Neuropsychological diagnosis: How Clinical Neuropsychological ...
Transcript of Neuropsychological diagnosis: How Clinical Neuropsychological ...
How Clinical Neuropsychological
assessment can inform research
Professor Lisa Cipolotti
Neuropsychological Diagnosis
1. Assess impairments arising from brain damage
2. Identify neuropsychological syndromes
3. Further our understanding of the brain
Contribution of
Neuropsychological Assessment
1. Diagnosis
• Short historical review on how the methods of assessing cognitivefunctions have developed
• Discuss some of the principal methods of assessing cognitivefunctions
2. Research
• Clinical research-FAD, MOCA
• Theoretically driven research-Dynamic aphasia, amnesia, inhibition
“..His vocabulary is copious, but he does not
talk much, and speaks in a drawling manner.
From time to time he misses a word or
construction...He repeats correctly whole
sentences, if not too long...”
(Lichtheim, 1885, p.p. 448-449; derived from
Shallice, 1988)
“...the methods in general use were too
crude to provide satisfactory records...”
(Head, 1926; derived from Shallice, 1988)
“...it would appear that the clinical
psychologists’ contribution to the problems of
the neurosurgeon and the psychiatrist is of
little value owing to the lack of proper
diagnostic tools...”
(Meyer, 1957)
“...The assessment of organic impairment of
intellect is a task which might be expected to
be within the competence of a clinical
psychologist. Nevertheless, recent literature
on the subject contains statements by
psychologists disclaiming their ability to do
so with an adequate degree of validity...”
(Piercy, 1959)
Halstead-Reitan Battery
“...little, if anything, could be gained by
translating neuropsychological deficits into
quantitative values...”
Letter from Luria to Reitan (1967; translated)
Early sixties: Clinical tests usually
adopted fell into two categories:
1. Psychometric tests, originally developed for the
measurement of either scholastic attainment or
occupational guidance
2. ‘Qualitative’ tests often improvised by the
various clinicians. These tests were developedin order to explore specific cognitive skills
Clock, bicycle and daisy drawing
(Zangwill)
Lawson, 2006
e.g. Lezak, 1983; McFie & Zangwill, 1960
Incomplete Letters
Phonemic fluency
Cognitive neuropsychology –
three principles
1. The cerebral cortex has a high degree of
functional specialisation
2. Complex cognitive skills are organised in
a broadly modular fashion
3. Brain damage can selectively disrupt
these cognitive skills
Brain damage can selectively disrupt
cognitive skills (Cipolotti, 2000; Incisa della
Rocchetta et al, 2004 )
Patients
BF TM AD SMcD TF
STM
Non
Verbal
LTM
Verbal
LTM
Patients with selective preservation
of country names (Cipolotti, 2000; Incisa della
Rocchetta et al, 2004 )
BF TM AD SMcD TF
Maps
(%) Correct 100 100 90 100 90
Colours
(%) Correct 50 40 60 70 70
Objects
(%) Correct 30 10 60 30 10
Animals
(%) Correct 60 10 40 40 20
Body Parts
(%) Correct 20 50 90 50 10
The development of cognitive neuropsychologyand its three principles resulted in series ofimportant research studies.
This led to a far better understanding of thefunctioning of complex cognitive skills.
They stimulated the development of a largenumber of measurement tools designed toinvestigate cognitive functions in neurologicalpatients.
Identification of acquired
cognitive impairments
1. Whether the individual is functioning at
his premorbid optimal level or whether
there has been deterioration
2. Whether the individual is suffering
from an organic or a functional
condition
Assessment of premorbid
intellectual functioningReading skill
1. Highly correlated with general intelligencein a normal population
2. Highly resistant to brain damage
National Adult Reading Test (NART)
NART
Assessment of current intellectual
functioning
Intelligence tests
1. Raven tests
2. Wechsler Adult Intelligence Scales
(WAIS; WAIS-R; WAIS-III; WAIS-IV)
WAIS-III Verbal subtest
Similarities
• Piano-Drum
• Orange- Banana
• Eye-Ear
• Work-Play
• Steam-Fog
• Poem-Statue
• Praise-Punishment
• Fly-Tree
• Hibernation-Migration
• Enemy-Friend
WAIS-III Performance subtest
Picture Completion
Differential diagnosis:
Organic and functional memory
impairments
Can be distinguished by:
a) Highlighting discrepancies between subjective
complaints and objective performance
b) Identifying improbabilities in the patient’s apparent
pattern of impairment
Implicit learning task – Degraded words
Implicit learning task – Degraded words
Implicit learning task – Degraded words
Assessing the extent of the cognitive
impairment I
NEUROPSYCHOLOGICAL ASSESSMENT
1. Premorbid ability
2. General intelligence
3. Memory
4. Language
5. Calculation
6. Executive function
7. Alertness and attention
8. Visual and space perception
(1) RELIABLE
in the same circumstances they produce the same results
(2) VALID
they measure what they are designed to measure
i.e. they probe an established module of cognition.
(3) OF COMPARABLE DIFFICULTY
so the results can be compared across tasks
(4) SENSITIVE TO CHANGE
graded difficulty tests for which normally distributed scores are
available allow the rate of disease progression to be monitored and
avoid uninformative ceiling and floor effects
Assessing the extent of the cognitive
impairment II
Recognition Memory Test –
Words and Faces
Contribution of
Neuropsychological Assessment
1. Diagnosis
• Short historical review on how the methods of assessing cognitivefunctions have developed
• Discuss some of the principal methods of assessing cognitivefunctions.
2. Research
• Clinical research:
• Theoretically driven neuropsychological research
Contribution of
Neuropsychological Assessment
1. Diagnosis
• Short historical review on how the methods of assessing cognitivefunctions have developed
• Discuss some of the principal methods of assessing cognitivefunctions.
2. Research
• Clinical research:
Familial Dementia; cognitive screening tests
• Theoretically driven neuropsychological research
FAD Performance on The RMT (Godbolt et al,. 2006)
Words (max. 50) Faces (max. 50)
Session Session
1 2 3
4.3 49 48 45 48 46 48
4.13 46 45 46 45
4.5 49 49 47 45 47 45
4.9 37± 48 47 47 46 44
4.1 40* 28± 38 49 31± 36†
4.12 40* 27± 42 37
4.10 33± 25± 13±§ 33± 35± 11†§
Discrepancy score: * <25%; † <5%; ± <1%. § Maximum 25
1 2 3
Cognitive screening tests
1. Identify major cognitive deficits
2. Overcome resource limitations
Clinical research: Cognitive screening
tests
The UK national guidelines recommends that, within
6 weeks from stroke, patients should be assessed for
cognitive impairment (e.g. NCGS, 2012; Nice, 2013).
The assessment should entail a validated tool such
as the MoCA (e.g. Nasreddine et al, 2011).
Determining the presence of cognitive impairment
Stroke Screening
Normal ≥ 25
Impaired < 25
For example, memory and executive functioning are good
predictors for:
length of hospital stay
long-term impairment
burden on community services
(e.g. Barker- Collo, Feigin, 2006;Galski, et al., 1993; Tatemichi et al, 1994; Van
Zandvoort et al., 2005).
Domain Specific cognitive impairment are
good predictors of post-stroke outcomes
Intellectual functioning
Speed of information
processing
Non-verbal memory
Determining the nature of cognitive
impairment
174 acute stroke patients with MoCA and
neuropsychology
(Chan et al., 2014 and Chan et al., submitted)
1. Are MoCA intact patients also intact on the
neuropsychological assessment?
2. How do patients with MoCA intact cognitive domains
perform on the corresponding neuropsychological domain?
3. Does lesion side impact on the sensitivity of the MoCA?
1. Are MoCA intact patients also intact on the
neuropsychological assessment? NO!
MoCA Intact% of patients with neuropsychological
impairment
≥2 Cognitive Domain 70%
1 Cognitive Domain only 30%
40 MoCA intact patients – all neuropsychologically
impaired
2. How do patients with MoCA intact cognitive domains
perform on the corresponding neuropsychological
domain?
MoCA-specified domain% of patient scoring full marks on
the MoCA
% of patients impaired in neuropsychological
corresponding domains
Attention 30% 59%
Memory 14% 35%
Visuospatial/executive 18% 30%
Naming 68% 21%
Abstraction 42% 12%
Language 26% 9%
3. Does the lesion laterality impact on
sensitivity of the MoCA? YES!
LateralityMoCA Intact
(n = 40, 23.6%)
Right Side lesion 32 (80%)
Left Sided lesion 3 (7.5%)
Bilateral Lesion 5 (12.5%)
The neuropsychological assessment allows us to
evaluate cognitive screening tests.
In acute stroke it demonstrated that MoCA
underestimates cognitive impairment, particularly in
right brain damaged patients.
Contributions of Neuropsychological
Assessment to Clinical Research
Powerful methodology!
1. Diagnose cognitive impairment at an early pre-
symptomatic stage - FAD
2. Evaluate popular cognitive screening tests -
MoCA
Contribution of
Neuropsychological Assessment
1. Diagnosis
• Short historical review on how the methods of assessing cognitivefunctions have developed
• Discuss some of the principal methods of assessing cognitivefunctions.
2. Research
• Clinical research:
Familial Dementia; cognitive screening tests
• Theoretically driven neuropsychological research
Theoretically driven research has proven of fundamental
importance in the study of the organisation of cognitive
functions.
• Dynamic Aphasia
• Amnesia
• Executive Function - Inhibition
Dynamic Aphasia
• Marked impairment of propositional language
• Absence of impaired nominal and phonologicalskills
Dynamic Aphasia patient CH
‘Tell me about the stage show Miss Saigon.’
‘…Miss Saigon was . . . {60 s} . . . MissSaigon was . . . {90 s} a poor unfortunate. . .poor unfortunate . . . poor unfortunate lady{120 s})...’
Robinson et al, 2005
Sentence Generation Tasks
(Robinson et al., 1998; 2005; 2006)
No. Correct
ANG CH
Generation of a sentence from a single
word2/15 11/20
or picture (e.g. phone) 0/6 nt
Generation of a sentence from a scene
(e.g. “Describe the scene.”)
34/34 20/20
Hypothesis
• The patients’ impairment was due to aninability to select a verbal response insituations where the stimulus activated manycompeting response options.
• In a situation where a stimulus activates asingle ‘prepotent’ response option, theyshould overcome their impairment.
Predictions
1. The patients’ ability to generate sentences fromproper nouns should be superior to their ability togenerate sentences from common nouns.
2. Sentence generation from sentences with highresponse predictability should be superior tosentence generation from sentences with lowpredictability.
Verbal Generation: Experimental TestsNumber Correct
ANG CH Controls (n=5)
Proper Nouns
Tell me a sentence which includes
the word Hitler
26/28 22/28 28/28
Common Nouns
Tell me a sentence which includes
the word sea
11/28* 10/28* 28/28
Sentences (high predictability)
“The man sat in the dentist’s
chair…”
9/12 19/24 12/12
Sentences (low predictability)
“The man sat in his chair…”
3/12* 12/24* 12/12
* = impaired (p<0.05)
Summary
• Both patients were impaired in the
generation of sentences when the target
stimulus activated many competing verbal
response options.
• In sharp contrast, they were unimpaired
when the target stimulus activated a
prepotent response option.
Language generation involves a mechanism of conceptual
preparation requiring the ability to select verbal response
options among competitors.
A failure at this stage results in a conflict condition and an
inability to select between competing verbal responses.
However, if a stimulus activates prepotent responses, less
stress is placed on the damaged verbal selection mechanism.
• ANG had a frontal
meningioma impinging on
the left IFG (BA 45, and
44 to a lesser extent).
• CH had focal atrophy in
the left IFG (BA 44, and
BA 45 to a lesser extent).
• Some atrophy in the left
superior temporal gyrus.
Sentence Generation Task: Group Study
(Robinson, Shallice, Bozzali & Cipolotti 2012)
Frontal Patient Sub-Groups
LIFG (n=11) Non-LIFG (n=36)
Mean No. Correct (/15) (SD)
Proper Nouns 14.7 (0.6) 14.4 (1.8)
Common Nouns 12.9 (3.3)***~ 14.1 (3.2)
LIFG = Left Inferior Frontal Gyrus
***~ = p<0.001
Conclusions
1.The LIFG plays a crucial role in one of the
mechanisms involved in conceptual
preparation.
2.This mechanism is responsible for the
selection of verbal response option among
competitors.
Theoretically driven research has proven of fundamental
importance in the study of the organisation of cognitive
functions.
• Dynamic Aphasia
• Amnesia
• Executive Function - Inhibition
Dr Brenda Milner
Amnesia: The
profound loss of
memory in the
presence of
relatively preserved
cognitive abilities
Amnesia - Patient HM
The Hippocampus Plays a Crucial Role in
Amnesia
Impaired Functions: Episodic Memory
(EM)
• Episodic refers to memory for episodes with a
spatial temporal context involving a detailed re-
experience of the initial event, such as, for
example, autobiographical memories (Tulving,
1972).
Impaired Episodic Memory
Impaired Functions
timelesion
mem
ory retrograde anterograde
i) Retrograde Amnesia
ii) Anterograde Amnesia
Hippocampus
Squire’s Standard Consolidation Model
Neocortex
Neocortex
Neocortex
Hippocampus allows the learning of new declarative
memories which are stored in the permanent neocortical
memory store.
Larry Squire
Hippocampus
Squire’s Standard Consolidation Model
Neocortex
Neocortex
Neocortex
Time
Hippocampus
Neocortex
Neocortex
Neocortex
Consolidation allows declarative memory traces to
become gradually independent from the hippocampus
and dependent on neocortical storage sites
Assessment of Retrograde Memory
• Tests for non-personal events - famous
public events/personalities
• Tests for autobiographical events
HM’s remote memories are highly “semantic” in nature (Steinvorth et al,
Neuropsychologia 2005)
See Cipolotti & Moscovitch Lancet Neurol. 2005 (4):792-3
versus Squire & Bayley Lancet Neurol. 2006 (5):112-3
HM: Performance on Non Personal Retrograde
Memory Tests
More distant memories relatively preserved
taken as support for consolidation.
BUT are test items equally salient
across decades?
Retrograde Amnesia - Non Personal
Events (Reed and Squire, 1998)
Famous Public Events Questionnaire Test
120 Questions
1960-1964 15
1965-1969 15
1970-1974 15
1975-1979 15
1980-1984 15
1985-1989 15
1990-1994 15
1994-1998 15
Examples of Questions
1994-1998
Recall condition: Who is Paula Jones?
Recognition condition: Widow of Kurt Cobain
the rock singer who died of an overdose…
Woman who accused President Clinton of
sexual harassment… Famous tennis player.
1970-1974
Recall condition: How was the Queen
Elizabeth liner destroyed in Hong Kong?
Recognition condition:
Fire…..Bombed…..Crashed into by another
boat.
Coronal sections through temporal lobe at the level of
the body of the hippocampus. High signal return seen in
each hippocampus.
Control Patient VC
Midsaggital section of the
hippocampus
VC’s neuroimaging
investigations
• Volumetry
• Voxel-Based Morphometry
• Magnetic Resonance Spectroscopy
• Functional MRI
All reporting selective bilateral hippocampal damage
(Cipolotti et al, 2001; 2006; Maguire et al, 2005; Bird et al, 2007)
Hippocampal patient VC
Percentage Correct for each 5 year period on Famous Public
Events Questionnaire
(Cipolotti et al., 2001)
Multiple Trace Theory
• Hippocampal complex encodes learned
information and binds the neocortical neurons
representing that experience into a memory
trace.
Morris Moscovitch Lynn Nadel
Nadel and Moscovitch, 1997
Critical Distinction between SMC
and MTT
Hippocampal Lesion
SMC’s
prediction
MTT’s
prediction
Remote Memories Remote Memories
Rosenbaum, Gilboa, Levine, Winocur, Moscovitch,
2009: internal and external details given by KC
Evidence against a temporal gradient
in R.A. Autobiographical memory tests
Viskontas et al, 2000:
P’s with MTL resections
Kopelman’s Autobiographical Memory test
Autobiographical Memory
Interview
No. Correct Comment
Autobiographical 3/27 Definitely abnormal
Childhood 1/9 Definitely abnormal
Early Adult Life 2/9 Definitely abnormal
Recent Life 0/9 Definitely abnormal
Hippocampal patient VC
• The hippocampus serves a critical role for
memory
• Remote memories rely on the hippocampus
Neuropsychological
assessment of amnesic
patients
Theoretically driven research has proven of fundamental
importance in the study of the organisation of cognitive
functions.
• Dynamic Aphasia
• Amnesia
• Executive Function - Inhibition
Executive Functions
Variety of general purpose control
mechanisms thought to modulate and
organize more basic cognitive sub-
processes to achieve effective
behaviour (e.g. Stuss and Levine, 2002)
Inhibition: The ability to
suppress a pre-potent response
Patients with PFC lesions are impaired in tasks requiring
inhibitory control
Inappropriate and/or perseverative behaviour
3 different inhibitory tasks: Stop-signal, Stroop, Hayling
Inhibition: Stop-Signal
Aron and colleagues (2003) reported a
significant correlation between right inferior
frontal gyrus (RIFG) lesions and stop-signal
reaction time (RT). They suggested that the
RIFG is critical for inhibitory control in
general.
Inhibition: Stroop Colour-Word
Test
Inhibition: Stroop Colour-Word
Test - Lesions
• Left dorsolateral PFC (e.g. Perret, 1974; Stuss et al., 2001)
• Right lateral PFC (Vendrell et al., 1995)
• Anterior cingulate cortex (ACC) (e.g. Swick and Turken, 2002;
but see for opposite results Fellows and Farah, 2005; Baird et al., 2006).
• Recent Voxel-based Lesion Symptom Mapping (VLSM)
Left lateral PFC (Tsuchida and Fellows, 2013)
Left ventral lateral PFC (Geddes et al., 2014)
Left dorsolateral frontal cortex (Glascher et al., 2012)
Inhibition: The Hayling Sentence
Completion Test
The patient is asked to complete sentences by providingwords that are unrelated to the sentence frame.
‘London is a very busy. . .’, could be completed bysaying. . .‘banana’
Frontal patients may:
Produce Suppression errors (SS)
‘London is a very busy. . .’ may be completed with‘. . .city. . .’
and/or
Require longer reaction times (RT2 SS)
Inhibition:
The Hayling Sentence
Completion Test - Lesions
• Right PFC (Roca et al., 2010)
• Right lateral PFC (Robinson et al., 2015; Cipolotti
et al., 2015)
Part 2 of the Hayling and Stroop Colour-
Word Tests (Cipolotti et al., submitted)
Legend. Scores with significant p-values are in red; *p <0.05; **p< 0.01, compared with
Healthy Comparison; SS: Scaled Score; (SD): Standard Deviation; RT: reaction time
Left Frontal
Patients
Right Frontal
Patients
Healthy
Comparison
Suppression Error
SS
5.47 4.13* 6.05
(SD) (2.64) (2.47) (1.80)
Suppression RT2
SS
5.07 4.40** 6.00
(SD) (1.71) (1.80) (0.63)
Stroop (No. of
colours named in
2 minutes)
90.21* 99.31 114.49
(SD) (27.96) (35.23) (20.30)
A deficit in fluid intelligence can explain most
the reported executive impairments in frontal
patients (e.g. Duncan et al., 1995; Roca et al., 2010)
Three separate 2x2 mixed-method ANOVAs with:
• Type of measure - Hayling measure/Stroop (z-scores) - as thewithin-groups factor
• Site of damage - left/right - as the between-groups factor
• Fluid intelligence - RAPM - as covariate
For:
1. Suppression errors and Stroop
2. Suppression RT2 and Stroop
3. Suppression errors and Suppression RT2
Significant interactions:
Type of measure – Site of damage
1. Suppression errors and Stroop (p=.008)
2. Suppression RT2 and Stroop (p=.028)
3. Suppression errors and Suppression RT2 (p=.468)
Results of voxel lesion-symptom mapping
analyses (VLSM): Hayling
Voxels in red show the
area found to be
significant (p<0.05 FWE-
corrected at cluster level)
(A) Hayling Suppression
errors
(B) Hayling Suppression RT 2
Results of voxel lesion-symptom mapping
analyses (VLSM): Stroop
Voxels in red show the area found to be significant
(p<0.05 FWE-corrected at cluster level)
Inhibition: Conclusion I
1. Lesion location, right or left PFC, is a criticalfactor in producing impairments on twoinhibitory tasks loading similarly on verbalcontrol
2. Hayling and Stroop assess dissociablecomponents of executive functions, relatedto separate and lateralized PFC circuits
3. Inhibition may actually comprise qualitativelydifferent forms with different neuronalsubstrates
Inhibition: Conclusion II
The assessment of inhibition in frontal
patients need:
• to use a variety of tests
• to develop different types of treatments
The clinical neuropsychological
assessment can inform research by:
1. Developing a powerful neuropsychological methodology
Pre-symptomatic changes in FAD; cognitive screening tests - MoCA
2. Refining the diagnosis of neuropsychological syndromes
Dynamic aphasia, amnesia and impairments in inhibition
3. Furthering our understanding of the functioning of the brain
The role of the LIFG in propositional speech
The role of the hippocampus in remote memory
The lateralized PFC contributions to inhibition