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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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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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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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

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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