the interactive brain: frontal-lobe function and dysfunction

THE INTERACTIVE BRAIN:
FRONTAL-LOBE FUNCTION
AND DYSFUNCTION
Elkhonon Goldberg, Ph.D., ABPP
Oslo, 2012
Brodmann s Areas
Brodmann (1909):
Based on cytoarchitectonics: study of
differences in cortical layers between areas
Most common delineation of cortical areas
The Frontal Lobe
From E. Goldberg. (2005). The Wisdom Paradox: How
Your Mind Can Grow Stronger as Your Brain Grows
Older. New York: Gotham Books, Penguin
Evolution of the Frontal Cortex
From E. Goldberg. (2005). The Wisdom Paradox: How
Your Mind Can Grow Stronger as Your Brain Grows
Older. New York: Gotham Books, Penguin
FRONTAL LOBES IN EVOLUTION
- The development of the frontal lobes in evolution
is associated with the emergence of
consciousness and the capacity for insight into
the mental world of others
- Frontal lobe damage often results in the loss of
insight into the mental world of others
FRONTAL LOBES DURING LIFE
SPAN
- Frontal lobes are very late to complete their
development (not before the age of 18 or even
later). This is the approximate age recognized by
modern societies as the age of social and legal
maturity
- Frontal lobe damage often results in the loss of
social maturity in an adult patient
- Frontal lobes are the earliest to succumb to the
effects of normal aging
Map of Brain Regions Affected in Aging
From E. Goldberg. (2005). The Wisdom Paradox: How Your
Mind Can Grow Stronger as Your Brain Grows Older. New
York: Gotham Books, Penguin
FRONTAL LOBES ARE CENTRAL TO
COMPLEX DECISION MAKING
- goal-directed behavior
- planning and temporal organization of
cognitive processes
- mental flexibility
- critical judgement
- ability to project into the future and
anticipate the consequences of
behavior
- capacity for insight into other
people s mind
- impulse control
FRONTAL LOBES ARE VULNERABLE
- 
- 
- 
- 
- 
- 
- 
- 
- 
Normal aging
Traumatic Brain Injury (TBI)
Post-Traumatic Stress Disorder (PTSD)
Depression
Dementias
Schizophrenia
Autism
ADHD
Tourette s/OCD
EXECUTIVE FUNCTIONS
-PREFRONTAL CORTEX
-ANTERIOR CINGULATE CORTEX
-STRIATUM (CAUDATE, PUTAMEN)
RELATED FUNCTIONS
ATTENTION
AROUSAL
EMOTIONS
ATROUSAL/ACTIVATION
-VENTRAL PONS
-VENTRAL MESENCEPHALON
-MIDLINE THALAMUS
ATTENTION
-VENTRAL MESENCEPHALON
-MIDLINE THALAMUS
-PREFRONTAL CORTEX
EMOTIONS
-AMYGDALA
-PREFRONTAL CORTEX
NEUROMODULATORS
-
NOREPINEPHRINE (AROUSAL)
DOPAMINE (REWARD)
SEROTONIN (MOOD)
ACETYLCHOLYNE (LEARNING)
NEUROMODULATORS
NE
- RIGHT HEMISPHERIC PREPONDERANCE
- MEDIATES EXPLORATORY BEHAVIOR
AND ORIENTING RESPONSE TO
PERCEPTUAL NOVELTY
DA
- LEFT HEMISPHERE PREPONDERANCE
- MEDIATES MOTOR STEREOTYPIES
FRONTAL LOBE
SYNDROMES
-DORSOLATERAL ( PESUDODEPRESSED )
-ORBITOFRONTAL
( PSEUDOPSYCHOPATHIC )
-VENTROMEDIAL
-FRONTOPOLAR
-ANTERIOR CINGULAR
LEFT-RIGHT ??????????????????????
INABILITY TO TERMINATE
ACTION ONCE STARTED IN
FRONTAL LOBE DAMAGE
INABILITY TO TEMINATE BEHAVIOR
FOLLOWING FRONTAL DAMAGE
From E. Goldberg. (1986). Varieties of perseveration: Comparison of two taxonomies.
Journal of Clinical and Experimental Neuropsychology, 8, 710-726.
Types of Executive Operations
1) Guidance by internal representations (e.g.,
plans)
-behavior is driven by a cognitive context
2) Responding to unanticipated environmental
contingencies - behavior is driven by stimulus;
not necessarily context
In healthy individuals they work in balance
Deficits found following prefrontal damage
Perseveration
-inability to completely switch
from an earlier behavior to a new one
-previously formed cognitive content
Persists in disregard of changing contingencies
Field-dependent
-distractibility toward incidental external
stimuli, causing an inability to maintain an
internally driven cognitive context
- response selection is determined by
external stimuli, which trigger the
elements of the knowledge base, which
are stimulus appropriate but contextinappropriate
Varieties of
Perseverations
From Goldberg & Tucker
(1978). Motor perseverations
and the levels of encoding a
visual form. Journal of
Clinical Neuropsychology, 4,
273-288
Varieties of
Perseverations
From Goldberg & Tucker
(1978). Motor perseverations
and the levels of encoding a
visual form. Journal of
Clinical Neuropsychology, 4,
273-288
Story Recall After Prefrontal Lesion
The story A Hen and Golden Eggs reads as follows: A man
owned a hen that was laying golden eggs. The man was greedy
and wanted to get more gold at once. He killed the hen and cut it
open hoping to find lot of gold inside, but there was none.
After an oral presentation of the story, the patient s recall was as
follows:
A man was living with a hen….or rather the man was the hen s
owner. She was producing gold….The man….the owner….wanted
more gold at once….so he cut the hen into pieces but there was
no gold….No gold at all….he cuts the hen more,…no gold…the hen
remains empty….So he searches again and again….No gold….he
searches all around…in all places. The search is going on with a
tape recorder…they are looking here and there, nothing new
around. They leave the tape recorder turned on, something is
twisting there…what the hell are they recording there…some digits
0, 2, 3, 0
Story Recall After Prefrontal Lesion (Cont.)
…so, they are recording all these digits…not very many of them…
that s why all the other digits were recorded…turned out to be
not very many of the either…so, everything was recorded…and I ll
tell you what…there were only 5-6 digits there… (Experimenter:
Have you finished?) Not yet, I ll finish soon…so, there were only
5-6 digits there….When they they took the bus #5 and went along
Lefortoff Drive…so, you get there and transfer to bus #5
(Experimenter: You better finish!) Not yet! Wait a moment! So
you take bus #5 and get to the Bauman Square…From the
Bauman Square you go further on…further on. Here you take off.
And again you take bus #5….I ll make it precise…so you take
off…and take bus #5…and you get to cafeteria…number 5 point
6….(monologue continues).
Goldberg, E. & Costa, L. (1986) In:
Grant and K.Adams(Eds.)
Neuropsychological Assessment of Neuropsychiatric Disorders
NY Oxford U. Press
ASSESSING EXECUTIVE
FUNCTIONS
MEASURABLE CONSTRUCTS
-GENERATIVITY (fluency tests, e.g. DKEFS)
- MENTAL FLEXIBILITY (WCST)
-OVERCOMING PREPOTENT TENDENCY
(Stroop, DKEFS)
-PLANNING (Tower, 20 questions)
-WORKING MEMORY - ?????????????
WORKING MEMORY
-ANIMAL STUDIES
- HUMAN STUDIES
-SELECTIVITY OF MEMORY
EMERGING CONSTRUCTS
- COOL vs. HOT EXECUTIVE FUNCTIONS
- COOL (WCST)
- HOT (IGT)
MISSING CONSTRUCTS
-ACTOR-CENTERED DECISION MAKING
- COGNITIVE NOVELTY
Functions of particular interest
Prefrontal cortex is critical for
decision making in ambiguous or
novel environments
FRONTAL LOBES IN NOVELTY AND
UNCERTAINTY
- Frontal lobes are particularly important in
dealing with novel, unexpected situations
characterized by uncertainty
- Damage to the frontal lobes impairs the
ability to deal with unanticipated, novel
situations
MISSING CONSTRUCTS
-ACTOR-CENTERED DECISION MAKING
VERIDICAL (DESCRIPTIVE) vs.
ACTOR-CENTERED (PRESCRIPTIVE)
DECISION MAKING
! 
! 
! 
DESCRIPTIVE DECISION-MAKING: WHAT
IS TRUE AND WHAT IS FALSE?
PRESCRIPTIVE DECISION MAKING: WHAT
IS MY PREFERENCE, WHAT SHOULD I DO?
THEIR NEUROANATOMICAL TERRITORIES
ARE DIFFERENT
NEW PARADIGM TO STUDY
FRONTAL-LOBE FUNCTION AND
DYSFUNCTION:
ACTOR-CENTERED DECISION
MAKING
Descriptive and Prescriptive Knowledge Territories
From E. Goldberg. (2005). The Wisdom Paradox: How
Your Mind Can Grow Stronger as Your Brain Grows
Older. New York: Gotham Books, Penguin
ACTOR-CENTERED (PRESCRIPTIVE)
DECISION MAKING IS CRITICAL FOR
SURVIVAL AND SUCCESS
BUT TRADITIONAL NEUROPSYCHOLOGY
AND CLINICAL NEUROSCIENCE FOCUSED
ON VERIDICAL (DESCRIPTIVE) DECISION
MAKING AND MOSTLY IGNORED ACTORCENTERED DECISION MAKING
VERIDICAL (DESCRIPTIVE) vs ACTORCENTERED (PRESCRIPTIVE) DECISION
MAKING
Veridical decision is about finding the correct
response. The solution is inherent in the
situation, unambiguous and does not
depend on who is solving the problem.
The true/false distinction applies and there
is usually only one correct response:
5+5 = ?
The capital of Denmark is ?
VERIDICAL (PRESCRIPTIVE) vs ACTORCENTERED (DESCRIPTIVE) DECISION
MAKING
Actor-centered decision making is about personal
preference. It is often different for different
people in the same situation; it is not inherent in
the situation; and the true/false distinction does
not apply:
What should I order from a restaurant
menu?
Should I go to graduate school, medical
school, law school, or just marry and be
happy after college?
ACTOR-CENTERED (PRESCRIPTIVE) DECISION
MAKING IS CRITICAL FOR SURVIVAL AND
SUCCESS
BUT TRADITIONAL NEUROPSYCHOLOGY AND
COGNITIVE NEUROSCIENCE FOCUSED ON
VERIDICAL (DESCRIPTIVE) DECISION MAKING
AND IGNORED ACTOR-CENTERED DECISION
MAKING
CBT CARD
Appearance of free choice, but in
reality constrained and counterbalanced in ways that enable us to
track the subjects response
selection strategies and to
disambiguate tasks
Various versions: stochastic,
Markovian, etc
Allow transparent subtraction tasks
CBT on SPECT
H. Shimoyama, M. Aihara, H. Fukuyama, K. Hashikawa, K. Ayoagu,
E. Goldberg, S. Nakazawa. Brain & Development, 26 (2004), 37-42
Cognitive Bias Task in fMRI
(K. Vogeley et al., 2003)
prf > all
n = 11; random effects model (SPM99); height threshold p = 0.0005; extent threshold = 30
voxel
Cognitive Bias Task in fMRI
(K. Vogeley et al., 2003)
dif > all
n = 11; random effects model (SPM99); height threshold p = 0.0005; extent threshold = 30
voxel
Cognitive Bias Task in fMRI
(K. Vogeley et al., 2003)
sim > all
n = 11; random effects model (SPM99); height threshold p = 0.0005; extent threshold = 30
voxel
RIGHT TO LEFT SHIFT DURING TASK FAMILIARIZATION
Target Card
Choice Cards
(EEG spectral power in the gamma frequency band (30-40 Hz) (Kamiya et al, 2004))
2sec
µV2
2.00
1.00
0.00
EEG Spectral Power during the First
Target Card Half (Kamiya et al, 2004) Choice Cards
1 sec
1 sec
EEG Spectral Power during the Latter
Half (Kamiya et al, 2004) Choice Cards
Target Card
sec
sec
CBT converted score
Performance levels on the cognitive
bias task (CBT)
70
60
50
40
30
20
10
0
Normal
*
*
Mild AD
Moderate AD
* p < .05 (re Normal Group)
A. Kluger, E. Goldberg, T. Griesing, L. Malta, M. Shapiro, and S. Ferris.
Early diagnosis of frontal-lobe dementias. (1997).
Eighth Congress of International Psychogeriatric Association. Jerusalem, Israel.
Performance levels on the
perceptual matching task
Similarity score
270
250
230
210
*
190
170
Normal
Mild AD
Moderate AD
* p < .05 (re Normal group)
E. Goldberg, A. Kluger, T. Griesing, L. Malta, M. Shapiro, and S. Ferris.
Early diagnosis of frontal-lobe dementias. (1997).
Eighth Congress of International Psychogeriatric Association. Jerusalem, Israel.
Actor-centered decision making in
substance abusers
Verdejo-Garcia, A., Vilar-Lopez, R., Perez-Garcia, M., & Goldberg, E. (2006).
Altered adaptive but not veridical decision-making in substance dependent individuals
Journal of the International Neuropsychological Society, 12, 90–99.
FUNCTIONAL
LATERALIZATION IN THE
FRONTAL LOBES
HEMISPHERIC DIFFERENCES
ACROSS MAMMALIAN SPECIES
! 
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! 
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Yakovlevian torque – frontal poles (R>L)
Yakovlevian torque – occipital poles (L>R)
Cortical thickness (R>L in males)
Planum temporale (L>R)
Frontal operculum (L>R)
Spindle cells (R>L)
NE (R>L)
DA (L>R)
CBT CARD
Means and standard
deviations for converted
CBT scores in strictly righthanded healthy subjects
70
60
50
40
30
20
10
0
40.4
(21.8)
14.9
(12.4)
Males
Females
E. Goldberg, K. Podell, R. Harner, M. Lovell, S. Riggio.
Journal of Cognitive Neuroscience, 1994
Means and standard deviations for converted
CBT scores in strictly right-handed healthy
and lesioned males
70
62.3
60
(4.2)
50
40
30
0
36.4
(18.6)
(26.5)
19.3
20
10
35.9
13
(5.1
(4.2)
(
LFRM
LPRM
HCM
RPRM
E. Goldberg, K. Podell, R. Harner, M. Lovell, S. Riggio.
Journal of Cognitive Neuroscience, 1994
RFRM
Mean group scores for the explicit
conditions and CBT administration in
strictlt right-handed males
R
FR
M
R
M
R
P
H
C
M
R
M
Different
CBT
Similar
LP
LF
R
M
220
200
180
160
140
120
100
80
E. Goldberg, K. Podell, R. Harner, M. Lovell, S. Riggio.
Journal of Cognitive Neuroscience, 1994
Individual Cognitive Bias Task (CBT) score distribution in frontal lesion groups. LFRM
= left frontal right-handed males (n = 5); RFRM = right frontal right-handed males (n
= 8); HCM = healthy control males (n = 21).
K. Podell, M. Lovell, M. Zimmerman, and E. Goldberg. (1995). The Cognitive Bias Task
and lateralized frontal lobe functions in males. Journal of Neuropsychiatry and Clinical
Neuroscience, 7, 491-501.
Individual Wisconsin Card Sorting Test score distribution in frontal lesion groups. Number of
categories achieved (WCST-CAT). LFRM = left frontal right-handed males (n = 4); RFRM = right
frontal right-handed males (n = 8).
K. Podell, M. Lovell, M. Zimmerman, and E. Goldberg. (1995). The Cognitive Bias Task and lateralized
frontal lobe functions in males. Journal of Neuropsychiatry and Clinical Neuroscience, 7, 491-501.
Individual Wisconsin Card Sorting Test score distribution in frontal lesion groups.
Number of perseverative responses (WCST-PR). LFRM = left frontal right-handed males
(n = 4); RFRM = right frontal right-handed males (n = 8).
K. Podell, M. Lovell, M. Zimmerman, and E. Goldberg. (1995). The Cognitive Bias Task
and lateralized frontal lobe functions in males. Journal of Neuropsychiatry and Clinical
Neuroscience, 7, 491-501
GENDER DIFFERENCES IN
THE FRONTAL LOBES
Means and standard
deviations for converted
CBT scores in strictly righthanded healthy and
lesioned females
70
60
50
40
30
20
10
0
64.8
54.5
(2.1)
(12.6)
12
14.6
(10.9)
LFRF
LPRF
HCF
E. Goldberg, K. Podell, R. Harner, M. Lovell, S. Riggio.
Journal of Cognitive Neuroscience, 1994
7.2
(4.2)
RPRF
RFRF
Converted CBT mean score
comparison betw een male
and female lesion groups
54.5
36.4
14.6
7.2
Male
E. Goldberg, K. Podell, R. Harner, M. Lovell, S. Riggio.
Journal of Cognitive Neuroscience, 1994
Female
F
F
P
R
R
H
C
F
F
LP
R
F
R
R
F
R
LF
M
M
P
R
R
M
C
H
M
LP
R
M
0
R
12
F
19.3
13
R
35.9
R
LF
64.8
62.3
70
60
50
40
30
20
10
0
HANDEDNESS DIFFERENCES
IN THE FRONTAL LOBES
Comparison of CBT scores between strictly
right-handed and non right-handed healthy
subjects
220
210
200
190
180
170
160
Males
150
140
130
Female
s
120
110
100
90
80
S tr ic tly 2r ig ht5 ha nde d
E. Goldberg, K. Podell, R. Harner, M. Lovell, S. Riggio.
Journal of Cognitive Neuroscience, 1994.
N on2r ig ht5 ha nde d
70
60
50
40
30
20
10
0
CBT scores in strictly right-handed
(SRH) and non-right-handed (NRH)
lesioned males
SRH
NRH
LF
LP
HC
RP
E. Goldberg, K. Podell, R. Harner, M. Lovell, S. Riggio.
Journal of Cognitive Neuroscience, 1994
RF
CBT scores in strictly right-handed (SRH) and
non-right-handed (NRH) lesioned females
70
60
50
40
30
20
10
0
SRH
NRH
LF
LP
HC
RP
E. Goldberg, K. Podell, R. Harner, M. Lovell, S. Riggio.
Journal of Cognitive Neuroscience, 1994
RF
MISSING CONSTRUCTS
- COGNITIVE NOVELTY
a) NAIVE
b) PRACTICED
c) NOVEL
From E. Goldberg. (2001). The Executive Brain: Frontal Lobes and
the Civilized Mind. New York: Oxford University Press.
FUNCTIONAL NEUROIMAGING STUDIES OF THE
NEUROBIOLOGY OF LEARNING
a)
L
NAÏVE
b) PRACTICED
R
L
R
Right-to-left shift of hippocampal activation with memorization
(PET): words, paralogs, object drawings and nonsense
drawings (Martin et al, 1997)
Hemispheres and Novelty
Cognitive Bias Task
(K. Vogeley et al, 2003)
Similarity
Dissimilarity
Preference
• Similarity left fronto-parietal
• Dissimilarity right fronto-parietal
fixed effects model
height threshold p = 0.001, corr.
extent threshold 30 voxels
RIGHT TO LEFT SHIFT DURING TASK FAMILIARIZATION
Target Card
Choice Cards
(EEG spectral power in the gamma frequency band (30-40 Hz) (Kamiya et al, 2004))
2sec
µV2
2.00
1.00
0.00
FUTURE STUDIES:
TOWARD MORE
PERSONALIZED COGNITIVE
REHABILITATION IN TBI, CVA:
GENDER, HANDEDNESS,
LATERALITY
FUTURE STUDIES OF
FUNCTIONAL LATERALIZATION
IN THE FRONTAL LOBES AND
RELATED STRUCTURES:
fMRI
TMS (with Volker Homberg)
Tourette s subtyping