Anthony J.-W. Chen

Advances in neuroimaging of traumatic brain injury and posttraumatic stress disorder

Improved diagnosis and treatment of traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are needed for our military and veterans, their families, and society at large. Advances in brain imaging offer important biomarkers of structural, functional, and metabolic information concerning the brain. This article reviews the application of various imaging techniques to the clinical problems of TBI and PTSD. For TBI, we focus on findings and advances in neuroimaging that hold promise for better detection, characterization, and monitoring of objective brain changes in symptomatic patients with combat-related, closed-head brain injuries not readily apparent by standard computed tomography or conventional magnetic resonance imaging techniques.

Training of goal-directed attention regulation enhances control over neural processing for individuals with brain injury

Deficits in attention and executive control are some of the most common, debilitating and persistent consequences of brain injuries. Understanding neural mechanisms that support clinically significant improvements, when they do occur, may help advance treatment development. Intervening via rehabilitation provides an opportunity to probe such mechanisms. Our objective was to identify neural mechanisms that underlie improvements in attention and executive control with rehabilitation training. We tested the hypothesis that intensive training enhances modulatory control of neural processing of perceptual information in patients with acquired brain injuries. Patients (n=12) participated either in standardized training designed to target goal-directed attention regulation, or a comparison condition (brief education). Training resulted in significant improvements on behavioural measures of attention and executive control. Functional magnetic resonance imaging methods adapted for testing the effects of intervention for patients with varied injury pathology were used to index modulatory control of neural processing. Pattern classification was utilized to decode individual functional magnetic resonance imaging data acquired during a visual selective attention task. Results showed that modulation of neural processing in extrastriate cortex was significantly enhanced by attention regulation training. Neural changes in prefrontal cortex, a candidate mediator for attention regulation, appeared to depend on individual baseline state. These behavioural and neural effects did not occur with the comparison condition. These results suggest that enhanced modulatory control over visual processing and a rebalancing of prefrontal functioning may underlie improvements in attention and executive control.

Rehabilitation of executive functioning with training in attention regulation applied to individually defined goals: a pilot study bridging theory, assessment, and treatment.

Objective:To assess feasibility and effects of training in goal-oriented attentional self-regulation for patients with brain injury and chronic executive dysfunction. Participants:Sixteen individuals with chronic brain injury and mild to moderate executive dysfunction. Design:Participants were divided into 2 groups: one group completed goal-oriented attentional self-regulation training during the first 5 weeks, followed by a brief (2-hour) educational instruction session as a control midway through the second 5 weeks; the other group participated in reverse order. Measures:Neuropsychological and functional performance assessed at baseline and at weeks 5 and 10. Results:Participants found training in goal-oriented attentional self-regulation engaging, incorporated some trained strategies into daily life, and reported subjective improvements in personal functioning. At week 5, participants who completed goals training significantly improved on tests of attention and executive function and had fewer functional task failures, while performance did not change after educational instruction. At week 10, participants who crossed over from educational instruction to goals training also significantly improved on attention and executive function tests. Participants who crossed from goals training to educational instruction maintained their week 5 gains. Conclusions:Training in goal-oriented attentional self-regulation is theoretically driven and feasible in a research setting. Pilot results suggest improvements in cognitive and functional domains targeted by the intervention.

Traumatic Brain Injury: From Bench to Bedside to Society

Traumatic injury to the brain is a problem as old as humanity, but advances in cognitive neuroscience and a long-term view of the dynamic nature of the brain across the lifespan may change how the disorder is understood and treated.

Functional reintegration of prefrontal neural networks for enhancing recovery after brain injury.

Functions of the prefrontal cortex (PFC) are fundamental to learning and rehabilitation after brain injuries, but the PFC is particularly vulnerable to trauma. We propose approaches to cognitive training that are hypothesized to specifically enhance PFC function. We present a theoretical framework that generates hypotheses regarding the effects of training on the functional integration of processes across distributed networks of brain regions. Specific outcome measurements that may be used to test these hypotheses in clinical trials are proposed. This neural network-level approach may guide cognitive rehabilitation and facilitate development of adjunctive biologic treatments to enhance the effects of training.

Functional brain network modularity predicts response to cognitive training after brain injury

Objective: We tested the value of measuring modularity, a graph theory metric indexing the relative extent of integration and segregation of distributed functional brain networks, for predicting individual differences in response to cognitive training in patients with brain injury. Methods: Patients with acquired brain injury (n = 11) participated in 5 weeks of cognitive training and a comparison condition (brief education) in a crossover intervention study design. We quantified the measure of functional brain network organization, modularity, from functional connectivity networks during a state of tonic attention regulation measured during fMRI scanning before the intervention conditions. We examined the relationship of baseline modularity with pre- to posttraining changes in neuropsychological measures of attention and executive control. Results: The modularity of brain network organization at baseline predicted improvement in attention and executive function after cognitive training, but not after the comparison intervention. Individuals with higher baseline modularity exhibited greater improvements with cognitive training, suggesting that a more modular baseline network state may contribute to greater adaptation in response to cognitive training. Conclusions: Brain network properties such as modularity provide valuable information for understanding mechanisms that influence rehabilitation of cognitive function after brain injury, and may contribute to the discovery of clinically relevant biomarkers that could guide rehabilitation efforts.

Tonic and phasic alertness training: a novel treatment for executive control dysfunction following mild traumatic brain injury

Many individuals with traumatic brain injury (TBI) suffer difficulty regulating fundamental aspects of attention (focus, sustained attention) and may also exhibit hypo- or hyper-states of alertness. Deficits in the state of attention may underlie or exacerbate higher order executive dysfunction. Recent studies indicate that computerized cognitive training targeting attentional control and alertness can ameliorate attention deficits evident in patients with TBI or acquired brain injury. The current study examined whether improvements in attentional state following training can also influence performance on higher-order executive function and mood in individuals with mild TBI (mTBI). The current study examined five patients with executive control deficits as a result of mTBI, with or without persistent anxiety. Three patients engaged in ~5 hours of an executive control training task targeting inhibitory control and sustained attention; two additional patients were re-tested following the same period of time. Performance on standard neuropsychological measures of attention, executive function, and mood were evaluated pre- and post-training. The results indicate that tonic and phasic alertness training may improve higher-order executive function and mood regulation in individuals with TBI.

The Effect of Disruption of Prefrontal Cortical Function with Transcranial Magnetic Stimulation on Visual Working Memory

It is proposed that feedback signals from the prefrontal cortex (PFC) to extrastriate cortex are essential for goal-directed processing, maintenance, and selection of information in visual working memory (VWM). In a previous study, we found that disruption of PFC function with transcranial magnetic stimulation (TMS) in healthy individuals impaired behavioral performance on a face/scene matching task and decreased category-specific tuning in extrastriate cortex as measured with functional magnetic resonance imaging (fMRI). In this study, we investigated the effect of disruption of left inferior frontal gyrus (IFG) function on the fidelity of neural representations of two distinct information codes: (1) the stimulus category and (2) the goal-relevance of viewed stimuli. During fMRI scanning, subjects were presented face and scene images in pseudo-random order and instructed to remember either faces or scenes. Within both anatomical and functional regions of interest (ROIs), a multi-voxel pattern classifier was used to quantitatively assess the fidelity of activity patterns representing stimulus category: whether a face or a scene was presented on each trial, and goal relevance, whether the presented image was task relevant (i.e., a face is relevant in a “Remember Faces” block, but irrelevant in a “Remember Scenes” block). We found a reduction in the fidelity of the stimulus category code in visual cortex after left IFG disruption, providing causal evidence that lateral PFC modulates object category codes in visual cortex during VWM. In addition, we found that IFG disruption caused a reduction in the fidelity of the goal relevance code in a distributed set of brain regions. These results suggest that the IFG is involved in determining the task-relevance of visual input and communicating that information to a network of regions involved in further processing during VWM. Finally, we found that participants who exhibited greater fidelity of the goal relevance code in the non-disrupted right IFG after TMS performed the task with the highest accuracy.

Assessment of subcomponents of executive functioning in ecologically valid settings: the goal processing scale.

Objectives:To validate a new functional assessment tool, the Goal Processing Scale (GPS), and to apply it for testing for sources of dysfunction in patients with acquired brain injury. Determining which component processes of executive functioning underlie poor performance in complex, low-structure settings would be valuable for the assessment of deficits and for evaluating the effectiveness of treatments. Participants:Nineteen individuals with chronic acquired brain injury (mean age = 41.4 years; chronicity: 6 months to 39 years). Main Measures:Two functional assessment tasks: (1) GPS, which evaluates functional performance in the context of achieving a goal in a “real-world” setting, with rating scales measuring overall performance and 8 subdomains of executive functioning; (2) Multiple Errands Test, an unstructured assessment of ability to adhere to rules and complete multiple “real-world” tasks in a short time; and (3) a neuropsychological battery. Results:Intraclass correlation coefficients for 2 independent raters ranged from 0.75 to 0.98 for the GPS overall composite score and the subdomain scores. Performance on GPS overall and several subdomain scores correlated with performance on the Multiple Errands Test. Working memory and learning/memory neuropsychological measures predicted functional performance as measured using the GPS. Discussion:The GPS shows high interrater reliability, suggesting convergent validity with an established functional performance measure, and produces useful information regarding strengths and weaknesses in different subdomains of executive functioning. Working memory and learning/memory appear to be key determinants of goal-directed functioning for these individuals with brain injury.

Brain Changes Following Executive Control Training in Older Adults

Background. While older adults are able to attend to goal-relevant information, the capacity to ignore irrelevant or distracting information declines with advancing age. This decline in selective attention has been associated with poor modulation of brain activity in sensory cortices by anterior brain regions implicated in cognitive control. Objective. Here we investigated whether participation in an executive control training program would result in improved selective attention and associated functional brain changes in a sample of healthy older adults (N = 24, age 60-85 years). Methods. Participants were enrolled in a goal-oriented attentional self-regulation (GOALS) program (n = 11) or a brain health education workshop as an active control condition (n = 13). All participants performed a working memory task requiring attention to or suppression of visual stimuli based on goal-relevance during functional magnetic resonance imaging. Results. We observed a pattern of enhanced activity in right frontal, parietal and temporal brain regions from pre- to posttraining in the GOALS intervention group, which predicted the selectivity of subsequent memory for goal-relevant stimuli. Conclusions. Executive control training in older adults alters functional activity in brain regions associated with attentional control, and selectively predicts behavioral outcome.