Toward an endophenotype for ADHD: Exploring the duration mismatch negativity in drug-free children with ADHD

Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent disorders in children that is considered to affect early stages of information processes. Inefficient processing of temporal information, which is a vital auditory processing skill suggests itself as a potential candidate for investigating ADHD deficits. The Research Domain Criteria (RDoC), a neuroscience-based research framework, has been introduced to study mental illness without relying on pre-established diagnostic categories. In this regard, Mismatch Negativity (MMN) has been considered an ideal electrophysiological marker for investigating ADHD deficits. This study investigates alterations in the amplitude and latency of the MMN component in response to changes in the duration and Inter-Stimulus Interval (ISI) of basic sound stimuli within an oddball task. The MMN paradigm was employed to examine duration deviations in ADHD (n = 25, 84% male, mean age: 7.3 years, SD = 2.01) compared to Control group of typically developing (TD) children (n = 25, 72% male, mean age: 7.2 years, SD = 1.92). Participants with ADHD were introduced from an accredited psychiatrist. TD children were recruited from social media and online forms. Both groups were matched in terms of gender, age and IQ. The psychological tests conducted in this study included Conners' Parent Rating Scale (CPRS), Gilliam Autism Rating Scale|Third Edition (Gars3), Sensory profile questionnaire and Edinburgh Handedness inventory. Our findings revealed reduced MMN amplitudes in response to two blocks of duration and ISI-based deviations in ADHD children. To elaborate in greater detail, at Fz, in Duration and ISI block, respectively, the ADHD group showed an amplitude of -1.2097 ± 0.2938 and -0.8553 ± 0.4423, while the normal group showed an amplitude of -1.8325 ± 0.3689 and -2.0855 ± 0.3802. Additionally, at Cz, the ADHD group exhibited a shorter amplitude (-1.2515 ± 0.3261 and -0.9367 ± 0.3432) compared to the normal group (-2.1319 ± 0.4445 and -2.7561 ± 0.4883), in the duration and ISI blocks, respectively. Furthermore, children with ADHD display longer MMN latencies in both experimental blocks, suggesting atypical responses. To provide more detail, at Fz, the ADHD group displayed MMN latencies of 239.68 ± 5.059 and 226.88 ± 4.885 in the Duration and ISI blocks, respectively, whereas the normal group showed MMN latencies of 228.56 ± 6.584 and 213.56 ± 4.153. Similarly, at Cz, the ADHD group exhibited longer MMN latencies (234.40 ± 5.741 and 231.44 ± 5.464) compared to the normal group (227.52 ± 6.710 and 218.00 ± 5.261) in the Duration and ISI blocks, respectively. Our findings were interpreted in the context of the internal clock model, which involves the pace of an internal pacemaker regulated by dopamine (DA) levels. The convergence of MMN and auditory timing abnormalities within the RDoC framework suggests their potential as endophenotypes for ADHD, highlighting the significance of sensory processing in understanding the disorder.