The randomized controlled clinical trial showed that the KAD_SCL_01 significantly improved performance on the primary outcome measure, an objective measure of inattention and impulsivity (CPT-C), in pediatric patients with ADHD compared with the control group. Across the range of secondary outcomes, additional inattentive and impulsivity scores in perseverations (CPT-P) and detectability (CPT-d’) in the CPT-C showed significant greater improvements in the experimental group from pre-intervention to post-intervention. Furthermore, other cognitive secondary measures, including the ability to inhibit automatic responses in favor of novel responses and the ability to switch between response types, cognitive flexibility and spatial working memory showed significant improvements in the experimental group compared to the controls in the post intervention assessment. In the other cognitive and clinical measures, the effect of KAD_SCL_01 from pre intervention to post intervention were not different from the control group.
The current study findings of improved attention and impulsivity (via CPT-3) following treatment with KAD_SCL_01 are consistent with positive results reported in previous studies (He et al., 2023). As a digital cognitive treatment, KAD_SCL_01 could address several challenges faced by traditional interventions. First, its risk–benefit profile is favorable, none of the patients assigned to the experimental group had AEs, compared with rates of 40–60% in trials of commonly used stimulant medications59. Second, the digital nature of this intervention could reduce barriers to access that are inherent in other forms of behavioral or nonpharmacological interventions60. Digital interventions have been cited as possible ways to improve otherwise poor access to mental health services, reducing waiting lists and providing an earlier neuropsychological recovery21.
The primary outcome measure for this trial, the CPT-3, differs from most pharmacological efficacy trials for ADHD, which typically use parent-rated or clinician-rated symptom measures. The selection of the CPT-3 was based on several factors. First, because the digital tool was designed specifically to target inattention, sustained attention, impulsivity, and vigilance, we sought an outcome that would most precisely and validly index these processes. The CPT-3 is a tool for the objective assessment of attention and inhibitory control as part of an ADHD diagnosis or for monitoring intervention outcomes and has been widely used in both clinical practice and research studies. Second, the CPT-C measures cognitive functions that are relevant to the clinical presentation of ADHD, and attention performance metrics such as commissions, omission, perseverations, and reaction times metrics are well characterized indicators of ADHD-relevant cognitive processes and are associated with clinically relevant outcomes including academic behavior and inattention and social problems61.
In the current study, there were no differences between the experimental and the control condition on the other secondary measures, and several factors might explain these findings. First, it is possible that parent or clinician reported outcomes (i.e., EDAH and BRIEF) are not sensitive to the effects of the KAD_SCL_01. In other words, the shown effects of the intervention on cognitive processes may not be as readily observable by parents and clinicians. The clinical implications of this possibility will be important to explore in future studies. Second, expectations of efficacy have been shown to moderate intervention effects in general, and for digital interventions62. In our study, parents of patients in both groups believed that their child received a novel intervention for ADHD; thus, the expectation of intervention effect can be assumed for both interventions and may partially explain improvements in both groups. This design feature is different from most pharmacological studies in which patients and their caregivers are aware of a non-active, placebo condition. Finally, specific mechanisms common to KAD_SCL_01 and the control condition may have resulted in improvements in both groups. Both interventions required continued perseverance, sometimes in the face of failure, and may have trained coping and reappraisal skills or even increased the sense of self-efficacy and mastery63. Thus, any intervention that requires the patient to engage in a regular, structured setting that may include repeated failure or repetitiveness can be seen as a potential intervention for ADHD.
In the magnetoencephalography analysis, we investigated the neurophysiological basis of improvements in ADHD performance after a cognitive training intervention. The findings revealed a positive association between changes in neuropsychological functions and electrophysiological patterns, providing biological evidence of neuromaturation10. Specifically, improvements in attention and inhibitory control were associated with a reduction in power within the alpha and beta frequency bands for both, KAD_SCL_01 and control treatments.
Regarding impulsivity domain, the neurophysiological correlates were predominantly observed in parietal and temporal cortex, related to voluntary sensorimotor control and visuospatial processing. On the other hand, in the case of inattentiveness domain, the correlated brain regions were associated with visuospatial imagery, episodic memory retrieval, and self-processing operations.
An important finding from this study was that digital cognitive stimulation driven by artificial intelligence (AI) appears to enhance neurocognitive maturation, as indicated by the stronger associations between brain activation and cognitive improvements observed in the experimental group. Particularly noteworthy is the impact on impulsivity: ADHD patients who underwent KAD_SCL_01 treatment demonstrated that greater improvements in inhibitory control were linked to a more substantial reduction in electrophysiological activity within the alpha and beta frequencies. Interestingly, it has been reported that these findings are further supported by clinical outcomes in EDAH-H, which exhibited a reduction in parents’ reported hyperactivity symptomatology associated with decreases in power across all cortex areas.
These results are in line with several previous studies on the electrophysiological mechanisms of cognitive training in ADHD43,44,64,65. In consequence, reductions in relative power induced by the digital cognitive treatment might be reflecting an increase in the efficiency of neural networks involved in inhibitory control, involving a process of neuroplasticity through long term potentiation66. Finally, responder analyses showed that KAD_SCL_01 intervention exhibited significant reductions in the main outcome of commission scores CPT-3, suggesting that the digital cognitive stimulation program may have a positive behaviorally effect on the disorder.
Limitations and future studies
The current study has several important limitations. First, the sample size was small because the first inclusion criteria required that patients had an ADHD-C diagnosis. Second, children could not be taking medication for ADHD during the trial and could not have significant psychiatric comorbidity. Therefore, it is unclear if these findings will generalize to the broader population of patients with ADHD who have comorbid conditions or patients taking medication. Third, the study evaluated a 12-weeks intervention period with approximately 15-min per 3-days sessions. It is unclear if the benefits in attentional functioning might have been observed with a different dosing schedule. Additional studies with different intervention periods are needed, also including durability of effects 1 month after the intervention. In addition, studies investigating whether the intervention has effects in children currently treated with stimulant medication, which will help address questions of generalizability.
Given these limitations, the transfer of benefit of the KAD_SCL_01 intervention to real-world settings and the full clinical meaningfulness of the findings, as well as the mechanisms underlying these effects, should be explored in further studies.