Unraveling robust brain-behavior links of depressive complaints through granular network models for understanding heterogeneity.

BACKGROUND: Depressive symptoms are highly prevalent, present in heterogeneous symptom patterns, and share diverse neurobiological underpinnings. Understanding the links between psychopathological symptoms and biological factors is critical in elucidating its etiology and persistence. We aimed to evaluate the utility of using symptom-brain network models to parse the heterogeneity of depressive complaints in a large adolescent sample. METHODS: We used data from the third wave of the IMAGEN study, a multi-center panel cohort study involving 1317 adolescents (52.49 % female, mean ± SD age = 18.5 ± 0.7). Two network models were estimated: one including an overall depressive symptom severity sum score based on the Adolescent Depression Rating Scale (ADRS), and one incorporating individual ADRS item scores. Both networks included measures of cortical thickness in several regions (insula, cingulate, mOFC, fusiform gyrus) and hippocampal volume derived from neuroimaging. RESULTS: The network based on individual item scores revealed associations between cortical thickness measures and specific depressive complaints, obscured when using an aggregate depression severity score. Notably, the insula's cortical thickness showed negative associations with cognitive dysfunction (partial cor. = -0.15); the cingulate's cortical thickness showed negative associations with feelings of worthlessness (partial cor. = -0.10), and mOFC was negatively associated with anhedonia (partial cor. = -0.05). LIMITATIONS: This cross-sectional study relied on the self-reported assessment of depression complaints and used a non-clinical sample with predominantly healthy participants (19 % with depression or sub-threshold depression). CONCLUSIONS: This study showcases the utility of network models in parsing heterogeneity in depressive complaints, linking individual complaints to specific neural substrates. We outline the next steps to integrate neurobiological and cognitive markers to unravel MDD's phenotypic heterogeneity.

A Network Approach to Understanding the Role of Executive Functioning and Alpha Oscillations in Inattention and Hyperactivity-Impulsivity Symptoms of ADHD.

OBJECTIVE: ADHD is a prevalent neurodevelopmental disorder characterized by symptoms of inattention and hyperactivity-impulsivity. Impairments in executive functioning (EF) are central to models of ADHD, while alpha-band spectral power event-related decreases (ERD) have emerged as a putative electroencephalography (EEG) biomarker of EF in ADHD. Little is known about the roles of EF and alpha ERD and their interactions with symptoms of ADHD. METHOD: We estimated network models of ADHD symptoms and integrated alpha ERD measures into the symptom network. RESULTS: EF emerges as a bridge network node connecting alpha ERD and the hyperactivity/impulsivity and inattention symptoms. We found that EF most closely relates to a subset of symptoms, namely the motoric symptoms, "seat" (difficulty staying seated), and "runs" (running or climbing excessively). CONCLUSIONS: EF functions as a bridge node connecting alpha ERD and the ADHD symptom network. Motoric-type symptoms and EF deficits may constitute important nodes in the interplay between behavior/symptoms, cognition, and neurophysiological markers of ADHD.

Alpha event-related decreases during encoding in adults with ADHD - An investigation of sustained attention and working memory processes.

BACKGROUND: Executive functioning deficits are central to established neuropsychological models of ADHD. Oscillatory activity, particularly the alpha rhythm (8-12 Hz) has been associated with cognitive impairments in ADHD. However, most studies to date examined such neural mechanisms underlying executive dysfunction in children and adolescents with ADHD, raising the question of whether and to what extent those ADHD-related working memory impairments are still present in adults. To this end, the current study aimed to investigate the role of alpha event-related decreases (ERD) during working memory processes in adults with and without ADHD. METHODS: We collected electroencephalographic (EEG) data from 85 adults with a lifetime diagnosis of ADHD and 105 controls (aged 32-64), while they performed a continuous performance (CPT) and a spatial delayed response working memory task (SDRT). Time-frequency and independent component analysis (ICA) was used to identify alpha (8-12 Hz) clusters to examine group and condition effects during the temporal profile of sustained attention and working memory processes (encoding, maintenance, retrieval), loads (low and high) and trial type (go and nogo). RESULTS: Individuals with ADHD exhibited higher reaction time-variability in SDRT, and slower response times in SDRT and CPT, despite no differences in task accuracy. Although working memory load was associated with stronger alpha ERD in both tasks and both groups (ADHD, controls), we found no consistent evidence for attenuated alpha ERD in adults with ADHD, failing to replicate effects reported in children. In contrast, when looking at the whole sample, the correlations of alpha power during encoding with inattention and hyperactivity-impulsivity symptoms were significant, replicating prior findings in children with ADHD, but suggesting an alternate source for these effects in adults. CONCLUSIONS: Our results corroborate the robustness of alpha as a marker of visual attention and suggest that occipital alpha ERD normalizes in adulthood, but with unique contributions of centro-occipital alpha ERD, suggesting a secondary source. This implies that deviations in processes other than previously reported visuospatial cortex engagement may account for the persistent symptoms and cognitive deficits in adults with a history of ADHD.

Pupillary dilations in a Target/Distractor visual task paradigm and attention deficit hyperactivity disorder (ADHD).

ADHD is a neurocognitive disorder characterized by attention difficulties, hyperactivity, and impulsivity, often persisting into adulthood with substantial personal and societal consequences. Despite the importance of neurophysiological assessment and treatment monitoring tests, their availability outside of research settings remains limited. Cognitive neuroscience investigations have identified distinct components associated with ADHD, including deficits in sustained attention, inefficient enhancement of attended Targets, and altered suppression of ignored Distractors. In this study, we examined pupil activity in control and ADHD subjects during a sustained visual attention task specifically designed to evaluate the mechanisms underlying Target enhancement and Distractor suppression. Our findings revealed some distinguishing factors between the two groups which we discuss in light of their neurobiological implications.

Unravelling Robust Brain-Behavior Links of Depressive Symptoms Through Granular Network Models: Understanding Heterogeneity and Clinical Implications.

Background: Depressive symptoms are highly prevalent, present in heterogeneous symptom patterns, and share diverse neurobiological underpinnings. Understanding the links between psychopathological symptoms and biological factors is critical in elucidating its etiology and persistence. We aimed to evaluate the utility of using symptom-brain networks to parse the heterogeneity of depressive symptomatology in a large adolescent sample. Methods: We used data from the third wave of the IMAGEN study, a multi-center panel cohort study involving 1,317 adolescents (52.49% female, mean±SD age=18.5±0.72). Two network models were estimated: one including an overall depressive symptom severity sum score based on the Adolescent Depression Rating Scale (ADRS), and one incorporating individual ADRS symptom/item scores. Both networks included measures of cortical thickness in several regions (insula, cingulate, mOFC, fusiform gyrus) and hippocampal volume derived from neuroimaging. Results: The network based on individual symptom scores revealed associations between cortical thickness measures and specific symptoms, obscured when using an aggregate depression severity score. Notably, the insula's cortical thickness showed negative associations with cognitive dysfunction (partial cor.=-0.15); the cingulate's cortical thickness showed negative associations with feelings of worthlessness (partial cor. = -0.10), and mOFC was negatively associated with anhedonia (partial cor. = -0.05). Limitations: This cross-sectional study included participants who were relatively healthy and relied on the self-reported assessment of depression symptoms. Conclusions: This study showcases the utility of network models in parsing heterogeneity in depressive symptoms, linking individual symptoms to specific neural substrates. We outline the next steps to integrate neurobiological and cognitive markers to unravel MDD's phenotypic heterogeneity.

Variability in Cognitive Task Performance in Early Adolescence Is Associated With Stronger Between-Network Anticorrelation and Future Attention Problems.

Background: Intraindividual variability (IIV) during cognitive task performance is a key behavioral index of attention and a consistent marker of attention-deficit/hyperactivity disorder. In adults, lower IIV has been associated with anticorrelation between the default mode network (DMN) and dorsal attention network (DAN)-thought to underlie effective allocation of attention. However, whether these behavioral and neural markers of attention are 1) associated with each other and 2) can predict future attention-related deficits has not been examined in a developmental, population-based cohort. Methods: We examined relationships at the baseline visit between IIV on 3 cognitive tasks, DMN-DAN anticorrelation, and parent-reported attention problems using data from the Adolescent Brain Cognitive Development (ABCD) Study (N = 11,878 participants, ages 9 to 10 years, female = 47.8%). We also investigated whether behavioral and neural markers of attention at baseline predicted attention problems 1, 2, and 3 years later. Results: At baseline, greater DMN-DAN anticorrelation was associated with lower IIV across all 3 cognitive tasks (B = 0.22 to 0.25). Older age at baseline was associated with stronger DMN-DAN anticorrelation and lower IIV (B = -0.005 to -0.0004). Weaker DMN-DAN anticorrelation and IIV were cross-sectionally associated with attention problems (B = 1.41 to 7.63). Longitudinally, lower IIV at baseline was associated with less severe attention problems 1 to 3 years later, after accounting for baseline attention problems (B = 0.288 to 0.77). Conclusions: The results suggest that IIV in early adolescence is associated with worsening attention problems in a representative cohort of U.S. youth. Attention deficits in early adolescence may be important for understanding and predicting future cognitive and clinical outcomes.

Beyond the Beta Rebound: Post-Task Responses in Oscillatory Activity follow Cessation of Working Memory Processes.

Post-task responses (PTRs) are transitionary responses occurring for several seconds between the end of a stimulus/task and a period of rest. The most well-studied of these are beta band (13 - 30 Hz) PTRs in motor networks following movement, often called post-movement beta rebounds, which have been shown to differ in patients with schizophrenia and autism. Previous studies have proposed that beta PTRs reflect inhibition of task-positive networks to enable a return to resting brain activity, scaling with cognitive demand and reflecting cortical self-regulation. It is unknown whether PTRs are a phenomenon of the motor system, or whether they are a more general self-modulatory property of cortex that occur following cessation of higher cognitive processes as well as movement. To test this, we recorded magnetoencephalography (MEG) responses in 20 healthy participants to a working-memory task, known to recruit cortical networks associated with higher cognition. Our results revealed PTRs in the theta, alpha and beta bands across many regions of the brain, including the dorsal attention network (DAN) and lateral visual regions. These PTRs increased significantly (p < 0.05) in magnitude with working-memory load, an effect which is independent of oscillatory modulations occurring over the task period as well as those following individual stimuli. Furthermore, we showed that PTRs are functionally related to reaction times in left lateral visual (p < 0.05) and left parietal (p < 0.1) regions, while the oscillatory responses measured during the task period are not. Importantly, motor PTRs following button presses did not modulate with task condition, suggesting that PTRs in different networks are driven by different aspects of cognition. Our findings show that PTRs are not limited to motor networks but are widespread in regions which are recruited during the task. We provide evidence that PTRs have unique properties, scaling with cognitive load and correlating significantly with behaviour. Based on the evidence, we suggest that PTRs inhibit task-positive network activity to enable a transition to rest, however, further investigation is required to uncover their role in neuroscience and pathology.

Methylphenidate, Guanfacine, and Combined Treatment Effects on Electroencephalography Correlates of Spatial Working Memory in Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: The combination of d-methylphenidate and guanfacine (an α-2A adrenergic agonist) may be an effective alternative to either agent as monotherapy in children with attention-deficit/hyperactivity disorder (ADHD). This study investigated the neural mechanisms underlying medication effects using cortical source analysis of electroencephalography (EEG) data. METHOD: A total of 172 children with ADHD (aged 7-14; 118 boys) completed an 8-week randomized, double-blind, comparative study with 3 treatment arms: d-methylphenidate, guanfacine, or their combination. EEG modulations of brain oscillations at baseline and end point were measured during a spatial working memory task from cortical sources localized within the anterior cingulate (midfrontal) and primary visual cortex (midoccipital), based on previously reported ADHD and control differences. Linear mixed models examined treatment effects on EEG and performance measures. RESULTS: Combined treatment decreased midoccipital EEG power across most frequency bands and task phases. Several midoccipital EEG measures also showed significantly greater changes with combined treatment than with monotherapies. D-methylphenidate significantly increased midoccipital theta during retrieval, while guanfacine produced only trend-level reductions in midoccipital alpha during maintenance and retrieval. Task accuracy improved with combined treatment, was unchanged with d-methylphenidate, and worsened with guanfacine. Treatment-related changes in midoccipital power correlated with improvement in ADHD severity. CONCLUSION: These findings show that combined treatment ameliorates midoccipital neural activity associated with treatment-related behavioral improvements and previously implicated in visuo-attentional deficits in ADHD. Both monotherapies had limited effects on EEG measures, with guanfacine further showing detrimental effects on performance. The identified midoccipital EEG profile may aid future treatment monitoring for children with ADHD. CLINICAL TRIAL REGISTRATION INFORMATION: Single Versus Combination Medication Treatment for Children With Attention Deficit Hyperactivity Disorder (Project1); https://clinicaltrials.gov/; NCT00429273. DIVERSITY & INCLUSION STATEMENT: We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure sex and gender balance in the recruitment of human participants. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. We actively worked to promote sex and gender balance in our author group.

Electrophysiological and Clinical Predictors of Methylphenidate, Guanfacine, and Combined Treatment Outcomes in Children With Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: The combination of d-methylphenidate and guanfacine (an α-2A agonist) has emerged as a potential alternative to either monotherapy in children with attention-deficit/hyperactivity disorder (ADHD), but it is unclear what predicts response to these treatments. This study is the first to investigate pretreatment clinical and electroencephalography (EEG) profiles as predictors of treatment outcome in children randomized to these different medications. METHOD: A total of 181 children with ADHD (aged 7-14 years; 123 boys) completed an 8-week randomized, double-blind, comparative study with d-methylphenidate, guanfacine, or combined treatments. Pretreatment assessments included ratings on ADHD, anxiety, and oppositional behavior. EEG activity from cortical sources localized within midfrontal and midoccipital regions was measured during a spatial working memory task with encoding, maintenance, and retrieval phases. Analyses tested whether pretreatment clinical and EEG measures predicted treatment-related change in ADHD severity. RESULTS: Higher pretreatment hyperactivity-impulsivity and oppositional symptoms and lower anxiety predicted greater ADHD improvements across all medication groups. Pretreatment event-related midfrontal beta power predicted treatment outcome with combined and monotherapy treatments, albeit in different directions. Weaker beta modulations predicted improvements with combined treatment, whereas stronger modulation during encoding and retrieval predicted improvements with d-methylphenidate and guanfacine, respectively. A multivariate model including EEG and clinical measures explained twice as much variance in ADHD improvement with guanfacine and combined treatment (R2= 0.34-0.41) as clinical measures alone (R2 = 0.14-.21). CONCLUSION: We identified treatment-specific and shared predictors of response to different pharmacotherapies in children with ADHD. If replicated, these findings would suggest that aggregating information from clinical and brain measures may aid personalized treatment decisions in ADHD. CLINICAL TRIAL REGISTRATION INFORMATION: Single Versus Combination Medication Treatment for Children With Attention Deficit Hyperactivity Disorder; https://clinicaltrials.gov; NCT00429273.

Event-related brain oscillations in attention-deficit/hyperactivity disorder (ADHD): A systematic review and meta-analysis.

Previous studies have associated attention-deficit/hyperactivity disorder (ADHD) with several alterations in electroencephalographic (EEG) activity. Time-frequency analyses capturing event-related power modulations are becoming an increasingly popular approach, but a systematic synthesis of the time-frequency literature in ADHD is currently lacking. We conducted the first systematic review and meta-analysis of time-frequency studies of children and adults with ADHD in comparison to neurotypical controls. Searches via Medline, Embase, and Web of Science, as well as reference lists, identified 28 eligible articles published until March 2021. Of these, 13 articles with relevant data were included in a multi-level meta-analysis. Most studies examined power modulations of alpha, theta and/or beta frequencies (N = 21/28), and focused on children (N = 17/28). Meta-analyses showed significantly weaker theta increases (Cohen's d = -0.25, p = 0.039; NADHD = 346, NCONTROL = 327), alpha decreases (d = 0.44, p < 0.001; NADHD = 564, NCONTROL = 450), and beta increases (Cohen's d = -0.33, p < 0.001; NADHD = 222, NCONTROL = 263) in individuals with ADHD relative to controls. These patterns indicate broad brain-oscillatory alterations in individuals with ADHD with small (theta) and small-to-moderate (alpha and beta) effect sizes. These group differences were partly consistent when repeating analyses by age group (<18 and 18+ years) and task type (cognitive control, working memory, and simple attention tasks). Overall, our findings identify widespread event-related brain-oscillatory alterations in individuals with ADHD during a range of neurocognitive functions. Future research requires larger samples, a broader range of frequency bands (including delta and gamma) during a wider type of cognitive-affective processes, and should clarify whether atypical event-related power profiles are ADHD-specific or shared with other neuropsychiatric conditions.

EEG Data Quality in Real-World Settings: Examining Neural Correlates of Attention in School-Aged Children.

Advances in mobile electroencephalography (EEG) technology have made it possible to examine covert cognitive processes in real-world settings such as student attention in the classroom. Here, we outline research using wired and wireless EEG technology to examine attention in elementary school children across increasingly naturalistic paradigms in schools, ranging from a lab-based paradigm where children met one-on-one with an experimenter in a field laboratory to mobile EEG testing conducted in the same school during semi-naturalistic classroom lessons. Despite an increase of data loss with the classroom-based paradigm, we demonstrate that it is feasible to collect quality data in classroom settings with young children. We also provide a test case for how robust EEG signals, such as alpha oscillations, can be used to identify measurable differences in covert processes like attention in classrooms. We end with pragmatic suggestions for researchers interested in employing naturalistic EEG methods in real-world, multisensory contexts.

Effects of context on the neural correlates of attention in a college classroom.

Activities that are effective in supporting attention have the potential to increase opportunities for student learning. However, little is known about the impact of instructional contexts on student attention, in part due to limitations in our ability to measure attention in the classroom, typically based on behavioral observation and self-reports. To address this issue, we used portable electroencephalography (EEG) measurements of neural oscillations to evaluate the effects of learning context on student attention. The results suggest that attention, as indexed by lower alpha power as well as higher beta and gamma power, is stronger during student-initiated activities than teacher-initiated activities. EEG data revealed different patterns in student attention as compared to standardized coding of attentional behaviors. We conclude that EEG signals offer a powerful tool for understanding differences in student cognitive states as a function of classroom instruction that are unobservable from behavior alone.

Neurocognitive subprocesses of working memory performance.

Working memory (WM) has been defined as the active maintenance and flexible updating of goal-relevant information in a form that has limited capacity and resists interference. Complex measures of WM recruit multiple subprocesses, making it difficult to isolate specific contributions of putatively independent subsystems. The present study was designed to determine whether neurophysiological indicators of proposed subprocesses of WM predict WM performance. We recruited 200 individuals defined by care-seeking status and measured neural responses using electroencephalography (EEG), while participants performed four WM tasks. We extracted spectral and time-domain EEG features from each task to quantify each of the hypothesized WM subprocesses: maintenance (storage of content), goal maintenance, and updating. We then used EEG measures of each subprocess as predictors of task performance to evaluate their contribution to WM. Significant predictors of WM capacity included contralateral delay activity and frontal theta, features typically associated with maintenance (storage of content) processes. In contrast, significant predictors of reaction time and its variability included contingent negative variation and the P3b, features typically associated with goal maintenance and updating. Broadly, these results suggest two principal dimensions that contribute to WM performance, tonic processes during maintenance contributing to capacity, and phasic processes during stimulus processing that contribute to response speed and variability. The analyses additionally highlight that reliability of features across tasks was greater (and comparable to that of WM performance) for features associated with stimulus processing (P3b and alpha), than with maintenance (gamma, theta and cross-frequency coupling).

A new era for executive function research: On the transition from centralized to distributed executive functioning.

"Executive functions" (EFs) is an umbrella term for higher cognitive control functions such as working memory, inhibition, and cognitive flexibility. One of the most challenging problems in this field of research has been to explain how the wide range of cognitive processes subsumed as EFs are controlled without an all-powerful but ill-defined central executive in the brain. Efforts to localize control mechanisms in circumscribed brain regions have not led to a breakthrough in understanding how the brain controls and regulates itself. We propose to re-conceptualize EFs as emergent consequences of highly distributed brain processes that communicate with a pool of highly connected hub regions, thus precluding the need for a central executive. We further discuss how graph-theory driven analysis of brain networks offers a unique lens on this problem by providing a reference frame to study brain connectivity in EFs in a holistic way and helps to refine our understanding of the mechanisms underlying EFs by providing new, testable hypotheses and resolves empirical and theoretical inconsistencies in the EF literature.

Modulation of attention and stress with arousal: The mental and physical effects of riding a motorcycle.

Existing theories suggest that moderate arousal improves selective attention, as would be expected in the context of competitive sports or sensation-seeking activities. Here we investigated how riding a motorcycle, an attention-demanding physical activity, affects sensory processing. To do so, we implemented the passive auditory oddball paradigm and measured the EEG response of participants as they rode a motorcycle, drove a car, and sat at rest. Specifically, we measured the N1 and mismatch negativity to auditory tones, as well as alpha power during periods of no tones. We investigated whether riding and driving modulated non-CNS metrics including heart rate and concentrations of the hormones epinephrine, cortisol, DHEA-S, and testosterone. While participants were riding, we found a decrease in N1 amplitude, increase in mismatch negativity, and decrease in relative alpha power, together suggesting enhancement of sensory processing and visual attention. Riding increased epinephrine levels, increased heart rate, and decreased the ratio of cortisol to DHEA-S. Together, these results suggest that riding increases focus, heightens the brain's passive monitoring of changes in the sensory environment, and alters HPA axis response. More generally, our findings suggest that selective attention and sensory monitoring seem to be separable neural processes.

Alpha modulation during working memory encoding predicts neurocognitive impairment in ADHD.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is associated with working memory (WM) deficits. However, WM is a multiprocess construct that can be impaired through several pathways, leaving the source of WM impairments in ADHD unresolved. In this study, we aim to replicate, in an independent sample, previously reported deficits in component processes of WM deficits in ADHD and expand to consider their implications for neurocognitive outcomes. METHODS: In 119 children (7-14 years old, 85 with ADHD), we used electroencephalography measures to quantify component processes during performance of a spatial working memory task. We quantified stimulus encoding using alpha range (8-12 Hz) power; vigilance by the P2 event-related potential to cues; and WMmaintenance by occipital-alpha and frontal-theta (4-7 Hz) power. These measures were evaluated against metrics of executive function, ADHD symptoms, and academic achievement. RESULTS: Encoding alpha-power decreases and cue P2 amplitude were attenuated in ADHD, whereas occipital-alpha power during maintenance was significantly greater in ADHD, consistent with a compensatory response to weak encoding. Weak alpha modulation during encoding was associated with poorer reading comprehension and executive function, as well as enhanced ADHD symptoms. Previously reported effects in frontal-theta power failed to replicate. CONCLUSIONS: Stimulus encoding, a component process of WM coupled to alpha modulation, is impaired in ADHD, and, unlike WM maintenance or vigilance processes, has implications outside of the laboratory via a relationship with executive function, and, to a weaker extent, reading comprehension.

Classification Accuracy of Neuroimaging Biomarkers in Attention-Deficit/Hyperactivity Disorder: Effects of Sample Size and Circular Analysis.

BACKGROUND: Motivated by an inconsistency between reports of high diagnosis-classification accuracies and known heterogeneity in attention-deficit/hyperactivity disorder (ADHD), this study assessed classification accuracy in studies of ADHD as a function of methodological factors that can bias results. We hypothesized that high classification results in ADHD diagnosis are inflated by methodological factors. METHODS: We reviewed 69 studies (of 95 studies identified) that used neuroimaging features to predict ADHD diagnosis. Based on reported methods, we assessed the prevalence of circular analysis, which inflates classification accuracy, and evaluated the relationship between sample size and accuracy to test if small-sample models tend to report higher classification accuracy, also an indicator of bias. RESULTS: Circular analysis was detected in 15.9% of ADHD classification studies, lack of independent test set was noted in 13%, and insufficient methodological detail to establish its presence was noted in another 11.6%. Accuracy of classification ranged from 60% to 80% in the 59.4% of reviewed studies that met criteria for independence of feature selection, model construction, and test datasets. Moreover, there was a negative relationship between accuracy and sample size, implying additional bias contributing to reported accuracies at lower sample sizes. CONCLUSIONS: High classification accuracies in neuroimaging studies of ADHD appear to be inflated by circular analysis and small sample size. Accuracies on independent datasets were consistent with known heterogeneity of the disorder. Steps to resolve these issues, and a shift toward accounting for sample heterogeneity and prediction of future outcomes, will be crucial in future classification studies in ADHD.

Nicotine effects on associative learning in human non-smokers.

Tobacco smoking is the most common preventable cause of death in the US. Nicotine is considered the primary constituent responsible for tobacco addiction. Its paradoxically high abuse potential may reflect behavioral control by drug-associated stimuli, which appears to play a larger role for tobacco dependence than for other abused drugs. We tested a potential explanation, hypothesizing that nicotine enhances associative learning, the mechanism underlying the conditioning of drug-associated stimuli. Thirty-two non-smokers were exposed to transdermal nicotine (7 mg/24 h) and placebo in a double-blind cross-over study and tested with behavioral paradigms designed to isolate incidental stimulus-stimulus or stimulus-response learning. The stop signal task required speeded gender judgments of face stimuli. A tone signaled when to withhold the response. Unbeknownst to participants, some faces were always paired with stop trials. Nicotine enhanced the facilitation of stop-responses to these stimuli, and the slowing of go-responses when previously stop-associated stimuli were paired with go trials, indicating stronger associations between paired stimuli and the stop signal/stop response. Another task required feedback-based learning of associations between pairs of shape stimuli. Five pairs were made from either ten different stimuli, or from different combinations of two identical sets of five stimuli with correct associations depending on contextual information. Nicotine increased incorrect choices of stimuli that were associated in a different context, indicating stronger stimulus-stimulus associations at the expense of flexible context-adaptive behavior. The results indicate that nicotine can enhance incidental associative learning, a mechanism that may promote the formation of smoking-associated stimuli and cue-controlled drug-taking.

Aberrant Modulation of Brain Oscillatory Activity and Attentional Impairment in Attention-Deficit/Hyperactivity Disorder.

Electroencephalography and magnetoencephalography are noninvasive neuroimaging techniques that have been used extensively to study various resting-state and cognitive processes in the brain. The purpose of this review is to highlight a number of recent studies that have investigated the alpha band (8-12 Hz) oscillatory activity present in magnetoencephalography and electroencephalography, to provide new insights into the maladaptive network activity underlying attentional impairments in attention-deficit/hyperactivity disorder (ADHD). Studies reviewed demonstrate that event-related decrease in alpha is attenuated during visual selective attention, primarily in ADHD inattentive type, and is often significantly associated with accuracy and reaction time during task performance. Furthermore, aberrant modulation of alpha activity has been reported across development and may have abnormal or atypical lateralization patterns in ADHD. Modulations in the alpha band thus represent a robust, relatively unexplored putative biomarker of attentional impairment and a strong prospect for future studies aimed at examining underlying neural mechanisms and treatment response among individuals with ADHD. Potential limitations of its use as a diagnostic biomarker and directions for future research are discussed.

Putting the brakes on the brakes: negative emotion disrupts cognitive control network functioning and alters subsequent stopping ability.

The ability to inhibit unwanted responses is critical for effective control of behavior, and inhibition failures can have disastrous consequences in real-world situations. Here, we examined how prior exposure to negative emotional stimuli affects the response-stopping network. Participants performed the stop-signal task, which relies on inhibitory control processes, after they viewed blocks of either negatively emotional or neutral images. In Experiment 1, we found that neural activity was reduced following negative image viewing. When participants were required to inhibit responding after neutral image viewing, we observed activation consistent with previous studies using the stop-signal task. However, when participants were required to inhibit responding after negative image viewing, we observed reductions in the activation of ventrolateral prefrontal cortex, dorsolateral prefrontal cortex, medial frontal cortex, and parietal cortex. Furthermore, analysis of neural connectivity during stop-signal task blocks indicated that across participants, emotion-induced changes in behavioral performance were associated with changes in functional connectivity, such that greater behavioral impairment after negative image viewing was associated with greater weakening of connectivity. In Experiment 2, we collected behavioral data from a larger sample of participants and found that stopping performance was impaired after negative image viewing, as seen in longer stop-signal reaction times. The present results demonstrate that negative emotional events can prospectively disrupt the neural network supporting response inhibition.