واکنش پذیری انزجار کاهش در فراموشی پیشانی گیجگاهی نوع دیگر رفتاری

Abstract Frontotemporal dementia is a neurodegenerative disease that impacts emotion and social behavior. Using laboratory measures of emotional reactivity, our past work has found that reactivity to loud noises and to thematically simple happy and sad emotional films are preserved in the early stages of the disease while other emotional responses (e.g., embarrassment) are severely compromised. In the present study we examined disgust, an emotion whose function is to distance us from offending objects and situations. We measured disgust reactivity in 21 patients with behavioral variant frontotemporal dementia (bvFTD, a subtype of frontotemporal dementia characterized by emotional blunting) and 25 neurologically healthy controls. Disgust is an emotion of particular interest in bvFTD, due to caregiver and clinician reports that patients engage in acts that suggest this emotion may be compromised; in addition, the pattern of neurodegeneration in bvFTD includes atrophy of key frontotemporal structures (e.g., anterior insula) with known roles in visceral emotions such as disgust. In the present study, participants had their emotional facial behavior, physiology, and self-reported emotional experience measured while watching a disgust-eliciting film. We found that behavioral, physiological, and self-reported experiential responses were all reduced in bvFTD patients compared to controls (with behavioral and physiological differences still found after controlling for patients’ cognitive deficits). We discuss the implications of these findings for bvFTD patients’ problems in social functioning and their typical patterns of neurodegeneration.

1. Introduction Frontotemporal dementia is a neurodegenerative disease that selectively affects the frontal and anterior temporal lobes of the brain, regions that are crucial for proper social and emotional functioning (Rosen et al., 2005 and Werner et al., 2007). Dramatic social and emotional changes (e.g., emotional blunting, lack of empathy, disinhibition, and poor insight) are early and striking manifestations of this disease (Boxer and Miller, 2005 and Neary et al., 2005). Frontotemporal dementia includes three clinical subtypes: behavioral variant frontotemporal dementia (bvFTD), semantic dementia, and progressive non-fluent aphasia. In bvFTD, the subtype that primarily affects the frontal lobes and is the focus of the present study, early and profound emotional and social deficits (e.g., impulsive and inappropriate behavior and a lack of insight into deficits) are common (Boxer and Miller, 2005 and Kipps et al., 2009). The anterior cingulate cortex and anterior insula are among the earliest brain regions affected in bvFTD (Rosen et al., 2002, Seeley, 2010 and Seeley et al., 2008). The anterior cingulate cortex, which is important for the generation of visceromotor emotional responding, is reciprocally connected with the anterior insula (Bush et al., 2000 and Devinsky et al., 1995). The anterior insula, located deep between the frontal and temporal lobes within the lateral fissure, integrates afferent visceral information with higher-order subjective emotional processing (Craig, 2002 and Critchley, 2005). Activation of the insula is commonly found in neuroimaging studies while participants are exposed to disgust-eliciting stimuli (Wicker et al., 2003 and Wright et al., 2004). Together, the anterior cingulate cortex and anterior insula play key roles in the generation of emotional responses and interoceptive processing of feeling states. Thus, loss in these structures in the context of neurodegenerative disease may result in social and emotional impairment as patients fail to generate emotional reactions and/or lose access to internal physiological cues that typically guide behavior (Damasio, Tranel, & Damasio, 1990). In our own work, we have used methods derived from affective science (Levenson et al., 2008) to provide a detailed assessment of emotional functioning in bvFTD. These laboratory-based methods enable us to examine preservation and loss of emotional functioning objectively and directly, using measures that are not as subject to biases that can occur with caregiver retrospective reports or clinician observations. Taking this approach, we have found evidence that suggests that while many aspects of emotional reactivity are clearly disrupted in bvFTD, other aspects remain intact in the early stages of the disease. For example, we have found that patients with bvFTD have intact emotional responses to unexpected loud noises (i.e., a 115 db acoustic startle stimulus; Sturm, Rosen, Allison, Miller, & Levenson, 2006) and to thematically simple film clips that elicit happiness and sadness (Werner et al., 2007) but have deficits in self-conscious emotions (Sturm et al., 2008 and Sturm et al., 2006). In terms of the emotion of disgust, a previous study of reaction times in lexical and numerical judgment tasks did not find deficits when patients with bvFTD processed disgusting stimuli (Bedoin, Thomas-Antérion, Dorey, & Lebert, 2009). However, we are aware of no previous studies that measured the physiological and facial reactions of patients with bvFTD while they viewed disgusting stimuli. In the present study we addressed the need to examine disgust reactivity in bvFTD. Disgust is an emotion with a characteristic facial expression (wrinkled nose, raised upper lip, and tongue moving forward in the mouth), action tendency (distancing of the self from the offensive object), and physiological profile (nausea, gagging) that directs us away from unpleasant objects in the environment (Ekman et al., 1980, Rozin and Fallon, 1987 and Rozin et al., 1994). Behaviorally, disgust is thought to have evolved with an oral/nasal focus; the origins of the facial muscle movements that occur during a disgust display may have served to reject offensive foods, smells, and other contaminated materials (Rozin, Haidt, & McCauley, 2008). Physiologically, disgust is a highly visceral emotion (i.e., it is often accompanied by the experience of nausea). Sensations associated with these visceral changes play an important role in disgust, providing a signal that helps us to avoid potentially harmful food and other contaminated substances (Rozin & Fallon, 1987). In humans, disgust has generalized into a “moral” emotion, helping guide us away from a wide range of ethically undesirable objects, situations, acts, and people (Rozin, Haidt, & Fincher, 2009). For example, a person may feel disgusted by someone who has performed a morally reprehensible act. In the present study, we examined disgust reactivity (i.e., facial behavior, physiological activation, and subjective experience) in patients with bvFTD and neurologically healthy controls while they watched a disgust-eliciting film. Anecdotal evidence and early neurodegeneration of the insula (Seeley, 2010) suggest that disgust may be particularly vulnerable in bvFTD. Consistent with this, caregivers have reported that some patients with bvFTD pick up garbage, drink beverages found on the street, eat out of trashcans, and sample food from strangers’ plates in restaurants. Thus, we hypothesized that patients with bvFTD would show deficits in disgust reactivity compared to controls.

Conclusions The present study underscores the usefulness of applying techniques derived from basic affective science to the study of emotional functioning in patients with neurodegenerative disease (Levenson et al., 2008). Using our laboratory methods, we were able to document robust deficits in behavioral and physiological aspects of disgust reactivity and also found some evidence for reduced subjective experience of disgust reactivity in response to a disgust-eliciting film in patients with bvFTD. These findings build on our previous work and provide additional information about areas of preserved and compromised emotional functioning in this disease.