gained are quite large, the benefits clearly outweigh the risks.