1. THE MANY FACES OF ADHD Francis M. Crinella, Ph.D. Clinical Professor of Pediatrics, Psychiatry & Human Behavior, and Physical Medicine & Rehabilitation Director, Neuropsychology Laboratory Child Development Center University of California, Irvine 25 JAN 10

2. WHAT IS ATTENTION? A special [mental] 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]

3. WHAT IS ATTENTION? Everyone knows what attention is. It is the taking possession in 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]

4. CONSIDER YOUR LIFE WITHOUT ATTENTION-- SOME IMPORTANT FEATURES OF ATTENTION

5. ATTENTION HELPS US TO MANAGE CONFLICTING PERCEPTUAL INPUTS

6. ATTENTION ALLOWS US TO PERSIST IN TASK PERFORMANCE

7. ATTENTION HELPS US FOCUS ON THE TASK AT HAND

8. ATTENTION ENABLES US TO PERFORM TASKS THAT REQUIRE PLANNING AND WORKING MEMORY

9. ATTENTION ENABLES US TO MAINTAIN VIGILANCE WHEN MONITORING SIGNALS

10. ATTENTION ENABLES US TO AVOID COSTLY ERRORS

11. HOWEVER: ATTENTION ITSELF IS ONE OF THE MOST FRAGILE OF ALL MENTAL FUNCTIONS IT CAN BE ADVERSELY AFFECTED BY ANY NUMBER OF INFLUENCES IT CAN BE ADVERSELY AFFECTED BY ANY NUMBER OF INFLUENCES ALMOST EVERY NEUROPSYCHIATRIC DISORDER IS ACCOMPANIED BY SOME KINDS OF ATTENTION DEFICITS ALMOST EVERY NEUROPSYCHIATRIC DISORDER IS ACCOMPANIED BY SOME KINDS OF ATTENTION DEFICITS ADHD IS BUT ONE OF THE PSYCHIATRIC DISORDERS IN WHICH ATTENTION IF AFFECTED ADHD IS BUT ONE OF THE PSYCHIATRIC DISORDERS IN WHICH ATTENTION IF AFFECTED ADHD MAY AFFECT SEVERAL DIFFERENT COMBINATIONS OF ATTENTIONAL COMPONENTS ADHD MAY AFFECT SEVERAL DIFFERENT COMBINATIONS OF ATTENTIONAL COMPONENTS

12. DSM-IV SYMPTOMS OF ADHD INATTENTION CAN’T ATTEND TO DETAILS CAN’T ATTEND TO DETAILS CAN’T SUSTAIN ATTENTION CAN’T SUSTAIN ATTENTION DOESN’T LISTEN DOESN’T LISTEN FAILS TO FINISH FAILS TO FINISH CAN’T ORGANIZE TASKS CAN’T ORGANIZE TASKS AVOIDS SCHOOLWORK AVOIDS SCHOOLWORK LOSES THINGS LOSES THINGS EASILY DISTRACTED EASILY DISTRACTED FORGETFUL FORGETFULHYPERACTIVITY/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

13. CONFIGURATION OF DSM-IV SYMPTOMS OF ADHD IN PATIENT #1 INATTENTION HYPERACTIVITY /IMPULSIVITY 1 CAN’T ATTEND TO DETAILS YESFIDGETSYES 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 THINGS EASILYNO BLURTS OUT ANSWERS NO 8DISTRACTEDNO CAN’T WAIT TURN YES 9FORGETFULYES INTERRUPTS OR INTRUDES YES NUMBER OF INATTENTION SYMPTOMS 4 NUMBER OF HYPERACTIVITY SYMPTOMS 7

14. SYMPTOM CHECKLISTS FOR TWO PATIENTS WHO MEET CRITERIA FOR ADHD, HYPERACTIVE/IMPULSIVE SUBTYPE HYPERACTIVITY/IMPULSIVITY PATIENT #1 PATIENT #2 1FIDGETSYESNO 2 CAN’T STAY SEATED YESNO 3 RUNS ABOUT AND CLIMBS YESNO 4 CAN’T PLAY QUIETLY YESYES 5 IS OFTEN ON THE GO YESYES 6 TALKS TOO MUCH YESYES 7 BLURTS OUT ANSWERS NOYES 8 CAN’T WAIT TURN NOYES 9 INTERRUPTS OR INTRUDES NOYES TOTAL”YES”66

15. NUMBER OF POSSIBLE OF DSM-IV SYMPTOM CONFIGURATIONS THAT MEET CRITERIA FOR DIAGNOSIS OF ADHD FOR HYPERACTIVE SUBTYPE ONLY: –NUMBER OF VARIATIONS ON 9 CRITERIA 9/6 = 84 9/7 = 36 9/8 = 9 9/9 = 1 ∑ = 130 ∑ = 130

16. NUMBER OF POSSIBLE OF DSM-IV SYMPTOM CONFIGURATIONS THAT MEET CRITERIA FOR DIAGNOSIS OF ADHD—ALL SUBTYPES HYPERACTIVE SUBTYPE: 130 INATTENTIVE SUBTYPE: 130 COMBINED SUBTYPE: 260 SUM OF POSSIBLE CONFIGURATIONS: 520

17. DOMAIN OF ADHD SYMPTOMS 1 3 2 4 10 17 8 18 14 13 7 9 12 65 16 11 15

18. ADHD SYMPTOMS AS SUBDOMAIN OF MORE INCLUSIVE DOMAIN OF ALL SYMPTOMS OF NEUROPSYCHIATRIC DISORDER 1 3 2 4 8 11 7 9 6 5 10 13 15 12 16 17 18 14

19. INDIVIDUAL WITH “PURE”ADHD, REPRESENTED AS SUBSET OF SYMPTOMS IN ADHD SUB-DOMAIN, EXCLUSIVE OF ALL NON- ADHD SYMPTOMS IN LARGER DOMAIN OF ALL MALADAPTIVE BEHAVIORS 1 3 2 4 8 11 7 9 6 5 10 13 15 12 16 1718 14

20. MORE COMMON CASE: INDIVIDUAL WHO MEETS DSM- IV DIAGNOSTIC CRITERIA FOR ADHD, BUT ALSO PRESENTS WITH SYMPTOMS NOT CONSIDERED DIAGNOSTIC OF ADHD 1 3 2 4 8 11 7 9 6 5 10 13 15 12 16 17 18 14

21. IS THIS ADHD? INDIVIDUAL STILL MEETS DSM-IV DIAGNOSTIC CRITERIA FOR ADHD, BUT ALSO PRESENTS WITH MANY MORE SYMPTOMS NOT CONSIDERED DIAGNOSTIC CRITERIA FOR ADHD 1 3 2 4 8 11 7 9 6 5 10 13 15 12 16 17 18 14

22. PROBLEM: MANY CONFIGURATIONS OF MALADAPTIVE BEHAVIOR ARE LABELED “ADHD” Should the label, ADHD, be assigned to a potpourri of disorders with only some features in common? Should the label, ADHD, be assigned to a potpourri of disorders with only some features in common? Are there “core” features of “true” ADHD? Are there “core” features of “true” ADHD? What are the most common non-core accompaniments of ADHD? What are the most common non-core accompaniments of ADHD? When do these non-core features signify that a diagnosis other than ADHD is more appropriate? When do these non-core features signify that a diagnosis other than ADHD is more appropriate?

23. BIOLOGICAL EVIDENCE FOR A CORE ADHD SYNDROME 1.NEUROCHEMICAL 2.GENETIC 3.ELECTROPHYSIOLOGICAL 4.FUNCTIONAL IMAGING 5.NEUROPSYCHOLOGICAL

25. NEUROCHEMICAL MOST EFFECTIVE TREATMENT--CNS STIMULANTS DEXTROAMPHETAMINES DEXTROAMPHETAMINES METHYLPHENIDATES METHYLPHENIDATES EFFECTS: EFFECTS: –Improved classroom behavior –Improved academic productivity –Improved peer/adult interactions –Less frequent oppositional conduct –Reduced aggression

26. 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)

27. 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 BASAL GANGLIA

29. RECENT BRAIN IMAGING STUDIES IN ADHD

30. 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. Biological Psychiatry, 48,238-46. Finding: Event related potentials identify the processing component and timing of an impaired right-frontal response- inhibition mechanism.

32. COGNITIVE NEUROPSYCHOLOGY BASED ON TRADITIONAL APPROACH TO STUDYING BRAIN-BEHAVIOR RELATIONSHIPS 1.Experimental removal of brain structures 2.Observation of effect on specific behavioral functions 3.Identification of brain structures/networks that are correlated with ADHD-like behavior

33. DISTINCT ANATOMICAL NETWORKS CARRY OUT SPECIFIC ASPECTS OF ATTENTION ALERTING NETWORK ALERTING NETWORK –LOCATION: ARAS, ETC. –FUNCTION: ACHIEVE AND MAINTAIN STATE OF READINESS ORIENTING NETWORK ORIENTING NETWORK –LOCATIONS: PARIETAL LOBE, SUPERIOR COLLICULUS & PULVINAR –FUNCTION: REACT TO SENSORY STIMULI EXECUTIVE NETWORK EXECUTIVE NETWORK –LOCATION: ANTERIOR CINGULATE; DORSOLATERAL FRONTAL CORTEX & BASAL GANGLIA –FUNCTIONS: CONTROL NEURAL RESPONSES TO STIMULI CONTROL NEURAL RESPONSES TO STIMULI GENERATE NEW INFORMATION FROM LONG TERM MEMORY GENERATE NEW INFORMATION FROM LONG TERM MEMORY PRIORITIZE OPERATION OF OTHER BRAIN AREAS PRIORITIZE OPERATION OF OTHER BRAIN AREAS

34. ADHD IS A DISORDER THAT PRIMARILY AFFECTS THE EXECUTIVE NETWORK

35. SOME FEATURES OF EXECUTIVE FUNCTION— STERNBERG (1985) Decision as to just what the problem is that needs to be solved Decision as to just what the problem is that needs to be solved Selection of lower-order components Selection of lower-order components Selection of one or more representations of organizations for information Selection of one or more representations of organizations for information Selection of a strategy for combining lower order components Selection of a strategy for combining lower order components Decision regarding tradeoffs in the speed and accuracies with which various components are executed Decision regarding tradeoffs in the speed and accuracies with which various components are executed Solution monitoring Solution monitoring

36. TESTS OF EXECUTIVE FUNCTION IN THE HUMAN NEUROPSYCHOLOGY LABORATORY By definition, no test can be performed in the absence of executive control By definition, no test can be performed in the absence of executive control Executive functions must be differentiated from other cognitive 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? Which tests do this best?

37. SPECIFIC NEUROPSYCHOLOGICAL APPROACHES TO IDENTIFICATION OF ADHD EXAMPLE OF LABORATORY MEASURE OF EXECUTIVE FUNCTION--CONTINUOUS PERFORMANCE TEST (CPT) –FOCUSES ON SPECIFIC AREAS OF EXECUTIVE FUNCTION TASK PERSISTENCE TASK PERSISTENCE VIGILANCE VIGILANCE IMPULSE CONTROL IMPULSE CONTROL REGULATION OF AROUSAL LEVEL REGULATION OF AROUSAL LEVEL

38. PRESS BUTTON EVERY TIME A LETTER APPEARS A

39. EXCEPT WHEN THE LETTER “X” APPEARS X

40. CONTINUOUS PERFORMANCE TEST SCORING CATEGORIES: OmissionsOmissions CommissionsCommissions Overall Processing SpeedOverall Processing Speed Overall Attentional VariabilityOverall Attentional Variability Perceptual SensitivityPerceptual Sensitivity Risk TakingRisk Taking PerseverationsPerseverations Speed Decrement Over timeSpeed Decrement Over time Variability Over timeVariability Over time Activation/arousalActivation/arousal

41. HIT REACTION TIME 300 325 350 375 400 425 450 475 500 525 550 575 600 625 650 675 700 MILLISECONDS TYPICAL ADHD 1 SEC 2 SEC 4 SEC

42. STANDARD ERROR OF HIT REACTION TIME 0 10 20 30 40 50 60 70 80 90 100 MILLISECONDS TYPICAL ADHD 1 SEC 2 SEC 4 SEC

43. COMMISSION ERRORS 0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 1.8 MILLISECONDS CONTROLS ADHD 1 SEC 2 SEC 4 SEC

44. NON-ADHD CONDITIONS THAT CAN AFFECT SCORES ON CPT: Commissions: anxiety; toxic irritabilityCommissions: anxiety; toxic irritability Omissions: depression; dyspraxia; schizophreniaOmissions: depression; dyspraxia; schizophrenia Overall Processing Speed: depression; anxiety; metabolic conditions (e.g., hypoglycemia)Overall Processing Speed: depression; anxiety; metabolic conditions (e.g., hypoglycemia) Perceptual Sensitivity: Visual acuity; dyseidetic dyslexia; cataracts;Perceptual Sensitivity: Visual acuity; dyseidetic dyslexia; cataracts; Risk Taking: psychopathy; anxiety; bipolar disorderRisk Taking: psychopathy; anxiety; bipolar disorder Perseverations: psychomotor retardation; frontal lobe damage; frank mental retardationPerseverations: psychomotor retardation; frontal lobe damage; frank mental retardation Speed Decrement Over time: depression; diabetes; hypothyroidismSpeed Decrement Over time: depression; diabetes; hypothyroidism Activation/arousal: schizotypal conditions (blocking); obsessional states; malnutritionActivation/arousal: schizotypal conditions (blocking); obsessional states; malnutrition

45. CPT AND DSM-IV COMMONALITIES FOR INDIVIDUALS WITH ADHD AND INDIVIDUALS WITH ANXIETY UNDERAROUSED IMPERSISTENT RECKLESS PERSEVERATIVE IMPULSIVE RESTLESS AND ON EDGE DIFFICULTY CONCENTRATING IRRITABLE TENSE DISTURBED SLEEP CPTDSM-IV

46. CPT AND DSM-IV COMMONALITIES FORINDIVIDUALS WITH ADHD AND INDIVDUALS WITH DEPRESSION IMPULSIVE IMPERSISTENT RECKLESS PERSEVERATIVE UNDERAROUSED LOW ENERGY OR FATIGUE POOR CONCENTRATION INSOMNIA/HYPERSOMNIA HOPELESSNESS POOR APPETITE CPTDSM-IV

47. CONCLUSIONS REGARDING THE DIAGNOSTIC SPECIFICITY OF TESTS OF EXECUTIVE FUNCTION The capacity to maintain attention is fragile, and may be affected by virtually any psychiatric and/or neurological condition Even on tests of executive function, thought to be quite specific for the “core” deficits found in ADHD, problems other than ADHD will affect performance

48. CONCLUSIONS Many individuals thought to have ADHD may have behavioral deficits that are commonly found among individuals with ADHD, but these deficits are also found in individuals with a host of other psychiatric disorders The incidence and prevalence of persons who have true ADHD, a hereditarily-transmitted disorder of the brain’s dopaminergic networks is probably much less than claimed by ADHD professionals and advocates Nevertheless: Those whose attentional processes are affected by neuropsychiatric conditions other than ADHD are as deserving of treatment and accommodations for their attentional deficits as are those with “true” ADHD