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• No response accuracy costs related to increasing cognitive load during walking. • No response speed costs related to increasing cognitive load during walking. • No gait consistency costs related to increasing cognitive load during walking. • Increasing cognitive load during walking came with widespread EEG changes. This study elucidates the neural mechanisms underlying increasing cognitive load while walking by employing 2 versions of a response inhibition task, the '1-back' version and the more cognitively demanding '2-back' version. By using the Mobile Brain/Body Imaging (MoBI) modality, electroencephalographic (EEG) activity, three-dimensional (3D) gait kinematics and task-related behavioral responses were collected while young adults (n = 61) performed either the 1-back or 2-back response inhibition task. Interestingly, increasing inhibitory difficulty from 1-back to 2-back during walking was not associated with any detectable costs in response accuracy, response speed, or gait consistency. However, the more difficult cognitive task was associated with distinct EEG component changes during both successful inhibitions (correct rejections) and successful executions (hits) of the motor response. During correct rejections, ERP changes were found over frontal regions, during latencies related to sensory gain control, conflict monitoring and working memory storage and processing. During hits, ERP changes were found over left-parietal regions during latencies related to orienting attention and subsequent selection and execution of the motor plan. The pattern of attenuation in walking-related EEG amplitude changes, during 2-back task performance, is thought to reflect more effortful recalibration of neural processes, a mechanism which might be a key driver of performance maintenance in the face of increased cognitive demands while walking. Overall, the present findings shed light on the extent of the neurocognitive capacity of young adults and may lead to a better understanding of how factors such as aging or neurological disorders could impinge on this capacity. [ABSTRACT FROM AUTHOR]

• High-density EEG was collected during treadmill walking and seated conditions. • Assessed long-term test-retest reliability of the N2 and P3 event-related potentials. • Adequate to excellent N2/P3 stability was found during sitting and walking. • Demonstration of reliability is essential for translational application of MoBI technique. Advancements in acquisition technology and signal-processing techniques have spurred numerous recent investigations on the electro-cortical signals generated during whole-body motion. This approach, termed Mobile Brain/Body Imaging (MoBI), has the potential to elucidate the neural correlates of perceptual and cognitive processes during real-life activities, such as locomotion. However, as of yet, no one has assessed the long-term stability of event-related potentials (ERPs) recorded under these conditions. Therefore, the objective of the current study was to evaluate the test-retest reliability of cognitive ERPs recorded while walking. High-density EEG was acquired from 12 young adults on two occasions, separated by an average of 2.3 years, as they performed a Go/No-Go response inhibition paradigm. During each testing session, participants performed the task while walking on a treadmill and seated. Using the intraclass correlation coefficient (ICC) as a measure of agreement, we focused on two well-established neurophysiological correlates of cognitive control, the N2 and P3 ERPs. Following ICA-based artifact rejection, the earlier N2 yielded good to excellent levels of reliability for both amplitude and latency, while measurements for the later P3 component were generally less robust but still indicative of adequate to good levels of stability. Interestingly, the N2 was more consistent between walking sessions, compared to sitting, for both hits and correct rejection trials. In contrast, the P3 waveform tended to have a higher degree of consistency during sitting conditions. Overall, these results suggest that the electro-cortical signals obtained during active walking are representative of stable indices of neurophysiological function. [ABSTRACT FROM AUTHOR]

Difficulty integrating inputs from different sensory sources is commonly reported in individuals with Autism Spectrum Disorder (ASD). Accumulating evidence consistently points to altered patterns of behavioral reactions and neural activity when individuals with ASD observe or act upon information arriving through multiple sensory systems. For example, impairments in the integration of seen and heard speech appear to be particularly acute, with obvious implications for interpersonal communication. Here, we explore the literature on multisensory processing in autism with a focus on developmental trajectories. While much remains to be understood, some consistent observations emerge. Broadly, sensory integration deficits are found in children with an ASD whereas these appear to be much ameliorated, or even fully recovered, in older teenagers and adults on the spectrum. This protracted delay in the development of multisensory processing raises the possibility of applying early intervention strategies focused on multisensory integration, to accelerate resolution of these functions. We also consider how dysfunctional cross-sensory oscillatory neural communication may be one key pathway to impaired multisensory processing in ASD. [ABSTRACT FROM AUTHOR]

Deficits in cognitive control have been considered a core dysfunction of psychopathy, responsible for disrupted self-control. We investigated cognitive control impairments, including difficulties with task switching, failure of response inhibition, and inability to adjust speed of responding. Participants included 16 subjects with psychopathic traits (Ps), and 22 healthy controls (HCs). We recorded behavioral responses during a Task Switching paradigm, a probe of flexible behavioral adaptation to changing contexts; and a Go/NoGo Task, which assesses response inhibition and indexes behavioral impulsivity. During task switching, Ps evidenced impairments shifting set when conflicting (incongruent) information was presented, but performed as well as HCs in the absence of such conflict. In addition, when they encountered these difficulties, they failed to adjust their speed of responding. Ps presented also with deficits in response inhibition, with many commission errors on the Go/NoGo Task. This study identified impairments in response inhibition and in set shifting in psychopathic individuals. When shifting set, they evidenced difficulties refocusing on a new task when it was incongruent with the previous task. These deficits interfere with regulation of ongoing behavior and disrupt self-regulation. Our findings suggest abnormal neural processing during suppression of inappropriate responses in psychopathic individuals. [ABSTRACT FROM AUTHOR]

Two sensory systems are intrinsic to learning to read. Written words enter the brain through the visual system and associated sounds through the auditory system. The task before the beginning reader is quite basic. She must learn correspondences between orthographic tokens and phonemic utterances, and she must do this to the point that there is seamless automatic ‘connection’ between these sensorially distinct units of language. It is self-evident then that learning to read requires formation of cross-sensory associations to the point that deeply encoded multisensory representations are attained. While the majority of individuals manage this task to a high degree of expertise, some struggle to attain even rudimentary capabilities. Why do dyslexic individuals, who learn well in myriad other domains, fail at this particular task? Here, we examine the literature as it pertains to multisensory processing in dyslexia. We find substantial support for multisensory deficits in dyslexia, and make the case that to fully understand its neurological basis, it will be necessary to thoroughly probe the integrity of auditory–visual integration mechanisms. [ABSTRACT FROM AUTHOR]

Abstract: Neuroimaging studies in current cocaine dependent (CD) individuals consistently reveal cortical hypoactivity across regions of the response inhibition circuit (RIC). Dysregulation of this critical executive network is hypothesized to account for the lack of inhibitory control that is a hallmark of the addictive phenotype, and chronic abuse is believed to compound the issue. A crucial question is whether deficits in this circuit persist after drug cessation, and whether recovery of this system will be seen after extended periods of abstinence, a question with implications for treatment course and outcome. Utilizing functional magnetic resonance imaging (fMRI), we examined activation in nodes of the RIC in abstinent CD individuals (n = 27) and non-using controls (n = 45) while they performed a motor response inhibition task. In contrast to current users, these abstinent individuals, despite extended histories of chronic cocaine-abuse (average duration of use = 8.2 years), performed the task just as efficiently as non-users. In line with these behavioral findings, no evidence for between-group differences in activation of the RIC was found and instead, robust activations were apparent in both groups within the well-characterized nodes of the RIC. Similarly, our complementary Electroencephalography (EEG) investigation also showed an absence of behavioral and electrophysiological deficits in abstinent drug abusers. These results are consistent with an amelioration of neurobiological deficits in inhibitory circuitry following drug cessation, and could help explain how long-term abstinence is maintained. Finally, regression analyses revealed a significant association between level of activation in the right insula with inhibition success and increased abstinence duration in the CD cohort suggesting that this region may be integral to successful recovery from cocaine addiction. [Copyright &y& Elsevier]

Abstract: Caffeine and l-theanine, both naturally occurring in tea, affect the ability to make rapid phasic deployments of attention to locations in space as reflected in behavioural performance and alpha-band oscillatory brain activity (8–14 Hz). However, surprisingly little is known about how these compounds affect an aspect of attention that has been more popularly associated with tea, namely vigilant attention: the ability to maintain focus on monotonous tasks over protracted time-periods. Twenty-seven participants performed the Sustained Attention to Response Task (SART) over a two-hour session on each of four days, on which they were administered caffeine (50 mg), theanine (100 mg), the combination, or placebo in a double-blind, randomized, cross-over fashion. Concurrently, we recorded oscillatory brain activity through high-density electroencephalography (EEG). We asked whether either compound alone, or both in combination, would affect performance of the task in terms of reduced error rates over time, and whether changes in alpha-band activity would show a relationship to such changes in performance. When treated with placebo, participants showed a rise in error rates, a pattern that is commonly observed with increasing time-on-task, whereas after caffeine and theanine ingestion, error rates were significantly reduced. The combined treatment did not confer any additional benefits over either compound alone, suggesting that the individual compounds may confer maximal benefits at the dosages employed. Alpha-band oscillatory activity was significantly reduced on ingestion of caffeine, particularly in the first hour. This effect was not changed by addition of theanine in the combined treatment. Theanine alone did not affect alpha-band activity. [Copyright &y& Elsevier]

Abstract: Introduction: Extensive evidence demonstrates that current cocaine abusers show hypoactivity in anterior cingulate and dorsolateral prefrontal cortex and respond poorly relative to drug-naïve controls on tests of executive function. Relatively little is known about the cognitive sequelae of long-term abstinence in cocaine addicts. Methods: Here, we use a GO–NOGO task in which successful performance necessitated withholding a prepotent response to assay cognitive control in short- and long-term abstinent cocaine users (1–5 weeks and 40–102 weeks, respectively). Results: We report significantly greater activity in prefrontal, cingulate, cerebellar and inferior frontal gyrii in abstinent cocaine users for both successful response inhibitions and errors of commission. Moreover, this relative hyperactivity was present in both abstinent groups, which, in the presence of comparable behavioral performance, suggests a functional compensation. Conclusions: Differences between the short- and long-abstinence groups in the patterns of functional recruitment suggest different cognitive control demands at different stages in abstinence. Short-term abstinence showed increased inhibition-related dorsolateral and inferior frontal activity indicative of the need for increased inhibitory control while long-term abstinence showed increased error-related ACC activity indicative of heightened behavioral monitoring. The results suggest that the integrity of prefrontal systems that underlie cognitive control functions may be an important characteristic of successful long-term abstinence. [Copyright &y& Elsevier]

Abstract: Current cocaine-dependent users show reductions in white matter (WM) integrity, especially in cortical regions associated with cognitive control that have been associated with inhibitory dysfunction. A key question is whether these white matter differences are present following abstinence from drug use. To address this, WM integrity was examined using diffusion tensor imaging (DTI) obtained on 43 cocaine abstinent patients (abstinence duration ranged between five days and 102 weeks) and 43 non-using controls. Additionally, a cross-sectional comparison separated the patients into three groups (short-term, mid-term and long-term) based upon duration of cocaine abstinence. The 43 cocaine abstinent patients showed lower fractional anisotropy (FA) in the left anterior callosal fibers, left genu of the corpus callosum, right superior longitudinal fasciculus, right callosal fibers and the superior corona radiata bilaterally when compared against non-using controls. Higher FA in the cocaine abstinent patients was observed in the splenium of the corpus callosum and right superior longitudinal fasciculus. Differences between the cocaine abstinent groups were observed bilaterally in the inferior longitudinal fasciculus, right anterior thalamic radiation, right ventral posterolateral nucleus of the thalamus, left superior corona radiata, superior longitudinal fasciculus bilaterally, right cingulum and the WM of the right precentral gyrus. The results identified WM differences between cocaine abstinent patients and controls as well as distinct differences between abstinent subgroups. The findings suggest that specific white matter differences persist throughout abstinence while other, spatially distinct, differences discriminate as a function of abstinence duration. These differences may, therefore, represent brain changes that mark recovery from addiction. [Copyright &y& Elsevier]

Objectives: Geriatric depression is associated with frontolimbic functional deficits, and this frontal dysfunction may underlie the marked executive control deficits often seen in this population. The authors' goal was to assess the integrity of frontal cortical functioning in geriatric depression, while these individuals performed a standard cognitive control task. The N2 component of the event-related potential (ERP), an evoked response generated within the anterior cingulate cortex (ACC), is significantly enhanced when nondepressed individuals successfully inhibit a response, providing an excellent metric of frontal inhibitory function. Design: The authors used a variant of a demanding Go/NoGo task-switching paradigm that required participants to inhibit response execution during NoGo trials by overcoming a potent response tendency established by frequent Go trials. Participants: The authors compared a cohort of depressed geriatric outpatients (N = 11) with a similarly aged group of nondepressed participants (TV = 11). Measurements: Reaction times, accuracy, and high-density event-related potential recordings from a 64-channel electrode montage were obtained. Results: A significantly enhanced N2 to NoGo trials was observed in nondepressed elderly participants, with generators localized to the ACC. In contrast, this enhancement was strongly reduced in the depressed sample. Source analysis and topographic mapping pointed to a displacement of N2 generators toward more posterior areas of the middle frontal gyrus in depressed subjects. Conclusions: Findings confirm previous reports of an inhibitory control deficit in depressed elderly who show significantly increased rates of commission errors (i.e., failures to inhibit responses on NoGo trials). Electrophysiologic data suggest underlying dysfunction in ACC as the basis for this deficit. [ABSTRACT FROM AUTHOR]

Abstract: Background: Recent studies have shown that schizophrenia is characterized by visual perceptual deficits, especially in the ability to integrate stimulus details into a global percept. Also, several studies have found amplitude attenuation of the visual P1 component of the event-related brain potential (ERP), probably indicating impaired visual feedforward processing in schizophrenia. However, there is little knowledge on the role of feedbackward processing in this group. This question is of importance, as recent studies indicate that feedback processing is critical in stimulus integration. Methods: In the present study we tested whether there is evidence for atypical recurrent processing in a group of 14 young adults with recent-onset schizophrenia (mean age 21.7 years, mean TIQ 92.7) and 17 age and IQ matched control subjects, all males. To achieve this aim, we used a texture segregation task and measured ERP activity concurrently. Results: We found normal amplitudes, but longer latencies of activity related to feedbackward processing in the schizophrenia group. In addition, we found enhanced occipito-temporal activity around 160ms that is probably the reflection of increased detail processing. Discussion: We show for the first time evidence for abnormal timing in feedback activity related to visual perception in subjects with schizophrenia. It is hypothesized that this latency effect is the functional reflection of abnormal structural connectivity in this group, and might result in increased processing of stimulus detail. [Copyright &y& Elsevier]

Abstract: Stimulus contrast fluctuations were controlled while the properties of a novel ERP known as the VESPA (Visual Evoked Spread Spectrum Analysis) were examined using data from 8 healthy human subjects. Substantial differences were seen between the morphologies of VESPAs obtained using low contrast stimuli when compared with those obtained using high contrast and full contrast range stimuli. Topographic distributions for both responses are compared and the findings are considered in terms of the response characteristics of the magnocellular and parvocellular visual pathways and the VESPA method itself. [Copyright &y& Elsevier]

The Adolescent Brain Cognitive Development (ABCD) Study of 11,880 youth incorporates a comprehensive range of measures assessing predictors and outcomes related to mental health across childhood and adolescence in participating youth, as well as information about family mental health history. We have previously described the logic and content of the mental health assessment battery at Baseline and 1-year follow-up. Here, we describe changes to that battery and issues and clarifications that have emerged, as well as additions to the mental health battery at the 2-, 3-, 4-, and 5-year follow-ups. We capitalize on the recent release of longitudinal data for caregiver and youth report of mental health data to evaluate trajectories of dimensions of psychopathology as a function of demographic factors. For both caregiver and self-reported mental health symptoms, males showed age-related decreases in internalizing and externalizing symptoms, while females showed an increase in internalizing symptoms with age. Multiple indicators of socioeconomic status (caregiver education, family income, financial adversity, neighborhood poverty) accounted for unique variance in both caregiver and youth-reported externalizing and internalizing symptoms. These data highlight the importance of examining developmental trajectories of mental health as a function of key factors such as sex and socioeconomic environment. [ABSTRACT FROM AUTHOR]

Recent neuropharmacological research has suggested that certain constituents of tea may have modulatory effects on brain state. The bulk of this research has focused on either L-theanine or caffeine ingested alone (mostly the latter) and has been limited to behavioral testing, subjective rating, or neurophysiological assessments during resting. Here, we investigated the effects of both L-theanine and caffeine, ingested separately or together, on behavioral and electrophysiological indices of tonic (background) and phasic (event-related) visuospatial attentional deployment. Subjects underwent 4 d of testing, ingesting either placebo, 100 mg of L-theanine, 50 mg of caffeine, or these treatments combined. The task involved cued shifts of attention to the left or right visual hemifield in anticipation of an imperative stimulus requiring discrimination. In addition to behavioral measures, we examined overall, tonic attentional focus as well as phasic, cue-dependent anticipatory attentional biasing, as indexed by scalp-recorded alpha-band (8–14 Hz) activity. We found an increase in hit rate and target discriminability (d') for the combined treatment relative to placebo, and an increase in d' but not hit rate for caffeine alone, whereas no effects were detected for L-theanine alone. Electrophysiological results did not show increased differential biasing in phasic alpha across hemifields but showed lower overall tonic alpha power in the combined treatment, similar to previous findings at a larger dosage of L-theanine alone. This may signify a more generalized tonic deployment of attentional resources to the visual modality and may underlie the facilitated behavioral performance on the combined ingestion of these 2 major constituents of tea. [ABSTRACT FROM AUTHOR]

Abstract: Kelly C, Foxe JJ, Garavan H. Patterns of normal human brain plasticity after practice and their implications for neurorehabilitation. Objectives: To illustrate how our knowledge about normal patterns of experience-induced plasticity can provide insights into the mechanisms of neurorehabilitation; to provide an overview of the practice-effects literature in order to simplify and amalgamate a large number of heterogeneous findings and identify typical patterns of practice effects and their determining factors; and to concentrate on the impact of practice on higher cognitive functions, such as working memory, and present some preliminary but promising behavioral data that show how practice on a complex cognitive task can benefit cognitive functioning more generally. Data Sources: We performed a systematic search for peer-reviewed journal articles using computerized databases (PubMed, ISI Web of Science, PsycINFO). Data Selection: Neuroimaging studies using functional magnetic resonance imaging (fMRI) or positron-emission tomography (PET) to examine functional activation changes as a result of practice on sensory, motor, or cognitive tasks in normal (healthy) populations were included in the review. Further studies were identified that examined the effects of rehabilitative training on functional activations in clinical populations using fMRI or PET. Data Extraction: Important characteristics of the selected studies were summarized in a systematic manner so to enable the extraction of specific factors impacting on the pattern of practice effects observed. Data Synthesis: We identified a number of factors that impact on the patterns of practice effects observed and discuss how the insights gained from the study of healthy populations can by applied to rehabilitation of cognitive deficits in clinical populations. Conclusions: Progress in our understanding of neurorehabilitative plasticity will be enabled by neuroimaging examinations of cognitive rehabilitation training grounded in a knowledge of normal (healthy) patterns of brain activation and practice-induced plasticity. [Copyright &y& Elsevier]

Neurobiologists have traditionally assumed that multisensory integration is a higher order process that occurs after sensory signals have undergone extensive processing through a hierarchy of unisensory subcortical and cortical regions. Recent findings, however, question this assumption. Studies in humans, nonhuman primates and other species demonstrate multisensory convergence in low level cortical structures that were generally believed to be unisensory in function. In addition to enriching current models of multisensory processing and perceptual functions, these new findings require a revision in our thinking about unisensory processing in low level cortical areas. [Copyright &y& Elsevier]

Background: Deficits in affect recognition are prominent features of schizophrenia. Within the auditory domain, patients show difficulty in interpreting vocal emotional cues based on intonation (prosody). The relationship of these symptoms to deficits in basic sensory processing has not been previously evaluated. Methods: Forty-three patients and 34 healthy comparison subjects were tested on two affective prosody measures: voice emotion identification and voice emotion discrimination. Basic auditory sensory processing was measured using a tone-matching paradigm and the Distorted Tunes Test (DTT). A subset of subjects was also tested on facial affect identification and discrimination tasks. Results: Patients showed significantly impaired performance on all emotion processing tasks. Within the patient group, a principal components analysis demonstrated significant intercorrelations between basic pitch perception and affective prosodic performance. In contrast, facial affect recognition deficits represented a distinct second component. Prosodic affect measures correlated significantly with severity of negative symptoms and impaired global outcome. Conclusions: These results demonstrate significant relationships between basic auditory processing deficits and impaired receptive prosody in schizophrenia. The separate loading of auditory and visual affective recognition measures suggests that within-modality factors may be more significant than cross-modality factors in the etiology of affect recognition deficits in schizophrenia. [Copyright &y& Elsevier]

Two fundamental requirements for multisensory integration are convergence of unisensory (e.g. visual and auditory) inputs and temporal alignment of the neural responses to convergent inputs. We investigated the anatomic mechanisms of multisensory convergence by examining three areas in which convergence occurs, posterior auditory association cortex, superior temporal polysensory area (STP) and ventral intraparietal sulcus area (VIP). The first of these was recently shown to be a site of multisensory convergence and the latter two are more well known as ‘classic’ multisensory regions. In each case, we focused on defining the laminar profile of response to the unisensory inputs. This information is useful because two major types of connection, feedforward and feedback, have characteristic differences in laminar termination patterns, which manifest physiologically. In the same multisensory convergence areas we also examined the timing of the unisensory inputs using the same standardized stimuli across all recordings. Our findings indicate that: (1) like somatosensory input [J. Neurophysiol., 85 (2001) 1322], visual input is available at very early stages of auditory processing, (2) convergence occurs through feedback, as well as feedforward anatomical projections and (3) input timing may be an asset, as well as a constraint in multisensory processing. [Copyright &y& Elsevier]

• We provide a publicly available spoken word stimulus set designed to evoke the N400. • Both semantic and syntactic errors can be assayed using this public stimulus set. • We provide 20 high-density neurotypical adult electrophysiological datasets. • The utility of these stimuli is demonstrated through robust evocation of the N400. • Cloze probability values for each stimulus are provided. During speech comprehension, the ongoing context of a sentence is used to predict sentence outcome by limiting subsequent word likelihood. Neurophysiologically, violations of context-dependent predictions result in amplitude modulations of the N400 event-related potential (ERP) component. While the N400 is widely used to measure semantic processing and integration, no publicly-available auditory stimulus set is available to standardize approaches across the field. Here, we developed an auditory stimulus set of 442 sentences that utilized the semantic anomaly paradigm, measured cloze probability for all stimuli, and was made for both children and adults. With 20 neurotypical adults, we validated that this set elicits robust N400′s, as well as two additional semantically-related ERP components: the recognition potential (∼ 250 ms) and the late positivity component (∼ 600 ms). This stimulus set (https://doi.org/10.5061/dryad.9ghx3ffkg) and the 20 high-density (128-channel) electrophysiological datasets (https://doi.org/10.5061/dryad.6wwpzgmx4) are made publicly available to promote data sharing and reuse. Future studies that use this stimulus set to investigate sentential semantic comprehension in both control and clinical populations may benefit from the increased comparability and reproducibility within this field of research. [ABSTRACT FROM AUTHOR]

• The temporal features of somatosensory processing can be assessed using EEG. • Mismatch negativity was not elicited between vibrations of 100 ms and 115 ms. • Mismatch negativity was elicited between vibrations of 100 ms and 130, 145 or 160 ms. Duration is an amodal feature common to all sensory experiences, but low-level processing of the temporal qualities of somatosensation remains poorly understood. The goal of the present study was to evaluate electrophysiological discrimination of parametric somatosensory stimuli to better understand how the brain processes the duration of tactile information. This research used a somatosensory mismatch negativity (sMMN) paradigm to evaluate electrophysiological sensitivity to differences in the duration of vibrotactile stimuli in healthy young adults. Specifically, a 100 ms standard vibration was presented 80% of the time while the remaining 20% of presentations were made up of deviant stimuli with one of the following durations: 115, 130, 145, or 160 ms. When a deviation from the anticipated tactile input is detected, the distinct electrophysiological signature of the sMMN is present. A companion behavioral task assessed individual thresholds for cognizant awareness of the standard and deviant vibrotactile stimuli. The results of the present study demonstrated a sMMN response when deviant stimuli were 130, 145, and 160 ms, but not when they were 115 ms. This suggests that on average the participants did not electrophysiologically discriminate between the 100 and 115 ms. Future work may apply this paradigm to better understand atypical tactile sensitivity in various clinical conditions. [ABSTRACT FROM AUTHOR]

• The neural basis of daily functional limitations related to cognition aging is unknown • We measured EEG brain activation during a common daily task: adjusting gait • Brain activation during gait adjustment is linked to risk of cognitive impairment Assessment of everyday activities is central to the diagnosis of dementia. Yet, little is known about brain processes associated with everyday functional limitations, particularly during early stages of cognitive decline. Twenty-six older adults (mean = 74.9 y) were stratified by risk using the Montreal Cognitive Assessment battery (MoCA, range: 0– 30) to classify individuals as higher (22–26) and lower risk (27+) of cognitive impairment. We investigated everyday function using a gait task designed to destabilize posture and applied Mobile Brain/Body Imaging. We predicted that participants would increase step width to gain stability, yet the underlying neural signatures would be different for lower versus higher risk individuals. Step width and fronto-parietal activation increased during visually perturbed input. Frontomedial theta increased in higher risk individuals during perturbed and unperturbed inputs. Left sensorimotor beta decreased in lower risk individuals during visually perturbed input. Modulations in theta and beta power were associated with MoCA scores. Our findings suggest that older adults at-risk of cognitive impairment can be characterized by a unique neural signature of everyday function. [ABSTRACT FROM AUTHOR]

• Cocaine dependence (CD) is a common comorbidity of HIV infection. • The effect of former cocaine dependence on brain integrity in HIV+ individuals was explored. • Higher caudate volume was observed in abstinent CD participants. • HIV identified as the primary driver of reduced cognitive performance on neurocognitive testing. • No interactions between HIV and CD history were identified. Evidence from animal research, postmortem analyses, and magnetic resonance imaging (MRI) investigations indicate substantial morphological alteration in brain structure as a function of human immunodeficiency virus (HIV) or cocaine dependence (CD). Although previous research on HIV+ active cocaine users suggests the presence of deleterious morphological effects in excess of either condition alone, a yet unexplored question is whether there is a similar deleterious interaction in HIV+ individuals with CD who are currently abstinent. To this end, the combinatorial effects of HIV and CD history on regional brain volume, cortical thickness, and neurocognitive performance was examined across four groups of participants in an exploratory study: healthy controls (n = 34), HIV-negative individuals with a history of CD (n = 21), HIV+ individuals with no history of CD (n = 20), HIV+ individuals with a history of CD (n = 15). Our analyses revealed no statistical evidence of an interaction between both conditions on brain morphometry and neurocognitive performance. While descriptively, individuals with comorbid HIV and a history of CD exhibited the lowest neurocognitive performance scores, using Principle Component Analysis of neurocognitive testing data, HIV was identified as the primary driver of neurocognitive impairment. Higher caudate volume was evident in CD+ participants relative to CD− participants. Findings indicate no evidence of compounded differences in neurocognitive function or structural measures of brain integrity in HIV+ individuals in recovery from CD relative to individuals with only one condition. [ABSTRACT FROM AUTHOR]

A significant hindrance to effective treatment of addiction is identifying those most likely to relapse. Cocaine addiction is characterized by deficits in inhibitory control and elevated reactivity to cocaine cues, both hypothesized to be integral to development of addiction and propensity to relapse. It follows that reduction of both impulsivity and cue-reactivity following abstinence is protective against relapse, and that persistence of these factors increases vulnerability. Using functional magnetic resonance imaging, we examined neural activation patterns in dorsal and ventral striatum in abstinent cocaine dependent (CD) individuals (N = 20) and non-using controls (N = 19) as they performed a cocaine craving task. We also examined activations in nodes of the response inhibition circuit (RIC) as they performed an inhibition task. At the between-groups level, no differences in RIC or striatal activation were seen in former users, in contrast to previous investigations in current users, suggesting large-scale functional recovery with abstinence. However, at the individual participant-level, abstinent CD individuals displayed an association between cocaine cue-related neural activations in the right ventral striatum and compulsive cocaine craving scores. Compulsive craving scores were also negatively correlated with duration of abstinence. Further, there was an association between motor impulsivity scores and inhibition-related activations in the right inferior frontal gyrus and pre-supplementary motor area in abstinent CD individuals. Thus, while former users as a group did not show deficits in inhibitory function or cocaine-cue reactivity, participant-level results pointed to activation patterns in a minority of these individuals that likely contributes to enduring relapse vulnerability. [ABSTRACT FROM AUTHOR]

Abstract: Background: Dependent drug users show a diminished neural response to punishment, in both limbic and cortical regions, though it remains unclear how such changes influence cognitive processes critical to addiction. To assess this relationship, we examined the influence of monetary punishment on inhibitory control and adaptive post-error behavior in abstinent cocaine dependent (CD) participants. Methods: 15 abstinent CD and 15 matched control participants performed a Go/No-go response inhibition task, which administered monetary fines for failed response inhibition, during collection of fMRI data. Results: CD participants showed reduced inhibitory control and significantly less adaptive post-error slowing in response to punishment, when compared to controls. The diminished behavioral punishment sensitivity shown by CD participants was associated with significant hypoactive error-related BOLD responses in the dorsal anterior cingulate cortex (ACC), right insula and right prefrontal regions. Specifically, CD participants’ error-related response in these regions was not modulated by the presence of punishment, whereas control participants’ response showed a significant BOLD increase during punished errors. Conclusions: CD participants showed a blunted response to failed control (errors) that was not modulated by punishment. Consistent with previous findings of reduced sensitivity to monetary loss in cocaine users, we further demonstrate that such insensitivity is associated with an inability to increase cognitive control in the face of negative consequences, a core symptom of addiction. The pattern of deficits in the CD group may have implications for interventions that attempt to improve cognitive control in drug dependent groups via positive/negative incentives. [Copyright &y& Elsevier]

Picture yourself on a crowded sideway with people milling about. The acoustic and visual signals generated by the crowd provide you with complementary information about their locations and motion which needs to be integrated. It is not well understood how such inputs from different sensory channels are combined into unified perceptual states. Coherence of oscillatory neural signals might be an essential mechanism supporting multisensory perception. Evidence is now emerging which indicates that coupled oscillatory activity might serve to link neural signals across uni- and multisensory regions and to express the degree of crossmodal matching of stimulus-related information. These results argue for a new view on multisensory processing which considers the dynamic interplay of neural populations as a key to crossmodal integration. [Copyright &y& Elsevier]

Caffeine, a very widely used and potent neuromodulator, easily crosses the placental barrier, but relatively little is known about the long-term impact of gestational caffeine exposure (GCE) on neurodevelopment. Here, we leverage magnetic resonance imaging (MRI) data, collected from a very large sample of 9157 children, aged 9–10 years, as part of the Adolescent Brain and Cognitive Developmentsm (ABCD ®) study, to investigate brain structural outcomes at 27 major fiber tracts as a function of GCE. Significant relationships between GCE and fractional anisotropy (FA) measures in the inferior fronto-occipito fasciculus and corticospinal tract of the left hemisphere (IFOF-LH; CST-LH) were detected via mixed effects binomial regression. We further investigated the interaction between these fiber tracts, GCE, cognitive measures (working memory, task efficiency), and psychopathology measures (externalization, internalization, somatization, and neurodevelopment). GCE was associated with poorer outcomes on all measures of psychopathology but had negligible effect on cognitive measures. Higher FA values in both fiber tracts were associated with decreased neurodevelopmental problems and improved performance on both cognitive tasks. We also identified a decreased association between FA in the CST-LH and task efficiency in the GCE group. These findings suggest that GCE can lead to future neurodevelopmental complications and that this occurs, in part, through alteration of the microstructure of critical fiber tracts such as the IFOF-LH and CST-LH. These data suggest that current guidelines regarding limiting caffeine intake during pregnancy may require some recalibration. • Caffeine is a known neuromodulator that is commonly consumed throughout pregnancy. • 4,135 mothers reported consuming caffeine more than once a week throughout gestation in a sample of 9,157. • Decreased fractional anisotropy in the left IFOF and CST fiber tracts were associated with gestational caffeine exposure. • Measures related to psychopathology were elevated in those with gestational caffeine exposure. • Gestational caffeine exposure modulated the relationship between task efficiency and fractional anisotropy in the left CST. [ABSTRACT FROM AUTHOR]

• RTT is a dynamic disorder involving stagnation and regression of brain development in early postnatal life. • Studies should be designed as longitudinal to analyze trajectories rather than taking snapshots in time. • New biomarkers and outcome measures that can be directly translated from animal models to patients have been identified. • Synergistic and multidisciplinary efforts are needed to decode and treat the pathogenesis of the complex MeCP2 disorders. Disruptions in the gene encoding methyl-CpG binding protein 2 (MECP2) underlie complex neurodevelopmental disorders including Rett Syndrome (RTT), MECP2 duplication disorder, intellectual disabilities, and autism. Significant progress has been made on the molecular and cellular basis of MECP2 -related disorders providing a new framework for understanding how altered epigenetic landscape can derail the formation and refinement of neuronal circuits in early postnatal life and proper neurological function. This review will summarize selected major findings from the past years and particularly highlight the integrated and multidisciplinary work done at eight NIH-funded Intellectual and Developmental Disabilities Research Centers (IDDRC) across the US. Finally, we will outline a path forward with identification of reliable biomarkers and outcome measures, longitudinal preclinical and clinical studies, reproducibility of results across centers as a synergistic effort to decode and treat the pathogenesis of the complex MeCP2 disorders. [ABSTRACT FROM AUTHOR]

• Operating in a multisensory context inextricably linked to intersensory attention. • Task switching and mixing costs account for the redundant signals effect. Individuals respond faster to presentations of bisensory stimuli (e.g. audio-visual targets) than to presentations of either unisensory constituent in isolation (i.e. to the auditory-alone or visual-alone components of an audio-visual stimulus). This well-established multisensory speeding effect, termed the redundant signals effect (RSE), is not predicted by simple linear summation of the unisensory response time probability distributions. Rather, the speeding is typically faster than this prediction, leading researchers to ascribe the RSE to a so-called co-activation account. According to this account, multisensory neural processing occurs whereby the unisensory inputs are integrated to produce more effective sensory-motor activation. However, the typical paradigm used to test for RSE involves random sequencing of unisensory and bisensory inputs in a mixed design, raising the possibility of an alternate attention-switching account. This intermixed design requires participants to switch between sensory modalities on many task trials (e.g. from responding to a visual stimulus to an auditory stimulus). Here we show that much, if not all, of the RSE under this paradigm can be attributed to slowing of reaction times to unisensory stimuli resulting from modality switching, and is not in fact due to speeding of responses to AV stimuli. As such, the present data do not support a co-activation account, but rather suggest that switching and mixing costs akin to those observed during classic task-switching paradigms account for the observed RSE. [ABSTRACT FROM AUTHOR]

• The association between polysubstance use and inhibition is as-yet-unknown. • This association was tested with a mega-analysis using individual participant data. • Only lifetime cannabis use was associated with suboptimal inhibition (stop-task). • Lifetime cannabis use moderated tobacco's effect on response inhibition. • In cannabis non-users only, tobacco use was associated with suboptimal inhibition. Many studies have reported that heavy substance use is associated with impaired response inhibition. Studies typically focused on associations with a single substance, while polysubstance use is common. Further, most studies compared heavy users with light/non-users, though substance use occurs along a continuum. The current mega-analysis accounted for these issues by aggregating individual data from 43 studies (3610 adult participants) that used the Go/No-Go (GNG) or Stop-signal task (SST) to assess inhibition among mostly "recreational" substance users (i.e., the rate of substance use disorders was low). Main and interaction effects of substance use, demographics, and task-characteristics were entered in a linear mixed model. Contrary to many studies and reviews in the field, we found that only lifetime cannabis use was associated with impaired response inhibition in the SST. An interaction effect was also observed: the relationship between tobacco use and response inhibition (in the SST) differed between cannabis users and non-users, with a negative association between tobacco use and inhibition in the cannabis non-users. In addition, participants' age, education level, and some task characteristics influenced inhibition outcomes. Overall, we found limited support for impaired inhibition among substance users when controlling for demographics and task-characteristics. [ABSTRACT FROM AUTHOR]

Executive function deficits and reward dysregulation, which mainly manifests as anhedonia, are well documented in drug abusers. We investigated specific aspects of executive function (inhibitory control and cognitive control), as well as anhedonia, in a cohort of current cocaine abusers in order to ascertain to what extent these factors are associated with more severe drug dependence. Participants filled out questionnaires relating to anhedonia and their addiction history. Participants also performed a response inhibition task while high-density event-related potentials (ERPs) were recorded. Electrophysiological responses to successful inhibitions (N2/P3 components) and to commission errors (ERN/Pe components) were compared between 23 current users of cocaine and 27 non-using controls. A regression model was performed to determine the association of our measures of reward dysregulation and executive function with addiction severity. As expected, cocaine users performed more poorly than controls on the inhibitory control task and showed significant electrophysiological differences. They were also generally more anhedonic than controls. Higher levels of anhedonia were associated with more severe substance use, whereas the level of executive dysfunction was not associated with more severe substance use. However, N2 amplitude was associated with duration of drug use. Further, inhibitory control and anhedonia were correlated, but only in controls. These data suggest that while executive dysfunction characterizes drug abuse, it is anhedonia, independent of executive dysfunction, that is most strongly associated with more severe use. [ABSTRACT FROM AUTHOR]

Abstract: Response inhibition deficits are well-documented in drug users, and are related to the impulsive tendencies characteristic of the addictive phenotype. Addicts also show significant motivational issues that may accentuate these inhibitory deficits. We investigated the extent to which these inhibitory deficits are present in abstinence. Salience of the task stimuli was also manipulated on the premise that emotionally-valenced inputs might impact inhibitory efficacy by overcoming the blunted responses to everyday environmental inputs characteristic of this population. Participants performed response inhibition tasks consisting of both neutral and emotionally valenced stimuli while high-density event-related potentials (ERPs) were recorded. Electrophysiological responses (N2/P3 components) to successful inhibitions in abstinent abusers (N = 20) and non-using participants (N = 21) were compared. In contrast to previous work in current users, our abstinent cohort showed no detectable behavioral or electrophysiological differences in their inhibitory responses, and no differences on self-reports of impulsivity, despite their long histories of chronic use (mean = 10.3 years). The current findings are consistent with a recovery of inhibitory control processes as a function of abstinence. Abstinent former users, however, did show a reduced modulation, relative to controls, of their ERPs to valenced input while performing successful inhibitions, although contrary to our hypothesis, the use of valenced inputs had no impact on inhibitory performance. Reduced ERP modulation to emotionally valenced inputs may have implications for relapse in emotional contexts outside the treatment center. [Copyright &y& Elsevier]

Individuals with a diagnosis of co-morbid HIV infection and cocaine use disorder are at higher risk of poor health outcomes. Active cocaine users, both with and without HIV infection, show clear deficits in response inhibition and other measures of executive function that are instrumental in maintaining drug abstinence, factors that may complicate treatment. Neuroimaging and behavioral evidence indicate normalization of executive control processes in former cocaine users as a function of the duration of drug abstinence, but it is unknown to what extent co-morbid diagnosis of HIV affects this process. To this end, we investigate the combinatorial effects of HIV and cocaine dependence on the neural substrates of cognitive control in cocaine-abstinent individuals with a history of cocaine dependence. Blood-oxygen level dependent signal changes were measured as 86 participants performed a Go/NoGo response inhibition task while undergoing functional magnetic resonance imaging (fMRI). Four groups of participants were selected based on HIV and cocaine-dependence status. Participants affected by both conditions demonstrated the lowest response accuracy of all participant groups. In a region of interest analysis, hyperactivation in the left putamen and midline-cingulate hyperactivation was observed in individuals with both HIV and cocaine dependence relative to individuals with only one condition. Results of a whole-brain analysis indicate response inhibition-related hyperactivation in the bilateral supplementary motor area, bilateral hippocampi, bilateral primary somatosensory areas, right dorsal anterior cingulate, and left insula in the CD+/HIV+ group relative to all other groups. These results indicate complex and interactive alterations in neural activation during response inhibition and highlight the importance of examining the neurocognitive effects of co-morbid conditions. • Drug abuse is a common comorbidity of HIV infection. • Effects of HIV on neural function were assessed using fMRI in former cocaine users. • Participants with both conditions showed poorest response inhibition performance. • Interactive effects of HIV and drug abuse observed in the cingulate and left putamen. • Whole-brain analysis revealed 18 additional regions showing interactive effects. [ABSTRACT FROM AUTHOR]

The article presents research on the neurobiological basis of inattentiveness in children with attention-deficit/hyperactivity disorder (ADHD), focusing on structural abnormalities in pathways connecting pulvinar nuclei to cortical/subcortical areas of the brain. The study used task-based functional magnetic resonance imaging (fMRI) to study children's brains, and it is concluded that abnormalities in pulvinar nuclei may lead to disrupted functional circuits for visual attention processing.

Abstract: Objective: This study sought to better characterize the contributions of deficits in attention allocation and distracter inhibition to the poor performance on attention tasks often seen in children with ADHD. Methods: Electrophysiological (Nd, P3b) and behavioral measures (speed and accuracy) were examined during an auditory selective attention task in children with ADHD, children with typical development (TD), and adults. Thirty children (15 ADHD; 13 females) between the ages of 7 and 13 and 16 adults (8 females) participated. Results: Nd waveforms were elicited from adults and children with TD, but not from children with ADHD. Further, those with ADHD exhibited significantly smaller auditory responses at 100ms (Ta). P3bs were elicited in all three groups by targets but not by unattended deviants. Performance was significantly poorer in children with ADHD than TD and RTs were more variable. Conclusions: Children with ADHD evidenced poorer attention allocation, as measured by Nd and hits, but were not more distracted by unattended deviants, as measured by P3b and false alarms, than children with TD. Significance: Findings for Nd, P3b, and Ta considered together suggest that deficits in auditory selective attention in children with ADHD may be attributable to reduced information early in the processing stream. [Copyright &y& Elsevier]

Abstract: The ability to detect and correct errors is critical to adaptive control of behaviour and represents a discrete neuropsychological function. A number of studies have highlighted that attention-deficit hyperactivity disorder (ADHD) is associated with abnormalities in behavioural and neural responsiveness to performance errors. One limitation of previous work has been a failure to determine the extent to which these differences are attributable to failures of conscious error awareness, a process that is dependent on the integrity of the frontal lobes. Recent advances in electrophysiological research make it possible to distinguish unconscious and conscious aspects of error processing. This study constitutes an extensive electrophysiological investigation of error awareness and error processing in ADHD. A Go/No-Go response inhibition task specifically designed to assess error awareness was administered to a group of adults diagnosed with ADHD and a group of matched control participants. The ADHD group made significantly more errors than the control group but was less likely to consciously detect these errors. An analysis of event-related potentials elicited by errors indicated that an early performance monitoring component (early positivity) was significantly attenuated in the ADHD group as was a later component that specifically reflects conscious error processing (Pe). Dipole source modelling suggested that abnormal Pe amplitudes were attributable to decreased activation of the anterior cingulate cortex. Decreased electrodermal activity in the ADHD group also suggested a motivational insensitivity to performance errors. Our data provide evidence that neuropsychological deficits associated with ADHD can be exacerbated by error processing abnormalities. Error awareness may represent an important cognitive and physiological phenotype for ADHD. [Copyright &y& Elsevier]

Abstract: Evidence has emerged for age-related amplification of basic sensory processing indexed by early components of the visual evoked potential (VEP). However, since these age-related effects have been incidental to the main focus of these studies, it is unclear whether they are performance dependent or alternately, represent intrinsic sensory processing changes. High-density VEPs were acquired from 19 healthy elderly and 15 young control participants who viewed alphanumeric stimuli in the absence of any active task. The data show both enhanced and delayed neural responses within structures of the ventral visual stream, with reduced hemispheric asymmetry in the elderly that may be indicative of a decline in hemispheric specialization. Additionally, considerably enhanced early frontal cortical activation was observed in the elderly, suggesting frontal hyper-activation. These age-related differences in early sensory processing are discussed in terms of recent proposals that normal aging involves large-scale compensatory reorganization. Our results suggest that such compensatory mechanisms are not restricted to later higher-order cognitive processes but may also be a feature of early sensory-perceptual processes. [Copyright &y& Elsevier]

Background: Mismatch negativity (MMN) is a negative-going event-related potential (ERP) component that occurs in response to intermittent changes in constant auditory backgrounds. A consistent finding across a large number of studies has been impaired MMN generation in schizophrenia, which has been interpreted as evidence for fundamental deficits in automatic auditory sensory processing. The aim of this study was to investigate the extent to which dysfunction in MMN generation might represent an endophenotypic marker for schizophrenia. Methods: We measured MMN to deviants in duration (25 msec, 1000 Hz) and deviants in pitch (50 msec, 1200 Hz) relative to standard tones (50 msec, 1000 Hz) in 45 chronic schizophrenia patients, 25 of their first-degree unaffected biological relatives, 12 first-episode patients, and 27 healthy control subjects. Results: In line with previous work, MMN amplitudes to duration deviants (but not to pitch deviants) were significantly reduced in patients with chronic schizophrenia compared with control subjects. However, both duration and pitch MMNs were completely unaffected in the first-degree biological relatives and this was also the case for the first-episode patients. Furthermore, length of illness did not predict the extent of MMN deficit. Conclusions: These findings suggest that the MMN deficit seen in schizophrenia patients is most likely a consequence of the disease and that MMN, at least to basic auditory feature deviants, is at best only weakly endophenotypic for schizophrenia. [Copyright &y& Elsevier]

Background: Variation at the dysbindin gene (DTNBP1) has been associated with increased risk for schizophrenia in numerous independent samples and recently with deficits in general and domain-specific cognitive processing. The relationship between dysbindin risk variants and sensory-level deficits in schizophrenia remains to be explored. We investigated P1 performance, a component of early visual processing on which both patients and their relatives show deficits, in carriers and noncarriers of a known dysbindin risk haplotype. Methods: Event-related potential responses to simple visual isolated-check stimuli were measured using high-density electrical scalp recordings in 26 individuals meeting DSM-IV criteria for schizophrenia, comprising 14 patients who were carriers of the dysbindin risk haplotype and 12 patients who were nonrisk haplotype carriers. Results: Carriers of the dysbindin risk haplotype demonstrated significantly reduced P1 amplitudes compared with noncarriers. A large effect size of d = .89 was calculated for the difference in P1 amplitude over scalp sites where the deficit was maximal. Conclusions: The P1 deficits associated with a dysbindin risk haplotype previously identified in our sample presents functional confirmation of its deleterious effect on brain activity. Building on evidence of dysbindin’s role in higher cognitive function, these early visual processing deficits suggest a generalized role for dysbindin in brain function and is likely to be part of the mechanism by which illness susceptibility is mediated. [Copyright &y& Elsevier]

Abstract: Seeing a speaker''s facial articulatory gestures powerfully affects speech perception, helping us overcome noisy acoustical environments. One particularly dramatic illustration of visual influences on speech perception is the “McGurk illusion”, where dubbing an auditory phoneme onto video of an incongruent articulatory movement can often lead to illusory auditory percepts. This illusion is so strong that even in the absence of any real change in auditory stimulation, it activates the automatic auditory change-detection system, as indexed by the mismatch negativity (MMN) component of the auditory event-related potential (ERP). We investigated the putative left hemispheric dominance of McGurk-MMN using high-density ERPs in an oddball paradigm. Topographic mapping of the initial McGurk-MMN response showed a highly lateralized left hemisphere distribution, beginning at 175ms. Subsequently, scalp activity was also observed over bilateral fronto-central scalp with a maximal amplitude at ∼290ms, suggesting later recruitment of right temporal cortices. Strong left hemisphere dominance was again observed during the last phase of the McGurk-MMN waveform (350–400ms). Source analysis indicated bilateral sources in the temporal lobe just posterior to primary auditory cortex. While a single source in the right superior temporal gyrus (STG) accounted for the right hemisphere activity, two separate sources were required, one in the left transverse gyrus and the other in STG, to account for left hemisphere activity. These findings support the notion that visually driven multisensory illusory phonetic percepts produce an auditory-MMN cortical response and that left hemisphere temporal cortex plays a crucial role in this process. [Copyright &y& Elsevier]

Abstract: Reed, Vernon, and Johnson [Reed, T. E., Vernon, P. A., & Johnson, A. M. (2004). Sex difference in brain nerve conduction velocity in normal humans. Neuropsychologia, 42, 1709–1714] reported that “nerve conduction velocity” (NCV) of visual transmission from retina to the primary visual area (V1) is significantly faster in males than females. The authors estimated the NCV by dividing head length (nasion-to-inion distance) by the latency of the well-known P100 component of the visual evoked potential (VEP). Here, we critically examine these metrics and we contend that knowledge of the underlying physiology of neural transmission across the initial stages of the visual processing hierarchy dictates that a number of their assumptions cannot be reasonably upheld. Alternative, and we believe, more parsimonious interpretations of the data are also proposed. [Copyright &y& Elsevier]