An fMRI study of self-related cognitive-emotional processing in adolescents with psychometric schizotypy

Psychometric schizotypy (or psychosis proneness) refers to the presence of
psychosis-like experiences that do not reach a clinical threshold of pathology.
Psychosis proneness can be considered as a dimensional trait, which may be
detected in the non-clinical population ranging from *normality* to clinical
cases of psychosis. In psychotic disorders, lack of insight is a common and
clinically relevant feature, and may be already present to some degree in
individuals with subclinical psychotic features (e.g., not recognizing symptoms
as abnormal). However, the cognitive and neural bases of insight are still
unknown, as cognitive factors do not seem to be a sufficient explanation.
Furthermore, late adolescence is regarded as a critical period for the
expression of psychosis, thus the presence of high psychosis proneness during
this period may have a role in the neurobiology of psychosis.

The aim of the proposed research is to test, by the use of functional magnetic
resonance imaging, the hypothesis that psychometric schizotypy (referring to,
e.g., subclinical hallucinations in healthy people) is associated with reduced
activation of brain circuits subserving self-evaluation and emotion regulation.
Hence, our study will be focused on the neural substrates of subclinical
psychotic features in healthy, non-medicated adolescents, from a
community-based approach.

In this study, right-handed subjects will undertake four fMRI tasks, to be
completed in one session. By the use of fMRI, we would like to investigate the
activation of distinct brain areas engaged during self-evaluation, emotion
regulation, 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).
For the reality monitoring task, participants will have to recollect whether
information had previously been perceived or imagined by themselves of by the
experimenter. 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 whether they did
this themselves or another person.

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).

In order to investigate differential patters of ToM functioning between high
and low psychosis prone subjects, we will implement a task designed by Castelli
et al. (2000, 2002), already used in fMRI settings as also with adolescent
samples (Moriguchi et al. 2007). In those studies, animations of geometrical
figures depicting a social scene were used. Also a control condition was
applied, in which the figures performed random movement sequences. Before each
fMRI experiment, subjects were told to watch the animations and think about
what the triangles were doing and thinking during the scanning. After scanning,
subjects saw again the stimuli on a computer screen outside the scanner and
were asked to recall what they had thought during the fMRI scan that the
triangles were doing.

The Stroop task (Stroop 1935) has been widely used for the study of cognitive
control. People with schizophrenia exhibit impaired performance on cognitive
control tasks (Cohen and Servan-Schreiber 1992), an ability that is supported
by a distributed neural network that includes the anterior cingulate cortex
(ACC) and dorsolateral prefrontal cortex. As differences in brain activation
with fMRI paradigms have been found also in healthy relatives of schizophrenia
patients (Becker et al. 2008), as well as in adolescents with depressed mood
(Killgore et al. 2007) and conduct problems (Banich et al. 2007), we expect to
find differences in activation in these areas supporting cognitive control in
our sample, with greater activation associated to better cognitive control for
those with low psychosis proneness.
Stimuli consist of one of three words (RED, GREEN, BLUE) printed in one of the
three colors. Trials are either congruent (eg, the word *BLUE* written in blue
ink) or incongruent (eg, the word *BLUE* written in red ink). For all trials,
participants are instructed to respond to the color of the stimulus and to
ignore the word, as quick as possible.
The Stroop task, which involves high response conflict and strongly activates
ACC in controls (both for response conflict and for errors), as is related to
the cognitive impairment in set-shifting found as related to impaired insight
in psychosis (Aleman et al. 2006).

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 selective attention, 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