ADHD in children and adolescents: examination of the association of neurological subtle signs with working memory problems

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1 ADHD in children and adolescents: examination of the association of neurological subtle signs with working memory problems Winther, J., Aggarwal, S., Hall, N, Rennie, K., C Prakash, Williams, J., & Vance, A.

2 Introduction Working Memory (WM) WM deficits are known to be associated with ADHD WM deficits are known to be associated with poorer academic achievement WM deficits are also linked to problems developing and maintaining social relationships Academic achievement and social skills are protective factors for young people with ADHD WM deficits may limit the effectiveness of cognitively based treatment programs

3 Executive Functioning involves the integration, processing, storage and retrieval of information directs attention to important information, suppresses irrelevant information and co-ordinates cognitive processes to do more than one task at a time Working Memory Temporal storage and manipulation of information

4 Attention and working memory involve the same brain regions

5 Working memory Verbal memory Visuo-spatial memory

6 Working memory Spatial working memory performance deficits in children with ADHD are not due to clumsiness / incoordination difficulties while completing the tasks Reaction times between ADHD subtypes and healthy control participants do not differ when completing spatial working memory tasks

7 Neurological Subtle Signs Subtle motor problems, often called neurological soft or subtle signs have been considered to reflect brain dysfunction There has been considerable debate about the reliability and validity of neurological subtle signs assessment, primarily due to the lack of consensus about their definition and interpretation However when a standardized method of assessment has been used adequate validity and inter-rater reliability have been demonstrated. Research has also demonstrated that cognitive deficits, behavioural and emotional problems are associated with neurological subtle signs

8 Neurological subtle signs (NSS) clinical measure that has been shown to be associated with brain dysfunction good inter rater reliability has been demonstrated some professionals already routinely use them in clinical practice easy and quick to administer NSS tests doesn t require a lot of clinical resources easy to train staff to assess NSS train a range of professionals in a number of CAMHS settings

9 Neurological Subtle Signs Smoothness / accuracy of movements: widespread neural networks Mirror movements: widespread neural networks Choreiform / athetoid movements: basal ganglia mediated neural networks Conjugate eye gaze: frontal eye fields mediated neural networks Cerebellar signs: cerebellum mediated neural networks

10 This study addresses the following questions: Do neurological subtle signs as a whole independently contribute to working memory problems? Which components of neurological subtle signs independently contribute to working memory problems?

11 Method Cross sectional study of young people with categorically and dimensionally defined ADHD N = 992 Spatial working memory (including strategy) and spatial span assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB) The Scored Developmental Neurological Examination was used to define total neurological subtle signs and its major components Standard multiple regression was used to examine the contribution of total neurological subtle signs and its key components to spatial working memory and its strategy and span components

12 Results Participant characteristics Combined Inattentive HyperImp p M,F 492, ,60 62,16 ns Age 9.84 (2.48) (2.53) 9.91 (2.64) ns Verbal IQ (13.63) (10.89) (12.23) ns Perf IQ (10.08) (11.61) (12.27) ns FSIQ (10.97) (11.65) (11.99) ns SAS 7.58 (1.77) 7.77 ( (1.15) ns

13 Results ADHD N RT subtype SWM Level 8 Combined ( ) Inattentive ( ) HyperImp ( ) Controls ( ) (matched for age, gender and IQ) F (3,821) = 1.72, p =.16, controlling age and IQ

14 Total neurological subtle signs on spatial working memory and span Variables NSS total R2 Adjusted R2 R B b sr2 BSE *** Strategy * Span *** p <.0005 *** p <.05 *

15 Spatial Working Memory Between Search Error r = -.4 r =.6 Spatial span Strategy

16 Independent contributions of specific NSS on between search errors Variables BSE ChAth SmAcc Mir Eye Cer B b sr2 ChAth SmAcc *** Mir * Eye Cer * p <.0005 *** p <.05 * R2 =.11 Adjusted R2 =.10 R =.33

17 Independent contributions of specific NSS on spatial span Variables SPAN ChAth SmAcc Mir Eye Cer B β sr2 ChAth SmAcc *** Mir Eye Cer *** p <.0005 *** R2 =.13 Adjusted R2 =.12 R =.35

18 Independent contributions of specific NSS on strategy Variables STRAT ChAth SmAcc Mir Eye Cer B β sr2 ChAth SmAcc ** Mir Eye Cer p <.01 ** R2 =.01 Adjusted R2 =.01 R =.12

19 Summary of findings Neurological subtle signs of smoothness / accuracy and cerebellar signs are good clinical indicators of: spatial working memory deficits [between search errors (8% of the variance)] spatial span deficits (11% of the variance) Neurological subtle signs could be a useful screening tool for early identification of working memory difficulties

20 Future prospects These findings further emphasize the importance of delayed neural network development in children and adolescents with ADHD Important to further elucidate the key neural networks involved and the associated key candidate genes implicated Further evaluation of working memory training and the inclusion of occupational therapy to traditional evidence based psychosocial interventions Neurological subtle signs may also be a useful marker to assess the effectiveness of stimulant medication Important to conduct randomized control trials to see if neurological subtle signs are effective in identifying children and young people s response to stimulant medication

Biological Risk Factors

Biological Risk Factors Ms Angelina Crea Provisional Psychologist Academic Child Psychiatry Unit Royal Children s Hospital Professor Alasdair Vance Head Academic Child Psychiatry Department of Paediatrics