The Neural Basis of Low-Dose versus Normal-Dose Psychostimulants on Executive Functions in Youth with Attention-Deficit / Hyperactivity Disorder: A Randomised Controlled Trial
Our work integrates behavioural, neuroanatomical, and genetic approaches to study cognitive abilities (called ‘executive functions’) dependent on prefrontal cortex (PFC) from their earliest beginnings throughout the lifespan in clinical and "normal" populations. Our methods include: neurocognitive testing, even of infants; functional neuroimaging (fMRI); preschool and school interventions; and molecular genetic analyses. We study the neural bases, genetic and neurochemical modulation, modification by the environment of executive functions and how they can become derailed in disorders. We hope our work might aid the understanding, prevention, and treatment of major mental disorders. Our work has already led to worldwide improvements in the treatment of a genetic disorder (PKU) and a developmental disorder (ADHD), thereby improving children's lives. Our research also has educational implications and has affected early education worldwide.
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In traumatized youth, can prefrontal cortex communication with the amygdala be restored by a stress-reduction program (e.g., Niroga’s yoga-based mindfulness program)? Are the benefits of music for improving executive functions (EFs), mood, and quality of life greater when the experience of listening to the music is socially shared? Can the benefits of listening to the spoken word be as great as those of listening to music for EFs, mood, and quality of life? Modeling gonadal hormone and COMT genotype modulation of the effects of mild stress on EFs pharmacologically with low-dose methylphenidate Will individuals be more emotionally invested in EF training if they have a say in shaping the training activity and will that translate into greater EF benefits?
There is a growing body of evidence that early stress such as neglect, maltreatment and other adverse childhood experiences (ACEs) affect the way a children’s brain develops, making them more vulnerable to mental health problems. When these children reach school age, they are more likely to be identified as having learning, behaviour or social problems, and becoming students “at-risk”. The literature suggests that one of the reasons why these children have difficulty in school is that their nervous systems may be geared to prioritize managing fear rather than to processing information. In other words, the lower-order stress response system is given priority over the higher-level functions of processing information and learning, including executive functions. This study was a naturalistic pilot project designed to assess the use of a Neurosequential Model of Therapeutics (NMT) assessment to inform a behaviour plan for elementary school students who have a history of adverse childhood experiences. The study involved two cohorts of four children, ages 6 – 9, who had a history of adverse childhood experiences and had been identified as needing a high level of behavioural support within the mainstream classroom. Over a period of 4 months, one cohort received a trauma-informed behaviour plan based on an NMT assessment, the other cohort received a behaviour plan based on a Functional Behaviour Assessment. Percentage of academic engaged time and heart rate variability were tracked over the course of the intervention. Pre and post measures of executive functions were gathered. For the four students in the NMT cohort, a pre and post NMT metric was produced, as well as a pre- and post NME mini map. Neither of the interventions were demonstrated to be effective, which is most likely due to the complex challenges of the naturalistic setting in the school context. However, some interesting trends were identified that would suggest that further research would be warranted.
Prefrontal cortex (PFC)-dependent executive functions (EFs) are critical for reasoning, problem-solving, self-control and planning. The PFC dopamine (DA) level has been demonstrated to modulate EFs in an inverted U-shaped curve, where an intermediate level of DA is optimal. Unlike in other brain regions, PFC DA systems: 1) relies highly on the catechol-O-methyltransferase (COMT) enzyme for clearing released DA; and 2) can be activated even by mild stress. Estradiol (E2) has been shown to down-regulate COMT gene transcription, causing the activity of COMT enzyme to be ~30% less in women than in men. Animal studies have repeatedly shown that stress facilitates cognitive functions dependent on the hippocampus and / or PFC in males, but impairs them in females. Therefore, based on Diamond’s hypothesis that baseline PFC DA levels are higher and closer to the optimal level in women during menstrual phases when their circulating E2 are elevated, than in men, we predicted that mild stress would facilitate EF performance in men but impair it in women when their circulating E2 levels are high. In a crossover design, healthy young adults (both men and women), all COMT Val¹⁵⁸Met heterozygotes, were each tested twice (once with social-evaluative stress and once without, order counterbalanced) on five EF tasks which tapped on the core EFs of inhibitory control, working memory and cognitive flexibility, and one higher-level EF, reasoning. Women were randomly assigned to the low-E2 (F-L) group or high-E2 (F-H) group. Women in the F-L group were tested during the early follicular phase (low E2 level). Women in the F-H group were tested during the midluteal phase (high E2 level). Our social-evaluative procedure was showed to succeed in inducing physiological and subjective stress responses and significantly impaired the performance of the F-H group on one index of inhibitory control, whereas the performance of the M and F-L groups showed a trend towards enhancement. Similar trends (M and F-L: stress-induced enhancement; F-H: stress-induced impairments) were found for some other indices in the first two tasks. These results emphasized that the ways of improving EFs need to be considered in a sex-specific and hormone-dependent manner.
The following is a selection of grants for which the faculty member was principal investigator or co-investigator. Currently, the list only covers Canadian Tri-Agency grants from years 2013/14-2016/17 and excludes grants from any other agencies.
Social Neuroscience of Human-Animal Interaction
Executive Function in Preschool-age Children: Integrating Measurement, Neurodevelopment and Translational Research
Annals of Sports Medicine and Researc
Journal of Neuroscience
Journal of Neuroscience