The influence of right frontotemporal dysfunction on social behavior in frontotemporal dementia

Methods.

Results.

Eleven of 12 right-sided and 2 of 19 left-sided FTD patients presented with socially undesirable behavior as an initial symptom. The resulting χ² was highly significant (χ = 23.3, p < 0.001). The tabletabulates the frequency of the socially undesirable behaviors for each of the 12 patients with right-sided FTD.

Discussion.

This study supports the relationship between right-sided FTD and socially undesirable behavior and suggests that frontotemporal regions of the right hemisphere are critical for normal social conduct. The maintenance of appropriate social behavior, however, is a very complex process with many contributing factors. Nevertheless, several areas of research seem particularly promising for explaining the prominent and often disturbing behavioral manifestations observed in patients with right-sided FTD. These include research on the dominance of the right hemisphere in emotional processing, global attention, self-awareness, and maintenance of a sense of self.

The right hemisphere is dominant in both the comprehension and expression of emotion, with its role having been confirmed with many studies of multiple modalities.12 The dominance of the right hemisphere in emotional comprehension, in particular, has been well established. Studies in brain-damaged patients have showed more deficits in the interpretation of facial expressions after right hemisphere damage than left,13-15⇓⇓ which is independent of deficits in processing nonemotional faces.16,17⇓ Preferential involvement of the right hemisphere in the analysis of emotional signals has also been supported by studies of normal subjects’ responses to neutral and emotional faces presented in left and right visual fields.18 The right hemisphere is also dominant for the auditory comprehension of emotion. Dichotic listening experiments have demonstrated a left ear advantage for processing the emotional tone of natural speech, nonverbal vocalization, and musical passages.19-22⇓⇓⇓ Furthermore, studies have shown that patients with right hemisphere damage are impaired in the identification,23,24⇓ discrimination,24 and comprehension25 of emotional prosody.

The right hemisphere is also dominant for the expression of emotions, primarily through speech intonation25,26⇓ and body gesturing.25 Facial expressions tend to be more pronounced on the left side of the face than on the right side, suggesting more intense involvement of the right hemisphere.27 In subjects with right anterior hemispheric lesions, spontaneous and posed facial expressions are less accurate.19 Patients with right hemisphere damage,13,25,26⇓⇓ and specifically right frontal damage,25 show deficits in producing emotional intonation in their speech relative to patients with left brain damage or normal controls.

Consistent with these findings, a distinctive feature of many of our patients with right-sided FTD is the bizarre expression of affect. Spouses commonly complained that the patient seemed foreign or ‘alien’, with a remote, blunted affect. For example, several of our patients with right-sided FTD had fixed expressions on their faces: one looked as if he were constantly glaring and another looked flat and expressionless, although both reported feeling happy. Furthermore, when asked to pose different expressions (e.g., happiness, sadness, anger, fear), both patients had great difficulty. This abnormal expression of affect made social interaction uncomfortable for the examiners and for other individuals who socialized with the patients. Therefore, it comes as no surprise that patients with FTD with predominantly right hemisphere degeneration have such difficulty in interpersonal interactions. They misinterpret others’ emotional states and, in turn, are misinterpreted. Furthermore, the empathic feeling usually present in social interactions was impaired in most of our patients with right-sided FTD. A common complaint among family members of these patients was a pervasive lack of empathy, with several spouses describing family crises during which the patient demonstrated a profound and uncharacteristic disregard for others’ feelings.

The right hemisphere is also dominant for maintaining a global attention to the environment. Whereas the left hemisphere is analytical and attends to details, the right hemisphere maintains attention to external surroundings as a whole.28 This ability allows accurate reading of the environment and enables a person to react appropriately to a situation, functions clearly necessary for appropriate social interaction and behavior. Heilman28 hypothesized that the right hemisphere directs attention to extrapersonal space (e.g., facial and emotional recognition, route finding), whereas the left hemisphere directs attention to peripersonal space (e.g., reading, writing, and praxis). Miller29 et al. studied a population of patients with FTD and concluded that those with right predominant degeneration had deficits in the nuances of social conduct and interaction.

Luria30 was one of the first to describe disturbance of social judgment after right hemisphere lesions. Descriptions of social inappropriateness in our patients with predominantly right hemisphere disease and the absence of social deficiencies in those with predominantly left hemisphere disease provide support for this theory. As examples, one of our patients began placing her head into the car window of strangers to strike up a conversation, another began making open remarks in public about strangers’ obesity, and yet another lost his job after commenting inappropriately on the breast size of women working with him. Importantly, all three patients had been thoughtful and reserved individuals premorbidly, and family members described these new behaviors as strikingly “out of character.”

Research in the area of self-awareness also supports the pivotal role of the right hemisphere in social behavior. Self-awareness is commonly defined as the ability to introspect on one’s own thoughts and to realize the relation of self to one’s social environment.31 Studies of brain-damaged patients with disturbances of self-awareness have shown such disorders are usually associated with lesions of the right frontal cortex.30,32,33⇓⇓ Common consequences of right frontal lobe dysfunction are a lack of awareness regarding alterations in behavior, emotions, and thought processes. Interviews with patients may suggest that all is normal, in contrast to descriptions of marked behavioral dysfunction provided by relatives and caregivers. This was a common occurrence in many of our patients. Furthermore, patients with limited awareness of impairments tend not to be motivated to improve their behavior and often have problems evaluating the consequences and implications of their own behavior. They may fail to see the significance of their decisions for themselves and for those around them. Their behavior suggests an inability to assess the value of each new action, or lack of action, in terms of goals that are not overtly specified in the immediate environment.

An important component of self-awareness is “autonoetic awareness,” a term coined by Tulving34 that is defined as the awareness of oneself as a continuous entity across time. This capacity allows a person to know that the self doing the experiencing now is the same self that did so at an earlier time, and thus is essential for maintaining a robust and consistent sense of self, or self-concept. Patients with right-sided FTD appear to have particular difficulty with autonoetic awareness. A frequent complaint made by the spouse is that the patient is no longer his or her self, or has “lost” his or her self. Striking changes in political convictions, religious ideology, and social loyalties often occur, reflecting alterations in self-concept. Importantly, this “loss of self” often precedes any significant cognitive decline, and it is at this point that the patient often receives a psychiatric misdiagnosis.

Autonoetic awareness also affects an individual’s management of future events, such as personally relevant plans, goals, and expectations. In other words, autonoetic awareness is the cornerstone of self-regulation in that it supports the formulation of goals and the implementation of a behavioral guidance system to achieve them.35 Thus, patients lacking this capacity are driven by irrelevant environmental goals or inappropriate habits or routines.36 Although intimately related to the “frontal dysexecutive syndrome” commonly observed in patients with frontal dysfunction, autonoetic awareness has broader implications for self-regulation in that the “self” serves as the standard against which behavior is measured. Thus, the lack of a consistent and coherent sense of self precludes successful self-regulation.

Episodic memory plays an essential role in autonoetic awareness.35 The right frontal lobe, in particular, is thought to be relevant for episodic memory that connects the recall of personal past, and the associated emotional associations, with plans for the future.33 Recent PET studies have shown an association between the retrieval of episodic memories and activation of the prefrontal cortex, predominantly on the right.37,38,39⇓⇓ Also, a PET study in which subjects retrieved emotional memories from their past showed activation of right prefrontal areas as well as other regions in the right hemisphere.40

However, it is well established that encoding processes differentially engage left prefrontal areas, whereas retrieval process for the same material predominantly involve right prefrontal areas. This observed difference is embodied in the hemispheric encoding/retrieval asymmetry model (HERA41), and the empirical observations on which the model is based have since been replicated many times.39,42⇓ Thus, Craik et al.43 conducted a PET study investigating the possibility that encoding of self-related material might also activate right frontal areas. Their results showed that self-related encoding yielded left frontal activations similar to those associated with other types of semantic encoding (consistent with the HERA model) but also specific activations in the right frontal lobe. The findings suggest that these activations signal the involvement of the self as a necessary component of episodic retrieval, and they may be attributable (at least in part) to the representation of self in this area of the brain. Thus, it follows that damage to the right frontal lobe might lead to shifts in personality and fundamental belief systems. This might explain some of the profound changes in behavior that occur in patients with right-sided FTD and is consistent with family members’ common complaint that the patient has lost his or her “self”.

In conclusion, this study suggests that the frontotemporal regions of the right hemisphere are critical for social behavior and the maintenance of an individual’s sense of self, or self-concept. Research showing the dominance of these regions of the brain in mediating the nuances of social conduct and interaction, the comprehension and expression of emotions, and self-awareness support these findings.