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Deep Brain Stimulation for Treatment Resistant Depression: Neuropsychological Impact

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Deep Brain Stimulation for Treatment Resistant Depression: Neuropsychological Impact Heather McNeely, Ph.D., C.Psych. Clinical Neuropsychologist – PowerPoint PPT presentation

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Title: Deep Brain Stimulation for Treatment Resistant Depression: Neuropsychological Impact


1
Deep Brain Stimulation for Treatment Resistant
DepressionNeuropsychological Impact
  • Heather McNeely, Ph.D., C.Psych.
  • Clinical Neuropsychologist
  • St. Josephs Healthcare, Hamilton
  • Associate Professor
  • Department of Psychiatry Behavioural
    Neurosciences McMaster University
  • Assistant Professor
  • Department of Psychiatry, University of Toronto

2
Todays Objectives
  • To become familiar with
  • Deep Brain Stimulation (DBS)
  • Use of DBS for treatment resistant depression
    (TRD)
  • Neuropsychological impact of DBS

3
What is DBS?
  • Chronic, high frequency electrical stimulation
    targeted to specific brain regions
  • Micro-electrodes implanted in the brain
  • Connected to a pulse generator
  • Individually calibrated to optimal stimulation
    parameters

4
What is DBS used for?
  • Approved as a treatment for
  • Parkinsons Disease
  • Essential Tremor
  • Dystonia
  • Investigational use in
  • Major Depressive Disorder (MDD)
  • Obsessive Compulsive Disorder (OCD)
  • Tourette Syndrome
  • Phantom Limb Pain
  • And others

5
Treatment Resistant Depression (TRD)
  • MDD impacts 10 - 25 of women and 5 - 12 of men
  • Up to 20 of MDD patients fail to respond to
    standard interventions
  • Psychotherapy
  • Medications
  • Electroconvulsive Therapy (ECT)
  • TRD represents a small, but very disabled
    population

Fava, 2003 Keller et al., 1992 Pincus Petit,
2001
6
Choosing a target for DBS in TRD
  • Evidence from PET studies has shown
  • The subgenual anterior cingulate (Cg25) is
    over-activated in depression
  • Cg25 activity increases with induced sadness
  • Cg25 activity down-regulates following standard
    treatments
  • Thus directly targeting Cg25 with DBS should
    elicit similar responses

Mayberg, 1997 Mayberg, Liotti et al., 1999
Mayberg, Brannan, et al., 2000
7
Limbic-Frontal Network
Mood
mb-p
Vegetative-Somatic
Mayberg, 1997
8
Hypotheses
  • DBS to Cg25 white matter will
  • Decrease over-active cingulate
  • Increase under-active frontal lobe regions
  • Impact functional pathways linking limbic and
    frontal regions
  • Leading to
  • Improved mood
  • ? Improved frontal lobe cognition

9
Why Include Neuropsychology in DBS Treatment
Protocol?
10
Neuropsychology of DBS for Parkinsons Disease
  • Unilateral DBS to subthalamic nucleus (STN) or
    globus pallidus interna (GPi) leads to
  • Improvements in motor symptoms
  • BUT
  • Mild frontal cognitive decline
  • Up to 10 of patients exhibit severe cognitive
    and psychiatric consequences

Funkiewiez et al., 2004, J Neurol Neurosurg
Funkiewiez et al., 2006, Mov Disord Pillon et
al., 2000, Neurology Rodriguez-Oroz, et al.,
2005, Brain Saint-Cyr et al., 2000, Brain
Vale, 2008, Exp Biol
11
Neuropsychological Assessment
  • Pre-operative screening
  • Monitor unexpected events
  • Evaluate functional outcomes
  • Ensure cognitive safety
  • Research purposes

12
Testing Protocol
13
Repeated Testing
  • Frontal / Executive Functions
  • Information Processing Speed
  • Learning and Memory
  • Manual Motor Skills
  • Emotional Processing

14
Repeated Measures
  • Frontal / Executive Skills
  • Wisconsin Card Sorting Test (WCST)
  • Object Alternation (OA)
  • Iowa Gambling Task (IGT)
  • Phonemic Verbal Fluency
  • Stroop Colour Word Test
  • Emotional Stroop Test

15
Wisconsin Card Sorting Test
16
Object Alternation Task
17
Iowa Gambling Task
A
B
C
D
WIN 250 LOSE 1000
18
Phonemic Fluency
F
19
Stroop Colour Word Tests
Standard
Emotional
RED BLUE GREEN
SAD LONELY STUPID
20
Repeated Measures
  • Emotional Processing
  • International Affective Picture System Ratings
  • Information Processing Speed
  • Word reading speed from standard Stroop
  • Memory
  • Hopkins Verbal Learning Test-Revised
  • Manual Motor Skills
  • Finger Tapping Test

21
IAPS Sad
22
IAPS Happy
23
IAPS Fear
24
IAPS Neutral
25
IAPS Ratings
26
Participant Requirements
  • Inclusion Criteria
  • Recurrent MDD current episode gt 12 months
  • Resistant to at least four adequate treatment
    trials
  • Hamilton Rating Scale for Depression (HDRS-17)
    score gt 20
  • Age 30 to 50 years (later extended to age 75)
  • Exclusion Criteria
  • Other Axis I disorders
  • Alcohol or substance abuse/dependence within 12
    months
  • Active suicidal ideation
  • Major medical illness, other implanted stimulator

27
Patient Demographics
Kennedy, Rizvi, McNeely, Giacobbe, Mayberg
Lozano (2009)
28
DBS Methods
  • Surgical Implantation Stimulation
  • 4 electrodes per side
  • Implanted in Cg25 white matter bilaterally
  • Under local anesthesia
  • Using MRI guidance

Mayberg et al, 2005
29
DBS Methods
  • Lead placement confirmed by post-op MRI
  • Optimization of stimulation over 5 days in
    hospital
  • 4 week adjustment period
  • 12 months of chronic DBS

Mayberg et al, 2005
30
Treatment Results
  • Treatment Response
  • Defined as a 50 reduction in baseline HRSD score
  • 60 of patients attained response

6 Months
Baseline
Kennedy et al 2009 Lozano et al., 2008 Mayberg
et al 2005
31
Change in Mood
32
Neuropsychology Results
  • Baseline
  • Patients scored in the average to high average
    range of general intellect (IQ)
  • Intact functioning on tests of
  • Language
  • Simple attention
  • Visual spatial skills

33
Changes in Frontal Lobe Function
  • Over 12 Months of Chronic Cg25 DBS

34
Wisconsin Card Sorting Test
Perseverative Errors
Non-perseverative Errors
35
Object Alternation
TRD Patients
Frontal Lobe Patients
Compared to a sample of patients with
orbital-frontal damage (Friedman et al., 1998)
36
Iowa Gambling Task
37
Phonemic Verbal Fluency
38
Stroop Colour Word
39
Emotional Stroop
Neutral
Negative
Positive
40
Information Processing Speed
41
Verbal Memory
Learning
Delayed Recall
Recognition
Note 4 alternate forms of HVLT used
42
Finger Tapping
Dominant Hand
Nondominant Hand
43
IAPS Valence Ratings
Note TRD group compared to mean control data
from Lang et al., 1999
44
IAPS Arousal Ratings
Neutral Positive Sad Fear
45
Can baseline emotional reactivity predict DBS
response?
Over 55 of variance in mood response predicted
above chance
Significant predictors IAPS sad valence IAPS
sad arousal IAPS happy valence
46
Summary of Findings
  • Following Cg25 DBS in treatment resistant
    depression
  • Cg25 activity went down
  • Frontal lobe activity went up
  • 60 of patients achieved clinical response

47
Summary of Findings
  • No consistent cognitive declines
  • Subtle cognitive improvements on some measures of
    frontal lobe function
  • Not secondary to mood benefits alone
  • Cg25 DBS appears effective and safe
  • Emotional reactivity at baseline may be
    predictive of treatment response

48
Acknowledgements
  • Original TRD Study Investigators
  • Dr. Helen Mayberg
  • Dr. Andres Lozano
  • Dr. Sidney Kennedy
  • Resident / Student / RA Support
  • Dr. Valerie Voon
  • Dr. Beverley Bouffard
  • Ms. Sakina Rizvi
  • Ms. Kari Fulton
  • Ms. Jennifer Bryan
  • Ms. Sarah Uzzaman
  • Ms. Pushpinder Saini
  • Ms. Jessica Hurdelbrink
  • Ms. Christina Velasco
  • National Alliance for Research on Schizophrenia
    and Affective Disorders

49
Thank you for your attention!
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