Marc Sollberger

Detecting sarcasm from paralinguistic cues: Anatomic and cognitive correlates in neurodegenerative disease

While sarcasm can be conveyed solely through contextual cues such as counterfactual or echoic statements, face-to-face sarcastic speech may be characterized by specific paralinguistic features that alert the listener to interpret the utterance as ironic or critical, even in the absence of contextual information. We investigated the neuroanatomy underlying failure to understand sarcasm from dynamic vocal and facial paralinguistic cues. Ninety subjects (20 frontotemporal dementia, 11 semantic dementia [SemD], 4 progressive non-fluent aphasia, 27 Alzheimers disease, 6 corticobasal degeneration, 9 progressive supranuclear palsy, 13 healthy older controls) were tested using the Social Inference - Minimal subtest of The Awareness of Social Inference Test (TASIT). Subjects watched brief videos depicting sincere or sarcastic communication and answered yes-no questions about the speakers intended meaning. All groups interpreted Sincere (SIN) items normally, and only the SemD group was impaired on the Simple Sarcasm (SSR) condition. Patients failing the SSR performed more poorly on dynamic emotion recognition tasks and had more neuropsychiatric disturbances, but had better verbal and visuospatial working memory than patients who comprehended sarcasm. Voxel-based morphometry analysis of SSR scores in SPM5 demonstrated that poorer sarcasm comprehension was predicted by smaller volume in bilateral posterior parahippocampi (PHc), temporal poles, and R medial frontal pole (pFWE<0.05). This study provides lesion data suggesting that the PHc may be involved in recognizing a paralinguistic speech profile as abnormal, leading to interpretive processing by the temporal poles and right medial frontal pole that identifies the social context as sarcastic, and recognizes the speakers paradoxical intentions.

Neural basis of interpersonal traits in neurodegenerative diseases

Several functional and structural imaging studies have investigated the neural basis of personality in healthy adults, but human lesions studies are scarce. Personality changes are a common symptom in patients with neurodegenerative diseases like frontotemporal dementia (FTD) and semantic dementia (SD), allowing a unique window into the neural basis of personality. In this study, we used the Interpersonal Adjective Scales to investigate the structural basis of eight interpersonal traits (dominance, arrogance, coldness, introversion, submissiveness, ingenuousness, warmth, and extraversion) in 257 subjects: 214 patients with neurodegenerative diseases such as FTD, SD, progressive nonfluent aphasia, Alzheimers disease, amnestic mild cognitive impairment, corticobasal degeneration, and progressive supranuclear palsy and 43 healthy elderly people. Measures of interpersonal traits were correlated with regional atrophy pattern using voxel-based morphometry (VBM) analysis of structural MR images. Interpersonal traits mapped onto distinct brain regions depending on the degree to which they involved agency and affiliation. Interpersonal traits high in agency related to left dorsolateral prefrontal and left lateral frontopolar regions, whereas interpersonal traits high in affiliation related to right ventromedial prefrontal and right anteromedial temporal regions. Consistent with the existing literature on neural networks underlying social cognition, these results indicate that brain regions related to externally focused, executive control-related processes underlie agentic interpersonal traits such as dominance, whereas brain regions related to internally focused, emotion- and reward-related processes underlie affiliative interpersonal traits such as warmth. In addition, these findings indicate that interpersonal traits are subserved by complex neural networks rather than discrete anatomic areas.

Role of right pregenual anterior cingulate cortex in self-conscious emotional reactivity

Self-conscious emotions such as embarrassment arise when ones actions fail to meet salient social expectations and are accompanied by marked physiological and behavioral activation. We investigated the neural correlates of self-conscious emotional reactivity in 27 patients with behavioral variant frontotemporal dementia (bvFTD), a neurodegenerative disease that disrupts self-conscious emotion and targets brain regions critical for emotional functioning early in the disease course, and in 33 healthy older controls. Subjects participated in an embarrassing karaoke task in which they watched a video clip of themselves singing. They also watched a sad film clip; these data were used to control for non-self-conscious emotional reactivity in response to audiovisual stimuli. Using Freesurfer to quantify regional brain volumes from structural magnetic resonance imaging, right pregenual anterior cingulate cortex (pACC) gray matter volume was the only brain region that was a significant predictor of self-conscious emotion. Smaller pACC volume was associated with attenuated physiological and behavioral self-conscious emotional reactivity, and this relationship was not specific to diagnosis. We argue that these results reflect the significant role that right pACC plays in the visceromotor responding that accompanies self-conscious emotion and that neurodegeneration in this region may underlie the self-conscious emotional decline seen in bvFTD.

CSF-Tau and CSF-Aβ1–42 in Posterior Cortical Atrophy

Objective: Our purpose was to measure Aβ1–42, T-tau and P-tau181 in the cerebrospinal fluid (CSF) of patients with posterior cortical atrophy (PCA), a presenile dementia likely to represent a variant of Alzheimer’s disease (AD). Methods: CSF samples from 34 subjects including 9 patients with PCA, 11 age-matched patients with AD and 14 age-matched cognitively healthy controls were analyzed using commercially available ELISA kits. Results: The Aβ1–42, T-tau and P-tau181 levels in PCA patients differed significantly (p < 0.02) from those in healthy controls but were indistinguishable from subjects with a clinical diagnosis of AD. Conclusion: High T-tau and P-tau181 and low Aβ1–42 levels in PCA – typically observed in AD – indicate that the underlying pathology of PCA is usually AD. If these findings are replicated in PCA patients with autopsy-confirmed AD neuropathology, PCA patients may be eligible for disease-modifying AD treatments.

Interpersonal traits change as a function of disease type and severity in degenerative brain diseases

Background Different degenerative brain diseases result in distinct personality changes as a result of divergent patterns of brain damage; however, little is known about the natural history of these personality changes throughout the course of each disease. Objective To investigate how interpersonal traits change as a function of degenerative brain disease type and severity. Methods Using the Interpersonal Adjective Scales, informant ratings of retrospective premorbid and current scores for dominance, extraversion, warmth and ingenuousness were collected annually for 1 to 4 years on 188 patients (67 behavioural variant frontotemporal dementia (bvFTD), 40 semantic dementia (SemD), 81 Alzheimers disease (AD)) and 65 older healthy controls. Using random coefficient models, interpersonal behaviour scores at very mild, mild or moderate-to-severe disease stages were compared within and between patient groups. Results Group-level changes from premorbid personality occurred as a function of disease type and severity, and were apparent even at a very mild disease stage (Clinical Dementia Rating=0.5) for all three diseases. Decreases in interpersonal traits were associated with emotional affiliation (ie, extraversion, warmth and ingenuousness) and more rigid interpersonal behaviour differentiated bvFTD and SemD patients from AD patients. Conclusions Specific changes in affiliative interpersonal traits differentiate degenerative brain diseases even at a very mild disease stage, and patterns of personality change differ across bvFTD, SemD and AD with advancing disease. This study describes the typical progression of change of interpersonal traits in each disease, improving the ability of clinicians and caregivers to predict and plan for symptom progression.

Neural substrates of socioemotional self-awareness in neurodegenerative disease

Neuroimaging studies examining neural substrates of impaired self‐awareness in patients with neurodegenerative diseases have shown divergent results depending on the modality (cognitive, emotional, behavioral) of awareness. Evidence is accumulating to suggest that self‐awareness arises from a combination of modality‐specific and large‐scale supramodal neural networks.

Serial position effects are sensitive predictors of conversion from MCI to Alzheimer's disease dementia

It is unclear whether the predictive strength of established cognitive variables for progression to Alzheimers disease (AD) dementia from mild cognitive impairment (MCI) varies depending on time to conversion. We investigated which cognitive variables were best predictors, and which of these variables remained predictive for patients with longer times to conversion.

Varying strength of cognitive markers and biomarkers to predict conversion and cognitive decline in an early-stage-enriched mild cognitive impairment sample.

BACKGROUND Several cognitive, neuroimaging, and cerebrospinal fluid (CSF) markers predict conversion from mild cognitive impairment (MCI) to Alzheimers disease (AD) dementia. However, predictors might be more or less powerful depending on the characteristics of the MCI sample. OBJECTIVE To investigate which cognitive markers and biomarkers predict conversion to AD dementia and course of cognitive functioning in a MCI sample with a high proportion of early-stage MCI patients. METHODS Variables known to predict progression in MCI patients and hypothesized to predict progression in early-stage MCI patients were selected. Cognitive (long-delay free recall, regional primacy score), imaging (hippocampal and entorhinal cortex volumes, fornix fractional anisotropy), and CSF (Aβ1-42/t-tau, Aβ1-42) variables from 36 MCI patients were analyzed with Cox regression and mixed-effect models to determine their individual and combined abilities to predict time to conversion to AD dementia and course of global cognitive functioning, respectively. RESULTS Those variables hypothesized to predict the course of early-stage MCI patients were most predictive for MCI progression. Specifically, regional primacy score (a measure of word-list position learning) most consistently predicted conversion to AD dementia and course of cognitive functioning. Both the prediction of conversion and course of cognitive functioning were maximized by including CSF Aβ1-42 and fornix integrity biomarkers, respectively, indicating the complementary information carried by cognitive variables and biomarkers. CONCLUSION Predictors of MCI progression need to be interpreted in light of the characteristics of the respective MCI sample. Future studies should aim to compare predictive strengths of markers between early-stage and late-stage MCI patients.

IC-P1-068: Structural anatomy of environmental dependency syndrome in neurodegenerative disease

Dong Won Yang, Howard J Rosen, Maria-Luisa Gorno-Tempini, Bruce L. Miller, Joel H Kramer, Michael Weiner, Marc Sollberger, Memory and Aging Center, UCSF Medical Center, San Francisco, CA, USA; St. Mary’s Hospital, Neurology Department, Catholic University of Korea, Seoul, Republic of Korea; UCSF Department of Neurology, San Francisco, CA, USA; San Francisco Veterans Affairs Hospital Magnetic Resonance Imaging Unit, San Francisco, CA, USA. Contact e-mail: neuroman@catholic.ac.kr