Examination of the Dynamic Relationships of Sleep, Physical Activity, and Circadian Rhythmicity With Neurobehavioral Heterogeneity in ADHD

Overview

Attention deficit/hyperactivity disorder (ADHD) can present differently in individuals, with some individuals having difficulty with attentional control, hyperactivity, impulsivity, emotion dysregulation, and/or neurobehavioral functioning. The factors contributing to these different presentations remain unclear, but altered patterns of physical activity, sleep, and circadian rest/activity rhythms may play a key role. The goal of this study is to leverage wearable technology (i.e., a wristband) to investigate the relationships between physical activity during the day, sleep patterns and disturbances, and 24-hour circadian rest/activity rhythms with differences in ADHD symptoms, emotion dysregulation, and related brain and behavioral features of attention-deficit/hyperactivity disorder (ADHD). The investigators hope this study will help improve assessment and intervention for individuals with ADHD by understanding how these factors relate to ADHD symptom expression and associated brain differences in ADHD. Participants taking stimulant medication must withhold stimulant medication 24 hours before their research appointment and the morning of their research appointment. Stimulant medication may be restarted after the appointment is complete. Participation in this study will require children to complete an initial 2-hour research appointment, two (2) weeks of activity and sleep monitoring at home using a wearable wristband and answering questions sent to a smartphone, and a second 4-hour research appointment after the 2-week period. During the first research appointment, children will complete a cognitive assessment and a practice magnetic resonance imaging (MRI) scan. Parents/legal guardians will participate in the 30-45-minute sleep device training session with one of the research staff. During the two weeks of activity/sleep monitoring at home, parents and children will answer questions about their sleep routine, ADHD symptoms, and emotional responding each morning and evening. Parents will be asked to install a questionnaire application on their smartphone. A prompt will be sent to their smartphone multiple times per day reminding parents to complete the brief assessment. After the 2-week period, children will complete a 4-hour research appointment. During this research appointment, children will complete a 60-minute MRI scan and computer-based activities that assess cognitive skills, reward-based decision-making, and frustration tolerance. At the end of the research appointment, children will return the device to our research team. Parents may delete the questionnaire application from their phone at the end of the research appointment. Participation will also require parents/legal guardians to complete questionnaires about their child. Questionnaires will be provided to the primary caregiver by email or at the beginning of their child's first research appointment. Parents agree to complete and return the questionnaires within one month of their child's research appointment. Parents may be provided with additional questionnaires to give to their child's primary schoolteacher. This information is collected to better understand children's abilities, behavior, strengths, and weaknesses. There are minimal risks associated with this study. Risks include fatigue, boredom, and mild discomfort. There is no cost to participating in this study. There is no direct benefit to participants for participating in this study.

Interventions

• Behavioral Go/No-Go Task
  A computerized test in which participants are presented with red and green spaceship stimuli. They are told to press the spacebar in response to green spaceships (80% of trials) and withhold their response to red spaceships (20% of trials).
• Behavioral Delay discounting task
  Participants make decisions between smaller, immediate rewards and larger, delayed rewards. The amount of the immediate reward and delay time are manipulated to identify individual delay discounting curves, or how the reward value decreases as a function of delay.
• Behavioral Mirror Tracing Persistence Task
  A computerized test in which participants trace a star line drawing with a computer cursor using a trackpad with reversed directional controls. There are increasing levels of difficulty with participants being told they could quit the task during the very hard third star that they try to trace.
• Behavioral Spatial Span
  Participants are instructed to attend to a computer screen to keep track of the order in which a happy face stimuli appears in a sequence of boxes positioned on the screen. They are presented with 2 trials at each level of difficulty, increasing from 2 stimuli by 1 additional stimuli per trial until they respond incorrectly for both trials within a level. There are two task conditions, forward and backward span, with the participant responding in the reverse order that the stimuli were presented
• Behavioral Stop Signal Task
  A computerized test in which participants are presented with a right or left facing arrow and are instructed to press a response button indicating the direction of the arrow. On 25% of the trials, an auditory beep is presented (i.e., stop signal) following the onset of the arrow (i.e., go signal) and participants are instructed to withhold their response when they hear the stop signal.
• Behavioral Flanker task
  A computerized test in which a group of arrows are presented on the screen with the central arrow (target) pointing in the same/opposite direction as the 4 surrounding arrows (flankers). Participants are instructed to respond as quickly and accurately as possible to the central target arrow.

Primary outcome measures

• Total Activity Counts (TAC) [Time frame: Two-week, real-time period of at-home activity monitoring]
• Children's Sleep Health Questionnaire (CSHQ) Total Score [Time frame: Within six months prior to the first research appointment.]
• ADHD-related Symptoms [Time frame: Within six months prior to the first research appointment.]
• Mean Fractional Anisotropy (FA) [Time frame: Completed during the MRI scan on Day 15]
• Stop Signal Reaction Time [Time frame: Task will be completed on Day 15]
• Congruency Effect on Reaction Time [Time frame: Task will be completed on Day 15]
• Commission Errors [Time frame: Task will be completed on Day 15]
• Backward Span Accuracy [Time frame: Task will be completed on Day 15]
• Delay Discounting Area Over the Curve (AOC) [Time frame: Task will be completed on Day 15]
• Mirror Tracing Persistance Task Latency to Quit [Time frame: Task will be completed on Day 15]

Eligibility criteria

ADHD Clinical Group. Meet criteria for attention deficit/hyperactivity disorder (ADHD) according to DSM-5 criteria.

Exclusion criteria

Prematurity Prenatal exposure to alcohol or other substances Traumatic brain injury Co-occurring neurodevelopmental disorders (e.g., autism spectrum disorder, intellectual disability) Anxiety/mood disorders Active psychosis Bipolar disorder Conduct disorder Currently taking longer acting psychotropic medications that cannot be discontinued the day before research appointments

Control Group. Does not meet criteria for psychological or neuropsychological disorders Does not meet criteria for intellectual disability Does not meet criteria for a learning disorder

Exclusion criteria

Prematurity Prenatal exposure to alcohol or other substances Traumatic brain injury Currently taking medications that cannot be discontinued the day before research appointments

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Basic science

Study locations

United States · 2 centers

• Hugo W. Moser Research Institute at Kennedy Krieger — Baltimore
• Kennedy Krieger Institute — Baltimore

Publications

• Sibley MH, Arnold LE, Swanson JM, Hechtman LT, Kennedy TM, Owens E, Molina BSG, Jensen PS, Hinshaw SP, Roy A, Chronis-Tuscano A, Newcorn JH, Rohde LA; MTA Cooperative Group. Variable Patterns of Remission From ADHD in the Multimodal Treatment Study of ADHD. Am J Psychiatry. 2022 Feb;179(2):142-151. doi: 10.1176/appi.ajp.2021.21010032. Epub 2021 Aug 13. PMID 34384227
• Mordre M, Groholt B, Kjelsberg E, Sandstad B, Myhre AM. The impact of ADHD and conduct disorder in childhood on adult delinquency: a 30 years follow-up study using official crime records. BMC Psychiatry. 2011 Apr 11;11:57. doi: 10.1186/1471-244X-11-57. PMID 21481227
• Fredriksen M, Dahl AA, Martinsen EW, Klungsoyr O, Faraone SV, Peleikis DE. Childhood and persistent ADHD symptoms associated with educational failure and long-term occupational disability in adult ADHD. Atten Defic Hyperact Disord. 2014 Jun;6(2):87-99. doi: 10.1007/s12402-014-0126-1. Epub 2014 Feb 5. PMID 24497125
• Faraone SV, Banaschewski T, Coghill D, Zheng Y, Biederman J, Bellgrove MA, Newcorn JH, Gignac M, Al Saud NM, Manor I, Rohde LA, Yang L, Cortese S, Almagor D, Stein MA, Albatti TH, Aljoudi HF, Alqahtani MMJ, Asherson P, Atwoli L, Bolte S, Buitelaar JK, Crunelle CL, Daley D, Dalsgaard S, Dopfner M, Espinet S, Fitzgerald M, Franke B, Gerlach M, Haavik J, Hartman CA, Hartung CM, Hinshaw SP, Hoekstra P PMID 33549739
• Hvolby A. Associations of sleep disturbance with ADHD: implications for treatment. Atten Defic Hyperact Disord. 2015 Mar;7(1):1-18. doi: 10.1007/s12402-014-0151-0. Epub 2014 Aug 17. PMID 25127644
• Buitelaar J, Bolte S, Brandeis D, Caye A, Christmann N, Cortese S, Coghill D, Faraone SV, Franke B, Gleitz M, Greven CU, Kooij S, Leffa DT, Rommelse N, Newcorn JH, Polanczyk GV, Rohde LA, Simonoff E, Stein M, Vitiello B, Yazgan Y, Roesler M, Doepfner M, Banaschewski T. Toward Precision Medicine in ADHD. Front Behav Neurosci. 2022 Jul 6;16:900981. doi: 10.3389/fnbeh.2022.900981. eCollection 2022. PMID 35874653

Identifiers

NCT: NCT06810180 · IRB00478295

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗