Jan Ferenc Brunner

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.

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.

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.

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.

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.

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.

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.

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.

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.