Kaisa M. Hartikainen

Persistent symptoms in mild to moderate traumatic brain injury associated with executive dysfunction

In order to improve detection of subtle cognitive dysfunction and to shed light on the etiology of persistent symptoms after mild-to-moderate traumatic brain injury (TBI), we employed an experimental executive reaction time (RT) test, standardized neuropsychological tests, and diffusion tensor imaging (DTI). The Executive RT-Test, an Executive Composite Score from standardized neuropsychological tests, and DTI-indices in the midbrain differentiated between patients with persistent symptoms from those fully recovered after mild-to-moderate TBI. We suggest that persistent symptoms in mild-to-moderate TBI may reflect disrupted fronto-striatal network involved in executive functioning, and the Executive RT-Test provides an objective and novel method to detect it.

Outcome from Complicated versus Uncomplicated Mild Traumatic Brain Injury

Objective. To compare acute outcome following complicated versus uncomplicated mild traumatic brain injury (MTBI) using neurocognitive and self-report measures. Method. Participants were 47 patients who presented to the emergency department of Tampere University Hospital, Finland. All completed MRI scanning, self-report measures, and neurocognitive testing at 3-4 weeks after injury. Participants were classified into the complicated MTBI or uncomplicated MTBI group based on the presence/absence of intracranial abnormality on day-of-injury CT scan or 3-4 week MRI scan. Results. There was a large statistically significant difference in time to return to work between groups. The patients with uncomplicated MTBIs had a median of 6.0 days (IQR = 0.75–14.75, range = 0–77) off work compared to a median of 36 days (IQR = 13.5–53, range = 3–315) for the complicated group. There were no significant differences between groups for any of the neurocognitive or self-report measures. There were no differences in the proportion of patients who (a) met criteria for ICD-10 postconcussional disorder or (b) had multiple low scores on the neurocognitive measures. Conclusion. Patients with complicated MTBIs took considerably longer to return to work. They did not perform more poorly on neurocognitive measures or report more symptoms, at 3-4 weeks after injury compared to patients with uncomplicated MTBIs.

Return to work following mild traumatic brain injury.

Objective:To examine factors relating to return to work (RTW) following mild traumatic brain injury (mTBI). Participants:One hundred and nine patients (Age: M = 37.4 years, SD = 13.2; 52.3% women) who sustained an mTBI. Design:Inception cohort design with questionnaires and neuropsychological testing completed approximately 3 to 4 weeks postinjury. Setting:Emergency Department of Tampere University Hospital, Finland. Main Outcome Measures:Self-report (postconcussion symptoms, depression, fatigue, and general health) and neurocognitive measures (attention and memory). Results:The cumulative RTW rates were as follows: 1 week = 46.8%, 2 weeks = 59.6%, 3 weeks = 67.0%, 4 weeks = 70.6%, 2 months = 91.7%, and 1 year = 97.2%. Four variables were significant predictors of the number of days to RTW: age, multiple bodily injuries, intracranial abnormality at the day of injury, and fatigue ratings (all P < .001). The largest amount of variance accounted for by these variables in the prediction of RTW was at 30 days following injury (P < .001, R2 = 0.504). Participants who returned to work fewer than 30 days after injury (n = 82, 75.2%) versus more than 30 days (n = 27, 24.8%) did not differ on demographic or neuropsychological variables. Conclusions:The vast majority of this cohort returned to work within 2 months. Predictors of slower RTW included age, multiple bodily injuries, intracranial abnormality at the day of injury, and fatigue.

Immediate effects of deep brain stimulation of anterior thalamic nuclei on executive functions and emotion–attention interaction in humans

Background: Deep brain stimulation (DBS) of anterior thalamic nuclei (ANT) is a novel promising therapeutic method for treating refractory epilepsy. Despite reports of subjective memory impairments and mood disturbances in patients with ANT–DBS, little is known of its effects on cognitive and affective processes. Hypothesis: The anterior thalamus has connections to prefrontal and limbic networks important for cognitive control and emotional reactivity. More specifically, anterior cingulate cortex (ACC), linked with ANT, has been assigned roles related to response inhibition and attention allocation to threat. Thus, we hypothesized ANT–DBS to influence executive functions, particularly response inhibition, and modulate emotional reactivity to threat. Method: Twelve patients having undergone ANT–DBS for intractable epilepsy participated in the study. Patients performed a computer-based executive reaction time (RT) test—that is, a go/no-go visual discrimination task with threat-related emotional distractors and rule switching, while the DBS was switched ON (5/5 mA constant current) and OFF every few minutes. Results: ANT–DBS increased the amount of commission errors—that is, errors where subjects failed to withhold from responding. Furthermore, ANT–DBS slowed RTs in context of threat-related distractors. When stimulation was turned off, threat-related distractors had no distinct effect on RTs. Conclusion: We found immediate objective effects of ANT–DBS on human cognitive control and emotion–attention interaction. We suggest that ANT–DBS compromised response inhibition and enhanced attention allocation to threat due to altered functioning of neural networks that involve the DBS-target, ANT, and the regions connected to it such as ACC. The results highlight the need to consider affective and cognitive side-effects in addition to the therapeutic effect when adjusting stimulation parameters. Furthermore, this study introduces a novel window into cognitive and affective processes by modulating the associative and limbic networks with direct stimulation of key nodes in the thalamus.

Propofol and isoflurane induced EEG burst suppression patterns in rabbits

The aim of this study was to compare propofol produced EEG burst suppression with isoflurane produced burst suppression in rabbits and to see whether rabbits can serve as models in studying the effects of different anaesthetics on human EEG. We recorded EEG of eight rabbits anaesthetised with isoflurane and propofol. The isoflurane bursts had higher amplitude than propofol bursts (P<0.005). Isoflurane bursts appeared on distinct DC‐shifts while propofol bursts were on slow waves. The EEG patterns were, however, different from those seen in humans. Rabbits did not have the rhythms seen in humans. We conclude that rabbits can be used to study the EEG effects of anaesthetics, such as the timing properties and reactivity of burst suppression pattern. However, this model seems less promising in the study of rhythmic activity seen in human EEG during burst suppression.

Emotionally arousing stimuli compete for attention with left hemispace.

Rapid interaction of the emotional and attentional networks is critical for adaptive behavior. Here, we examined the effects of emotional stimulation on hemifield attention allocation using event-related potential and behavioral measures. Participants performed a visual-discrimination task on nonemotional targets presented randomly in the left or right hemifield. A brief task-irrelevant emotional (pleasant or unpleasant; 150-ms duration) or neutral picture was presented centrally 350 ms before the next target (150-ms duration). Unpleasant stimuli interfered with the left visual field attention capacity, slowing behavioral responses to attended left field stimuli. In keeping with the behavioral data, event-related potential responses to nonemotional attended left field stimuli were reduced over the right parietal regions when preceded by an unpleasant event. The results provide electrophysiological and behavioral evidence that unpleasant, emotionally arousing stimuli interfere with the right hemisphere-dependent attention capacity.

Enhanced Attention Capture by Emotional Stimuli in Mild Traumatic Brain Injury

Mild traumatic brain injury (mTBI) may be associated with compromised executive functioning and altered emotional reactivity. Despite frequent affective and cognitive symptoms in mTBI, objective evidence for brain dysfunction is often lacking. Previously we have reported compromised performance in symptomatic mTBI patients in an executive reaction time (RT) test, a computer-based RT test engaging several executive functions simultaneously. Here, we investigated the cognitive control processes in mTBI in context of threat-related stimuli. We used behavioral measures and event-related potentials (ERP) to investigate attentional capture by task-relevant and task-irrelevant emotional stimuli during a Go-NoGo task requiring cognitive control. We also assessed subjective cognitive, somatic, and emotional symptoms with questionnaires. Twenty-seven subjects with previous mTBI and 17 controls with previous ankle injury participated in the study over 9 months post-injury. Electroencephalogram (EEG) was recorded while patients performed a modified executive RT-test. N2-P3 ERP component was used as a general measure of allocated attentional and executive processing resources. Although at the time of the testing, the mTBI and the control groups did not differ in symptom endorsement, mTBI patients reported having had more emotional symptoms overall since the injury than controls. The overall RT-test performance levels did not differ between groups. However, when threat-related emotional stimuli were used as Go-signals, the mTBI group was faster than the control group. In comparison to neutral stimuli, threat-related stimuli were associated with increased N2-P3 amplitude in all conditions. This threat-related enhancement of the N2-P3 complex was greater in mTBI patients than in controls in response to Go signals and NoGo signals, independent of relevance. We conclude that mTBI may be associated with enhanced attentional and executive resource allocation to threat-related stimuli. Along with behavioral evidence for enhanced attention allocation to threat stimuli, increased brain responses to threat were observed in mTBI. Enhanced attention capture by threat-related emotional stimuli may reflect inefficient top-down control of bottom-up influences of emotion, and might contribute to affective symptoms in mTBI.

Threat interferes with response inhibition

A potential threat, such as a spider, captures attention and engages executive functions to adjust ongoing behavior and avoid danger. We and many others have reported slowed responses to neutral targets in the context of emotional distractors. This behavioral slowing has been explained in the framework of attentional competition for limited resources with emotional stimuli prioritized. Alternatively, slowed performance could reflect the activation of avoidance/freezing-type motor behaviors associated with threat. Although the interaction of attention and emotion has been widely studied, little is known on the interaction between emotion and executive functions. We studied how threat-related stimuli (spiders) interact with executive performance and whether the interaction profile fits with a resource competition model or avoidance/freezing-type motor behaviors. Twenty-one young healthy individuals performed a Go–NoGo visual discrimination reaction time (RT) task engaging several executive functions with threat-related and emotionally neutral distractors. The threat-related distractors had no effect on the RT or the error rate in the Go trials. The NoGo error rate, reflecting failure in response inhibition, increased significantly because of threat-related distractors in contrast to neutral distractors, P less than 0.05. Thus, threat-related distractors temporarily impaired response inhibition. Threat-related distractors associated with increased commission errors and no effect on RT does not suggest engagement of avoidance/freezing-type motor behaviors. The results fit in the framework of the resource competition model. A potential threat calls for evaluation of affective significance as well as inhibition of undue emotional reactivity. We suggest that these functions tax executive resources and may render other executive functions, such as response inhibition, temporarily compromised when the demands for resources exceed availability.

Orbitofrontal cortex biases attention to emotional events.

We examined the role of orbitofrontal (OF) cortex in regulating emotion–attention interaction and the balance between involuntary and voluntary attention allocation. We studied patients with OF lesion applying reaction time (RT) and event-related potential (ERP) measures in a lateralized visual discrimination task with novel task-irrelevant affective pictures (unpleasant, pleasant, or neutral) preceding a neutral target. This allowed for comparing the effects of automatic attention allocation to emotional versus neutral stimuli on subsequent voluntary attention allocation to target stimuli. N2–P3a and N2–P3b ERP components served as measures of involuntary and voluntary attention allocation correspondingly. Enhanced N2–P3a amplitudes to emotional distractors and reduced N2–P3b amplitudes to targets preceded by emotional distractors were observed in healthy subjects, suggesting automatic emotional orienting interfered with subsequent voluntary orienting. OF patients showed an opposite pattern with tendency towards reduced N2–P3a responses to emotional distractors, suggesting impaired automatic orienting to emotional stimuli due to orbitofrontal damage. Enhanced N2–P3b responses to targets preceded by any affective distractor were observed in OF patients, suggesting bias towards voluntary target-related attention allocation due to orbitofrontal lesion. Behavioral evidence indicated that left visual field (LVF) attention performance was modulated by emotional stimuli. Specifically, OF patients responded faster to LVF targets subsequent to pleasant emotional distractors. We suggest that damage to the orbitofrontal circuitry leads to dysbalance between voluntary and involuntary attention allocation in the context of affective distractors with predisposition to posterior target-related processing over frontal novelty and affect-related processing. Furthermore, we suggest that orbitofrontal influence on emotion–attention interaction is valence and hemisphere dependent.

Adaptive segmentation of burst-suppression pattern in isoflurane and enflurane anesthesia

In this paper a developed novel algorithm for adaptive segmentation of Burst-suppression EEG is presented. The algorithm can detect bursts, suppression and artifacts dividing the signal into corresponding segments. A compact representation of burst-suppression EEG, useful in monitoring long-term recordings, is presented. In the second part of the paper the burst-suppression patterns of isoflurane and enflurane anesthesia are compared. It is found that bursts as well as suppression segments are shorter in enflurane anesthsia while the coefficient of variability of the segment lengths is similar for the two anesthetics.