Computerized cognitive training in attention-deficit/hyperactivity disorder (ADHD): a meta-analysis of randomized controlled trials with blinded and objective outcomes

Abstract

This meta-analysis investigated the effects of computerized cognitive training (CCT) on clinical, neuropsychological and academic outcomes in individuals with attention-deficit/hyperactivity disorder (ADHD). The authors searched PubMed, Ovid, and Web of Science until 19th January 2022 for parallel-arm randomized controlled trials (RCTs) using CCT in individuals with ADHD. Random-effects meta-analyses pooled standardized mean differences (SMD) between CCT and comparator arms. RCT quality was assessed with the Cochrane Risk of Bias 2.0 tool (PROSPERO: CRD42021229279). Thirty-six RCTs were meta-analysed, 17 of which evaluated working memory training (WMT). Analysis of outcomes measured immediately post-treatment and judged to be “probably blinded” (PBLIND; trial n = 14) showed no effect on ADHD total (SMD = 0.12, 95%CI[−0.01 to −0.25]) or hyperactivity/impulsivity symptoms (SMD = 0.12, 95%[−0.03 to−0.28]). These findings remained when analyses were restricted to trials (n: 5–13) with children/adolescents, low medication exposure, semi-active controls, or WMT or multiple process training. There was a small improvement in inattention symptoms (SMD = 0.17, 95%CI[0.02–0.31]), which remained when trials were restricted to semi-active controls (SMD = 0.20, 95%CI[0.04–0.37]), and doubled in size when assessed in the intervention delivery setting (n = 5, SMD = 0.40, 95%CI[0.09–0.71]), suggesting a setting-specific effect. CCT improved WM (verbal: n = 15, SMD = 0.38, 95%CI[0.24–0.53]; visual-spatial: n = 9, SMD = 0.49, 95%CI[0.31–0.67]), but not other neuropsychological (e.g., attention, inhibition) or academic outcomes (e.g., reading, arithmetic; analysed n: 5–15). Longer-term improvement (at ~6-months) in verbal WM, reading comprehension, and ratings of executive functions were observed but relevant trials were limited in number (n: 5–7). There was no evidence that multi-process training was superior to working memory training. In sum, CCT led to shorter-term improvements in WM, with some evidence that verbal WM effects persisted in the longer-term. Clinical effects were limited to small, setting specific, short-term effects on inattention symptoms.

Theobromine improves hyperactivity, inattention, and working memory via modulation of dopaminergic neural function in the frontal cortex of spontaneously hypertensive rats

“…While various mechanisms have been proposed for the development of ADHD, dysfunction in the dopamine system within the PFC stands out as one of the most supported hypotheses. [1][2][3]5 In this study, TB demonstrated an increase in dopaminergic neural transmission factors, including dopamine, TH, DRD2, and DRD4, within the PFC. These changes are speculated to have contributed to an improvement in ADHD-like behavior in SHR.…”

“…ADHD is a complex disorder influenced by various genetic and environmental factors. 1,2 Accumulating evidence indicates…”

“…[3][4][5][6] First-line treatments for ADHD patients typically involve psychostimulants such as methylphenidate and amphetamine. 2 These medications enhance attention and executive functions by modulating dopaminergic neural transmission in the PFC. However, some patients may experience adverse effects, including anorexia, weight loss, and headache, leading to discontinuation of treatment.…”

“…Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder, diagnosed in approximately 5% of children and adolescents and 2.5% of adults. 1,2 Beyond the common symptoms of inattention, hyperactivity, and impulsivity, individuals with ADHD frequently exhibit working memory impairment. 2,3 While the etiology of ADHD remains unclear, deficits in the dopaminergic neural system within the prefrontal cortex (PFC) may contribute to the disorder.…”

“…1,2 Beyond the common symptoms of inattention, hyperactivity, and impulsivity, individuals with ADHD frequently exhibit working memory impairment. 2,3 While the etiology of ADHD remains unclear, deficits in the dopaminergic neural system within the prefrontal cortex (PFC) may contribute to the disorder. 3–6 First-line treatments for ADHD patients typically involve psychostimulants such as methylphenidate and amphetamine.…”