1

Introduction

In order to illustrate the multidimensional aspect of behavioral changes following traumatic brain injury (TBI), this literature review focused on the manifestations of apathy, impulsivity and anosognosia, which constitute the most common behavioral changes associated with a TBI. This article presents a brief descriptive introduction of each problematic behavior followed by a synthesis of the most recent studies that have investigated the nature of these behaviors. Regarding the methodology for articles search, authors focused on these three main behavioral changes, which represented the most published studies reporting the psychological processes involved. Then, in PubMed, authors selected the original articles in order to illustrate the first studies and original definitions, followed by a selection of the most recent and significant articles describing the multidimensional nature of these manifestations.

Changes in behaviors and emotional attitudes are common symptoms often described in persons with TBI, regardless of its severity. These manifestations can be quite diverse such as irritability, apathy, impulsivity or intolerance to change, and they often represent the biggest barrier to rehabilitation in the acute phase as well as to socioprofessional reintegration on the long term. . Furthermore, these problematic behaviors are most often associated to manifestations of anosognosia, which makes care management as well as social, professional and familial reintegration even more difficult. Moreover, these changes have been related to negative consequences on the quality of life of patients but also of their closed ones. Indeed, behavioral and emotional changes exhibited by patients are better predictors of the subjective caregiver burden than injury severity or cognitive impairments .

Recently, Ciurli et al. sought to characterize neurobehavioral changes among a group of 120 individuals with severe TBI. Using the Neuropsychiatric Inventory , the authors found that family caregivers reported a wide range of neuropsychiatric symptoms such as: apathy (42%), irritability (37%), dysphoria/depression (29%), disinhibition (28%), eating disorders (27%), agitation/aggressiveness (24%), sleep disorders (15%), delusions (14%), euphoria and mania (13%), aberrant motor behaviors (9%), hallucinations (8%), and anxiety (8%). These data highlight the important proportion of problematic behaviors post-TBI, as well as the diversity of these manifestations. In clinical practice, these manifestations are most often related to executive function impairments due to brain damage, but increasingly data from the literature report that these manifestations are underpinned by a variety of mechanisms related in part to the brain damage (i.e. cognitive, psychoaffective impairments) but also to the patient’s personality traits and its environment. A precise identification and consideration of these multiple mechanisms are much needed to promote adapted and effective care management for these patients.

The objective of this article was to illustrate the multidimensional aspect of these behavioral changes through two types of manifestations: apathy and impulsivity. Furthermore, anosognosia, which is often associated to these problematic behaviors in patients with TBI, can be expressed in different ways, suggesting here also the involvement of multiple processes.

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Manifestations of apathy

Apathetic manifestations are commonly described after TBI and have been associated with major negative consequences, especially regarding patients’ participation in rehabilitation , family life and later social reintegration . The complaint from patients or family members is often “a lack of initiative, some passivity, disinterest towards oneself and others, lack of spontaneous conversation or even emotional blunting”. Conceptually, there is some agreement within the literature that apathy refers to a set of behavioral, cognitive and emotional features. More precisely, disorders of interest, action initiation and emotional reactivity are all dimensions of apathy and diminished goal-directed behavior is at the core of the disorder . However, current conceptions of apathy are based on descriptive and categorical approaches, without taking into account the several processes involved in each apathy manifestation as well as the interactions between these manifestations . Thus, according to the definition proposed by Mulin et al. , a diagnosis of apathy can be made in the presence of diminished motivation in comparison to the patient’s previous level of functioning, and at least two of the three following domains of apathy, which must be present for at least 4 weeks:

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  diminished goal-directed behavior;

  
  
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  diminished goal-directed cognitive activity;

  
  
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  diminished emotions.

However, different studies have underlined significant relationships between the different dimensions of apathy, and specifically between lack of goal-directed behaviors (i.e. lack of initiative) and lack of goal-directed cognitive activity (i.e. lack of interest) . These data are not surprising since a lack of interest is closely related to a lack of initiative and on the other hand, a lack of initiated actions may gradually lead to a lack of interest. More specifically, a recent study conducted in 68 patients with TBI showed the heterogeneity of apathetic manifestations, by using the caregiver version of the Apathy Inventory . Cluster analyses precisely identified four subgroups of patients: a group with high scores on all apathy dimensions, a group with low scores on all dimensions, a group with major emotional blunting and a group with high scores on lack of initiative and lack of interest. These data clearly indicate that apathy is not an accumulation of isolated symptoms but rather a dynamic concept with various associations and dissociations between the symptoms.

Furthermore, recent studies have shown the implication of different psychological mechanisms in the various facets of apathy. Thus, in elderly subjects, lack of initiative has been associated with difficulties in the ability to run multiple tasks simultaneously (“multitasking”) , difficulties in prospective memory and also low self-efficacy beliefs . To be more precise, Esposito et al. showed that the number of rules breaks on the modified Six Elements Test was a significant predictor of lack of initiative in persons with a diagnosis of Alzheimer’s disease. In addition, the multitude of mechanisms involved in apathetic manifestations is supported by the diversity of brain structures related to apathy in persons with TBI. A literature review reported the implication of a number of cortical and subcortical brain structures in the occurrence of apathetic behaviors such as the ventromedial prefrontal cortex, the lateral prefrontal cortex, basal ganglia, anterior cingulate cortex, insula and amygdala . Based on all these data, a multidimensional and integrative concept of apathy was recently proposed, taking into account on the one hand the diverse mechanisms involved in the various dimensions of apathy, including cognitive factors (e.g. executive functions), motivational factors (e.g. effort mobilization), emotional factors (e.g. negative mood), aspects related to the personal identity (e.g. self-esteem) and on the other hand, the direct relations (at a symptomatic level) between the different manifestations of apathy .

2

Manifestations of apathy

Apathetic manifestations are commonly described after TBI and have been associated with major negative consequences, especially regarding patients’ participation in rehabilitation , family life and later social reintegration . The complaint from patients or family members is often “a lack of initiative, some passivity, disinterest towards oneself and others, lack of spontaneous conversation or even emotional blunting”. Conceptually, there is some agreement within the literature that apathy refers to a set of behavioral, cognitive and emotional features. More precisely, disorders of interest, action initiation and emotional reactivity are all dimensions of apathy and diminished goal-directed behavior is at the core of the disorder . However, current conceptions of apathy are based on descriptive and categorical approaches, without taking into account the several processes involved in each apathy manifestation as well as the interactions between these manifestations . Thus, according to the definition proposed by Mulin et al. , a diagnosis of apathy can be made in the presence of diminished motivation in comparison to the patient’s previous level of functioning, and at least two of the three following domains of apathy, which must be present for at least 4 weeks:

• •
  

  diminished goal-directed behavior;

  
  
• •
  

  diminished goal-directed cognitive activity;

  
  
• •
  

  diminished emotions.

However, different studies have underlined significant relationships between the different dimensions of apathy, and specifically between lack of goal-directed behaviors (i.e. lack of initiative) and lack of goal-directed cognitive activity (i.e. lack of interest) . These data are not surprising since a lack of interest is closely related to a lack of initiative and on the other hand, a lack of initiated actions may gradually lead to a lack of interest. More specifically, a recent study conducted in 68 patients with TBI showed the heterogeneity of apathetic manifestations, by using the caregiver version of the Apathy Inventory . Cluster analyses precisely identified four subgroups of patients: a group with high scores on all apathy dimensions, a group with low scores on all dimensions, a group with major emotional blunting and a group with high scores on lack of initiative and lack of interest. These data clearly indicate that apathy is not an accumulation of isolated symptoms but rather a dynamic concept with various associations and dissociations between the symptoms.

Furthermore, recent studies have shown the implication of different psychological mechanisms in the various facets of apathy. Thus, in elderly subjects, lack of initiative has been associated with difficulties in the ability to run multiple tasks simultaneously (“multitasking”) , difficulties in prospective memory and also low self-efficacy beliefs . To be more precise, Esposito et al. showed that the number of rules breaks on the modified Six Elements Test was a significant predictor of lack of initiative in persons with a diagnosis of Alzheimer’s disease. In addition, the multitude of mechanisms involved in apathetic manifestations is supported by the diversity of brain structures related to apathy in persons with TBI. A literature review reported the implication of a number of cortical and subcortical brain structures in the occurrence of apathetic behaviors such as the ventromedial prefrontal cortex, the lateral prefrontal cortex, basal ganglia, anterior cingulate cortex, insula and amygdala . Based on all these data, a multidimensional and integrative concept of apathy was recently proposed, taking into account on the one hand the diverse mechanisms involved in the various dimensions of apathy, including cognitive factors (e.g. executive functions), motivational factors (e.g. effort mobilization), emotional factors (e.g. negative mood), aspects related to the personal identity (e.g. self-esteem) and on the other hand, the direct relations (at a symptomatic level) between the different manifestations of apathy .

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Manifestations of impulsivity

Impulsivity, generally defined as the tendency to express spontaneous and excessive behaviors, has been commonly described in persons with TBI . One of the significant conceptual advances should be attributed to the work of Whiteside and Lynam . On the basis of a factorial analysis performed on the data of 400 students who were administered several impulsivity assessments tools, they identified four dimensions of impulsivity: urgency (the tendency to experience strong reactions, frequently under conditions of negative affects), the lack of premeditation (the difficulty to think and reflect on the consequences of an act before engaging in that act), lack of perseverance (the difficulty to remain focused on a task that may be boring or difficult) and sensation seeking (the tendency to enjoy and pursue activities that are exciting and openness to trying new experiences). This multidimensional model of impulsivity has recently been confirmed in a sample of patients with TBI with a short form of the UPPS Impulsive Behaviour Scale, which was specifically designed by Rochat et al. to assess impulsivity changes after TBI. This scale includes 16 items (4 items per dimension) with a pre- and post-TBI evaluation for each item in order to evaluate impulsivity changes since the head injury. Results from validation studies have shown that the dimensions “urgency”, “lack of premeditation” and “lack of perseverance” increased significantly after TBI, whereas the dimension “sensation-seeking” decreased significantly according to the patients’ significant others.

In terms of psychological processes, sensation-seeking has been associated with motivational processes, whereas the other three impulsivity dimensions (urgency, lack of premeditation, lack of perseverance) were more related to self-control processes . Thus, Rochat et al. showed that the urgency dimension was significantly associated with dominant response inhibition difficulties in patients with TBI. The more patients had dominant response inhibition difficulties, the more they exhibited the urgency facet of impulsivity. Lack of perseverance was specifically associated with difficulties in mental flexibility and sustained attention in elderly subjects as well as difficulties in resisting proactive interference in working memory in healthy subjects . Furthermore, a study conducted on university students showed a significant relationship between a low level of premeditation and poor decision-making capacities . Regarding the motivational aspect of impulsivity, several studies have highlighted significant links between sensation-seeking and reward sensitivity. Besides, these four impulsivity dimensions have been related to different behavioral disorders and/or psychopathological states . Indeed, Rochat et al. recently reported significant correlations between the urgency dimension of impulsivity and a tendency to compulsive buying in a group of 74 patients with moderate to severe TBI. More specifically, results showed that urgency was a significant predictor of compulsive buying and that these two problematic behaviors significantly predicted the subjective burden perceived by the caregivers. This study illustrates the existing relationships between the different types of problematic behaviors and the potential implications of common psychological mechanisms in the various behavioral changes in patients with TBI.

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Manifestations of anosognosia

Anosognosia is a disorder characterized by the difficulty in being aware of deficits consecutive to brain damage. The manifestations of anosognosia are diverse and several dissociations exist since this disorder can affect one or several domains and be expressed on different severity levels . The first studies on anosognosia focused mostly on anosognosia for hemiplegia after ischemic stroke because of the easy evaluation of this motor component. Based on these observations, Levine formulated a “discovery theory” of anosognosia for hemiplegia, according to which cognitive deficits might contribute to denial by preventing the detection of limb weakness when combined with proprioceptive or sensory loss. More precisely, Gold et al. explained the denial behavior by referring to a cognitive model of motor control (“feedforward” hypothesis). In this model, anosognosia is assumed to be related to deficits of a comparator system that has to match the congruity between the intended movement and the sensory consequences of the actually executed movement.

Later on, studies have focused on other aspects of cognition and particularly on anosognosia for cognitive disorders and behavioral changes. Thus, Sherer et al. reported that anosognosia post-TBI can also concern behavioral, cognitive and emotional disorders. More precisely, it appears that visible or objective disorders (e.g. phasic disorders) are better identified by patients than more abstract disorders (e.g. attention disorders). In this context, global approaches to anosognosia have been proposed such as the one by Crosson et al. who described three hierarchical level of deficit awareness:

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  intellectual awareness which represents a patient’s ability to recognize his/her deficits or impaired functioning;

  
  
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  emergent awareness which represents a patient’s ability to detect their difficulties as they emerge in daily life;

  
  
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  anticipatory awareness which represents the awareness of long-term consequences enabling to build realistic projects for the future.

Further, Toglia and Kirk proposed a model taking into account other variables: “off-line” awareness namely metacognitive knowledge, encompassing the knowledge one has of its own functioning and “online” awareness corresponding to the anticipation abilities and self-monitoring of task execution (supported by executive control abilities and error-monitoring). These two models suggest that anosognosia of cognitive and behavioral difficulties might be supported by different psychological mechanisms. Among the cognitive process, Coben et al. showed in 14 patients with TBI that the executive processes of cognitive estimation, planning and word generation accounted for 61% of the anosognosia score variations on the Cognitive Estimation Test . Furthermore, Bogod et al. conducted a study on 45 patients with TBI, and found a significant and positive correlation between anosognosia as measured with the SADI scale and difficulties of dominant-response inhibition and mental flexibility during two tasks of error monitoring and go no-go. These data suggest that a deficit in one of the various executive functions could be involved in the occurrence of anosognosia in patients with TBI. Furthermore, studies have also showed the involvement of other types of cognitive mechanisms such as the capacity to take into account the mental state of another person and to detect false beliefs . Finally, emotional processes could also be involved as suggested by Spikman et al. who demonstrated that anosognosia for executive difficulties was significantly associated with difficulties to recognize facial emotions of anger and fear in patients with TBI.

Although these diverse data illustrate the multidimensional nature of anosognosia after TBI, there is to date no theoretical model of anosognosia for cognitive impairments and behavioral changes that takes into account the various mechanisms at play and their interactions. Interestingly, however, a multidimensional framework of anosognosia for hemiplegia was proposed by Vuilleumier , which accounts for different subtypes of unawareness. This model states that anosognosia may result from a combination of deficits in three different processes: appreciation of a deficit, verification of the information in case of uncertainty and modification of previous beliefs related to the impaired function. On the basis of this model, a recent study using a riddle test showed that patients with high level of anosognosia for hemiplegia presented high level of confidence for questions with few informative content about the target word. In addition, patients with anosognosia tended to perseverate with a first wrong answer even when faced with the incongruency of subsequent clues .

Finally, the analysis of neural correlates suggest the implication of a diffuse brain network in the onset of anosognosia after TBI, contrary to anosognosia for hemiplegia that was related to focal lesions of the right hemisphere . Among the cerebral regions involved in anosognosia after TBI, studies have identified the insula , cingulate cortex, precuneus as well as the anterior subcortical and medial temporoparietal regions . Furthermore, the connections between these different brain regions might be vulnerable to diffuse axonal injury frequently reported after TBI. Indeed, this type of injury could lead to disconnections between the different brain regions needed for awareness and information processing . For example, Dehaene et al. reported that being aware of a mental effort was possible with a unique global “workspace”, involving white matter tracts, which mainly regulate the functions of memory, attentional, perception and evaluation processes. All these data contribute to a better understanding of the multidimensional nature of these manifestations of anosognosia following TBI.