Alexander Olsen

Motor skills at 23 years of age in young adults born preterm with very low birth weight.

BACKGROUND Motor skills have previously not been reported in young adults born with very low birth weight (VLBW), although they are commonly reported in children and adolescents. AIM To compare fine and gross motor skills in VLBW young adults with matched term-born controls, and to study longitudinal changes in the VLBW group. STUDY DESIGN A geographically based follow-up study of a VLBW group and a control group. SUBJECTS Thirty-six VLBW (birth weight ≤ 1500 g) young adults, including four participants with cerebral palsy (CP), and 37 matched controls (birth weight ≥ 10th centile) were examined at 14 and 23 years of age. OUTCOME MEASURES Fine and gross motor skills were assessed using Grooved Pegboard test (GP), Trail Making Test-5 (TMT-5), Movement Assessment Battery for Children-2 (Movement ABC-2) and High-level Mobility Assessment Tool (HiMAT). RESULTS VLBW young adults were slower than controls on GP (p = 0.026) and TMT-5 (p < 0.001). Mean total Movement ABC-2 score was 69.7 ± 20.2 in the VLBW group compared with 74.1 ± 14.4 in the control group (p = 0.017). Differences were also seen in manual dexterity and balance. Additionally, HiMAT showed reduced balance and speed in gross motor skills in the VLBW group. The proportion of participants with motor problems did not change between age 14 and 23. After exclusion of participants with CP, scores were essentially the same. CONCLUSION VLBW young adults had overall poorer fine and gross motor skills compared with controls. Reduced speed seemed to be an underlying problem. Longitudinal findings indicate that VLBW children have not outgrown their motor problems when entering adulthood.

White matter microstructure in chronic moderate-to-severe traumatic brain injury: Impact of acute-phase injury-related variables and associations with outcome measures

This study examines how injury mechanisms and early neuroimaging and clinical measures impact white matter (WM) fractional anisotropy (FA), mean diffusivity (MD), and tract volumes in the chronic phase of traumatic brain injury (TBI) and how WM integrity in the chronic phase is associated with different outcome measures obtained at the same time. Diffusion tensor imaging (DTI) at 3 T was acquired more than 1 year after TBI in 49 moderate‐to‐severe‐TBI survivors and 50 matched controls. DTI data were analyzed with tract‐based spatial statistics and automated tractography. Moderate‐to‐severe TBI led to widespread FA decreases, MD increases, and tract volume reductions. In severe TBI and in acceleration/deceleration injuries, a specific FA loss was detected. A particular loss of FA was also present in the thalamus and the brainstem in all grades of diffuse axonal injury. Acute‐phase Glasgow Coma Scale scores, number of microhemorrhages on T2*, lesion volume on fluid‐attenuated inversion recovery, and duration of posttraumatic amnesia were associated with more widespread FA loss and MD increases in chronic TBI. Episodes of cerebral perfusion pressure <70 mmHg were specifically associated with reduced MD. Neither episodes of intracranial pressure >20 mmHg nor acute‐phase Rotterdam CT scores were associated with WM changes. Glasgow Outcome Scale Extended scores and performance‐based cognitive control functioning were associated with FA and MD changes, but self‐reported cognitive control functioning was not. In conclusion, FA loss specifically reflects the primary injury severity and mechanism, whereas FA and MD changes are associated with objective measures of general and cognitive control functioning.

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.

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.

Life after Adolescent and Adult Moderate and Severe Traumatic Brain Injury: Self-Reported Executive, Emotional, and Behavioural Function 2–5 Years after Injury

Survivors of moderate-severe Traumatic Brain Injury (TBI) are at risk for long-term cognitive, emotional, and behavioural problems. This prospective cohort study investigated self-reported executive, emotional, and behavioural problems in the late chronic phase of moderate and severe TBI, if demographic characteristics (i.e., age, years of education), injury characteristics (Glasgow Coma Scale score, MRI findings such as traumatic axonal injury (TAI), or duration of posttraumatic amnesia), symptoms of depression, or neuropsychological variables in the first year after injury predicted long-term self-reported function. Self-reported executive, emotional, and behavioural functioning were assessed among individuals with moderate and severe TBI (N = 67, age range 15–65 years at time of injury) 2–5 years after TBI, compared to a healthy matched control group (N = 72). Results revealed significantly more attentional, emotional regulation, and psychological difficulties in the TBI group than controls. Demographic and early clinical variables were associated with poorer cognitive and emotional outcome. Fewer years of education and depressive symptoms predicted greater executive dysfunction. Younger age at injury predicted more aggressive and rule-breaking behaviour. TAI and depressive symptoms predicted Internalizing problems and greater executive dysfunction. In conclusion, age, education, TAI, and depression appear to elevate risk for poor long-term outcome, emphasising the need for long-term follow-up of patients presenting with risk factors.

Difficult morning awakening from rapid eye movement sleep and impaired cognitive function in delayed sleep phase disorder patients

OBJECTIVES Difficult awakening is a key symptom of delayed sleep phase disorder (DSPD), but no studies have quantified awakening thresholds in a sleep laboratory. This study assessed whether cognitive function was impaired after awakening and whether difficult awakening was associated with specific polysomnographic features such as slow wave sleep stage N3. METHODS Nine patients with DSPD and nine sex- and age-matched healthy controls were included. Polysomnography was performed at our university hospital from midnight. An alarm clock was activated at 07:00 with sound intensity increasing from 72 to 104 dB. Participants performed a continuous performance test (CPT) the previous afternoon and immediately upon awakening. RESULTS Three DSPD patients and zero controls did not wake up to the maximum 104 dB alarm sound; all three patients were in rapid eye movement (REM) sleep when the alarm clock went off (difference in proportions, P = 0.047). In patients, CPT reaction time was prolonged in the morning compared to the afternoon [analysis of variance (ANOVA) interaction, P = 0.01]. DSPD patients made more omission errors than controls regardless of time of the day (ANOVA main effect, P = 0.046). CONCLUSION Difficult awakening from slow wave sleep was not observed. A subgroup of DSPD patients may have a severe problem waking up from REM sleep. DSPD patients may also have a state-like impairment in cognitive function in the morning and a trait-like impairment not depending on time of day, compared to normal sleepers.

Exercise Intensity-Dependent Effects on Cognitive Control Function during and after Acute Treadmill Running in Young Healthy Adults

The idea that physical activity differentially impacts upon performance of various cognitive tasks has recently gained increased interest. However, our current knowledge about how cognition is altered by acute physical activity is incomplete. To measure how different intensity levels of physical activity affect cognition during and after 1 bout of physical activity, 30 healthy, young participants were randomized to perform a not-X continuous performance test (CPT) during low (LI)- and moderate intensity (MI) running. The same participants were subsequently randomized to perform the not-X CPT post LI, MI, and high intensity (HI) running. In addition, exercise related mood changes were assessed through a self-report measure pre and post running at LI, MI, and HI. Results showed worsening of performance accuracy on the not-X CPT during one bout of moderate compared to low intensity running. Post running, there was a linear decrease in reaction time with increasing running intensity and no change in accuracy or mood. The decreased reaction times post HI running recovered back to baseline within 20 min. We conclude that accuracy is acutely deteriorated during the most straining physical activity while a transient intensity-dependent enhancement of cognitive control function is present following physical activity.

Traumatic axonal injury: Relationships between lesions in the early phase and diffusion tensor imaging parameters in the chronic phase of traumatic brain injury

This prospective study of traumatic brain injury (TBI) patients investigates fractional anisotropy (FA) from chronic diffusion tensor imaging (DTI) in areas corresponding to persistent and transient traumatic axonal injury (TAI) lesions detected in clinical MRI from the early phase. Thirty‐eight patients (mean 24.7 [range 13–63] years of age) with moderate‐to‐severe TBI and 42 age‐ and sex‐matched healthy controls were included. Patients underwent 1.5‐T clinical MRI in the early phase (median 7 days), including fluid‐attenuated inversion recovery (FLAIR) and T2* gradient echo (T2*GRE) sequences. TAI lesions from the early phase were characterized as nonhemorrhagic or microhemorrhagic. In the chronic phase (median 3 years), patients and controls were imaged at 3 T with FLAIR, T2*GRE, T1, and DTI sequences. TAI lesions were classified as transient or persistent. The FLAIR/T2*GRE images from the early phase were linearly registered to the FA images from the chronic phase and lesions manually segmented on the FA‐registered FLAIR/T2*GRE images. For regions of interest (ROIs) from both nonhemorrhagic and microhemorrhagic lesion, we found a significant linear trend of lower mean FA from ROIs in healthy controls to ROIs in patients without either nonhemorrhagic or microhemorrhagic lesions and further to transient and finally persistent lesion ROIs (P < 0.001). Histogram analyses showed lower FA in persistent compared with transient nonhemorrhagic lesion ROIs (P < 0.001), but this was not found in microhemorrhagic lesion ROIs (P = 0.08–0.55). The demonstrated linear trend of lower FA values from healthy controls to persistent lesion ROIs was found in both nonhemorrhagic and microhemorrhagic lesions and indicates a gradual increasing disruption of the microstructure. Lower FA values in persistent compared with transient lesions were found only in nonhemorrhagic lesions. Thus, clinical MRI techniques are able to depict important aspects of white matter pathology across the stages of TBI.

Preterm birth leads to hyper-reactive cognitive control processing and poor white matter organization in adulthood

&NA; Individuals born preterm with very low birth weight (VLBW; birth weight ≤ 1500 g) are at high risk for perinatal brain injuries and deviant brain development, leading to increased chances of later cognitive, emotional, and behavioral problems. Here we investigated the neuronal underpinnings of both reactive and proactive cognitive control processes in adults with VLBW. We included 32 adults born preterm with VLBW (before 37th week of gestation) and 32 term‐born controls (birth weight ≥10th percentile for gestational age) between 22 and 24 years of age that have been followed prospectively since birth. Participants performed a well‐validated Not‐X continuous performance test (CPT) adapted for use in a mixed block‐ and event‐related fMRI protocol. BOLD fMRI and DTI data was acquired on a 3T scanner. Performance on the Not‐X CPT was highly similar between groups. However, the VLBW group demonstrated hyper‐reactive cognitive control processing and disrupted white matter organization. The hyper‐reactive brain activation signature in VLBW adults was associated with lower gestational age, lower fluid intelligence score, and anxiety problems. Automated Multi‐Atlas Tract Extraction (AutoMATE) analyses revealed that this disruption of normal brain function was accompanied by poorer white matter organization in the anterior thalamic radiation and the cingulum, as reflected in both reduced fractional anisotropy and increased mean diffusivity. These findings show that the preterm behavioral phenotype is associated with predominantly reactive‐, rather than proactive cognitive control processing, as well as white matter abnormalities, that may underlie common difficulties that many preterm born individuals experience in everyday life.