Zhong-Xu Liu

Neurophysiological differences in inhibitory control between adults with ADHD and their peers

Inhibitory control allows individuals to suppress prepotent responses and resist irrelevant stimuli, and is thought to be a core deficit in Attention-deficit/hyperactivity disorder (ADHD). Whereas numerous studies have investigated neural mechanisms underlying inhibitory control deficits in children with ADHD, less is known about underlying mechanisms in young adults with ADHD. This study explores the neural correlates of inhibitory control in college students with ADHD-a population that, despite comparatively high educational attainment, still shows marked functional impairments in academic, social, and occupational functioning. Participants were 54 college students with ADHD and 29 typically developing peers. Specifically the fronto-centrally located N2 and the centro-parietal P3 event-related potential (ERP) components were hypothesized to show decreased amplitudes for the ADHD group due to their known association with inhibitory control. Dense array electroencephalography (EEG) data was collected during a Go/nogo task. Results show lower accuracy rates for the ADHD group and significant reductions in P3 amplitude as well as a trend for reduced N2 amplitude in nogo trials where subjects successfully inhibited a response. Notably, nogo N2 and P3 amplitudes correlated with the number of ADHD symptoms: namely, smaller amplitudes were associated with more symptoms. We conclude that when compared to their typically developing peers, relatively high functioning adults with ADHD still show a deviant neural signature. These results contribute to the growing literature of adult ADHD and increase our understanding of the neural correlates of inhibitory control associated with ADHD.

Resting state EEG oscillatory power differences in ADHD college students and their peers

BackgroundAmong the most robust neural abnormalities differentiating individuals with Attention-Deficit/Hyperactivity Disorder (ADHD) from typically developing controls are elevated levels of slow oscillatory activity (e.g., theta) and reduced fast oscillatory activity (e.g., alpha and beta) during resting-state electroencephalography (EEG). However, studies of resting state EEG in adults with ADHD are scarce and yield inconsistent findings.MethodsEEG profiles, recorded during a resting-state with eyes-open and eyes-closed conditions, were compared for college students with ADHD (n = 18) and a nonclinical comparison group (n = 17).ResultsThe ADHD group showed decreased power for fast frequencies, especially alpha. This group also showed increased power in the slow frequency bands, however, these effects were strongest using relative power computations. Furthermore, the theta/beta ratio measure was reliably higher for the ADHD group. All effects were more pronounced for the eyes-closed compared to the eyes-open condition. Measures of intra-individual variability suggested that brains of the ADHD group were less variable than those of controls.ConclusionsThe findings of this pilot study reveal that college students with ADHD show a distinct neural pattern during resting state, suggesting that oscillatory power, especially alpha, is a useful index for reflecting differences in neural communication of ADHD in early adulthood.

Developmental change in EEG theta activity in the medial prefrontal cortex during response control

Cognitive control functions continue to improve from infancy until early adulthood, allowing flexible adaptation to a complex environment. However, it remains controversial how this development in cognitive capabilities is mediated by changes in cortical activity: both age-related increases and decreases of mediofrontal neural activity have been observed and interpreted as neural underpinnings of this functional development. To better understand this developmental process, we examined EEG theta activity in the mediofrontal region using a Go/No-go response control task. We found that both pre-stimulus baseline theta-power and theta-power during the response control task, without baseline-correction, decreased with age. Conversely, when task-related theta-power was baseline corrected (using a ratio method), it exhibited a positive developmental trajectory. The age-related theta-power increase was source-localized to the anterior cingulate cortex. This increase in theta activity also partially mediated age-related improvements in response control and was greatest in a condition that demanded greater effort. Theta activity in older children also showed greater temporal reliability across trials as measured by inter-trial phase-coherence. Interestingly, directly subtracting baseline activity from task-related activity did not yield significant developmental effects, which highlights the necessity of separating and contrasting the pre-stimulus baseline with task-related processing in the understanding of neurodevelopmental changes.

Effects of Prior-Knowledge on Brain Activation and Connectivity During Associative Memory Encoding

Abstract Forming new associations is a fundamental process of building our knowledge system. At the brain level, how prior‐knowledge influences acquisition of novel associations has not been thoroughly investigated. Based on recent cognitive neuroscience literature on multiple‐component memory processing, we hypothesize that prior‐knowledge triggers additional evaluative, semantic, or episodic‐binding processes, mainly supported by the ventromedial prefrontal cortex (vmPFC), anterior temporal pole (aTPL), and hippocampus (HPC), to facilitate new memory encoding. To test this hypothesis, we scanned 20 human participants with functional magnetic resonance imaging (fMRI) while they associated novel houses with famous or nonfamous faces. Behaviorally, we found beneficial effects of prior‐knowledge on associative memory. At the brain level, we found that the vmPFC and HPC, as well as the parahippocampal place area (PPA) and fusiform face area, showed stronger activation when famous faces were involved. The vmPFC, aTPL, HPC, and PPA also exhibited stronger activation when famous faces elicited stronger emotions and memories, and when associations were later recollected. Connectivity analyses also suggested that HPC connectivity with the vmPFC plays a more important role in the famous than nonfamous condition. Taken together, our results suggest that prior‐knowledge facilitates new associative encoding by recruiting additional perceptual, evaluative, or associative binding processes.

Adult ADHD and working memory: Neural evidence of impaired encoding

OBJECTIVES To investigate neural and behavioural correlates of visual encoding during a working memory (WM) task in young adults with and without Attention-Deficit/Hyperactivity Disorder (ADHD). METHODS A sample of 30 college students currently meeting a diagnosis of ADHD and 25 typically developing students, matched on age and gender, performed a delayed match-to-sample task with low and high memory load conditions. Dense-array electroencephalography was recorded. Specifically, the P3, an event related potential (ERP) associated with WM, was examined because of its relation with attentional allocation during WM. Task performance (accuracy, reaction time) as well as performance on other neuropsychological tasks of WM was analyzed. RESULTS Neural differences were found between the groups. Specifically, the P3 amplitude was smaller in the ADHD group compared to the comparison group for both load conditions at parietal-occipital sites. Lower scores on behavioural working memory tasks were suggestive of impaired behavioural WM performance in the ADHD group. CONCLUSIONS Findings from this study provide the first evidence of neural differences in the encoding stage of WM in young adults with ADHD, suggesting ineffective allocation of attentional resources involved in encoding of information in WM. SIGNIFICANCE These findings, reflecting alternate neural functioning of WM, may explain some of the difficulties related to WM functioning that college students with ADHD report in their every day cognitive functioning.

Three Time Scales of Neural Self-Organization Underlying Basic and Nonbasic Emotions

Our model integrates the nativist assumption of prespecified neural structures underpinning basic emotions with the constructionist view that emotions are assembled from psychological constituents. From a dynamic systems perspective, the nervous system self-organizes in different ways at different time scales, in relation to functions served by emotions. At the evolutionary scale, brain parts and their connections are specified by selective pressures. At the scale of development, connectivity is revised through synaptic shaping. At the scale of real time, temporary networks of synchronized activity mediate responses to situations. To the degree that humans share common emotional functions, neural structuration is similar across scales, giving rise to “basic” emotions. However, unique developmental and situational factors select for neural configurations mediating emotional variants.

Similarities and differences in the default mode network across rest, retrieval, and future imagining

The default mode network (DMN) has been identified reliably during rest, as well as during the performance of tasks such as episodic retrieval and future imagining. It remains unclear why this network is engaged across these seemingly distinct conditions, though many hypotheses have been proposed to account for these effects. Prior to generating hypotheses explaining common DMN involvement, the degree of commonality in the DMN across these conditions, within individuals, must be statistically determined to test whether or not the DMN is truly a unitary network, equally engaged across rest, retrieval and future imagining. To provide such a test, we used comparable paradigms (self‐directed, uninterrupted thought of equal duration) across the three conditions (rest, retrieval, and future imagining) in a within‐participant design. We found lower than expected pattern similarity in DMN functional connectivity across the three conditions. Similarity in connectivity accounted for only 40–50% of the total variance. Partial Least Squares (PLS) analyses revealed the medial temporal regions of the DMN were preferentially coupled with one another during episodic retrieval and future imagining, whereas the non‐medial temporal regions of the DMN (e.g., medial prefrontal cortex, lateral temporal cortex, and temporal pole) were preferentially coupled during rest. These results suggest that DMN connectivity may be more flexible than previously considered. Our findings are in line with emerging evidence that the DMN is not a static network engaged commonly across distinct cognitive processes, but is instead a dynamic system, topographically changing in relation to ongoing cognitive demands. Hum Brain Mapp 38:1155–1171, 2017.

Laterality effects in functional connectivity of the angular gyrus during rest and episodic retrieval.

INTRODUCTION The angular gyrus (AG) is consistently reported in neuroimaging studies of episodic memory retrieval and is a fundamental node within the default mode network (DMN). Its specific contribution to episodic memory is debated, with some suggesting it is important for the subjective experience of episodic recollection, rather than retrieval of objective episodic details. Across studies of episodic retrieval, the left AG is recruited more reliably than the right. We explored functional connectivity of the right and left AG with the DMN during rest and retrieval to assess whether connectivity could provide insight into the nature of this laterality effect. METHODS Using data from the publically available 1000 Functional Connectome Project, 8min of resting fMRI data from 180 healthy young adults were analysed. Whole-brain functional connectivity at rest was measured using a seed-based Partial Least Squares (seed-PLS) approach (McIntosh and Lobaugh, 2004) with bilateral AG seeds. A subsequent analysis used 6-min of rest and 6-min of unconstrained, silent retrieval of autobiographical events from a new sample of 20 younger adults. Analysis of this dataset took a more targeted approach to functional connectivity analysis, consisting of univariate pairwise correlations restricted to nodes of the DMN. RESULTS The seed-PLS analysis resulted in two Latent Variables that together explained ~86% of the shared cross-block covariance. The first LV revealed a common network consistent with the DMN and engaging the AG bilaterally, whereas the second LV revealed a less robust, yet significant, laterality effect in connectivity - the left AG was more strongly connected to the DMN. Univariate analyses of the second sample again revealed better connectivity between the left AG and the DMN at rest. However, during retrieval the left AG was more strongly connected than the right to non-medial temporal (MTL) nodes of the DMN, and MTL nodes were more strongly connected to the right AG. DISCUSSION The multivariate analysis of resting connectivity revealed that the left and right AG show similar connectivity with the DMN. Only after accounting for this commonality were we able to detect a left laterality effect in DMN connectivity. Further probing with univariate connectivity analyses during retrieval demonstrates that the left preference we observe is restricted to the non-MTL regions of the DMN, whereas the right AG shows significantly better connectivity with the MTL. These data suggest bilateral involvement of the AG during retrieval, despite the focus on the left AG in the literature. Furthermore, the results suggest that the contribution of the left AG to retrieval may be separable from that of the MTL, consistent with a role for the left AG in the subjective aspects of recollection in memory, whereas the MTL and the right AG may contribute to objective recollection of specific memory details.

Visual sampling predicts hippocampal activity.

Eye movements serve to accumulate information from the visual world, contributing to the formation of coherent memory representations that support cognition and behavior. The hippocampus and the oculomotor network are well connected anatomically through an extensive set of polysynaptic pathways. However, the extent to which visual sampling behavior is related to functional responses in the hippocampus during encoding has not been studied directly in human neuroimaging. In the current study, participants engaged in a face processing task while brain responses were recorded with fMRI and eye movements were monitored simultaneously. The number of gaze fixations that a participant made on a given trial was correlated significantly with hippocampal activation such that more fixations were associated with stronger hippocampal activation. Similar results were also found in the fusiform face area, a face-selective perceptual processing region. Notably, the number of fixations was associated with stronger hippocampal activation when the presented faces were novel, but not when the faces were repeated. Increases in fixations during viewing of novel faces also led to larger repetition-related suppression in the hippocampus, indicating that this fixation–hippocampal relationship may reflect the ongoing development of lasting representations. Together, these results provide novel empirical support for the idea that visual exploration and hippocampal binding processes are inherently linked. SIGNIFICANCE STATEMENT The hippocampal and oculomotor networks have each been studied extensively for their roles in the binding of information and gaze function, respectively. Despite the evidence that individuals with amnesia whose damage includes the hippocampus show alterations in their eye movement patterns and recent findings that the two systems are anatomically connected, it has not been demonstrated whether visual exploration is related to hippocampal activity in neurologically intact adults. In this combined fMRI–eye-tracking study, we show how hippocampal responses scale with the number of gaze fixations made during viewing of novel, but not repeated, faces. These findings provide new evidence suggesting that the hippocampus plays an important role in the binding of information, as sampled by gaze fixations, during visual exploration.

Effects of working memory training on neural correlates of Go/Nogo response control in adults with ADHD: A randomized controlled trial

ABSTRACT Working memory and response control are conceptualized as functions that are part of a closely connected and integrated executive function system mediated by the prefrontal cortex and other related brain structures. In the present paper, we asked whether effects of intensive and adaptive computerized working memory training (CWMT) would generalize to enhancements in response control at behavioral and neural levels. A total of 135 postsecondary students with Attention‐Deficit/Hyperactivity Disorder (ADHD), a condition associated with executive function impairments, were randomized into a Standard‐length CWMT (45‐min /session, 25 sessions), Shortened‐length CWMT (15 min/session, 25 sessions), and a waitlist group. Both training groups received CWMT for 5 days a week for 5 weeks long. All participants completed a Go‐Nogo task while neural activity was measured using Electroencephalography (EEG), before and after CWMT. Behavioral results showed trend level evidence (p=0.061) for benefits of CWMT on response control (i.e., improved accuracy of Go responses). Among several neural measures results showed statistically significant changes after CWMT only for the Go trial ERP N2 and P3 in frontal electrodes (p=0.039 and 0.001, respectively). However, given the lack of relationship between behavioral and neural changes and especially the clear lack of predicted does effects (i.e., standard length > short length > control), we conclude that there is no convincing evidence that the working memory training per se changes neural activation patterns in untrained executive functions. The positive finding of general training related changes in this study should have no clinical implications, but may contribute to the literature in better understanding the relationship between neural plasticity and transfer. HIGHLIGHTSWe reported a randomized controlled clinical trial on effects of working memory training.We focused on training transfer effects in adults with ADHD, at both the behavioral and neural level.We used Go/Nogo task performance and ERPs (N2 and P3) as our main training transfer measures.We found no evidence for transfer effects from working memory training per se to response control.