In-situ formation of one-dimensional coordination polymers in molecular junctions.

We demonstrate the bottom-up in-situ formation of organometallic oligomer chains at the single-molecule level. The chains are formed using the mechanically controllable break junction technique operated in a liquid environment, and consist of alternating isocyano-terminated benzene monomers coordinated to gold atoms. We show that the chaining process is critically determined by the surface density of molecules. In particular, we demonstrate that by reducing the local supply of molecules within the junction, either by lowering the molecular concentration or by adding side groups, the oligomerization process can be suppressed. Our experimental results are supported by ab-initio simulations, confirming that the isocyano terminating groups display a high tendency to form molecular chains, as a result of their high affinity for gold. Our findings open the road for the controlled formation of one-dimensional, single coordination-polymer chains as promising model systems of organometallic frameworks.

Methylphenidate selectively modulates one sub-component of the no-go P3 in pediatric ADHD medication responders.

Methylphenidate (MPH) has been shown to modulate the amplitude of the no-go P3 component of the event-related potential (ERP; Øgrim, Aasen, & Brunner, 2016). Using group independent component analysis, the no-go P3 from a cued go/no-go task has been separated into two sub-components (Brunner et al., 2013). This study investigated whether sub-components of the no-go P3 could be identified in children with ADHD, and how MPH modulates their amplitudes. ERPs were registered twice (on/off MPH) in 57 children with ADHD classified as medication responders in a four-week medication trial. Two no-go P3 sub-components were identified. In the MPH session, the amplitude of one sub-component, the IC P3no-goearly (mean latency 378 ms, with a central distribution), was significantly larger than at baseline, whereas the other sub-component, the IC P3no-golate (mean latency 428 ms, with a centro-frontal distribution), was not significantly affected. These results add to the literature documenting that the no-go P3 consists of two overlapping phenomena with different functional correlates.

Correction: ERP Correlates of Proactive and Reactive Cognitive Control in Treatment-Naïve Adult ADHD.

[This corrects the article DOI: 10.1371/journal.pone.0159833.].

The relevance of the irrelevant: Attention and task-set adaptation in prematurely born adults.

OBJECTIVE: To investigate attention and task-set adaptation in a preterm born very low birth weight (PT/VLBW) population by means of event-related potential components from an adapted cued go/no-go task. METHODS: P3 components after target and non-target cues, as well as target, no-go and non-target imperative stimuli were compared in 30 PT/VLBW young adults and 33 term-born controls. Changes in P3 amplitudes as a function of time-on-task were also investigated. RESULTS: The PT/VLBW group had larger P3 amplitudes to non-target cues and non-targets compared with controls. There were no significant group differences in the P3s to target or no-go stimuli. Moreover, the amplitude of the P3 to non-target cues and non-targets decreased significantly over time in the control group but not in the PT/VLBW group. CONCLUSIONS: PT/VLBW young adults allocate more attention to behaviorally irrelevant information than term-born controls, and persist in attending to this information over time. SIGNIFICANCE: This is the first study to investigate ERP components in an adult population born preterm with very low birth weight.

Single-dose effects on the P3no-go ERP component predict clinical response to stimulants in pediatric ADHD.

OBJECTIVE: Approximately 30% of children and adolescents diagnosed with attention-deficit/hyperactivity disorder (ADHD) and treated with stimulants are considered non-responders (non-REs). Reliable predictors of response are missing. We examined changes in Event-Related Potentials (ERPs) induced by a single dose of stimulant medication in order to predict later clinical response. METHODS: ERPs were registered twice during performance of a visual cued go/no-go task in 87 ADHD patients (27 girls) aged 8-18years; the second recording on a single dose of stimulant medication, followed by a systematic medication trial lasting 4weeks. Based on the four-week trial, participants were categorized as responders (REs, N=62) or non-REs (N=25). Changes among REs and non-REs in ERP components (cueP3, CNV, P3go, N2no-go, P3no-go) and behavioral-test variables were then compared. RESULTS: REs and non-REs differed significantly in medication-induced changes in P3no-go, cue-P3, CNV, omission errors, reaction time, and reaction-time variability. The largest effect size was found for P3no-go amplitude (p<.001; d=1.76). Changes in P3no-go and omission errors correctly classified 90% of the REs and 76% of the non-REs, when controlling for the age of the participants. CONCLUSION: Clinical response to stimulants can be predicted by assessing single-dose changes in the P3no-go ERP component amplitude. SIGNIFICANCE: Changes in P3no-go may be a clinically useful marker of response to stimulants.

ERP Correlates of Proactive and Reactive Cognitive Control in Treatment-Naïve Adult ADHD.

This study investigated whether treatment naïve adults with Attention Deficit Hyperactivity Disorder (ADHD; n = 33; 19 female) differed from healthy controls (n = 31; 17 female) in behavioral performance, event-related potential (ERP) indices of preparatory attention (CueP3 and late CNV), and reactive response control (Go P3, NoGo N2, and NoGo P3) derived from a visual cued Go/NoGo task. On several critical measures, Cue P3, late CNV, and NoGo N2, there were no significant differences between the groups. This indicated normal preparatory processes and conflict monitoring in ADHD patients. However, the patients had attenuated Go P3 and NoGoP3 amplitudes relative to controls, suggesting reduced allocation of attentional resources to processes involved in response control. The patients also had a higher rate of Go signal omission errors, but no other performance decrements compared with controls. Reduced Go P3 and NoGo P3 amplitudes were associated with poorer task performance, particularly in the ADHD group. Notably, the ERPs were not associated with self-reported mood or anxiety. The results provide electrophysiological evidence for reduced effortful engagement of attentional resources to both Go and NoGo signals when reactive response control is needed. The absence of group differences in ERP components indexing proactive control points to impairments in specific aspects of cognitive processes in an untreated adult ADHD cohort. The associations between ERPs and task performance provided additional support for the altered electrophysiological responses.

Modulation of ERP components by task instructions in a cued go/no-go task.

The present study investigated how components of ERPs are modulated when participants optimize speed versus accuracy in a cued go/no-go task. Using a crossover design, 35 participants received instructions to complete the task prioritizing response speed in half of the task, and accurate responding in the other half of the task. Analysis was performed on the contingent negative variation (CNV), P3go, and P3no-go and the corresponding independent components (IC), as identified by group independent component analysis. After speed instructions, the IC CNV(late), P3go(anterior), P3no-go(early), and P3no-go(late) all had larger amplitudes than after accuracy instructions. Furthermore, both the IC P3go(posterior) and IC P3go(anterior) had shorter latencies after speed than after accuracy instructions. The results demonstrate that components derived from the CNV and P3 components are facilitated when participants optimize response speed. These findings indicate that these ERP components reflect executive processes enabling adjustment of behavior to changing demands.

Initial validation of a web-based self-administered neuropsychological test battery for older adults and seniors.

INTRODUCTION: Computerized neuropsychological tests are effective in assessing different cognitive domains, but are often limited by the need of proprietary hardware and technical staff. Web-based tests can be more accessible and flexible. We aimed to investigate validity, effects of computer familiarity, education, and age, and the feasibility of a new web-based self-administered neuropsychological test battery (Memoro) in older adults and seniors. METHOD: A total of 62 (37 female) participants (mean age 60.7 years) completed the Memoro web-based neuropsychological test battery and a traditional battery composed of similar tests intended to measure the same cognitive constructs. Participants were assessed on computer familiarity and how they experienced the two batteries. To properly test the factor structure of Memoro, an additional factor analysis in 218 individuals from the HUNT population was performed. RESULTS: Comparing Memoro to traditional tests, we observed good concurrent validity (r = .49-.63). The performance on the traditional and Memoro test battery was consistent, but differences in raw scores were observed with higher scores on verbal memory and lower in spatial memory in Memoro. Factor analysis indicated two factors: verbal and spatial memory. There were no correlations between test performance and computer familiarity after adjustment for age or age and education. Subjects reported that they preferred web-based testing as it allowed them to set their own pace, and they did not feel scrutinized by an administrator. CONCLUSIONS: Memoro showed good concurrent validity compared to neuropsychological tests measuring similar cognitive constructs. Based on the current results, Memoro appears to be a tool that can be used to assess cognitive function in older and senior adults. Further work is necessary to ascertain its validity and reliability.

Neuropsychological parameters indexing executive processes are associated with independent components of ERPs.

Lesion studies have indicated that at least the three executive processes can be differentiated in the frontal lobe: Energization, monitoring and task setting. Event related potentials (ERPs) in Go/NoGo tasks have been widely used in studying executive processes. In this study, ERPs were obtained from EEG recorded during performance of a cued Go/NoGo task. The Contingent Negative Variation (CNV) and P3NoGo waves were decomposed into four independent components (ICs), by applying Independent Component Analysis (ICA) to a collection of ERPs from 193 healthy individuals. The components were named IC CNVearly, IC CNVlate, IC P3NoGoearly and IC P3NoGolate according to the conditions and time interval in which they occurred. A sub-group of 28 individuals was also assessed with neuropsychological tests. The test parameters were selected on the basis of studies demonstrating their sensitivity to executive processes as defined in the ROtman-Baycrest Battery for Investigating Attention (ROBBIA) model. The test scores were categorized into the domain scores of energization, monitoring and task setting and correlated with the amplitudes of the individual ICs from the sub-group of 28 individuals. The energization domain correlated with the IC CNVlate and IC P3NoGoearly. The monitoring domain correlated with the IC P3NoGolate, while the task setting domain correlated with the IC CNVlate. The IC CNVearly was not correlated with any of the neuropsychological domain scores. The correlations between the domains and ICs remained largely unchanged when controlling for full-scale IQ. This is the first study to demonstrate that executive processes, as indexed by neuropsychological test parameters, are associated with particular event-related potentials in a cued Go/NoGo paradigm.

Altered Cognitive Control Activations after Moderate-to-Severe Traumatic Brain Injury and Their Relationship to Injury Severity and Everyday-Life Function.

This study investigated how the neuronal underpinnings of both adaptive and stable cognitive control processes are affected by traumatic brain injury (TBI). Functional magnetic resonance imaging (fMRI) was undertaken in 62 survivors of moderate-to-severe TBI (>1 year after injury) and 68 healthy controls during performance of a continuous performance test adapted for use in a mixed block- and event-related design. Survivors of TBI demonstrated increased reliance on adaptive task control processes within an a priori core region for cognitive control in the medial frontal cortex. TBI survivors also had increased activations related to time-on-task effects during stable task-set maintenance in right inferior parietal and prefrontal cortices. Increased brain activations in TBI survivors had a dose-dependent linear positive relationship to injury severity and were negatively correlated with self-reported cognitive control problems in everyday-life situations. Results were adjusted for age, education, and fMRI task performance. In conclusion, evidence was provided that the neural underpinnings of adaptive and stable control processes are differently affected by TBI. Moreover, it was demonstrated that increased brain activations typically observed in survivors of TBI might represent injury-specific compensatory adaptations also utilized in everyday-life situations.

Random telegraph signals in molecular junctions.

We investigate conductance fluctuations in molecular junctions using a mechanically controllable break junction setup in a liquid environment. In contrast to conventional break junction measurements, time-dependent conductance signals were recorded while reducing the gap size between the two contact electrodes. Only small amplitude fluctuations of the conductance are observed when measuring in pure solvent. Conductance traces recorded in solutions containing alkanedithiols show significantly larger fluctuations which can take the form of random telegraph signals. Such signals emerge in a limited conductance range, which corresponds well to the known molecular conductance of the compounds investigated. These large-amplitude fluctuations are attributed to the formation and thermally driven breaking of bonds between a molecule and a metal electrode and provide a still poorly explored source of information on the dynamics of molecular junctions formation. The lifetimes of the high and low conductance states are found to vary between 0.1 ms and 0.1 s.

Predicting the clinical outcome of stimulant medication in pediatric attention-deficit/hyperactivity disorder: data from quantitative electroencephalography, event-related potentials, and a go/no-go test.

BACKGROUND: We searched for predictors of the clinical outcome of stimulant medication in pediatric attention-deficit/hyperactivity disorder (ADHD), emphasizing variables from quantitative electroencephalography, event-related potentials (ERPs), and behavioral data from a visual go/no-go test. METHODS: Nineteen-channel electroencephalography (EEG) was recorded during the resting state in eyes-open and eyes-closed conditions and during performance of the cued go/no-go task in 98 medication-naïve ADHD patients aged 7-17 years and in 90 controls with the same age and sex distribution as the patients. For patients, the recording was followed by a systematic trial on stimulant medication lasting at least 4 weeks. Based on data from rating scales and interviews, two psychologists who were blind to the electrophysiological results independently rated the patients as responders (REs) (N=74) or non-responders (non-REs) (N=24). Using a logistic regression model, comparisons were made between REs and non-REs on the EEG spectra, ERPs (cue P3, contingent negative variation, and P3 no-go of the ERP waves and independent components [ICs] extracted from these waves), reaction time, reaction time variability, number of commission and omission errors, intelligence quotient, age, sex, ADHD subtype, and comorbidities. RESULTS: The two groups differed significantly on eight of the variables, with effect sizes (Cohen's d) ranging from 0.49 to 0.76. In the multivariate logistic regression analysis, only three of these variables were significantly associated with clinical outcome. The amplitude of the IC cue P3, which has a parietal-occipital distribution, was normal in REs but significantly smaller in non-REs, whereas the centrally distributed IC P3 no-go early was smaller in REs than in non-REs and controls. In addition, the REs had more power in the EEG theta band. A quartile-based index was calculated using these three variables. The group with the lowest scores comprised only 36% REs; response rates in the three other groups were 83%, 86%, and 89%. CONCLUSION: The clinical outcome of stimulant medication was best predicted by electrophysiological parameters. The brain dysfunctions of the REs appear to be primarily associated with prefrontal lobe hypoactivation. The non-REs were deviant from the controls in parietal-occipital functions.

Predicting acute side effects of stimulant medication in pediatric attention deficit/hyperactivity disorder: data from quantitative electroencephalography, event-related potentials, and a continuous-performance test.

BACKGROUND: The aim of this study was to search for predictors of acute side effects of stimulant medication in pediatric attention deficit/hyperactivity disorder (ADHD), emphasizing variables from quantitative electroencephalography (QEEG), event-related potentials (ERPs), and behavior data from a visual continuous-performance test (VCPT). METHODS: Seventy medication-naïve ADHD patients aged 7-16 years were tested with QEEG, including a go/no-go task condition (VCPT) from which behavior data and ERPs were extracted, followed by a systematic trial on stimulant medication lasting at least 4 weeks. Based on data from rating scales and interviews, two psychologists who were blind to the QEEG/ERP test results independently rated the patients as having no or small side effects (n = 37) or troublesome side effects (n = 33). We determined if the side effects were related to sex, age, IQ, ADHD subtype, comorbidities, clinical outcome, and variables in QEEG, ERPs, and VCPT. RESULTS: There was a moderate negative correlation between clinical outcome and side effects. Three variables were significantly associated with side effects in a multivariate logistic regression analysis. In the ERP independent component - contingent negative variation - which reflected action preparation and time evaluation, patients with high amplitudes (close to normal values) experienced more side effects than patients with lower amplitudes. A faster-than-normal reaction time in VCPT was associated with side effects, as was a high amplitude in an early ERP component (early visual independent component), reported to be influenced by attention, perceptual sensitivity, and anxiety. CONCLUSION: The group with troublesome side effects had normal action-preparation electrical brain activity, a faster-than-normal reaction time, and an increased level of anxiety (measured by ERP) compared with the no side-effects group.

Long-term test-retest reliability of the P3 NoGo wave and two independent components decomposed from the P3 NoGo wave in a visual Go/NoGo task.

The objective of the current study was to determine long-term test-retest reliability of the P3 NoGo wave as well as two independent components (IC P3 NoGo early and IC P3 NoGo late) decomposed from this wave by independent component analysis (ICA). For this purpose 19-channel EEG was recorded during a cued visual Go/NoGo task. First, spatial filters of the two independent components (ICs) were obtained by application of ICA to ERPs of 102 healthy adults. Second, in 26 individuals, ERPs were recorded from the same task a second time 6-18 months after the first recording. Statistical analyses were performed on both the P3 NoGo waves and the activation curves of the two ICs from both recordings. Amplitude and latency were estimated by "peak" and "fractional area" (FA) methods for both the P3 NoGo wave and ICs. Intraclass correlations (ICC) for latency were excellent (ICC>.90) for both the P3 NoGo wave and the two ICs when measured with the FA method, and good (ICC>.75) for amplitude measured by both methods (FA or peak). We conclude that the long-term stability of P3 NoGo wave and the two IC makes them well suited for reliable assessment of cognitive control function in research and clinic.

The functional topography and temporal dynamics of overlapping and distinct brain activations for adaptive task control and stable task-set maintenance during performance of an fMRI-adapted clinical continuous performance test.

Previous studies have demonstrated that stable and adaptive attention processes are mediated by partly overlapping, but distinct, brain areas. Dorsal medial PFC and anterior insula may form a "core network" for attention control, which is believed to operate on both temporal scales. However, both the existence of such a network as well as the unique functional topography for adaptive and stable attention processes is still highly debated. In this study, 87 healthy participants performed a clinical not-X continuous performance test optimized for use in a mixed block and event-related fMRI design. We observed overlapping activations related to stable and adaptive attention processes in dorsal medial PFC and anterior insula/adjacent cortex as well as in the right inferior parietal lobe and middle temporal gyrus. We also identified areas of activations uniquely related to stable and adaptive attention processes in widespread cortical, cerebellar, and subcortical areas. Interestingly, the functional topography within the PFC indicated a rostro-caudal distribution of adaptive, relative to stable, attention processes. There was also evidence for a time-on-task effect for activations related to stable, but not adaptive, attention processes. Our results provide further evidence for a "core network" for attention control that is accompanied by unique areas of activation involved in domain-specific processes operating on different temporal scales. In addition, our results give new insights into the functional topography of stable and adaptive attention processes and their temporal dynamics in the context of an extensively used clinical attention test.

Cognitive impairment 3 months after moderate and severe traumatic brain injury: a prospective follow-up study.

OBJECTIVE: To explore the magnitude and frequency of cognitive impairment 3 months after moderate to severe traumatic brain injury (TBI), and to evaluate its relationship to disability at 1-year follow-up. DESIGN: Prospective follow-up study. SETTING: Regional level I trauma center. PARTICIPANTS: Patients aged 15 to 65 years with definite TBI, defined as Glasgow Coma Scale score of 3 to 13 and injury documented by magnetic resonance imaging (n=59) or computed tomography (n=2); healthy volunteers (n=47) served as controls. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Neuropsychological assessment 3 months postinjury and Glasgow Outcome Scale Extended (GOSE) at 3 and 12 months postinjury. RESULTS: Patients with TBI performed worse than controls, most consistently in terms of information processing speed and verbal memory. However, a maximum of only 43% of patients with TBI had impaired test scores (defined as <1.5 SD below mean of normative data) on any one measure. Based on a selection of 9 tests, a 0 or 1 impaired score was seen in 46 (98%) of 47 controls, in 20 (57%) of 35 patients with moderate TBI, and in 9 (35%) of 26 patients with severe TBI. At 1 year postinjury, disability (defined as GOSE score ≤6) was present in 57% of those with 2 or more impaired test scores and in 21% of those with 0 or 1 impaired score (P=.005). CONCLUSIONS: In this sample of patients with recent, definite TBI and healthy volunteers, we found that TBI affected cognition in moderate as well as severe cases. The presence of cognitive impairment was associated with future disability. However, half of the patients with moderate TBI and even one third of those with severe TBI had a normal cognitive assessment 3 months postinjury.

Simple dual tasking recruits prefrontal cortices in chronic severe traumatic brain injury patients, but not in controls.

The ability to carry out two tasks simultaneously, dual tasking, is specifically impaired after traumatic brain injury (TBI). The aim of the present study was to investigate the neuronal correlates to this increased dual cost in chronic severe TBI patients (n = 10) compared to healthy controls (n = 11) using functional magnetic resonance imaging (fMRI) at 3 Tesla (T). The tasks were a visual search and a simple two-fingers button press motor task. Performance data demonstrated similar and significant dual task interference in both TBI patients and controls using a linear mixed model. However, principal component analysis showed that TBI patients and controls could be classified into different categories based on motor activity in the single compared to the dual task condition, thus reflecting the increased variability in the performance in the TBI group. Random effects between-group analysis demonstrated significantly reduced activation in the TBI group in both single task conditions in the occipital and posterior cingulate cortices, and for the visual task also in the thalami. This pattern was reversed in the dual task condition with significantly increased activation of a predominantly left lateralized prefrontal-anterior midline-parietal network in the TBI group compared to the controls. The increase in activation occurred within regions described to be engaged in healthy volunteers as dual task cost increases. This finding points to substitution, functional reorganization within the primary network subserving the task, following TBI, and demonstrates more effortful processing. Recruitment of these additional prefrontal resources may be connected to serial rather than parallel processing in low level dual tasking in TBI. Thus, in severe TBI, low level dual task performance depends on increased attentional and executive guidance.