Revealing individual neural underpinnings of anxiety in healthy subjects

Symptoms of anxiety are based on amygdala responsiveness, which can be evoked
by the activation of multiple different brain circuits. We aim to characterize
the following neural mechanisms that might cause amygdala hyper-responsiveness;
high locus coeruleus drive, low prefrontal control or increased amygdala
sensitivity. We hypothesize that variation in local sensitivity and variation
in specific control mechanisms may explain why certain individuals are more
fearful than others. The same phenotype may result from different neural
mechanisms.

In this proof-of-concept study, we aim to characterize healthy individuals with
regard to their individually predominant neural mechanism. Thereby, we aim to
divide a sample of healthy individuals into three clusters based on their
individual anxiety related circuit activation. Selection of high trait anxious
individuals will most probably increase the chance to identify anxiety related
neural mechanisms, which might not be detectable in a randomly drawn sample of
healthy participants. Furthermore, a comparison to a low anxious group secures
specificity of these mechanisms. We will validate our stratification procedure
by assessing different neural and behavioral measures.

The online link to our questionnaire on www.soscisurvey.de will be distributed
by flyers on campus and the study will be advertised during university
lectures. Participants are informed about the rationale of the study and the
potential possibility to take part in an fMRI investigation before filling out
an online questionnaire. Participants are asked to create an online-account on
soscisurvey.de and anonymously fill in the HADS questionnaire. After completion
of the questionnaire the participant*s score is calculated by the online
platform*s software and each participant receives a personal code. Participants
that reach a score of eight or higher are immediately after the questionnaire
informed by an on-screen message about the possibility to take part in an fMRI
investigation in our institute. In case they are interested, they are asked to
indicate their interest by button press. This will trigger an anonymous message
to our experimenter account on soscisurvey.de. Soscisurvey allows to
participate in the survey and indicate interest an fMRI investigation without
the chance on behalf of the experimenter to link questionnaire results to a
participant. Via soscisurvey, the experimenter can contact potential
participants anonymously and based on their score in the questionnaire. This
happens without any knowledge on and access to the personal or questionnaire
data of the potential participant. For selection of participants that score
according to our design, a corresponding algorithm is implemented in the survey
software. Hence, despite communicating with a participant based on their score,
the examiner does not have access to their personal data and the participant*s
individual answers on the questionnaire as long as these do not provide their
code and have signed the consent form. An appointment for the fMRI examination
will be arranged and participants will be asked to bring their code. At the
institute, participants will be fully informed about the rationale and
procedure of the fMRI investigation. They are asked to give their consent and
after signing the informed consent form to provide their code. This enables the
experimenter to retrieve the participant*s score from the soscisurvey database.
During the fMRI investigation, three tasks will be applied to probe the three
amygdala-centered networks. A pre-frontal regulation task will be applied to
monitor activity in the prefrontal cortex. Amygdala reactivity will be
monitored by applying an emotional face processing task. Salience processing
will be used to monitor activity in the locus coeruleus. Stimulus materials for
visual stimulation are taken from standardized stimulus sets. Tactile
stimulation is applied using stimulation by electrodermal stimulation. After
the fMRI session, participants are asked to complete the emotional adjustment
questionnaire (FEEL-E, Grob & Horowitz, 2014). This questionnaire evaluates
adaptive and maladaptive emotion regulation strategies.

MRI is a non-inversive imaging technique. Only occasionally (< 0,5%) subjects
report vertigo-like sensations and/ or slight nausea symptoms due to movement
in the static field of the scanner. Sensitivity to these effects varies
considerably between individuals. In rare cases, minimal muscle contractions
due to nerve stimulation abating when the scanning procedure stops. Acoustic
noise from the MRI scanner can be reduced wearing shielded earphones during the
scanning procedures.
Burdens and risks are very minimal to negligible. The HADS is a 14-item online
questionnaire that evaluates symptoms of anxiety and depression. The HADS is a
screening tool to evaluate trait anxiety in healthy and clinical populations,
without specification of certain affective disorder. Participation in the
questionnaire takes approximately two to six minutes. Administration of the
HADS in an unsupervised manner does not cause any known risks. The FEEL-E
questionnaire evaluates adaptive and maladaptive emotion regulation strategies
and takes approximately 30 minutes. The FEEL-E will be filled out in the
institute under supervision of the investigator. Hence, no risks for the
participants relating to the questionnaire procedures are expected.
Participants that reach a score of clincal relevance on the HADS (>10) are
advised to consult their GP or psychologist. Incidental neurological findings
during the fMRI session are reported to the participant's GP.