Joint Mental Health Research Symposium of Melbourne ... - NCNP

Progress in “Brain & Mind” study of the field of developmental disorder

research

Masumi Inagaki

Department of Developmental Disorders,National Institute of Mental Health,

National Center of Neurology and Psychiatry (NCNP)

Joint Mental Health Research Symposium of Melbourne University and NCNP

Intellectual Disabilities

Learning Disorders

Attention Deficit Hyperactivity Disorders (ADHD)

Autism Spectrum Disorders

Asperger syndrome

DCD

Pathophysiological study and new intervention to ADHD (attention deficit

hyperactivity disorder) in Japanese children

Masumi Inagaki

Department of Developmental DisordersNational Institute of Mental Health

National Center of Neurology and Psychiatry NCNP

Melbourne University and NCNP Symposium

2013-6-28

• What is ADHD?

• Core symptoms of ADHD

• Hypothesis of ADHD pathophysiology

• Electrophysiological approaches understanding attention function

• Study of executive function in ADHD

• New intervention to ADHD

• Characterized by significant difficulties either of inattention or hyperactivity and impulsiveness or a combination of the two.

• No distinct physical signs: identified through characteristic patterns of behavior

• These characteristic patterns may vary among children

• Associated with problems in social, cognitive, academic, familial, and emotional domains of development and adjustment

ADHD

Picturebook by Dr Hoffman, 1845

Still GF. "Some abnormal psychical conditions in children. Lancet, 1902;1:1008–1012

Great encephalitis epidemic of 1917-1918 gave rise to the concept of a “brain-injured child syndrome”, often associated with mental retardation

“Minimal brain damage” and “Minimal brain dysfunction” in the 1940s and 1950s

By 1970’s, deficits in attention and impulse control, in addition to hyperactivity, seen as the primary symptoms (DSM II, III )

DSM-IV-TR (1987)

Story of fidgety Phillip

Der Struwwelpeter by Heinrich Hoffmann(1845) History of ADHD

According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR), symptoms emerge before seven years of age.

Symptoms must be observed in two different settings for six months or more and to a degree that is greater than other children of the same age.

ADHD have an increased risk of experiencing difficulties with social skills, such as social interaction and forming and maintaining friendships. Handwriting difficulties seem to be common in children with ADHD.

Attention deficit hyperactivity disorder (ADHD) DSM-IV-TR

DSM-5 (2013)

Neurodevelopmental disorders

Intellectual Developmental DisordersCommunication disordersAutism spectrum disorderADHDSpecific Learning disorderMotor disordersOther

ADHD is a neurodevelopmental disorder defined by impairing levels of inattention, disorganization, and/or hyperactivity-impulsivity. Inattention and disorganization entail inability to stay on task, seeming not to listen, and losing materials, at levels that are inconsistent with age or developmental level. Hyperactivity-impulsivity entails overactivity, fidgeting, inability to stay seated, intruding into other people’s activities, and inability to wait---symptoms that are excessive for age or developmental level. In childhood, ADHD frequently overlaps with disorders that are often considered to be “externalizing disorders,” such as oppositional defiant disorder and conduct disorder. ADHD often persists into adulthood, with resultant impairments of social, academic and occupational functioning.

• inattention: six (or more) of the following symptoms of inattention have persisted for at least 6 months to a degree that is maladaptive and inconsistent with developmental level:

• (a) often fails to give close attention to details or makes careless mistakes in schoolwork, work, or other activities

• (b) often has difficulty sustaining attention in tasks or play activities • (c) often does not seem to listen when spoken to directly • (d) often does not follow through on instructions and fails to finish

school work, chores, or duties in the workplace (not due to oppositional behavior or failure to understand instructions)

• (e) often has difficulty organizing tasks and activities • (f) often avoids, dislikes, or is reluctant to engage in tasks that

require sustained mental effort (such as schoolwork or homework) • (g) often loses things necessary for tasks or activities (e.g., toys,

school assignments, pencils, books, or tools) • (h) is often easily distracted by extraneous stimuli • (i) is often forgetful in daily activities

• Hyperactivity

• (a) often fidgets with hands or feet or squirms in seat • (b) often leaves seat in classroom or in other situations in which

remaining seated is expected • (c) often runs about or climbs excessively in situations in which it is

inappropriate (in adolescents or adults, may be limited to subjective feelings of restlessness)

• (d) often has difficulty playing or engaging in leisure activities quietly • (e) is often "on the go" or often acts as if "driven by a motor" • (f) often talks excessively

• Impulsivity

• (g) often blurts out answers before questions have been completed • (h) often has difficulty awaiting turn • (i) often interrupts or intrudes on others (e.g., butts into

conversations or games)

The dual pathway model of AD/HDSonuga-Barke

2003

Neurosci Biobehav Rev(2003) 27: 593-604

Pathophysiology of ADHD

EF・

Reward system

Core symptom

Hyperactivity ・impulsivity・inattention

Clinical symptomsPsychosocial

ComorbidityAnxietyMood disorder・・・

Low school achievementLow academic careerLow self esteem・・・

6 EF domains(Pennington and Ozonoff, 1996)

・ inhibition・ working memory・ contextual memory・ generativity (fluency)・ planning・ cognitive shifting

Executive Function

ADHD is EF disorder. (Barkley RA. 4th World congress on ADHD, Milan, Italy June 7,2013 )

Poor inhibition to those in ADHD childrenAnd they easily react to trifling

Many stimulants in the world, especially for children

(Ozonoff et al.,1999)

(wikipedia)

【Background】

Test of inhibition

・Stroop task： Oxy-Hb changes in the inferior prefrontal cortex--- ADHD < TDC

(Negoro et al.,2010)

・Reverse Stroop : ADHD < TDC ( Both group n=15)Stroop task : ADHD ≒TDC

(Song and Hakoda, 2011)

【Inhibition of interference】

The relation between interference inhibition and Brain activity

(Matsumoto et al.,2004)

Brain activity of inhibitionNetwork between Cingulate and LPFC

【Task】

・Stroop task, Reverse Stroop task

・SNAP (ADHD severity)parental questionnaire

・RCPM (non verbal intelligence)

・EHI (handedness)・K-ABC

(sentence comprehension

・Ethics committee(approval #：A2011-003)

【Hypothesis】NIRS： ADHD ＜ ASD ≒ TDCBehavior ADHD ＜ ASD ≒ TDC

Data recording & analysis・Interference ratio・Number of error・Reaction time・Oxy-Hb concentration through OEG-16(NIRS)

SNAP IV rating scale

SubjectsParticipants： TDC group ASD group ADHD group

※Parentheses mean SD※RCPM：Raven’s Colored Progressive Matrices test※SNAP：Swanson, Nolan, and Pelham Scale※*, p < 0.05; **, p < 0.01; ***, p < 0.001※handedness：TDC(r:l=13:2)、ASD(r:l=8:3)、ADHD(r:l=9:1)

2.Procedure：task and measure・To evaluate inhibition, we use Stroop and Reverse-stroop tasks.・Using a touch panel display and near-infrared spectroscopy(NIRS : OEG-16).

Stroop task

Rest Task

20sec5sec


Reverse-stroop task

Rest Task

20sec5sec


Rest Task

20sec5sec

Behavioral results

Stroop task・no main effect

Reverse stroop task・ADHD < TDC in interference rate, number of

errors and correct rate.・correlate between inattention and number

of errors.※interference rate = (Neutral - Incongruent) / Neutral ×

100

0.0

0.5

1.0

1.5

TDC ASD ADHDError (n)

0

5

10

15

20

25

TDC ASD ADHD

Interferen

ce (%

)

*

Interference ratio

*

Error

Reverse Stroop task

（F(2,33)=3.03, p=0.053）ADHD＜TDC：p=0.099ADHD＜ASD：p=0.064

Non interference error 0 – 0.2

Characteristics of interference error in Reverse stroop task

Interference error

Non interference error

Correct

Brain activity

R×L(ADHD) : t(18) = 2.31, p = 0.033

Ch4 : F (2, 33) = 3.71, p = 0.035

Stroop task・no main effect

Reverse-stroop task・ADHD < TDC

in ch 4(rLPFC)・correlation between inattention

and brain activity in ch4・right hemisphere was higher

activated in ADHD

(r = 0.60, p = 0.068

(r = 0.60, p = 0.068

Inattention and Oxy-Hb at Ch4

Discussion・ ADHD children showed a higher interference rate compared to TDC in RST. → ADHD children have inhibition problems in color interference.

・Less brain activity correlates with inattention.Right dorsolateral prefrontal cortex activity is less in people with high

impulsivity(Asahi et al.,2004)→Decreases in brain activity can lead to problems such as ADHD inattention

and impulsivity

・laterality →It’s possible that ADHD children are supplementing their low right prefrontal activity with higher left prefrontal activity.

・ Only ADHD children showed problems in the areas of behavior and brain activity. → Children with ASD did not show any significant difficulties in the inhibition

tasks.

Conclusion

・In order to evaluate the inhibition in children with ADHD, children with ASD and TDC, we used the Stroop and Reverse-stroop tasks in combination with NIRS to measure changes in cerebral blood flow in the prefrontal cortex.

・ADHD children were found to be vulnerable to color interference in Reverse-stroop tasks.

・ADHD children with higher levels of inattention were also found to have low levels of right prefrontal brain activity.

Neurofeedback training in children with ADHD

New intervention for ADHD

NF (Neurofeedback) training

An operant conditioning procedure: participants learn to gain self-control over EEG patterns.

Heinrich et al. (2007)

The participant gets the impression of an online procedure.

Using a moving time window of about 1 to 2 seconds in length, feedback is calculated several times per second.

Many studies have shown the effectiveness of NF training in children with ADHD.

Why NF training?

e.g., Barbaresi et al. (2002)About 86.5% for ADHD are treated with stimulants.

However, there are several side effects: reduced growth, sleep disorders, and vegetative disturbances.

Drug treatment

Behavioral or cognitive therapies are also a treatment option.However, the long-term efficacy has been characterized as marginal.

Behavioral therapy

e.g., Dopfner & Lehmkuhl et al. (2002)

NF training appears to have no side effects and long-lasting effects.

The features of EEG/ERP in children with ADHD

ー larger amplitude of theta (4 to 8 Hz) and smaller amplitude of beta (13 to 30 Hz) bands. (EEG)

Children with ADHD, compared with control children, show…

ー smaller amplitude of CNV (contingent negative variation) and P300. (ERP)

Trillenberg et al. (2000)

These components are associated with cognitive preparation or attention.

NF training: SCP (slow cortical potential) training

The participants learn to increase and decrease their cortical excitability (positive/negative conditions).


The amplitude of slow negative waves is related to the allocation of neuronal resources. Birbaumer et al. (1990)

SCP: slow negativity under 0.5 Hz (100μ to 1mV)

Heinrich et al. (2004); Strehl et al. (2006); Drechsler et al. (2007); Wangler et al. (2011)

The SCP training affects the amplitude of CNV, but not P300 (P300 affected by 12 to 18 Hz: Egner

& Gruzelier, 2001).


In the SCP training, the amplitude of CNV appears to be an index.

NF training: SCP (slow cortical potential) trainingIn addition to the index of ERP (CNV), various cognitive and behavioral skills have been measured.

ー Parental and teacher ratings (ADHD rating scale)

ー Cognitive abilities (e.g., WISC-III)

ー Attention tasks (e.g., no-go task)

Many studies showed that scores on these cognitive and behavioral indexes were enhanced by the SCP training.

Heinrich et al. (2004); Strehl et al. (2006); Drechsler et al. (2007); Wangler et al. (2011)

Therefore, symptoms of ADHD may be effectively treated by SCP training resulting in higher EEG/ERP, cognitive,

and behavioral levels.

Example of NF (SCP training)

An advantage of NF training

ー No negative effects

ー Long-term effects (remains six months: e.g., Strehl et al., 2006)

Methodological problems of NF training

ー follow-up data on everyday life and academic performance.

ー comparisons with drug treatment and behavior therapy.

ー Non-invasive method

ー long-term effects (more than six months after treatment).

Future research should include…

Comorbidity in ADHD

Establishment of evaluation method of executive function in ADHD

Development of effective intervention strategy in ADHD

Future plan・・・・・

Thank you for your ATTENTION!

Can I have a pot of VBin August?

Joint Mental Health Research Symposium of Melbourne ... - NCNP

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