FRONTOTEMPORAL DEMENTIA: A WINDOW TO ALEXITHYMIA

Abstract

Alexithymia is pervasive among psychiatric patients, but its neurobiological mechanism is unclear. Patients with alexithymia cannot “read emotions”, a process involving interoception, or the perception of the body’s internal state, primarily in the insulae. The frontotemporal dementias are also associated with inability to correctly read emotions, hence these dementias can provide a window into the mechanism of alexithymia. Patients with behavioral variant frontotemporal dementia (bvFTD) have a weak emotional signal with impaired emotional recognition, hypoemotionality, and decreased physiological arousal. BvFTD affects the insulae, and the weak emotional signal facilitates impaired interoceptive accuracy resulting in an overreliance on cognitive appraisal rather than on internal sensations. In contrast, patients with semantic dementia (SD), another frontotemporal dementia syndrome, can have intact interoception, but they have disturbed cognitive appraisal of the meaning of their bodily sensations. This “alexisomia” in SD can lead to misinterpreted somatic symptoms. Together, the findings in alexithymic patients and frontotemporal dementia syndromes supports the model of impaired interoceptive accuracy as the mechanism of alexithymia, possibly from dysfunction in the insulae.

INTRODUCTION

Alexithymia, or the inability to identify and describe ones feelings, is a condition present in a broad range of psychiatric disorders. Although originally introduced to describe features of patients with psychosomatic disorders {^{1, 2}}, investigators have implicated alexithymia as part of the symptomatology of anxiety and obsessive-compulsive disorders, disturbances in eating and addiction, schizophrenia and other psychotic conditions, psychopathy, autism, and a range of other disorders {³}. Early theories for alexithymia stressed psychological traumas and high levels of psychological distress with overuse of defensive mechanisms resulting in somatic symptoms and affect-avoidance {^{4, 5}}. A further analysis of the neurobiological, rather than psychodynamic, mechanism of alexithymia could lead to a better understanding and management of this condition.

The term “alexithymia” means “lack of words, or inability to read, emotions” {¹}. Indeed, patients with alexithymia are deficient in the cognitive processing of emotions. For example, alexithymia impairs emotion recognition from faces and voices {^{6, 7}}, and it can result in atypical emotional facial expressions {^{7, 8}}. Unraveling the nature of alexithymia requires a grounding in the neurobiology of emotion.

THE NEUROBIOLOGY OF EMOTION

Emotion is a process that involves the insulae and a number of frontotemporal structures. Emotional processing in the brain begins with the identification of salient or emotional stimuli mediated by the amygdala. This results in physiological arousal and interoception, the perception of internal body or somatic sensations. Interoceptive sensitivity is strongly correlated with the strength of the physiological arousal in the posterior insulae {⁹}. The anterior insulae (AI), particularly on the right, merges these internal sensations with cognitive evaluation resulting in the awareness of feelings {¹⁰}. This process involves reciprocal interactions between the AI and the anterior cingulate cortex (ACC), which mediates emotional responding and the expression of affective arousal. The AI and ACC are core regions of the Salience Network (SN), which activates in response to emotionally salient cues in the environment {¹¹}. In addition to interoception, the cognitive appraisal of one’s internal and external environment also contributes towards emotional experience {¹²}. Cognitive appraisal involves frontal regions such as the orbitofrontal cortex for emotional control, the ventromedial prefrontal cortex for affective meaning, and the ventrolateral prefrontal cortex for emotional integration and regulation. Finally, other temporal lobe structures such as the inferior temporal and fusiform gyrus, are important for affective signal detection and integration, and the anterior temporal poles specifically link interoceptive stimuli with its conceptual meaning {¹³}.

ALEXITHYMIA AND INTEROCEPTION

The mechanism for alexithymia may be a disassociation between internal physiological arousal and externally-based cognitive appraisal {¹⁴}. In alexithymia, investigators describe difficulty “elevating emotions from a sensorimotor level of experience” to a representational level, where they can be used as signaling interoception {¹⁵}. On the cognitive appraisal side, others propose relative dysfunction of neocortical areas for symbolically and linguistically representing emotion {¹⁶}. Indeed, reports of patients with underwent a commissurotomy, or surgical incision into the callosal commissure, indicate increased alexithymia as preserved interoceptive feelings in the right hemisphere could no longer access left hemisphere language and symbolization {¹⁴}.

Still other information links alexithymia to a failure of interoception {^{17, 18}}. Persons with higher levels of alexithymia appear to have poor knowledge of their internal states and decreased interoceptive accuracy {⁹}, and alexithymia can impair interoception of cardiac, respiratory output, muscular effort, and taste sensitivity {¹⁷}. Poor cardiac sensitivity correlates with high levels of alexithymia {²⁴}, and higher self-reported interoceptive confusion occurs among alexithymic individuals {^{18, 25}}. In autism, alexithymia, is associated with decreased interoceptive sensitivity even in the presence of an intact interoceptive signal {^{19, 20}}. Much research also associates damage to the AI with both interoceptive difficulties and alexithymia {^{21, 22}}. Finally, poor recognition of facial negative emotions is linked to both high levels of alexithymia and low levels of interoception {²³}.

EVIDENCE FROM THE FRONTOTEMPORAL DEMENTIAS

An important degenerative disorder that alters emotion is behavioral variant frontotemporal dementia (bvFTD). This disorder is the second most common neurodegenerative dementia among patients <65 years, after early-onset Alzheimer’s disease {²⁶}. Patients with bvFTD have behavioral changes such as impaired emotionality and empathy, apathy or abulia, disinhibition or impulsivity, dietary changes, and dysexecutive cognition from disease affecting the frontal and anterior lobes {²⁶}. The early focus of neuropathology in this disorder is in the AI, ACC, and the SN.

In addition to bvFTD, the frontotemporal dementias include semantic dementia (SD), also known as semantic variant primary progressive aphasia in its early stages. SD results in a loss of semantics, or the meaning of words and objects, from atrophy in the anterior temporal lobes {²⁷}. The earliest changes in SD affect the meaning of words manifesting as a semantic anomia, but, as the disease progresses, there is a multimodal impairment in knowledge for objects, faces, sounds, smells, and other perceptions, regardless of modality, including confusion over the nature of somatic or bodily sensations {²⁷}.

Alexithymia in BvFTD

Most patients with bvFTD have emotional blunting with impaired recognition of emotions and decreased psychophysiological arousal to emotional stimuli {^28–33}. Studies have shown that these patients are impaired in the recognition of emotions in pictures or videos {^{34, 35}}. Multiple studies document lower baseline tonic levels and decreased or insufficient phasic reactivity in both sympathetic and parasympathetic activity in bvFTD {^{11, 28, 30, 32, 36, 37}}. Patients with FTD have shown reduced sensitivity to different types of emotional stimuli, such as pain {²⁹}, fear conditioning to a loud noise {³⁸}, and aversive odors {³⁹}, and, when exposed to an unpleasant stimulus, patients with bvFTD had attenuation of the expected initial heart rate deceleration characteristic of an orienting response {³³}. Hypoemotionality also contributes to the lack of insight for their disease, which is best characterized as an “anosodiasphoria”, or lack of emotional caring, rather than a true anosognosia, or lack of cognitive awareness {⁴⁰}. The emotional blunting and decreased physiological arousal in bvFTD may correspond with atrophy or hypometabolism involving the AI and pregenual and middle cingulate cortex {³⁷}.

Beyond their impaired recognition of emotions and decreased physiological arousal, patients with bvFTD cannot accurately read their own interoceptive signals and do not reliably report their degree of emotional arousal {³²}. Patients with bvFTD have impaired explicit awareness of their own heartbeat {⁴¹}, and they are unable to assess internal sensations for “gut level” cues {⁴²}. Investigators document a mismatch between intrinsic physiological arousal (implicitly feeling emotions) and reports of emotion or ratings of valence from the patients (explicit approval) {³²}. In general, those with bvFTD experience emotional stimuli as decreased in intensity, and they cannot estimate it except for differentiation of extremes of arousal {³²}. However, rather than underestimating emotional stimuli, patients with bvFTD may exaggerate their interoceptive sensations from an over-reliance on cognitive appraisal using external contextual information, established rules, or environmental cues to explain their feelings {^{32, 43, 44}}.

Alexisomia in SD

SD is a unique frontotemporal degeneration syndrome that affects the temporal poles, which are convergence zones for multimodal representations of knowledge, including interoceptive signals {⁴⁵}. In SD, dysfunction of anterior temporal regions can impair semantic meaning of interoceptive information. This results in impaired interoceptive accuracy from a disassociation of somatic sensations from semantic knowledge {^{46, 47}}. “Alexisomia”, or difficulty in reading somatic symptoms, is the alexithymia-related phenomenon in which somatic sensations are misread by patients with SD.

Because of their alexisomia, patients with SD may be prone to somatic symptom disorder from inability to identify the meaning of bodily sensations {⁴⁸}. Ten percent of autopsy-confirmed SD patients have presented with somatization, especially those with prominent right temporal lobe atrophy {⁴⁹}. They may become excessively concerned and “somaticize” over their normal bodily sensations because of confusion over their meaning, origin, and identity, and may even conclude that their unknown somatic sensations or symptoms mean that they are deteriorating or dying (“Cotard syndrome”) {⁵⁰}. Although pain and temperature awareness may be increased in patients with SD {²⁹}, this increased sensory awareness does not seem to reflect genuine hypersensitivity but, rather, an over-attribution of salience in SD {²⁹}, i.e., since they do not know what the sensations mean they are primed to overreact to them {⁴⁹}.

CONCLUSIONS

Alexithymia is an important but poorly-understood symptom, which is present among a wide range of psychiatric disorders. Early descriptions of the mechanism of alexithymia suggested a primary disorder from a dissociation of “limbic” or interoceptive physiological signals from cortical representations or interpretations {^{15, 16}}. Investigators suggested that psychological trauma with overactive defense mechanisms blocked this “limbic-cortical” association; however, more recent studies point to disturbed interoceptive processing itself as central to alexithymia. Similar difficulties among two frontotemporal dementia syndromes, bvFTD and SD, shed light on the neurobiological mechanism of this symptom. Alexithymia in bvFTD results from in a weak emotional and physiological signal with impaired interoceptive accuracy and a consequent overreliance on external context and rules for explaining the experience. Alexisomia in SD results from inability to correctly read intact interoception due to an impairment in the ability to derive the meaning of bodily sensations. These findings in brain syndromes known to affect the emotional centers of the brain, particularly insulae where interoception is centered, supports a deficit in interoceptive accuracy as central to alexithymia, either from a blunted emotional physiological signal, from impaired cognitive appraisal, or from disturbance in interoceptive processing in the insulae. Clearly, more research can offer further insights into the neurobiological basis of alexithymia based on this model.