Acquired Brain Injury in Adults: A Review of Pathophysiology, Recovery, and Rehabilitation

Abstract

Purpose:

To summarize existing literature from a range of fields (i.e., neurology, neuropsychology, neuroscience, neuroimaging, rehabilitation, speech-language pathology) that is relevant to the development and/or revision of cognitive rehabilitation programs for individuals with acquired brain injury (ABI) and in particular, for young adults.

Method:

This paper reviews a range of ABI-associated topics including: 1) mechanisms of injury; 2) biological, individual-specific, and behavioral drivers of recovery; and 3) current methods of cognitive rehabilitation. It then narrows focus to young adults, a frequently affected and growing population to sustain ABI. The paper concludes by providing: 1) suggestions for key components of cognitive rehabilitation for young adults with ABI; 2) an example from our own research providing intensive academically-focused cognitive rehabilitation for young adults with ABI pursuing college; and 3) recommendations for future behavioral and neuroimaging studies in this area.

Conclusions:

ABI is on the rise in the United States. Young adults have been sustaining ABI at higher rates over the past several decades. These injuries occur when they would otherwise be advancing their academic and career goals, making the cognitive deficits that often accompany ABI especially devastating for this group. Review of existing literature suggests cognitive rehabilitation programs that combine aspects of restorative, comprehensive, and contextualized approaches could promote recovery for young adults with ABI. Future intervention studies may benefit from including both behavioral and neural outcomes to best understand how principles of neuroplasticity— naturally embedded within many cognitive rehabilitation approaches—could be manipulated to promote cognitive recovery and long-lasting brain reorganization in this group.

Introduction

Acquired brain injury (ABI) often results in cognitive impairments that can drastically alter everyday functioning, independence, and overall quality of life. Its effect on young adults with ABI (i.e., 18–40; McLeod, 2018), a growing population to sustain brain damage (Benjamin et al., 2017; C. A. Taylor, 2017), is considerable given it occurs at a time of great development (Bonnie et al., 2015; The Society for Adolescent Health and Medicine, 2017). Fortunately, the damaged brain can adapt in response to biological, individual-specific, and behavioral factors to support cognitive recovery, and young adults with ABI are well-positioned for rehabilitation. They experience brain injury when they are attaining their academic goals and thus, improving cognitive skills for postsecondary education settings is especially important. Nonetheless, this group has been relatively understudied and underserved to date (McKinlay et al., 2008; Singhal et al., 2013) with few existing cognitive rehabilitation (CR) programs that address the unique needs of this population. This paper draws together extant literature from the field of brain injury rehabilitation to inform the development of interventions that explicitly promote the success of young adults with ABI who want to advance to college and beyond. Given the breadth of topics covered, the reader will find key terminology has either been defined inside parentheses throughout the text or within Table 1 (i.e., refer to this table for in-text italicized terms).

Table 1.

Definitions of key terms

Term	Definition
Angiogenesis	Creation of new blood vessels; neural plasticity/repair process
Axonal sprouting	New growth of axons
Biomarker	Biological indicator of an illness, condition, status; can be reflected via behavioral, blood, brain, and other physiological metrics
Default mode network	Set of brain regions that are engaged when the mind is at “rest” (e.g., not focusing attention, mind-wandering) and not engaged when the mind is “active” (e.g., focusing attention to a stimulus)
Dendritic spine production and arborization	Spines are protrusions from the dendrite that contain information about synapse strength. Arborization or dendritic branching refers to the process by which dendrites make new synaptic connections. These processes are associated with neural plasticity/repair (e.g., increase in spine density in area of lesion after stroke).
Diaschisis	When frank damage to brain region affects function to other areas of the brain that are distant from the damaged region
Diffusion tensor imaging	Neuroimaging tool for examining white matter tracts; relies on information regarding the diffusion of water in brain tissue
Free radicals	Unstable, cell-damaging molecules; associated with aging, neurological conditions, illness, etc.; antioxidants can prevent free radical damage by interfering with the process of taking electrons from other intact, stable molecules
Hemodynamic response	Change in blood flow in the brain (e.g., increase in oxygen-rich blood to language areas of the brain while speaking); often measured via neuroimaging modalities to understand the brain’s response to various stimuli
Hypometabolism	Abnormally low glucose consumption in a brain area; associated with loss of brain function, neurological condition, etc.
Hypoxic-ischemic injury	Combination of reduced oxygen and blood to the brain leading to brain damage and long-term impairment in physical, cognitive function, etc.
Microvascular injury	Damage to small blood vessels in the brain
Neurogenesis	Creation of new neurons; neural plasticity/repair process
Neuromodulation	Electrical stimulation of a brain area to either excite or inhibit synaptic activity (e.g., stimulate right hemisphere Broca’s area to improve language function in people with aphasia)
Reperfusion injury	Blood returned to an area of brain damage that can cause additional neuronal damage
Synaptogenesis	Creation of new connections in the brain through synaptic activity; neural plasticity/repair process
Edema, include cytotoxic and vasogenic	Edema: build-up of fluid in the brain increases brain volume Cytotoxic: Fluid build-up/swelling inside the cell due to sodium accumulation Vasogenic: Fluid build-up/swelling outside the cell in response to blood-brain barrier disruption

Acquired Brain Injury

ABI refers to any brain injury that occurs after birth that is not hereditary, congenital, degenerative, or related to birth trauma (What Is the Difference between an Acquired Brain Injury and a Traumatic Brain Injury?, 2018). Common causes for ABI include stroke, traumatic brain injury (TBI), tumor, infection, and hypoxic/anoxic injury.¹ Stroke and TBI are prevailing etiologies of ABI (Feigin et al., 2010) with approximately 795,000 individuals experiencing stroke (Benjamin et al., 2017) and nearly three million individuals sustaining a TBI in the US annually (C. A. Taylor, 2017). Further, the incidence of stroke (i.e., ages 20–44: 26 and 58/100,000 persons per year for whites and blacks, respectively; Kissela et al., 2012) and TBI (i.e., ages 15–24: 1,081/100,000; 25–34: 728/100,000; 35–44: 534/100,000 persons per year; C. A. Taylor, 2017) has been increasing in young adults (Benjamin et al., 2017; C. A. Taylor, 2017). Thus, stroke and TBI are the focus of the literature reviewed in this paper and the term ABI will be used to refer to concepts relevant to both conditions. Further, while the majority of TBIs are mild in nature (Cuthbert et al., 2015), the pathophysiology section addresses processes associated with moderate and severe TBI as it may lead to chronic disability (Colantonio et al., 2004) and a long-term need for CR, an area of emphasis in this paper.

Pathophysiology

The pathophysiology of ABI is complex and heterogeneous, varying by etiology as well as the extent and location of damage. In order to conceptualize the extensive biological impact of ABI on behavior, it is useful to understand whether the injury is focal or diffuse and primary or secondary in nature. Focal injuries are generally contained to a particular brain area, whereas diffuse injuries are typically widespread affecting many brain areas. Primary brain injury refers to the immediate damage to the neurovascular unit (i.e., interactions between neurons, glia, and vascular cells; Iadecola, 2017) as a result of the stroke or TBI (Arai et al., 2011; McKee & Daneshvar, 2015). Secondary brain injury pertains to 1) biochemical, cellular, and molecular processes triggered by the primary injury that evolve over time, leading to increased neuronal injury (Kochanek et al., 2013); and 2) medical conditions that arise in response to the primary injury (e.g., infection, seizures; McKee & Daneshvar, 2015). Similar secondary brain injury processes occur across ABI etiologies (Beez et al., 2017; Bramlett & Dietrich, 2004). Primary brain injury is often unalterable, while secondary brain injury may be treatable to some extent (Beez et al., 2017; McKee & Daneshvar, 2015).

Focal injury

Primary focal injury takes several forms: 1) blood flow through an artery is blocked by a clot traveling from another part of the body or generated within the artery itself (i.e., ischemic stroke); 2) blood leaks from a ruptured artery and compresses brain tissue (i.e., intracerebral and subarachnoid hemorrhage in stroke or TBI); and/or 3) there is direct trauma to brain structures (i.e., focal cortical contusion, epidural hematoma, focal vascular injury; Yokobori & Bullock, 2013) in TBI caused by falls, motor vehicle accidents, or penetrating injuries (e.g., gunshot, stabbing).

A multitude of secondary brain injury processes occur in response to the stroke, including excitotoxicity (i.e., excessive neuronal excitation), cytotoxic edema, and oxidative stress (i.e., antioxidant and free radical imbalance; Brouns & De Deyn, 2009). This initial set is followed by a cascade of inter-related processes: 1) post-ischemic inflammation (i.e., immune response to neuronal damage) disrupts the blood-brain barrier; 2) toxins pass into the brain, causing vasogenic edema; and 3) edema increases intracranial pressure, raising the potential for cerebral herniation (i.e., compression of the brainstem against the skull) and death (Brouns & De Deyn, 2009). Excluding reperfusion injury, analogous processes occur in hemorrhagic stroke with the inclusion of a cytotoxic response to blood in the brain tissue (Aronowski & Zhao, 2011). Comparable secondary injury processes lead to damage in focal TBI with the addition of 1) secondary hemorrhage; 2) microvascular injury; and 3) hypoxic-ischemic injury (Povlishock & Katz, 2005).

Impact of focal injury on behavior

Functional impairment in primary focal injury is relatively focused to the area of initial damage, although it can be expanded to surrounding tissue and structures via secondary brain injury processes as detailed above (e.g., mass effect or brain tissue/structure compression associated with space-occupying blood, cerebrospinal fluid, or edema in constrained skull space; (Rush, 2011). Further, disruption of structural and functional connections to the damaged area can also impact function in areas remote to the injury (i.e., diaschisis in stroke; Cramer, 2008, regional and distal hypometabolism in TBI; Povlishock & Katz, 2005).

Cognitive processes are supported by large-scale brain networks (e.g., default mode, attention, language) made up of cortical and subcortical brain areas, which communicate via structural (i.e., white matter tracts) and functional connections (i.e., synchronized activity; Petersen & Sporns, 2015). As these networks are distributed with overlapping brain regions, a single focal injury could impact multiple networks and their associated cognitive processes (McDonald et al., 2019). In fact, recent studies suggest the degree of white matter disruption (i.e., altered inter-hemispheric, intra-hemispheric and within-network connectivity) contributes to the behavioral impairments seen after stroke (Siegel et al., 2016). Similarly, recent applications of advanced neuroimaging techniques (e.g., diffusion tensor imaging) have revealed TBI as a disorder of network dysfunction and brain connectivity (Hayes et al., 2016; Sharp et al., 2014).

Cognitive deficits (i.e., impaired attention, memory, language, executive function, visuospatial skills, processing speed) are common after stroke (McDonald et al., 2019). The middle cerebral artery (MCA) supplies blood to the much of the frontal, temporal, and parietal lobes in addition to the basal ganglia and thalamus (i.e., subcortical structures) and is the most frequent location of stroke (Musuka et al., 2015). While clinical profiles vary due to a myriad of factors (e.g., extent of subcortical damage), MCA stroke in the left hemisphere commonly leads to deficits in language (i.e., aphasia; Kiran, 2012), while in the right hemisphere, it often leads to deficits in other cognitive domains (e.g., executive function, attention; Hier et al., 1983; Lehman Blake et al., 2013).²

Focal injuries in TBI generally occur in the anterior frontal and temporal lobes, leading to deficits in attention, executive function, memory, behavior regulation, and social functioning (McAllister, 2011). Medial structures like the anterior cingulate cortex (i.e., important for motivation and cognitive control) and medial temporal lobes (i.e., essential for learning and memory) can also be affected. Individuals with contusions or hemorrhage in the frontal or lateral temporal lobes may present with aphasia (Norman et al., 2013; Povlishock & Katz, 2005). These patterns vary according to the location and extent of the injury with larger, deeper, and/or bilateral injuries leading to more severe impairment.

Diffuse injury

Primary diffuse injury includes 1) axonal damage or death associated with rotational forces acting on the brain; and/or 2) cerebral microbleeds caused by ruptured small vessels (Povlishock & Katz, 2005). Secondary brain injury in diffuse injury is similar to that of focal injury with the exception that the damaging processes occur throughout the brain as opposed to a relatively focused area (Povlishock & Katz, 2005).

Diffuse axonal injury (DAI) is the most common injury type associated with TBI. In DAI, white matter tracts (i.e., bundled axons connecting different brain areas) are damaged as a result of acceleration and deceleration forces acting on the brain, and in turn, causing large-scale dysfunction in brain regions throughout multiple networks (Hayes et al., 2016; Sharp et al., 2014). The corpus callosum, fornix, internal capsule, superior longitudinal fasciculi, and inferior longitudinal fasciculi are some of the most commonly damaged white matter tracts due to their midline location, which makes them susceptible to rotational forces acting on the brain and subsequent axonal shearing (Hayes et al., 2016; Kraus et al., 2007). Cerebellar fibers and the brainstem may also be impacted due to head orientation in the skull at the time of injury and/or elevated intracranial pressure compressing these structures (Hayes et al., 2016).

Impact of diffuse injury on behavior

Individuals who have sustained diffuse injury often proceed through the following stages of domain-general cognitive impairment: 1) unconscious, 2) confused with difficulty generating new memories, and 3) cognitive deficits without confusion (e.g., executive function, attention, memory, processing speed; Povlishock & Katz, 2005). In terms of language performance, they may present with cognitive-communication impairment (Coelho et al., 1996; Togher et al., 2014), in that their verbal output is linguistically accurate, but impaired in its efficiency, topical relevance, organization, and pragmatic use (Coelho, 2013). It has been proposed that these impairments are driven by domain-general cognitive deficits in attention, memory, and executive function, although this notion has not been examined empirically. Finally, TBI is inherently heterogeneous; focal and diffuse injury can co-occur; and thus, clinical profiles are often complex (McKee & Daneshvar, 2015; Povlishock & Katz, 2005).

Drivers of Recovery in ABI

Neuroplasticity is a fundamental mechanism of recovery after ABI (Cramer, 2008; Dobkin, 2004; Robertson & Murre, 1999). It refers to the brain’s dynamic ability to adapt in response to experience via the propagation of synaptic connections between neurons (Bach-y-Rita, 1990; Kleim & Jones, 2008; Warraich & Kleim, 2010). It is driven by a combination of biological, individual-specific, and behavioral factors.

Biological

Neuroscientific research has uncovered a host of processes that occur throughout the brain in response to both focal and diffuse injuries (Chen et al., 2010; Cramer, 2008; McGinn & Povlishock, 2015). Animal models of brain injury have provided a foundation for understanding the biological processes involved in ABI and recovery. As discussed in the previous section, some of these processes are harmful (e.g., excitotoxicity) and lead to neuronal degeneration and death. However, these harmful processes decline within days to weeks post-injury. In contrast, protective processes and neuroplastic reorganization (i.e., neurotrophins, angiogenesis, neurogenesis, axonal sprouting, dendritic arborization, synaptogenesis, brain reorganization) increase as harmful processes fade out. While these protective processes happen at higher rates immediately post-injury, they continue at lower rates for months and years in response to behavioral drivers of recovery, such as rehabilitation. The fact that these processes persist well after the initial injury emphasizes the potential for recovery in the chronic phase of injury and the benefit of long-term rehabilitation in the ABI population (Chen et al., 2010).

Neurotrophins (i.e., proteins produced in the brain that support neural development, function, and plasticity via activation of complex signaling pathways; Huang & Reichardt, 2001) are found at increased levels after injury. They may encourage recovery after injury via lesion size reduction in stroke and blood-brain barrier stabilization in TBI (Font et al., 2010; Houlton et al., 2019). Research has demonstrated that neurogenesis is possible in the adult human brain (Alvarez-Buylla & García-Verdugo, 2002; Eriksson et al., 1998); however, more work is needed to understand the extent to which it occurs in areas of brain damage and functionally contributes to recovery (Jin et al., 2006; Kernie & Parent, 2010; Shen et al., 2008). Axonal sprouting and dendritic spine production proliferate to return reduced post-synaptic activity to pre-injury levels as demonstrated in animal models (Harris et al., 2010; Murphy & Corbett, 2009). It has been proposed that these new connections rapidly generated via synaptogenesis are then pruned to solidify learning via Hebbian processes — when adjacent neurons that are connected to one another via synapse are simultaneously activated and the synapse is strengthened (Robertson & Murre, 1999). Finally, the formation of new synaptic connections and strengthening of existing synaptic circuits is the basis of brain reorganization after ABI. See these reviews (Cramer, 2008; Hayes et al., 2016; McGinn & Povlishock, 2015) for a more detailed discussion of reorganization patterns seen in stroke and TBI.

Individual-specific

In addition to biological factors, demographic factors (Dikmen et al., 2009; Dillahunt-Aspillaga et al., 2017; Keyser-Marcus et al., 2002; Levin, 1995; Nunnari et al., 2014; Ponsford, 2013; Seagly et al., 2018), such as younger age, higher education level, and higher pre-morbid IQ/ability have all been associated with better outcomes after ABI. In alignment with the principle of “age matters,” (Kleim & Jones, 2008) neuroplasticity may be larger in magnitude and faster to occur in younger than older brains, underscoring that young adults are well-positioned to benefit from rehabilitation. Social support (e.g., family, friends, and/or companions) also supports recovery (Palmer, 2015). Finally, research investigating the role of motivation, resilience, and other intrinsic traits on ABI outcomes is emerging (Cattran et al., 2011; Watila & Balarabe, 2015).

Behavioral

A body of neuroscientific research emphasizing that behavioral experiences promote neuroplasticity has amassed over the last three decades (Cramer, 2008; Dobkin, 2004; Kiran & Thompson, 2019; Kleim & Jones, 2008; Turkstra et al., 2003). Motor, sensory, and cognitive impairments that accompany ABI make it challenging to perform activities in the same manner as pre-injury, and thus, new behavioral experiences are ubiquitous throughout all stages of ABI recovery. For example, following TBI, someone may struggle to concentrate when multiple people are talking in a group, a function they had no difficulty performing pre-injury that now may require repeated practice and exposure to improve post-injury. According to Kleim & Jones (2008) in their seminal review paper on neuroplasticity, learning occurs similarly in the damaged brain to what has been demonstrated in the healthy brain (e.g., through motor, sensory, cognitive experiences). They went on to identify ten principles of experience-dependent neuroplasticity, including repetition, intensity, and salience among others that can be used to inform rehabilitation for individuals with ABI with some caveats: 1) much of this work was conducted on animals with focal lesions in relation to motor recovery and needs to be confirmed with respect to cognitive impairment and diffuse injuries; 2) some principles overlap (e.g., repetition and intensity), are not well-defined or understood (e.g., salience, detailed in a later section), and 3) the amount of supporting evidence varies across principles.³ Cognitive rehabilitation (CR) is one behavioral experience that can influence recovery and reorganization after brain injury and improve functioning. Current CR approaches are inherently embedded with principles of neuroplasticity as will be highlighted in the next section.

Cognitive Rehabilitation (CR)

According to a well-accepted definition of CR put forth by Cicerone and his group,“Cognitive rehabilitation is defined as a systematic, functionally oriented service of therapeutic activities that is based on assessment and understanding of the patient’s brain-behavioral deficits (Cicerone et al., 2000, pp. 1596–1597).” CR takes a number of forms, largely derived from different theoretical perspectives on recovery mechanisms after ABI (Bayley et al., 2014; Cicerone, 2013; Hart, 2010; IOM (Institute of Medicine), 2011; Wilson, 2002; Ylvisaker et al., 2002). Given its heterogeneity, it can be useful to consider a CR approach from a multi-dimensional perspective, such as 1) its focus on restoration and/or compensation, 2) the breadth and concurrence of domains targeted (e.g., single, multiple), and 3) the degree of contextualization (e.g., occurs in clinic, occurs in real-life setting). Notably, these dimensions are not mutually exclusive, in that there may overlap within an approach. Further, as laid out in the next sections, identifying how these dimensions of CR align with principles of experience-dependent neuroplasticity may support the development of future interventions that promote long-term brain-behavior change.

Restorative/Compensatory CR

The first three principles of experience-dependent neuroplasticity put forth by Kleim & Jones (2008) include: 1) “use it or lose it” (i.e., specific brain functions must be engaged to avoid loss of function); 2) “use it and improve it” (i.e., function can be improved by engaging specific brain functions); and 3) “specificity” (i.e., functions explicitly targeted in training improve). Restorative approaches most closely align with these three principles as they focus on “reinforcing, strengthening, or reestablishing previously learned patterns of behavior.” In contrast, compensatory approaches diverge from these principles as they concentrate on “establishing new patterns of cognitive activity through compensatory cognitive mechanisms for impaired neurologic systems (Cicerone et al., 2000, p. 1597).” Although in accordance with the principle of “specificity,” restorative approaches (e.g., repetitive attention drills via Attention Process Training; APT; Sohlberg et al., 2000) have been criticized for targeting cognitive domains in the absence of a functional task (i.e., decontextualized), which is the standard in compensatory approaches (e.g., metacognitive strategy training to improve attention within a real-world activity; Kennedy, Coelho, et al., 2008).

Yet, this ostensible advantage of compensatory approaches over restorative approaches may be outweighed (Hart, 2010) by research investigating learned non-use after stroke (e.g., using unaffected limb only; Taub et al., 2006) that suggests compensation can impede recovery in some contexts. These findings underscore the principle of “interference” (i.e., formation of neural connections in one area can interfere with brain reorganization in another area and negatively affect behavioral performance; Kleim & Jones, 2008). Constraint-induced therapy approaches promote the use of the affected limb/modality in alignment with the first three principles of neuroplasticity detailed previously and have been shown to support motor recovery after stroke (Kwakkel et al., 2015). These approaches also employ massed practice in agreement with the principle “repetition matters” (i.e., skills should be sufficiently repeated to be acquired; Kleim & Jones, 2008); follow intense training schedules in concurrence with the principle “intensity matters” (i.e., the frequency or magnitude of stimulation should be adjusted for sufficient skill training intensity; Kleim & Jones, 2008); and target skills within a meaningful activity in accordance with the principle “salience” (i.e., a stimulus must be sufficiently interesting for it to be encoded into memory or learned; Kleim & Jones, 2008). Relevant to this paper, there is relatively strong evidence that intensive language action therapy (Difrancesco et al., 2012) or constraint-induced aphasia therapy promotes language recovery for aphasia (Wang et al., 2020; Zhang et al., 2017). Constraint-induced approaches also pertain to the recovery of domain-general cognition. Yet, to date, only one research group has applied this restorative approach to the memory domain for individuals with ABI (Lillie & Mateer, 2006) by forcing participants to rely on the affected process (i.e., conscious recall) and suppress the unaffected process (i.e., automatic recall). Task-related gains in memory (i.e., successful recognition of studied words) were seen after intense training with massed practice (i.e., four 15-minute sessions/day for seven consecutive days), providing preliminary evidence for the application of constraint-induced therapy to domain-general cognitive deficits in ABI.

Single modality/Multi-modality CR

CR approaches may also focus on an impaired domain in isolation (i.e., modular treatment, such as memory or language therapy via restorative or compensatory means) or multiple impaired domains simultaneously (i.e., multiple modular treatments, such as comprehensive, holistic CR programs; Cicerone et al., 2019; Institute of Medicine (IOM), 2011). Focusing on a single domain naturally provides many opportunities to rehearse the target behavior, in line with the principle of “repetition matters” (Kleim & Jones, 2008). Further, narrowing the focus of therapy to a single domain aligns with the principle of “salience” in that training tasks are tailored to elicit the target skill/behavior. On the other hand, targeting multiple domains inherently may require training tasks to be broad (i.e., less “specific”), and thus, this approach may be more likely to elicit generic, unskilled behaviors that do not drive specific patterns of brain reorganization (Kleim & Jones, 2008).

According to the most recent systematic review of the literature conducted by Cicerone and his group, adequate evidence (i.e., at least one well-designed randomized controlled trial with support from studies with lower levels of evidence) was available to develop practice standards for using modular treatment approaches to target cognitive impairment after ABI (Cicerone et al., 2019). Practice standards were developed for treating: 1) attention after stroke or TBI via restorative (i.e., drill-based attention training) and compensatory (i.e., metacognitive strategy training) approaches; 2) memory (e.g., use of internal or external strategies to support prospective memory for individuals with mild memory impairment after stroke or TBI); 3) language (e.g., aphasia therapy after left-hemisphere stroke) and social communication (e.g., pragmatic conversation skills after TBI); 4) executive function (i.e., metacognitive strategy instruction after TBI to improve emotional self-regulation and support problem solving in everyday contexts); and 5) visuospatial deficits (i.e., visual scanning training for neglect after right hemisphere stroke).

Cicerone’s systematic review also extended a practice standard for treating multiple impaired domains simultaneously in individuals with ABI across all severities and recovery phases via comprehensive-holistic neuropsychological rehabilitation (Cicerone et al., 2019). These programs consider the multi-dimensional nature of ABI and thus, aim to 1) improve cognitive function through more effective use of spared cognition (i.e., compensatory); 2) provide clinic-based intervention in individual and group contexts; and 3) address social-emotional functioning and self-awareness. Day treatment programs are the most prevalent service delivery model (Cicerone et al., 2004, 2008; Malec et al., 1993; Shany-Ur et al., 2020). Comprehensive programs most closely align with the “intensity matters” and “salience matters” principles (Kleim & Jones, 2008) as treatment often takes place on a daily basis for several hours/day and involves individually-tailored intervention and functional activities, including work and academic readiness experiences (Cicerone et al., 2004). In terms of outcomes, some comprehensive CR programs have reported gains in functional outcomes, such as productivity (i.e., return to work/school) and independence; (Cicerone et al., 2019). However, as the percentage of participants enrolled in school post-program has generally been small in number or it has not been reported separately from those who transitioned to employment post-program, it is challenging to understand the benefit of this approach on academic goal attainment, a point which will be revisited in a later section (Cicerone et al., 2004, 2008; High et al., 2006; Klonoff et al., 1998; Malec et al., 1992).

Contextualized CR

Ylvisaker and colleagues took the multi-modal, comprehensive CR approach one step further, expanding the focus on the therapeutic context (Ylvisaker et al., 2002). Contextualized CR programs are distinct from comprehensive programs in their emphasis that all aspects of therapy occur within the real-world context (i.e., train to enter appointment in cell phone calendar at the doctor’s office via contextualized CR approach versus train the behavior in the speech therapy office before transferring to the doctor’s office via comprehensive CR approach). Contextualized CR approaches strive to support individuals to meet real-world goals and participate in real-world activities (Ylvisaker et al., 2002). They operate under five tenets: 1) cognitive training should follow task-specific hierarchies and stages of normal cognitive development (e.g., concrete thinking precedes abstract thinking, context-dependent skills are followed by context-independent skills); 2) it should occur in personally-meaningful settings (i.e. home, community) with personally-relevant content in alignment with the principle of “salience” (Kleim & Jones, 2008), and expand to other functional tasks and contexts with acquisition in agreement with the principle of “transference” (Kleim & Jones, 2008); 3) participation should increase by providing environmental supports (i.e., education and training of people in their everyday life to increase engagement); 4) activity limitation should decrease with compensatory strategies and equipment (e.g., use written notes taken while reading the night before to participate in the next day’s class discussion); and 5) cognitive function may improve via strategies and behaviors acquired via contextualized training that have since been internalized. While much of the empirical evidence for this approach has been derived from studies of the pediatric brain injury population (Braga et al., 2005; Feeney & Ylvisaker, 2006, 2008), it also has applicability to adults with ABI. A recent study investigating the effect of contextualized treatment compared to decontextualized treatment for individuals with TBI found that increasing the amount of time spent in contextualized treatment activities was associated with increased performance on measures of community participation upon discharge (Bogner et al., 2019). Although there has been longstanding enthusiasm for this approach within the field of CR (O’Brien & Krause, 2014; Ylvisaker, 2003), its broad application would necessitate modifications to existing brain injury service delivery models, and thus, requires the support of more efficacy studies in this area.

Summary and proposal for an integrated CR approach

If the goal of rehabilitation is to support an individual’s participation in everyday life, and impaired cognition as a result of ABI is impeding an individual’s participation, then, cognition is the most logical target for rehabilitation. Yet, a range of CR approaches exist, each with their own strengths and weaknesses. A reasonable path forward then may be to develop a revised integrated approach to CR that combines individual approaches— naturally embedded with principles of experience-dependent neuroplasticity (Kleim & Jones, 2008)— to maximize recovery after ABI.

For instance, restorative approaches work to strengthen impaired cognitive processes via specific training and thus, have the benefit of aligning with the principles of “use it or lose it,” “use it and improve it,” and “specificity.” Yet, they are often decontextualized and criticized for limited generalization, and thus, lacking in the principles of “salience” and “transference.” To account for this weakness, an integrated approach could augment a restorative approach with aspects of the contextualized CR approach, such as targeting cognition in personally-meaningful settings (i.e., salience) and expanding to other functional tasks with mastery (i.e., transference). In order to fulfill the goal of sufficient repetition and intensity to instantiate the trained behaviors, aspects of comprehensive rehabilitation could also be included (e.g., daily individual and group treatment sessions that are several hours in length to allow many opportunities for rehearsal). Further, components of CR approaches that strictly rely on spared processes and/or solely train strategy usage may be avoided to minimize learned non-use or the induction of the principle of “interference.” Taken together, an integrated approach to CR, as shown in Figure 1, that 1) targets impaired processes; 2) minimizes reliance on spared processes; 3) provides many opportunities for rehearsal; 4) occurs in a variety of contexts; and 5) encourages transfer of learning should lead to behavior change and brain reorganization, although that remains to be tested in future studies.

Figure 1.

A revised integrated approach to CR. Caption: This figure illustrates a revised integrated CR approach. It recommends five key objectives for an integrated CR approach (first column), details what current CR approach (second column) and principle of experience-dependent neuroplasticity (third column) aligns with each recommendation, and provides examples of how these have been implemented within the Intensive Cognitive and Communication Rehabilitation program at Boston University (ICCR; fourth column).

Significance for young adults with ABI

Sustaining an ABI at a young age is particularly disadvantageous as it disrupts major developmental milestones (Bonnie et al., 2015; The Society for Adolescent Health and Medicine, 2017), including participation in education and work with potentially devastating effects on economic independence (Kayani et al., 2009; Singhal et al., 2013). Many individuals with TBI live with their families after injury and do not work or attend school (Jacobs, 1988; Sigurdardottir et al., 2018). The overall cost of TBI to individuals, their families, and society is substantial given the expense of ongoing medical care, rehabilitation, residential needs, and lost earnings (Kayani et al., 2009). The situation is similarly dire for individuals with stroke. Younger stroke survivors suffer greater financial burden than older stroke survivors with the greatest weight on young men in their mid-twenties (Kang et al., 2011; T. N. Taylor et al., 1996). Post-stroke aphasia further increases the cost of injury (i.e., longer length of stay, need for supportive care upon discharge; Ellis et al. 2012), as this population returns to work less often than those without aphasia (Graham et al., 2011).

In order to return to work post-injury, one must have first secured a job, which may be unlikely for many young adults who sustain ABI. College has become a common intermediary step to a future career in the US. Therefore, at the time of their injury, many of these individuals were furthering their education before entering the workforce. Research suggests that attention, memory, language, and executive function skills contribute to academic success (Cohen, 2012; Dunlosky & Rawson, 2012; Hassanbeigi et al., 2011; Krumrei-Mancuso et al., 2013; Taraban et al., 2000). Given that these cognitive domains are frequently impaired after brain injury, young adults with ABI often struggle to enroll and/or succeed in college as reported by the studies detailed in Table 2 (Cahill et al., 2014; Kennedy, Krause, et al., 2008; Mattuzzi & Pfenninger, 2018; Mealings et al., 2012; Todis & Glang, 2008). These studies investigating the college experiences of young adults with ABI demonstrate that 1) cognitive deficits associated with ABI make return to academics challenging; and 2) young adults could benefit from CR that addresses cognitive skills important for the academic context.

Table 2.

Studies investigating the college experience of young adults with ABI

Study	Study Design	N	Population	Major Findings
Todis & Glang (2008)	Longitudinal–qualitative interview approach	33	TBI	55% of students in training program or college after HS ~25% used disability services Due to fear of stigma or not seeing the need
Kennedy, O’Krause, & Turkstra (2008)	Cross-sectional–survey approach	35	TBI	80% of students challenged by schoolwork > 50% endorsed deficits in attention, executive function, & memory
Cahill et al. (2014)	Qualitative–interview approach	8	TBI	Endorsed balancing college demands with TBI-related deficits Refused disability services due to fear of stigma
Mealings et al. (2012)	Narrative review	107 across 8 studies	TBI	Endorsed difficulty with cognitive, emotional, physical, & psychosocial functioning Reported TBI-related deficits impacted academic participation
Mattuzzi & Pfenninger (2018)	Mixed methods–survey approach	35	Stroke	94% of students found language-related class activities “stressful” Reported anxiety related to attention, executive function, & memory deficits impacting academic performance

Note: HS = high-school, TBI = traumatic brain injury

Nevertheless, from our perspective, currently available CR approaches reviewed in the Drivers of Recovery: Behavioral section may not be sufficiently specific, repetitive, intensive, salient, and/or appropriately situated within an academic context to support young adults toward this goal. An integrated CR approach that targets cognitive domains important for academic success (i.e., attention, memory, executive function, language) as proposed in the previous section and depicted in Figure 1 may be ideal for a young adult with ABI working toward college.

One example of an integrated CR approach is Boston University’s Intensive Cognitive and Communication Rehabilitation (ICCR) program. It was developed for young adults with cognitive deficits after ABI who wish to pursue college (Gilmore et al., 2019). They attend the program six hours/day, four days/week for 12-week sessions. In a typical day, they attend classroom-style lectures; review lecture material; answer practice quiz questions; learn and apply metacognitive strategies; participate in technology-based training; and receive individual CR.⁴ An initial efficacy study demonstrated that ICCR participants significantly improved on standardized neuropsychological assessments, classroom performance, individual therapy, and at least one aspect of life participation and quality of life (Gilmore et al., 2019). Current work is focused on 1) identifying what cognitive domains important for academic success improve as a function of the ICCR program; and 2) how the brain may reorganize to support gains in cognition using functional near-infrared spectroscopy (Boas et al., 2014).

Support for this latter aim was derived from the fact that while neuroimaging studies have uncovered how the brain reorganizes in response to behavioral intervention for many clinical conditions, less work has been conducted in this area for ABI and for TBI in particular (Galetto & Sacco, 2017; Hartwigsen & Saur, 2019; Kiran & Thompson, 2019). Longitudinal neuroimaging studies that measure the effects of CR approaches could inform models of cognitive rehabilitation-induced recovery in a number of ways. For example, they could elucidate hemodynamic biomarkers of recovery (e.g., unique pre-treatment brain activation patterns for individuals who improved after therapy versus those who did not). They could also help identify sites for neuromodulation (e.g., electrical stimulation to promote synaptic activity in brain areas where change in activation has been positively correlated with treatment gains). Relevant to the proposed integrated CR approach, future neuroimaging studies in which a principle of neuroplasticity (Kleim & Jones, 2008) is isolated, incorporated into an intervention approach, administered to a group of individuals, and measured against a control will be important to test how these principles influence behavior change and brain reorganization. This type of work demands a systematic, incremental approach to research and will be challenging as it requires well-supported models of how neurotypicals perform a particular cognitive process and its neural substrates; operational definitions of the principles (and cognitive domains being targeted); robust experimental design for both the behavioral and neuroimaging aspects of the study; and application to different cognitive impairment profiles and brain injury types.

Conclusions

ABI often leads to cognitive deficits that can be detrimental for young adults who want to attend college and/or start their careers. Research has uncovered drivers of recovery after ABI that can inform the development of rehabilitation programs for this population. CR programs that integrate aspects of restorative, comprehensive, and contextualized approaches and align with principles of experience-dependent neuroplasticity to target cognition within everyday contexts could optimize outcomes for this unique group. However, future research is needed to understand how these principles can be methodically employed within rehabilitation paradigms and if they indeed promote long-lasting cognitive recovery and brain reorganization after ABI.