Alexithymia as a Transdiagnostic Precursor to Empathy Abnormalities: The Functional Role of the Insula

Distorted empathic processing has been observed across multiple psychiatric disorders. Simulation theory provides a theoretical framework that proposes a mechanism through which empathy difficulties may arise. Specifically, introspection-centric simulation theory (IST) predicts that an inability to accurately interpret and describe internal affective states may lead to empathy difficulties. The purpose of this review is to synthesize and summarize an empirical literature suggesting that simulation theory provides insights into a cognitive and neurobiological mechanism (i.e., alexithymia and insula pathology) that negatively impacts empathic processing, in addition to how disruptions in these processes manifest across psychiatric disorders. Specifically, we review an emerging non-clinical literature suggesting that consistent with IST, alexithymia and associated insula pathology leads to empathy deficits. Subsequently, we highlight clinical research suggesting that a large number of disorders characterized by empathy pathology also feature alexithymia. Collectively, these findings motivate the importance for future work to establish the role of alexithymia in contributing to empathy deficits across clinical symptoms and disorders. The current review suggests that simulation theory provides a tractable conceptual platform for identifying a potential common cognitive and neural marker that is associated with empathy deficits across a wide array of diagnostic classes.


The role of the insula in alexithymia and concurrent empathic deficits
Self-report measures (Bermond-Vorst Alexithymia Questionnaire -BVAQ) Five subscales of the BVAQ resulted in a two-factor solution in all cultural groups and explained between 55-66% of the variance. These two factors (i.e., cognitive and affective alexithymia) were independent rather than correlated. (Bird et al., 2010) ASD and control participants combined and divided into low alexithymia (n=18) and high alexithymia (n=18) groups.
Self-report measures (Toronto Alexithymia Scale -TAS-20, Bermond-Vorst Alexithymia Questionnaire -BVAQ, Interpersonal Reactivity Index -IRI), empathy for pain task, fMRI Empathic brain responses were associated with increased left anterior insula activation. The response magnitude predicted alexithymia severity in ASD and controls, and did not vary as a function of group.
(Craig, 2009) Review paper Review paper Evidence suggesting role of the anterior insula in the re-representation of interoception and involvement in all subjective feelings. Argues for role of anterior insula in awareness and as a neural correlate of consciousness.
(Damasio & Carvalho, 2013) Review paper Review paper Discusses the role of the insula in sensing and mapping body states and generating feelings. Also discusses the role of the insula in modulating the processing and experience of interoceptive and emotional states, connecting them with memory, language, and reasoning-related regions.

Self-report measures (Toronto Alexithymia Scale -TAS-20) fMRI (Emotional Imagery task)
High relative to low alexithymia exhibited lower imagery vividness and emotional intensity during imagery for past and future sad events. High alexithymia group showed less posterior cingulate activity during past and future happy imagery, compared to rest and neutral imagery conditions.
(Zaki, Davis, & Ochsner, 2012) Healthy participants (n=16) fMRI (Task 1: viewing emotional videos and rating emotion and eye gaze; Task 2: rating heartbeat, tones, and heartbeat with tones) Activity in the anterior insula and inferior frontal operculum correlated with heartbeat monitoring (interoception), and scaled with trial by trial intensity of participants' emotional experience.
Regarding the empathy for pain task, both groups had increased anterior insula activation, and the strength of this association was predictive of alexithymia.
No difference between ASD and controls in the degree of empathy related insula activation after controlling for alexithymia. Males with no reported psychiatric illness (n=46) Self-report measures (Self-Report Psychopathy Scale, Short Form -SRP-SF), fMRI (empathy for pain task) Affective-interpersonal psychopathy traits were negatively associated with insula response while empathizing, where as lifestyle-antisocial traits were positively associated. NPD patients (n=20), patients with a Cluster C spectrum personality disorder (n=20), healthy controls (n=20) Self-report measures (Interpersonal Reactivity Index -IRI, behavioral task (facial emotion recognition) No empathy deficits found on the IRI. NPD patients performed worse in facial emotion recognition compared to other groups. NPD patients also showed a specific deficit in fear and disgust emotions. The DTDD traits were positively associated with alexithymia and negatively associated with empathy. Difficulty identifying feelings and reduced emotional reactivity were significant predictors of narcissism and the DTDD total score.
(Schulze et al., 2013) NPD patients (n=17), controls (n=17) Self-report measures (Interpersonal Reactivity Index -IRI), MRI (measure gray matter volume) NPD patients had smaller GM volume in the left anterior insula relative to controls. Independent of group, GM volume in the left anterior insula was positively associated with emotional empathy Borderline personality disorder (Beeney, Hallquist, Ellison, & Levy, 2016) Females with BPD (n=17), controls (n=21) Self-report measures (Differentiation of Self Inventory -DSI), behavioral task (Self-Aspects Card Sort Task), fMRI (evaluate personality traits of the self and others) Insula activation mediated poorer consistency in rating the self and others in BPD.
( Bungert et al., 2015) Females with BPD (n=20), controls (n=20) Pain task (high temperature pain administration), fMRI (cyberball paradigm) Social exclusion led to higher reported physical pain sensitivity in both groups, and this was accompanied by enhanced anterior insula activation. In BPD, physical pain processing after exclusion was linked to enhanced posterior insula activation.  (n=145) Semistructured interview (CI-BPD), computerized diagnostic measure (C-DISC), self-report measures (BES, DERS), parent-report measure (CBCL), task (MASC) BPD was associated with higher affective empathy than controls. Increased emotional dysregulation was associated with decreased affective empathy in BPD. Undergraduate students (n=100) Self-report measures (Levenson Self-Report Psychopathy Scale -LSRP, Toronto Alexithymia Scale -TAS-20, Coolidge Axis II Inventory -CATI, Difficulties in Emotion Regulation Scale -DERS) Alexithymia positively correlated with both emotional dysregulation and BPD tendencies.
(Wolff, Stiglmayr, Bretz, Lammers, & Auckenthaler, 2007) Females with BPD (n=30), female controls (n=28) The MINITOR program: handheld device that administers self-report items while participants engage in everyday life BPD patients exhibited more intense unpleasant emotions, greater difficulties with identifying their emotions, and increased aversive inner tension, relative to controls. Increased aversive inner tension was associated with increased difficulty identifying internal emotions.