Effects of Low-dose versus Normal-dose Psychostimulants
on Executive Functions
in Children with ADHD
We hypothesize that the stimulant dose for controlling hyperactivity in patients with attention-deficit hyperactivity disorder (ADHD) is too high for aiding cognition. Most ADHD patients on stimulants are taking a dose targeting behavioural dysregulation (parents base feedback to doctors on the child’s behavior; no one uses cognitive tests to determine dose). We’ll test the prediction that ADHD patients will perform better on tests of attention, working memory, reading & math, when on half their dose.
ADHD is characterized by lower levels of dopamine (DA) in 2 brain regions, prefrontal cortex and the striatum. Prefrontal cortex is most linked to ADHD cognitive deficits and the striatum to behavioural problems. At doses most commonly prescribed for ADHD, stimulants primarily act on DA in the striatum. At low doses they work differently, increasing DA specifically in prefrontal cortex.
Eighty ADHD patients, ages 6-18, will be tested on a cognitive battery at UBC Hospital. Half will be tested first on their current stimulant dose and 2 weeks later on half that; half will be tested in the reverse order. Version A of tests will be used in Session 1 and Version B in Session 2. A pharmacy will compound each child’s regular dose and half that in identical capsules. Even the researchers won’t know who is getting which dose when. We’ll also test typically-developing youths not on stimulants to estimate practice effects of doing our tests twice, albeit different versions. Performance will be converted to Z scores for combining results on related measures. Each child will be his own control; we’ll compare performance on that child’s current dose and half that. Each family will receive a report of their child’s performance at both doses.
This study could have a major impact on medical practice and the standard of care for ADHD in Canada and worldwide, and might help many of those with ADHD to think more clearly, more easily pay attention, and make better use of their working memory for reasoning, problem-solving, and planning.
Possible Benefits to Mood, Quality of Life, Memory, and Executive Functions of Beloved Music with or without Social Interaction or Beloved Writings (e.g., Poetry, Stories, Psalms) for Adults Experiencing Mild Cognitive Decline
Music on iPods has been found to tap wells of emotion in older adults with significant cognitive decline, bringing back memories and remarkable cognitive reserve that had been thought lost.
Our goal here is to investigate 2 research questions:
1) Is music special? Might listening to writings that are meaningful to, and treasured by, a person with mild cognitive decline improve that person’s mood, cognition, and quality of life as much as meaningful and treasured music?
No one has looked at whether listening to beloved writings might be beneficial to older adults, much less how its benefits compare to listening to beloved music. We’ll break entirely new ground here. We hypothesize that music IS special and that listening to the spoken word without music won’t be as beneficial as listening to songs.
2) Does interacting with a music therapist together with music improve mood, cognition, and quality of life even more than listening to music alone on a machine?
Social interaction with a caring other and social connection are powerful needs. We predict that listening to music in the context of interacting with a music therapist will yield greater benefits on our dependent measures than listening to music alone on a portable music player.
The Effect on Executive Functions, if any, of one week
of being Active (for normally sedentary university students) and
one week of being Sedentary (for normally active university students)
We had predicted
that one week of exercise would benefit executive functions, but the strongest
effect we are finding is one we had not predicted: One week of refraining
from exercising if you are used to regular exercise results in much worse
Differences in the Effects of Mild Stress on Executive Functions
We hypothesize that
stress reactivity in PFC is different for males and females. We predict
opposite effects of mild stress on executive functions in men and women (at
least when their estradiol levels are high [midluteal phase of the menstrual
cycle].) We predict that mild stress will improve men’s executive functions but
impair women’s executive functions (when their estradiol levels are high).
our hypothesis is correct about why mild stress has opposite
effects on the executive functions of males and females – that (a) mild stress
increases prefrontal cortex (PFC) dopamine levels and (b) males and females
have different baseline levels of dopamine in PFC, then if we increase PFC DA
levels pharmacologically we should be able to mimic the sex difference in the
effect of mild stress on executive functions. We predict that low-dose
methylphenidate (MPH) will mimic the effects of mild stress on executive
functions (because both mild stress and low-dose MPH selectively increase PFC
DA levels). Thus we predict that low-dose MPH will improve men’s
executive functions but impair women’s executive functions (when their
estradiol levels are high).
Role of COMT Genotype in Mediating the Effects of Mild Stress on Executive Functions
We hypothesize that mild stress will have opposite effects on the executive functions of those
homozygous for methionine (Met) and those homozygous for valine (Val) at codon
158 of the catechol-O-methyltransferase (COMT) gene. We predict that
COMT-Vals will show better executive functions when mildly stressed than when
relatively calm, while COMT-Mets will perform better when relatively calm than
when mildly stressed. While studies usually find COMT-Mets show better
executive functions than COMT-Vals, we predict that under conditions of mild
stress, COMT-Vals will show better executive functions than COMT-Mets.
To better understand the underlying mechanism, we are looking at whether we can mimic the effect of mild stress on prefrontal cortex (PFC) pharmacologically by increasing PFC dopamine levels pharmacologically in the absence of stress, thereby reproducing, we hope, the opposing effects of stress on executive functions by COMT genotype. We predict that low-dose methylphenidate will improve executive functions of COMT-Val158 homozygotes but impair executive functions of COMT-Met158 homozygotes.
A Randomized Control Trial of Tools of the Mind in Kindergartens in the Lower Mainland
The BC Ministry of Health and BC Mental Health Foundation have funded the random assignment of Tools of the Mind (Tools) to Kindergartens in Vancouver and Surrey -- the very FIRST introduction of Tools to public schools in Canada.
We are applying for funding to continue our evaluation of outcomes from this. We predict that among children and teachers in Tools classes, we’ll find less stress and stress-related illnesses (such as asthma), longer telomeres (stress reduces telomeres; telomeres help cells stay healthy and help determine how long cells live, and by extension, how healthy we are and how long we live) than in control classes. We predict that children from Tools classes will have better executive functions (especially self-control, attentional focus, and discipline), show more compassion, kindness, and assistance to others, be less likely to bully or exclude others, feel more socially supported and less lonely, have better language and math skills, and greater self-confidence than children from control classes. Conversely, we predict stronger epigenetic signatures of early-life stress and older epigenetic age, and less robust health currently, in control children than those from Tools classes.
Test of the Efficacy of Modified Kangaroo Care by a Non-Relative for Reducing Stress of Infants, Nurses and Parents, and for yielding Health and Executive Function Benefits for Infants in Neonatal Intensive Care
This project looks at whether the social support and loving, physical touch of a non-relative can reduce the stress of an infant in the Neonatal Intensive Care Unit (NICU) and, if so, will thusly reducing a newborn’s stress translate into better executive functions later in life? In particular, can modified Kangaroo-Care (cuddling through a hospital gown instead of skin-to-skin contact) by a non-relative (a volunteer in the NICU) in addition to parental Kangaroo care produce more stress-reduction, health and EF benefits than parental Kangaroo care alone? If our predictions are confirmed, cuddling by volunteers could be taken to scale across many NICUs. This could be an important resource for low-income communities and countries. This study addresses something we can do as a society to help buffer the impact of toxic stress and to help give more children a better start in life.
Plus we are actively collaborating with colleagues on research primarily going on in their
with Tim Oberlander: longitudinal study of the effects on the EFs of children of their mother’s mood (more depressive vs. calmer or happier), whether their mom took SSRIs when she was pregnant with this child, and child’s genotype (on genes that affect serotonin and dopamine
with Dan Skarlicki: Effect of Mindfulness and/or Yoga training on the EFs and Workplace Effectiveness of Business Executives
with Kim Schonert-Reichl: Effect of Mindfulness, Practices of Expressing Gratitude, and
Practices of doing Kind, Thoughtful Deeds for Others on Executive Functions and
Academic Performance of Grade School Children
with Sara Cordes and Ellen Winner: Does a US-Based El Sistema Music Program Improve Executive Functions, Academic Achievement, and Affective Development in Young Children? A Randomized Study
with Catherine Davis, Eduardo Bustamante: A Crossover Randomized-control Trial of an Evidence-based 3-month Exercise Intervention for Children with ADHD
with Sylvain Moreno: Understanding Brain Plasticity and Transfer of Skills Mechanisms (this includes piloting MAX-T software for acquiring EEG signals while a person is moving for better understanding the neural mechanisms underlying cognitive improvements from music training
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