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. • Di ff erent 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 of 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

Kinarm Kinarm with visual display and seated participant of the participant’s arm(s). of the participant’s arm(s).

Task parameters • Dependent variables divided into four categories: • Inhibition variables : distractor hits, distractor proportion, object 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 overlap, hand transition, or hand bias (in terms of movement area, speed, hitting targets, or misses).

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 Inhibition Controls Tic Between- tics-without- p-value tics-plus- p-value Between- variables (adjusted disorders groups F- ADHD versus ADHD versus groups F- mean and group stat and p- controls controls stat and p- 95% CI) value value 0.000 23.56% Distractor hits 15.61% 23.00% F=36.063; 22.71% 0.000 F=18.513; p=0.000 p=0.000 (14.28, (20.98, (19.81, 25.61) (20.66, 16.95) 25.02) 26.46) 0.000 16.49% Distractor 0.000 F=20.339; 11.31% 16.21% F=40.323; 15.99% proportion p= 0.000 p=0.000 (10.48, (14.94, (14.17, 17.81) (14.68, 12.15) 17.47) 18.31) 0.032 1.83 Object 1.97 1.85 F=12.752; 1.87 (1.79, 0.002 F=6.202; processing p=0.000 p=0.002 (1.93, (1.79, 1.95) (1.75, rate 2.00) 1.90) 1.91)

Results: main findings • In addition to striking more distractors, patients with comorbid ADHD di ff ered 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).

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 Task-level Controls Tic Between- tics-without- p-value tics-plus- p-value Between- variables (adjusted disorders groups F- ADHD versus ADHD versus groups F- mean group stat and controls controls stat and and 95% p-value p-value CI) 0.157 119.74 Target hits 126.86 120.82 F=6.848; 122.66 0.018 F=3.341; p=0.010 (117.20, p=0.037 (124.35, (117.02, (114.28, 128.13) 129.36) 124.61) 125.21) Kinematic Controls Tic Between- tics- p-value tics- p-value Between- variables (adjusted disorders groups F- without- versus plus- versus groups F- mean and group stat and ADHD controls ADHD controls stat and 95% CI) p-value p-value 0.342 0.216 Movement F=6.439; 0.193 m/s 0.001 F=5.317; 0.183 0.203 speed p=0.012 (0.175, p=0.006 m/s m/s m/s dominant 0.211) (0.175, (0.190, (0.198, 0.192) 0.216) 0.234) 0.326 0.192 Movement 0.173 m/s 0.186 m/s 3F=.246; 0.182 m/s 0.047 F=2.204; speed non- (0.165, (0.174, p=0.073 (0.166, p=0.113 m/s dominant 0.181) 0.198) 0.199) (0.175, 0.209)

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 outside age-predicted norms.

1. object 1. movement speed processing (dominant) 1. hand selection 1. target hits rate 2. movement speed overlap 2. miss bias 2. distractor (non-dominant) 2. hand transition 3. median error proportion 3. movement area 3. movement area bias 3. distractor hits (dominant) 4. hand bias of hits 4. movement area 5. hand speed bias (non-dominant)

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 (a ff ecting 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 di ff erent components of inhibitory control.

Challenges • Clinical relevance of hitting distractors remains to be demonstrated. Our task di ff ers 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