SCAN (2009) 4, 313–327
Medial cortex activity, self-reflection anddepression
Marcia K. Johnson, Susan Nolen-Hoeksema, Karen J. Mitchell, and Yael LevinDepartment of Psychology, Yale University, PO Box 208205, New Haven, CT 06520-8205, USA
Using functional magnetic resonance imaging, we investigated neural activity associated with self-reflection in depressed[current major depressive episode (MDE)] and healthy control participants, focusing on medial cortex areas previously shownto be associated with self-reflection. Both the MDE and healthy control groups showed greater activity in anterior medial cortex(medial frontal gyrus, anterior cingulate gyrus) when cued to think about hopes and aspirations compared with duties andobligations, and greater activity in posterior medial cortex (precuneus, posterior cingulate) when cued to think about dutiesand obligations (Experiment 1). However, the MDE group showed less activity than controls in the same area of medial frontalcortex when self-referential cues were more ambiguous with respect to valence (Experiment 2), and less deactivation in a non-self-referential condition in both experiments. Furthermore, individual differences in rumination were positively correlated withactivity in both anterior and posterior medial cortex during non-self-referential conditions. These results provide convergingevidence for a dissociation of anterior and posterior medial cortex depending on the focus of self-relevant thought. They alsoprovide neural evidence consistent with behavioral findings that depression is associated with disruption of positively valencedthoughts in response to ambiguous cues, and difficulty disengaging from self-reflection when it is appropriate to do so.
Keywords: self-reflection; medial frontal cortex; posterior medial cortex; rumination; depression
Anterior medial cortex (e.g., medial frontal gyrus, anterior
In addition, individual differences in chronic promotion
cingulate cortex) and posterior medial cortex (e.g., posterior
orientation (i.e. a focus towards approach goals; Higgins,
cingulate cortex, precuneus) show increased activity during
1997, 1998) were positively correlated with activity in
self-referential processing (Johnson et al., 2002; Fossati et al.,
medial prefrontal cortex (PFC) during hopes/aspirations
2003; Macrae et al., 2004; Ochsner et al., 2005; Vogt and
trials. Similarly, in a medial frontal area near the location
Laureys, 2005; Amodio and Frith, 2006; Johnson et al.,
that Johnson et al. (2006) found correlated with promotion
2006; Northoff et al., 2006). Furthermore, activity in these
focus, Sharot et al. (2007) found that more optimistic people
two areas may be associated with different types of self-
showed greater activity when thinking about positive events,
referential processing. Based on the idea that different
relative to negative events. Together, these findings suggest
types of self-relevant agendas (e.g. goals; Johnson and
that anterior medial PFC may be recruited during positive,
Reeder, 1997) are an important part of one's self-definition
approach-oriented self-relevant thought (see also, Mitchell
and play a key role in determining one's emotions and reg-
et al., 2009).
ulating interactions with others (Markus and Nurius, 1986;
Differences in medial cortex activity have been observed in
Cantor and Kihlstrom, 1987; Higgins, 1997), Johnson et al.
comparisons of depressed individuals with healthy controls,
(2006) investigated two broad classes of agendashopes and
both in resting state and active tasks (Mayberg et al., 1999;
aspirations, and duties and obligations. Replicating others,
Drevets, 2000; Charney and Manji, 2004; see Drevets et al.,
they observed greater activity in anterior and posterior
2008; Gotlib and Hamilton, 2008, for reviews). In addition,
medial areas for self-referential than for non-self-referential
depression is associated with rumination about negative self-
processing [e.g. thinking about concrete things such as polar
relevant information (Nolen-Hoeksema et al., 2008), and the
bears fishing (Nolen-Hoeksema, 2004)]. They also found a
tendency to ruminate may be related to differences in ante-
dissociation: there was greater activity in anterior medial
rior medial cortex activity (e.g. Ray et al., 2005; Greicius
et al., 2007). However, the specific factors (e.g. types of
aspirations, but greater activity in posterior medial areas
self-focus) that affect whether depressed individuals show
when participants thought about duties and obligations.
elevated or reduced activity in medial cortical regions (andin which subregions) remain to be specified (Drevets, 2000;
Received 19 June 2008; Accepted 21 June 2009
Davidson et al., 2002; Mayberg, 2003a; Phillips et al., 2003;
Advance Access publication 20 July 2009
These studies were funded by National Institutes of Health (AG09253). We thank MR technologists Hedy
Mayberg et al., 2005).
Sarofin and Cheryl McMurray for assistance in collecting the MR data; Kathleen Muller for help
The present experiments begin to address this issue by
with figures and scoring of the participants' post-scan reports; and Anna Swan for help with report scoring.
comparing medial cortex activity of individuals experiencing
Correspondence should be addressed to Marcia K. Johnson, Department of Psychology, Yale University, PO
Box 208205, New Haven, CT 06520-8205, USA. E-mail: [email protected]
a major depressive episode (MDE) and control participants
ß The Author (2009). Published by Oxford University Press. For Permissions, please email: [email protected]
M. K. Johnson et al.
as they engaged in different types of self-reflective thought
disorder, and normal, or corrected to normal, vision. Beck
compared with non-self-reflective thought. On self-reflection
Depression Inventory (BDI-II; Beck et al., 1996) scores were
trials in Experiment 1, we cued participants either to think
obtained on the day of the scan. Control participants [n ¼ 24
about hopes and aspirations or duties and obligations, con-
(11 females)] had BDI scores 8 (M ¼ 4.04, s.d. ¼ 2.65);
ditions shown previously to differentially engage anterior and
MDE participants [n ¼ 20 (9 females)] had BDI scores 21
posterior medial cortex in healthy controls. In Experiment 2,
(M ¼ 27.85, s.d. ¼ 6.23). All MDE participants met full
we cued participants either to engage in self-evaluation or to
criteria for a current MDE according to the Structured
think about their current state, activities that previously have
Clinical Interview for DSM-IV (SCID; First et al., 1998),
been shown to differentially induce rumination in depressed
administered at the end of the scan session. None of the
participants. Thus, Experiment 1 assessed whether depressed
participants in the control group met the criteria for either
participants differed from controls in engagement of anterior
current or past MDE. Inter-rater reliability on the SCID was
medial cortex associated with positive thoughts such as
good ( ¼ 0.67, P < 0.0001). The groups did not differ on age
hopes and aspirations when specifically cued to do so;
[Mcontrol ¼ 20.6
and Experiment 2 assessed whether depressed participants
(s.d. ¼ 2.9 years); P > 0.05] or education [reported in years;
differed from controls in the engagement of this area under
Mcontrol ¼ 14.4 (s.d. ¼ 1.9 years), MMDE ¼ 15.3 (s.d. ¼ 2.2
conditions that did not specifically cue positive thoughts.
years); P > 0.10]. Four of the MDE participants self-reportedtaking psychotropic medications (lamictal, effexor, zyprexa,
zoloft). Because the pattern of findings remained the same
Emotional distress (depression and anxiety) has been asso-
when participants taking medications were removed, we
ciated with reductions in promotion or approach goals and
report the data with these participants included. The
increases in avoidance goals (Gray, 1982; Fowles, 1988;
Davidson, 1998; Dickson and MacLeod, 2006). Building on
Medical School approved the protocol, and consent was
the finding that anterior medial PFC is especially associated
obtained according to the Declaration of Helsinki (1991,
with thinking about promotion or approach goals (e.g.
Br Med J, 302, 1194). All participants were paid.
hopes and aspirations; Johnson et al., 2006), we predicted
Design and procedure.
The study was a mixed 2
that, when asked to think about hopes and aspirations, indi-
(group: control, MDE) 3 (condition: hopes, duties, dis-
viduals experiencing a MDE would show less activity in
traction) design. Participants saw short phrases and were
anterior medial cortex than controls. The prediction was
instructed to ‘focus on the idea expressed by the phrase
less clear about the relative activity in the two groups in
and use your imagination to visualize or think about the
posterior medial cortex in the hopes and aspirations vs
idea . .'. They were asked to press a button when they had
duties and obligations conditions. Activity in this region
‘formed a really clear thought, or idea, or image' and to keep
was not found to correlate with either promotion or preven-
thinking about the idea until a cross-hair appeared. There
tion orientation (Johnson et al., 2006) or with optimism
were six practice trials outside the scanner. During the scan,
(Sharot et al., 2007). In addition, although duties and obli-
participants saw the cue ‘hopes and aspirations' 12 times
gations may be associated with avoidance goals (Higgins,
(‘hopes' condition), the cue ‘duties and obligations' 12
1998), such thoughts are not necessarily negatively valenced.
times (‘duties' condition) and 12 different concrete ‘distrac-
Depression can be associated with difficulty disengaging
tion' cues (e.g. pattern on oriental rug, shape of USA;
from self-focus, particularly from negative self-relevant
Nolen-Hoeksema, 2004). Cue types were pseudo-randomly
thoughts, when the task demands it. For example, people
intermixed in 3 runs of 12 trials each (four trials per condi-
who tend to ruminate when distressed (i.e. who passively
tion). Each trial was 18 s, with the cue shown for 14 s and
focus on feelings of distress and their meanings and conse-
a cross-hair shown for 4 s.
quences; Nolen-Hoeksema, 1991) show greater difficulty
Immediately after the scan session
compared with non-ruminators in disengaging attention
(which included Experiment 2, described later), participants
from or inhibiting irrelevant information (Siegle et al.,
moved to another room where they were asked to write a
2002; Joormann, 2004, 2005, 2006; Donaldson et al., 2007).
paragraph or two describing what they thought about during
Thus, we predicted that individuals experiencing a MDE,
the scan when they saw the phrases ‘hopes and aspirations'
and individuals prone to ruminate, would show greater
and ‘duties and obligations', with order of reports counter-
neural activity (i.e. less deactivation) in either or both ante-
balanced. Two research assistants, blind to the participants'
rior and posterior medial areas associated with self-reflection
MDE status, coded each report for both positivity and nega-
when directed to focus on non-self-relevant thoughts during
tivity (1 ¼ not at all to 4 ¼ very). Inter-rater reliability was
the distraction trials.
good ( ¼ 0.83, P < 0.0001), and each participant wasassigned the average of the scores of the two raters. One
rater counted the words in each report and also gave each
Participants self-reported being in good phy-
a global detail rating on a scale from 1 (no detail, very vague)
sical health, with no history of cardiovascular or neurological
to 5 (extremely detailed).
Medial cortex, self-reflection and depression
Visual analog scale of mood.
1995), or a group (control, MDE) condition time inter-
mood was measured using a 14-item visual analog scale at
action with a minimum of six contiguous voxels, each being
three points in the procedure: before going into the scanner,
significant at P < 0.001 (Forman et al., 1995). For the regions
between Experiments 1 and 2 and again after the post-scan
thus identified, subsequent analyses were conducted on
report. Adjectives appeared one-at-a-time on the screen and
percent signal change (from Time 1) for the region at
participants indicated for each item how much it described
Times 4–7, which is the period during which event-related
how they were currently feeling on a scale from 0% (not at
hemodynamic responses tended to peak in this task. Here,
all) to 100% (very much). The scale was in 10% intervals,
we focus on the medial areas identified and, for these areas,
and participants pressed a button to indicate their response
we report results of planned group condition contrasts in
for each item. There were six relatively negative items
percent signal change when each self-focus condition was
(anxious, guilty, hopeless, irritable, sad and worthless),
separately compared with distraction. We also conducted
four positive items (calm, energetic, happy and mellow)
planned contrasts between conditions within each group,
and four filler items that we considered to be relatively neu-
and between the groups for each condition. These contrasts
tral in this context (bored, hungry, talkative and tired) pre-
were performed on regions initially identified using
sented in a different pseudorandom order each time.
the stringent criteria described above, and had specific
Individual difference measures.
After the scan, parti-
directional predictions (P < 0.05, one-tailed); therefore,
cipants filled out questionnaires that assessed depressive
we note all two-tailed effects significant at P < 0.10.
symptoms (BDI-II; Beck et al., 1996) and tendency to rumi-
Conditions for Experiment 2 will be described in the
nate (Treynor et al., 2003). Participants were also adminis-
‘Methods' section, but the analysis strategy was identical to
tered the mood module of the SCID (First et al., 1998).
that used in Experiment 1. For completeness, Tables 1 and 2
Anatomical images were acquired
report all areas identified in Experiments 1 and 2,
using a 1.5T Siemens Sonata scanner at the Magnetic
Resonance Research Center at Yale University. Functional
In addition, for each region in Figures 1–3, the mean
scans were acquired with a single-shot echoplanar gradi-
percent change scores (Times 5–8 or 6–9) for each partici-
ent-echo pulse sequence [repetition time (TR) ¼ 2000 ms,
pant for each condition were correlated with their scores on
echo time (TE) ¼ 35 ms, flip angle ¼ 808 and field of view
the post-scan rumination questionnaire. We used slightly
(FOV) ¼ 24]. The 24 oblique axial slices (3.8 mm thick with
later time frames than used to assess peak activations in
an in-plane resolution of 3.75 3.75 mm) were aligned with
the main analysis (Times 4–7) because it seems likely that
the anterior commissure-posterior commissure (AC-PC)
ruminative tendencies would be more related to differences
line. Each run began with 12 blank seconds to achieve
seen later in trials. Scatter plots are provided for all signifi-
steady state magnetization, and was followed by a 1-min
cant correlations in the areas shown in Figures 1–3.
rest interval. One volume was collected every 2 s, or ninefull brain images for each trial (108 images per participant
Results and discussion
Figure 1A (see also Table 1) shows an area of medial frontal
After reconstruction, time series were
gyrus and anterior cingulate [Brodmann areas (BA) 10, 32]
shifted by sinc interpolation to correct for slice acquisition
identified in our initial whole brain analysis (see ‘Methods'
times. Data were motion-corrected using a six parameter
section). Subsequent planned comparisons between distrac-
automated algorithm (AIR; Woods et al., 1992). A 12 para-
tion and each of the two self-referential conditions showed
meter AIR algorithm was used to co-register participants'
that the difference in activity between hopes and distraction
images to a common reference brain. Data were mean-nor-
(F ¼ 5.42, P ¼ 0.025) and between duties and distraction
malized across time and participant and spatially smoothed
(F ¼ 6.56, P ¼ 0.014) was greater for control than MDE par-
(3D, 8 mm FWHM gaussian kernel). The data were analyzed
ticipants. These interactions largely arose because the MDE
using NeuroImaging Software (http://kraepelin.wpic.pitt
group showed less deactivation in the distraction condition
.edu/nis/). We used voxel-based analysis of variance
than the controls (F ¼ 4.65, P ¼ 0.04), and the groups did
(ANOVA) with participant as a random factor and all
not differ in the other conditions (both P's > 0.10). Within
other factors fixed. F-maps were transformed to Talairach
the control group in this area, activity in the hopes condition
space using Analysis of Functional NeuroImages (AFNI)
was greater than (>) the activity in the distraction condition
(Cox, 1996), and areas of activation were localized using
(F ¼ 75.71, P < 0.001), duties > distraction (F ¼ 50.12,
AFNI and Talairach Daemon software (Lancaster et al.,
P < 0.001) and hopes > duties (F ¼ 4.28, P ¼ 0.05). Within
1997) and manually checked against atlases (Talairach and
the MDE group in this area, hopes > distraction (F ¼ 36.38,
Tournoux, 1988; Duvernoy, 1999).
P < 0.001), duties > distraction (F ¼ 8.20, P ¼ 0.01) and
hopes > duties (F ¼ 8.23, P ¼ 0.01).
(hopes, duties, distraction) time within trial (images
Figure 1B shows an area of superior frontal gyrus, medial
1–9) interaction with a minimum of six contiguous voxels,
frontal gyrus (BA 10) somewhat superior to the region in
each being significant at P < 1.0 1021 (Forman et al.,
Figure 1A. In subsequent comparisons of activity in this area,
M. K. Johnson et al.
Table 1 Regions of activation in Experiment 1
Hopes > duties > distraction
Medial frontal gyrus, anterior cingulate (Figure 1A)
Duties > hopes > distraction
Precuneus, posterior cingulate, cuneus (Figure 1C)
Duties > hopes ¼ distraction
Cuneus, lingual gyrus (Figure 1D)
Hopes ¼ duties > distraction
Superior, medial frontal gyri (Figure 1B)
Middle temporal gyrus, angular gyrus
Distraction > hopes ¼ duties
Middle, inferior frontal gyri
Inferior frontal gyrus, precentral gyrus
Inferior frontal gyrus (inferior precentral gyrus)
Inferior temporal gyrus, fusiform gyrus, middle temporal gyrus
Inferior, middle temporal gyri
Inferior parietal lobule
Inferior parietal lobule
Superior/middle occipital gyrus
Areas were identified via either a condition time interaction (with a minimum of six contiguous voxels each significant at P < 1 1021; Forman et al., 1995) or a group condition time (six contiguous voxels, P < 0.001) in an initial whole-brain ANOVA. Talairach coordinates (X, Y, Z) are shown for the voxel with the maximum F-value in eacharea of activation. For identified areas, planned contrasts were performed on percent signal change from Time 1 at Times 4, 5, 6 and 7 (see ‘Methods' section). Headings refer topatterns for Controls. Major anatomical regions and BA numbers are listed in descending order of approximate size, with areas of approximately equal size indicated by a slash(parentheses indicate a small extent relative to other areas listed). Different patterns for MDE group: aDiscussed in text; bDistraction > hopes > duties. H, hemisphere; L, left; M,medial; R, right; BA, Brodmann area.
the difference between duties and distraction conditions was
hopes > distraction (F ¼ 134.22, P < 0.001), duties > distrac-
greater for the controls than the MDE group (F ¼ 5.06,
tion (F ¼ 161.66, P < 0.001) and duties > hopes (F ¼ 6.09,
P ¼ 0.030). The difference in this region between hopes
P ¼ 0.018). For the control group, hopes > distraction
and distraction did not differ between groups (P > 0.10),
(F ¼ 56.51, P < 0.001), duties > distraction (F ¼ 82.88,
and the difference between groups was not significant for
and duties > hopes
any of the conditions (all P > 0.10). Within the control
Similarly, within the MDE group, hopes > distraction
group, hopes > distraction (F ¼ 18.41, P < 0.001) and
(F ¼ 94.39, P < 0.001), duties > distraction (F ¼ 83.08,
duties > distraction (F ¼ 18.15, P < 0.001), but hopes and
P < 0.001) and duties > hopes (F ¼ 3.17, P ¼ 0.09).
duties did not differ significantly (P > 0.10). In the MDE
An additional posterior medial area [cuneus, lingual
group, hopes > distraction (F ¼ 10.03, P ¼ 0.005) and
gyrus, BA 18 (19); Figure 1D] showed an interesting pattern:
hopes > duties (F ¼ 3.94, P ¼ 0.062), while duties and dis-
greater difference in activity between the hopes and distrac-
traction did not differ (P > 0.10).
tion conditions for the MDE group than for controls
Thus, both groups showed a more inferior area of anterior
(F ¼ 5.33, P ¼ 0.026). The groups did not differ when
medial PFC where activity was greater on hopes than duties
duties and distraction were compared (P > 0.10). The MDE
trials and a more superior area of anterior medial PFC in
group showed greater activity than the controls in the hopes
which activity in the two self-referential conditions did not
condition (F ¼ 4.53, P ¼ 0.039), but the groups did not differ
differ, replicating and extending Johnson et al. (2006) to
in the other two conditions (both P's > 0.10). For controls,
MDE participants. Contrary to our expectations, MDE par-
hopes did not differ significantly from distraction (P > 0.10),
ticipants did not show less activity than controls during the
while duties > distraction (F ¼ 11.71, P ¼ 0.002) and duties
hopes trials. However, as expected, the MDE group did show
> hopes (F ¼ 9.11, P ¼ 0.006). For the MDE group, hopes >
less deactivation than controls during distraction trials
distraction (F ¼ 8.47, P ¼ 0.009) and duties > distraction
(F ¼ 7.09, P ¼ 0.015), while hopes and duties did not differ
Figure 1C shows an area of precuneus, posterior cingulate,
(P > 0.10).
cuneus (BAs 7, 31, 23, 19) where the difference between
Thus, as in Johnson et al. (2006), both groups showed an
each of the two self-focus conditions and distraction
area (Figure 1C) of posterior medial cortex where activity
did not differ between groups (both P's > 0.10), and the
was greater in the duties than hopes condition. In addition,
difference between groups was not significant in any of the
in this area, MDE and control groups looked very similar. In
three conditions (all P > 0.10). Collapsed across groups,
a more inferior and posterior area (Figure 1D), controls
Medial cortex, self-reflection and depression
Table 2 Regions of activation in Experiment 2
Analytical > experiential > distraction
Medial frontal gyrus, anterior cingulate (Figure 2A)
Medial, superior frontal gyri (Figure 2B)
Medial, superior frontal gyri (anterior cingulate) (Figure 2C)
Precuneus, cuneus, cingulate gyrus (Figure 3A)
Experiential > analytical > distraction
Cingulate gyrus (Figure 3B)
Analytical ¼ experiential > distraction
Inferior frontal gyrus (precentral gyrus)
Inferior frontal gyrus
Middle, superior temporal gyri
Superior temporal, supramarginal, angular gyrus
Analytical ¼ experiential ¼ distractionLingual gyrus
Distraction > experiential ¼ analytical
Parahippocampal gyrus (hippocampus)
Parahippocampus (hippocampus), fusiform gyrus
Distraction > experiential > analytical
Middle, inferior frontal gyri
Middle frontal gyrus
Precentral gyrus, inferior frontal gyrus
Inferior, middle temporal gyri, middle occipital gyrus
Inferior, middle temporal gyri
Middle temporal gyrus
Inferior parietal lobule
Superior parietal lobule
Precuneus, superior parietal lobule
Superior occipital gyrus
Superior occipital gyrus
Areas were identified via either a condition time interaction (with a minimum of six contiguous voxels each significant at P < 1 1021; Forman et al., 1995) or a group condition time (six contiguous voxels, P < 0.001) in an initial whole-brain ANOVA. For identified areas, planned contrasts were performed on percent signal change from Time1 at Times 4, 5, 6 and 7 (see ‘Methods' section). Headings refer to patterns for controls. Major anatomical regions and BA numbers are listed in descending order of approximatesize, with areas of approximately equal size indicated by a slash (parentheses indicate a small extent relative to other areas listed). Different patterns for MDE group: aDiscussed intext; bA > E ¼ D; cD > E ¼ A; dD ¼ E > A; eD ¼ E ¼ A. H, hemisphere; L, left; M, medial; R, right.
again showed greater activity for duties than hopes, but the
offered a career in intelligence. For duties trials, topics
MDE group showed equal activity for these two self-refer-
included: keep[ing] parents and friends at home updated
on my life, studying for finals, [attending] family reunions,
Individual differences in rumination.
Higher trait rumi-
accepting and seeing people for their best, helping my
nation scores were associated with less activity in anterior
younger sister, volunteering, [thinking of] friends who
medial cortex during hopes trials (r ¼ 0.28, P ¼ 0.07,
expect me to be there and how I find it very difficult,
Figure 1A) and with more activity in posterior medial
[owing] bills, and [being married] and the level of commit-
ment one must have-even during the rocky times. There
Figure 1B). During duties trials, rumination scores did not
were no significant group or condition differences in
correlate with activity in any of the areas identified in
number of words (M ¼ 100.5; all P > 0.10) or amount of
detail (M ¼ 3.20; all P > 0.10) in the post-scan reports.
Participants reported thinking of a
With respect to valence ratings, there was a valence
wide range of topics in response to the self-relevant cues. For
report type interaction (F ¼ 108.79, P < 0.001). As might be
hopes cues, topics included: help[ing] developing and poor
expected, for the hopes reports positivity ratings (M ¼ 3.02)
countries, finding the cure for cancer, writing a screenplay,
were higher than negativity ratings (M ¼ 1.20), while for the
owning a large house, helping my uncle's business grow,
duties reports, negativity ratings (M ¼ 1.85) were higher
winning scholarships, being worry-free about money/debt,
than positivity ratings (M ¼ 1.29). A group main effect
be[ing] able to say intelligent things and hav[ing] people
(MMDE ¼ 1.97, Mcontrols ¼ 1.71; F ¼ 6.19, P < 0.05) was
listen and respect me, find[ing] a research mentor for this
qualified by a group valence interaction (F ¼ 4.43,
summer, meet[ing] a woman my mother will like, and being
P < 0.05) because the MDE participants' (M ¼ 1.79) reports
M. K. Johnson et al.
Fig. 1 Experiment 1. Bar graphs show the mean percent change in bold signal value for control (left) and MDE (right) groups and scatter plots show significant correlationswithin conditions (distraction and hopes) between mean percent signal change and rumination score (see text). See Table 1 for details regarding coordinates, BA and maximum Ffor the region. (A) Area of anterior medial cortex showing hopes > duties > distraction for both groups, and MDE > controls in the distraction condition. (B) A more superiorarea of anterior medial cortex showing hopes ¼ duties > distraction for both groups, with no significant condition differences between the groups. (C) Area of posterior medialcortex showing duties > hopes > distraction for both groups, with no significant condition differences between the groups. (D) Area of posterior medial cortex showing duties >hopes and duties >distraction, but hopes ¼ distraction for controls; duties ¼ hopes > distraction for the MDE group, and MDE > controls in the hopes condition.
Fig. 2 Experiment 2. Bar graphs show the mean percent change in bold signal value for control (left) and MDE (right) groups and scatter plots show significant correlationswithin conditions (distraction and hopes) between mean percent signal change and rumination score (see text). See Table 2 for details regarding coordinates, BA and maximum Ffor the region. (A and B) Areas of anterior medial cortex showing control > MDE in the analytical condition and MDE > control in the distraction condition, with no difference inthe experiential condition. (C) Area of anterior medial cortex showing MDE > control in the distraction condition only.
Medial cortex, self-reflection and depression
interpretation. However, the means were in the expecteddirection of less activity in medial PFC during hopes trialsin the MDE group (Figure 1A), and rumination scores werenegatively correlated (P < 0.07) with activity in medial PFCduring hopes trials. In addition, post-scan reports of MDEparticipants were rated as significantly more negative thanthose of controls. Taken together, these findings suggest thatunder the right cuing conditions, we might observe a sig-nificant reduction in medial PFC activity associated withdepression. Specifically, we might expect larger differencesin medial PFC activity between groups to emerge when par-ticipants are cued to think about themselves, but are notspecifically cued to think about positively valenced topicssuch as hopes and aspirations. This hypothesis was testedin Experiment 2.
When depressed participants are given emotionally neutralself-focused cues, they tend to ruminate about negative per-sonal experiences more than non-depressed participants do
Fig. 3 Experiment 2. Bar graphs show the mean percent change in bold signal value
(Lyubomirsky et al., 1999). Watkins (2008) distinguished
for control (left) and MDE (right) groups and scatter plots show significant correla-
between two types of self-focused rumination cues: ‘analy-
tions within conditions (distraction and hopes) between mean percent signal change
tical cues', which focus participants' attention on self-evalua-
and rumination score (see text). See Table 2 for details regarding coordinates, BA and
tions (e.g. who you strive to be, why things turn out as they
maximum F for the region. (A) Area of posterior medial cortex showing MDE >
do), and ‘experiential cues', which focus participants' atten-
controls in the distraction condition, with no other condition differences between thegroups. (B) Area of posterior medial cortex showing no differences between MDE and
tion on their current state (e.g. current physical sensations,
controls for any of the conditions.
how alert you feel). Both types of cues direct participants'attention to the self, but not specifically to positive or nega-tive aspects (Lyubomirsky and Nolen-Hoeksema, 1993).
were rated as more negative than the control participants'
Watkins and Teasdale (2001; also Rimes and Watkins,
(M ¼ 1.26) for both types of reports, with no difference in
2005) found that for depressed individuals, both types of
positive ratings (MMDE ¼ 2.15, Mcontrols ¼ 2.16).
cues maintain depressed mood, but analytical cues are espe-
In short, in Experiment 1, for control participants, we
cially likely to result in negative self-referential thought. That
replicated two findings reported by Johnson et al. (2006):
is, for depressed but not control participants, analytical cues
(i) a double dissociation where activity was greater in ante-
result in self-focus that is evaluative, perseverative and nega-
rior medial cortex when participants thought about hopes
tive. In addition, such cues prompt depressed individuals to
than duties and greater in posterior medial cortex when
retrieve more negative autobiographical memories, give
participants thought about duties than hopes, and (ii) a
more negative interpretations of current personal events
dissociation within anterior medial PFC where a more infer-
and make more negative predictions about their future
ior area showed hopes > duties and a more superior area
than control participants (Nolen-Hoeksema et al., 2008;
showed hopes ¼ duties. We expected that the MDE group
would show less activity in anterior medial cortex during
These behavioral findings, in combination with the fMRI
hopes trials and less deactivation in this region during dis-
findings from Experiment 1, suggest that analytical cues, but
traction trials. While the second prediction was confirmed,
perhaps not experiential cues, would result in less activity in
the first was not (Figure 1A and B). These findings suggest
medial PFC in MDE participants compared with controls.
that MDE participants were relatively successful in engaging
This is because MDE participants should be less likely to
positive self-referential processing when cued to do so, but
spontaneously generate positive self-focused thoughts in
were less successful in disengaging from self-referential pro-
thinking about self-evaluations, and more likely to turn to
cessing in the distraction task. Thus, when MDE participants
negative rumination. We also expected to replicate and
were specifically cued to think about hopes and aspirations
extend the results from Experiment 1 showing less deactiva-
and duties and obligations, the activity in anterior and pos-
tion in anterior medial cortex when MDE participants are
terior medial cortex suggests that they were doing so. The
given distraction cues. This would indicate that these parti-
fact that MDE and control participants' post-scan reports
cipants have more difficulty disengaging from self-focused
did not differ in positivity ratings is consistent with this
M. K. Johnson et al.
Participants were the same as in Experiment 1 (Experiment 2
P ¼ 0.027), but the groups did not differ in the other condi-
followed Experiment 1 in the same scanning session). The
tions (both P's > 0.10). Within the control group, analytical
study was a mixed 2 (group: control, MDE) 3 (condition:
> distraction (F ¼ 60.18, P < 0.001), experiential > distrac-
analytical self-focus, experiential self-focus, distraction)
tion (F ¼ 18.91, P < 0.001) and analytical > experiential
design. Twelve of each cue type were randomly intermixed
(F ¼ 28.49, P < 0.001). Within the MDE group, analytical >
as in Experiment 1: new distraction cues (e.g. truckload of
distraction (F ¼ 16.16, P < 0.001), experiential did not differ
watermelons, shape of Italy), analytical cues (e.g. who you
from distraction (P > 0.10) and analytical > experiential
strive to be, why things turn out as they do, what your
(F ¼ 13.62, P ¼ 0.002).
feelings mean, quality of your friendships) and experiential
In short, relative to controls, for MDE participants, sub-
cues (e.g. current physical sensations, how alert you feel, how
regions of anterior medial PFC were less engaged during the
motivated you feel, how decisive you feel). The procedure,
analytical condition (Figure 1A and B) and less likely to be
fMRI acquisition and analyses paralleled Experiment 1.
disengaged (i.e. deactivate) during the distraction condition(Figure 1A–C). The groups did not differ in any of these
Results and discussion
areas in the experiential condition.
Two areas of posterior medial cortex were also identified
Three areas of anterior medial cortex were identified
(Figure 3, Table 2). An area of precuneus and cuneus,
(Figure 2 and Table 2). An area of medial frontal gyrusand anterior cingulate (BAs 10 and 32) is shown in
extending into cingulate gyrus (BAs 7, 31, 23), is shown in
Figure 2A. Comparisons of each self-referential condition
Figure 3A. Comparisons of each self-referential condition
with distraction resulted in group
with distraction found no significant group condition
(analytical, F ¼ 12.16, P ¼ 0.001; experiential, F ¼ 13.22,
interaction for the analytical condition (P > 0.10), but there
P ¼ 0.001). As predicted, the MDE group showed less activ-
was an interaction for the experiential condition (F ¼ 3.38,
ity in this area than controls during the analytical condition
P ¼ 0.073). The MDE group showed greater activity than
(F ¼ 2.99, P ¼ 0.091) and more activity during the distrac-
tion condition (F ¼ 14.43, P ¼ 0.001); they did not differ in
P ¼ 0.042), but the groups did not differ in the other condi-
the experiential condition (P > 0.10). Within the control
tions (both P's > 0.10). Within the control group, analytical
group, analytical > distraction (F ¼ 31.76, P < 0.001), experi-
> distraction (F ¼ 35.64, P < 0.001), experiential > distrac-
ential > distraction (F ¼ 7.18, P ¼ 0.013) and analytical >
tion (F ¼ 28.18, P < 0.001) and analytical > experiential
experiential (F ¼ 38.54, P < 0.001). In contrast, in the MDE
(F ¼ 3.22, P ¼ 0.086). Within the MDE group, analytical >
group, the analytical and distraction conditions did not
distraction (F ¼ 18.89, P < 0.001) and experiential > distrac-
differ in this area (P > 0.10), but distraction > experiential
tion (F ¼ 25.12, P < 0.001), but analytical did not differ from
(F ¼ 6.22, P ¼ 0.022) and analytical > experiential (F ¼ 5.85,
experiential (P > 0.10).
P ¼ 0.026).
An area of cingulate gyrus (BAs 23/24) is shown in
In an area of medial, superior frontal gyrus (BAs 9, 10)
Figure 3B. Comparisons of each self-referential condition
represented in Figure 2B, comparisons of each self-referential
with distraction resulted in no significant group condition
condition with distraction also resulted in group condi-
interactions (both P's > 0.10), and there were no group
tion interactions for analytical (F ¼ 13.18, P ¼ 0.001) and
differences for the individual conditions (all P > 0.10).
experiential (F ¼ 10.83, P ¼ 0.002) conditions. As with the
Within the control group, however, analytical > distraction
region in Figure 2A, the MDE group showed less activity
(F ¼ 17.35, P < 0.001), experiential > distraction (F ¼ 36.40,
than controls during the analytical condition (F ¼ 3.78,
P < 0.001) and experiential > analytical (F ¼ 3.33, P ¼ 0.081).
P ¼ 0.059) and more activity than controls during the dis-
Within the MDE group, analytical > distraction (F ¼ 33.75,
traction condition (F ¼ 10.76, P ¼ 0.002) in this area; the
groups did not differ in the experiential condition
(P > 0.10). Within the control group, analytical > distraction
experiential (P > 0.10).
(F ¼ 56.49, P < 0.001), experiential > distraction (F ¼ 12.30,
Overall, in posterior medial cortex, the only difference
between the control and MDE groups was less deactivation
P < 0.001). Within the MDE group, neither analytical nor
during distraction in the precuneus, cuneus area as shown in
experiential differed from distraction (both P's > 0.10), but
Figure 3A. In contrast to the pattern in anterior medial
analytical > experiential (F ¼ 7.05, P ¼ 0.016).
cortex, in posterior medial cortex there was little difference
A region of medial, superior frontal gyrus, extending into
in activity between the two self-referential conditions or
anterior cingulate [BAs 9, 10 (32)] is shown in Figure 2C.
between groups in the self-referential conditions.
Comparisons of each self-referential condition with dis-
Individual differences in rumination.
As expected, higher
traction resulted in a group condition interaction for
rumination scores were associated with less activity in ante-
analytical (F ¼ 3.31, P ¼ 0.076) and experiential (F ¼ 6.39,
rior medial cortex during analytical trials (r ¼ 0.30,
P ¼ 0.015). The MDE group showed more activity than
P ¼ 0.046, Figure 2B). In addition, higher rumination
Medial cortex, self-reflection and depression
scores were associated with more activity during distraction
Table 3 Mean mood ratings (s.e. of the cell mean) for three time points
trials in anterior medial cortex (r ¼ 0.45, P < 0.001,
P ¼ 0.072, Figure 2C), and in posterior medial cortex
Experiments 1 and 2
Figure 3B). Rumination scores were not significantly corre-
lated with activity in regions shown in Figures 2 and 3
during experiential trials (P > 0.10).
Visual analog mood scale results.
scores obtained pre-scan (Time 1), between Experiments 1
and 2 (Time 2) and post-scan (Time 3) are presented in
Table 3 (n ¼ 18 in the MDE group because two participants
were each missing one measure and thus were excluded fromanalysis). A 2 (group: control, MDE) 3 (valence: negative,neutral, positive) 3 (Time: 1, 2, 3) ANOVA on the moodscale scores showed a three-way interaction (F ¼ 3.06,
group gave higher ratings to the filler items than did the
P ¼ 0.018). As might be expected, compared with controls,
control group at Time 1 (t ¼ 2.23, P ¼ 0.032) and Time 3
the ratings of the MDE group were significantly more nega-
(t ¼ 2.47, P ¼ 0.02), suggesting that they may have been
tive for the negative items, and significantly less positive for
more sensitive to their bodily feelings than were the control
the positive items, at all three time points (all P's < 0.001).
participants before and after the scan session, but not
However, the full pattern of mood data argues against an
interpretation that the current fMRI findings are based
In sum, as predicted, when participants were induced to
merely on a task-induced worsening of mood during the
think about themselves and their life with cues that did not
scans in the MDE group. Specifically, the MDE group's rat-
explicitly direct them toward thoughts with a particular
ings for negative items became less negative over time: from
valence, MDE participants showed less activity in anterior
Time 1 to 2, the ratings decreased 3.15% (P > 0.10) and from
medial cortex than did controls. That this pattern was
Time 2 to 3, they decreased 6.39% (t ¼ 3.81, P ¼ 0.001).
observed during analytical but not experiential trials is con-
Hence from Time 1 to 3, the MDE group's ratings on nega-
sistent with previous behavioral findings suggesting that ana-
tive items decreased on average 9.54% (t ¼ 2.69, P ¼ 0.015).
lytical cues are more likely than experiential cues to induce
For control participants, the decrease from Time 1 to 3 was
rumination (Watkins, 2008). Rumination scores were also
only 3.38%, which, although a reliable change (t ¼ 2.48,
negatively correlated with activity in anterior medial cortex
P < 0.02), was marginally less than that of the MDE group
during analytical trials and positively correlated with activity
(t ¼ 1.79, P ¼ 0.081). The MDE group showed no changes in
in both anterior and posterior medial cortex during distrac-
their ratings of the positive items (all P's > 0.10). The control
tion trials. Thus, the results of Experiment 2 demonstrate
group showed a 7.5% decrease on the positive items from
that, when responding to valence-neutral cues that induce
Time 1 to 2 (t ¼ 3.60, P ¼ 0.002), but a small increase (3.9%)
self-evaluative thought, depression is associated with
from Time 2 to 3 (t ¼ 3.89, P ¼ 0.079); thus, the change from
reduced likelihood of engaging regions of anterior medial
Time 1 to 3 was not significant (P > 0.10).1 Finally, although
cortex that have been shown to be associated with positive
there was not much change in ratings of the filler items (e.g.
thoughts about one's hopes and aspirations. The findings
hungry, tired, bored) over time in either group, the MDE
also indicate that depression is associated with less deactiva-tion of medial regions associated with self-referentialthought, suggesting difficulties disengaging from self-focusedthought when the task demands (Siegle et al., 2002; Joorman,
As noted in the introduction to Experiment 2, we knew from existing behavioral literature (Watkins and
Teasdale, 2001; also Rimes and Watkins, 2005) that the self-reflection manipulations used in Experiment 2
Finally, the relative absence of activity associated with self-
were likely to induce rumination in the MDE group. We thus tested everyone first in Experiment 1 to minimizepotential carryover effects that might have attenuated MDE participants' likelihood of recruiting medial cortex
reflection in posterior medial cortex in both groups in
areas when specifically prompted with cues that we knew would recruit these areas in controls. Of course,
Experiment 2, especially in the experiential condition, pro-
there could have been carryover effects of the Experiment 1 manipulation on the nature of participants' self-
vides further evidence that this region is not simply a ‘self'
reflection in Experiment 2, as well. For example, if MDE participants failed to come up with compelling hopesin Experiment 1, or failed to feel hopeful about the ones they did generate, they may have had more negative
area. Rather it may be involved in more specific functions,
thoughts in the analytical condition in Experiment 2 than they otherwise would have. If so, this would be
such as the revival of episodic memories (Hassabis et al.,
consistent with findings that depression leads to a cycle of negative thinking that pervades even ostensibly
2007), that may occur more as one thinks about self-relevant
neutral situations. However, the significant rise in mood scores in the MDE group suggests that priming ofpositive ideas might have worked against our predictions for Experiment 2. That is, being prompted to come
agendas such as hopes and duties (Experiment 1; Johnson
up with specific hopes in Experiment 1 may have attenuated differences between groups in Experiment 2 by
et al., 2006) than less concrete issues associated with self-
priming positive thoughts for MDE participants that would not otherwise have been accessed. Thus, the group
evaluation (e.g. analytic cues such as considering the nature
difference we found in medial PFC in Experiment 2 actually might have underestimated the true (unprimed)difference in these groups in the nature of their spontaneous self-reflection.
of one's relationships).
M. K. Johnson et al.
thought (Johnson et al., 2006; see also Moran et al., 2006).
To our knowledge, these are the first fMRI studies to com-
Converging evidence for the hypothesis that inferior
pare medial cortex activity of MDE and control individuals
medial PFC is associated with positively valenced thoughts
contrasting self-focused cues about two types of personally
(Johnson et al., 2006; Sharot et al., 2007) was reported by
relevant agendas (hopes, duties; Experiment 1) and contrast-
D'Argembeau et al. (2008), who cued participants to think of
ing self-referential cues that have been shown to differen-
positive and negative future events (generated by the same
tially induce rumination in depressed individuals (analytic,
participants in a previous session) and found positive >
experiential; Experiment 2).
negative in an area of inferior medial PFC close to the area
In Experiment 1, activity in an inferior area of anterior
we found in both experiments (0, 51, 4, compare with
medial cortex (Figure 1A) was greater in response to cues to
current Figures 1A and 2A). Nonetheless, the areas of ante-
think about hopes and aspirations than cues to think about
rior medial cortex associated with valence do vary some
across self-referential studies (Gutchess et al., 2007;
(Johnson et al., 2006). Furthermore, activity in this region
Yoshimura et al., 2009). Thus, differentiating functional
did not differ significantly between control and MDE parti-
sub-regions of anterior medial cortex with respect to valence
cipants. These findings suggest that MDE participants were
and the interaction between valence and self-reference
able to recruit this area when explicitly given cues to engage
remains a challenge.
the sorts of self-reflective processing previously shown to
Investigators have also begun to identify sub-regions of
activate this region in control participants, and are consis-
anterior medial cortex that appear to be involved in other
tent with behavioral studies showing that depressed indivi-
duals can generate positive memories and thoughts when
Cunningham (in press) investigated whether greater medial
guided to do so (Wenzlaff et al., 1988). However, behavioral
PFC activity for hopes than duties might be related to the
studies also indicate that depressed individuals have diffi-
more distant time frame that is likely to be considered for
culty generating positive memories and thoughts on their
hopes than for duties. They cued participants to the time
own (Wenzlaff et al., 1988), and findings from Experiment
frame to consider (e.g. this week, next year, 10 years from
2 provide neural evidence consistent with these behavioral
now) and found hopes > duties in an area (6, 46, 1)
very close to the inferior medial PFC area as shown in
In Experiment 2, a similar area of anterior medial PFC
Figures 1A and 2A. In addition, this area was not sensitive
(Figure 2A) was more engaged in response to analytical self-
to time frame. Rather, both Packer and Cunningham (in
focus cues (e.g. ‘why things turn out as they do') than experi-
press) and D'Argembeau et al. (2008) reported evidence
ential cues (e.g. ‘current physical sensations'), consistent
that an even more inferior PFC region (BA 11: 0, 28, 19;
with findings from Experiment 1 that this region is not
and 3, 45, 19, respectively) than found in the present
simply a self-focus region, but rather is especially sensitive
study is differentially active when participants think about
to certain types of self-focus (see also Johnson et al., 2006;
distant compared with near events. Packer and Cunningham
Mitchell et al., 2009). Further, control participants showed
also found an area of more superior medial PFC (3, 49, 29)
greater activation in medial PFC compared with MDE
near the areas in Figures 1B (4, 60, 21) and 2B (4, 57, 21),
participants in the analytical cue condition. This pattern of
which they associated with more domain general processes
activation would be expected if this sub-region of medial
invoked when the task was more difficult (in their experi-
PFC is associated with positively valenced self-focus
ment near hopes and far duties were more difficult than far
(Johnson et al, 2006; Sharot et al., 2007) and if analytical
hopes and near duties). (Where published papers reported
self-focus led to negative self-thought (rumination) in
MNI coordinates, to facilitate comparison, we converted to
susceptible individuals (Watkins, 2008). That is, depressed
Talairach using BioImage Suite http://www.bioimagesuite
individuals may show reduced medial PFC activity, com-
pared with those without depression, because they are less
It is notable that across five studies comparing hopes and
likely or able to generate positive ideas in response to
duties conditions (Johnson et al., 2006, Experiments 1 and 2;
analytical cues, because the positive thoughts they do
Mitchell et al., 2009; Packer and Cunningham, in press,
generate feel less positive, and/or negative thoughts offset
and the present Experiment 1), the z coordinates of local
the impact of positive thoughts.
maxima in anterior medial regions showing hopes > duties
The present findings provide additional evidence for dif-
(in young/control participants) ranged from 7 to 16 and
ferent functional sub-regions of medial PFC (Ochsner et al.,
the z coordinates of anterior medial regions showing hopes
2004; Mitchell et al., 2005; Amodio & Frith, 2006; Northoff
¼ duties ranged from 21 to 32. This pattern is consistent
et al., 2006). In particular, these results provide converging
with suggestions of a ventral/dorsal division of functions in
support for the conclusion that an area of inferior medial
medial PFC with respect to more/less valenced self-
PFC is associated with more positive thought, while a more
processing (Ochsner et al., 2005; Johnson et al., 2006;
superior medial PFC area is associated with either more
Moran et al., 2006) and, more generally, similar to the
general self-focus or with less-affective aspects of self-focused
ventral/dorsal division of anterior cingulate cortex into
Medial cortex, self-reflection and depression
more/less emotional processing areas (Bush et al., 2000).
the MDE and control groups in length or rated detail.
Thus, the relatively reduced recruitment of the two areas
Thus, the difference in anterior medial cortex activity
of medial PFC found in Experiment 2 for the MDE group
in the analytical condition in Experiment 2, coupled with
likely reflects a combination of more goal-specific factors
no under-recruitment of posterior medial cortex in the
(e.g. affective content, Figure 2A) and more general factors
MDE group in either experiments, suggests a difference
(e.g. the type or complexity of reflective processes engaged,
between groups not in ‘how much' participants were think-
Figure 2B), but not differences in the time frames considered
ing, but in ‘what' they were thinking, i.e. a difference in
by the two groups.
specific content and/or valence. Further studies will be
Posterior medial cortex has also been found to be active
needed to dissociate the impact of the amount of detail in
during self-referential processing (Johnson et al., 2002; Vogt
what is thought from the valence, specificity or other features
and Laureys, 2005; Northoff et al., 2006), and more so when
of what is thought. Nevertheless, the fact that the MDE
people are cued to think about their duties and obligations
group did not show reduced activity relative to controls in
than their hopes and aspirations (Johnson et al., 2006). We
posterior medial cortex during self-reflection in a range of
replicated this latter finding in both control and MDE par-
cuing conditions represented in the two experiments argues
ticipants in Experiment 1 (Figure 1C). Control participants
for a relatively specific reduction in anterior medial cortex
also showed greater activity on duties trials than hopes trials
activity associated with depression.
in a more inferior and posterior area, whereas MDE partici-
In short, the overall pattern across these two experiments
pants did not (Figure 1D). The similar activity in hopes and
suggests that a primary difference between MDE and control
duties trials in the posterior medial area in Figure 1D in the
individuals when engaging in self-reflection is an under-
MDE group suggests that the thoughts of MDE participants
recruitment in MDE participants of anterior medial areas
in response to cues meant to elicit hopes and aspirations
associated with positively valenced thoughts (e.g. hopes
were in some way more similar to those meant to elicit
and aspirations) when cues are ambiguous in terms of
duties and obligations than was the case for controls.
valence and do not specifically elicit such thoughts.
Activity in the posterior medial cortex is associated with
This fits with models of depression suggesting it is charac-
autobiographical retrieval (Cavanna and Trimble, 2006;
terized by an underactive approach system, leading to
Hassabis et al., 2007), and thinking about duties may gen-
low motivation and a failure to experience positive effect
erate more episodic recall of past events (e.g. specific com-
(Gray, 1982; Fowles, 1988; Davidson, 1998; Schaefer et al.,
mitments made to others) than thinking about hopes
(Johnson et al., 2006). Thus, one hypothesis is that the pat-
When Johnson et al. (2006) originally reported a double
tern seen in the area of posterior medial cortex shown in
dissociation between the nature of self-relevant agendas
Figure 1D may reflect a greater tendency of MDE partici-
(hopes vs duties) and the medial regions that are most
pants to think back to past episodes during attempts to think
active (anterior vs posterior medial cortex, respectively),
of future-oriented hopes. However, the area in Figure 1D is
they suggested a number of potential factors to explore
more posterior and inferior to those (such as the area in
that could contribute to this finding: (i) differences in con-
Figure 1C) typically associated with self-referential proces-
tent; (ii) differences in the component processes engaged
sing and with episodic memory. Thus, this interesting pat-
(e.g. generating/discovering new relations vs retrieving epi-
tern needs to be replicated using more systematic
sodic information); (iii) differences in affective/motivational
manipulations in order to isolate its role in self-referential
significance; (iv) differences in subjective experience of self
(e.g. instrumental control vs experience of awareness); and
Anterior, as well as posterior, medial cortex has been asso-
(v) differences in social/contextual factors (e.g. duties may be
ciated with autobiographical memory and with imagining
more likely to involve others; differences in perspective
future events (Addis et al., 2007; Hassabis et al., 2007;
taking). Of course, these are not entirely orthogonal factors.
D'Argembeau et al., 2008). Given that depression is not
For example, differences in the subjective experience of self
only associated with less positive thinking, but also with
should be related to differences in the component processes
less specific, more general thoughts, both for autobiographi-
engaged (Johnson and Reeder, 1997). The present results add
cal memories and for imagining future events, particularly
to other recent findings (e.g. Vogt and Laureys, 2005;
when depression involves analytical rumination (Williams
Cavanna and Trimble, 2006; Johnson et al., 2006; Hassabis
et al., 1996; Williams et al., 2000; Dickson and Bates, 2006;
et al., 2007; Sharot et al., 2007; D'Argembeau et al., 2008;
Watkins, 2008), the reduced activity in the MDE group in
Packer and Cunningham, in press) that together suggest that
anterior medial cortex in the analytical condition of
specific sub-regions of medial cortex are differentially asso-
Experiment 2 might reflect more impoverished thoughts.
ciated with factors such as type of processing engaged, type
However, it is of note that we found no evidence of reduced
of goal, valence and time-frame considered. Such factors
activity associated with depression in posterior medial cortex
would be expected to show important group and individual
in either experiment. Recall also that the post-scan reports
differences and thus should be promising targets for further
about what participants were thinking did not differ for
M. K. Johnson et al.
It is also important to note that regions in anterior and
Our findings provide strong support for the idea that indi-
posterior medial cortex are part of a network that has come
viduals with depression engage in self-focused thought even
to be called the ‘default network' because activity is found in
when the task is to engage in non-self-relevant processing
these regions when people do not have any particular cog-
(see also, e.g. Sheline et al., 2009, for a similar suggestion).
nitive task to do (Gusnard et al., 2001). Commonly, in fMRI
These findings are in line with behavioral data that depressed
studies, these areas are active at rest and ‘deactivate' during
individuals have difficulty withdrawing attention from self-
performance of a cognitive task. In both Experiments 1 and
relevant information when it would be appropriate to do so
2, the MDE group showed less deactivation than did the
(Joormann, 2004, 2006; Donaldson et al., 2007). If deactiva-
control group in medial cortex during distraction trials, sug-
tion of medial cortex is necessary for the activation of other
gesting that they may be disengaging these default areas less
areas in response to certain cognitive task demands (e.g.
than controls when presented with a non-self-referential,
attention and memory tasks, Grady et al., 2006), then
cognitive task. In individuals with major depression, the
depression would be expected to disrupt cognitive perfor-
medial cortex regions associated with the default network,
mance, and there is behavioral evidence that it does so
especially more inferior anterior regions including subgenual
(Strack et al., 1985; Hertel, 1998; Nolen-Hoeksema et al.,
cingulate cortex, show hypermetabolism (e.g. Drevets et al.,
2002; Mayberg, 2003b) and increased functional connectivity
Together, the findings discussed may help explain why,
(e.g. Greicius et al., 2007) during the resting state (see
across studies of depression, the specific patterns of findings
Drevets et al., 2008; Gotlib and Hamilton, 2008, for recent
in medial cortex are mixed. For example, in medial PFC,
reviews). These areas also demonstrate less deactivation
studies sometimes show hypofrontality and sometimes
during cognitive or emotion processing tasks in depressed,
hyperfrontality (Mayberg, 2003a; Phillips et al., 2003;
compared with control, participants (e.g. Vasic et al., 2008;
Drevets et al., 2008; Gotlib and Hamilton, 2008 for reviews
Grimm et al., 2009; Sheline et al., 2009; see also, Drevets
and discussion). Our results are generally consistent with
et al., 2008; Gotlib and Hamilton, 2008, for recent reviews).
earlier neuroimaging studies finding reduced task-related
Moreover, such differences correlate with depressive symp-
activity in medial PFC associated with depression (Bench
toms. For example, amount of subgenual cingulate cortex
et al., 1993; Drevets, 2000; Charney and Manji, 2004), and
connectivity within the default network correlates with the
consistent with the idea that depression involves dysfunction
duration of current episode of depression (Grecius et al.,
in the ability to self-regulate emotion via the recruitment
2007), and less deactivation during the processing of (nega-
and maintenance of approach-related self-relevant agendas
tive) emotional pictures in ventromedial PFC correlates with
(as in Joormann and Siemer, 2004; Wenzlaff et al., 1988).
subjective ratings of hopelessness and less deactivation in
But, our results also suggest that some variability in findings
posterior cingulate cortex correlates with level of depression
with depressed individuals across studies may in part reflect
(i.e. scores on the Hamilton Depression Scale) (Grimm et al.,
differences in the nature of the spontaneous thoughts
engaged by participants during, for example, resting periods
Because fMRI data are correlational, the present findings
or baseline assessments.
alone cannot differentiate whether: (i) the observed group
Our results also suggest that some variability in findings
differences in medial cortex activity signal differences in
with depressed individuals may depend in part on whether
what is motivationally significant or salient during self-
and what kind of self-reflective processing is relevant to the
relevant thinking in individuals with depression, so that
task at hand, and how well cues engage that specific proces-
changes in focus or content lead to changes in medial
sing. For example, if self-relevant processing of positive
cortex activity; or (ii) changes in the functioning of medial
information such as hopes and aspirations is specifically
cortex in depression promote differences in the content or
cued, based on our findings, we would expect less difference
focus of self-relevant thinking. However, based on a range
between controls and depressed participants in medial PFC
of neurophysiological evidence, including developmental
activity than in tasks that put fewer constraints on the nature
trajectories, it has been suggested that default network con-
of self-referential thinking. Group differences should be most
nectivity is sculpted by experience (Sheline et al., 2009).
likely in the unconstrained case because depressed partici-
Thus, it may be that long-term self-focused, negative rumi-
pants are less likely to spontaneously generate positive
native thinking, such as that engaged by many depressed
thoughts and more likely to spontaneously generate negative
individuals, strengthens connectivity of certain medial
thoughts (Wenzlaff et al., 1988). If self-relevant processing
areas of the default network (Greicius et al., 2007), making
(positively or negatively valenced) is not appropriate to the
it more difficult to disengage when appropriate (e.g. during
task at all (as in many cognitive tasks), we would expect to
find more medial PFC activity (i.e. less deactivation) asso-
In any event, differences in activity within specific areas of
ciated with depression (Siegle et al., 2002), consistent with a
the ‘default network' may provide an index of the extent and
failure to disengage from self-relevant processing when it is
type of self-focused thought that is spontaneously engaged,
not appropriate. In other words, increases in activity in
and these may differ systematically between populations.
medial PFC associated with depression, relative to controls,
Medial cortex, self-reflection and depression
would be expected if depressed participants are less able to
and aspirations when the cues to self-reflection are ambig-
disengage self-focused thought and engage processes
uous. Furthermore, a tendency to ruminate is correlated
required for other tasks.
with greater activation in anterior and posterior medial
Depression is a heterogeneous disorder. Studies of dys-
cortex during tasks where these regions typically deactivate,
phoric and MDD/MDE participants along the lines of the
suggesting a persisting self-focus when it may not be appro-
present study, that manipulate the specific nature of both
priate. Exploring differential engagement and disengagement
self-relevant and non-self-relevant processing, would help
of specific regions in anterior and posterior medial cortex in
distinguish between individual differences in dysfunction
different populations under different circumstances should
of the self-relevant and self-regulatory processing networks
help clarify the role that these regions normally play in self-
that involve anterior and posterior medial cortex regions and
reflection and emotion regulation and in the interaction
could clarify individual differences in the circumstances
between motivation, emotion and cognition more generally.
under which these areas are engaged, which could be clini-cally useful. For example, in subclinical dysphoric popula-
Conflict of Interest
tions, the extent to which medial PFC is engaged under
specific instructions to think about hopes and aspirationsor the extent to which engagement is predicted by rumina-tion scores may provide an early biomarker of susceptibility
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2011 Survey on Reperfusion on STEMI in Europe Survey on reperfusion therapy for ST-elevation myocardial infarction in the ESC membership countries. When the Stent for Life initiative started 3 years ago one of the first tasks was to collect data on the use of reperfusion therapy in Europe. The first survey published by Petr Widimsky et al in the European Heart Journal revealed a huge variation in reperfusion therapy in the participating 30 ESC membership countries. With the help of the National Society Country's champions and contact persons we are now collecting data on reperfusion therapy in 2011 as
LIVING IN KARST Iowa Geological Survey Guidebook Series No. 25 IOWA FIELD CONFERENCE FOR PUBLIC POLICY MAKERS OCTOBER 11-12, 2005 Iowa Department of Natural Resources Jeffrey R. Vonk, Director October 2005 The collapse of rock and soil into underground crevices and caves causes sinkholes (circular pits)