An fMRI investigation of the neural substrate of cognitive insight in non-clinical subjects

Insight into illness is impaired in 50-80% of patients with schizophrenia and
has been associated with treatment non-adherence and poorer prognosis in
general. Several theories have been proposed to explain the etiology of
impaired insight and we propose a multifactorial etiology combining different
theories, hypothesizing that impaired cognitive insight has neurobiological,
neuropsychological, and psychological aspects. A distinction between cognitive
and clinical insight is made. Cognitive insight is the ability to reflect upon
one*s own thoughts and behaviors and to be open to corrective feedback from
others, while clinical insight involves (1) awareness of being ill, (2)
attribution of symptoms to the illness and (3) realizing need for treatment.
Multiple studies have examined the neural basis of clinical insight in
psychosis. Measures of clinical insight do not address the impaired ability to
evaluate aberrant experiences and the openness to corrective feedback from
others, even though these cognitive deficiencies may contribute to impaired
clinical insight. Patients may therefore sometimes appear to have good clinical
insight, while this may just reflect superficial beliefs or repetition of
explanations from psychiatrists. Cognitive insight can also be measured in
people without a mental disorder (i.e. non-clinical subjects). Learning more
about the neural substrate of cognitive insight in non-clinical subjects could
improve our understanding of impaired insight in psychotic disorders and could
also be of value for treatment, as these aberrant cognitive thinking styles can
be used as targets for intervention.

To investigate the neural substrate of cognitive insight in non-clinical
subjects.

In this project we will test several hypotheses: (1) individuals with lower
levels of cognitive insight will be less able to use feedback to correct
self-evaluation, and will show less brain activation and/or connectivity of
relevant brain areas during processing of self-related feedback compared to
individuals with higher levels of cognitive insight, (2) individuals with lower
levels of cognitive insight will show less brain activation and/or connectivity
of relevant brain areas (associated with attentional regulation: re-shifting
and sustaining attention) during a brief mindfulness induction, (3) individuals
with lower levels of cognitive insight will show less functional and structural
connectivity of the default mode network (DMN) during resting state, and (4)
individuals with lower levels of cognitive insight will have more problems with
sustained attention, inhibition and meta-awarenesss.

This observational study will combine fMRI and behavioral measurements.
Participants will be recruited from different places in Groningen via
advertisements (for example at the RUG, UMCG, Hanze University of Applied
Sciences, and different institutes that offer courses on meditation, yoga or
mindfulness, etc). We will include both participants with and without
mindfulness experience. 200 participants will be screened of which 60
participants will be included based on their score on the self-reflection (SR)
subscale of the Beck Cognitive Insight Scale (BCIS): 20 individuals with low
(25% lowest scores), 20 with average (middle 50%) and 20 with high (25% highest
scores) cognitive insight. They will participate in two experimental sessions
that involve filling in of several questionnaires (22 minutes), a computer task
(30 minutes), a monopoly game as preparation for one of the fMRI-tasks (45
minutes), rating of their own and other*s traits (max 30 minutes), scanning (78
minutes) and cognitive tests (15 minutes). The scanning session will consist of
the following: two different fMRI tasks, a resting state fMRI scan, a diffusion
weighted image (DWI) and a structural MRI-scan.

The participant's burden consists of online screening questionnaires (duration:
25 min), a screening interview (duration: 15 min) and two experimental sessions
(1st session of 135 minutes; 2nd session of 145 minutes). Participants will be
selected based on their response on four questionnaires and the interview
during the screening moment. During the screening moment it is ensured that all
requirements are met. The first experimental session will take approximately 2
hours and 15 minutes at most including a break. During the first session,
participants will complete several questionnaires on a PC (22 minutes),
complete a computer task (30 minutes), complete a cognitive test (5 min), play
a game in preparation of one of the fMRI tasks (45 minutes), rate three other
participants on trait characteristics (18 minutes), and will be shown the dummy
MRI scanner. The second experimental session will take place the day after and
will last approximately 2 hours and 25 minutes including a break. During this
session, participants will be scanned (78 minutes), they have to rate
themselves and one other participant (12 minutes), and a cognitive test will be
conducted (10 minutes). Before the scanning session the participant will be
required to fill and sign a safety-specific questionnaire. The participants
will perform two computer-based paradigms during scanning, with a duration of
approximately 48 minutes (social feedback task: 36 minutes; mindfulness
induction: 12 minutes). We do not expect these paradigms to be problematic in
the current group of participants.

To undergo an MRI scan involves: exposure to loud noise (addressed with ear
protection, by means of both ear plugs and headphones), a moderate amount of
physical restraint (the head is inside an MRI coil; the feeling is similar to
wearing a motorbike helmet), as well as to a strong constant magnetic field
(3Tesla), and small variable electromagnetic fields. Functional MRI is an
eminently safe technique; there are no risks that have been associated with the
acquisition of fMRI data per se. Participants will be exposed to a magnetic
field of 3 Tesla and rapidly alternating gradients and radio frequency fields.
These field and gradients' changes are routinely used in fMRI and MRI research.
The strong magnetic fields used by fMRI can dislocate ferromagnetic particles
inside the brain and the eyes, interfere with the functioning of electronic
devices implanted inside a person's body (pacemakers, insulin pumps, etc.), as
well as induce heating in artificially metal-rich regions (red tattoos,
metallic supports to previously fractured bones, prosthetic implants). In order
to avoid the risks involved with such possible conditions, participants will be
required to complete a questionnaire and only if none of the exclusion criteria
are met the participant will be allowed to participate in our experiment.

The environmental conditions of being inside an MR scanner and of being
partially restrained can induce claustrophobic feelings. Three steps will be
taken to reduce this risk: 1) the participant will be explicitly asked about
being claustrophobic, 2) the participant will experience a training moment in a
dummy scanner and 3) prior to the beginning of the actual experiment, and
during pauses between scans, participant will be asked about their wellbeing.
Additionally, they will receive an alarm trigger that they will be able to use
at any moment to interrupt the scanning. Finally, an experimenter will be in
close proximity of the participant during the session, which will allow a close
monitoring of the participant*s wellbeing.

The study is not intended to benefit the participants directly. Participants
will receive compensation for their contribution.