Imaging Emotion: from Normal Feelings to Abnormal Mood States

1
Imaging Emotion from Normal Feelings to Abnormal
Mood States

• Mary L. Phillips, MD
• University of Pittsburgh
• Western Psychiatric Institute and Clinic
• Pittsburgh, Pennsylvania
• Department of Psychological Medicine
• Cardiff University
• Institute of Psychiatry
• London, United Kingdom

2
Neuroimaging Why Important in Psychiatry?

• To understand the functional neural basis of
  psychiatric disorders
• To identify neural markers / disease biomarkers
  to aid diagnosis
• To identify disease endophenotypes in at risk
  populations
• To identify treatment-relevant
• endophenotypes

3
Phenotype Bipolar Disorder and Bipolar
spectrum
Endophenotypes
Genotype
Hasler G, et al. Biol Psychiatry
200660(2)93-105.
4
Laboratory of Neuro Imaging, UCLA
5
Re-appraisal of negative scenes
Phan et al., 2005
Blue inverse correlation with intensity of
negative emotion Orange positive correlation
relationship with intensity of negative emotion
6
Rostral Anterior Cingulate Gyrus Regulates
Amygdala
Etkin et al., 2006
7
Voluntary Sub-processes Voluntary Behavioral
Control Suppression of emotion
expression Voluntary Attentional Control
Avoidance of emotionally-salient
material Selective attention Inhibition of
emotional motor responses Voluntary Cognitive
Change Processes Reappraisal
LATERAL/DORSAL PFC bilateral DLPFC
(VLPFC) bilateral MdPFC bilateral dorsal
ACG (mediated by bilateral OFC)
VENTRAL/MEDIAL PFC bilateral subgenual
ACG bilateral OFC left rostral ACG bilateral
MdPFC midline dorsal ACG Hippocampus/parahippocamp
us
Automatic Sub-processes Automatic Behavioral
Control Extinction Behavioral
regulation Automatic Attentional Control
Cognitive disengagement Repressive and
avoidant personality styles Automatic Cognitive
Change Processes Covert appraisal and
reappraisal Covert response (e.g. error
monitoring) Covert learning that serves to
automatically adjust behavior
Phillips, Ladouceur, Drevets, in submission
8
Voluntary Emotion Regulation Feedback Pathway
DLPFC
Dorsal ACG
MdPFC
Rostral ACG
Ventral Striatum
VLPFC
Thalamus
OFC Subgenual ACG
Hipp/parahipp
Amygdala
Orienting/Emotion Identification Automatic
Emotion Regulation Voluntary Emotion Regulation
Regions implicated in both
Phillips, Ladouceur, Drevets, in submission
9
Automatic Emotion Regulation Feedforward Pathway
DLPFC
Dorsal ACG
MdPFC
Rostral ACG
Ventral Striatum
VLPFC
Thalamus
OFC Subgenual ACG
Hipp/parahipp
Amygdala
Orienting/Emotion Identification Automatic
Emotion Regulation Voluntary Emotion Regulation
Regions implicated in both
Phillips, Ladouceur, Drevets, in submission
10
Unipolar Depression
11
Attentional bias toward negative emotional,
self-relevant events
12
(No Transcript)
13
Linear Increases to Increasing Intensity of
Happiness Healthy Individuals gtMDD
Healthy
Depressed
Surguladze S, et al. Biol Psychiatry
200557201-209.
14
Linear Increases to Increasing Intensity of
Sadness MDD gt Healthy individuals
Depressed
Healthy
Surguladze S, et al. Biol Psychiatry
200557201-209.
15
(No Transcript)
16
Anhedonia
17
(No Transcript)
18
Keedwell et al., 2005
19
Keedwell et al., 2005, Biological Psychiatry
20
Suicidal Ideation
21
Jollant et al., 2008, in press, American Journal
of Psychiatry
22
Suicide Attempters and Affective Controls
Angry vs Neutral faces
ACgtSA
SAgtAC
Jollant et al., 2008, in press. American Journal
of Psychiatry
23
Anhedonia
DLPFC
Dorsal ACG
MdPFC
Rostral ACG
Ventral Striatum
VLPFC
Thalamus
OFC Subgenual ACG
Hipp/parahipp
Amygdala
Orienting/Emotion Identification Automatic
Emotion Regulation Voluntary Emotion Regulation
Regions implicated in both
24
Suicidal behavior
DLPFC
Dorsal ACG
MdPFC
Rostral ACG
Ventral Striatum
VLPFC
Thalamus
OFC Subgenual ACG
Hipp/parahipp
Amygdala
Orienting/Emotion Identification Automatic
Emotion Regulation Voluntary Emotion Regulation
Regions implicated in both
25
Bipolar Disorder
26
Emotion Processing
27
fMRI amygdala reactivity paradigm
Altshuler et al., 2005
28
(No Transcript)
29
INTENSE FEAR
L amygdala / ventrolateral PFC
CON BD MDD
Lawrence NS, et al. Biol Psychiatry
200455578-587.
30
MILD HAPPY
MDD
CON
BD
L amygdala / putamen
ventromedial PFC
.04
neural response
0
- .02
CON BD MDD
CON BD MDD
Lawrence NS, et al. Biol Psychiatry
200455578-587
31
Hassel et al., 2008, final revision, Bipolar
Disorders
32
Hassel et al., 2008, final revision, Bipolar
Disorders
33
Increased striatal activity in euthymic bipolar
disorder to emotional stimuli
Affective Go No Go Task
Wessa et al., 2006
34
Increased hippocampal/parahippocampal activity
in euthymic bipolar disorder to negative
emotional stimuli
Lagopoulos et al., 2007 Emotional Stroop
Mahli et al., 2007 Facial Expressions
35
Structural Abnormalities
36
Gray matter volume reduction in Bipolar Disorder
Almeida et al., in press, 2008, Psych. Res.
Neuroimaging
37
Gray matter volume reduction in Bipolar Disorder
Left parahippocampus
Left putamen
Almeida et al., in press, 2008, Psych. Res.
Neuroimaging
38
Elevated left orbito-medial prefrontal white
matter fractional anisotropy in bipolar adults
revealed by tract-based spatial statistics
Versace et al., In revision
39
Elevated left orbito-medial prefrontal white
matter fractional anisotropy in bipolar adults
revealed by tract-based spatial statistics
Versace et al., 2008 in press, Arch. Gen
Psychiatry
40
Increased white matter connectivity in euthymic
bipolar patients diffusion tensor tractography
between left subgenual cingulate and the
amygdalo-hippocampal complex
Houenou et al., 2006
41
Bipolar Depression gt Bipolar when Euthymic
Fractional Anisotropy
Mean diffusivity
Zanetti et al., in submission
42
Automatic Emotion Regulation Feedforward Pathway
DLPFC
Dorsal ACG
MdPFC
Rostral ACG
Ventral Striatum
VLPFC
Thalamus
OFC Subgenual ACG
Hipp/parahipp
Amygdala
Orienting/Emotion Identification Automatic
Emotion Regulation Voluntary Emotion Regulation
Regions implicated in both
Phillips, Ladouceur, Drevets, in submission
43
Voluntary Emotion Regulation Feedback Pathway
DLPFC
Dorsal ACG
MdPFC
Rostral ACG
Ventral Striatum
VLPFC
Thalamus
OFC Subgenual ACG
Hipp/parahipp
Amygdala
Orienting/Emotion Identification Automatic
Emotion Regulation Voluntary Emotion Regulation
Regions implicated in both
Phillips, Ladouceur, Drevets, in submission
44
Potential Impairments in Neural Systems of
Emotion Regulation in Bipolar Disorder
DLPFC
Dorsal ACG
MdPFC
Ventral striatum
Rostral ACG
VLPFC
OFC Subgenual ACG
Thalamus
Hipp/parahipp
Amygdala
Phillips, Ladouceur, Drevets, Molecular
Psychiatry, in press
45
Effective ConnectivityDynamic Causal Modeling
46
Happy and Neutral Face Emotion Labeling Best-fit
Model
overt
covert
Almeida et al., 2008, in submission
47
BipolargtControl
P0.03
Significantly greater positive effective
connectivity in BD patients versus HC between
right PHC and right sgGC to Intense, mild happy
and neutral faces
Almeida et al., 2008, in submission
48
Summary

• Identifying neural markers of bipolar versus
  unipolar depression multimodal neuroimaging
  approach

49
Bipolar At Risk Youth
50
Demographic Characteristics of Participants
Note HBO Healthy Bipolar Offspring CONT
Low-Risk Control Participants Pubertal scores
ranged from 1 to 4. There were no significant
group differences for any of these variables.
Ladouceur et al., in press, JAACCP
51
Increased GM Volume in Parahippocampus -
Hippocampus in HBO Compared to CONT
Left Parahippocampal/Hippocampal Gyrus. Cluster
size 124 voxels, t3.93, punc.lt.001 SVC, plt.05.
Ladouceur et al., in press, JAACAP
52
Demographic Characteristics of Participants
Note HBO Healthy Bipolar Offspring CONT
Low-Risk Control Participants Pubertal scores
ranged from 1 to 4. There were no significant
group differences for any of these variables
Ladouceur et al., in prep
53
Greater OFC Activation when Processing Intense
Expressions of Fear in HBO vs. CONT
OFC (BA 11) (MNI 21, 21, -15)
Ladouceur et al., in prep
54
Potential Abnormalities in Neural Systems of
Emotion Regulation in Bipolar At Risk
DLPFC
Dorsal ACG
MdPFC
Rostral ACG
Ventral Striatum
VLPFC
OFC Subgenual ACG
Thalamus
Hipp/parahipp
Amygdala
55
Treatment Response Endophenotypes
56
Siegle et al. (2006). American Journal of
Psychiatry, 163, 735
57
Decreases in elevated limbic-cortical neural
activity to sad faces post treatment associated
with greater response to antidepressants in MDD
Change in trend 100gt50gtneutral Sad
Happy
Keedwell et al., 2008, in press J. Psychopharm
58
Neuroimaging Why Important in Psychiatry?

• To understand the functional neural basis of
  psychiatric disorders - YES
• To identify neural markers / disease biomarkers
  to aid diagnosis - YES
• To identify disease endophenotypes in at risk
  populations - YES
• To identify treatment-relevant endophenotypes -
  YES

59

• Institute of Psychiatry, London, UK
• Simon A. Surguladze Natalia Lawrence
• Maike Heining Jeffrey Gray
• Paul Keedwell Tamara Russell
• Andrew Williams Catherine Herba
• Sophia Frangou
• Natalie Kerr
• David Mataix-Cols
• Sarah Wooderson
• University of Cambridge, UK University of Sao
  Paulo, Brazil
• Dina Kronhaus Marcus Zanetti
• Luke Clarke Geraldo Bussato
• Barbara Sahakian
• Univeristy of Pittsburgh
• Cecile Ladouceur
• Jorge Almeida
• Amelia Versace

Grant Support 1R01 MH076971-01 NARSAD Medical
Research Council (UK) The Wellcome Trust
(UK) James McDonnell Pew Foundation