Skin Conduction Levels Differentiate Frontotemporal Dementia From Alzheimer's Disease.

Patients with behavioral variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD) differ in basic emotional tone. Skin conduction levels (SCLs), a measure of sympathetic tone, may be a sensitive test for discriminating these two dementias early in their course. Previous research has shown differences in resting SCLs between patients with bvFTD and AD, but no study has evaluated the discriminability of SCLs during different environmental conditions. The authors compared bvFTD patients (N=8), AD patients (N=10), and healthy control subjects (N=9) on SCL measures pertaining to real-life vignettes or scenarios differing in valence and emotional intensity. The SCLs among the bvFTD patients were decreased across all conditions, whereas the SCLs among the AD patients were increased compared with control participants. On analysis, the SCLs in response to emotional stimuli differentiated bvFTD from AD with an area under the receiver operator characteristic curve of 95.3%. At a cutoff ≤0.77 µS, emotional vignettes distinguished bvFTD from AD with a sensitivity of 86% and a specificity of 96%. These preliminary results indicate the potential utility of SCLs for differentiating bvFTD from AD early in their course, regardless of environmental condition.

The attribution of animacy and agency in frontotemporal dementia versus Alzheimer's disease.

Impaired attribution of animacy (state of living or being sentient) and of agency (capability of intrinsically-driven action) may underlie social behavior disturbances in behavioral variant frontotemporal dementia (bvFTD). We presented the Heider and Simmel film of moving geometric shapes to 11 bvFTD patients, 11 Alzheimer's disease (AD) patients, and 12 healthy controls (HCs) and rated their recorded verbal responses for animacy attribution and agency attribution. All participants had skin conductance (SC) continuously recorded while viewing the film, and all dementia participants underwent magnetic resonance imaging (MRI) for regions of interest. The bvFTD patients, but not the AD patients, were impaired in animacy attribution, compared to the HCs. In contrast, both bvFTD and AD groups were impaired in agency attribution, compared to the HCs, and only the HCs had increasing SC responsiveness during viewing of the film. On MRI analysis of cortical thicknesses, animacy scores significantly correlated across groups with the right pars orbitalis and opercularis; agency scores with the left inferior and superior parietal cortices and the supramarginal gyrus; and both scores with the left cingulate isthmus involved in visuospatial context. These findings suggest that bvFTD is specifically associated with impaired animacy attribution from right inferior frontal atrophy. In contrast, both dementias may have impaired agency attribution from left parietal cortical atrophy and absent SC increases during the film, a sympathetic indicator of attribution of a social "story" to the moving shapes. These findings clarify disease-related changes in social attribution and corroborate the neuroanatomical origins of animacy and agency.

Behavioral and autonomic reactivity to moral dilemmas in frontotemporal dementia versus Alzheimer's disease.

The personal/impersonal distinction of moral decision-making postulates intuitive emotional responses from medial frontal activity and rational evaluation from lateral frontal activity. This model can be analyzed in behavioral variant frontotemporal dementia (bvFTD), a disorder characterized by impaired emotional intuitions, ventromedial prefrontal cortex (vmPFC) involvement, and relative sparing of lateral frontal regions. Moral dilemmas were presented to 10 bvFTD, 11 Alzheimer's disease (AD), and 9 healthy control (HC) participants while recording skin conductance responses, a measure of emotional arousal. We evaluated their personal versus impersonal conflict, subjective discomfort, and adherence to social norms. Replicating prior work, bvFTD participants were more willing to harm in the personal, but not the impersonal, dilemma compared to AD and HC groups. BvFTD participants had lower arousal and less of an increase in conflict on the personal versus the impersonal dilemma, in contrast to increased arousal and conflict for the AD and HC groups. Furthermore, bvFTD participants verbalized less discomfort, a correlate of low adherence to social norms. These findings support impaired emotional reactions to moral dilemmas in bvFTD and vmPFC lesions and the personal/impersonal model. It suggests a reversion to utilitarian-like considerations when emotional intuition is impaired in the brain.

An investigation of care-based vs. rule-based morality in frontotemporal dementia, Alzheimer's disease, and healthy controls.

Behavioral changes in dementia, especially behavioral variant frontotemporal dementia (bvFTD), may result in alterations in moral reasoning. Investigators have not clarified whether these alterations reflect differential impairment of care-based vs. rule-based moral behavior. This study investigated 18 bvFTD patients, 22 early onset Alzheimer's disease (eAD) patients, and 20 healthy age-matched controls on care-based and rule-based items from the Moral Behavioral Inventory and the Social Norms Questionnaire, neuropsychological measures, and magnetic resonance imaging (MRI) regions of interest. There were significant group differences with the bvFTD patients rating care-based morality transgressions less severely than the eAD group and rule-based moral behavioral transgressions more severely than controls. Across groups, higher care-based morality ratings correlated with phonemic fluency on neuropsychological tests, whereas higher rule-based morality ratings correlated with increased difficulty set-shifting and learning new rules to tasks. On neuroimaging, severe care-based reasoning correlated with cortical volume in right anterior temporal lobe, and rule-based reasoning correlated with decreased cortical volume in the right orbitofrontal cortex. Together, these findings suggest that frontotemporal disease decreases care-based morality and facilitates rule-based morality possibly from disturbed contextual abstraction and set-shifting. Future research can examine whether frontal lobe disorders and bvFTD result in a shift from empathic morality to the strong adherence to conventional rules.

Observation of social behavior in frontotemporal dementia.

BACKGROUND: The most characteristic manifestations of behavioral variant frontotemporal dementia (bvFTD) are abnormalities in social behavior. However, distinguishing bvFTD based on social behavior can be difficult in structured clinical settings. METHODS: Using a Social Observation Inventory, 10 patients with bvFTD and 10 patients with Alzheimer's disease (AD) were compared to their caregiver interlocutors on 1-hour mealtime, in-home videotaped segments. RESULTS: Compared to caregivers and patients with AD, patients with bvFTD were significantly disturbed in social behavior. In contrast, patients with AD were indistinguishable from their caregivers. The lack of "you" comments and decreased tact and manners distinguished 92.6% of the patients with bvFTD from patients with AD and caregivers. The Social Observation Inventory scores correlated with scores on frontal-executive tests and socioemotional scales. CONCLUSIONS: The systematic observation of social behavior during routine activities may be one of the best ways to distinguish patients with bvFTD from normal individuals and from patients with other dementias.

Suicidal behavior and loss of the future self in semantic dementia.

Semantic dementia impairs semantic autobiographical memory, but tends to spare its episodic components that are critical for the sense of self. Investigators have recently discovered disturbances in the "future self" in semantic dementia. We report a 63-year-old man with semantic dementia who was hospitalized after suicide attempts that he attributed to his loss of a sense of future self. He complained of a decreased sense of being human, because he could not imagine doing things in the future that he had done in the past. Suicidal thinking and inability to place himself in future tasks persisted despite resolution of depression. Clinical assessment revealed a crossmodal loss of semantic knowledge, and neuroimaging showed bilateral anterior temporal atrophy and hypometabolism. On specific tests of autobiographical memory, identity, attribute knowledge, and future projection, the patient could return to the past and visualize himself in familiar scenarios, but he could not visualize himself even passively in these scenarios in the future. His future self was impaired not from seeing himself disabled; it was from an absence of semantic details of potential experiences, associated with impaired semantic autobiographical memory. His self-representations were concrete and specific rather than abstract and generalizable. This patient and recent publications indicate that semantic dementia impairs the ability to imagine oneself as capable in the future, leading some patients to suicidal behavior. We discuss possible mechanisms for these findings, including the potential role of abstract construals for future thinking.

Somatosensory-evoked potential asymmetry in medullary ischemia during cervical spine surgery.

This report describes how somatosensory-evoked potentials (SEPs) can detect acute medullary ischemia during cervical spine surgery. This article describes how asymmetric SEP intraoperative monitoring changes can localize medullary ischemia. Localization of change was validated by postoperative magnetic resonance imaging (MRI). A 68-year-old man underwent cervical posterior fusion with monitoring of bilateral SEPs of the upper and lower extremities. The SEPs disappeared during initial exposure of the C1 lamina. Changes were asymmetric in degree and duration. Brain MRI postoperatively demonstrated bilateral posterior inferior cerebellar artery (PICA) territory infarcts involving the left lateral medulla. This illustrates how intraoperative SEP monitoring can provide important information on the functional integrity of brainstem structures even during cervical surgery. A knowledge of medullary anatomy and vascular territories is necessary for interpreting SEP changes. In cervical surgery, SEPs incidentally monitor the integrity of the brainstem while monitoring the spinal cord. The asymmetry of SEP change seen here was consistent with medullary level impairment, where the vascular territory is lateralized in contrast to the symmetric anterior spinal artery territory.