Patterns of Cognitive and Emotional Empathy in Frontotemporal Lobar Degeneration : Cognitive and Behavioral Neurology

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Original Article

Patterns of Cognitive and Emotional Empathy in Frontotemporal Lobar Degeneration

Rankin, Katherine P PhD; Kramer, Joel H PsyD; Miller, Bruce L MD

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Cognitive and Behavioral Neurology 18(1):p 28-36, March 2005. | DOI: 10.1097/01.wnn.0000152225.05377.ab
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The capacity to have an empathic response to another person is one of the most important elements of higher social functioning. Empathy provides powerful motivation to address the needs of others in one's social group, and helps forge bonds of affiliation and affection that support long-term social commitment to particular valued individuals in one's social environment. Perhaps even more importantly, empathy is self-reinforcing for both the responder and the recipient and allows social relationships to be experienced as inherently enjoyable and meaningful, even beyond any material benefits such relationships provide.

Despite the importance of this cognitive process to human society, empathy has only recently begun to be studied with the scientific rigor that has already been applied to more concrete cognitive processes such as memory and language. Though many neurocognitive systems have been proven to have a modular architecture in the brain, with dedicated nodes that work in parallel to produce a memory or a spoken sentence, empathy is still often seen as an epiphenomenon without a dedicated neural substrate. However, recent research utilizing techniques such as functional magnetic resonance imaging (fMRI) and neural network analysis to examine empathy have begun to reveal that this function may also be subserved by a specific modular system. With use of psychologic modeling, empathy can be broken down into its component neurocognitive functions, which allows a theoretical “empathy circuit” to be proposed and tested.

This study was designed to test the relationship between empathy and the cognitive mechanisms underpinning it. We briefly review the theoretical structure of empathy used in this study, as well as some of empathy's purported cognitive substrates, both of which were directly assessed via neuropsychological testing in this study. Because we examined patients with frontotemporal lobar degeneration (FTLD) and Alzheimer disease (AD), we will also briefly review the clinical features of these diseases in relation to empathy.


Superordinate Structure of Empathy

Theoretical models of empathy suggest that it has both cognitive and emotional aspects.1-4 Perspective taking is a form of cognitive empathy that may occur apart from a particular emotional response and involves coming to a cognitive understanding of what the other may be thinking or feeling. Well-developed cognitive empathy may also be seen in individuals who can easily project themselves into fictional situations and who experience a strong sense of identification with the characters while reading or watching movies (often termed “fantasy”).2,5 Emotional empathy, on the other hand, may manifest as a sudden surge of emotional concern upon observing someone in distress and does not necessarily require a cognitive understanding of why the other is suffering. Developmentally, the most primitive precursor of empathy to appear in children is personal distress (or “emotional contagion”), which occurs when an observer of someone else's distress becomes agitated or emotionally distraught, but does not distinguish between his/her experience and that of the observed individual. In this form, the observed individual's distress becomes secondary to that of the observer's emotional reaction. As greater capacity for perspective taking develops, this personal distress will decrease and will be replaced by emotional concern, in which the observer's emotional response is grounded in the recognition that the other is the one who has been hurt and that the other's experience is of primary importance. These specific aspects of both cognitive and emotional empathy (perspective taking, fantasy, personal distress, and emotional concern) are the higher-level outcome measures of empathy that themselves can be broken down into component processes.

Cognitive Components of Empathy

Attention/Working Memory

As with most cognitive processes, failure to attend to the requirements of a situation will result in diminished performance. With regard to empathy, simple attention is necessary to note and process situational cues in a social interaction. Complex attention (or “working memory”) is also required to hold and manipulate information from multiple sources of input, particularly in a more complex social situation where information is derived from the other's facial expression, voice prosody, and physical gestures, as well as from the content of his/her speech.

Perspective Taking/Theory of Mind

One of the central cognitive processes involved in generating an empathic response is imagining other's cognitive and emotional state based on cues from visual, auditory, or situational cues. This process has elements in common with theory of mind tasks, in which one must not only imagine that another individual has a set of thoughts and emotions that are distinct from one's own but must also accurately imagine what that mental state might be. fMRI studies suggest that the common neuroanatomical structures activated during performance of theory of mind tasks are the left temporal pole, left superior temporal sulcus, anterior paracingulate cortex, and medial or right orbitofrontal cortex.6-10 Shamay et al11 showed that patients with orbitofrontal lesions evidence diminished cognitive but not emotional empathy, which may support the hypothesis that the perspective-taking aspect of empathy is mediated by the ventromedial orbitofrontal cortex.

Abstract Reasoning

The capacity for general abstract reasoning may allow imagination of an implicit, higher-order interpretation of another's observed behavior, which in turn may facilitate empathy. One who is capable only of making concrete interpretations may fail to see beyond the other's immediate behavior and its direct consequences and may fail to perform higher-level reasoning about the other's perspective, motivations, or intentions simply owing to a failure to make the leap into abstract reasoning about implicit factors.

Spontaneous Cognitive Flexibility/ Generational Fluency

The capacity to spontaneously generate various ideas about another's cognitive or emotional state is likely to be another node in the cognitive circuit for empathy. Eslinger and Grattan12 showed that dissociations in patients' performance of various cognitive flexibility tasks provided evidence that there are actually two distinct types of cognitive flexibility. They called tasks requiring shifting of response set among predetermined options “reactive flexibility” and identified the capacity to produce diverse ideas as “spontaneous flexibility.” Thus, tasks requiring generation of both verbal and nonverbal cognitive material fall in the category of spontaneous cognitive fluency, which appears to be mediated by the frontal lobes. Studies have shown that better performance on measures of verbal3 and nonverbal11 fluency is directly associated with greater cognitive empathy.13

Reactive Cognitive Flexibility/Set Shifting

The ability to shift one's attention back and forth to compare and contrast one's own cognitive and emotional state and that of another may be necessary to reliably produce an appropriate empathic response. This reactive cognitive flexibility also supports the process of sorting through various hypotheses about the other's mental state and rapidly updating one's working model on the basis of incoming information. Studies have specifically linked increased perseveration and mental rigidity, as measured by neuropsychological tests such as the Wisconsin Card Sorting Test and the Trail Making Test, with lower scores on measures of empathy.3,13,14

Emotional Aspects of Empathy

Recognizing Others' Emotions

Fundamental processes involved in the experience of empathy include correctly interpreting others' emotions on the basis of their facial expressions, body gestures, and voice prosody. Emotion recognition systems in the brain have been elucidated by a number of studies during recent years and appear to be predominantly mediated by temporal lobe structures. Basic face perception and identification have been shown to be mediated by the right (and sometimes left) fusiform gyri or the “face area” of the brain,15-17 which is also involved in judgments of familiarity of faces as well as direction of eye gaze. Interpretation of facial emotions,18-21 voice prosody,22-24 and the social or emotional salience of movement,25,26 as well as explicit judgments about people's trustworthiness19,27 and significance of direct eye gaze,28 have all been associated with the right superior temporal sulcus and the amygdala. The orbitofrontal cortex also has been associated with judgment of facial emotions.20,29

Emotional Responsiveness

To have an emotional response to another's situation or display of emotion, one's own system for emotional arousal must be intact. An individual may experience emotional arousal without expressing that emotion facially or through other modalities such as voice, posture, or physical motion. However, there is evidence that basic emotions are so strongly linked to their facial expressions that prototypical muscle activity patterns can be detected via electromyography in individuals who show no visible change in facial activity but report experiencing a strong emotion.30 Responsiveness to more basic emotions such as fear and anger has been linked to bilateral amygdala function.22-24

Correctly Identify One's Own Emotional State

Though conscious recognition that one is having an empathic response to another's situation may not be strictly necessary to have intact empathy, more accurate self-reflection and higher levels of insight tend to occur in individuals who have higher social functioning and, by extension, have higher levels of empathy.2 Patient groups with right posterior cortical damage have shown deficits in self-reflection and empathy,31 and right parietal damage has long been associated with anosognosia for physical and emotional symptoms.32,33

Expressing One's Empathic State

Ostensibly, one can have empathic thoughts and feelings without choosing to express or act upon them; however, people who have a well-developed sense of empathy are likely to either display that empathy through emotional or verbal expressions or will act empathically to help the other who is in need. Recent work with corticobasal degeneration suggests that facial expression of emotion may be disrupted by an “emotional apraxia” that is linked to the often-observed buccofacial apraxia and opercular syndrome resulting from peri-insular damage.34,35 Patients with anterior cingulate damage may evidence significant apathy, not only making it less likely that they will experience strong emotions but also diminishing the likelihood that they will express their emotional state overtly.


Historically, studies of brain-behavior relationships in humans have begun with case-controlled lesion studies, in which patients with strokes or tumor resections can be carefully grouped by area of damage and the clinical manifestations of this damage can be measured. However, recent advances in brain-imaging technology have allowed researchers to recognize that, rather than having unpredictable, unique patterns of brain damage, dementia patients typically have specific patterns of neurodegeneration consistent with their disease. Though these will vary somewhat among patients within a single disease group, there is significant overlap, particularly in structures that have come to be pathognomonic to the disease, such as hippocampal atrophy in AD or amygdala atrophy in semantic dementia (SD). This has allowed the advent of a huge body of clinical research with dementia patients, building on the foundations laid by animal and human lesion studies, which has further elucidated many structure-function relationships in the brain. (For examples, see the work of Sullivan clarifying the neural substrate of memory in AD patients36,37 and that of Hodges examining the anatomic correlates of specific language functions in FTLD and AD patients.)38,39 Because the neurodegeneration specific to each diagnosis has been studied extensively, characteristic group differences in brain damage can legitimately be inferred from an accurate clinical diagnosis, meaning that direct measurement of brain atrophy is not always necessary to make logical statements about the neuroanatomic etiology of clinical deficits observed in a particular research sample. Such studies using patients with neurodegenerative conditions have clarified cognitive functions such as memory and language, but it is becoming increasingly clear that other neuropsychological features such as personality and social behavior also change as a direct result of neurodegeneration. Studying groups of dementia patients in whom a direct temporal link has been established between altered behavior and the onset of neurodegeneration can elucidate these brain-behavior relationships.

Structural MRI and fMRI studies suggest that many of the subprocesses most likely involved in empathy appear to be mediated by specific structures in the dorsolateral prefrontal lobe, orbitofrontal cortex, amygdala and periamygdalar structures, and other anterior temporal lobe structures. Because FTLD causes diverse patterns of anatomic damage throughout the frontal and temporal lobes, either bilaterally or predominantly unilaterally, as well as equally diverse changes in social and empathic functioning, FTLD patients are a population uniquely suited to examine the neuroanatomic foundations of empathy. FTLD is commonly broken down into two primary clinical subtypes. In frontotemporal dementia (FTD), the predominant areas of anatomic damage are in the frontal lobes, whereas in SD, the primary site of pathology is the temporal lobes. Both subtypes also show atrophy in the orbitofrontal cortex.40

Existing clinical criteria for both FTD and SD subtypes of FTLD suggest that loss of sympathy or empathy is an important element of the impaired social functioning often described in the disease.41,42 However, few studies have examined the potential mechanisms for this loss of empathy in detail. Some studies have attempted to link neuroanatomy with social behavior in FTLD patients by selecting patients on the basis of predominant area of brain atrophy, then describing behavioral changes on the basis of patient and family interviews. Symptoms commonly seen in patients with frontal atrophy include social withdrawal, apathy, disinhibition, and impaired judgment.43 In patients with right hemisphere damage to either the frontal or the temporal lobes, apathy, disinhibition, impaired judgment, and various types of bizarre behavior have been described.44,45 When patients with FTD and SD are contrasted using these general clinical descriptions, there is a high degree of overlap of social behavioral deficits between the two groups.46 The appearance of these early and often severe social and behavioral deficits sets FTLD patients apart from AD patients, in whom these functions typically remain intact until late in the disease course.

However, use of more specific, quantitative measures of social functioning in these dementia patients has yielded clearer anatomic dissociations. Rosen et al21 studied nine SD patients and found that they were deficient in comprehension of facial emotions, particularly for emotions with a negative valence. These deficits correlated with atrophy in the right amygdala and the right orbitofrontal cortex. Recently, Perry et al47 performed the first descriptive case study in which SD patients were divided by whether their atrophy was primarily in the language-dominant or -nondominant hemisphere (two of each). This group found that patients with nonlanguage hemisphere damage evidenced social withdrawal, loss of empathy, impaired judgment, bizarre behavior, denial of illness, and mental rigidity, whereas patients with corresponding damage to the language-dominant hemisphere evidenced preserved social functioning. Their results suggested not only that empathy was lateralized to the right hemisphere but that the anterior temporal cortex in particular may be critical for this skill. Rankin et al48 used a questionnaire measure of personality to compare the interpersonal functioning of frontal and temporal lobe FTLD patients. They found that temporal-variant patients (grouped together regardless of hemispheric laterality) showed a 2.5-SD increase in interpersonal coldness and lack of empathy, whereas patients with primarily frontal atrophy did not evidence this dramatic increase in coldness.

The current study was designed to investigate empathy loss in FTLD patients from two different perspectives. First, FTLD patients were divided into FTD and SD groups, and their overall empathy functioning was measured to determine if there was a quantitative difference in empathy loss between the FTD and SD variants compared with control groups of AD patients and healthy adult volunteers (NC). For this component of the study, we hypothesized that (a) both FTLD groups would show significantly lower levels of empathy than ADs or NCs and (b) SD patients would show disruption of both emotional and cognitive components of empathy, while FTDs would show only disruption of cognitive empathy.

The second component of this study was a more detailed investigation of the cognitive circuits underlying empathy in these patients to determine if part of the variance in overall empathy could be accounted for by neuropsychological tests of specific functions that are likely to be part of the neural circuit contributing to empathic functioning. Thus, our third hypothesis was that (c) deficits in reactive cognitive flexibility, verbal and nonverbal fluency, working memory, and abstract reasoning would each account for a portion of the variance in cognitive empathy scores, regardless of diagnostic group.



Fifty-three patients were recruited through the Memory and Aging Center at the University of California San Francisco. Patients seen at this dementia clinic represented a broad sample of the population in terms of ethnicity, sex, education level, and socioeconomic status, and an attempt was made to recruit all available patients for this study. Patient diagnosis was derived by a multidisciplinary team of neurologists, neuropsychologists, psychiatrists, and nurses. Thirty-seven of the patients were diagnosed with FTLD according to the Neary clinical criteria,42 including 18 FTD patients and 19 SD patients. Probable AD was diagnosed in 16 of the patients using the National Institute of Neurological and Communication Diseases and Stroke/Alzheimer's Disease and Related Disorders Association criteria.49 MRI scans of patients with FTLD and AD were done to rule out dementia due to cerebrovascular disease.

Ten age-matched healthy control subjects were also recruited from the pool of available study participants from the Memory and Aging Center. The center recruited these subjects from the San Francisco Bay Area through advertisements in local newspapers and recruitment talks at local senior community centers. Interested individuals underwent telephone screening for a history of problems with their physical or psychiatric health or a substance abuse history. Participants who passed the telephone screen were then brought in for a 1.5-hour neuropsychological evaluation, routine labs, and a brain MRI. Following this initial evaluation, a multidisciplinary team consisting of a neurologist, a neuropsychologist, and a nurse reviewed the data to determine if the patient met criteria to be a healthy control. For inclusion as a healthy control subject for this study, subjects had to have a normal neurologic examination, a Clinical Dementia Rating Scale score of 0, a Mini-Mental State Examination (MMSE) score of ≥28/30, and delayed memory performance of ≥25th percentile in both verbal and visuospatial domains. They also had to have an informant that was a first-degree family member, meaning a spouse or partner, adult child, sibling, or parent. Demographic data are summarized in Table 1.

IRI Empathy Scores by Diagnostic Group

Groups did not show significant differences in education, sex, or race. All patient groups had significantly lower MMSE scores than controls, but patient groups did not differ on MMSE. FTD patients were significantly younger than controls (FTD = 59.78 ± 9.25 years, NC = 71.96 ± 9.73 years; P < 0.05), so age was used as a covariate for all analyses.


Patients were identified from the clinic subject pool by diagnosis and then were recruited as potential study participants. These subjects and their caregivers signed an institutional review board-approved research consent form including an agreement to fill out questionnaires for research purposes.

The Interpersonal Reactivity Index (IRI) is a measure of both cognitive and emotional components of empathy that is administered in questionnaire form.2 Its 28 items include two seven-item subscales measuring Cognitive Empathy: Perspective Taking (PT; the tendency to spontaneously imagine the cognitive perspective of another person), and Fantasy (FS; the tendency to project oneself into the place of fictional characters in books and movies), as well as two seven-item subscales measuring Emotional Empathy: Empathic Concern (EC; the other-centered emotional response resulting from the perception of another's emotional state), and Personal Distress (PD; the self-centered emotional response involving fear or distress that results from witnessing another's stressful circumstances or negative emotional state). Theoretically, the PD subscale reflects a primitive form of empathy that actually interferes with an effective empathic response; thus, it tends to drop as the other scales rise (particularly in relation to the PT scale) and is negatively related to measures of overall social functioning. Higher scores on the PT, FS, and EC scales are associated with a more highly developed capacity for empathy.

Caregivers were asked to fill out the IRI describing the patients' current level of empathy. Raters were selected on a case-by-case basis with consideration given to the informant's frequency of contact with the patient, their described level of closeness, the rater's own cognitive capacity (eg, in the case of an aging spouse), and their willingness to participate. Spouses were used whenever possible (76%) and an adult child if no spouse was available (16%); in 7% of the cases, a sibling caregiver was used as an informant.

Neuropsychological tests of frontal-executive functioning were also administered to the patients as a part of a larger battery of tests measuring their general cognitive functioning. To evaluate their ability to generate verbal and nonverbal material, patients were asked to generate as many D words (phonemic fluency), animals (semantic fluency), and 4-line designs (subtest 1 of the Delis Kaplan Executive Functioning Scale Design Fluency Test)50 as they could for 1 minute each. Patients' reactive cognitive flexibility was measured using a version of the Trails B Test51 that was modified for a geriatric population (using days of the week rather than letters of the alphabet). Abstract reasoning was measured by asking patients to interpret a series of four similarities and three proverbs. Working memory was measured by number of digits backward on the Digit Span Test.52


Analysis of Group Differences

Analysis-of-covariance procedures were run, controlling for age, to determine if there were overall differences among the four groups. All four empathy subscales on the IRI showed significant group differences (see Table 1). Post-hoc Scheffé tests were run to determine whether there were significant differences among pairs of groups. These analyses supported the first hypothesis 1, showing that both FTLD groups had significantly lower levels of empathy than both ADs and NCs. AD patients did not show significant differences from NCs on any of the four IRI subscales. Supporting the second hypothesis, FTD patients showed significantly lower levels of PT than NCs (P < 0.01) but were not different from NCs on any other empathy measure. SDs also showed significantly lower levels of PT (P < 0.001) but, in addition, showed significantly lower levels of FS (P < 0.01) and EC (P < 0.001) and higher levels of PD (P < 0.05). Thus, SDs showed disruption of both emotional and cognitive empathy, whereas FTDs showed only disruption of cognitive empathy. When the two FTLD groups were compared directly, however, this effect was not strong enough to reach significance.

Correlational and Regression Analyses

The second component of the analysis was done to determine if part of the variance in empathy could be accounted for by certain neuropsychological measures, beyond the effect of global cognitive functioning. To analyze this, data reduction was performed by deriving a partial correlation matrix with all four empathy scale scores and the six neuropsychological measures chosen to represent subcomponents of empathy, controlling for MMSE. IRI PT score correlated significantly with Phonemic Fluency, Category Fluency, and Abstract Reasoning score but did not correlate significantly with other cognitive variables (Table 2). FS score correlated significantly with Design Fluency, Phonemic Fluency, and Category Fluency. EC score correlated significantly with Phonemic Fluency, Category Fluency, and Abstract Reasoning. PD score did not correlate with any neuropsychological variables. Many of the neuropsychological variables also showed moderate intercorrelations.

Partial Correlation Matrix of IRI Empathy Subscales and Selected Cognitive Scores, Controlling for MMSE

Next, simple linear regressions were run with the IRI subscale scores as the dependent variables and using only age, MMSE, and the cognitive variables that correlated significantly with that subscale score as predictor variables. The only cognitive variable that survived the regression with the PT subscale scores was the Category Verbal Fluency score (Fig. 1). Category Fluency accounted for 32% of the variance in PT score (β = 0.414, P < 0.05; F[5,50] = 4.66, P < 0.001). However, Category Fluency did not survive the analysis with the other cognitive empathy score. Instead, Phonemic Fluency accounted for 25% of the FS score (β = 0.417, P < 0.05; F[5, 52] = 3.37, P < 0.01), though all other cognitive variables dropped out of the analysis (Fig. 2). Neither of the emotional empathy scores was significantly predicted by any of the cognitive variables.

Perspective Taking (cognitive empathy) score versus Category Verbal Fluency (R 2 = 32%, pr = 0.45, P < 0.001).
Fantasy (cognitive empathy) score versus Phonemic Verbal Fluency (R 2 = 25%, pr = 0.44, P < 0.001).


The primary findings of this study were that, based on an observational measure of empathy, (a) FTLD patients showed significantly diminished levels of empathy compared with NCs, whereas AD patients did not differ from NCs; (b) FTD patients had significantly lower levels of Perspective Taking than NCs, whereas SDs had significantly lower levels of Perspective Taking as well as Empathic Concern and significantly higher levels of Personal Distress; (c) though three of the four empathy subscales (PT, FS, and EC) and many of the neuropsychological scores (except for Reactive Flexibility and Working Memory) were highly intercorrelated, only the verbal generation scores still accounted for variance in cognitive empathy once the effects of the intercorrelation were removed. No neuropsychological score predicted emotional empathy.

Neuroanatomic Implications of Group Differences

First, the fact that Alzheimer's patients did not show deficits in empathy despite an equivalent level of dementia (as measured by MMSE score) supports the hypothesis that empathy deficits are due to damage to specific, primarily anterior brain regions rather than to a general decrease in overall cognitive function. Second, the fact that SD and FTD patients showed divergent patterns of empathy loss suggests a more specific neuroanatomy for the cognitive and emotional components of empathy, consistent with the different locations of neuropathology that typifies these two diseases. SD patients showed significant decreases in all four empathy subscales, meaning that, as we hypothesized, both cognitive and emotional aspects of empathy were disrupted by the combination of anatomic damage to the anterior temporal lobes, amygdala, and ventromedial orbitofrontal cortex that is specific to SD patients.

Importantly, SD patients typically show sparing of dorsolateral prefrontal structures and functions, retaining near-normal performance on set-shifting and sequencing tasks such as the Trail Making Test and normal working memory even at a late stage in their disease course.53 Though this uniformly diminished empathy in temporal-variant (SD) patients does not provide information about the contribution of set shifting to empathy, it does suggest that retention of this function is not adequate to maintain normal cognitive empathy or emotional empathy in the context of temporal lobe damage. A third consideration with regard to the SD patients is that they evidenced not only a lower but also a less variable range of scores on Perspective Taking than the FTDs (see Fig. 1). This is particularly important, given the fact that upon post-hoc analysis of their MRI, the gross atrophy of the SD group was fairly evenly split into thirds, with some predominantly right, some predominantly left, and some bilateral temporal damage, though all showed some orbitofrontal cortex atrophy. If the predominantly left temporal SD patients had maintained normal levels of Perspective Taking, the group would have evidenced greater variance (like what was seen in the FTD group); thus, either structures in both the left and right temporal lobes are necessary for healthy Perspective Taking or only the right side is necessary for this function, but patients with predominantly left temporal atrophy still have enough damage to their right temporal and ventromedial orbitofrontal cortex to cause significant disruption in Perspective Taking.

FTD patients showed a wider range of functioning on all measures of empathy, which is consistent with the observation that they are likely to sustain divergent damage throughout dorsolateral, medial, and orbitofrontal cortices, and sometimes damage can spread to the temporal lobes.40 However, even in the cases where FTD-variant patients show some temporal involvement, there is much less damage to the amygdala and other temporal lobe structures such as the fusiform gyrus and superior temporal sulcus than is seen in SD. This may explain why their level of emotional empathy did not differ significantly from that of NCs. Though their diminished cognitive empathy cannot be precisely linked to either their orbitofrontal or their dorsolateral prefrontal damage used on this study, it is interesting to note that only their Perspective Taking was diminished, whereas caregivers reported that they still maintained near-normal ability to project themselves into fantasy situations (unlike SD patients). As SD and FTD patients have equivalent levels of ventromedial orbitofrontal atrophy, this dissociation suggests that the fantasy elements of empathy may be mediated by structures other than the orbitofrontal cortex, while Perspective Taking is more likely to be at least partly mediated by orbitofrontal structures. Last, the fact that elements of emotional empathy were preserved in the FTD patients suggests that despite significant interconnections between the orbitofrontal cortex and amygdala/temporal lobe structures, orbitofrontal damage does not entirely block the experience or interpretation of the emotional components of empathy.

Neuropsychological Correlates of Empathy

This study used neuropsychological measures of specific components of empathy to test neural network models of empathy. We found significant correlations between both cognitive (PT, FS) and emotional (EC) empathy and neuropsychological measures that have been hypothesized to contribute to empathy, including generation of nonverbal material, generation of verbal material to both a category and a phonemic prompt, and abstract reasoning. However, neither Trails speed (reactive flexibility) nor working memory score correlated significantly with any of the empathy scores, contrary to our hypothesis. This may have been due to the limited nature of the working memory measure (span of digits backward), and more detailed testing of this function (eg, with an N-back task) may actually yield significant correlations with empathy measures. Trail Making speed may not have been an adequate measure of the kind of cognitive rigidity that has previously been shown to correlate negatively with empathy, whereas a more direct measure of perseveration may have shown a more significant relationship. Design fluency also correlated with only one element of cognitive empathy: the fantasy (FS) score. However, the verbal fluency tasks and abstract reasoning correlated significantly with both cognitive and emotional empathy, replicating previous research with other patient populations that found that spontaneous cognitive flexibility corresponds to the ability to generate a diversity of ideas and significantly predicts level of empathy.3,11

Once these measures were entered into a regression analysis to determine their relative impact on the empathy outcome scores, however, all neuropsychological measures other than the verbal fluency measure dropped out of the analysis, including general cognitive functioning (MMSE). In a similar analysis with orbitofrontal patients, Shamay et al11 found that measures of reactive cognitive flexibility (e.g., Trails and Wisconsin Card Sorting Test) did not survive the regression analysis, whereas measures of spontaneous flexibility (in this case, design fluency, Alternate Uses Test, and Torrance Test of Creative Thinking) predicted 44.4% of the variance in cognitive empathy. In our analysis, three tests of spontaneous flexibility were used, and we found a dissociation between type of verbal generation and aspect of cognitive empathy. Only one of the cognitive empathy scores (Perspective Taking) was significantly predicted specifically by Category Fluency, and though Phonemic Fluency was highly correlated with Category Fluency (r = 0.55, P < 0.001), Phonemic Fluency did not account for a significant portion of the variance in Perspective Taking score. Conversely, 25% of the FS score variance was significantly predicted by Phonemic Fluency rather than Category Fluency. One hypothesis explaining this finding is that the anatomic dissociation between Category Fluency (which is generated by more posterior structures in the left temporal lobe and angular gyrus) and Phonemic Fluency (which is performed by left dorsolateral frontal structures) may actually correspond to an anatomic/functional dissociation between the Perspective Taking and fantasy elements of cognitive empathy that needs to be further explored.

Importantly, none of the standard neuropsychological tests used for this analysis was able to significantly predict level of emotional empathy. This suggests that to provide better empirical verification of the component processes of emotional empathy, direct neuropsychological assessment of the emotional system (such as the ability to discriminate emotions through facial expressions and voice prosody) may be required. Also, the usefulness of the PD subscale as an empirical measure of emotional empathy was called into question by these data, because it correlated highly with general cognitive functioning and appeared to have no other more specific cognitive correlations.

The group differences in empathic functioning shown in FTLD patients in this study are potentially useful, for differentiating the FTD and SD variants of the disease and suggest that more detailed empathy testing (among other tests of social functioning) holds promise for differential diagnostic evaluations in the future. Though this study confirmed that spontaneous flexibility does contribute to both cognitive and emotional aspects of empathy, further study must be done to confirm other proposed elements of the empathy circuit, including reactive cognitive flexibility, abstract reasoning, and working memory, as well as measures of facial affect discrimination. More detailed neuropsychological and social testing with larger groups of patients, as well as continued fMRI studies of tasks proximal to empathy, can continue to provide a more comprehensive picture of the neuroanatomic correlates of empathy in the brain.


The authors acknowledge Richard Perry, Jennifer Beer, and Paula M. Mychack for their work in laying the foundation for this research.


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empathy; frontotemporal dementia

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