Inhibitory control deficits in children with Tourette syndrome - - PowerPoint PPT Presentation

Inhibitory control deficits in children with Tourette syndrome revealed by object-hit-and-avoid task

Nicholas Cothros Clinical and research fellow, adult and paediatric movement disorders Fellowship supervisors: Dr. Tamara Pringsheim and Dr. Davide Martino 29 April 2020

Introduction

• Tics manifest as brief and intermittent movements (motor

tics) or sounds (phonic tics), most commonly caused by Tourette syndrome (TS).

• As tics can be voluntarily suppressed, this has motivated

study of inhibitory control in patients with tic disorders.

• Different behavioural tasks used in the study of inhibitory
• control. Varying operational definitions of inhibitory control.
• Studies have yielded mixed results in terms of the degree or

presence of inhibitory control deficits. This may reflect variations in study tasks.

A novel approach

• Novel methods of studying inhibitory control may add new information,

particularly with a task that:

• requires multiple aspects of skilled action (e.g. goal selection, action

selection, action execution) and may be more sensitive to performance abnormalities;

• entails motor decision-making more akin to time-sensitive demands
• f everyday activities; and
• requires considerable reallocation of attention, to contrast between

those with and without comorbid ADHD.

• Our study used a robotic exoskeleton (Kinarm) and a bimanual task

involving rapid motor selection and inhibitory control.

Methods

• Sixty-four children diagnosed with TS or chronic motor tic

disorder (mean age 12.4 years; range 7.5-18.5) recruited from Calgary Tourette and Pediatric Movement Disorders Clinic.

• Task: object-hit-and-avoid. Two target objects presented

first, followed by presentation of targets and distractors moving across the screen simultaneously. Goal: hit only the targets while avoiding distractors, using either hand freely.

• Performance compared to previously assembled, normative

database pertaining to 146 healthy control children on same task (mean age 13.0 years; 6.1-19.9).

Targets presented at task outset Object-hit-and-avoid task

• f the participant’s arm(s).
• f the participant’s arm(s).

Kinarm Kinarm with visual display and seated participant

Task parameters

• Dependent variables divided into four categories:
• Inhibition variables: distractor hits, distractor proportion,
• bject processing rate.
• Task-level variables: target hits, median error, miss bias.
• Kinematic variables: movement speed and movement

area (for both dominant and non-dominant sides).

• Inter-limb variables: hand selection overlap, hand

transition, and hand bias (in terms of hits, hand speed, and movement area).

Analyses

• Analysis of covariance (ANCOVA) for each of the

dependent variables, with age as covariate, and group (tic disorders group versus controls) as the independent variable.

• Each ANCOVA was repeated such that the tic disorders

group was split into two groups: those with and without comorbid ADHD.

• Planned contrasts between each of these two patient

groups and controls. Post-hoc pairwise comparisons between each possible pair of groups.

Results: main findings

• Main findings: patients with tic disorders hit a greater

number distractors than controls.

• Those without comorbid ADHD did not show a

decrease in performance in terms of correctly striking targets.

• This tendency to hit distractors occurred without

statistically significant changes in motor behaviour, such as movement speed, movement area, hand selection

• verlap, hand transition, or hand bias (in terms of

movement area, speed, hitting targets, or misses).

Inhibition variables Controls (adjusted mean and 95% CI) Tic disorders group Between- groups F- stat and p- value tics-without- ADHD p-value versus controls tics-plus- ADHD p-value versus controls Between- groups F- stat and p- value Distractor hits

15.61%

(14.28, 16.95)

23.00%

(20.98, 25.02) F=36.063; p=0.000

22.71%

(19.81, 25.61) 0.000 23.56% (20.66, 26.46) 0.000 F=18.513; p=0.000 Distractor proportion

11.31%

(10.48, 12.15)

16.21%

(14.94, 17.47) F=40.323; p=0.000

15.99%

(14.17, 17.81) 0.000 16.49% (14.68, 18.31) 0.000 F=20.339; p= 0.000 Object processing rate

1.97

(1.93, 2.00)

1.85

(1.79, 1.90) F=12.752; p=0.000

1.87 (1.79,

1.95) 0.032 1.83 (1.75, 1.91) 0.002 F=6.202; p=0.002 ANCOVAs for inhibition variables: controls vs. patients with tics; and for controls vs. patients, split into two groups (those without ADHD and those with ADHD); and planned contrasts comparing each of the two patient groups to the control group

Results: main findings

• In addition to striking more distractors, patients with

comorbid ADHD differed from controls by striking fewer targets, and:

• greater average speed; larger movement area using

dominant hand;

• greater movement area bias favouring dominant hand;

and a hand transition point further away from midline (greater encroachment of dominant limb into non- dominant side of the workspace).

Task-level variables Controls (adjusted mean and 95% CI) Tic disorders group Between- groups F- stat and p-value tics-without- ADHD p-value versus controls tics-plus- ADHD p-value versus controls Between- groups F- stat and p-value Target hits

126.86

(124.35, 129.36)

120.82

(117.02, 124.61) F=6.848; p=0.010 122.66 (117.20, 128.13) 0.157 119.74 (114.28, 125.21) 0.018 F=3.341; p=0.037 ANCOVAs for task-level and kinematic variables: controls vs. patients with tics; and for controls vs. patients, split into two groups (those without ADHD and those with ADHD); and planned contrasts comparing each of the two patient groups to the control group Kinematic variables Controls (adjusted mean and 95% CI) Tic disorders group Between- groups F- stat and p-value tics- without- ADHD p-value versus controls tics- plus- ADHD p-value versus controls Between- groups F- stat and p-value Movement speed dominant

0.183 m/s

(0.175, 0.192)

0.203 m/s

(0.190, 0.216) F=6.439; p=0.012 0.193 m/s (0.175, 0.211) 0.342 0.216

m/s

(0.198, 0.234) 0.001 F=5.317; p=0.006 Movement speed non- dominant 0.173 m/s (0.165, 0.181) 0.186 m/s (0.174, 0.198) 3F=.246; p=0.073 0.182 m/s (0.166, 0.199) 0.326 0.192

m/s

(0.175, 0.209) 0.047 F=2.204; p=0.113

Performance relative to age-predicted norms

• The parameters for which a notably large percentage

performed abnormally were the inhibition variables;

• distractor hits – 20.31%
• distractor proportion – 23.44%
• and task-level variable of median error – 18.75%
• For nearly all remaining task parameters, <10% fell
• utside age-predicted norms.

1.

• bject

processing rate 2. distractor proportion 3. distractor hits 1. target hits 2. miss bias 3. median error 1. movement speed (dominant) 2. movement speed (non-dominant) 3. movement area (dominant) 4. movement area (non-dominant) 1. hand selection

• verlap

2. hand transition 3. movement area bias 4. hand bias of hits 5. hand speed bias

Conclusions

• Patients with tics showed clearly impaired performance,

with a tendency to strike distractors. Over 20% of patients performed below age-predicted norms in this area.

• Patients with tics can be clearly distinguished from

controls in this tendency to hit distractors.

• Patients without comorbid ADHD behaved otherwise

similarly to controls, and therefore worse performance in hitting distractors not an idiosyncrasy of moving limbs unusually.

Conclusions

• For patients with ADHD, attention deficits may have

accounted for reduced attention directed to non- dominant side of workspace (affecting hand transition and movement area bias).

• Greater average speed may be explained by

inattentiveness/hyperactivity, or to ADHD-specific deficits in upper limb function, or compensatory speeding up due to delayed reaction time.

Challenges

• Prevailing research suggests inhibitory control is a

multidimensional construct, comprising early/automatic inhibition, and late/volitional inhibition.

• However, the object-hit-and-avoid task was not

designed to distinguish between these different components of inhibitory control.

Challenges

• Clinical relevance of hitting distractors remains to be
• demonstrated. Our task differs from classical tests of

inhibitory control, limiting direct comparison to several previous studies.

• Correlations with tic severity… Negative correlations

between YGTSS total score and: target hits with non- dominant hand, miss bias, and movement speed with non- dominant hand. Positive correlation with hand transition.

• Consistent with previous studies showing association

between tic suppression and reduced lateralization (i.e reduced inhibition of the non-dominant side).

Summary

• Our study represents a novel approach to the study of

inhibitory control in tic disorders and yields further evidence of deficient inhibitory control in patients with tics.

• Further study is needed to explore the relationship

between Kinarm performance deficits and clinically relevant outcomes.

Acknowledgments

• Dr. Sean Dukelow
• Dr. Rachel Hawe
• Dr. Adam Kirton
• Dr. Davide Martino
• Dr. Alex Medina
• Elaheh Nosratmirshekarlou
• Dr. Tamara Pringsheim
• Funding acknowledgement: Owerko Centre at the Alberta Children’s Hospital

Research Institute

• Bourke, T. C. et al. A robot-based behavioural task to quantify impairments in rapid motor

decisions and actions after stroke. J. Neuroeng. Rehabil. 13, 91 (2016).

• Ganos, C. Tics and Tourette’s: update on pathophysiology and tic control. Curr. Opin. Neurol.

29, 513–518 (2016).

• Ganos, C. et al. Action inhibition in Tourette syndrome. Mov. Disord. 29, 1532–1538 (2014).
• Ganos, C., Rothwell, J. & Haggard, P. Voluntary inhibitory motor control over involuntary tic
• movements. Mov. Disord. 33, 937–946 (2018).
• Hawe, R. L., Kuczynski, A. M., Kirton, A. & Dukelow, S. P. Assessment of bilateral motor skills

and visuospatial attention in children with perinatal stroke using a robotic object hitting task. J.

• Neuroeng. Rehabil. 17, 18 (2020).
• Hotham, E., Haberfield, M., Hillier, S., White, J. M. & Todd, G. Upper limb function in children

with attention-deficit/hyperactivity disorder (ADHD). J. Neural Transm. 125, 713–726 (2018).

• Krakauer, J. W., Hadjiosif, A. M., Xu, J., Wong, A. L. & Haith, A. M. Motor Learning. Compr.
• Physiol. 9, 613–663 (2019).
• Martino, D., Ganos, C. & Pringsheim, T. M. Tourette Syndrome and Chronic Tic Disorders:

The Clinical Spectrum Beyond Tics. Int. Rev. Neurobiol. 134, 1461–1490 (2017).

• Martino, D. et al. Abnormal lateralization of fine motor actions in Tourette syndrome persists

into adulthood. PLoS One 12, e0180812 (2017).

• McCombe Waller, S., Forrester, L., Villagra, F. & Whitall, J. Intracortical inhibition and

facilitation with unilateral dominant, unilateral nondominant and bilateral movement tasks in left- and right-handed adults. J. Neurol. Sci. 269, 96–104 (2008).

• Morand-Beaulieu, S. et al. The puzzling question of inhibitory control in Tourette syndrome: A

meta-analysis. Neurosci. Biobehav. Rev. 80, 240–262 (2017).

• Rawji, V. et al. Impaired automatic but intact volitional inhibition in primary tic disorders. Brain

143, 906–919 (2020).

• Rommelse, N. N. J. et al. Motor control in children with ADHD and non-affected siblings:

deficits most pronounced using the left hand. J. Child Psychol. Psychiatry 48, 1071–1079 (2007).