Joseph_Biederman_AIA_rX8AEq.png.jpgThis blog addresses the relationship between executive function deficits in general and working memory (WM) deficits in particular and attention-deficit/hyperactivity disorder (ADHD). Although some neuropsychological models of ADHD have proposed that ADHD arises from deficits in executive functions, accumulating clinical evidence show that it afflict some but not all individuals with ADHD and suggests that ADHD and executive function deficits represent separate clinical condition. Because executive functions refer to a wide and diverse group of high order mental functions, one approach to evaluate this important issue is to focus on one prominent facet of executive functions, mainly working memory. Working memory (WM) refers to a key brain system that provides temporary storage and manipulation of information essential for adequate cognitive functioning. It focuses attention, inhibits irrelevant stimuli, recognizes priority patterns and hierarchies and selects the goals that are best suited to solving a problem. Since these cognitive processes are critical for learning, their impairment can lead to deficits in functioning including social and educational dysfunction, low educational achievement and can have a serious impact on educational success. To address this issue we examined referred youth with and without ADHD with and with without WM deficits in functional, social and academic outcomes. We used Resting State FMRI imaging to examine whether the neural circuits subserving WM deficits overlap with those of ADHD. We investigated this issue in preclinical studies where we examined spatial WM and dopamine receptor activity in rodents. In human studies, we examined whether the most standard treatment for ADHD has a different effect on measures of WM and ADHD. This body of research provides evidence for a clinical, pharmacological and neurobiological dissociation between ADHD and WM deficits. Our preclinical findings demonstrate that the magnitude of improvement in WM produced by the D4 receptor agonist is significantly greater than that produced by methylphenidate. Our human treatment study with methylphenidate provide evidence for very different effects for ADHD and WM deficits Our clinical studies show that significantly more youth with ADHD had WM deficits than controls (31.9% vs. 13.7%) and their presence is significantly and specifically associated with academic failure. In our imaging study, we found that brain activations to a WM test were different in subjects with ADHD with associated WM deficits compared to controls and ADHD subjects without WM deficits. This body of work indicates that WM deficits afflict a minority of subjects with ADHD and when present they significantly and selectively increase the risk for academic dysfunction in subjects with ADHD, they have separate neural underpinning, and respond differently to treatments for ADHD. Screening for WM deficits may help identify individuals with ADHD at high risk for academic dysfunction.
 

References
K. P. LEE, N. PINEDA, T. BRUNE, K. PATEL, A. GANNON, T. J. SPENCER, J. BIEDEMAN, P. G. BHIDE, J. ZHU. Hyperactivity and working memory deficits induced by prenatal nicotine exposure are associated with dopamine D1 and D4 receptor dysfunction. Society for Neuroscience Annual Meeting, Washington, DC, November, 2014.
Fried R, Chan J, Feinberg L, Pope A, Woodworth KY, Faraone SV, et al. Clinical correlates of working memory deficits in youth with and without ADHD: A controlled study. Journal of clinical and experimental neuropsychology. 2016;38(5):487-96.

Mattfeld AT, Whitfield-Gabrieli S, Biederman J, Spencer T, Brown A, Fried R, et al. Dissociation of working memory impairments and attention-deficit/hyperactivity disorder in the brain. NeuroImage Clinical. 2016;10:274-82.
Biederman J, Chan J, Spencer TJ, Woodworth KY, Kenworthy T, Fried R, Bhide P, Faraone SV. Evidence of a pharmacological dissociation between the robust effects of methylphenidate on ADHD symptoms and weaker effects on working memory. Journal of Brain Sciences. 2015; 1(2): 43-53.

Joseph Biederman, MD

About Joseph Biederman, MD

Joseph L. Biederman, MD is Chief of the Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD at the Massachusetts General Hospital, professor of psychiatry at Harvard Medical School.