Strengthening goal-directed functioning after traumatic brain injury

Handbook of Clinical Neurology, Vol. 163 (3rd series) The Frontal Lobes M. D’Esposito and J.H. Grafman, Editors https://doi.org/10.1016/B978-0-12-804281-6.00023-9 Copyright © 2019 Elsevier B.V. All rights reserved

Chapter 23

Strengthening goal-directed functioning after traumatic brain injury 1

ANTHONY J.-W. CHEN1,2* AND FRED LOYA1 VA Northern California Health Care System, Martinez, CA, United States

2

Department of Neurology, University of California San Francisco, San Francisco, CA, United States

Abstract Acute trauma to the brain can lead to chronic changes in an individual’s neurologic functioning, with some of the most debilitating and far-reaching consequences leading to compromised goal-directed functioning. Underlying sources of dysfunction can be dynamic, complex, and challenging to effectively address. This chapter delineates key principles that can be valuable for improving goal-directed functioning. The chapter is grounded in neuroscience and theoretical underpinnings while emphasizing practical approaches to maximizing functional improvements in an individual’s personal life. Rehabilitation efforts can be maximized by taking into account multiple levels and facets of goal-directed functioning in cohesive, individualized treatments. Core functions subserved by prefrontal cortical networks may be targeted and strengthened through specific approaches to training. Optimization of functioning may require unraveling and addressing some of the many factors that can modulate brain processes. We dedicate special emphasis to considering the regulation of cognitive–emotional functioning during goal pursuit, especially pertinent to treatment of combined physical and experiential trauma that is a hallmark of military service injuries. These foundations point to frontiers for innovation in strengthening goal-directed functioning after brain injury.

A FRAMEWORK FOR IMPROVING GOAL-DIRECTED FUNCTIONING AFTER BRAIN INJURY In an instant, traumatic injury to the brain can affect the core functions that make us human. Although injury is acute, functional deficits that result from traumatic brain injury (TBI) can produce tremendous chronic burden. TBI can alter the fundamental balance of cognitive–emotional–behavioral control that underlies goal-direction—the very functions mediated by frontal lobes and associated brain networks. Consequences of TBI frequently include impaired attention, learning, and executive abilities (e.g., prioritization, planning, and organization), as well as dysregulation of emotions.

Such difficulties can become compounded, having long-term and far-reaching consequences. For example, individuals who cannot pay attention, hold information in mind, and actively participate in learning activities will experience less benefit from rehabilitation, school, job training, or other efforts. Furthermore, individuals who have suffered a TBI may also be at increased risk for cognitive deterioration later in life. Effective approaches to improving functioning are needed, and the benefits may be far-reaching. We discuss a framework of principles to guide treatment approaches. Interventions are more likely to be effective when we take into account multiple levels of brain functioning, bridging from the dynamics of brain network systems to functional goal pursuit in personal life.

*Correspondence to: Anthony J.-W. Chen, MD, Center for Integrated Brain Health and Wellness, VA Northern California Health Care System, 150 Muir Road, Martinez, CA, 94553, United States. Tel: +1-925-372-2530, Fax: +1-925-372-2111, E-mail: anthony. [email protected]

436 A.J.-W. CHEN AND F. LOYA The effects of TBI can be difficult to understand for cerebral end targets and those that connect the PFC with the affected individual, as well as for family, work relaother brain regions. Some of the most common deficits tions, and even clinicians. Residual effects may be variwith distributed axonal injury, even in the absence of corable and dynamic, often involving complex interactions tical lesions, are in speed of processing, executive funcbetween various biologic, social, and environmental tions, emotion processing, and memory (Scheid et al., modulators. Conceptualizing challenges to higher-level 2006; Levine et al., 2008). Thus understanding the cognitive functioning for individuals with TBI as a form importance of network interactions is an important foundation for understanding the functional consequences of of cognitive–emotional dysregulation is often more TBI, which might otherwise be labeled “nonfocal.” informative than adopting a “deficit” model. A deficit The potential to improve core abilities via training is model typically presumes or implies that abilities are of special importance. Key principles for training include static. More often, functioning is marked by variability. strategically targeting specific skills, designing progresFor example, an intelligent individual may at times be sive challenges for these skills, anchoring training in a distractible, other times derailed by frustration and goal framework, and strengthening regulation of undernegative emotions, other times hyperfocused on an issue, lying brain states. Benefits of training may synergize and at other times demotivated, all leading to ineffective with pharmacologic and other adjunctive approaches. goal pursuit. Furthermore, the nature of dysfunction may Other important and common approaches, such as makbe poorly defined or missed altogether when “deficits” ing use of compensatory tools and developing external cannot be reliably documented. Understanding the structures, are given less emphasis in this chapter, as underlying problems and dynamic influences is key to these are well addressed in other rehabilitation texts. effective treatment and management. There is significant variability in the rate and end point of recovery, and the major concern here is functional Goal frameworks to inform treatment difficulties that become chronic. Multiple factors may A goal framework is vital for successful goal pursuit for contribute to, modulate, and even prolong symptoms. any individual. A goal framework serves to guide, coorSignificant benefits can be gained by understanding and addressing important modulators of neurocognitive dinate, and integrate aspects of cognition–emotion– functioning. Addressing such modulators as sleep can behavior in the service of achieving a goal. In the context aid in optimizing functioning for any given level of of treatment, especially given the complexities of brain ability. injury, it is highly valuable to define individualized From an anatomic perspective, one must consider goal frameworks explicitly. This can aid not only the multiple possible forms of injury to cortical as well as individual in pursuing his/her life path, but also the clinical team in helping build an individualized treatment subcortical structures, as well as the white matter connecplan. In this chapter, a number of approaches to treattions vital for network functioning. Among cortical regions, prefrontal and mesial temporal structures are ment are discussed, and all are strengthened when convulnerable to contusions and hemorrhages. Deficits in nected back to a clear goal framework informed by the goal-directed or executive control functions are generally patient’s own interests, aspirations, functional needs, attributable to damage to prefrontal systems, which and specific goals. include not only prefrontal cortex (PFC) per se but also Goal frameworks can be considered at multiple extensive interconnections with subcortical and posterior possible levels. Defining a goal framework is a process and skill in and of itself. For purposes of illustrating a cortical structures (D’Esposito and Chen, 2006). Often, the microscopic injuries are not visible to clinicians even goal framework with an injured individual, it is valuable with current clinical techniques for magnetic resonance to consider frontal lobe function and dysfunction in the imaging. Clues to axonal injury may be better seen in context of a particular example goal. For any given goal, the form of microhemorrhages with hemosiderin deposifrom those that are relatively simple (such as running an tion on gradient echo or susceptibility weighted imaging errand, e.g., buying milk), to those that are more complex (Mukherjee, 2005), but in most cases, dysfunction occurs (such as accomplishing a multistep project, e.g., starting despite otherwise unremarkable imaging findings. a small business), there are fundamental requirements The importance of axonal injuries in TBI highlights that can be broken down into facets of neurologic procesthe need to understand brain functioning in terms of sing. The goal not only provides an end objective, but distributed but coordinated network processes (Chen also anchors the selection of possible steps, processes, et al., 2006). Diffuse or multifocal axonal injury may methods, and actions that influence goal pursuit efforts. affect commissural, callosal, and association as well as The work required to successfully accomplish particularly vulnerable long fibers, including those carryany given goal requires the ability to functionally orgaing neuromodulators in projections from the brainstem to nize multiple neural processes, including selecting the

STRENGTHENING GOAL-DIRECTED FUNCTIONING 437 relevant pathways or processes (while excluding symptoms or to misattribute difficulties to a particular others), coordinating these processes at any given and vague symptom. For example, individuals with very moment in time, and dynamically adjusting this coordidifferent problems may complain of the same failures nation, all while maintaining a consistent goal focus. and symptoms—“my memory is terrible.” For one indiWhile traversing various goal pathways, any of a numvidual, emotional tone may be incongruent with encodber of possible processes may be emphasized. For ing of relevant information (e.g., high anxiety when example, accomplishing goals requires mechanisms speaking to a professor in school), while, in other circumof selection, maintenance, and protection of goalstances, there may be different difficulties with selective relevant information from disruption during working attention (being susceptible to distraction during encodmemory, learning, decision-making, and/or probleming)—or there may be a dynamic combination of both. solving. The protection of information processing from During goal pursuit, when disrupted by someone else, distractions anywhere along this pathway is crucial to an individual might forget the goal to be accomplished, efficient and effective goal attainment, especially when or another person might be “derailed” by frustration or multiple steps are required or goal activity must be negative feelings of self-doubt. At the other end of the maintained over time. Thus, the organization of training goal pursuit pathway, retrieval of vital information from explicitly around goals can be helpful with addressing a memory might be hampered by poor encoding in the first number of impairments to frontal functions. place vs current anxiety vs lack of sleep vs interference Directly valuable for treatment planning, the goal from drug effects. Symptoms may actually differ in difdefines the overall context for considering roadblocks ferent contexts. The identical complaint of “bad or challenges, problems to be solved, decision points, memory” is poorly understood unless these various rules, and other considerations important for guiding possibilities are considered. functioning. In addition to framing more obvious exterEstablishing a goal framework also involves fostering nal challenges (e.g., a road being blocked by construca sense of goal mindedness in the injured individual. This tion), this frame helps to highlight and put in context involves helping the person to consider motivations, cogintrinsic personal challenges. As one walks through a nitions, emotions, and, ultimately, behaviors in terms of goal with an individual, points for intervention become the goal. Better understanding this “big picture,” and the more apparent. For example, we can consider different place of specific neurologic processes, can be useful for phases in the continuum of goal pursuit and review sucthe individual as well as clinicians in considering needs cesses or difficulties with each. We may consider issues and approaches for improving functioning. Very often, with defining a goal, planning an approach, initiating we need to address multiple targets in an individualized action, and aspects of selectively encoding, maintaining, therapeutic approach. Importantly, it may be possible to and using goal-relevant information. The latter may identify and isolate specific processes with advances in include considering how effectively an individual is neuropsychologic and neuroscientific assessments, but keeping the goal in mind while traversing the many steps to best achieve functional gains, we need to take into through to completion. We may consider aspects of account the integration and coordination of multiple prioritization or organization when there are multiple processes in the formulation of treatment approaches. options and decisions to be made. Along the goal pathThus, much of this chapter is dedicated to elaborating way, we can consider an individual’s agility with shifting principles to guide treatment within a goal framework. resources to deal with distractions or disruptions, as well Making use of this general principle is feasible and as redirecting cognitive effort when transitioning helpful in any healthcare system. The basic principle between tasks (especially when multiple tasks are can be implemented at different possible levels. First, required to achieve a goal). Needs for retrieval of inforthere is the matter of translating this to individual intermation or skills may occur at multiple possible points, personal encounters. A contrast with typical approaches and successful retrieval can be especially vital for navimight be illustrative. Traditionally, a clinician might ask gating the multiple transitions required to attain many something along the lines of “What is bothering you?” or goals. Cognitive–emotional difficulties as well as fluctu“What are you having problems with?” and then make a ating motivation can affect any of these processes. An list of complaints. This approach is dependent on the overall goal framework can make the place and impact individual’s personal abilities of self-assessment, awareof any specific issue more clear. ness, and synthesis of processes that could be poorly Without anchoring a review of a patient’s symptoms understood, subtle, or complex. In a goal framework and reported problems in a goal framework, the nature approach, the clinician could walk through various of any difficulties an individual is having in personal life personal goals or scenarios, and consider the nature of may not be obvious to that individual or to others. It is roadblocks or difficulties along the way. Symptoms easy and common to get lost in the plethora of possible could be understood in the context of activities and

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pursuits, and issues that the patient may not be fully aware of may be better understood in the context of their effects on personal goals. A neurologist could certainly take this approach, helping to provide some differentiation of contributors to dysfunction, increasing precision in translating from patient history to specific contributors or modulators of functioning, and informing directions to treatment in an individualized goal framework. This approach could be expanded by therapists working directly with an individual in specific scenarios or in working through the pursuit of actual goals (e.g., grocery shopping or schoolwork). Clinicians may then work with patients in a manner that integrates rehabilitation goals for certain strategies, skills, or even biologic treatments into the overall framework. At this individual level, framing rehabilitation treatment around patient-centered goals in their personal life contexts supports motivation, awareness, and even opportunities for personally relevant markers of progress. Some form of goal setting is often standard in rehabilitation therapies; however, in an illustrative contrast, goals may be therapist goals rather than patient-centered goals. Therapist-driven goals, such as a goal of accomplishing a certain number of repetitions of a particular task, can be very useful for achieving basic steps, but may be limited in achieving broader gains. The goal framework approach, furthermore, has an even greater potential value when care is provided via multiple clinicians or via an interdisciplinary team. Care provided by different clinicians has much greater potential for benefit when the clinicians, individual, and other caregivers are working in a common framework with collaborative goals. In contrast, care has a high potential for fragmentation, confusion, and even conflict when the members of a potential team are working in different frameworks toward uncoordinated goals. One might argue that a key difference between multiple clinician care and interdisciplinary care is a foundation for coordination of care across disciplines by a clear individualized goal framework.

GUIDING PRINCIPLES FOR OPTIMIZING AND IMPROVING GOAL-DIRECTED FUNCTIONING The following are key points to consider in determining interventions for improving functioning after brain injury. After injury, sources of dysfunction may be multifactorial, and each factor or interaction of factors represents a potential target for intervention. It is helpful to consider possible approaches in a conceptual framework that considers core abilities (neurocognitive processes and functions), their dynamic interactions with other neurologic functions

(we highlight here cognitive–emotional interactions), as well as modulatory influences on functioning. Core targets of intervention include specific neural–cognitive processes important for healthy, goal-directed functioning after brain injuries, such as attention, working memory, set shifting/task-switching, and memory retrieval. However, these processes may also be affected by myriad influences: factors that modulate physiologic brain states; emotions (e.g., anxiety, fear, irritability, anger, depression); factors that regulate brain functioning via homeostatic and restorative processes (e.g., sleep); pharmacologic influences (e.g., medications, other drugs); and other comorbidities (e.g., chronic pain). All of these facets must be dynamically regulated to optimize goal-directed functioning. Any or all of these may have to be taken into account for a therapeutic intervention to be effective. Simply put, “unraveling the tangled ball of yarn” may be required to begin to make therapeutic progress. Often, it is ideal to take an integrated approach that addresses multiple targets based on the therapeutic goal—the focus here being on improving goal-directed functioning. We consider tiers of interventions based on the preceding conceptual framework. In many clinical situations, it is valuable to address modulators that adversely affect the core functions early on, clearing some of the fog in order to optimize functioning but also so that the core functions can be better addressed. With each intervention target, and as a general theme, we place a special emphasis on nonpharmacologic approaches as a foundation before considering pharmacotherapeutics as adjunctive treatment. Pharmacologic approaches rarely provide a full answer on their own, and they continue to evolve very slowly over time. Until new and more efficacious pharmacologic treatments are developed, the current leading edge is in selective and strategic individualized use of medications to augment learning and rehabilitation.

Gateway processes as therapeutic targets In considering approaches to optimizing functioning, certain domain-general processes deserve special consideration as “gateways” to learning, adaptability, and behavioral change that are key processes in rehabilitation. Such processes may be worth targeting even if “deficits” are not measurable in those processes. In particular, it is valuable to consider functions for regulating brain states (encompassing attention–arousal–emotions) as foundational to learning. Aspects of selective attention and working memory are the next gateways in learning in a goal-directed manner. Complementing these from the top-down, “meta-cognitive” processes such as selfawareness (awareness of one’s abilities, strengths,

STRENGTHENING GOAL-DIRECTED FUNCTIONING weaknesses, and goals, with the ability to monitor and review one’s actions in these contexts) and goal framing help to organize learning and behavior. Addressing these processes, whether as direct targets of therapy or as scaffolding supportive of a person’s rehabilitation, are valuable in maximizing the ‘learning curves’ of rehabilitation. These processes are also crucial for continued learning, adaptation, and problem-solving outside of clinician-guided settings—that is, in real life. The major challenge for many individuals with TBI is that these are the very functions likely to be dysregulated after injury. Thus, consideration of these gateway processes should be made at every stage of intervention formulation, and plans will need to adjusted as treatment progresses (or regresses).

Optimizing functioning by addressing modulators The importance of modulators of functioning is highlighted with trauma for veterans of military service. With the increase in military injuries and the combination of physical and experiential trauma, so-called “mild TBI” and cognitive–emotional targets of therapy deserve special consideration. Consideration of other modulators of functioning is also made clear in the context of veterans. Issues with sleep, affect/mood conditions, pain, and medication effects are all common and highly relevant to overall functioning. In particular, numerous individuals returning from combat activities suffer from both TBI and varying symptoms of post-traumatic stress disorder (PTSD)—a combined combat neurotrauma syndrome (Chen and Novakovic-Agopian, 2012). Experience suggests that the combination of TBI with PTSD may result in more prolonged or more complicated courses of recovery. One of the first studies to track recovery over the long term for post-9/11 veterans of military combat service found that symptoms and functioning worsened in those with TBI over 5 year’s time (Dams-O’Connor and Tsao, 2017; Mac Donald et al., 2017). The combination of TBI–PTSD further challenges us to consider multifaceted approaches for optimizing functioning, with explicit consideration of cognition, emotion, and their interactions in guiding goal-directed behavior.

Cognition–emotion interactions in goal-directed functioning Understanding the connections between cognition and emotions in guiding goal-directed behavior highlights the importance of considering these interactions in treatment formulations. One of the most vexing challenges in rehabilitation is to improve the regulation of cognitive– emotional states, where any combination of cortical

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and/or subcortical injury, sleep dysfunction, reactive emotions, cognitive deficits, and other factors can contribute to dysregulation. In order to optimally guide personal functioning, cognitive–emotional processes need to be regulated and coordinated in an integrated manner. These regulation processes must be dynamically adjusted and sustained all along the pathway to a goal. Dysregulation can lead to an individual being “derailed” by any combination of goal-disruptive cognitive or emotional processing. For example, external distractions may direct attention and associated neural resources to nonrelevant information or actions, while “internal distractions,” such as reactive frustration, worries, anxieties, or anger, can disrupt processes of goal pursuit as well. Furthermore, goalincongruent emotional states may not support the cognitive processes needed to accomplish a goal. For example, a highly aroused, hypervigilant state may be incongruent with the need for sustained attention to one extended task (e.g., taking a test in a classroom setting). Any of these can lead to increased effort and energy exhaustion with a reduced ability to actually accomplish the intended goal. Overall, it is worth considering the complexity of cognitive–emotional interactions in a goal framework. In a goal framework, it is clear that cognition and emotion must be coordinated and integrated into a complex and dynamic interplay to effectively and efficiently accomplish goals, especially as complexity and challenges increase. Therefore, it is beneficial to treat cognitive– emotional dysregulation not only in parallel treatments, but ideally in an integrated treatment plan anchored by a goal framework. We discuss example approaches in this chapter.

PRINCIPLES FOR TRAINING TO STRENGTHEN GOAL-DIRECTED FUNCTIONING Training forms the most fundamental core of postinjury rehabilitation. Training can be conceptualized as guidance and activity that facilitates learning of skills or strategies or fosters other behavioral change in support of individualized rehabilitation goals. In rehabilitation, training is often combined with psychoeducation, environmental modifications and adaptations, and psychotherapy to address different aspects of the patient’s postinjury functioning in a complementary fashion. Training also may need to be combined with approaches that optimize biologic and other modulators of functioning (e.g., sleep) to maximize therapeutic benefit. Various approaches to training emphasize different learning goals and training methods. Training may emphasize the learning and application of neurocognitive

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skills intended to improve one’s ability to accomplish certain tasks or goals and/or strategies aimed to organize and guide behavior in specific circumstances. An alternative approach aims to cultivate neurologic abilities or behavioral change in the absence of explicitly training neurocognitive skills or strategies. This approach characterizes many forms of computerized “brain training” programs. In this section, we share some basic principles of training that can be incorporated into interventions to target and maximize improvements in goal-directed functioning. These principles may not only bolster therapies where goal-directed cognition is the primary target of therapy but may also be incorporated into cognitive, motor, speech, or other therapies in order to maximize the targeting of frontal systems functions in any of those contexts. Training across modalities and across contexts may be particularly important for training frontal functions, even more so than for other neurologic functions. Strategic synergies with pharmacotherapy can also be valuable, although optimal combinations remain a frontier for research. We start with some general considerations before we elaborate on principles of specific training approaches emphasizing metacognitive strategy training and taskbased approaches to cognitive rehabilitation. Of critical importance, training needs to challenge and effectively engage the targeted processes one hopes to strengthen. While this may appear self-evident, achieving this goal in neurorehabilitation is often not straightforward, especially with respect to “top-down” control processes mediated by PFC networks (D’Esposito and Chen, 2006). As noted at the outset of this chapter, we recommend a goal-based approach as a means to engage core frontal lobe functions commonly affected by TBI. This can translate to a number of possible approaches. Strategy training typically focuses on teaching a specific approach to achieving a goal or desired outcome, and progresses from explicit, external cueing and reinforcement of strategy use to attempts to internalize strategies and independently initiate their use. Once internalized, strategies can be thought of as intrinsic “tools” that an individual can use to help accomplish particular tasks. Examples of strategies taught in neurorehabilitation include use of compensatory tools (e.g., day planners; Storzbach et al., 2017) and direct training within domains of time management (e.g., Fassoti et al., 2000), goal setting (e.g., Levine et al., 2000), and self-monitoring and self-awareness (e.g., Goverover et al., 2007) as well as using external cues for reminders (e.g., Manly et al., 2002). Factors to consider when formulating clinical interventions include to what extent the strategies are task- or context-specific vs transferable to other tasks and/or contexts, to what

extent the individual can learn and remember the strategy, and to what extent the individual will be able to prospectively initiate use of the strategy in the appropriate situations. For example, it is not uncommon for an individual to be able to learn a strategy during therapy (e.g., a method for breaking problems into manageable steps), but then fail to apply this strategy when faced with a real-world problem. Such limitations in transfer may be directly related to an individual’s cognitive deficits. A skills-based approach emphasizes improving an individual’s target abilities as the primary means of improving goal-directed functioning. Stated slightly differently, skills can generally be considered as the integrated use of particular neurologic functions or processes for the accomplishment of functional tasks or goals. Skill training may emphasize practice on specific functional tasks (e.g., making a sandwich) or target specific processes (e.g., working memory across tasks). The choice of approach often depends on the nature and severity of cognitive deficits. For example, it has been argued that functional approaches (i.e., training on specific tasks) may be more appropriate for patients with severe deficits (Giles, 2010) where the capacity for abstraction, self-reflection, and generalization are often limited. When employing a skills-based approach, it is ideal for training tasks to progressively challenge the patient (D’Esposito and Chen, 2006; Chen et al., 2017). The importance of progressive increases in challenge is underscored by the ability of the brain to adapt to tasks. That is, tasks become less effective at encouraging learning in the targeted domain unless challenges are increased. In particular, goal-directed control functions and the associated prefrontal networks become progressively disengaged with tasks that become more automatic with repetition (D’Esposito and Chen, 2006). Certain domain general factors are also valuable to consider when formulating clinical interventions in order to maximize learning. Active participation on the part of the patient is often the greatest determinant of the success of any training approach. Ways to enhance engagement can include raising awareness of one’s abilities and difficulties, identifying opportunities for self-direction during treatment, bolstering motivation, and supporting opportunities to apply and transfer training to personally relevant situations and goals. Establishing the direct relevance of training to individuals’ unique pursuits, aspirations, difficulties, and life situations is of paramount importance (Novakovic-Agopian et al., 2018). These considerations become even more important when deficits affect awareness, motivation, attention, and other aspects of self-regulation. In addition, careful attention needs to be paid to patients who actively avoid or develop negative reactions to training, as these behaviors can

STRENGTHENING GOAL-DIRECTED FUNCTIONING have strong deleterious effects on rehabilitation. Issues of avoidance and emotional reactivity are often heightened when TBI is combined with PTSD or other psychologic health conditions. Addressing the fundamental ability to regulate one’s cognitive–emotional (brain) state can also have a farreaching impact on goal-directed functioning. Brain states play an important role in an individual’s readiness to learn during training and rehabilitation (Seager et al., 2002; Bassett et al., 2011; Filevich et al., 2012; Tang et al., 2012), and we therefore consider it a universal and fundamental target in therapy. Approaches to improving brain state regulation, particularly in situations where individuals with brain injury are prone to becoming overwhelmed and/or dysregulated, remain at the frontier of cognitive rehabilitation research and development (e.g., Tang et al., 2007; Chen et al., 2017). Finally, for any approach to neurorehabilitation to be maximally effective, training must explicitly support transfer of gains to new contexts as well as generalization of learning to an individual’s personal life. One means of helping promote transfer and generalization is for targets of training to be practiced to the point of near-automaticity, not just on isolated tasks but across a range of contexts and challenges. Intensive training across multiple modalities may maximize engagement of core networks leading to improved functioning across contexts (Chen et al., 2006; D’Esposito and Chen, 2012). Transfer and generalization can be aided by clearly delineated goals, which can help increase awareness of potential opportunities for use of trained skills or strategies, as well as guide the establishment of plans for use of skills or strategies in these situations. Explicitly training implementation intentions (Gollwitzer and Sheeran, 2006) based upon goals (i.e., if “X” goal situation and/or challenge arises, then I will apply “Y” skill) can also help increase the likelihood of effective skill or strategy use. Bridging training experiences to individual goals and life situations often requires creativity, flexibility, persistence, and collaboration from patients.

Metacognitive strategy training for higher-order cognitive dysfunction Metacognitive strategy trainings (MSTs) are among the most researched and empirically supported approaches to remediate executive dysfunction following brain injury, and they are currently classified as a “practice standard” (Cicerone et al., 2011) in the field of cognitive rehabilitation. Metacognition, often described as “thinking about thinking,” includes the dual roles of self-knowledge/self-awareness of one’s cognitive abilities, strengths, and vulnerabilities, as well as the ability to actively monitor and consciously control one’s

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cognitive processes and behaviors in a goal-directed manner (Kennedy et al., 2008). MSTs represent a “topdown” approach to cognitive rehabilitation that largely involves training stepwise procedures for structuring goal activities. In addition, MSTs may train strategies to address specific deficits in other aspects of cognition such as limited self-awareness, impulsivity, goal neglect, concrete thinking, and/or poor self-monitoring. The ultimate goal of MSTs is to help an individual with brain injury assert greater intentional control over goaldirected behaviors and related processes. Critically, the degree to which individuals are able to achieve this lofty goal varies widely, often reflecting the severity of initial injury and associated impairments. Thus, a key clinical challenge is to delineate the amount of ongoing, external supports (e.g., cues) an individual may require to structure their goal activities vs their capacity to internalize strategies and utilize them independently and flexibly. The basic structure of many MSTs reflects the very nature of executive functions themselves: setting a goal, establishing an action plan, executing the plan, monitoring behaviors and outcomes, and updating and adapting plans in light of changing circumstances and feedback. We consider key principles within each of these steps, noting that different approaches broadly considered MSTs emphasize these points to varying degrees. We then review select examples of trainings that illustrate these key principles.

Goal setting Often the initial step is teaching individuals with brain injury how to establish realistic, feasible goals involving outcomes that are clearly defined and well delineated. At this stage, issues such as limited self-awareness of cognitive–emotional vulnerabilities may interfere with learning how to establish realistic goals. Consequently, therapists may need to work with patients to improve aspects of self-awareness and insight in tandem with instruction in formal goal-setting procedures. Use of goal-setting systems like SMART goals (i.e., goals that are Specific, Measurable, Achievable, Relevant, and Time-based (Bovend’Eerdt et al., 2009), or technology-based applications for smartphone devices can provide necessary external support and guidance for learning how to set realistic goals. At another level and as previously mentioned, cultivating a sense of goal mindedness, in which behaviors are conceptualized in terms of goals, may also be clinically useful. Adopting an overall goal framework can help facilitate application of a wide range of training strategies by providing a concrete point of reference to judge if current behaviors are misaligned with stated objectives, thus helping to cue or trigger strategy application in the moment.

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Establishing a plan Second, individuals may work toward developing action plans for accomplishing their defined goals. This typically involves breaking down the ultimate goal into a series of tasks, subgoals, and/or steps, and then structuring these activities into rationally defined sequences or series of actions (e.g., Ylvisaker and Feeney, 1998). This process may also involve predetermining resources required for the individual to accomplish a given task or subgoal, as well as identifying and resolving obstacles that potentially could derail or impede progress. The process of creating action plans and sequencing behaviors must take into account the nature and extent of frontal dysfunction in combination with the nature of the stated goal (e.g., learning procedures for dressing vs applying for a job), with supports and expectations adjusted accordingly.

Executing plans and monitoring behaviors Third, individuals may be trained to enact their plan and monitor their behaviors. Key challenges involve helping individuals maintain a goal focus and stay on track, especially when faced by distractions or when behaviors must be coordinated and maintained over time. Additional strategies can be helpful with promoting goal-directed behaviors and follow through and need to be selected on an individual basis. Examples include training selftalk procedures to help individuals stay on-task and minimize the impact of potential distractions or disruptions to goal activity (Sohlberg and Mateer, 2001); relaxation and/or other cognitive–emotion–regulation strategies to apply in instances when feeling overwhelmed and frustrated (Novakovic-Agopian et al., 2018); cognitive– behavioral strategies to help manage poor self-efficacy beliefs (e.g., “I can’t do this”) or address maladaptive cognitions (e.g., “I am an incompetent failure”) (Rath et al., 2003); or procedures, often aided by external cues (e.g., alarm) for stopping activity periodically to evaluate performance (Fish et al., 2007). Application of these strategies is not limited to task execution, but often is of distinct utility when traversing the multiple, distributed, and contingent steps required to accomplish a complex goal.

Incorporating feedback and adjusting plans Finally, individuals may be trained to evaluate their actual performance in light of their desired outcomes and to make adjustments accordingly. This process is often aided by having individuals explicitly predict outcomes associated with their plans prior to initiating action, and then to compare their actual performance with these predictions (e.g., see Sohlberg and Mateer, 2001). One goal

of this final step is to facilitate increased self-awareness and self-monitoring and assist with problem-solving efforts. Periodic reminders (e.g., cell alarm) or other external cues to complete self-assessments in the moment can help minimize issues related to poor memory or biased recall. Overall, MSTs provide explicit guidance and strategies to help structure goal activity initially and then support the internalization of trained processes via sufficient practice and reinforcement. This general approach has received wide support within the intervention literature, with multiple variants emphasizing different training targets (e.g., time management vs problem-solving) and metacognitive strategies (e.g., self-monitoring vs behavioral self-regulation) as well as incorporating additional therapeutic components (e.g., mindfulness meditation). While any number of activities can be selected to practice implementation of these stepwise procedures, supported application to the patient’s individual goals may be of greatest clinical utility (e.g., Novakovic-Agopian et al., 2018). Use of MSTs is supported by both clinical observations (e.g., Levine et al., 2000) and meta-analytic outcomes (Kennedy et al., 2008).

Examples of MSTs Problem-solving therapies (PSTs; e.g., Ylvisaker and Feeney, 1998) represent one of the oldest variants of MSTs. The objective of PSTs is for individuals with brain injury to internalize a sequence of steps effective for problem solving, so the steps can be effectively applied to novel situations and tasks in the absence of external cues or direct therapist support. For PSTs, participants are trained on a basic problem-solving procedure, which includes elements of problem definition, setting goals, brainstorming possible solutions, evaluating benefits and potential costs of identified solutions, selecting and executing the best option, and evaluating the effectiveness of the chosen solution. PST approaches may emphasize varying numbers of problem-solving steps and/or different metacognitive strategies, but most follow a general process of facilitating self-awareness of problems, planning for a solution, executing the plan, and evaluating its effectiveness. Executing stepwise procedures can be aided by training use of a simple metacognitive mantra, such as Goal-Plan-Do-Review, which explicitly guides the individual throughout the problem-solving process as well as provides cues to reflect upon which trained strategies may be most helpful at any given moment. Problem-solving approaches have also shown to be clinically effective (von Cramon et al., 1991; Levine et al., 2000; Haskins et al., 2012). Goal Management Training (GMT) is another example of MST that has received empirical support.

STRENGTHENING GOAL-DIRECTED FUNCTIONING Developed by Robertson (1996), GMT is an interactive, manualized protocol that seeks to help individuals with brain injury structure and guide their goal activities. This intervention line was inspired by Duncan et al.’ (1996) theory of “goal neglect,” which posits that impaired frontal functioning following brain injury results in a general “life disorganization” due to improper construction and utilization of goal lists. The primary objective of GMT is training individuals with brain injury to stop ongoing activity in order to construct goal hierarchies and actively monitor and adjust their behaviors (Levine et al., 2011). GMT involves didactics on absentmindedness and habitual ways of responding; techniques for setting goals and establishing action plans; and actively monitoring attentional “slips,” stopping activities, and reconsidering current behaviors in light of stated goals to inform problem solving and decision-making. Controlled trials of GMT have reported positive effects on neurocognitive measures of sustained attention and visual–spatial problem solving (Levine et al., 2011) and questionnaire-based assessments of everyday executive functioning (Tornås et al., 2016). Research on the effectiveness of GMT has shown that this approach is particularly helpful when combined with adjunctive approaches to cognitive rehabilitation that address functional skill application and emotion regulation (Miotto et al., 2009; Krasny-Pacini et al., 2014). Time pressure management (TPM; Fassoti et al., 2000) training is a collection of stepwise procedures for addressing deficits in speed of information processing, particularly under time constraints. Reflecting a basic problem-solving approach, patients are trained to regulate and control multiple levels of information inputs, each of which are potentially subject to varying demands and time pressures. The broad goal of TPM is to help patients identify and apply problem-solving skills to potential obstacles prior to beginning a task, as well as during task execution. TPM emphasizes four problem-solving steps to effectively address three levels of behaviors: long-term “strategic” planning, short-term “tactical” maneuvers, and rapid “operational” decisions made under time pressures and when encountering problems. In addition, TPM may include training in metacognitive strategies, including self-monitoring, self-pacing, rehearsal, anticipation of problems, and asking for clarification and specific information. One of the more recent clinical innovations with respect to MSTs is Gist reasoning training (see Chapman and Mudar, 2014). Gist reasoning training teaches strategies to improve the ability to abstract generalized meanings from complex information (i.e., to get the “gist”) and to incorporate this procedure into day-to-day life. Training emphasizes three primary strategies: strategic attention, which involves the intentional blocking of

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distractions; integrated reasoning, which involves extracting abstract concepts from specific facts; and innovation, which specifically targets generalizing these strategies to new information and contexts. Strategy instruction proceeds in a hierarchical and interdependent fashion, with individual strategies building on one another. Gist training has received empirical support from multiple patient groups, including individuals with chronic TBI (Vas et al., 2011; Chapman and Mudar, 2014).

Task-based approaches to neurorehabilitation Another approach to neurorehabilitation following brain injury includes attempts to directly remediate deficient cognitive processes through intensive and repetitive task-based training. This line of intervention development was inspired by basic neuroscience research on neuroplasticity (Merzenich and Sameshima, 1993; Mahncke et al., 2006a) as well as advances in task development for parsing different cognitive processes. This approach is also attractive in that it is relatively accessible and typically does not require trainer resources to implement. The overarching rationale of this approach is that the restoration of deficient cognitive processes may be achieved through repetitive practice on tasks that target the deficient processes themselves (Mateer and Kerns, 2000; Rabipour and Raz, 2012). In turn, cognitive gains are theorized to support functional improvements on real-world tasks that incorporate the remediated cognitive functions. Key examples include training to improve attention and/or working memory (e.g., Klingberg et al., 2005)—frontally mediated functions that are frequently impaired following brain injury and that influence the efficiency of higher-order executive abilities. Clinical application of this approach has been inspired by findings that cognitive training can improve performance in areas such as working memory (see Klingberg, 2010) and produce corresponding changes to associated brain regions such as frontal and parietal cortex (Olesen et al., 2004). As currently envisioned, direct training of cognitive processes is often achieved through repetition on relatively simple and isolated tasks that potentially allow for strengthening the underlying neural circuitry and cognitive functions on which task-performance is based. Task repetition has been facilitated in recent years by computerization—some reflecting “gamified” versions of tasks designed for measurement purposes. This has contributed, in part, to the significant increase in popular interest as well as the commercial availability

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of task-based cognitive trainings, often marketed as “brain training games” (see Simons et al., 2016). A stand-alone, task-based approach to cognitive training often follows several general principles. First, training may begin with an assessment of cognitive abilities, and training tasks can be selected to target cognitive domains identified as deficient. Training tasks may also be designed to target cognitive functions in relative isolation rather than in an integrated fashion, allowing for a high degree of specificity with training. Second, training is primarily designed to be highly repetitive and of a sufficient intensity (e.g., duration, challenge). Repetition and intensity are both theorized to be necessary to improve the targeted ability (Chen et al., 2006; Rabipour and Raz, 2012; Chen et al., 2017). Third, the challenge levels of tasks are often individually calibrated and adapted based upon performance, ensuring that participants are consistently engaged at the upper bounds of their cognitive abilities. Fourth, data-driven feedback is often utilized to enhance motivation or allow patients to better self-monitor and learn from their performance. Finally, training typically does not explicitly teach neurocognitive skills, reflecting a theory of neuroplasticity that postulates engaging repetitively and intensively with training tasks is sufficient to achieve neural and cognitive changes. Despite its potential, the place of stand-alone, taskbased training approaches in brain injury rehabilitation remains unclear. First, much of the extant research has been conducted on healthy adults, notably the aging population (e.g., Mahncke et al., 2006b). Second, many researchers have not found evidence for direct cognitive benefits from task-based training (Owen et al., 2010; Shipstead et al., 2012a,b; Jacoby and Ahissar, 2013; Melby-Lervåg and Hulme, 2013; see Simons et al., 2016 for a comprehensive analysis and review). However, one recent systematic review (Bogdanova et al., 2016) of computerized cognitive rehabilitation of attention and executive functions following acquired brain injury found statistically significant training-associated cognitive improvements in 23 of 28 studies included in the review, with the additional 5 studies demonstrating promising trends. While available evidence suggests that stand-alone, task-based approaches to cognitive rehabilitation may be able to strengthen some aspects of cognition, significant questions remain regarding to what extent cognitive gains transfer and generalize beyond trained tasks (or those highly similar in nature). In addition, the exact nature of what is being transferred or generalized is often unclear (e.g., what has the individual learned, if anything, that can be transferred to novel tasks and contexts?). Given the empirical and clinical evidence currently available, we acknowledge that task-based training may assist in developing certain abilities, but

we recommend that it is best implemented in the context of a treatment program that addresses other key principles for improving goal-directed functioning.

Integration of task-based and metacognitive trainings One example that highlights this integrated approach is Attention Processing Training (APT) developed by Sohlberg and Mateer (1987). APT integrates a combination of computerized task-based skill practice, metacognitive strategy instruction, and guidance. The ultimate goal of this approach is to help the patient transfer training experiences and acquired skills to patient-defined goals. APT is rooted in the author’s hierarchical theory of attention, which consists of interrelated processes of focused, sustained, selective, alternating, and divided attention. Training begins with a thorough assessment of attentional difficulties, which is utilized to not only select training activities but also the metacognitive strategies included in training. Following assessment, training is individualized to first target the “lowest” level of attentional impairment, and then progresses to higher levels of complexity once basic proficiencies have been demonstrated. APT consists of several training modules that target various levels of attentional impairments, and a well-delineated treatment manual specifies metacognitive strategies to accompany each impairment domain. Feedback is a hallmark of this approach, with both quantitative (e.g., performance metrics on computerized tasks) and qualitative metrics (e.g., discrepancies between predicted and observed performance) informing the progression of training. Training in generalization also represents a fundamental aspect of APT, with the therapists’ role consisting of identifying, coaching, and providing feedback on how trained strategies can best be utilized in the real world. APT is an empirically supported training for attentional impairments. Another integrated approach to training targets goaldirected brain state regulation (Chen et al., 2017). Training emphasizes intensive and repetitive practice with regulating brain states during different phases of goal pursuit, particularly under conditions of stress and challenge. This approach supports guided experiential learning of state-regulation skills by providing individualized guidance and coaching on skill use during a wide variety of training exercises, including digital scenario-based challenges, self-identified difficulties in daily life, and real-life goals. However, unlike APT, digital scenarios are not limited to various aspects of attention. Rather, digital scenarios require the integration of multiple frontal functions commonly affected by TBI, including complex attention and working memory, set shifting, management of distractions, and goal-based decision

STRENGTHENING GOAL-DIRECTED FUNCTIONING making. Digital scenario-based experiences were designed to be low-risk, progressively challenging opportunities for individuals to develop and hone stateregulation skills, with the goal that this practice would facilitate skill application to daily life situations and personal goals with increased effectiveness. We have successfully implemented this training in multiple settings in a series of pilot studies, including traditional face-to-face clinical encounters, in the classroom environment, and even via televideo. Participant feedback of this approach has been consistently positive, with participants endorsing the value of having digital training activities to intensively and repetitively practice skill use augmented by individualized guidance and feedback. Participants also have reported success with applying state-regulation skills to a variety of life situations and personal goal contexts. Preliminary objective evidence also supports the plausibility that this approach can improve goal-directed cognition. Overall, task-based approaches to cognitive training represent a promising intervention line worthy of increased patient-oriented research. They allow for a degree of intensity, repetition, and control that is difficult to achieve in traditional clinical settings, factors that may potentially facilitate the development of core neurocognitive skills and abilities. It will be valuable to consider how to capitalize on these unique characteristics of a task-based approach, while simultaneously incorporating other therapeutic elements, such as individualized coaching, necessary to best promote improved realworld functioning. In particular, it will be worthwhile to develop a better understanding of how task-based approaches can be rationally combined with other types of training and treatment (Whyte, 2006).

INTERACTIONS OF COGNITION AND EMOTION IN GOAL-DIRECTED FUNCTIONING Dysregulation in the control of cognitive–emotional functions can lead to variability in behavior, lability in mood, and inconsistency in almost any level of cognitive processing. As a classic example, some individuals with TBI display emotional lability, in one instant cooperative and friendly, in the next instant irritable and angry. The bidirectional relationship with impairments in cognitive and emotional control can form a vicious cycle that can be one of the greatest challenges to the clinician. Dysregulated emotions can worsen cognitive functioning and cognitive difficulties can likewise negatively influence emotional processing. These matters are even more complex and pronounced when TBI co-occurs alongside psychiatric conditions such as PTSD (see Vasterling et al., 2009) or depression (Alderfer et al., 2005).

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At the neural level, interactions of multiple networks of PFC are involved in the regulation of cognition and emotion (Silbersweig and Loscalzo, 2017). Networks connecting dorsolateral, ventrolateral, dorsomedial, orbitofrontal, and ventromedial frontal regions likely interact to monitor, coordinate, and modulate functions vital for goal pursuit (Stuss and Knight, 2002). In one example, PFC networks play a significant inhibitory role in modulating the limbic system, allowing higher-order cognitive functions to moderate less volitional limbicbased emotional responses. Because TBI may involve damage to any of the cortical or connector structures of prefrontal circuits, the dynamic interactions normally required to manage the ever-changing demands of goal pursuit can become dysregulated. For example, disruption of interactions between prefrontal networks may result in corresponding changes in cognitive processing and/or lack of awareness, and any of these can manifest as emotional dysregulation. Behaviorally, cognitive dysfunction can clearly lead to emotional dysregulation, which can, in turn, further diminish goal-directed functioning. As a prototypical example, cognitive difficulties can result in frustration, irritability, and even reactive depression. Issues with cognitive processing can also lead to misinterpreting or overreacting to environmental stimuli. Difficulties with regulating attention can hamper the ability to filter out information and demands that are not directly related to a current goal (additional “cognitive noise”) and this may lead to increased feelings of being overwhelmed. Indeed, given the known limitations of neural processing resources, it is logical that an increase in “load,” whether from cognitive or emotional sources, would lead to less efficient overall functioning. Ineffective regulation of emotions can likewise interfere with goal-directed functioning. It is common to observe the emotional states of patients exert a negative influence on goal pursuit efforts, often resulting in poor follow through and lack of persistence in the face of obstacles. Feelings of anxiety or depression can result in injured individuals being less able to effectively initiate tasks, solve problems, and follow through to complete tasks as well as apply therapeutic recommendations (e.g., applying skills), especially when faced with unexpected challenges. Moreover, individuals with TBI can be prone to overreact to challenge situations, resulting in a reduced ability to employ cognitive resources needed for effective goal attainment. States of hyperarousal, common with PTSD and anxiety, may lead to rapid shifts in attention to potential sources of perceived threat (Bardeen et al., 2017; Goodwin et al., 2017), and certain emotional states can also bias processing of information (Gotlib et al., 2004).

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Emotion dysregulation disorders can also, in and of themselves, result in diminished cognitive abilities. In a classic example, severe depression is well known as a cause of pseudodementia, with alterations of cognitive functioning as a hallmark manifestation. This likely involves frontal dysregulation with hallmarks of decreased initiation and decreased persistence in goal pursuit. Symptom clusters that transcend current diagnostic definitions are associated with neurocognitive and brain network functioning. For example, anxious arousal appears correlated with cognitive control and working memory (Grisanzio et al., 2018). Emotion dysregulation disorders are also common after TBI and frontal injury (Kim et al., 2007).

Considering PTSD in the context of TBI PTSD deserves special attention when considering cognitive–emotional dysregulation, although it is sometimes not considered in discussions of frontal pathology. Either TBI or PTSD alone may alter cognitive, emotional, and behavioral functioning. Interactions of emotion and cognition are particularly important to address with TBI–PTSD, with these comorbidities perhaps reflecting a combined combat neurotrauma syndrome (Chen and Novakovic-Agopian, 2012). Features of each may interact to worsen functioning and/or make treatment more difficult. There are likely multidirectional and very close interactions between TBI and PTSD, and the co-occurrence of these conditions is very common, especially for veterans of military combat (e.g., Lew et al., 2008). PTSD and TBI may interact at multiple levels, including at the genesis of injury, the maintenance of symptoms, various aspects of cognitive–emotional functioning, and at the level of neural mechanisms. Emotional and cognitive control are directly tied together in that the underlying neural systems interact significantly in achieving selfregulatory control necessary for goal-directed behavior. While medial PFC interacts with dorsolateral and dorsomedial structures in this regulatory process, dysregulation may result in loss of inhibitory control of the limbic system (Phelps et al., 2004). This example of the loss of top-down influence could play a role in maintaining and/or exacerbating emotional dysregulation, such as PTSD symptoms. A number of aspects of PTSD etiology and symptomatology involve frontal dysfunction. PTSD alone has been documented to affect frontally mediated cognitive functions involving sustained and selective attention, executive functions, and memory (Gilbertson et al., 2001; Brandes et al., 2002; Vasterling and Brewin, 2005), for example, causing impaired ability to gate, monitor, and regulate the flow of incoming information

and environmental stimuli (Vasterling et al., 1998). PTSD could be considered a syndrome of dysregulated frontal control of emotional memories with prefrontal– mesial temporal interactions important in the genesis and propagation of PTSD symptoms. Ventromedial PFC to mesio-temporal circuitry is vulnerable to injury with trauma. It is possible that lack of frontal regulation preceding or during traumatic experiences may contribute to the genesis of PTSD. Furthermore, frontal dysregulation may contribute to chronic and sustained PTSD symptoms, as the combination of cognitive processing, awareness, and self-regulatory mechanisms for managing symptoms can be compromised by frontal dysregulation. The addition of PTSD to TBI may contribute to both emotion and cognitive difficulties. Current experience suggests that PTSD in individuals who also sustain a TBI may be more complicated, and the chronicity of symptoms may be extended. Patients with TBI–PTSD may respond differently to standard treatments compared to those with only TBI or PTSD. Cognitive limitations may make it necessary to modify cognitive–behavioral psychotherapies. Conversely, the emotional dysregulation, avoidance, and potential for triggering may impede engagement in cognitive rehabilitation therapies. Severe emotional control dysfunction, including anxiety, hypervigilance, and avoidance, may become significant barriers to treatment of cognitive issues. On the other hand, cognitive deficits, especially those affecting aspects of attention, learning, and memory, may become barriers to effective treatment of emotional issues. In one study (Sayer et al., 2008), the US Department of Veterans Affairs (VA) rehabilitation providers reported that patients with TBI–PTSD required more repetition, attention, and time to complete assignments in PTSD-focused treatment.

Treatment considerations for cognitive– emotional dysregulation In order to improve goal-directed functioning among persons with TBI and related emotional dysfunction, it often is necessary to address both cognitive and emotional self-regulation in tandem. Treatment approaches may differentially address cognitive aspects of emotional processing, the effects of mood and emotion on aspects of cognition, or the interactions of cognition and emotion that interfere with goal-directed functioning. One approach may be to target aspects of cognition or emotion as the starting point, with the goal that improving one aspect of functioning will improve the other. In this scenario, elucidating “causal” connections between dysregulated cognitions and emotions can be elusive but highly informative. For example, determining that

STRENGTHENING GOAL-DIRECTED FUNCTIONING cognitive difficulties completing a task leads to frustration and negative self-efficacy beliefs (e.g., “I can’t do this”) provides insight into potential ways of intervening. Providing scaffolding and support and engineering mastery experiences in which individuals can demonstrate success may be helpful with bolstering selfefficacy. Consequently, these approaches may improve emotional functioning. Careful consideration of how to apply cognitive rehabilitation techniques to address aspects of one’s emotional experience, such as emphasizing the accomplishment of even minor goals, can be extremely beneficial. Rath et al. (2003) developed a serial approach to addressing issues of cognitive and emotional dysfunction. They created a two-stage intervention, which first emphasizes aspects of emotional self-regulation (e.g., teaching techniques to combat the intrusion of uncontrolled emotional responses into the thinking process) and then cognitive problem-solving procedures. The last few sessions of this protocol emphasize these two techniques together. Results of this approach have been promising, with participants reporting improvements in their abilities to solve problems and regulate emotions. An alternative approach may consider core intervention targets that are common to both TBI and emotional dysfunction. This orientation may be particularly relevant to the case of TBI and PTSD. As previously argued, one of the most fundamental and generalizable targets of training is the regulation of one’s brain state, as all cognition, emotion, and behavior occur within the context of an underlying brain state. The effectiveness and efficiency of goal-directed functioning depends on the regulation of these states as appropriate to any of the possible stages and challenges to goal pursuit. Accumulating evidence supports the relevance of brain states to goaldirected control functions (Arnsten and GoldmanRakic, 1998; Gold and Shadlen, 2001; Jazayeri, 2008; Papo, 2013). Valuable approaches have been developed to train state regulation skills in the context of cognitive and emotional challenges (Novakovic-Agopian et al., 2011, 2018; Cole et al., 2015; Azulay and Mott, 2016; Chen et al., 2017). One goal of these approaches is to maximize goal-directed control while reducing the load of nonrelevant cognitive or emotional processing on limited neurocognitive resources. One critical consideration in skill training is addressing gaps that may exist between learning of skills on the one hand and their successful application in challenge situations on the other. Many traditional approaches to training state regulation utilize quiet, nondistracting environments as their primary training context (e.g., meditation); however, situations marked by disruptions, competing demands, ambiguity, and other pressures are

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the contexts where skill use may be most needed. In order to maximize the usefulness of self-regulation skills in improving goal-directed functioning, it can be valuable to train the skills in a range of goal-pursuit situations that contain the cognitive challenges worsened by dysregulation. Indeed, we have found that training in state regulation applied in challenge contexts can improve performance on cognitive tasks requiring attention, working memory, and executive functioning (Chen et al., 2017; Novakovic-Agopian et al., 2018).

SLEEP AS A MAJOR MODULATOR OF PREFRONTAL FUNCTIONING Sleep and frontal functions Sleep has long been a mysterious function of the human brain, but it is becoming clear that sleep is essential for optimal cognitive functioning. The neurocognitive, behavioral, and physiological effects of poor sleep within the general population have been well documented (Durmer and Dinges, 2005; Walker and van der Helm, 2009). At the cognitive level, basic and clinical studies have documented that attention, working memory, and long-term memory are all modulated by sleep (Durmer and Dinges, 2005; McCoy and Strecker, 2011; Krause et al., 2017). At the neural level, mechanisms that underlie the importance of sleep for optimal frontal functioning may involve modulation of prefrontal cortical activation; connectivity between prefrontal cortical regions and other regions that underlie distributed cognitive processes, for example, hippocampal regions with associative memory tasks; and connectivity or coordination across the PFC subregions, as may be pertinent to coordinating medial, lateral, and orbitofrontal PFC functions subserving the integration of motivation, emotion and attention, and executive functioning (Verweij et al., 2014; Kaufmann et al., 2016; Krause et al., 2017). Thus poor sleep quality and/or disrupted sleep patterns may result from multiple influences and be associated with myriad negative consequences. Elucidating contributory factors and consequences is critical for effective intervention and also remains at the frontiers of clinical research.

Sleep and TBI Sleep disturbance is one of the most common sequelae of TBI, but treatment of sleep disturbances after TBI remains a sparsely studied frontier. Issues with sleep can be framed as both consequences of TBI and as factors that modulate functioning after TBI. Up to 84% of persons with a TBI experience some form of sleep disturbance (Lew et al., 2007), with symptoms of insomnia being the most frequent complaint (Castriotta and

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Murthy, 2011). Importantly, sleep disturbance may persist for years after mild to moderate TBI (Fichtenberg et al., 2000; Mahmood et al., 2004; Castriotta et al., 2007; Orff et al., 2009; Zeitzer et al., 2009; Kempf et al., 2010; Ponsford et al., 2013), underscoring the importance of addressing this potential chronic sequel of brain injury. Insomnia and other sleep disturbances are also exceedingly common for veterans and other individuals with TBI–PTSD. Thus, partial sleep deprivation becomes a chronic condition for many. At a minimum, disrupted sleep may undermine recovery after TBI, given its critical role in supporting cognitive functions vital for rehabilitation. Sleep deprivation may adversely affect functions crucial for learning, such as alertness, sustained attention (Bloomfield et al., 2009), and other forms of attention and memory, with particularly adverse effects on the overall functioning of frontal systems (Muzur et al., 2002; Mahmood et al., 2004; Yoo et al., 2007). Sleep-related disturbances may exert independent or additive effects on cognitive abilities following TBI (Struchen et al., 2008; Bloomfield et al., 2009) resulting in potentially poorer rehabilitation outcomes. For instance, Bloomfield et al. (2009) documented worse performance on tasks of sustained attention among individuals with TBI who reported poor vs good quality of sleep. Clinically, it is not uncommon for an injured individual’s level of engagement, ability to encode newly presented information and/or recall information discussed in prior therapies, and/or capacity to effectively tolerate stress to fluctuate following times of relatively intact vs impoverished sleep. Sleep disturbance may also be associated with increased psychiatric symptoms (Neckelmann et al., 2007), compounding cognitive– emotional difficulties more directly related to TBI and leading to worse rehabilitation outcomes.

Considerations for targeting sleep within context of TBI Despite a growing appreciation for the relevance of sleep to healthy functioning and rehabilitation broadly, relatively little intervention research has specifically targeted sleep disturbance within the context of TBI. The limited literature on sleep interventions presents a challenge to the clinician interested in helping TBI patients improve this critical function. As we have emphasized throughout this chapter, an important consideration is to determine the mechanism or point of intervention to target when intervening clinically. We briefly consider two separable aspects of sleep disturbance that should be considered clinically when deciding upon potential intervention pathways. We then discuss direct implications on interventions to improve goal-directed functioning within the context of sleep disturbance and TBI.

First, and often what is most distressing to patients, is disruption to characteristics of sleep itself, such as the quantity and/or quality of sleep obtained. Patients may complain of not getting enough sleep, having nights of fitful sleep defined by multiple awakenings and difficulty returning to sleep, or waking feeling tired despite an adequate amount of time spent in bed. Behaviorally, results of these types of disturbances often manifest in patients feeling fatigued and internal pressures to nap throughout the day, in addition to previously mentioned effects on cognitive abilities such as attention, memory, and speed of information processing. Research in noninjured populations suggests that impairments to frontal functions following brief sleep deprivation can be reversed following sleep recovery (Krause et al., 2017) and empirically validated approaches to treating sleep disturbances are available. Still, noteworthy questions remain. Perhaps most important is whether effects of chronic sleep deprivation in TBI populations are reversible. Closely related is also the question of whether sleep disturbance in the context of TBI and related conditions such as PTSD are as amenable to behavioral and/or pharmacologic therapies. More research in these areas is clearly needed. Sleep apnea is another type of sleep disorder that can negatively affect cognitive functioning, with some shared and distinct effects and mechanisms. Some of the cognitive effects are similar to sleep deprivation or fragmentation (Fulda and Schulz, 2003); however, sleep apnea is also associated with hypoxemia and cortical arousals (Zeitzer et al., 2009; Leng et al., 2017). One hypothesis is that hypoxemic neural damage contributes to deficits (Naëgel
e et al., 1995; Engleman et al., 2000), with some research documenting persistent neurophysiologic changes months after treatment with positive airway pressure (Rumbach et al., 1991; Sangal and Sangal, 1997). It is unclear to what extent changes related to sleep apnea are reversible and concern has been raised about the nonreversibility of changes to executive functioning (Durmer and Dinges, 2005). Sleep-disordered breathing also appears to be associated with the development of cognitive disorder in the long run, with aging (Rumbach et al., 1991; Leng et al., 2017). Properly identifying and addressing sleep apnea for individuals with TBI is an important point of intervention. A second point of importance is the effects of TBI on disruptions to sleep–wake cycles. The rhythm of sleep and wakefulness is in itself an important factor to address in order to optimize cognitive functioning. Attention, alertness, working memory, and related functions all have been shown to vary with schedule, including time of day and/or length of time awake (Krause et al., 2017). Optimizing cognitive functioning may thus include both regularizing a sleep schedule and considering the timing of cognitively demanding activities in

STRENGTHENING GOAL-DIRECTED FUNCTIONING the individual’s rhythm. Much of this work can be investigated experimentally to determine optimal sleep/ wake patterns and addressed through a combination of behavioral and psychopharmacologic interventions.

Approaches to improving goal-directed functioning through improving sleep Despite the importance of sleep for optimizing functioning and enhancing learning after TBI, no strong evidence base exists to guide clinical best practice (Orff et al., 2009; Weber et al., 2013). However, there are a number of clinically useful options available to address sleep deprivation, disruption, and rhythm. Factors that contribute to insomnia also need to be identified and addressed. Nonpharmacologic therapies aimed at addressing psychologic factors thought to perpetuate sleep disturbance have shown great potential. For many individuals, there may be opportunities for improving functioning by addressing basic aspects of sleep hygiene, for example, aspects of nighttime habits, caffeine use, and other basic considerations. Consequences of disorganization and irregularity in lifestyle can be counteracted with effective sleep hygiene counseling. For other individuals, more comprehensive treatment options may be required. One particularly promising treatment is cognitive behavioral therapy for insomnia (CBT-I), which incorporates both cognitive (e.g., addressing maladaptive sleep-related beliefs) and behavioral (e.g., stimulus control) approaches to combat insomnia (Murtagh and Greenwood, 1995; Ouellet and Morin, 2004; Morin et al., 2006; Ouellet and Morin, 2007). CBT-I has received good empiric support, although research on its application to TBI populations is still in its infancy. Clearly, sleep apnea should be identified and treated. Caution should be exercised regarding prescription of sleep-inducing medications such as benzodiazepines within this context, as they may actually exacerbate apnea. Treatment via a CPAP machine has been shown to be helpful for obstructive sleep apnea following TBI (Castriotta et al., 2009). Issues of treatment adherence within the context of TBI always need to figure prominently in considering interventions. Specific to the case of TBI is establishing a system to ensure individuals remember to use the CPAP in the first place. This may take the form of cues at bedtime, such as establishing consistent routines (e.g., have the CPAP machine at the bedside), setting automated reminders to use the machine, and enlisting the help of significant others and/or caretakers to ensure use. Many current models of CPAP machines have technology that enables use to be monitored remotely, thus helping clinicians to provide feedback and reinforcement on treatment adherence.

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One therapeutic goal with potentially far-reaching consequences is the establishment of a healthy sleep– wake rhythm, and it may be particularly advantageous to link cognitive demands to the individual’s rhythm. For example, certain tasks that demand a high level of working memory and task switching might be scheduled for peak wakefulness hours, while more automatic tasks, such as exercise workouts, might be scheduled at times when individuals are more prone to fatigue. Careful monitoring and recording of correlations in functioning and internal rhythms can facilitate these goals. There is also some suggestive evidence that treatments targeting the regulation of the circadian rhythm and sleep–wake cycle are helpful in the context of TBI-related sleep disturbance. Intensive schedule regularization in combination with efforts to augment sleep or wake signaling (e.g., melatonin supplementation at night, sunlight, exercise, possibly stimulants in the morning) may be valuable. Exogenous melatonin, taken in a regular timing prior to sleep, may be helpful in the “learning phase” of regularization of sleep timing (Kemp et al., 2004). From another perspective, sleep, including in the form of brief naps, has been shown to benefit learning of information or skills learned prior to sleeping (Walker et al., 2002; Mednick et al., 2003), even in the absence of REM sleep (Tucker et al., 2006). Thus promoting sleep as a prospective intervention (i.e., encouraging sleep after learning) may be a valuable component of rehabilitation, especially with increased need for sleep after injury. However, this will need to be balanced with a sleep restriction approach sometimes used with insomnia therapy to maximize nighttime sleep. If sleep deprivation is severe, impeding success in other aspects of treatment, then strategic, temporary increase in sleep may be aided with pharmacotherapy. Pharmacologic agents for inducing or prolonging sleep all have potential side effects, and balancing effects become more complex when cognitive dysfunction and other medications, among other factors, intermix. Benzodiazepines and atypical GABA-agonists, some of the most commonly used sleep agents, may have adverse effects on cognition as well as neuroplasticity following injury (Larson and Zollman, 2010) as well as rebound effects. Judicious short-term use can be beneficial in limited situations (e.g., when overwhelming anxiety contributes to insomnia), but rapid tolerance and dependence can make management difficult. Other agents, such as trazodone, or newer antidepressants such as mirtazapine, may have clinical utility, though there is little data to guide their use after TBI. Assistance with impediments to sleep, such as nightmares, can have a significant positive impact, and thus agents that modulate adrenergic systems, such as prazosin, can be helpful.

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Individuals with TBI may have increased sensitivity to adverse effects, such as prolonged cognitive effects the next day, so, in general, low doses or slow titrations may be important. In sum, sleep-supportive agents may play an important short-term role during rehabilitation. Use of such drugs would ideally be limited in time, matched with nonpharmacologic therapies with the goal of eventually improving sleep management and tapering off medications. Complementing efforts to address nighttime sleep/ daytime wakefulness may need to be supported. Light exposure and active physical exercise may be the most important interventions. Light therapy may also be helpful in regularizing daytime wakefulness (Ponsford et al., 2012). Additionally, energy management during the daytime may be valuable. Further, wakefulness may be supported by selective pharmacotherapy, although, again, it is ideal to consider this temporary and framed for strategic use only. The potential for stabilizing brain states with self-regulation and other techniques in the context of sleep dysregulation is an important area for further exploration. Management of sleep as a direct, explicit target of therapy is a vital primary consideration in TBI rehabilitation. Methods for improving sleep quantity and quality, as well as sleep–arousal rhythms, are an important frontier.

ENERGY AND CENTRAL FATIGUE Fatigue is reported to be one of the most common and debilitating symptoms after TBI (Olver et al., 1996; Hillier et al., 1997; Bushnik et al., 2008). Although fatigue can be a difficult-to-define symptom, it is worth mentioning some intersections with efforts to improve goal-directed functioning. Fatigue may represent not only the end result of any or all of the functions and modulators discussed in this chapter (e.g., poor sleep or cognitive difficulties), but fatigue itself may also influence the efficiency and effectiveness of goal-directed functioning (e.g., fatigue-related impairments in attention). Fundamentally, in line with the framework of this chapter, fatigue can be conceptualized as difficulty sustaining goal-directed efforts (Fellus and Elovic, 2007). Adequate energy is required to drive cognition and behavior, particularly for the effortful pursuit of higher-order goals and learning and rehabilitation. After injury, there is a general requirement for increased effort to maintain mental activities. For example, fatigue can arise from poor sleep, dysregulation of emotional reactions (anger, frustration), increased effort from distractibility or poor organization, or overexertion from lack of self-awareness.

In addition to general recommendations of determining potential contributing factors (sleep, medications, depression, pain), and the clinical best practice of supporting regular physical exercise (Fulcher and White, 1997; Mock et al., 2005; Englander et al., 2010; Ponsford et al., 2012), there may be additional insights gained from considering frontal functioning. Understanding the neural bases of fatigue may help inform treatments, and a general theory relates to increased recruitment of neural resources not required for uninjured persons. As a general pattern, PFC networks tend to be recruited in accomplishing tasks after TBI (Van Zomeren et al., 1984; McAllister et al., 1999; DeLuca et al., 2008). This may relate to the increased need for effort, energy, attentional scaffolding, or other aspects of compensatory adaptation given dysfunction in networks that would work more efficiently in health. Thus many of the approaches described in this chapter for improving goal-directed functioning may be of benefit in reducing fatigue and increasing effectiveness of goal pursuit given limited energy resources. For example, improved regulation of attention and other aspects of cognitive processing may help improve cognitive efficiency. Similarly, improving regulation of emotions, such as anger, may also be helpful in reducing nonrelevant emotional energy costs. Compensatory strategies to manage energy use, such as setting restrictions on the length of time to engage in certain activities, may also be helpful. Overall, helping an injured individual to manage available energy, including increasing available energy for select goals, would be of great benefit for optimizing current functioning and encouraging learning for longer-term improvements.

PHARMACOTHERAPY: PRINCIPLES OF INTEGRATED PHARMACOTHERAPY AND REHABILITATION Careful application of pharmacotherapy can play an important role in improving cognitive functioning after brain injury. Tailored pharmacotherapy should take into account factors optimizing functioning (Chen and Novakovic-Agopian, 2012; Chen and Loya, 2014), and we selectively emphasize here principles for synergizing with nonpharmacologic efforts to improve goal-directed functioning. It is valuable to consider not only the immediate effects of pharmacologic agents but also the potential influences on processes of learning. As a general principle, it is best to initiate pharmacotherapy in the context of a plan for nonpharmacologic treatment, and to have clear rationale for how the pharmacotherapy will support the long-term goals of treatment along with plans to eventually taper or more selectively use pharmacotherapy.

STRENGTHENING GOAL-DIRECTED FUNCTIONING Some guidance for prescriptions might come from definition of the treatment target (e.g., speed of processing vs memory), theoretical considerations (e.g., likelihood of cholinergic vs dopaminergic vs noradrenergic dysfunction), as well as management of other comorbidities (e.g., depression, fatigue, insomnia, anxiety, headaches). Clinical evidence to support particular medications post-TBI is slowly accumulating (reviewed in Warden et al., 2006; Jorge and Arciniegas, 2014; Bhatnagar et al., 2016). One of the more important aspirations is that the use of some agents may increase the rate of learning and recovery. Neuromodulator systems of the brain, such as dopamine, norepinephrine, acetylcholine, and serotonin, are primary targets. Dopaminergic and mixed catecholamine agents may be useful for improving specific aspects of goal-directed cognitive functioning in patients with TBI. Methylphenidate probably has the greatest amount of supportive evidence for use after TBI (Warden et al., 2006; Writer and Schillerstrom, 2009), with evidence of effects on aspects of attention and speed of information processing (Whyte et al., 2004). Dextroamphetamine may also help to improve aspects of attention and speed of processing, but there is little data fully testing its effects in chronic TBI (Hornstein et al., 1996). Bromocriptine may enhance aspects of executive functioning in patients with severe TBI (McDowell et al., 1998), but again data are mixed (Whyte et al., 2008). Amantadine may improve executive function, in addition to alertness (Sawyer et al., 2008). Atomoxetine has shown promise in other settings, but when tested in a relatively large randomized, controlled trial for TBI, no effects on testing and subjective measures of attention could be detected relative to a control group (Ripley et al., 2014). As a general guideline, dosing of agents that modulate catecholaminergic function should be based on individual response with step-wise dose adjustments, noting that neuromodulatory effects tend to follow a U-shaped curve that may vary in dose-relationship for each individual. Acetylcholine systems may be particularly important to address given the predilection for TBI to damage the basal forebrain and long tracts that connect structures important for memory processing (Arciniegas et al., 1999), with some evidence to support use of cholinesterase inhibitors such as donepezil (Whelan et al., 2000; Zhang et al., 2004; Warden et al., 2006; Wortzel and Arciniegas, 2012), as well as rivastigmine (Tenovuo, 2005; Silver et al., 2006). Mood stabilization may improve response to interventions, with increasing engagement and a reduction to the emotional derailment that can occur during goal pursuit. Selective serotonin and/or norepinephrine reuptake inhibitors may help reduce emotional lability and

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higher doses may improve attention and related adrenergic functions. Additional considerations of the interaction of TBI with anxiety and PTSD need to be considered. Psychostimulants may increase noradrenergic tone and therefore anxiety. On the other hand, individuals for whom distractibility and being overwhelmed by poor information processing may actually find that anxiety improves with such agents. In one study, modulation of cholinergic systems improved anxiety symptoms (McAllister et al., 2016). Helpful and hurtful effects of drugs must be considered together. These may occur simultaneously due to differential effects of a given drug on separate brain systems, for example, ventral tegmental vs substantia nigra dopamine systems (Cools et al., 2001). In another example, antidopaminergic medications may be helpful for reducing behavioral instability, but the same medication may slow down learning (Stanislav, 1997; Wilson et al., 2003; Meintzschel and Ziemann, 2006; Hoffman et al., 2008; Kline et al., 2008). On the other hand, limited strategic use at night may improve sleep and daytime functioning, especially for some individuals with nightmares and anxiety related to PTSD. Maximizing synergies between pharmacotherapy and training therapies is an important frontier. This approach could contribute to a long-term goal of improving an individual’s intrinsic functioning and allowing pharmacotherapy to be reduced over time.

CONCLUSIONS AND DIRECTIONS FOR FUTURE WORK Processes of goal direction are vital for any individual to traverse a chosen life path. The effects of TBI on goaldirected functioning are complex, and the complexity is compounded by combinations of physical and experiential injury, variability, and a number of potential modulators of functioning. However, a tremendous difference can be made via treatment approaches that are informed by a solid understanding of the multiple levels of functioning as well as multiple facets that can influence functioning. This work starts with a thorough assessment of function and can be aided by adapting a goal framework to intervention development. Much additional work needs to be done to better develop and define more effective therapies, particularly treatments that take a long-term view on the wide range of potential ways an individual’s life and functioning can be affected. Research, development, and innovation that bridges the neuroscience of neural–cognitive functioning with the practical realities of rehabilitation will be valuable in improving the lives of individuals after brain injury.

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FURTHER READING D’Esposito M, Chen AJW (2013). Remediating frontal lobe function: from bench to bedside, Principles of frontal lobe function, Oxford University Press, Oxford. Watson NF, Dikmen S, Machamer J et al. (2007). Hypersomnia following traumatic brain injury. J Clin Sleep Med 3: 363–368. Zafonte R, Lombard L, Elovic E (2004). Antispasticity medications: uses and limitations of enteral therapy. Am J Phys Med Rehabil 83: S50–S58.