Progress in Brain & Mind study of the field of developmental disorder research

Transcription

1 Joint Mental Health Research Symposium of Melbourne University and 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)

2 Learning Disorders Autism Spectrum Disorders Asperger syndrome Intellectual Disabilities Attention Deficit Hyperactivity Disorders (ADHD) DCD

3 Melbourne University and NCNP Symposium Pathophysiological study and new intervention to ADHD (attention deficit hyperactivity disorder) in Japanese children Masumi Inagaki Department of Developmental Disorders National Institute of Mental Health National Center of Neurology and Psychiatry NCNP

4 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

5 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

6 Der Struwwelpeter by Heinrich Hoffmann(1845) History of ADHD Picturebook by Dr Hoffman, 1845 Still GF. "Some abnormal psychical conditions in children. Lancet, 1902;1: Great encephalitis epidemic of gave rise to the concept of a brain-injured child syndrome, often associated with mental retardation Story of fidgety Phillip 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)

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

8 DSM-5 (2013) Neurodevelopmental disorders Intellectual Developmental Disorders Communication disorders Autism spectrum disorder ADHD Specific Learning disorder Motor disorders Other

9 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.

10 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

11 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)

12 The dual pathway model of AD/HD Sonuga-Barke 2003 Neurosci Biobehav Rev (2003) 27:

13 Pathophysiology of ADHD Anxiety Mood disorder Comorbidity Clinical symptoms Core symptom EF Reward system Hyperactivity impulsivity inattention Psychosocial Low school achievement Low academic career Low self esteem

14 Executive Function 6 EF domains (Pennington and Ozonoff, 1996) inhibition working memory contextual memory generativity (fluency) planning cognitive shifting ADHD is EF disorder. (Barkley RA. 4 th World congress on ADHD, Milan, Italy June 7,2013 )

15 Many stimulants in the world, especially for children Poor inhibition to those in ADHD children And they easily react to trifling

16 Background Test of inhibition (Ozonoff et al.,1999) (wikipedia)

17 Inhibition of interference 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) The relation between interference inhibition and Brain activity Brain activity of inhibition Network between Cingulate and LPFC (Matsumoto et al.,2004)

18 Task Stroop task, Reverse Stroop task SNAP (ADHD severity) parental questionnaire RCPM (non verbal intelligence) EHI (handedness) K-ABC (sentence comprehension Data recording & analysis Interference ratio Number of error Reaction time Oxy-Hb concentration through OEG-16(NIRS) Hypothesis NIRS: ADHD < ASD TDC Behavior ADHD < ASD TDC Ethics committee (approval #:A )

19 SNAP IV rating scale

20 Subjects Participants: 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 < handedness:tdc(r:l=13:2) ASD(r:l=8:3) ADHD(r:l=9:1)

21 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 5sec 20sec Rest Task

22 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). Reverse-stroop task 5sec 20sec Rest Task

23 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). 5sec 20sec Rest Task

24 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

25 Reverse Stroop task Interference ratio Interference (%) * Error Error (n) * 0 TDC ASD ADHD 0.0 TDC ASD ADHD

26 Characteristics of interference error in Reverse stroop task Non interference error Interference error Correct (F(2,33)=3.03, p=0.053) ADHD<TDC:p=0.099 ADHD<ASD:p=0.064 Non interference error 0 0.2

27 Brain activity Ch4 : F (2, 33) = 3.71, p = R L(ADHD) : t(18) = 2.31, p = 0.033

28 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

29 Inattention and Oxy-Hb at Ch4 (r = 0.60, p = 0.068

30 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.

31 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.

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33 New intervention for ADHD Neurofeedback training in children with ADHD

34 NF (Neurofeedback) training An operant conditioning procedure: participants learn to gain self-control over EEG patterns. Heinrich et al. (2007) Using a moving time window of about 1 to 2 seconds in length, feedback is calculated several times per second. The participant gets the impression of an online procedure. Many studies have shown the effectiveness of NF training in children with ADHD.

35 Why NF training? Drug treatment About 86.5% for ADHD are treated with stimulants. e.g., Barbaresi et al. (2002) However, there are several side effects: reduced growth, sleep disorders, and vegetative disturbances. Behavioral therapy Behavioral or cognitive therapies are also a treatment option. However, the long-term efficacy has been characterized as marginal. e.g., Dopfner & Lehmkuhl et al. (2002) NF training appears to have no side effects and long-lasting effects.

36 The features of EEG/ERP in children with ADHD Children with ADHD, compared with control children, show ー larger amplitude of theta (4 to 8 Hz) and smaller amplitude of beta (13 to 30 Hz) bands. (EEG) ー smaller amplitude of CNV (contingent negative variation) and P300. (ERP) These components are associated with cognitive preparation or attention. Trillenberg et al. (2000)

37 NF training: SCP (slow cortical potential) training SCP: slow negativity under 0.5 Hz (100μ to 1mV) The participants learn to increase and decrease their cortical excitability (positive/negative conditions). Heinrich et al. (2004); Strehl et al. (2006); Drechsler et al. (2007); Wangler et al. (2011) The amplitude of slow negative waves is related to the allocation of neuronal resources. Birbaumer et al. (1990) 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. Heinrich et al. (2007) Heinrich et al. (2004)

38 NF training: SCP (slow cortical potential) training In 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.

39 Example of NF (SCP training)

40 An advantage of NF training ー No negative effects ー Non-invasive method ー Long-term effects (remains six months: e.g., Strehl et al., 2006) Methodological problems of NF training Future research should include ー long-term effects (more than six months after treatment). ー follow-up data on everyday life and academic performance. ー comparisons with drug treatment and behavior therapy.

41 Comorbidity in ADHD

42 Future plan Establishment of evaluation method of executive function in ADHD Development of effective intervention strategy in ADHD

43 Thank you for your ATTENTION! Can I have a pot of VB in August?