More Than Words: Extra-Sylvian Neuroanatomic Networks Support Indirect Speech Act Comprehension and Discourse in Behavioral Variant Frontotemporal Dementia.

Indirect speech acts-responding "I forgot to wear my watch today" to someone who asked for the time-are ubiquitous in daily conversation, but are understudied in current neurobiological models of language. To comprehend an indirect speech act like this one, listeners must not only decode the lexical-semantic content of the utterance, but also make a pragmatic, bridging inference. This inference allows listeners to derive the speaker's true, intended meaning-in the above dialog, for example, that the speaker cannot provide the time. In the present work, we address this major gap by asking non-aphasic patients with behavioral variant frontotemporal dementia (bvFTD, n = 21) and brain-damaged controls with amnestic mild cognitive impairment (MCI, n = 17) to judge simple question-answer dialogs of the form: "Do you want some cake for dessert?" "I'm on a very strict diet right now," and relate the results to structural and diffusion MRI. Accuracy and reaction time results demonstrate that subjects with bvFTD, but not MCI, are selectively impaired in indirect relative to direct speech act comprehension, due in part to their social and executive limitations, and performance is related to caregivers' judgment of communication efficacy. MRI imaging associates the observed impairment in bvFTD to cortical thinning not only in traditional language-associated regions, but also in fronto-parietal regions implicated in social and executive cerebral networks. Finally, diffusion tensor imaging analyses implicate white matter tracts in both dorsal and ventral projection streams, including superior longitudinal fasciculus, frontal aslant, and uncinate fasciculus. These results have strong implications for updated neurobiological models of language, and emphasize a core, language-mediated social disorder in patients with bvFTD.

Cognitive and Neuroanatomic Accounts of Referential Communication in Focal Dementia.

The primary function of language is to communicate-that is, to make individuals reach a state of mutual understanding about a particular thought or idea. Accordingly, daily communication is truly a task of social coordination. Indeed, successful interactions require individuals to (1) track and adopt a partner's perspective and (2) continuously shift between the numerous elements relevant to the exchange. Here, we use a referential communication task to study the contributions of perspective taking and executive function to effective communication in nonaphasic human patients with behavioral variant frontotemporal dementia (bvFTD). Similar to previous work, the task was to identify a target object, embedded among an array of competitors, for an interlocutor. Results indicate that bvFTD patients are impaired relative to control subjects in selecting the optimal, precise response. Neuropsychological testing related this performance to mental set shifting, but not to working memory or inhibition. Follow-up analyses indicated that some bvFTD patients perform equally well as control subjects, while a second, clinically matched patient group performs significantly worse. Importantly, the neuropsychological profiles of these subgroups differed only in set shifting. Finally, structural MRI analyses related patient impairment to gray matter disease in orbitofrontal, medial prefrontal, and dorsolateral prefrontal cortex, all regions previously implicated in social cognition and overlapping those related to set shifting. Complementary white matter analyses implicated uncinate fasciculus, which carries projections between orbitofrontal and temporal cortices. Together, these findings demonstrate that impaired referential communication in bvFTD is cognitively related to set shifting, and anatomically related to a social-executive network including prefrontal cortices and uncinate fasciculus.

Cognitive and Affective Perspective-Taking: Evidence for Shared and Dissociable Anatomical Substrates.

Perspective-taking refers to the ability to recognize another person's point of view. Crucial to the development of interpersonal relationships and prosocial behavior, perspective-taking is closely linked to human empathy, and like empathy, perspective-taking is commonly subdivided into cognitive and affective components. While the two components of empathy have been frequently compared, the differences between cognitive and affective perspective-taking have been under-investigated in the cognitive neuroscience literature to date. Here, we define cognitive perspective-taking as the ability to infer an agent's thoughts or beliefs, and affective perspective-taking as the ability to infer an agent's feelings or emotions. In this paper, we review data from functional imaging studies in healthy adults as well as behavioral and structural imaging studies in patients with behavioral variant frontotemporal dementia in order to determine if there are distinct neural correlates for cognitive and affective perspective-taking. Data suggest that there are both shared and non-shared cognitive and anatomic substrates. For example, while both types of perspective-taking engage regions such as the temporoparietal junction, precuneus, and temporal poles, only affective perspective-taking engages regions within the limbic system and basal ganglia. Differences are also observed in prefrontal cortex: while affective perspective-taking engages ventromedial prefrontal cortex, cognitive perspective-taking engages dorsomedial prefrontal cortex and dorsolateral prefrontal cortex (DLPFC). To corroborate these findings, we also examine if cognitive and affective perspective-taking share the same relationship with executive functions. While it is clear that affective perspective-taking requires emotional substrates that are less prominent in cognitive perspective-taking, it remains unknown to what extent executive functions (including working memory, mental set switching, and inhibitory control) may contribute to each process. Overall results indicate that cognitive perspective-taking is dependent on executive functioning (particularly mental set switching), while affective perspective-taking is less so. We conclude with a critique of the current literature, with a focus on the different outcome measures used across studies and misconceptions due to imprecise terminology, as well as recommendations for future research.

Establishing zebrafish as a model to study the anxiolytic effects of scopolamine.

Scopolamine (hyoscine) is a muscarinic acetylcholine receptor antagonist that has traditionally been used to treat motion sickness in humans. However, studies investigating depressed and bipolar populations have found that scopolamine is also effective at reducing depression and anxiety symptoms. The potential anxiety-reducing (anxiolytic) effects of scopolamine could have great clinical implications for humans; however, rats and mice administered scopolamine showed increased anxiety in standard behavioural tests. This is in direct contrast to findings in humans, and complicates studies to elucidate the specific mechanisms of scopolamine action. The aim of this study was to assess the suitability of zebrafish as a model system to test anxiety-like compounds using scopolamine. Similar to humans, scopolamine acted as an anxiolytic in individual behavioural tests (novel approach test and novel tank diving test). The anxiolytic effect of scopolamine was dose dependent and biphasic, reaching maximum effect at 800 µM. Scopolamine (800 µM) also had an anxiolytic effect in a group behavioural test, as it significantly decreased their tendency to shoal. These results establish zebrafish as a model organism for studying the anxiolytic effects of scopolamine, its mechanisms of action and side effects.

Social Coordination in Older Adulthood: A Dual-Process Model.

BACKGROUND/STUDY CONTEXT: In a variety of collaborative circumstances, participants must adopt the perspective of a partner and establish a shared mental representation that helps mediate common understanding. This process is referred to as social coordination. Here, the authors investigate the effect of aging on social coordination and consider separately the component processes related to perspective-taking and working memory. METHODS: Twelve young adults and 14 older adults completed an experimental, language-based coordination task. Subjects were asked to describe a scene with sufficient detail so that a conversational partner could identify a target object in the context of other, competing objects that shared a variable number of features. Trials varied in the information available to the partner (perspective-taking demand) and in the number of competing objects present in the scene (working memory demand). Responses were scored according to adjective use. RESULTS: Results indicated that social coordination performance decreases with age. Whereas young adults performed close to ceiling, older adults were only precise in 49.70% of trials. In analyses examining perspective-taking conditions with no competitors, older adults were consistently impaired relative to young adults; in analyses examining the number of competitors during the simplest perspective-taking condition, both older and younger adults became more impaired with increasing numbers of competitors. CONCLUSION: The experimental data suggest that social coordination decreases with age, which may affect communicative efficacy. Older adults' tendency to provide insufficient responses suggests a limitation in perspective-taking, and the pattern of decline in common ground performance with increasing competitors suggests that this is independent of working memory decline. In sum, our results suggest that social coordination deficits in aging may be multifactorial.

Processing ambiguity in a linguistic context: decision-making difficulties in non-aphasic patients with behavioral variant frontotemporal degeneration.

Some extent of ambiguity is ubiquitous in everyday conversations. For example, words have multiple meaning and very common pronouns, like "he" and "she" (anaphoric pronouns), have little meaning on their own and refer to a noun that has been previously introduced in the discourse. Ambiguity triggers a decision process that is not a subroutine of language processing but rather a more general domain resource. Therefore non-aphasic patients with limited decision-making capability can encounter severe limitation in language processing due to extra linguistic limitations. In the present study, we test patients with behavioral variant frontotemporal degeneration (bvFTD), focusing on anaphora as a paradigmatic example of ambiguity resolution in the linguistic domain. bvFTD is characterized by gray matter (GM) atrophy in prefrontal cortex, but relative sparing of peri-Sylvian cortex. A group of patients with parietal disease due to corticobasal syndrome (CBS) was also tested here in order to investigate the specific role of prefrontal cortex in the task employed in the current study. Participants were presented with a pair of sentences in which the first sentence contained two nouns while the second contained a pronoun. In the experimental (ambiguous) condition, both nouns are plausible referents of the pronoun, thus requiring decision-making resources. The results revealed that bvFTD patients are significantly less accurate than healthy seniors in identifying the correct referent of a pronoun in the ambiguous condition, although CBS patients were as accurate as healthy seniors. Imaging analyses related bvFTD patients' performance to GM atrophy in ventromedial prefrontal cortex (vmPFC). These results suggest that bvFTD patients have difficulties in decision processes that involve the resolution of an ambiguity.

Brain activity and connectivity during poetry composition: Toward a multidimensional model of the creative process.

Creativity, a multifaceted construct, can be studied in various ways, for example, investigating phases of the creative process, quality of the creative product, or the impact of expertise. Previous neuroimaging studies have assessed these individually. Believing that each of these interacting features must be examined simultaneously to develop a comprehensive understanding of creative behavior, we examined poetry composition, assessing process, product, and expertise in a single experiment. Distinct activation patterns were associated with generation and revision, two major phases of the creative process. Medial prefrontal cortex (MPFC) was active during both phases, yet responses in dorsolateral prefrontal and parietal executive systems (DLPFC/IPS) were phase-dependent, indicating that while motivation remains unchanged, cognitive control is attenuated during generation and re-engaged during revision. Experts showed significantly stronger deactivation of DLPFC/IPS during generation, suggesting that they may more effectively suspend cognitive control. Importantly however, similar overall patterns were observed in both groups, indicating the same cognitive resources are available to experts and novices alike. Quality of poetry, assessed by an independent panel, was associated with divergent connectivity patterns in experts and novices, centered upon MPFC (for technical facility) and DLPFC/IPS (for innovation), suggesting a mechanism by which experts produce higher quality poetry. Crucially, each of these three key features can be understood in the context of a single neurocognitive model characterized by dynamic interactions between medial prefrontal areas regulating motivation, dorsolateral prefrontal, and parietal areas regulating cognitive control and the association of these regions with language, sensorimotor, limbic, and subcortical areas distributed throughout the brain.

Getting on the same page: the neural basis for social coordination deficits in behavioral variant frontotemporal degeneration.

For social interactions to be successful, individuals must establish shared mental representations that allow them to reach a common understanding and "get on the same page". We refer to this process as social coordination. While examples of social coordination are ubiquitous in daily life, relatively little is known about the neuroanatomic basis of this complex behavior. This is particularly true in a language context, as previous studies have used overly complex paradigms to study this. Although traditional views of language processing and the recent interactive-alignment account of conversation focus on peri-Sylvian regions, our model of social coordination predicts prefrontal involvement. To test this hypothesis, we examine the neural basis of social coordination during conversational exchanges in non-aphasic patients with behavioral variant frontotemporal degeneration (bvFTD). bvFTD patients show impairments in executive function and social comportment due to disease in frontal and anterior temporal regions. To investigate social coordination in bvFTD, we developed a novel language-based task that assesses patients' ability to convey an object's description to a conversational partner. Experimental conditions manipulated the amount of information shared by the participant and the conversational partner, and the associated working memory demands. Our results indicate that, although patients did not have difficulty identifying the features of the objects, they did produce descriptions that included insufficient or inappropriate adjectives and thus struggled to communicate effectively. Impaired performance was related to gray matter atrophy particularly in medial prefrontal and orbitofrontal cortices. Our findings suggest an important role for non-language brain areas that belong to a large-scale neurocognitive network for social coordination.

The processing of speech, gesture, and action during language comprehension.

Hand gestures and speech form a single integrated system of meaning during language comprehension, but is gesture processed with speech in a unique fashion? We had subjects watch multimodal videos that presented auditory (words) and visual (gestures and actions on objects) information. Half of the subjects related the audio information to a written prime presented before the video, and the other half related the visual information to the written prime. For half of the multimodal video stimuli, the audio and visual information contents were congruent, and for the other half, they were incongruent. For all subjects, stimuli in which the gestures and actions were incongruent with the speech produced more errors and longer response times than did stimuli that were congruent, but this effect was less prominent for speech-action stimuli than for speech-gesture stimuli. However, subjects focusing on visual targets were more accurate when processing actions than gestures. These results suggest that although actions may be easier to process than gestures, gestures may be more tightly tied to the processing of accompanying speech.