The Relationship Between Emotion Dysregulation and Error Monitoring in Adolescents with ADHD.

Attention-deficit/hyperactivity disorder (ADHD) is emblematic of the limitations of existing diagnostic categories. One potential solution, consistent with the Research Domain Criteria (RDoC) initiative, is to interrogate psychological mechanisms at the behavioral and physiological level together to try and identify meaningful subgroups within existing categories. Such approaches provide a way to revise diagnostic boundaries and clarify individual variation in mechanisms. Here, we illustrate this approach to help resolve heterogeneity in ADHD using a combination of behaviorally-rated temperament measures from the Early Adolescent Temperament Questionnaire; cognitive performance on three difference conditions of an emotional go/no-go task; and electroencephalogram (EEG)-measured variation in multiple stages of error processing, including the error-related negativity (ERN) and positivity (Pe). In a large (N = 342), well-characterized sample of adolescents with ADHD, latent profile analysis identified two ADHD temperament subgroups: 1) emotionally regulated and 2) emotionally dysregulated (with high negative affect). Cognitive and EEG assessment in a subset of 272 adolescents (nADHD = 151) found that the emotionally dysregulated group showed distinct patterns of change in early neural response to errors (ERN) across emotional task conditions as compared to emotionally-regulated ADHD adolescents and typically-developing controls. Both ADHD groups showed blunted later response to errors (Pe) that was stable across emotional task conditions. Overall, neural response patterns identified important differences in how trait and state emotion interact to affect cognitive processing. Results highlight important temperament variation within ADHD that helps clarify its relationship to the ERN, one of the most prominent putative neural biomarkers for psychopathology.

Electroencephalogram aperiodic power spectral slope can be reliably measured and predicts ADHD risk in early development.

The aperiodic exponent of the electroencephalogram (EEG) power spectrum has received growing attention as a physiological marker of neurodevelopmental psychopathology, including attention-deficit/hyperactivity disorder (ADHD). However, its use as a marker of ADHD risk across development, and particularly in very young children, is limited by unknown reliability, difficulty in aligning canonical band-based measures across development periods, and unclear effects of treatment in later development. Here, we investigate the internal consistency of the aperiodic EEG power spectrum slope and its association with ADHD risk in both infants (n = 69, 1-month-old) and adolescents (n = 262, ages 11-17 years). Results confirm good to excellent internal consistency in infancy and adolescence. In infancy, a larger aperiodic exponent was associated with greater family history of ADHD. In contrast, in adolescence, ADHD diagnosis was associated with a smaller aperiodic exponent, but only in children with ADHD who had not received stimulant medication treatment. Results suggest that disruptions in cortical development associated with ADHD risk may be detectable shortly after birth via this approach. Together, findings imply a dynamic developmental shift in which the developmentally normative flattening of the EEG power spectrum is exaggerated in ADHD, potentially reflecting imbalances in cortical excitation and inhibition that could contribute to long-lasting differences in brain connectivity.

More than off-task: Increased freely-moving thought in ADHD.

Off-task thought has been found to occur at high rates and is related to impairment in ADHD. However, off-task thought is heterogenous and it remains unclear which specific dimensions of off-task thought are more prevalent in this disorder. It is therefore important to dissociate different aspects of off-task thought in order to better understand the mechanisms underlying impairment. The current study focused on the dimension of constrained (focused) to freely moving off-task thought. Self-report and neurophysiological measures during a computerized attention tasks provided convergent evidence that individuals with ADHD not only have more off-task thought than those without, but also engaged in a greater proportion of freely moving off-task thought than non-ADHD controls. Overall, this work demonstrated differences in both the quantity and type of off-task thought in adults with ADHD. It provides novel insight into both the phenomenology of off-task thought, as well as potential mechanisms underlying impairment in ADHD.

Behavioral and cognitive correlates of the aperiodic (1/f-like) exponent of the EEG power spectrum in adolescents with and without ADHD.

Efficient information processing facilitates cognition and may be disrupted in a number of neurodevelopmental conditions. And yet, the role of inefficient information processing and its neural underpinnings remains poorly understood. In the current study, we examined the cognitive and behavioral correlates of the aperiodic exponent of the electroencephalogram (EEG) power spectrum, a putative marker of disrupted, inefficient neural communication, in a sample of adolescents with and without ADHD (n = 184 nADHD = 87; Mage = 13.95 years, SD = 1.36). Exponents were calculated via FOOOF (Donoghue et al., 2020a) from EEG data recorded during an 8-minute baseline episode. Reaction time speed and variability, as well as drift diffusion parameters (including the drift rate parameter, a cognitive parameter directly related to inefficient information processing) were calculated. Adolescents with ADHD had smaller aperiodic exponents (a "flattened" EEG power spectrum) relative to their typically-developing peers. After controlling for ADHD, aperiodic exponents were related to reaction time variability and the drift rate parameter, but not in the expected direction. Our findings lend support for the aperiodic exponent as a neural correlate of disrupted information processing, and provide insight into the role of cortical excitation/inhibition imbalance in the pathophysiology of ADHD.

The relationship between alpha asymmetry and ADHD depends on negative affect level and parenting practices.

Atypical frontal alpha asymmetry is associated with the approach/withdrawal and affective processes implicated in many psychiatric disorders. Rightward alpha asymmetry, associated with high approach, is a putative endophenotype for attention deficit/hyperactivity disorder (ADHD). However, findings are inconsistent, likely because of a failure to consider emotional heterogeneity within the ADHD population. In addition, how this putative risk marker interacts with environmental factors known to increase symptom severity, such as parenting practices, has not been examined. The current study examined patterns of alpha asymmetry in a large sample of adolescents with and without ADHD, including the moderating role of negative affect and inconsistent discipline. Resting-state EEG was recorded from 169 well-characterized adolescents (nADHD = 79). Semi-structured clinical interviews and well-validated rating scales were used to create composites for negative affect and inconsistent discipline. The relationship between alpha asymmetry and ADHD diagnosis was moderated by negative affect. Right asymmetry was present only for those with ADHD and low levels of negative affect. In addition, greater right alpha asymmetry predicted severity of ADHD symptoms for those with the disorder, but only in the context of inconsistent parenting practices. Results confirm right alpha asymmetry is a possible endophenotype in ADHD but highlight the need to consider emotional heterogeneity and how biological risk interacts with child environment in order to fully characterize its relationship to disorder liability and severity.

The relationship between early and late event-related potentials and temperament in adolescents with and without ADHD.

Differences in emotional processing are prevalent in adolescents with attention deficit/hyperactivity disorder (ADHD) and are related to clinical impairment, but substantial heterogeneity exists. Within ADHD, some individuals experience difficulty with positive/approach emotions, negative/withdrawal emotions, or both. These problems may reflect differences in emotional reactivity, emotion regulation, or a combination, and the neurophysiological correlates remain unclear. Event-related potentials were collected from 109 adolescents (49 with ADHD) while they completed an emotional go/no-go task with three conditions: happy (positive/approach), fear (negative/withdrawal), and neutral. The P1 and N170 were used as a marker of early emotional processing and the P3b and late positive potential (LPP) were used as markers of later elaborative emotional processing. Emotional response style was assessed with parent and adolescent report on the Early Adolescent Temperament Questionnaire. There were no effects of emotion or group for the P1. Typically-developing adolescents exhibited a larger N170 to emotional vs. neutral faces while adolescents with ADHD showed the opposite pattern. All adolescents exhibited a larger P3b to fearful versus other faces and a larger LPP to emotional vs. non-emotional faces. Within the ADHD group, N170 responses to happy faces predicted parent ratings of positive/approach emotions. Findings highlight the importance of considering within-group heterogeneity when studying clinical populations and help clarify the time-locked neurophysiological correlates of emotion dysregulation.

Increased Early Processing of Task-Irrelevant Auditory Stimuli in Older Adults.

The inhibitory deficit hypothesis of cognitive aging posits that older adults' inability to adequately suppress processing of irrelevant information is a major source of cognitive decline. Prior research has demonstrated that in response to task-irrelevant auditory stimuli there is an age-associated increase in the amplitude of the N1 wave, an ERP marker of early perceptual processing. Here, we tested predictions derived from the inhibitory deficit hypothesis that the age-related increase in N1 would be 1) observed under an auditory-ignore, but not auditory-attend condition, 2) attenuated in individuals with high executive capacity (EC), and 3) augmented by increasing cognitive load of the primary visual task. ERPs were measured in 114 well-matched young, middle-aged, young-old, and old-old adults, designated as having high or average EC based on neuropsychological testing. Under the auditory-ignore (visual-attend) task, participants ignored auditory stimuli and responded to rare target letters under low and high load. Under the auditory-attend task, participants ignored visual stimuli and responded to rare target tones. Results confirmed an age-associated increase in N1 amplitude to auditory stimuli under the auditory-ignore but not auditory-attend task. Contrary to predictions, EC did not modulate the N1 response. The load effect was the opposite of expectation: the N1 to task-irrelevant auditory events was smaller under high load. Finally, older adults did not simply fail to suppress the N1 to auditory stimuli in the task-irrelevant modality; they generated a larger response than to identical stimuli in the task-relevant modality. In summary, several of the study's findings do not fit the inhibitory-deficit hypothesis of cognitive aging, which may need to be refined or supplemented by alternative accounts.

Changes in Neural Activity Underlying Working Memory after Computerized Cognitive Training in Older Adults.

Computerized cognitive training (CCT) may counter the impact of aging on cognition, but both the efficacy and neurocognitive mechanisms underlying CCT remain controversial. In this study, 35 older individuals were randomly assigned to Cogmed adaptive working memory (WM) CCT or an active control CCT, featuring five weeks of five ∼40 min sessions per week. Before and after the 5-week intervention, event-related potentials were measured while subjects completed a visual n-back task with three levels of demand (0-back, 1-back, 2-back). The anterior P3a served as an index of directing attention and the posterior P3b as an index of categorization/WM updating. We hypothesized that adaptive CCT would be associated with decreased P3 amplitude at low WM demand and increased P3 amplitude at high WM demand. The adaptive CCT group exhibited a training-related increase in the amplitude of the anterior P3a and posterior P3b in response to target stimuli across n-back tasks, while subjects in the active control CCT group demonstrated a post-training decrease in the anterior P3a. Performance did not differ between groups or sessions. Larger overall P3 amplitudes were strongly associated with better task performance. Increased post-CCT P3 amplitude correlated with improved task performance; this relationship was especially robust at high task load. Our findings suggest that adaptive WM training was associated with increased orienting of attention, as indexed by the P3a, and the enhancement of categorization/WM updating processes, as indexed by the P3b. Increased P3 amplitude was linked to improved performance; however. there was no direct association between adaptive training and improved performance.

One of the most well-established age-related changes in neural activity disappears after controlling for visual acuity.

Numerous studies using a variety of imaging techniques have reported age-related differences in neural activity while subjects carry out cognitive tasks. Surprisingly little attention has been paid to the potential impact of age-associated changes in sensory acuity on these findings. Studies in the visual modality frequently report that their subjects had "normal or corrected- to-normal vision." However, in most cases, there is no indication that visual acuity was actually measured, and it is likely that the investigators relied largely on self-reported visual status of subjects, which is often inaccurate. We investigated whether differences in visual acuity influence one of the most commonly observed findings in the event-related potentials literature on cognitive aging, a reduction in posterior P3b amplitude, which is an index of cognitive decision-making/updating. Well-matched young (n=26) and old adults (n=29) participated in a visual oddball task. Measured visual acuity with corrective lenses was worse in old than young adults. Results demonstrated that the robust age-related decline in P3b amplitude to visual targets disappeared after controlling for visual acuity, but was unaffected by accounting for auditory acuity. Path analysis confirmed that the relationship between age and diminished P3b to visual targets was mediated by visual acuity, suggesting that conveyance of suboptimal sensory data due to peripheral, rather than central, deficits may undermine subsequent neural processing. We conclude that until the relationship between age-associated differences in visual acuity and neural activity during experimental tasks is clearly established, investigators should exercise caution attributing results to differences in cognitive processing.

Investigating age-related changes in anterior and posterior neural activity throughout the information processing stream.

Event-related potential (ERP) and other functional imaging studies often demonstrate age-related increases in anterior neural activity and decreases in posterior activity while subjects carry out task demands. It remains unclear whether this "anterior shift" is limited to late cognitive operations like those indexed by the P3 component, or is evident during other stages of information processing. The temporal resolution of ERPs provided an opportunity to address this issue. Temporospatial principal component analysis (PCA) was used to identify underlying components that may be obscured by overlapping ERP waveforms. ERPs were measured during a visual oddball task in 26 young, 26 middle-aged, and 29 old subjects who were well-matched for IQ, executive function, education, and task performance. PCA identified six anterior factors peaking between ∼140 ms and 810 ms, and four posterior factors peaking between ∼300 ms and 810 ms. There was an age-related increase in the amplitude of anterior factors between ∼200 and 500 ms, and an age-associated decrease in amplitude of posterior factors after ∼500 ms. The increase in anterior processing began as early as middle-age, was sustained throughout old age, and appeared to be linear in nature. These results suggest that age-associated increases in anterior activity occur after early sensory processing has taken place, and are most prominent during a period in which attention is being marshaled to evaluate a stimulus. In contrast, age-related decreases in posterior activity manifest during operations involved in stimulus categorization, post-decision monitoring, and preparation for an upcoming event.

The impact of executive capacity and age on mechanisms underlying multidimensional feature selection.

This study examined the role of executive capacity (EC) and aging in multidimensional feature selection. ERPs were recorded from healthy young and old adults of either high or average EC based on neuropsychological testing. Participants completed a color selective attention task in which they responded to target letter-forms in a specified color (attend condition) while ignoring letter-forms in a different color (ignore condition). Two selection negativity (SN) components were computed: the SN(Color) (attend-ignore), indexing early color selection, and the SN(Letter) (targets-standards), indexing early letter-form selection. High EC subjects exhibited self-terminating feature selection; the processing of one feature type was reduced if information from the other feature type suggested the stimulus did not contain the task-relevant feature. In contrast, average EC subjects exhaustively selected all features of a stimulus. The self-terminating approach was associated with better task accuracy. Higher EC was also linked to stronger early selection of target letter-forms, but did not modulate the seemingly less demanding task of color selection. Mechanisms utilized for multidimensional feature selection appear to be consistent across the lifespan, although there was age-related slowing of processing speed for early selection of letter features. We conclude that EC is a critical determinant of how multidimensional feature processing is carried out.

Age-related differences in early novelty processing: using PCA to parse the overlapping anterior P2 and N2 components.

Previous work demonstrated age-associated increases in the anterior P2 and age-related decreases in the anterior N2 in response to novel stimuli. Principal component analysis (PCA) was used to determine if the inverse relationship between these components was due to their temporal and spatial overlap. PCA revealed an early anterior P2, sensitive to task relevance, and a late anterior P2, responsive to novelty, both exhibiting age-related amplitude increases. A PCA factor representing the anterior N2, sensitive to novelty, exhibited age-related amplitude decreases. The late P2 and N2 to novels inversely correlated. Larger late P2 amplitude to novels was associated with better behavioral performance. Age-related differences in the anterior P2 and N2 to novel stimuli likely represent age-associated changes in independent cognitive operations. Enhanced anterior P2 activity (indexing augmentation in motivational salience) may be a compensatory mechanism for diminished anterior N2 activity (indexing reduced ability of older adults to process ambiguous representations).

Age-related decline in differentiated neural responses to rare target versus frequent standard stimuli.

One mechanism hypothesized to contribute to cognitive aging is the failure to recruit specialized neural modules and generate differentiated neural responses to various classes of stimuli. Here, ERPs were used to examine the extent to which target and standard stimulus types were processed differently by well-matched adults ages 19-99. Subjects responded to designated visual target letters under low and high load conditions. Temporospatial PCA was used to parse the P3b component, an index of categorization/memory updating. The P3b amplitude difference between targets and standards decreased substantially as a function of age. Dedifferentiation began in middle age, and continued into old-old age. The reduced differentiation of neural responses was driven by an age-related decline in the size of the P3b to targets and an age-related increase in the P3b to standards. Larger P3b amplitude to standards among older subjects was associated with higher executive capacity and better task performance. In summary, dedifferentiation begins relatively early in adulthood and progresses in a linear fashion throughout the lifespan. The age-related augmentation of the P3b to standards appears to reflect a compensatory mechanism that helps maintain task performance.

Age-related decline in bottom-up processing and selective attention in the very old.

Previous research demonstrating age-related deficits in selective attention have not included old-old adults, an increasingly important group to study. The current investigation compared event-related potentials in 15 young-old (65-79 years old) and 23 old-old (80-99 years old) subjects during a color-selective attention task. Subjects responded to target letters in a specified color (Attend) while ignoring letters in a different color (Ignore) under both low and high loads. There were no group differences in visual acuity, accuracy, reaction time, or latency of early event-related potential components. The old-old group showed a disruption in bottom-up processing, indexed by a substantially diminished posterior N1 (smaller amplitude). They also demonstrated markedly decreased modulation of bottom-up processing based on selected visual features, indexed by the posterior selection negativity (SN), with similar attenuation under both loads. In contrast, there were no group differences in frontally mediated attentional selection, measured by the anterior selection positivity (SP). There was a robust inverse relationship between the size of the SN and SP (the smaller the SN, the larger the SP), which may represent an anteriorly supported compensatory mechanism. In the absence of a decline in top-down modulation indexed by the SP, the diminished SN may reflect age-related degradation of early bottom-up visual processing in old-old adults.

Does the age-related "anterior shift" of the P3 reflect an inability to habituate the novelty response?

Old adults often generate larger anterior neural responses than young adults when carrying out task requirements. A common finding in the ERP literature is an "anterior shift" of the P3b to targets. Utilizing principal component analysis (PCA), we recently demonstrated that rather than the P3b moving anteriorly, old adults generate a large P3a that temporally overlaps with their P3b. A dominant hypothesis for the age-related increase in anterior P3 is the failure to habituate the brain's novelty response to rare targets. We tested this hypothesis in young and old adults by comparing the amplitude of the PCA factor representing P3a to targets presented in the first versus last of eight blocks of a visual oddball task. If, unlike young adults, old adults are unable to habituate a novelty response, one would expect (1) the P3a amplitude to decrease between the first and last blocks for young, but not old subjects and (2) the difference in P3a amplitude between young and old subjects to be greater in the last than the first block. Our results indicate the amplitude of the P3a was larger in old adults than young adults. However, this effect was not modulated by block. These findings argue against the hypothesis that an age-related increase in the P3a to targets reflects an inability of old subjects to habituate a novelty response. An alternative hypothesis is that the augmented P3a indexes the increased utilization of frontal executive functions to provide compensatory scaffolding to carry out a task.

Investigating the age-related "anterior shift" in the scalp distribution of the P3b component using principal component analysis.

An age-related "anterior shift" in the distribution of the P3b is often reported. Temporospatial principal component analysis (PCA) was used to investigate the basis of this observation. ERPs were measured in young and old adults during a visual oddball task. PCA revealed two spatially distinct factors in both age groups, identified as the posterior P3b and anterior P3a. Young subjects generated a smaller P3a than P3b, while old subjects generated a P3a that did not differ in amplitude from their P3b. Rather than having a more anteriorly distributed P3b, old subjects produced a large, temporally overlapping P3a. The pattern of the age-related "anterior shift" in the P3 was similar for target and standard stimuli. The increase in the P3a in elderly adults may not represent a failure to habituate the novelty response, but may reflect greater reliance on executive control operations (P3a) to carry out the categorization/updating process (P3b).

Age-related differences in the automatic processing of single letters: implications for selective attention.

Older adults exhibit diminished ability to inhibit the processing of visual stimuli that are supposed to be ignored. The extent to which age-related changes in early visual processing contribute to impairments in selective attention remains to be determined. Here, 103 adults, 18-85 years of age, completed a color selective attention task in which they were asked to attend to a specified color and respond to designated target letters. An optimal approach would be to initially filter according to color and then process letter forms in the attend color to identify targets. An asymmetric N170 ERP component (larger amplitude over left posterior hemisphere sites) was used as a marker of the early automatic processing of letter forms. Young and middle-aged adults did not generate an asymmetric N170 component. In contrast, young-old and old-old adults produced a larger N170 over the left hemisphere. Furthermore, older adults generated a larger N170 to letter than nonletter stimuli over the left, but not right hemisphere. More asymmetric N170 responses predicted greater allocation of late selection resources to target letters in the ignore color, as indexed by P3b amplitude. These results suggest that unlike their younger counterparts, older adults automatically process stimuli as letters early in the selection process, when it would be more efficient to attend to color only. The inability to ignore letters early in the processing stream helps explain the age-related increase in subsequent processing of target letter forms presented in the ignore color.

The dissociation between early and late selection in older adults.

Older adults exhibit a reduced ability to ignore task-irrelevant stimuli; however, it remains to be determined where along the information processing stream the most salient age-associated changes occur. In the current study, ERPs provided an opportunity to determine whether age-related differences in processing task-irrelevant stimuli were uniform across information processing stages or disproportionately affected either early or late selection. ERPs were measured in young and old adults during a color-selective attention task in which participants responded to target letters in a specified color (attend condition) while ignoring letters in a different color (ignore condition). Old participants were matched to two groups of young participants on the basis of neuropsychological test performance: one using age-appropriate norms and the other using test scores not adjusted for age. There were no age-associated differences in the magnitude of early selection (attend-ignore), as indexed by the size of the anterior selection positivity and posterior selection negativity. During late selection, as indexed by P3b amplitude, both groups of young participants generated neural responses to target letters under the attend versus ignore conditions that were highly differentiated. In striking contrast, old participants generated a P3b to target letters with no reliable differences between conditions. Individuals who were slow to initiate early selection appeared to be less successful at executing late selection. Despite relative preservation of the operations of early selection, processing delays may lead older participants to allocate excessive resources to task-irrelevant stimuli during late selection.

The impact of visual acuity on age-related differences in neural markers of early visual processing.

The extent to which age-related differences in neural markers of visual processing are influenced by changes in visual acuity has not been systematically investigated. Studies often indicate that their subjects had normal or corrected-to-normal vision, but the assessment of visual acuity seems to most frequently be based only on self-report. Consistent with prior research, to be included in the current study, subjects had to report normal or corrected-to-normal vision. Additionally, visual acuity was formally tested using a Snellen eye chart. Event-related potentials (ERPs) were studied in young adults (18-32years old), young-old adults (65-79years old), and old-old adults (80+ years old) while they performed a visual processing task involving selective attention to color. Age-related differences in the latency and amplitude of ERP markers of early visual processing, the posterior P1 and N1 components, were examined. All results were then re-analyzed after controlling for visual acuity. We found that visual acuity declined as a function of age. Accounting for visual acuity had an impact on whether older and younger adults differed significantly in the size and latency of the posterior P1 and N1 components. After controlling for visual acuity, age-related increases in P1 and N1 latency did not remain significant, and older adults were found to have a larger P1 amplitude than young adults. Our results suggest that until the relationship between age-associated differences in visual acuity and early ERPs is clearly established, investigators should be cautious when interpreting the meaning of their findings. Self-reports about visual acuity may be inaccurate, necessitating formal measures. Additional investigation is needed to help establish guidelines for future research, especially of very old adults.