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NEUROPSYCHOLOGICAL CONSIDERATIONS IN THE
EVALUATION OF ADHD
Francis M. Crinella, Ph.D.Clinical Professor of Pediatrics, Psychiatry & Human
Behavior, & Physical Medicine & RehabilitationDirector, Neuropsychology Laboratory
Child Development CenterUniversity of California, Irvine
HISTORICAL OVERVIEW OF ADHD
1920-1937 Post-encephalitic syndrome
1937 Minimal Brain Damage
1960s Minimal Brain Dysfunction
1968 Hyperkinetic Reaction of Childhood (DSM-II)
1980 Attention Deficit Disorder, with or without hyperactivity (DSM-III)
1987 Attention Deficit Hyperactivity Disorder (DSM III-R)
1994 Attention Deficit/Hyperactivity Disorder (DSM-IV)
DSM-IV SYMPTOMS OF ADHD
INATTENTION
• CAN’T ATTEND TO DETAILS• CAN’T SUSTAIN ATTENTION• DOESN’T LISTEN• FAILS TO FINISH• CAN’T ORGANIZE TASKS• AVOIDS SCHOOLWORK• LOSES THINGS• EASILY DISTRACTED• FORGETFUL
HYPERACTIVITY/IMPULSIVITY
• FIDGETS• CAN’T STAY SEATED• RUN ABOUT AND CLIMBS• CAN’T PLAY QUIETLY• IS OFTEN ON THE GO• TALKS TOO MUCH• BLURTS OUT ANSWERS• CAN’T WAIT TURN• INTERRUPTS OR INTRUDES
METHODS OF ARRIVING AT DIAGNOSIS OF ADHD
• BEHAVIORAL
• PSYCHIATRIC INTERVIEW/BIOSOCIAL HISTORY
• STANDARDIZED RATING TECHNIQUES• CHECKLISTS/minimum criteria (e.g., DSM-IV criteria)• RATING SCALES/cut-off scores (e.g., Conners, SWAN)
• DIRECT OBSERVATION• BEHAVIOR SAMPLING• PSYCHOMETRIC• NEUROPSYCHOLOGICAL
CRITIQUE OF BEHAVIORAL METHODS
• PSYCHIATRIC INTERVIEW
– Biosocial history--95% of diagnosis is history (Adolf Meyer, 1915)
But:
• Getting adequate history is an extraordinarily lengthy process
• Focus of history may be based on interviewer experience and/or idiosyncracies (e.g., adaptation level)
• Interviewee may not be accurate (or even biased)
CRITIQUE OF BEHAVIORAL METHODS
• PSYCHIATRIC INTERVIEW
– Biosocial history augmented by in-office observations
• Artificial setting—symptoms of concern may not be observed
CRITIQUE OF BEHAVIORAL METHODS
• RATING TECHNIQUES
• CHECKLISTS
• Minimum criteria for diagnosis (e.g., DSM-IV criteria)
• Must be observed in more than one setting
• Problem: Different sets of items will all satisfy Diagnostic Criteria
SAMPLE CONFIGURATION OF A CHILD’S DSM-IV SYMPTOMS OF ADHD—CASE MEETS CRITERIA FOR PRIMARILY HYPERACTIVE
SUBTYPEINATTENTION HYPERACTIVITY/
IMPULSIVITY
1 CAN’T ATTEND TO DETAILS
YES FIDGETS YES
2 CAN’T SUSTAIN ATTENTION
NO CAN’T STAY SEATED
YES
3 DOESN’T LISTEN NO RUN ABOUT AND CLIMBS
YES
4 FAILS TO FINISH YES CAN’T PLAY QUIETLY
YES
5 CAN’T ORGANIZE TASKS
YES IS OFTEN ON THE GO
YES
6 AVOIDS SCHOOLWORK
NO TALKS TOO MUCH
NO
7 LOSES THINGSEASILY
NO BLURTS OUT ANSWERS
NO
8 DISTRACTED NO CAN’T WAIT TURN
YES
9 FORGETFUL YES INTERRUPTS OR INTRUDES
YES
NUMBER OF INATTENTION SYMPTOMS
4 NUMBER OF HYPERACTIVITY
SYMPTOMS
7
SYMPTOM CHECKLISTS FOR TWO CHILDREN WHO MEET CRITERIA FOR ADHD, HYPERACTIVE/IMPULSIVE SUBTYPE
HYPERACTIVITY/IMPULSIVITY CHILD #1 CHILD #2
1 FIDGETS YES NO
2 CAN’T STAY SEATED YES NO
3 RUNS ABOUT AND CLIMBS YES NO
4 CAN’T PLAY QUIETLY YES YES
5 IS OFTEN ON THE GO YES YES
6 TALKS TOO MUCH YES YES
7 BLURTS OUT ANSWERS NO YES
8 CAN’T WIAT TURN NO YES
9 INTERRUPTS OR INTRUDES NO YES
∑ “YES” 6 6
NUMBER OF POSSIBLE DSM-IV SYMPTOM CONFIGURATIONS THAT MEET CRITERIA FOR DIAGNOSIS OF
ADHD
• FOR HYPERACTIVE SUBTYPE:– NUMBER OF VARIATIONS ON 9 CRITERIA
9/6 = 849/7 = 369/8 = 99/9 = 1
∑ = 130
CRITIQUE OF BEHAVIORAL METHODS
• RATING SCALES
• Score based on sum of scores for individual items (e.g., “fidgety” Always = 3; Often = 2; Sometimes = 1; never = 0)
• Total score used for cut-off lacks differentiation
• Profile analysis reveals multiple subtypes
• Subtype profiles lack external validation
RATING ITEM: “FIDGETS”
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0 1 2 3
ADHDTYPICAL
UCI-CDC Parent/Teacher Ratings of Behavioral Competencies
• 48 items
• Subjects rated on positive traits
• Age-based reference group (i.e., “Compared to same-age children, how well is your child able to sit still in class?”)
• Rating scheme:
1. Very poorly—worse than all but as few children this age2. Not too well—most children this age do better (well <average3. Fair—better than quite a few children this age (slightly <average)4. Fairly well—better than many children this age, (slightly
>average)5. Good—better than most children this age (well >average)6. Excellent—better than all but a few children this age
UCI-CDC PARENT/TEACHER RATINGS OF BEHAVIORAL COMPETENCIES
• ADVANTAGES:
– Multiple dimensions of behavior determined by factor analysis
– Inter-rater reliability established for each dimension
– Norms for mothers, fathers & teachers
– Raw scores converted to percentile rankings
TYPICAL DISTRIBUTION OF RATINGS ON UCI-CDC PARENT-TEACHER RATING SCALE
Rating Item: "fidgets"
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140
1 2 3 4 5 6
Frequency
BEHAVIORAL COMPETENCIES
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Rank
Mother
Father
Teacher
BEHAVIORAL COMPETENCIES
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Rank
Mother
Father
Teacher 1
Teacher 2
Teacher 3
UCI-CDC Parent/Teacher Ratings of Behavioral Competencies
Major drawbacks:Must clinically account for differences among raters
Fails to elucidate neurocognitive processes underlying behavioral competencies
NEUROPSYCHOLOGICAL EVALUATION
• Assumptions:– ADHD has a biological basis – ADHD reflects dysfunction in specific neural
networks– Variations in neuropsychological test
performance reflect integrity of underlying neural systems
– Specific neurocognitive deficits in ADHD reflect impairment of attentional network
EVIDENCE FOR BIOLOGICAL BASIS OF ADHD
1. NEUROCHEMICAL
2. GENETIC
3. ELECTROPHYSIOLOGICAL RECORDINGS
4. FUNCTIONAL IMAGING
5. CORRELATIVE NEUROANATOMICAL STUDIES
BIOLOGICAL BASIS OF ADHD
1. NEUROCHEMICAL
– PSYCHOPHARMACOLOGY
MOST EFFECTIVE TREATMENT--CNS STIMULANTS• DEXTROAMPHETAMINES• METHYLPHENIDATES
• EFFECTS:– Improved classroom behavior– Improved academic productivity– Improved peer/adult interactions– Less frequent oppositional conduct– Reduced aggression
BIOLOGICAL BASIS OF ADHD
2. GENETIC
• BEFORE MOLECULAR BIOLOGY• Catecholamine hypothesis—genetic variations in brain
neurochemistry (Wender, 1971)
• Family genetic studies (e.g., Faroane, Biederman, Chen et al., 1992)
• AFTER MOLECULAR BIOLOGY• Subsensitive dopamine receptor hypothesis; DRD4
gene (LaHoste, Swanson, Wigal, et al., 1996) • Dopamine transporter gene (Cook, Stein, Krasowski, et
al., 1995)
BIOLOGICAL BASIS OF ADHD GENETICS
1. Coding region of DRD4 gene for D4 receptor2. Located on chromosome 11p3. High degree of variability in 3rd cytoplasmic loop4. 48 bp region can be repeated two to eleven times5. Variants display different pharmacological properties6. DRD4 mRNA in frontal and prefrontal brain regions
BIOLOGICAL BASES OF ADHD
3. FUNCTIONAL BRAIN IMAGING
• Evidence before modern imaging methods• MBD hypothesis (Clements et al, 1963)• Neuropsychology of MBD (Crinella, 1972)
• Evidence from modern imaging methods• Methods used: PET; SPECT; fMRI• Results: Variations in size and symmetry of brain
structures (e.g., Swanson & Castellanos, 1997)• Structures involved:
FRONTO-STRIATAL NETWORK
CAUDATE NUCLEUS BASAL GANGLIA
RECENT BRAIN IMAGING STUDIES IN ADHD
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DL Frontal
Putamen-gp
Occipital
Temporal
Insula
A. Cingulate
Premotor
Thalamus
Hippocampus
Insula
CC (genu)
CC (splenium)
Periventricular
Premotor
basal gangial
BIOLOGICAL BASIS OF ADHD
4. ELECTROPHYSIOLOGY
Early studies of analog EEG
Satterfield, J.H., & Schell, A.M. (1984). Childhood brain function differences in delinquent and non-delinquent hyperactive boys. Electroencephalography and Clinical Neurophysiology, 57, 199-207.
Finding: Abnormal maturational effects of auditory event-related potential differentiated ADHD from non-ADHD subjects
Recent brain mapping studies
Pliszka, S.R., Liotti, M., & Woldorff, M.G. (2000). Inhibitory control in children with attention-deficit/hyperactivity disorder: event related potential identify the processing component and timing of an
impaired r right-frontal response-inhibition mechanism. Biological Psychiatry, 48, 238-46.
BIOLOGICAL BASIS OF ADHD
5. CORRELATIVE NEUROANATOMY
TRADITIONAL APPROACH TO STUDYING BRAIN-BEHAVIOR RELATIONSHIPS
• Experimental removal of brain structures
• Observation of effect on specific behavioral functions
• Necessary to identify functions affected by ADHD
DEFINITIONS OF ATTENTION
“A special function was instituted which had periodically to search the outer world in order that its data might be already familiar if an urgent inner need should arise: This function was attention. Its activity meets the sense impressions half way, instead of awaiting their appearance. At the same time, there was probably introduced a system of notation, whose task was to deposit the result of this periodic activity of consciousness—a part of which we call memory.”
“A special function was instituted which had periodically to search the outer world in order that its data might be already familiar if an urgent inner need should arise: This function was attention. Its activity meets the sense impressions half way, instead of awaiting their appearance. At the same time, there was probably introduced a system of notation, whose task was to deposit the result of this periodic activity of consciousness—a part of which we call memory.”
Sigmund Freud
“Formulations regarding the two principles of mental functioning.”
(1911)
Everyone knows what attention is. It is the taking possession of the mind in clear and vivid form of one out of what seem several simultaneous object or trains of thought.
William James
“The Principles of Psychology,” 1890
Attention operates by changing the relative activity within specified anatomical areas that perform computations
Michael Posner
“Images of Mind,” 1996
DISTINCT ANATOMICAL NETWORKS CARRY OUT SPECIFIC ASPECTS OF ATTENTION
• ALERTING NETWORK– LOCATION: ARAS, ETC.– FUNCTION: ACHIEVE AND MAINTAIN STATE OF READINESS
• ORIENTING NETWORK– LOCATIONS: PARIETAL LOBE, SUPERIOR COLLICULUS & PULVINAR– FUNCTION: REACT TO SENSORY STIMULI
• EXECUTIVE NETWORK– LOCATION: ANTERIOR CINGULATE; DORSOLATERAL FRONTAL CORTEX
& BASAL GANGLIA– FUNCTIONS:
• CONTROL NEURAL RESPONSES TO STIMULI
• GENERATE NEW INFORMATION FROM LONG TERM MEMORY
• PRIORITIZE OPERATION OF OTHER BRAIN AREAS
ADHD and EF
• ADHD is a disorder of Executive Function (Barkley, 1997)
SOME FEATURES OF EXECUTIVE FUNCTION
• Decision as to just what the problem is that needs to be solved
• Selection of lower-order components• Selection of one or more representations of
organizations for information• Selection of a strategy for combining lower order
components• Decision regarding tradeoffs in the speed and
accuracies with which various components are executed
• Solution monitoring STERNBERG, 1985
BRIEF DEFINITIONS OF EXECUTIVE FUNCTION
• Processes used to plan, monitor and revise strategies of information processing (STERNBERG. 1985)
• Appropriate set maintenance to achieve a future goal (PENNINGTON, WELSH & GROSSIER, 1990)
• A process which enables the brain to function as many machines in one, setting and resetting itself dozens of times in the course of a day, now for one type of operation, now for another (SPERRY, 1955)
• A process that alters the probability of subsequent responses to an event, thereby altering the probability of later consequences (Barkley, 1997).
EXECUTIVE FUNCTION DEFICITS ASSOCIATED WITH LESIONS IN RODENT
DOPAMINE NETWORK
• Shifting cognitive sets
• Planning behavioral sequences
• Inhibition of motor reactivity
• Response flexibility
TESTS OF EXECUTIVE FUNCTION IN THE HUMAN NEUROPSYCHOLOGY
LABORATORY
• By definition, no test can be performed in the absence of executive control
• Executive functions must be differentiated from other cognitive– abstract reasoning– crystallized problem solving– long term memory– sensory-perceptual processing – motor control systems– Motivational states
• Which tests do this best?
TRADITIONAL PSYCHOMETRIC APPROACHES TO IDENTIFICATION OF
ADHDWISC-III:
1. PERFORMANCE > VERBAL IQ
2. VERBAL > PERFORMANCE IQ
3. ACID/ACIDS PROFILE
4. FREEDOM FROM DISTRACTIBILITY INDEX
5. PROCESSING SPEED INDEX
TRADITIONAL PSYCHOMETRIC APPROACHES TO IDENTIFICATION OF
ADHD
WISC-III
1. PERFORMANCE > VERBAL
TRADITIONAL PSYCHOMETRIC APPROACHES TO IDENTIFICATION OF
ADHD
Critique: PERFORMANCE > VERBAL
• Same pattern occurs in:
– English as 2nd language
– Receptive and/or expressive dysphasia
– Left hemisphere tumors
– Conduct disorder
– Specific learning disabilities
TRADITIONAL PSYCHOMETRIC APPROACHES TO IDENTIFICATION OF
ADHD
WISC-III
2. VERBAL>PERFORMANCE
EVIDENCE OF INATTENTIVE SUBTYPE?
TRADITIONAL PSYCHOMETRIC APPROACHES TO IDENTIFICATION OF
ADHD
Critique: VERBAL>PERFORMANCE
• Same pattern occurs in:
– Non-verbal learning disability
– Cerebral palsy/fine motor control deficits
– Depression
– Obsessive compulsive disorder
– Visual-spatial defects
TRADITIONAL PSYCHOMETRIC APPROACHES TO IDENTIFICATION OF
ADHD• WISC-III
3. “ACIDS” Index:
• Arithmetic• Coding• Information• Digit Span• Symbol Search)
TRADITIONAL PSYCHOMETRIC APPROACHES TO IDENTIFICATION OF
ADHDCritique of ACIDS Index
• Arithmetic is sensitive to specific learning disabilities (e.g., dyscalculia secondary to developmental Gerstmann syndrome), dysphasias, anxiety states, psychotic states, etc.
• Coding is sensitive to deficits in motor control, visual perception, anxiety, depression, OCD, etc.
• Information is sensitive to cultural bias, lack of educational opportunity, specific learning disabilities (e.g., dyslexias), dysphasias, long term memory disorders, etc.
• Digit Span is affected by anxiety, schizophrenia, bipolar illness, dysphasia, etc. Digits reversed, but not forward, has high correlation with general intelligence.
• Symbol Search is sensitive to deficits in visual acuity, visual perception, motor control, depression, anxiety, obsessive compulsive disorder, etc.
TRADITIONAL PSYCHOMETRIC APPROACHES TO IDENTIFICATION OF
ADHDWISC-III
4. Processing Speed index
• Based on Coding and symbol search subtests
TRADITIONAL PSYCHOMETRIC APPROACHES TO IDENTIFICATION OF
ADHDCritique of Processing Speed index:
Both Coding and Symbol search are are timed
1. Coding is sensitive to deficits in motor control, visual perception, anxiety, obsessive compulsive disorder, depression, etc.
2. Symbol Search is sensitive to deficits in visual acuity, visual perception, depression, anxiety, obsessive compulsive disorder, etc.
TRADITIONAL PSYCHOMETRIC APPROACHES TO IDENTIFICATION OF
ADHDWISC-III
5. FREEDOM FROM DISTRACTIBILITY
Based on Arithmetic and Digit Span
TRADITIONAL PSYCHOMETRIC APPROACHES TO IDENTIFICATION OF
ADHDCRITIQUE OF FREEDOM FROM
DISTRACTIBILITY INDEX:1. Arithmetic is sensitive to specific learning
disabilities (e.g., dyscalculia), dysphasias, anxiety states, psychotic states, etc.
2. Digit Span is affected by anxiety, schizophrenia, bipolar illness, dysphasia, etc.
3. Digits Backward, but not forward, has moderately high correlation with general intelligence
TRADITIONAL PSYCHOMETRIC APPROACHES TO IDENTIFICATION OF
ADHD
PERFORMANCE DISCREPANCY SCORE
Observed academic achievement vs IQ-based academic achievement expectation
TRADITIONAL PSYCHOMETRIC APPROACHES TO IDENTIFICATION OF
ADHD
Critique: Observed vs expected achievement
Can reflect specific learning disabilities, low motivation, depression, adjustment disorder, test-taking anxiety, memory defects, etc.
MORE SPECIFIC NEUROPSYCHOLOGICAL APPROACHES
TO IDENTIFICATION OF ADHD
• BASED ON LABORATORY MEASURES OF EXECUTIVE FUNCTION
• CONTINUOUS PERFORMANCE TEST– FOCUSES ON SPECIFIC AREAS OF EXECUTIVE
FUNCTION• TASK PERSISTENCE• VIGILANCE• IMPULSE CONTROL• REGULATION OF AROUSAL LEVEL
MORE SPECIFIC NEUROPSYCHOLOGICAL APPROACHES
TO IDENTIFICATION OF ADHD
1. CONTINUOUS PERFORMANCE TEST
– FOCUSES ON SPECIFIC AREAS OF EXECUTIVE FUNCTION
• TASK PERSISTENCE• VIGILANCE• IMPULSE CONTROL• REGULATION OF AROUSAL LEVEL
PRESS BUTTON EVERY TIME A LETTER APPEARS
A
EXCEPT WHEN THE LETTER “X” APPEARS
X
CONTINUOUS PERFORMANCE TESTSCORING CATEGORIES:
• Omissions• Commissions• Overall Processing Speed• Overall Attentional Variability• Perceptual Sensitivity• Risk Taking• Perseverations• Speed Decrement Over time• Variability Over time• Activation/arousal
HIT REACTION TIME
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MIL
LIS
EC
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TYPICAL
ADHD 1 SEC
2 SEC
4 SEC
STANDARD ERROR OF HIT REACTION TIME
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COMMISSION ERRORS
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CONTINUOUS PERFORMANCE TEST• NON-ADHD CONDITIONS THAT CAN
AFFECT SCORES:
• Commissions: anxiety; toxic exposure
• Omissions: depression; dyspraxia
• Overall Processing Speed: depression; anxiety
• Perceptual Sensitivity: Visual acuity; dyseidetic dyslexia
• Risk Taking: psychopathy; anxiety
• Perseverations: psychomotor retardation; frontal lobe damage
• Speed Decrement Over time: diabetes; hypothyroidism
• Activation/arousal: schizotypal conditions (blocking)
MORE SPECIFIC NEUROPSYCHOLOGICAL APPROACHES
TO IDENTIFICATION OF ADHD
2. WISCONSIN CARD SORTING TEST
FOCUSES ON SPECIFIC AREAS OF EXECUTIVE FUNCTION:
• SET FORMATION• SET MAINTENANCE• SET SHIFTING
WISCONSIN CARD SORTING TEST
SORT BY COLOR OR SHAPE?
MORE SPECIFIC NEUROPSYCHOLOGICAL APPROACHES
TO IDENTIFICATION OF ADHD
CRITIQUE OF WISCONSIN CARD SORTING TEST
Set formation can be affected by depression, lowered motivational states, frank retardation
Set shifting difficulties are sometimes seen in anxious people
Loss of set is seen in major psychiatric illness, substance abuse, etc.
MORE SPECIFIC NEUROPSYCHOLOGICAL APPROACHES
TO IDENTIFICATION OF ADHD
3. WIDE RANGE ASSESSMENT OF LEARNING AND MEMORY (WRAML)
FOCUSES ON SPECIFIC AREAS OF EXECUTIVE FUNCTION:
1. WORKING MEMORY 2. SEQUENCING AND MENTAL CONTROL 3. RESISTANCE TO INTERFERENCE
GENERAL MEMORY
Verbal Memory
Visual Memory
Attention
Story Memory
Verbal Learning
Sentence Memory
Sound Symbol
Verbal Working
Symbolic Working
Design Memory
Picture Memory
Finger Windows
Number/LetterStory Delayed
Recall
Verbal Delayed recall
Story Recognition
Verbal Recognition
Design Recognition
Picture Recognition
MORE SPECIFIC NEUROPSYCHOLOGICAL APPROACHES
TO IDENTIFICATION OF ADHD
CRITIQUE OF WIDE RANGE ASSESSMENT OF LEARNING AND MEMORY (WRAML)
AUDITORY WORKING MEMORY DEFICITS MUST BE DIFFERENTIATED FROM AUDITORY PROCESSING DEFICITS, DYSPHASIAS, ANXIETY STATES, ETC.
SEQUENCING AND MENTAL CONTROL DEFICITS ARE ALSO CHARACTERISTICS OF THOUGHT AND DISORDERS
SUSCEPTIBILITY TO INTERFERENCE MAY BE ASSOCIATED WITH ALMOST ANY NEURODEVELOPMENTAL OR PSYCHIATRIC CONDITIION
CONCLUSIONS
THE BEST WAY TO ENSURE AN ACCURATE DIAGNOSIS IS TO USE A COMBINATION OF HISTORY, RATING SCALES, DIRECT OBSERVATIONS, AND A CAREFULLY SELECTED BATTERY OF NEUROPSYCHOLOGICAL TESTS
NEUROPSYCHOLOGICAL TESTS THAT ARE BASED ON LABORATORY METHODS OF ASSESSING EXECUTIVE FUNCTION PROVIDE INFORMATION THAT IS MOST PERTINENT TO THE COGNITIVE DEFICITS FOUND IN ADHD
NEVERTHELESS, PERFORMANCE DEFICITS ON SPECIFIC TESTS MAY BE ATTRIBUTABLE TO ANY NUMBER OF NON-ADHD SYMPTOM COMPLEXES