A Functional Neuroimaging Study of Self-related Cognitive-Emotional Processing in Psychometric Schizotypy

Psychosis-like experiences (or *schizotypal* signs) without reaching a clinical
threshold of pathology can be explored in non-clinical populations. Psychosis
proneness can be considered as a dimensional trait ranging from *normality* to
clinical cases of psychosis. When a pathological level of psychosis is reached,
lack of insight (unawareness of illness) is a common and clinically relevant
feature (Amador & David, 2004). Insight can be subdivided into three
components: (1) awareness of having an illness, (2) recognizing psychotic
symptoms as abnormal, and (3) acceptance of prescribed treatment (David, 1990).
If a diagnosed patient lacks insight in his or her illness, this can lead to
poor treatment compliance and medical adherence, poorer global functioning,
severity of psychopathology, recurrence and poorer outcome (David, 2004). This
is not only harmful to the patient, it can also lead to great frustration in
family members, friends and treating clinicians since it hampers their attempt
to help. The cognitive and neural bases of insight in psychosis remain unclear,
however, rendering it a scientific mystery. In light of the modest magnitude of
the associations that have been established between poor insight in psychosis
and reduced cognitive functioning, especially with regard to cognitive
set-shifting thought to be mediated by the frontal cortex, it is feasible that
cognitive factors can not sufficiently explain impaired insight (Aleman et al.,
2006).

The aim of the proposed research is to test the hypothesis that psychometric
schizotypy (or psychosis-proneness, i.e. subclinical hallucinations and
delusions in healthy people) is associated with reduced activation of brain
circuits subserving self-evaluation and emotion regulation.

In this study, right-handed subjects will undertake five fMRI tasks, to be
completed in two different sessions. By the use of fMRI, we would like to
investigate the activation of distinct brain areas engaged during
self-evaluation, emotion regulation, self-perspective inhibition, affective and
cognitive mentalizing, and reality monitoring, all being crucial
cognitive-emotional processes involved in insight.
In order to assess emotion regulation, subjects will be presented with a set of
pictures containing either a neutral or a negative emotional valence
(International Affective Picture System, IAPS; Lang et al 1997). In one
condition, they will be required to let themselves experience naturally the
emotional experience that the picture elicits in them (Attend condition),
whereas in the other they will have to reinterpret the content of the
photograph so that it no longer elicits a negative state (Reappraise condition).
The self-perspective inhibition task will require subjects to watch a video and
to perform two different types of perspective taking: to inhibit one*s own
perspective (self-perspective inhibition), and the ability to infer someone
else*s perspective as such (other-perspective taking).
For the reality monitoring task, participants will have to recollect whether
information had previously been perceived or imagined, or whether information
had been presented on the left or right of a monitor screen. Subjects will be
presented with a set of common word-pairs (i.e., rock and roll, bacon and eggs)
and it will comprise a learning phase and then a test phase, in which they will
have to recall either if the information was self-generated or perceived
(internal vs external source), or its position on the screen.
To assess the ability to perform a conscious reflection on one*s sense of self,
we will adapt a task applied by Johnson et al. (2002) as a functional MRI
paradigm. Participants will be asked to make decisions about themselves on
specific statements requiring self-evaluation in the domains of mood, social
interactions, cognitive and physical abilities (Self-reflection condition). In
the control condition (used to control for visual processing, attention,
language comprehension, decision making, the motor response and memory
retrieval), participants will be instructed to make decisions about statements
of semantic knowledge. For the present study, a third condition will be added,
in which participants will be asked to reflect about a familiar person, that
is, a good acquaintance of the subject (Familiar other-reflection condition).
Finally, for the affective/cognitive mentalizing task, subjects will have to
judge first (A thinks that*) and second order (A thinks that B thinks that*)
affective vs. cognitive mental state attribution, based on eye gaze.
For the tasks, we will use a custom-made MRI-compatible device (button box)
which will be placed on the lower abdomen of the subject who is lying on the
scanner table. The subject can touch the button box with both hands and,
through a mirror, see the box and his/her own fingers to ensure pressing the
desired button.
Aside from the fMRI experiments, a behavioral assessment battery will be
administered to complement and extend the data obtained through scanning, with
instruments that have been proved to be effective in the detection of deficits
in those brain regions of interest that will also be tested through fMRI.
Therefore, subjects will be tested for theory of mind (through pictures and
stories), automatic-response inhibition, and perspective taking abilities.

Subjects will be exposed to a magnetic field of 3 Tesla and rapidly alternating
magnet gradients and radio frequency fields. This field strength is used on a
routinely basis in fMRI and MRI research. So far, no side effects have been
described. On rare occasions, a peripheral nerve (abdomen) is stimulated by the
changing magnet gradients. This will cause an itching feeling, but it is not
harmful.