Rescuing the Ruminating Brain: Identifying Biomarkers of Rumination and Mindfulness Through Concurrent EEG and Functional Magnetic Resonance Imaging (fMRI) Studies of Schizophrenia and Depression

Is "the idle mind the devil's playground?" It depends on where the wandering mind goes. If it
is busy reflecting on recent activity, consolidating recent material into long term memories,
and envisioning the future, then these thought patterns may be highly adaptive, allowing us
to learn from the past and plan for the future. But when the mind turns to the dark side and
rumination takes over, these thought patterns are maladaptive. Rumination involves recursive
negative thinking focused on causes and consequences rather than solutions. It cuts across
diagnostic boundaries: it is both a cause and consequence of major depressive disorder (MDD)
and is related to hallucinations and delusions in schizophrenia (SZ). It affects cognitive
and emotional responses, yet it can be treated with mindfulness-based therapies.

Mindfulness-meditation is a type of behavioral therapy that focuses on cultivating present
focused attention, is a stress-reduction intervention that targets rumination, and improves
many medical and psychiatric conditions: Trait mindfulness is associated with less distress
from auditory hallucinations and fewer residual depressive symptoms. It is the practice of
attending to present moment experiences and allowing emotions and thoughts to come and go
without judgment, thereby avoiding a downward spiral into rumination.

Compared to simple mind wandering, a brief mindfulness induction recruits an attention
network including parietal and prefrontal structures while mind wandering only recruits the
default mode network (DMN) Based on data from the last funding period, the investigators know
that activation of the DMN affects both basic sensory and semantic processing in SZ. The
investigators propose to extend this by focusing specifically on rumination and adding
patients with depression. The investigators ask how rumination affects basic sensory,
cognitive and emotional responses, and if mindfulness can rescue these functions, across
diagnoses and the wellness spectrum.

The investigators will acquire simultaneous EEG and fMRI data from Veterans with depression
and schizophrenia and mentally healthy Veterans to assess early sensory responses, context
updating, and responses to emotional images. Understanding how rumination affects engagement
with the environment is the first step towards assessing its far-reaching cognitive and
emotional costs, which cut across traditional diagnostic boundaries. Understanding how
mindfulness restores information processing will increase our understanding of how, and for
whom, it works.

The investigators predict rumination inductions will prevent the brain from fully processing
a spectrum of external events, and mindfulness inductions will restore these abilities. The
investigators predict trait rumination and mindfulness will modulate the effects in all
groups, with exaggerated effects in those with depression or schizophrenia. The outcome
variables will be EEG-based event related potentials (ERPs) and fMRI, and their integration.
Symptom severity, trait rumination, and trait mindfulness will be considered in the analyses.

Aim 1: Simple effects of rumination inductions on fMRI connectivity. The investigators will
compare the effects of rumination and mindfulness inductions on the connectivity between DMN
and rumination-sensitive brain regions. Compared to mindfulness inductions, the investigators
predict rumination will increase this connectivity, with greater effects in depressed and
schizophrenia patients than in healthy controls.

Aim 2: Carry-over effects of mindfulness inductions on ERPs and fMRI and their integration.
The investigators predict the effects of 30-second mindfulness inductions will persist into
the subsequent visual oddball task, thereby augmenting sensory, attention, and emotional ERP
components and fMRI activation in sensory, cognitive and emotional networks, compared to
rumination inductions. The investigators will explore the covariance between fMRI and ERP
data fusion methods as they have done previously.

Aim 3: Effects of trait rumination and mindfulness. The investigators will assess the
relationship between neural data and trait rumination, mindfulness, and symptom severity in
all groups.

Inclusion Criteria:

(All)

- Veterans

- 18-65 years of age

- Negative metal screen for MR scanning

- Corrected to normal vision

Inclusion Criteria (patients):

- Meet criteria for SZ or MDD as assessed using the Structured Clinical Interview for
DSM (SCID), with a consensus diagnosis between trained research staff member and an
attending psychiatrist or psychologist.

- Stable medication regime for > 1 month

Exclusion Criteria:

(All)

- Past or present neurological problems (including seizures and head trauma resulting in
neurological or cognitive sequelae)

- Loss of consciousness (LOC) greater than 30 minutes or any LOC with neurologic
sequelae

- Major medical conditions (e.g., significant hypertension, diabetes not controlled by
diet alone, seizure disorders, treatment with anticonvulsant medication, endocrine
disorders, significant cardiac pathology)

- Substance abuse within three months of participation or any history of substance
dependence

- History of HIV risk behaviors

- Known claustrophobia

- Pregnancy. If the participant cannot rule out pregnancy, a pregnancy urine test will
be conducted moments before scanning.

- Uncorrected vision as assessed by the Snellen chart.

Exclusion criteria (patients only):

- Any primary Diagnostic and Statistical Manual Diploma in Social Medicine (DSM) Axis I
diagnosis other than SZ or MDD

Exclusion criteria (controls only):

- Any past or present DSM Axis I diagnosis

- Chronic treatment with medication that affects cognitive function