Novel approaches to investigating Executive Functions in Depression: the effect of mindfulness

Introduction

Research has demonstrated an association between depression and impaired
processing of emotional information (Persad & Polivy, 1993), often manifested
in memory processing, where negative informtaion is better remembered. This
bias to recall negative stimuli in depression could be related to enhanced
attentional engagement with, stronger encoding of, and/or delayed disengagement
from, negative information. In studies using the emotional Stroop task
depressed patients were found to be more distracted by negative rather than
positive or neutral words (Gotlib & McCann, 1984). Furthermore, depression is
charactersised by a lack of capacity in working memory (Channon, Baker &
Robertson, 1993). This impaired processing of emotional information is an
important factor in maintaining depression.

It is not yet clear whether these deficits in processing emotional information
only exist in current depressive states, or if they remain during remission
(Joormann & Gotlib, 2007), making a patient vulnerable to recurrence of
depression.

Mindfulness based cognitive therapy is an innovative treatment developed to
reduce risk of relapse in patients with recurrent depression. Mindfulness
training consists of 8 weekly meetings and a silent day, drawing upon
meditation exercises and cognitive therapy (Segal et al., 2002). During
mindfulness training patients learn to focus their attention on the 'here and
now' and to remain open to the present moment and their current experience,
whether positive, negative or neutral. Mindfulness training has shown to reduce
relapse rates by 50% in paitents with three or more previous episodes.
However, the precise mechanism and neural basis of the mindfulness process
remains poorly understood.

The aim of the study is twofold:

1) Examining cognitive and memory biases in depressed patients, patients in
remission, and healthy controls. This will be investigated using an emotional
Stroop task, working memory task and eye-tracking equipment.

2) The investigation of EEG correlates of cognitive and memory biases in
currently depressed patients and those in remission before and after
mindfulness based cognitive therapy, compared to a 'wait list' control group.

- Cross-sectional study

The first part of the study is cross-sectional comparison between depressed
patients, patients in remission, and healthy individuals who have registered
for a mindfulness-based cognitive therapy course. Healthy subjects will be
matched on gender, age and education level.

Prior to the investigation, patients and controls will undergo a
neuropsychological screening of their visual attention, visual-motor speed and
verbal fluency. Also, a test for verbal IQ will be administered and whether
people can recognize emotional facial expressions will be checked. These tests
will be used to determine any differences between groups to control for
possible confounds of intelligence or motivation.

Furthermore, information about any mental health problems will be collected:
• Age of onset of first depressed episode, number of depressive episodes, and
treatment history.
• Beck Depression Inventory (BDI, Beck, Ward, Mendelsohn, Mock, & Erbaugh,
1961).
• State Trait Anxiety Intentory, state subscale (STAI, Laux, Glanzmann,
Schaffner, & Spielberger, 1981).
• Life events (Caspi, A. et al., 2003).

Finally, the following neuropsychological computing tasks will be administered:

Task 1) Emotional Stroop task with faces. The Stroop test is used to measure
the interference of emotions when processing presented stimuli. The expectation
is that depressed patients will be more distracted by sad and angry faces, thus
interfering with performance, compared to patients in remission and healthy
subjects.
Task 2) Working memory. Participants will be asked to remember task-relevant
stimuli and suppress task-irrelevant stimuli. They will be asked where unseen
faces were located: top left, bottom left, right, top or bottom right. The
effect of emotional facial expression on correct memory recall will be
examined.
Task 3) Using eye-tracking equipment will determine how much time participants
spend on the different facial expressions.


- Controlled study

The second part of the study a controlled study on the effects of
mindfulness-based cognitive therapy vs. a waiting list control condition in
patients with current depression or in remission.

Before and after the intervention or waiting list condition, the following EEG
/ ERP measurements will be collected:

Task 1) Auditory "Novelty Oddball" paradigm eliciting the P300 (P3) ERP
component; an index of attention and memory processing (Cahn & Polich, 2006).
Participants are presented "standard" 1000 Hz tones (80%), "non-standard
"1500Hz tones (10%) and novel (10%) sounds. They are instructed to respond as
fast and accurately as possible to non-standard tones, whilst ignoring the
standard and novel stimuli. Previous research presents the P3 to be a robust
biological marker of depression, in which patients produce significantly lower
P3 amplitudes to stimuli compared to healthy controls. We hypothesize that
these cortical components could 'normalise' in patients after mindfulness
training.

Task 2) Alpha (α) Lateralisation task, indexing the margin of α-lateralization
in attentional processing. Two grey-coloured squares will be presented in the
lower left and right corners of a computer monitor, presenting rotated *L* and
*T* shapes. Participants will be instructed to refrain from moving their head
or eyes but maintain focus on a fixation cross placed centrally onscreen, and
indicate the position of the horizontal bar relative to the vertical bar in the
rotated *L*. According to the approach-withdrawal model of emotion (Davidson,
1993), α-band asymmetry is a stable *trait*, whereby left frontal hypoactivity
relative to right frontal hyperactivity has been demonstrated as a robust
cortical marker of depression, in alignment with the behavioural disposition to
*withdraw* or avoid unpleasant stimuli/life events. It is our hypothesis that
mindfulness will reduce this cortical asymmetry. Additional measures of vagal
tone (heart rate/variability, HR/V) aim to provide further insight into
possible alterations of the affective and physiological pathways in response to
the mindfulness training.

Task 3) Cognitive (letter stimuli) and Affective (standardized word stimuli) Go
/ NoGo tasks, eliciting the error-related negativity (ERN) ERP component.
Error-related negativity (ERN / Ne) and error-related positivity (Pe)
components are associated with the detection of errors and response monitoring,
indexing both motivational and affective variables mediated by the anterior
cingulate cortex (ACC). ERN amplitude reflects an error detection and / or an
affective response to the error. Depression reflects an increase in behavioral
sensitivity to making mistakes, in addition to increased neural sensitivity to
errors reflected by a higher ERN amplitudes compared to healthy controls. It is
our hypothesis that mindfulness will result in reduced ERN amplitudes.

The mindfulness based cognitive therapy (MBCT) course consists of eight weekly
sessions of 2.5 hours and a silent day. The groups consist of 8 to 15 people.
During the course, patients exercise with meditation and cognitive behavioral
therapy. They are also asked during the course to meditate for three minutes
each day outside of the classes.

Participants may experience some fatigue during testing. However, we will
offer frequent breaks during the testing and inform participants that they may
also request breaks from testing as needed.